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    Obesity phenotypes and their paradoxical association with cardiovascular diseases. Vecchié Alessandra,Dallegri Franco,Carbone Federico,Bonaventura Aldo,Liberale Luca,Portincasa Piero,Frühbeck Gema,Montecucco Fabrizio European journal of internal medicine The pro-inflammatory state of the visceral adipose tissue (VAT) is supposed to accelerate cardiovascular (CV) and metabolic diseases in obese subjects. Some studies have recently reported an improved CV prognosis in certain obese and overweight patients as compared with leaner ones. This phenomenon, known as the "obesity paradox" (OP), has been described in many chronic diseases. This narrative review is based on the material searched for and obtained via PubMed and Web of Science up to May 2017. The search terms we used were: "obesity, paradox, adipose tissue" in combination with "cardiovascular, coronary heart disease, heart failure, arrhythmias". Using the current Body Mass Index (BMI)-based obesity definition, individuals with different clinical and biochemical characteristics are gathered together in the same category. Emerging evidence point to the existence of many "Obesity phenotypes" with different association with CV risk, accordingly to physical and life-style features. In this narrative review, we discussed if obesity phenotypes may be associated with a different CV risk, potentially explaining the OP. As a globally accepted definition of obesity is still lacking, we emphasized the need of a new approach, which should consider the heterogeneity of obesity. Better defining "obesities" and related CV risk is critical to markedly improve the classical BMI-based definition of obesity. 10.1016/j.ejim.2017.10.020
    Therapeutic potential of cPLA2 inhibitor to counteract dilated-cardiomyopathy in cholesterol-treated H9C2 cardiomyocyte and MUNO rat. Huang Jiung-Pang,Cheng Mei-Ling,Wang Chao-Hung,Huang Shiang-Suo,Hsieh Po-Shiuan,Chang Chih-Chun,Kuo Chao-Yu,Chen Kuan-Hsing,Hung Li-Man Pharmacological research BACKGROUND AND PURPOSE:The pathogenesis of cardiomyopathy in metabolically unhealthy obesity (MUO) has been well studied. However, the pathogenesis of cardiomyopathy typically associated with high cholesterol levels in metabolically unhealthy nonobesity (MUNO) remains unclear. We investigated whether cholesterol-generated LysoPCs contribute to cardiomyopathy and the role of cytosolic phospholipase A2 (cPLA2) inhibitor in cholesterol-induced MUNO. EXPERIMENTAL APPROACH:Cholesterol diet was performed in Sprague-Dawley rats that were fed either regular chow (C), or high cholesterol chow (HC), or HC diet with 10 % fructose in drinking water (HCF) for 12 weeks. LysoPCs levels were subsequently measured in rats and in MUNO human patients. The effects of cholesterol-mediated LysoPCs on cardiac injury, and the action of cPLA2 inhibitor, AACOCF3, were further assessed in H9C2 cardiomyocytes. KEY RESULTS:HC and HCF rats fed cholesterol diets demonstrated a MUNO-phenotype and cholesterol-induced dilated cardiomyopathy (DCM). Upregulated levels of LysoPCs were found in rat myocardium and the plasma in MUNO human patients. Further testing in H9C2 cardiomyocytes revealed that cholesterol-induced atrophy and death of cardiomyocytes was due to mitochondrial dysfunction and conditions favoring DCM (i.e. reduced mRNA expression of ANF, BNP, DSP, and atrogin-1), and that AACOCF3 counteracted the cholesterol-induced DCM phenotype. CONCLUSION AND IMPLICATIONS:Cholesterol-induced MUNO-DCM phenotype was counteracted by cPLA2 inhibitor, which is potentially useful for the treatment of LysoPCs-associated DCM in MUNO. 10.1016/j.phrs.2020.105201
    Ectopic fat, insulin resistance and metabolic disease in non-obese Asians: investigating metabolic gradation. Tamura Yoshifumi Endocrine journal Although metabolic abnormalities commonly occur in non-obese Asians, their pathogenesis is not fully understood. Proton magnetic resonance spectroscopy has been used to analyze intracellular lipids in humans, and results suggest that ectopic fat accumulation in muscle and liver may induce insulin resistance in each tissue independently of obesity. Thus, measurement of ectopic fat currently plays an important role in the study of insulin resistance in non-obese Asians. In addition, studies using 2-step hyperinsulinemic euglycemic clamp with a glucose tracer may clarify how tissue-specific insulin resistance in muscle, liver, and adipose tissue contributes to the development of metabolic disease in non-obese Japanese. Although numerous studies have elucidated the pathophysiology of insulin resistance in obese subjects, research on "metabolic gradation," defined as the gradual transition from an insulin-sensitive to an insulin-resistant state, is less common, especially in terms of early metabolic changes. This review addresses a simple question: when and how is insulin resistance induced in non-obese East Asians? Several studies revealed that impaired insulin clearance and hyperinsulinemia not only compensated for insulin resistance, but also secondarily facilitated insulin resistance and weight gain. In this regard, we recently found that impaired insulin clearance and hyperinsulinemia could occur in apparently healthy subjects without significant insulin resistance, suggesting that this change may be an initial trigger that drives subsequent insulin resistance and weight gain. Further research is required to clarify the pathogenesis of metabolic gradation in non-obese Asians. 10.1507/endocrj.EJ18-0435
    Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis. Perez-Martinez Pablo,Alcala-Diaz Juan F,Delgado-Lista Javier,Garcia-Rios Antonio,Gomez-Delgado Francisco,Marin-Hinojosa Carmen,Rodriguez-Cantalejo Fernando,Delgado-Casado Nieves,Perez-Caballero Ana I,Fuentes-Jimenez Francisco J,Camargo Antonio,Tinahones Francisco J,Ordovas Jose M,Perez-Jimenez Francisco,Lopez-Miranda Jose European journal of clinical investigation BACKGROUND:We examined the degree of postprandial triglyceride (TG) response over the day, representing a highly dynamic state, with continuous metabolic adaptations, among normal-weight, overweight and obese patients, according to their metabolically healthy or abnormal status. MATERIALS AND METHODS:A total of 1002 patients from the CORDIOPREV clinical trial (NCT00924937) were submitted to an oral fat load test meal with 0·7 g fat/kg body weight (12% saturated fatty acids (SFA), 10% polyunsaturated fatty acids (PUFA), 43% monounsaturated fatty acids (MUFA), 10% protein and 25% carbohydrates). Serial blood test analysing lipid fractions and inflammation markers (high-sensitivity C-reactive protein (hs-CRP)) were drawn at 0, 1, 2, 3 and 4 h during postprandial state. We explored the dynamic response according to six body size phenotypes: (i) normal weight, metabolically healthy; (ii) normal weight, metabolically abnormal; (iii) overweight, metabolically healthy; (iv) overweight, metabolically abnormal; (v) obese, metabolically healthy; and (vi) obese, metabolically abnormal. RESULTS:Metabolically healthy patients displayed lower postprandial response of plasma TG and large triacylglycerol-rich lipoproteins (TRLs)-TG, compared with those metabolically abnormal, independently whether or not they were obese (P < 0·001 and P < 0·001, respectively). Moreover, the area under the curve (AUC) of TG and AUC of large TRLs-TG were greater in the group of metabolically abnormal compared with the group of metabolically healthy (P < 0·001 and P < 0·001, respectively). Interestingly, metabolically abnormal subjects displayed higher postprandial response of plasma hs-CRP than did the subgroup of normal, overweight and obese, metabolically healthy patients (P < 0·001). CONCLUSIONS:Our findings showed that certain types of the metabolic phenotypes of obesity are more favourable modulating phenotypic flexibility after a dynamic fat load test, through TG metabolism and inflammation homoeostasis. To identify, these phenotypes may be the best strategy for personalized treatment of obesity. 10.1111/eci.12339
    Body weight and physical fitness in women with ischaemic heart disease: does physical fitness contribute to our understanding of the obesity paradox in women? European journal of preventive cardiology AIMS:Body mass index (BMI) defined obesity is paradoxically associated with lower all-cause mortality in patients with known cardiovascular disease. This study aims to determine the role of physical fitness in the obesity paradox in women with ischaemic heart disease (IHD). METHODS AND RESULTS:Women undergoing invasive coronary angiography with signs/symptoms of IHD in the Women's Ischemia Syndrome Evaluation (WISE) prospective cohort (enrolled 1997-2001) were analysed. This study investigated the longer-term risk of major adverse cardiovascular events (MACE) and all-cause mortality associated with BMI and physical fitness measured by Duke Activity Status Index (DASI). Overweight was defined as BMl ≥25 to 30 kg/m2, obese as BMI ≥30 kg/m2, unfit as DASI scores <25, equivalent to ≤7 metabolic equivalents. Among 899 women, 18.6% were normal BMI-fit, 11.4% overweight-fit, 10.4% obese-fit, 15.3% normal BMI-unfit, 23.8% overweight-unfit, and 30.4% obese-unfit. In adjusted models compared to normal BMI-fit, normal BMI-unfit women had higher MACE risk [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.17-2.32; P = 0.004]; whereas obese-fit and overweight-fit women had lower risk of mortality (HR 0.60, 95% CI 0.40-0.89; P = 0.012 and HR 0.62, 95% CI 0.41-0.92; P = 0.018, respectively). CONCLUSION:To address the paradox of body weight and outcomes in women, we report for the first time that among women with signs/symptoms of IHD overweight-fit and obese-fit were at lower risk of long-term all-cause mortality; whereas normal BMI-unfit were at higher risk of MACE. Physical fitness may contribute to the obesity paradox in women, warranting future studies to better understand associations between body weight, body composition, and physical fitness to improve cardiovascular outcomes in women. 10.1093/eurjpc/zwac046
    Different Metabolic Phenotypes of Obesity and Risk of Coronary Artery Calcium Progression and Incident Cardiovascular Disease Events: The CARDIA Study. Arteriosclerosis, thrombosis, and vascular biology BACKGROUND:To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. METHODS:A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. RESULTS:During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. CONCLUSIONS:Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. REGISTRATION:URL: https://www. CLINICALTRIALS:gov; Unique identifier: NCT00005130. 10.1161/ATVBAHA.122.317526
    [Establishment of a nomogram prediction model for coronary artery disease risk in elderly patients with acute myocardial infarction]. Yang Yanmei,Yang Dongliang,Zhao Wentao,He Xuejuan,Wang Xin,Wang Jiawang,Liu Fan,Meng Qinglan Zhonghua wei zhong bing ji jiu yi xue OBJECTIVE:To establish a nomogram model for predicting the risk of coronary artery disease in elderly patients with acute myocardial infarction (AMI). METHODS:The clinical data of elderly patients with AMI who underwent coronary angiography in the department of cardiology of Cangzhou Central Hospital from July 2015 to March 2020 were analyzed, including age, gender, smoking history, underlying diseases, family history, blood pressure, left ventricular ejection fraction (LVEF), and several biochemical indicators at admission, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein [Lp(a)], apolipoproteins (ApoA, ApoB), ApoA/B ratio, total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), fasting blood glucose (FBG) and uric acid (UA). Patients were divided into model group (2 484 cases) and validation group (683 cases) according to the ratio of 8:2. According to Gensini score, the model group and validation group were divided into mild lesion group (0-20 points) and severe lesion group (≥ 81 points). The differences of each index between different coronary lesion degree groups were compared. Lasso regression and Logistic regression were used to analyze the risk factors of aggravating coronary lesion risk in elderly patients with AMI, and then the nomogram prediction model was established for evaluation and external validation. RESULTS:(1) In the model group, there were significant differences in the family history of coronary heart disease, FBG and HDL-C between the mild lesion group (411 cases) and the severe lesion group (417 cases) [family history of coronary heart disease: 3.6% vs. 7.7%, FBG (mmol/L): 5.88±1.74 vs. 6.43±2.06, HDL-C (mmol/L): 1.48±0.69 vs. 1.28±0.28, all P < 0.05]. In the validation group, there were significant differences between the mild lesion group (153 cases) and the severe lesion group [132 cases; FBG (mmol/L): 5.58±0.88 vs. 6.85±0.79, HDL-C (mmol/L): 1.59±0.32 vs. 1.16±0.21, both P < 0.05]. (2) Lasso regression analysis showed that family history of coronary heart disease, FBG, and HDL-C were risk factors of coronary artery disease in elderly patients with AMI, with coefficients 0.118, 0.767, and -0.558, respectively. Logistic regression analysis showed that FBG [odds ratio (OR) = 1.479, 95% confidence interval (95%CI) was 1.051-2.082, P = 0.025] and HDL-C (OR = 0.386, 95%CI was 0.270-0.553, P < 0.001] were independent risk factors of coronary artery disease in elderly patients with AMI. (3) According to the rank score of FBG and HDL-C, the nomogram prediction risk model of aggravating coronary artery disease degree was established for each patient. It was concluded that the risk of coronary artery disease in elderly people with higher FBG level and (or) lower HDL-C level was significantly increased. (4) The nomogram model constructed with the model group data predicted the risk concordance index (C-index) was 0.689, and the C-index of the external validation group was 0.709. CONCLUSIONS:FBG and HDL-C are independent risk factors for aggravating coronary artery disease in elderly patients with AMI. The nomogram model of aggravating coronary artery disease in elderly patients with AMI has good predictive ability, which can provide more intuitive research methods and clinical value for preventing the aggravation of coronary artery disease in elderly patients. 10.3760/cma.j.cn121430-20200604-00797
    Obesity and hypertension. Jiang Shu-Zhong,Lu Wen,Zong Xue-Feng,Ruan Hong-Yun,Liu Yi Experimental and therapeutic medicine The imbalance between energy intake and expenditure is the main cause of excessive overweight and obesity. Technically, obesity is defined as the abnormal accumulation of ≥20% of body fat, over the individual's ideal body weight. The latter constitutes the maximal healthful value for an individual that is calculated based chiefly on the height, age, build and degree of muscular development. However, obesity is diagnosed by measuring the weight in relation to the height of an individual, thereby determining or calculating the body mass index. The National Institutes of Health have defined 30 kg/m as the limit over which an individual is qualified as obese. Accordingly, the prevalence of obesity in on the increase in children and adults worldwide, despite World Health Organization warnings. The growth of obesity and the scale of associated health issues induce serious consequences for individuals and governmental health systems. Excessive overweight remains among the most neglected public health issues worldwide, while obesity is associated with increasing risks of disability, illness and death. Cardiovascular diseases, the leading cause of mortality worldwide, particularly hypertension and diabetes, are the main illnesses associated with obesity. Nevertheless, the mechanisms underlying obesity-associated hypertension or other associated metabolic diseases remains to be adequately investigated. In the present review, we addressed the association between obesity and cardiovascular disease, particularly the biological mechanisms linking obesity and hypertension. 10.3892/etm.2016.3667
    An Overview and Update on Obesity and the Obesity Paradox in Cardiovascular Diseases. Elagizi Andrew,Kachur Sergey,Lavie Carl J,Carbone Salvatore,Pandey Ambarish,Ortega Francisco B,Milani Richard V Progress in cardiovascular diseases Obesity increases a number of cardiovascular disease (CVD) risk factors, but patients with many types of CVD may have a better prognosis if classified as overweight or obese, a phenomenon known as the "obesity paradox". This paradoxical benefit of a medically unfavorable phenotype is particularly strong in the overweight and class I obesity, and less pronounced in the more severe or morbidly obese populations (class II-III and greater). Rather than an obesity paradox, it is possible that this phenomenon may represent a "lean paradox", in which individuals classified as normal weight or underweight may have a poorer prognosis with respect to CVD, as a result of a progressive catabolic state and lean mass loss. Cardiorespiratory fitness (CRF) is a fundamental part of this discussion. A greater CRF is associated with lower CVD risk, regardless of body mass index (BMI). Also, the assessment of body composition compartments (i.e., fat mass, fat-free mass, lean mass) and the presence of metabolic derangements may be better indicators of CVD risk than BMI alone. The focus of this review is to summarize the current evidence of the obesity paradox. Moreover, we discuss the utility and limitations of BMI for cardiometabolic risk stratification, in addition to concepts such as "metabolically healthy obesity" (MHO) and the "fat but fit" phenomenon, which describe patients who are diagnosed with obesity using BMI, but without major metabolic derangements and with greater CRF, respectively. Finally, we propose that obese patients presenting with an excess body fat, yet without metabolic abnormalities, should still be viewed as an "at risk" population, and as such should receive advice to change their lifestyle to improve their CRF and to prevent the development of impaired fasting glucose, diabetes mellitus and other CVD risk factors as a form of primary prevention. 10.1016/j.pcad.2018.07.003
    Body composition and the obesity paradox in coronary heart disease: can heavier really be healthier? Lavie Carl J,De Schutter Alban,Milani Richard V Heart (British Cardiac Society) 10.1136/heartjnl-2015-307966
    Short- and long-term systolic blood pressure changes have different impacts on major adverse cardiovascular events: Results from a 12.5 years follow-up study. Zheng Jia,Xie Yanxia,Wang Yali,Guo Rongrong,Dai Yue,Sun Zhaoqing,Xing Liying,Zhang Xingang,Sun Yingxian,Zheng Liqiang International journal of cardiology BACKGROUND:Systolic blood pressure increased in middle-aged person contributes significantly to the risk of major adverse cardiovascular events (MACE). Meanwhile, different patterns (short- or long-term change) of SBP increase may result in differential risk and lead to differences in predictive ability. METHODS:A total of 19,544 and 22,610 participants in the Fuxin Cardiovascular Cohort Study underwent measurement of SBP at 2 examinations for short- and long-term change study population. Cox proportional hazards models were used to relate future clinical outcomes with change in SBP. RESULTS:During a median follow-up period of 12.5 years, 1064 (772 stroke, 247 myocardial infarction, 528 CVD deaths) and 1316 (958 stroke, 301 myocardial infarction, 660 CVD deaths) MACE were identified during short- and long-terms SBP change, respectively. For SBP increased participants, short-term change in SBP was associated with future MACE (hazard ratio [HR]: 1.241 per 1-SD increase; 95% confidence interval [CI]: 1.146-1.344; P < 0.001), long-term change in SBP (HR: 1.218; 95% CI: 1.123-1.322; P < 0.001). For prehypertension participants, long-term changes conferred a strong impact than short-term. For hypertensive participants, short-term changes conferred a strong impact than long-term. CONCLUSIONS:Having a SBP rise in short- or long-term both confer an increased risk of MACE and its subgroups. Furthermore, short- and long-term SBP increase patterns adds different additional information beyond one single baseline examination. Change in SBP may be a prognostic surrogate marker and future studies are needed to clarify the possible mechanism for predicting MACE. 10.1016/j.ijcard.2019.11.122
    Severe Hypoglycemia, Cardiac Structure and Function, and Risk of Cardiovascular Events Among Older Adults With Diabetes. Echouffo-Tcheugui Justin B,Daya Natalie,Lee Alexandra K,Tang Olive,Ndumele Chiadi E,Windham B Gwen,Shah Amil M,Selvin Elizabeth Diabetes care OBJECTIVE:To assess the association of severe hypoglycemia measured at baseline with cardiovascular disease (CVD) among community-dwelling older individuals with diabetes, a group particularly susceptible to hypoglycemia. RESEARCH DESIGN AND METHODS:We included older adults with diabetes from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 5 (2011-2013, baseline). Severe hypoglycemia at baseline was defined with use of first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls. We examined cross-sectional associations of severe hypoglycemia with echocardiographic indices of cardiac structure-function. We prospectively evaluated the risks of incident or recurrent CVD (coronary heart disease, stroke, or heart failure) and all-cause mortality, from baseline to 31 December 2018, using negative binomial and Cox regression models. RESULTS:Among 2,193 participants (mean [SD] age 76 [5] years, 57% female, 32% Blacks), 79 had a history of severe hypoglycemia at baseline. Severe hypoglycemia was associated with a lower left ventricular (LV) ejection fraction (adjusted β-coefficient -3.66% [95% CI -5.54, -1.78]), higher LV end diastolic volume (14.80 mL [95% CI 8.77, 20.84]), higher E-to-A ratio (0.11 [95% CI 0.03, 0.18]), and higher septal E/e' (2.48 [95% CI 1.13, 3.82]). In adjusted models, severe hypoglycemia was associated with incident or recurrent CVD (incidence rate ratio 2.19 (95% CI 1.24, 3.88]) and all-cause mortality (hazard ratio 1.71 [95% CI 1.10, 2.67]) among those without prevalent CVD. CONCLUSIONS:Our findings suggest that a history of severe hypoglycemia is associated with alterations in cardiac function and is an important marker of future cardiovascular risk in older adults. 10.2337/dc20-0552
    Body mass, cardiorespiratory fitness, and cardiometabolic risk over time: Findings from the Cooper Center Longitudinal Study. Leonard David,Shuval Kerem,Finley Carrie E,Barlow Carolyn E,Haskell William L,Farrell Stephen W,Pavlovic Andjelka,DiPietro Loretta,Scheinowitz Mickey,DeFina Laura F Preventive medicine Few studies have adequately assessed the simultaneous effects of changes in cardiorespiratory fitness (fitness) and body mass on cardiometabolic risk. Hence, the current study's aims were twofold: (1) To determine whether increases in body mass result in higher cardiometabolic risk after controlling for fitness changes; and (2) To assess whether increases in fitness result in lower cardiometabolic risk after controlling for weight changes. The study consisted of 3534 patients who came for preventive medicine visits ≥4 times over any 10-year period (1979-2019). The primary independent variables were body mass and fitness, and the dependent variable was metabolic syndrome (MetS) and its components. Mixed-effects regression was used to model the relationship between changes in body mass, fitness, and MetS. Results indicate that increasing body mass up to a 10-year period was significantly related to increasing risk of MetS while controlling for changes in fitness. Specifically, a 1-kg increase in body mass was associated with a 17% (OR = 1.17; 95% CI 1.15-1.19) increased odds for MetS, while adjusting for fitness changes. A 1-MET increase in fitness was related to a 23% (OR = 0.77; 95% CI 0.70-0.84) decrease in odds for MetS, while adjusting for body mass changes up to 10 years. Moreover, body mass change was significantly related to changes in all cardiometabolic components of MetS. Fitness change was significantly associated with changes in MetS components. Future interventions should focus concurrently on increasing fitness and on body mass loss (or maintenance) to improve cardiometabolic health. 10.1016/j.ypmed.2021.106720
    The Change in Metabolic Syndrome Status and the Risk of Nonviral Liver Cirrhosis. Chung Goh-Eun,Chang Young,Cho Yuri,Cho Eun-Ju,Yoo Jeong-Ju,Park Sang-Hyun,Han Kyungdo,Shin Dong-Wook,Yu Su-Jong,Kim Yoon-Jun,Yoon Jung-Hwan Biomedicines BACKGROUND:Nonalcoholic fatty liver disease is considered to be the hepatic component of metabolic syndrome (MetS). However, the association between changes in MetS status and the risk of liver cirrhosis (LC) has not been investigated to date. This study assessed the association between changes in MetS and subsequent nonviral LC development. METHODS:Data were obtained from the Korean National Health Insurance Service. Individuals who participated in health screenings from both 2009 to 2010 and 2011 to 2012 were included. The primary outcome was LC development according to the static and dynamic MetS status. Subjects were stratified into four groups according to the change in MetS status observed from the two-year interval screening (2009-2011). Cox regression analysis was used to examine the hazard ratios of LC. RESULTS:During a median of 7.3 years of follow-up, 24,923 incident LC cases developed among 5,975,308 individuals. After adjusting for age, sex, smoking, alcohol, regular exercise, and body mass index, the adjusted hazard ratios (95% confidence intervals) for LC development were 1.39 (1.33-1.44) for the MetS-Developed group, 1.32 (1.26-1.37) for the MetS-Recovered group, and 1.51 (1.45-1.56) for the MetS-Sustained group, relative to the MetS-Free group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results. CONCLUSIONS:Both static and dynamic MetS status are independent risk factors for LC development. The risk of LC was the highest in people with sustained MetS and was lower in the MetS-Recovered group than in the MetS-Sustained group. These results suggest that improving a person's MetS status may be helpful in preventing LC. 10.3390/biomedicines9121948
    Genetic Determinants of Clustering of Cardiometabolic Risk Factors in U.K. Biobank. Lind Lars Metabolic syndrome and related disorders The metabolic syndrome (MetS) is a description of a clustering of cardiometabolic risk factors in the same individual. This study searched for genetic loci associated with all five prespecified components of MetS to find a common pathophysiological link for this risk factor clustering. Using data from 291,107 individuals in the U.K. biobank, a genome-wide association study (GWAS) was performed versus each of the five components of the syndrome as continuous variables (glucose, systolic blood pressure, triglycerides, waist circumference, and high-density lipoprotein-cholesterol). Using false discovery rate <0.05, three loci were related to all five MetS components (rs7575523; nearest gene , rs3936511; intron of , and rs111970447; intron of ). Of those, seems the most interesting candidate for clustering of risk factors, since previous GWASs in other samples have identified this locus as being related to all five risk factors. Also, genetic loci being related to the different combinations of four or three MetS components were presented. Generally, each MetS component combination was related to a unique genetic profile, and the genetic overlap between these combinations was low. A genetic locus was discovered being related to each of the five MetS components, being a candidate for a common pathophysiological link for risk factor clustering. In addition, genetic loci being related to different combinations of four or three MetS components were presented, and the genetic overlap between those combinations of MetS was low. 10.1089/met.2019.0096
    Risk for cardiovascular disease associated with metabolic syndrome and its components: a 13-year prospective study in the RIVANA cohort. Guembe María J,Fernandez-Lazaro Cesar I,Sayon-Orea Carmen,Toledo Estefanía,Moreno-Iribas Conchi, Cardiovascular diabetology BACKGROUND:We aimed to investigate the association of metabolic syndrome (MetS) and its single components with cardiovascular risk and estimated their impact on the prematurity of occurrence of cardiovascular events using rate advancement periods (RAPs). METHODS:We performed prospective analyses among 3976 participants (age range: 35-84, 55% female) in the Vascular Risk in Navarre (RIVANA) Study, a Mediterranean population-based cohort. MetS was defined based on the modified criteria of the American Heart Association/National Heart, Lung, and Blood Institute and the International Diabetes Federation. The primary endpoint was major cardiovascular event (a composite of myocardial infarction, stroke, or mortality from cardiovascular causes). Secondary endpoints were incidence of non-fatal myocardial infarction and non-fatal stroke, cardiovascular mortality, and all-cause mortality. Cox proportional hazards models, adjusted for potential confounders, were fitted to evaluate the association between MetS and its single components at baseline with primary and secondary endpoints. RESULTS:During a median follow-up of 12.8 years (interquartile range, 12.5-13.1), we identified 228 primary endpoint events. MetS was associated with higher risk of incidence of major cardiovascular event, cardiovascular and all-cause mortality, but was neither associated with higher risk of myocardial infarction nor stroke. Compared with participants without MetS, the multivariable hazard ratio (95% confidence interval [CI]) among participants with MetS was 1.32 (1.01-1.74) with RAP (95% CI) of 3.23 years (0.03, 6.42) for major cardiovascular event, 1.64 (1.03-2.60) with RAP of 3.73 years (0.02, 7.45) for cardiovascular mortality, and 1.45 (1.17-1.80) with RAP of 3.24 years (1.21, 5.27) for all-cause mortality. The magnitude of the associations of the single components of MetS was similar than the predicted by MetS. Additionally, for each additional trait of MetS, incidence of major cardiovascular event relatively increased by 22% (1.22, 95% CI 1.09-1.36) with RAP of 2.31 years (0.88, 3.74). CONCLUSIONS:MetS was independently associated with CVD risk, cardiovascular and all-cause mortality. Components of the MetS were associated with similar magnitude of increased CVD, which suggests that MetS was not in excess of the level explained by the presence of its single components. Further research should explore the association of different combinations of the components of MetS with CVD. 10.1186/s12933-020-01166-6
    Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease. Parra-Peralbo Esmeralda,Talamillo Ana,Barrio Rosa Frontiers in cell and developmental biology Adipose tissue is a dynamic organ, well known for its function in energy storage and mobilization according to nutrient availability and body needs, in charge of keeping the energetic balance of the organism. During the last decades, adipose tissue has emerged as the largest endocrine organ in the human body, being able to secrete hormones as well as inflammatory molecules and having an important impact in multiple processes such as adipogenesis, metabolism and chronic inflammation. However, the cellular progenitors, development, homeostasis and metabolism of the different types of adipose tissue are not fully known. During the last decade, has demonstrated to be an excellent model to tackle some of the open questions in the field of metabolism and development of endocrine/metabolic organs. Discoveries ranged from new hormones regulating obesity to subcellular mechanisms that regulate lipogenesis and lipolysis. Here, we review the available evidences on the development, types and functions of adipose tissue in and identify some gaps for future research. This may help to understand the cellular and molecular mechanism underlying the pathophysiology of this fascinating key tissue, contributing to establish this organ as a therapeutic target. 10.3389/fcell.2021.786129
    The metabolic syndrome, thiazolidinediones, and implications for intersection of chronic and inflammatory disease. Colca Jerry R,Scherer Philipp E Molecular metabolism BACKGROUND:Chronic disease appears connected to obesity. However, evidence suggests that chronic metabolic diseases are more specifically related to adipose dysfunction rather than to body weight itself. SCOPE OF REVIEW:Further study of the first generation "insulin sensitizer" pioglitazone and molecules based on its structure suggests that is possible to decouple body weight from the metabolic dysfunction that drives adverse outcomes. The growing understanding of the mechanism of action of these agents together with advances in the pathophysiology of chronic metabolic disease offers a new approach to treat chronic conditions, such as type 2 diabetes, fatty liver disease, and their common organ and vascular sequelae. MAJOR CONCLUSIONS:We hypothesize that treating adipocyte dysfunction with new insulin sensitizers might significantly impact the interface of infectious disease and chronic metabolic disease. 10.1016/j.molmet.2021.101409
    The Influence of the Western Diet on Microbiota and Gastrointestinal Immunity. Annual review of food science and technology Diet exerts a major influence upon host immune function and the gastrointestinal microbiota. Although components of the human diet (including carbohydrates, fats, and proteins) are essential sources of nutrition for the host, they also influence immune function directly through interaction with innate and cell-mediated immune regulatory mechanisms. Regulation of the microbiota community structure also provides a mechanism by which food components influence host immune regulatory processes. Here, we consider the complex interplay between components of the modern (Western) diet, the microbiota, and host immunity in the context of obesity and metabolic disease, inflammatory bowel disease, and infection. 10.1146/annurev-food-052720-011032
    Associations between DNA methylation and BMI vary by metabolic health status: a potential link to disparate cardiovascular outcomes. Do Whitney L,Nguyen Steve,Yao Jie,Guo Xiuqing,Whitsel Eric A,Demerath Ellen,Rotter Jerome I,Rich Stephen S,Lange Leslie,Ding Jingzhong,Van Den Berg David,Liu Yongmei,Justice Anne E,Guan Weihua,Horvath Steve,Assimes Themistocles L,Bhatti Parveen,Jordahl Kristina,Shadyab Aladdin,Valencia Celina I,Stein Aryeh D,Smith Alicia,Staimez Lisa R,Conneely Karen,Narayan K M Venkat Clinical epigenetics BACKGROUND:Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. RESULTS:The discovery study population was derived from three Women's Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6-10% in two sites over 25 years. CONCLUSIONS:Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health. 10.1186/s13148-021-01194-3
    Obesity Duration, Severity, and Distribution Trajectories and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study. Journal of the American Heart Association Background Research examining the role of obesity in cardiovascular disease (CVD) often fails to adequately consider heterogeneity in obesity severity, distribution, and duration. Methods and Results We here use multivariate latent class mixed models in the biracial Atherosclerosis Risk in Communities study (N=14 514; mean age=54 years; 55% female) to associate obesity subclasses (derived from body mass index, waist circumference, self-reported weight at age 25, tricep skinfold, and calf circumference across up to four triennial visits) with total mortality, incident CVD, and CVD risk factors. We identified four obesity subclasses, summarized by their body mass index and waist circumference slope as decline (4.1%), stable/slow decline (67.8%), moderate increase (24.6%), and rapid increase (3.6%) subclasses. Compared with participants in the stable/slow decline subclass, the decline subclass was associated with elevated mortality (hazard ratio [HR] 1.45, 95% CI 1.31, 1.60, <0.0001) and with heart failure (HR 1.41, 95% CI 1.22, 1.63, <0.0001), stroke (HR 1.53, 95% CI 1.22, 1.92, =0.0002), and coronary heart disease (HR 1.36, 95% CI 1.14, 1.63, =0.0008), adjusting for baseline body mass index and CVD risk factor profile. The moderate increase latent class was not associated with any significant differences in CVD risk as compared to the stable/slow decline latent class and was associated with a lower overall risk of mortality (HR 0.85, 95% CI 0.80, 0.90, <0.0001), despite higher body mass index at baseline. The rapid increase latent class was associated with a higher risk of heart failure versus the stable/slow decline latent class (HR 1.34, 95% CI 1.10, 1.62, =0.004). Conclusions Consideration of heterogeneity and longitudinal changes in obesity measures is needed in clinical care for a more precision-oriented view of CVD risk. 10.1161/JAHA.121.019946
    Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies. European heart journal AIMS:The aim of this study was to investigate the causal relationship and evidence of an association between increased adiposity and the risk of incident cardiovascular disease (CVD) events or mortality. METHODS AND RESULTS:Observational (informing association) and Mendelian randomization (MR) (informing causality) studies were assessed to gather mutually complementary insights and elucidate perplexing epidemiological relationships. Systematic reviews and meta-analyses of observational and MR studies that were published until January 2021 and evaluated the association between obesity-related indices and CVD risk were searched. Twelve systematic reviews with 53 meta-analyses results (including over 501 cohort studies) and 12 MR studies were included in the analysis. A body mass index (BMI) increase was associated with higher risks of coronary heart disease, heart failure, atrial fibrillation, all-cause stroke, haemorrhagic stroke, ischaemic stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thrombo-embolism. The MR study results demonstrated a causal effect of obesity on all indices but stroke. The CVD risk increase for every 5 kg/m2 increase in BMI varied from 10% [relative risk (RR) 1.10; 95% confidence interval (CI) 1.01-1.21; certainty of evidence, low] for haemorrhagic stroke to 49% (RR 1.49; 95% CI 1.40-1.60; certainty of evidence, high) for hypertension. The all-cause and CVD-specific mortality risks increased with adiposity in cohorts, but the MR studies demonstrated no causal effect of adiposity on all-cause mortality. CONCLUSION:High adiposity is associated with increased CVD risk despite divergent evidence gradients. Adiposity was a causal risk factor for CVD except all-cause mortality and stroke. Half (49%; 26/53) of the associations were supported by high-level evidence. The associations were consistent between sexes and across global regions. This study provides guidance on how to integrate evidence from observational (association) and genetics-driven (causation) studies accumulated to date, to enable a more reliable interpretation of epidemiological relationships. 10.1093/eurheartj/ehab454
    [Relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people: a cohort study]. Zhang L N,Zheng X X,Song L L,Li H,Liu B Q,Wu M Y,Wang L L,Wang Y J Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] To explore the relationship between weight change and the changes in blood pressure, blood glucose and blood lipid profiles in middle-aged and elderly Chinese people. All participants were from the Dongfeng-Tongji cohort study. The study included 16 606 middle-aged and elderly Chinese people with complete information in the baseline survey in 2008 and the first follow-up survey in 2013. We collected the data on demographic characteristics, lifestyle, history of diseases and medication, and the results of medical health examinations, including height, weight, blood pressure, fasting blood glucose and lipid profiles. We divided the weight change into five groups, moderate or above weight loss (<-8.0%), slight weight loss (-8.0%, -3.1%), weight maintenance (-3.0%, 3.0%), slight weight increased (3.1%, 8.0%), and moderate or above weight increased (>8.0%). Generalized linear regression model was used to analyze the relationship between weight change and the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG). Subgroup analyses were used to explore the influences of gender, age and baseline BMI level on the relationship between weight change and the above-mentioned metabolic indicators. The average age of participants in baseline survey was (62.19±7.28) years with a range of 45 to 89 years. During the five-year period, there were 18.86% (2 633), 28.03% (4 655), 35.87% (5 956), 13.96% (2 319), 6.28% (1 043) people with moderate or above weight loss, slight weight loss, weight maintenance, slight weight increased, and moderate or above weight increased, respectively. Regression analyses showed that body weight change were positively correlated with changes in SBP, DBP, FBG, TC, LDL-C and TG, and negatively correlated with change in HDL-C (all linear trend values were<0.05); As every 10% of weight changed, the β (95) of changes in SBP (mmHg) (1 mmHg=0.133 kPa), DBP (mmHg), FBG (mmol/L), TC (mmol/L), LDL-C (mmol/L), HDL-C (mmol/L) and TG (mmol/L) were 4.94 (4.32, 5.55), 2.50 (2.11, 2.88), 0.05 (0.02, 0.08), 0.13 (0.11, 0.16), 0.14 (0.12, 0.16), -0.05 (-0.07, -0.04) and 0.16 (0.14, 0.18), respectively. Furthermore, subgroup analyses showed that weight change can lead to greater changes in blood pressure in older and overweight or obesity elderly people (all for interaction0.05). Weight loss was beneficial for middle-aged and elderly people to improve the blood pressure, blood glucose and blood lipid profiles, regardless of the weight at the baseline, while weight gain was not. 10.3760/cma.j.issn.0253-9624.2018.09.009
    Coronary heart disease mortality trends during 50 years as explained by risk factor changes: The European cohorts of the Seven Countries Study. Menotti Alessandro,Puddu Paolo E,Kromhout Daan,Kafatos Anthony,Tolonen Hanna European journal of preventive cardiology OBJECTIVES:The purpose of this study was to relate risk factor changes during decades with 50-year coronary heart disease mortality in European cohorts of middle-aged men of the Seven Countries Study. MATERIAL AND METHODS:In the 1950s-early 1960s, nine cohorts of 6518 men aged 40-59 years were examined in five European countries. Smoking habits, systolic blood pressure and serum cholesterol were measured at entry and five times during the next 35 years and a comprehensive Risk Factor Change Score was created. Coronary heart disease mortality data was collected during a 50-year follow-up, modelled by the Weibull distribution, whose shape (Weibull shape) was related to the Risk Factor Change Score by linear regression. RESULTS:The Risk Factor Change Score showed slight declines in the Finnish and Dutch cohorts, moderate or large increases in the other cohorts. These effects were related to a decrease of smoking habits in all cohorts, an increase of blood pressure in all cohorts except East Finland, a decrease of serum cholesterol in Finland and the Netherlands, whereas serum cholesterol increases were slight in Italy and large in Serbia and Greece. Weibull distribution shape for coronary heart disease mortality showed slight deceleration in one Finnish and the Dutch cohorts, large acceleration in the Serbian and Greek cohorts. The correlation coefficient of the Risk Factor Change Score versus Weibull shape for the nine cohorts was 0.78 (= 0.60;  = 0.0132). CONCLUSIONS:Spontaneous long-term changes of major coronary risk factor levels were associated with changes in the same direction of coronary heart disease mortality risk modelled by the Weibull distribution, expressing a kind of 'natural experiment' with an outcome that matches those of controlled preventive trials. 10.1177/2047487318821250
    A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN. Satoh Michihiro,Ohkubo Takayoshi,Asayama Kei,Murakami Yoshitaka,Sugiyama Daisuke,Waki Takashi,Tanaka-Mizuno Sachiko,Yamada Michiko,Saitoh Shigeyuki,Sakata Kiyomi,Irie Fujiko,Sairenchi Toshimi,Ishikawa Shizukiyo,Kiyama Masahiko,Okayama Akira,Miura Katsuyuki,Imai Yutaka,Ueshima Hirotsugu,Okamura Tomonori, Journal of atherosclerosis and thrombosis AIM:Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS:We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP <130/<80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS:During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS:High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments. 10.5551/jat.52613
    Brown adipose tissue is associated with cardiometabolic health. Nature medicine White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear. Here we retrospectively categorized 134,529 F-fluorodeoxyglucose positron emission tomography-computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health. 10.1038/s41591-020-1126-7
    Associations of blood pressure categories according to the 2017 American College of Cardiology/American Heart Association hypertension guideline and long-term blood pressure change with incident cardiovascular disease in middle-aged and elderly Chinese: the Dongfeng-Tongji cohort study. Ma Lin,Guo Wenting,Yang Liangle,Lai Xuefeng,Fang Qin,Liu Miao,Yang Huihua,Zhou Lve,Wang Hao,Xiao Yang,He Meian,Guo Huan,Wang Chongjian,Zhang Xiaomin Journal of hypertension OBJECTIVE:To assess the associations of newly defined blood pressure (BP) categories by the 2017 American College of Cardiology/American Heart Association guideline and changes in BP with the risk of cardiovascular disease (CVD) among the middle-aged and older Chinese. METHODS:Among 29 086 participants aged 61.6 years from the Dongfeng-Tongji (DFTJ) cohort, we estimated the hazard ratio for CVD using Cox proportional hazard models. RESULTS:As BP increased, we found a significant trend for greater risk of incident CVD, coronary heart disease (CHD) or stroke. Compared with the BP <120/<80 mmHg, those having stage 1 hypertension (BP of 130-139/80-89 mmHg) had an increased risk of CVD [hazard ratio of 1.29 (1.18-1.42)], CHD [hazard ratio of 1.27 (1.15-1.41)] and stroke [hazard ratio of 1.36 (1.10-1.70)], respectively. The effect of stroke was only presented in those aged at least 60 years, but not for those aged less than 60 years; whereas no age-specific association for CHD and CVD was found. Particularly, significantly increased risk of CVD (18%), CHD (14%) and stroke (37%) appeared even with elevated BP (120-129/<80 mmHg). Over a 5-year period, compared with individuals with stable BP less than 130/80 mmHg, those who maintained stage 1 hypertension had 43% increased risk for CVD, which was more prominent among those age at least 60 years. Relative to stable BP (-5 to 5 mmHg), a rise in SBP at least 15 mmHg and DBP at least 5 mmHg conferred 15 and 16% higher CVD risk; whereas the risk of CVD and CHD had 25 and 22% reduction with a decrease in SBP greater than15 mmHg, but not with DBP. CONCLUSION:Newly defined stage 1 hypertension and elevated BP were associated with increased risk of incident CVD, whereas long-term changes of SBP and DBP had effects of varying degree on CVD incidence. 10.1097/HJH.0000000000002137
    The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease. DiNicolantonio James J,Lucan Sean C,O'Keefe James H Progress in cardiovascular diseases Dietary guidelines continue to recommend restricting intake of saturated fats. This recommendation follows largely from the observation that saturated fats can raise levels of total serum cholesterol (TC), thereby putatively increasing the risk of atherosclerotic coronary heart disease (CHD). However, TC is only modestly associated with CHD, and more important than the total level of cholesterol in the blood may be the number and size of low-density lipoprotein (LDL) particles that contain it. As for saturated fats, these fats are a diverse class of compounds; different fats may have different effects on LDL and on broader CHD risk based on the specific saturated fatty acids (SFAs) they contain. Importantly, though, people eat foods, not isolated fatty acids. Some food sources of SFAs may pose no risk for CHD or possibly even be protective. Advice to reduce saturated fat in the diet without regard to nuances about LDL, SFAs, or dietary sources could actually increase people's risk of CHD. When saturated fats are replaced with refined carbohydrates, and specifically with added sugars (like sucrose or high fructose corn syrup), the end result is not favorable for heart health. Such replacement leads to changes in LDL, high-density lipoprotein (HDL), and triglycerides that may increase the risk of CHD. Additionally, diets high in sugar may induce many other abnormalities associated with elevated CHD risk, including elevated levels of glucose, insulin, and uric acid, impaired glucose tolerance, insulin and leptin resistance, non-alcoholic fatty liver disease, and altered platelet function. A diet high in added sugars has been found to cause a 3-fold increased risk of death due to cardiovascular disease, but sugars, like saturated fats, are a diverse class of compounds. The monosaccharide, fructose, and fructose-containing sweeteners (e.g., sucrose) produce greater degrees of metabolic abnormalities than does glucose (either isolated as a monomer, or in chains as starch) and may present greater risk of CHD. This paper reviews the evidence linking saturated fats and sugars to CHD, and concludes that the latter is more of a problem than the former. Dietary guidelines should shift focus away from reducing saturated fat, and from replacing saturated fat with carbohydrates, specifically when these carbohydrates are refined. To reduce the burden of CHD, guidelines should focus particularly on reducing intake of concentrated sugars, specifically the fructose-containing sugars like sucrose and high-fructose corn syrup in the form of ultra-processed foods and beverages. 10.1016/j.pcad.2015.11.006
    Prevalence and impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome. Zhou Jinying,Liu Chen,Zhou Peng,Li Jiannan,Chen Runzhen,Wang Ying,Zhao Xiaoxiao,Zhao Hanjun,Song Li,Yan Hongbing Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIMS:Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular diseases in patients initially free from these diseases. However, its prognostic value in patients with established coronary artery diseases remains controversial. Therefore, we aimed to illustrate the prevalence and investigate the impact of MetS in patients with multivessel coronary artery disease (MVD) and acute coronary syndrome (ACS). METHODS AND RESULTS:This was a large registry of consecutive patients with ACS referred to primary percutaneous coronary intervention (PCI) and those with MVD were eligible for this analysis. MetS was defined based on modified Adult Treatment Panel III definition. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction and stroke. A total of 2532 patients were included in the current analysis and 993 (39.2%) of them had MetS. The prevalence of MetS increased from 2010 to 2016 (p  = 0.005). In patients over 60 years old, the prevalence of MetS decreased with aging (p  = 0.002). Female subjects had a higher prevalence than their male counterparts (61.5% verse 32.9% and p < 0.001). Over a median follow-up of 2.3 years, MetS was not significantly associated with MACE (adjusted 95% CI from 0.92 to 1.54). CONCLUSION:MetS was frequently observed in patients with MVD and ACS. Patients with MetS were more likely to be young and female. However, it was not an independent predictor for MACE after primary PCI in those patients. 10.1016/j.numecd.2021.05.029
    Metabolic syndrome and its individual components with mortality among patients with coronary heart disease. Chen Qian,Zhang Yuan,Ding Ding,Li Dan,Xia Min,Li Xinrui,Yang Yunou,Li Qing,Hu Gang,Ling Wenhua International journal of cardiology BACKGROUND:The metabolic syndrome (MetS) and its metabolic risk factors appear to promote the development of atherosclerotic cardiovascular disease. The aim of this study was to examine the association of MetS and its individual components with all-cause and cardiovascular mortality among patients with coronary heart disease (CHD). METHODS:We performed a prospective, hospital-based cohort among 3599 CHD patients in China. Cox proportional hazards regression models were used to estimate the association of MetS and its components at baseline with risk of mortality. RESULTS:During a mean follow-up period of 4.9years, 308 deaths were identified, 200 of which were due to cardiovascular disease. Compared with patients without MetS, patients with MetS according to the AHA/NHLBI statement had a 1.26-fold higher risk (95% CI, 1.01-1.59) of all-cause mortality and a 1.41-fold higher risk (1.06-1.87) of cardiovascular mortality. Patients with increasing numbers of components of MetS had a gradually increased risk for all-cause and cardiovascular mortality (P<0.05). When each component of MetS was considered as a dichotomized variable separately, only low high-density lipoprotein cholesterol (HDL-C) and elevated fasting blood glucose (FBG) were associated with all-cause and cardiovascular mortality. After using restricted cubic splines, we found a U-shaped association of HDL-C, body mass index and blood pressure, a positive association of FBG, and no association of triglycerides with the risks of all-cause and cardiovascular mortality. CONCLUSIONS:MetS is a risk factor for all-cause and cardiovascular mortality among CHD patients. It is very important to control metabolic components in a reasonable control range. 10.1016/j.ijcard.2016.08.324
    Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study. Wang Jingya,Niratharakumar Krishnarajah,Gokhale Krishna,Tahrani Abd A,Taverner Tom,Thomas G Neil,Dasgupta Indranil American journal of kidney diseases : the official journal of the National Kidney Foundation RATIONALE & OBJECTIVE:Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. STUDY DESIGN:Retrospective population-based cohort study. SETTING & PARTICIPANTS:4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. EXPOSURE:11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). OUTCOME:Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of<60mL/min/1.73m for≥90 days, or a urinary albumin-creatinine ratio>3mg/mmol for≥90 days. RESULTS:Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4±4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n=1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. LIMITATIONS:Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. CONCLUSIONS:Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality. 10.1053/j.ajkd.2021.05.008
    Prevalence of metabolic syndrome and individual metabolic abnormalities in China, 2002-2012. He Yuna,Li Yanping,Bai Guoyin,Zhang Jian,Fang Yuehui,Zhao Liyun,Zhao Wenhua,Yang Xiaoguang,Ding Gangqiang Asia Pacific journal of clinical nutrition BACKGROUND AND OBJECTIVES:The purpose of our study was to estimate the national prevalence of metabolic syndrome, its individual components and its changes in the past decade. METHODS AND STUDY DESIGN:Two national-representative cross-sectional surveys: the China National Nutrition and Health Survey 2002 (CNNHS 2002) and the Chinese National Nutrition and Health Surveillance 2010-2012 (CNNHS 2010-2012). A total of 48,235 and 104,098 participants aged 18 years or older who had completed data on physical examination, blood lipids, and fasting glucose tests from CNNHS 2002 and CNNHS 2010-2012, respectively, were included in current study. RESULTS:The prevalence of metabolic syndrome in Chinese adults increased from 9.5% (95% confident interval [CI]: 9.2%-9.7%) in 2002 to 18.7% (18.3%-19.1%) in 2010-2012, corresponding to an estimated 83.6 million adults in 2002 and 189 million adults in 2010-2012 living with metabolic syndrome in China. The increment was more than doubled among young, rural residents and those from poor households. Abdominal obesity, hyperglycemia, high triglycerides, low HDL-C, and elevated blood pressure were found in 18.9% (18.5%-19.3%), 6.4% (6.2%-6.7%), 13.8% (13.5%-14.2%), 19.3% (18.9%-19.7%), and 34.0% (33.5%-34.5%) of adults in 2002, respectively, which was 25.8% (25.3%-26.2%), 16.2% (15.8%-16.5%), 23.7% (23.3%-24.2%), 32.6% (32.0%-33.1%), and 34.4% (33.9%-34.9%), respectively, in 2010-2012. CONCLUSIONS:Based on two nationally representative surveys, our results indicated that the prevalence of metabolic syndrome is widespread and increasing in China. 10.6133/apjcn.201909_28(3).0023
    Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants. ,Lu Yuan,Hajifathalian Kaveh,Ezzati Majid,Woodward Mark,Rimm Eric B,Danaei Goodarz Lancet (London, England) BACKGROUND:Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. METHODS:We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57,161 coronary heart disease and 31,093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m(2), or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. FINDINGS:The HR for each 5 kg/m(2) higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m(2)) and obesity (BMI ≥30 kg/m(2)) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m(2)), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. INTERPRETATION:Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits. FUNDING:US National Institute of Health, UK Medical Research Council, National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, Lown Scholars in Residence Program on cardiovascular disease prevention, and Harvard Global Health Institute Doctoral Research Grant. 10.1016/S0140-6736(13)61836-X
    Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus: A Mendelian Randomization Analysis. Dale Caroline E,Fatemifar Ghazaleh,Palmer Tom M,White Jon,Prieto-Merino David,Zabaneh Delilah,Engmann Jorgen E L,Shah Tina,Wong Andrew,Warren Helen R,McLachlan Stela,Trompet Stella,Moldovan Max,Morris Richard W,Sofat Reecha,Kumari Meena,Hyppönen Elina,Jefferis Barbara J,Gaunt Tom R,Ben-Shlomo Yoav,Zhou Ang,Gentry-Maharaj Aleksandra,Ryan Andy, ,Mutsert Renée de,Noordam Raymond,Caulfield Mark J,Jukema J Wouter,Worrall Bradford B,Munroe Patricia B,Menon Usha,Power Chris,Kuh Diana,Lawlor Debbie A,Humphries Steve E,Mook-Kanamori Dennis O,Sattar Naveed,Kivimaki Mika,Price Jacqueline F,Davey Smith George,Dudbridge Frank,Hingorani Aroon D,Holmes Michael V,Casas Juan P Circulation BACKGROUND:The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) and general adiposity (body mass index [BMI]) with cardiometabolic disease. METHODS:Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits. RESULTS:Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio [OR] for CHD, 1.48; 95% confidence interval [CI], 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD). CONCLUSIONS:Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity. 10.1161/CIRCULATIONAHA.116.026560
    Reducing the Population Burden of Coronary Heart Disease by Modifying Adiposity: Estimates From the ARIC Study. Gellert Kapuaola S,Keil Alexander P,Zeng Donglin,Lesko Catherine R,Aubert Ronald E,Avery Christy L,Lutsey Pamela L,Siega-Riz Anna Maria,Windham B Gwen,Heiss Gerardo Journal of the American Heart Association Background Excess adiposity, which affects 69% of US adults, increases coronary heart disease (CHD) risk in an association that manifests below conventional obesity cut points. The population-level impact on CHD risk that is attainable through modest adiposity reductions in populations is not well characterized. We estimated the effect of hypothetical reductions in both body mass index (BMI) and waist circumference (WC) on CHD incidence. Methods and Results The study population included 13 610 ARIC (Atherosclerosis Risk in Communities) participants. Our hypothetical reduction in BMI or WC was applied relative to the temporal trend, with no hypothetical reduction among those with BMI >24 or WC >88 cm, respectively. This threshold for hypothetical reduction is near the clinical guidelines for excess adiposity. CHD risk differences compared the hypothetical reduction with no reduction. Sensitivity analysis was conducted to estimate the effect of applying the hypothetical BMI reduction at the established overweight cut point of 25. Cumulative 12-year CHD incidence with no intervention was 6.3% (95% CI, 5.9-6.8%). Risk differences following the hypothetical BMI and WC reductions were -0.6% (95% CI, -1.0% to -0.1%) and -1.0% (95% CI, -1.4% to -0.5%), respectively. These results were robust for the sensitivity analyses. Consequently, we estimated that this hypothetical reduction of 5% in BMI and WC, respectively, could have prevented 9% and 16%, respectively, of the CHD events occurring in this study population over 12 years, after adjustment for established CHD risk factors. Conclusions Meaningful CHD risk reductions could derive from modest reductions in adiposity attainable through lifestyle modification. 10.1161/JAHA.119.012214
    Weight change during middle age and risk of stroke and coronary heart disease: The Japan Public Health Center-based Prospective Study. Kisanuki Koichi,Muraki Isao,Yamagishi Kazumasa,Kokubo Yoshihiro,Saito Isao,Yatsuya Hiroshi,Sawada Norie,Iso Hiroyasu,Tsugane Shoichiro, Atherosclerosis BACKGROUND AND AIMS:The impact of weight changes in middle age on the incidence of cardiovascular disease has not been well elucidated. We investigated whether a 5-year weight change was associated with risk of stroke and coronary heart disease (CHD) in middle-aged individuals. METHODS:We analyzed data of 74,928 participants aged 40-69 years who provided responses to the baseline and 5-year follow-up questionnaires in the Japan Public Health Center-based Prospective Study. Weight change was calculated by subtracting self-reported weight at baseline from that at 5-year follow-up. Stroke and CHD events were confirmed by reviewing hospital records. RESULTS:During 997,406 person-years of follow-up, we documented 3,975 stroke and 914 CHD events. The multivariable HRs of stroke for losing ≥5 kg compared to stable weight (change ≤2 kg) was 1.17 (95% CI, 1.01-1.37) in men versus 1.33 (1.13-1.57) for losing ≥5 kg and 1.61 (1.36-1.92) for gaining ≥5 kg in women (U-shaped association). These associations did not change after the exclusion of early events. The multivariable HR of CHD for gaining ≥5 kg was 1.22 (0.95-1.58) in men. After exclusion of early events within another 5 years, that positive association became stronger [multivariable HR 1.34 (1.00-1.82)]. CONCLUSIONS:Weight gain during middle age was associated with an increased risk of stroke in women and an increased risk of CHD in men. Weight loss was associated with an increased risk of stroke in both men and women. 10.1016/j.atherosclerosis.2021.02.017
    Obesity paradox in patients with chronic total occlusion of coronary artery. Tsai Chuan-Tsai,Huang Wei-Chieh,Lu Ya-Wen,Teng Hsin-I,Huang Shao-Sung,Tsai Yi-Lin,Lee Wen-Lieng,Lu Tse-Min European journal of clinical investigation BACKGROUND:Obesity is associated with metabolic syndrome which increases further risk of coronary artery disease and adverse cardiovascular events. Impact of body mass index (BMI) on long-term outcome in patients with coronary chronic total occlusion (CTO) is less clear. METHOD AND RESULTS:From January 2005 to November 2020, a total of 1301 patients with coronary angiographic confirmed CTO were enrolled in our study. Patients were divided into two groups: low BMI group: 18-24.99 kg/m and high BMI group ≥25 kg/m . Clinical outcomes were 3-year all-cause mortality, 3-year cardiovascular mortality and 3-year non-fatal myocardial infarct. During the 3-year follow-up period, all-cause mortality was significantly higher in patients with low BMI group compared to those in high BMI groups (14% vs. 6%, p = .0001). Kaplan-Meier analysis showed patients with high BMI groups had significant better survival compared with those in low BMI group (p = .0001). In multivariate analysis, higher BMI was independently associated with decreased risk of 3-year all-cause mortality (Hazard ratio [HR]: 0.534; 95% confidence interval [CI]: 0.349-0.819, p = .004) after controlling for age, renal function, prior history of stroke, coronary artery bypass graft, co-morbidities with peripheral arterial disease, heart failure and revascularization status for CTO. In propensity-matched multivariate analysis, high BMI remained a significant predictor of 3-year all-cause mortality (HR, 0.525; 95% CI, 0.346-0.795, p = .002). CONCLUSION:Higher BMI was associated with better long-term outcome in patients with coronary CTO. 10.1111/eci.13698
    Body mass index and cardiovascular outcomes in patients with acute coronary syndrome by diabetes status: the obesity paradox in a Korean national cohort study. Park Se-Jun,Ha Kyoung Hwa,Kim Dae Jung Cardiovascular diabetology BACKGROUND:The "obesity paradox" has not been elucidated in the long-term outcomes of acute coronary syndrome (ACS). We investigated the association between obesity and cardiovascular (CV) outcomes in ACS patients with and without diabetes. METHODS:We identified 6978 patients with ACS aged 40-79 years from the Korean National Health Insurance Service-Health Screening Cohort between 2002 and 2015. Baseline body mass index (BMI) was categorized as underweight (< 18.5 kg/m), normal weight (18.5-22.9 kg/m), overweight (23.0-24.9 kg/m), obese class I (25.0-29.9 kg/m), and obese class II (≥ 30.0 kg/m). The primary outcome was major adverse CV events (MACE)-CV death, myocardial infarction (MI), and stroke. The secondary outcomes were the individual components of MACE, hospitalization for heart failure (HHF), and all-cause death. RESULTS:After adjustment for confounding variables, compared to normal-weight patients without diabetes (reference group), obese class I patients with and without diabetes had a lower risk of MACE, but only significant in patients without diabetes (with diabetes: hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.78-1.14; without diabetes: HR 0.78, 95% CI 0.62-0.97). Obese class II patient with diabetes had a higher risk of MACE with no statistical significance (HR 1.14, 95% CI 0.82-1.59). Underweight patients with and without diabetes had a higher risk of MACE, but only significant in patients with diabetes (with diabetes: HR 1.79, 95% CI 1.24-2.58; without diabetes: HR 1.23, 95% CI 0.77-1.97). CONCLUSION:In ACS patients, obesity had a protective effect on CV outcomes, especially in patients without diabetes. 10.1186/s12933-020-01170-w
    Cardiometabolic disease risk in metabolically healthy and unhealthy obesity: Stability of metabolic health status in adults. Guo Fangjian,Garvey W Timothy Obesity (Silver Spring, Md.) OBJECTIVE:To assess the stability of metabolic status and body mass index (BMI) status and their relative contribution to risk of diabetes, cardiovascular events, and mortality. METHODS:A total of 14,685 participants from the Atherosclerosis Risk in Communities Study and 4,990 from the Coronary Artery Risk Development in Young Adults Study were included. People with healthy obesity (HO) are defined as those meeting all three indices of blood pressure, blood glucose, and blood lipids. People with unhealthy obesity crossed the risk threshold for all three criteria. RESULTS:In both healthy and unhealthy subgroups, risks for coronary heart disease (CHD), stroke, and mortality were comparable among BMI status during a mean 18.7-year follow-up. When compared with HO, hazard ratios were increased for diabetes (5.56, 95% confidence interval [CI] 4.12-7.48), CHD (5.60, 95% CI 3.14-9.98), stroke (4.84, 95% CI 2.13-10.97), and mortality (2.6, 95% CI 1.88-3.61) in people with unhealthy obesity. BMI only moderately increased the risks for diabetes among healthy subjects. In the Coronary Artery Risk Development in Young Adults Study over 20 years, 17.5% of lean subjects and 67.3% of overweight subjects at baseline developed obesity during follow-up. Despite rising BMI, metabolic status remained relatively stable. CONCLUSIONS:Metabolic status is relatively stable despite rising BMI. HO had lower risks for diabetes, CHD, stroke, and mortality than unhealthy subjects but increased diabetes risks than healthy lean people. Cardiometabolic risk factors confer much higher risk than obesity per se. 10.1002/oby.21344
    [Clinical guidelines for prevention and treatment of type 2 diabetes mellitus in the elderly in China (2022 edition)]. , , , , Zhonghua nei ke za zhi According to the data of seventh national census in China, the elderly population (≥60 years old) accounts for 18.7% (260.4 million) of the total population in 2020. Among them, 30% are diabetes (78.13 million, and more than 95% being type 2 diabetes). Diabetic complications caused by poor glycemic control are the main risk factors influencing the healthy and survival of the elderly, and thus, diabetes prevention and treatment has been to be one of the key actions of Healthy China (2019-2030). The present guideline-"Clinical guidelines for prevention and treatment of type 2 diabetes mellitus in the elderly in China (2022 edition)" is formulated on the basis of the " Expert consensus of the diagnosis and treatment measures for Chinese elderly patients with type 2 diabetes (2018 edition)" and summarizes the domestic and foreign related guidelines for elderly diabetes and research information. The aim of the guide is to optimize the elderly diabetes prevention and control concept, to promote the implementation of standardized clinical prevention, diagnosis and treatment strategy and to improve the level of overall management of diabetes in the elderly. 10.3760/cma.j.cn112138-20211027-00751
    Body-Weight Fluctuations and Outcomes in Coronary Disease. Bangalore Sripal,Fayyad Rana,Laskey Rachel,DeMicco David A,Messerli Franz H,Waters David D The New England journal of medicine BACKGROUND:Body-weight fluctuation is a risk factor for death and coronary events in patients without cardiovascular disease. It is not known whether variability in body weight affects outcomes in patients with coronary artery disease. METHODS:We determined intraindividual fluctuations in body weight from baseline weight and follow-up visits and performed a post hoc analysis of the Treating to New Targets trial, which involved assessment of the efficacy and safety of lowering low-density lipoprotein cholesterol levels with atorvastatin. The primary outcome was any coronary event (a composite of death from coronary heart disease, nonfatal myocardial infarction, resuscitated cardiac arrest, revascularization, or angina). Secondary outcomes were any cardiovascular event (a composite of any coronary event, a cerebrovascular event, peripheral vascular disease, or heart failure), death, myocardial infarction, or stroke. RESULTS:Among 9509 participants, after adjustment for risk factors, baseline lipid levels, mean body weight, and weight change, each increase of 1 SD in body-weight variability (measured according to average successive variability and used as a time-dependent covariate) was associated with an increase in the risk of any coronary event (2091 events; hazard ratio, 1.04; 95% confidence interval [CI], 1.01 to 1.07; P=0.01), any cardiovascular event (2727 events; hazard ratio, 1.04; 95% CI, 1.02 to 1.07; P<0.001), and death (487 events; hazard ratio,1.09; 95% CI, 1.07 to 1.12; P<0.001). Among patients in the quintile with the highest variation in body weight, the risk of a coronary event was 64% higher, the risk of a cardiovascular event 85% higher, death 124% higher, myocardial infarction 117% higher, and stroke 136% higher than it was among those in the quintile with the lowest variation in body weight in adjusted models. CONCLUSIONS:Among participants with coronary artery disease, fluctuation in body weight was associated with higher mortality and a higher rate of cardiovascular events independent of traditional cardiovascular risk factors. (Funded by Pfizer; ClinicalTrials.gov number, NCT00327691 .). 10.1056/NEJMoa1606148
    BMI, Weight Change, and Dementia Risk in Patients With New-Onset Type 2 Diabetes: A Nationwide Cohort Study. Nam Ga Eun,Park Yong Gyu,Han Kyungdo,Kim Mee Kyoung,Koh Eun Sil,Kim Eun Sook,Lee Min-Kyung,Kim Bongsung,Hong Oak-Kee,Kwon Hyuk-Sang Diabetes care OBJECTIVE:This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS:Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models. RESULTS:We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables ( for trend <0.001). The percentage weight change during the 2 years after a diagnosis of type 2 diabetes showed significant U-shaped associations with the risk of all-cause dementia development ( < 0.001); the HRs of the disease increased significantly when weight loss or gain was >10% (1.34 [95% CI 1.11-1.63] and 1.38 [1.08-1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01-1.59]). CONCLUSIONS:A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD. 10.2337/dc18-1667
    Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records. The lancet. Diabetes & endocrinology BACKGROUND:Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). METHODS:In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions. FINDINGS:We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period. INTERPRETATION:A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care. FUNDING:The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research. 10.1016/S2213-8587(21)00207-2
    Altered Risk for Cardiovascular Events With Changes in the Metabolic Syndrome Status: A Nationwide Population-Based Study of Approximately 10 Million Persons. Park Sehoon,Lee Soojin,Kim Yaerim,Lee Yeonhee,Kang Min Woo,Han Kyungdo,Han Seung Seok,Lee Hajeong,Lee Jung Pyo,Joo Kwon Wook,Lim Chun Soo,Kim Yon Su,Kim Dong Ki Annals of internal medicine Background:Population-scale evidence for the association between dynamic changes in metabolic syndrome (MetS) status and alterations in the risk for major adverse cardiovascular events (MACE) is lacking. Objective:To investigate whether recovery from or development of MetS in a population is associated with an altered risk for MACE. Design:Nationwide cohort study. Setting:An analysis based on the National Health Insurance Database of Korea. Participants:A total of 27 161 051 persons who received national health screenings from 2009 to 2014 were screened. Those with a history of MACE were excluded. We determined the MetS status of 9 553 042 persons using the following harmonizing criteria: MetS-chronic (n = 1 486 485), MetS-developed (n = 587 088), MetS-recovery (n = 538 806), and MetS-free (n = 6 940 663). Measurements:The outcome was the occurrence of MACE, including acute myocardial infarction, revascularization, and acute ischemic stroke, identified from the claims database. The incidence rate ratios (IRRs) were calculated with adjustments for body mass index, comorbidity scores, previous metabolic variables, and other clinical or demographic variables. Results:At a median follow-up of 3.54 years, the MetS-recovery group (incidence rate, 4.55 per 1000 person-years) had a significantly lower MACE risk (adjusted IRR, 0.85 [95% CI, 0.83 to 0.87]) than that of the MetS-chronic group (incidence rate, 8.52 per 1000 person-years). The MetS-developed group (incidence rate, 6.05 per 1000 person-years) had a significantly higher MACE risk (adjusted IRR, 1.36 [CI, 1.33 to 1.39]) than that of the MetS-free group (incidence rate, 1.92 per 1000 person-years). Among the MetS components, change in hypertension was associated with the largest difference in MACE risk. Limitation:Limited assessment of mortality and short follow-up. Conclusion:Recovery from MetS was significantly associated with decreased risk for MACE, whereas development of MetS was associated with increased risk. Primary Funding Source:Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. 10.7326/M19-0563
    Impact of the Dynamic Change of Metabolic Health Status on the Incident Type 2 Diabetes: A Nationwide Population-Based Cohort Study. Kim Jung A,Kim Da Hye,Kim Seon Mee,Park Yong Gyu,Kim Nan Hee,Baik Sei Hyun,Choi Kyung Mook,Han Kyungdo,Yoo Hye Jin Endocrinology and metabolism (Seoul, Korea) BACKGROUND:Metabolically healthy obese (MHO) is regarded as a transient concept. We examined the effect of the dynamic change of metabolic health status on the incidence of type 2 diabetes mellitus (T2DM) both in obese and normal weight individuals. METHODS:We analyzed 3,479,514 metabolically healthy subjects aged over 20 years from the Korean National Health Screening Program, who underwent health examination between 2009 and 2010, with a follow-up after 4 years. The relative risk for T2DM incidence until the December 2017 was compared among the four groups: stable metabolically healthy normal weight (MHNW), unstable MHNW, stable MHO, and unstable MHO. RESULTS:During the 4 years, 11.1% of subjects in the MHNW group, and 31.5% in the MHO group converted to a metabolically unhealthy phenotype. In the multivariate adjusted model, the unstable MHO group showed the highest risk of T2DM (hazard ratio [HR], 4.67; 95% confidence interval [CI], 4.58 to 4.77). The unstable MHNW group had a higher risk of T2DM than stable MHO group ([HR, 3.23; 95% CI, 3.16 to 3.30] vs. [HR, 1.81; 95% CI, 1.76 to 1.85]). The stable MHO group showed a higher risk of T2DM than the stable MHNW group. The influence of the transition into a metabolically unhealthy phenotype on T2DM incidence was greater in subjects with aged <65 years, women, and those with weight gain. CONCLUSION:Metabolically healthy phenotype was transient both in normal weight and obese individuals. Maintaining metabolic health was critical for the prevention of T2DM, irrespective of their baseline body mass index. 10.3803/EnM.2019.34.4.406
    Association of long-term dynamic change in body weight and incident hypertension: The Rural Chinese Cohort Study. Zhao Yang,Liu Yu,Sun Haohang,Sun Xizhuo,Yin Zhaoxia,Li Honghui,Ren Yongcheng,Wang Bingyuan,Zhang Dongdong,Liu Xuejiao,Liu Dechen,Zhang Ruiyuan,Liu Feiyan,Chen Xu,Liu Leilei,Cheng Cheng,Zhou Qionggui,Hu Dongsheng,Zhang Ming Nutrition (Burbank, Los Angeles County, Calif.) OBJECTIVES:The association of long-term dynamic change in body weight and incident hypertension among general Chinese adults is still unknown. The aim of this study was to evaluate the hypertension risk in a large prospective study of rural Chinese adult using relative weight gain or loss. METHODS:A total of 10 149 nonhypertensive Chinese adults 18 to 75 y of age completed a questionnaire interview and anthropometric and laboratory measurements at both baseline (2007-2008) and follow-up (2013-2014). Participants were divided into five categories based on relative weight change. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension risk by categories of weight change. RESULTS:During 6 y of follow-up, about one-third of the participants retained a stable weight (33.3%) or gained >6% (32.7%). Only 7.9% lost >6% weight. For every 1% increase in relative body weight, systolic and diastolic blood pressures increased 0.27 and 0.22 mm Hg, respectively. Risk for hypertension was reduced and increased with weight loss >6% (OR, 0.78; 95% CI, 0.61-0.99) and gain >6% (OR, 2.08; 95% CI, 1.79-2.42), respectively, compared with weight loss or gain ≤3%. With baseline prehypertension, compared with maintaining a stable weight, weight loss >6% reduced the risk for hypertension (OR, 0.71; 95% CI, 0.54-0.95). With baseline overweight, compared with maintaining the overweight status during follow-up, changing to normal weight reduced the risk for hypertension (OR, 0.67; 95% CI, 0.49-0.92), but changing to general obesity increased the risk (OR, 1.73; 95% CI, 1.35-2.22). CONCLUSIONS:Long-term excessive weight gain is positively associated with increased risk for incident hypertension. Losing weight by lifestyle modification could be helpful for the primary prevention of hypertension in the general rural Chinese population. 10.1016/j.nut.2018.02.020
    Effect of dynamic change in body mass index on the risk of hypertension: Results from the Rural Chinese Cohort Study. Zhang Ming,Zhao Yang,Sun Haohang,Luo Xinping,Wang Chongjian,Li Linlin,Zhang Lu,Wang Bingyuan,Ren Yongcheng,Zhou Junmei,Han Chengyi,Zhang Hongyan,Yang Xiangyu,Pang Chao,Yin Lei,Feng Tianping,Zhao Jingzhi,Hu Dongsheng International journal of cardiology OBJECTIVES:To examine the effect of change in body mass index (BMI) on incident hypertension by gender and age groups. METHODS:A total of 10,145 non-hypertensive participants 18-75years old from rural areas in the middle of China were selected for this cohort study. Questionnaire interview and anthropometric and laboratory measurements were performed at baseline (during July to August 2007 and July to August 2008) and follow-up (during July to August 2013 and July to October 2014). Multiple logistic regression analysis was used to examine the relationship between change in BMI and incident hypertension. RESULTS:During a mean follow-up of 6.03±0.69years, hypertension developed in 794 of 3986 men and 1184 of 6159 women. Both genders who were obese (BMI ≥28kg/m for Chinese people) at follow-up, regardless of their obesity status at baseline, showed greater risk of hypertension than those who were non-obese (BMI <28kg/m) at both baseline and follow-up. We found a dose-response relationship between change in BMI and incident hypertension. Risk of hypertension was markedly greater with a BMI gain of the highest quartile or more as compared with a BMI reduction of the lowest quartile or more, except for women 60-75years old. CONCLUSIONS:Risk of hypertension was high for non-hypertensive people in rural China with stable obesity. BMI dynamic gain may be related to incident hypertension for men of all ages and young and middle-aged women. 10.1016/j.ijcard.2017.03.025
    The association between body composition and metabolically unhealthy profile of adults with normal weight in Northwest China. Fan Ling,Qiu Jiangwei,Zhao Yu,Yin Ting,Li Xiaoxia,Wang Qingan,Jing Jinyun,Zhang Jiaxing,Wang Faxuan,Liu Xiuying,Liu Lan,Zhao Yi,Zhang Yuhong PloS one OBJECTIVE:Related evidences of metabolically unhealthy profile of adults with normal weight are not well characterized in the Chinese population. This is because they cannot be effectively identified by regular measurements (such as body mass index [BMI]). To overcome this gap in literature, this study aimed at investigating the association between body composition and metabolically unhealthy profile in Chinese adults with normal weight. METHODS:A total of 5427 individuals with normal-weight were recruited from 15820 people living in Ningxia Hui Autonomous Region in Northwest China. Normal-weight was defined as a BMI of 18.5-23.9 kg/m2. Metabolically unhealthy profile was assessed by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Metabolically unhealthy normal-weight (MUHNW) profile was defined in individuals who had normal weight and at least two cardiometabolic risk factors. Generalized linear model was used to investigate the association between body composition measured by bioelectrical impedance and metabolically unhealthy profile in adults with normal-weight. RESULTS:The percentage of metabolically unhealthy profile was 35.86% in adults with normal weight. Different MUHNW distributions were found between males and females depending on age. The percentage of the MUHNW profile significantly increased in women after the age of 55, contrary to men. The association between body composition and MUHNW was affected by age and sex. The increased adiposity indices (fat mass index [FMI], visceral fat level [VFL], waist circumference [WCF]), and reduced skeletal muscle mass ratio [SMR] showed significant differences between MUHNW and metabolically healthy with normal weight (MHNW) (p < 0.05). CONCLUSION:The distribution of MUHNW differed between ages and sexes. FMI, VFL, WCF and SMR could be responsible for the MUHNW adults, providing a new insight into the potential metabolic risks for the adults with normal weight in China. This directs us in the management of the MUHNW for their early prevention. 10.1371/journal.pone.0248782
    Metabolically Healthy and Unhealthy Normal Weight and Obesity. Stefan Norbert Endocrinology and metabolism (Seoul, Korea) Increased fat mass is an established risk factor for the cardiometabolic diseases type 2 diabetes and cardiovascular disease (CVD) and is associated with increased risk of all-cause and CVD mortality. However, also very low fat mass associates with such an increased risk. Whether impaired metabolic health, characterized by hypertension, dyslipidemia, hyperglycemia, insulin resistance, and subclinical inflammation, may explain part of the elevated risk of cardiometabolic diseases that is found in many subjects with very low fat mass, as it does in many obese subjects, is unknown. An important pathomechanism of impaired metabolic health is disproportionate fat distribution. In this article the risk of cardiometabolic diseases and mortality in subjects with metabolically healthy and unhealthy normal weight and obesity is summarized. Furthermore, the change of metabolic health during a longer period of follow-up and its impact on cardiometabolic diseases is being discussed. Finally, the implementation of the concept of metabolic health in daily clinical practice is being highlighted. 10.3803/EnM.2020.301
    Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population. Park Jae-Min,Park Da-Hyun,Song Youhyun,Kim Jung Oh,Choi Ja-Eun,Kwon Yu-Jin,Kim Seong-Jin,Lee Ji-Won,Hong Kyung-Won Scientific reports Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes-metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes. 10.1038/s41598-021-81940-y
    Deciphering Biochemical and Molecular Signatures Associated with Obesity in Context of Metabolic Health. Masih Daisy,Tripathi Jitendra Kumar,Rakhra Gurseen,Vats Annu,Verma Saroj Kumar,Jha Prabhash Kumar,Sharma Manish,Ashraf Mohammad Zahid,Singh Som Nath Genes This study aims to identify the clinical and genetic markers related to the two uncommon nutritional statuses-metabolically unhealthy normal-weight (MUNW) and metabolically healthy overweight/obese (MHOW) individuals in the physically active individuals. Physically active male volunteers ( = 120) were recruited, and plasma samples were analyzed for the clinical parameters. Triglycerides, HDL-Cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein, and insulin resistance were considered as markers of metabolic syndrome. The subjects were classified as 'healthy' (0 metabolic abnormalities) or 'unhealthy' (≥1 metabolic abnormalities) in their respective BMI group with a cut-off at 24.9 kg/m. Analysis of biochemical variables was done using enzyme linked immunosorbent assay (ELISA) kits with further confirmation using western blot analysis. The microarray was conducted, followed by quantitative real-time PCR to identify and analyze differentially expressed genes (DEGs). The MHOW group constituted 12.6%, while the MUNW group constituted 32.4% of the total study population. Pro-inflammatory markers like interleukin-6, tumor necrosis factor (TNF)-α, and ferritin were increased in metabolically unhealthy groups in comparison to metabolically healthy groups. Gene expression profiling of MUNW and MHOW individuals resulted in differential expression of 7470 and 5864 genes, respectively. The gene ontology (GO) biological pathway analysis showed significant enrichment of the 'JAK/STAT signaling pathway' in MUNW and 'The information-processing pathway at the IFN-β enhancer' pathway in MHOW. The gene has genetically emerged as a new distinct gene showing its involvement in insulin resistance. Biochemical, as well as genetic analysis, revealed that MUNW and MHOW are the transition state between healthy and obese individuals with simply having fewer metabolic abnormalities. Moreover, it is possible that the state of obesity is a biological adaptation to cope up with the unhealthy parameters. 10.3390/genes12020290
    Coronary Heart Disease Risk Associated with Primary Isolated Hypertriglyceridemia; a Population-Based Study. Saadatagah Seyedmohammad,Pasha Ahmed K,Alhalabi Lubna,Sandhyavenu Harigopal,Farwati Medhat,Smith Carin Y,Wood-Wentz Christina M,Bailey Kent R,Kullo Iftikhar J Journal of the American Heart Association Background Hypertriglyceridemia is associated with increased risk of coronary heart disease but the association is often attributed to concomitant metabolic abnormalities. We investigated the epidemiology of primary isolated hypertriglyceridemia (PIH) and associated cardiovascular risk in a population-based setting. Methods and Results We identified adults with at least one triglyceride level ≥500 mg/dL between 1998 and 2015 in Olmsted County, Minnesota. We also identified age- and sex-matched controls with triglyceride levels <150 mg/dL. There were 3329 individuals with elevated triglyceride levels; after excluding those with concomitant hypercholesterolemia, a secondary cause of high triglycerides, age <18 years or an incomplete record, 517 patients (49.4±14.0 years, 72.0% men) had PIH (triglyceride 627.6±183.6 mg/dL). The age- and sex-adjusted prevalence of PIH in adults was 0.80% (0.72-0.87); the diagnosis was recorded in 60%, 46% were on a lipid-lowering medication for primary prevention and a triglyceride level <150 mg/dL was achieved in 24.1%. The association of PIH with coronary heart disease was attenuated but remained significant after adjustment for demographic, socioeconomic, and conventional cardiovascular risk factors (hazard ratio [HR], 1.53; 95% CI, 1.06-2.20; = 0.022). There was no statistically significant association between PIH and cerebrovascular disease (HR, 1.06; 95% CI, 0.65-1.73, = 0.813), peripheral artery disease (HR, 1.27; 95% CI, 0.43-3.75; = 0.668), or the composite end point of all 3 (HR, 1.28; 95% CI, 0.92-1.80; =0.148) in adjusted models. Conclusions PIH was associated with incident coronary heart disease events (although there was attenuation after adjustment for conventional risk factors), supporting a causal role for triglycerides in coronary heart disease. The condition is relatively prevalent but awareness and control are low. 10.1161/JAHA.120.019343
    Evidence on the applicability of the ATPIII, IDF and CDS metabolic syndrome diagnostic criteria to identify CVD and T2DM in the Chinese population from a 6.3-year cohort study in mid-eastern China. Zhou Hui,Guo Zhi-rong,Yu Lu-gang,Hu Xiao-shu,Xu Bao-hui,Liu Hai-bo,Wu Ming,Zhou Zheng-yuan Diabetes research and clinical practice AIMS:This study evaluates the effectiveness of three metabolic syndrome (MS) criteria in identifying cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) in the Chinese population. METHODS:3598 subjects were recruited from a cohort study on Prevention of Multiple Metabolic disorders and MS in Jiangsu of China (PMMJS), followed at 6.3 years. MS was diagnosed using criteria of the National Cholesterol Education Program's Adult Treatment Panel III (ATPIII), the International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS). Cox regression model was used to analysis the association between MS and onset of CVD and T2DM. Receiver operating characteristic (ROC) curve, sensitivity and specificity were also used to test the ability of three MS criteria to identify CVD or T2DM. RESULTS:Among three criteria, CDS has the highest specificity but lowest sensitivity. Using the CDS criterion, over 50 percent of patients would be misdiagnosed. ATPIII criterion has the shortest distance in ROC curve, lowest false positive rate and false negative rate for identifying CVD and T2DM. ATPIII+/IDF+ has lower ability to predict CVD than ATPIII+/IDF-. ATPIII+/IDF+ and ATPIII+/IDF- has similar ability to predict T2DM. CONCLUSIONS:The ATPIII-MS criterion has the highest ability to predict CVD and T2DM. ATPIII is the best MS criterion for the Chinese population. 10.1016/j.diabres.2010.09.001
    Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Alberti K G M M,Eckel Robert H,Grundy Scott M,Zimmet Paul Z,Cleeman James I,Donato Karen A,Fruchart Jean-Charles,James W Philip T,Loria Catherine M,Smith Sidney C, , , , , , Circulation A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used. 10.1161/CIRCULATIONAHA.109.192644
    Distribution of metabolic/obese phenotypes and association with diabetes: 5 years' cohort based on 22,276 elderly. Liu Miao,Tang Ru,Wang Jianhua,He Yao Endocrine AIMS:To describe the distribution and changes of different metabolic/obese phenotypes among more than 22,000 male elderly in China, and also explore the association with diabetes incidence. METHODS:A cohort study based on 22,276 male elderly was conducted in Beijing, from 2009 to 2013. Multiple Cox model was used to calculate the relative risk. RESULTS:There were only 53.8% of total participants who kept the same phenotype for the 5 years. On the whole, participants with metabolically unhealthy phenotypes had higher relative risks (RRs) than those with metabolically healthy phenotypes. RRs for diabetes showed an increasing trend along with metabolic abnormalities (p < 0.001). However, no statistically significant difference was found across different obese status with the same number of metabolic abnormalities. Changes of metabolic/obese status also showed the same trend. Those who had kept metabolic unhealthy had the highest RRs for diabetes incidence, which was higher than those who kept obesity. CONCLUSIONS:Both metabolically healthy obesity and metabolically unhealthy normal weight phenotypes had an increased risk for diabetes incidence, and metabolic abnormalities might have more influence on diabetes than obesity itself. Changes of metabolic/obese status also had an important impact on diabetes incidence. 10.1007/s12020-018-1672-7
    Metabolic health is a more important determinant for diabetes development than simple obesity: a 4-year retrospective longitudinal study. Rhee Eun-Jung,Lee Min Kyung,Kim Jong Dae,Jeon Won Seon,Bae Ji Cheol,Park Se Eun,Park Cheol-Young,Oh Ki-Won,Park Sung-Woo,Lee Won-Young PloS one BACKGROUND:Recent studies report the importance of metabolic health beyond obesity. The aim of this study is to compare the risk for diabetes development according to different status of metabolic health and obesity over a median follow-up of 48.7 months. METHODS:6,748 non-diabetic subjects (mean age 43 years) were divided into four groups according to the baseline metabolic health and obesity status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO) and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined by having less than 2 components among the 5 components, that is, high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and being in the highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index. Obesity status was assessed by body mass index (BMI) higher than 25 kg/m2. The development of diabetes was assessed annually from self-questionnaire, fasting glucose and HbA1c. RESULTS:At baseline, 45.3% of the subjects were MHNO, 11.3% were MHO, 21.7% were MUHNO, and 21.7% were MUHO. During a median follow-up of 48.7 months, 277 subject (4.1%) developed diabetes. The hazard ratio for diabetes development was 1.338 in MHO group (95% CI 0.67-2.672), 4.321 in MUHNO group (95% CI 2.702-6.910) and 5.994 in MUHO group (95% CI 3.561-10.085) when MHNO group was considered as the reference group. These results were similar after adjustment for the changes of the risk factors during the follow-up period. CONCLUSION:The risk for future diabetes development was higher in metabolically unhealthy subgroups compared with those of metabolically healthy subjects regardless of obesity status. 10.1371/journal.pone.0098369
    Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: A cohort study. Gao Meng,Lv Jun,Yu Canqing,Guo Yu,Bian Zheng,Yang Ruotong,Du Huaidong,Yang Ling,Chen Yiping,Li Zhongxiao,Zhang Xi,Chen Junshi,Qi Lu,Chen Zhengming,Huang Tao,Li Liming, PLoS medicine BACKGROUND:Metabolically healthy obesity (MHO) and its transition to unhealthy metabolic status have been associated with risk of cardiovascular disease (CVD) in Western populations. However, it is unclear to what extent metabolic health changes over time and whether such transition affects risks of subtypes of CVD in Chinese adults. We aimed to examine the association of metabolic health status and its transition with risks of subtypes of vascular disease across body mass index (BMI) categories. METHODS AND FINDINGS:The China Kadoorie Biobank was conducted during 25 June 2004 to 15 July 2008 in 5 urban (Harbin, Qingdao, Suzhou, Liuzhou, and Haikou) and 5 rural (Henan, Gansu, Sichuan, Zhejiang, and Hunan) regions across China. BMI and metabolic health information were collected. We classified participants into BMI categories: normal weight (BMI 18.5-23.9 kg/m²), overweight (BMI 24.0-27.9 kg/m²), and obese (BMI ≥ 28 kg/m²). Metabolic health was defined as meeting less than 2 of the following 4 criteria (elevated waist circumference, hypertension, elevated plasma glucose level, and dyslipidemia). The changes in obesity and metabolic health status were defined from baseline to the second resurvey with combination of overweight and obesity. Among the 458,246 participants with complete information and no history of CVD and cancer, the mean age at baseline was 50.9 (SD 10.4) years, and 40.8% were men, and 29.0% were current smokers. During a median 10.0 years of follow-up, 52,251 major vascular events (MVEs), including 7,326 major coronary events (MCEs), 37,992 ischemic heart disease (IHD), and 42,951 strokes were recorded. Compared with metabolically healthy normal weight (MHN), baseline MHO was associated with higher hazard ratios (HRs) for all types of CVD; however, almost 40% of those participants transitioned to metabolically unhealthy status. Stable metabolically unhealthy overweight or obesity (MUOO) (HR 2.22, 95% confidence interval [CI] 2.00-2.47, p < 0.001) and transition from metabolically healthy to unhealthy status (HR 1.53, 1.34-1.75, p < 0.001) were associated with higher risk for MVE, compared with stable healthy normal weight. Similar patterns were observed for MCE, IHD, and stroke. Limitations of the analysis included lack of measurement of lipid components, fasting plasma glucose, and visceral fat, and there might be possible misclassification. CONCLUSIONS:Among Chinese adults, MHO individuals have increased risks of MVE. Obesity remains a risk factor for CVD independent of major metabolic factors. Our data further suggest that metabolic health is a transient state for a large proportion of Chinese adults, with the highest vascular risk among those remained MUOO. 10.1371/journal.pmed.1003351
    Metabolically healthy versus metabolically unhealthy obesity. Iacobini Carla,Pugliese Giuseppe,Blasetti Fantauzzi Claudia,Federici Massimo,Menini Stefano Metabolism: clinical and experimental Obesity-related disease complications reduce life quality and expectancy and increase health-care costs. Some studies have suggested that obesity not always entails metabolic abnormalities and increased risk of cardiometabolic complications. Because of the lack of universally accepted criteria to identify metabolically healthy obesity (MHO), its prevalence varies widely among studies. Moreover, the prognostic value of MHO is hotly debated, mainly because it likely shifts gradually towards metabolically unhealthy obesity (MUO). In this review, we outline the differential factors contributing to the metabolic heterogeneity of obesity by discussing the behavioral, genetic, phenotypical, and biological aspects associated with each of the two metabolic phenotypes (MHO and MUO) of obesity and their clinical implications. Particular emphasis will be laid on the role of adipose tissue biology and function, including genetic determinants of body fat distribution, depot-specific fat metabolism, adipose tissue plasticity and, particularly, adipogenesis. Finally, the emerging role of gut microbiota in obesity and adipose tissue dysfunction as well as the search for novel biomarkers for the obesity-related metabolic traits and associated diseases will be briefly presented. A better understanding of the main determinants of a healthy metabolic status in obesity would allow promotion of this favorable condition by targeting the relevant pathways. 10.1016/j.metabol.2018.11.009
    Metabolically healthy overweight/obesity are associated with increased risk of cardiovascular disease in adults, even in the absence of metabolic risk factors: A systematic review and meta-analysis of prospective cohort studies. Opio Jacob,Croker Emma,Odongo George S,Attia John,Wynne Katie,McEvoy Mark Obesity reviews : an official journal of the International Association for the Study of Obesity This review examined the risk of cardiovascular disease in adults with metabolically healthy overweight/obesity. A systematic review and meta-analysis using data from Medline, EMBASE, SCOPUS and Cochrane Library searched from inception up to 31st October 2019. We included prospective cohort studies of adults who are metabolically healthy or unhealthy. Outcomes were fatal and nonfatal cardiovascular events, all-cause mortality. Pooled relative risk was calculated for each outcome in populations with metabolically healthy overweight and metabolically healthy obesity using metabolically healthy normal weight as reference. A random-effects model was used for meta-analysis, and risk of bias assessment tool for nonrandomized studies assessed risk of bias within each study. Twenty-three prospective cohort studies with 4,492,723 participants were included. Cardiovascular disease risk was increased in metabolically healthy groups with overweight (RR = 1.34, CI: 1.23-1.46, n = 20, I = 90.3%) and obesity (RR = 1.58, CI: 1.34-1.85, n = 21, I = 92.2) compared with a reference group with metabolically healthy normal weight. Cardiovascular disease risk was similar irrespective of the number of risk factors used to define metabolically healthy and the risk remained in the group with no metabolic risk factors. Cardiovascular disease risk is increased in populations with overweight and obesity classified as metabolically healthy even when there were no metabolic risk factors. 10.1111/obr.13127
    Metabolically healthy obesity and cardiovascular events: A nationwide cohort study. Fauchier Grégoire,Bisson Arnaud,Bodin Alexandre,Herbert Julien,Semaan Carl,Angoulvant Denis,Ducluzeau Pierre Henri,Lip Gregory Y H,Fauchier Laurent Diabetes, obesity & metabolism AIM:To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. MATERIALS AND METHODS:All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE-HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS:In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted HR 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95% CI 1.31-1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30-1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87-0.98), ischaemic stroke (HR 0.93, 95% CI 0.88-0.98) and cardiovascular death (HR 0.99, 95% CI 0.93-1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12-1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49-0.99). CONCLUSIONS:In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new-onset HF and new-onset AF. However, notable differences were observed in men and women in the sex-stratified analysis. 10.1111/dom.14492
    Metabolically healthy obesity and lipids may be protective factors for pathological changes of alzheimer's disease in cognitively normal adults. Huang Shu-Juan,Ma Ya-Hui,Bi Yan-Lin,Shen Xue-Ning,Hou Xiao-He,Cao Xi-Peng,Ou Ya-Nan,Zhao Bing,Dong Qiang,Tan Lan,Yu Jin-Tai Journal of neurochemistry The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E-ɛ4 (APOE-ɛ4). The results showed the lower CSF levels of total tau protein (t-tau: p = .0048) and phosphorylated tau protein (p-tau: p = .0035) in obese participants than in non-obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t-tau (β: -0.15, p = .0145) and p-tau (β: -0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were associated with decreased CSF t-tau (TC: β: -0.16, p = .0115; LDL-C: β: -0.16, p = .0082) and p-tau (TC: β: -0.15, p = .0177; LDL-C: β: -0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late-life obesity and APOE-ɛ4 non-carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes. 10.1111/jnc.15306
    Metabolically healthy obesity and metabolically obese normal weight: a review. Gómez-Zorita Saioa,Queralt Maite,Vicente Maria Angeles,González Marcela,Portillo María P Journal of physiology and biochemistry Despite the general relationship between obesity and its co-morbidities, there are both obese individuals who scarcely present the associated pathologies (metabolically healthy obese; MHO) and individuals who present obesity alterations despite having normal weight (metabolically obese normal weight; MONW). It is still difficult to define metabolically MHO and MONW individuals because different classifications have been used in the studies reported. Indeed, different inclusion criteria have been used to discriminate between metabolically healthy and metabolically unhealthy subjects. Due to this and other reasons, such as differences in ethnicity, genetics, and lifestyle of the populations, data concerning the prevalence of MHO and MONW are very variable. The main determinants of MHO are type of growth (hypertrophy or hyperplasia), anatomical location, inflammation of adipose tissue, ectopic fat accumulation, genetic factors, and lifestyles factors. In the case of MONW, the main determinants are genetic background and lifestyle factors. With regard to treatment, it is not clear whether MHO subjects would benefit from traditional lifestyle interventions, based on diet energy restriction and increased physical activity. For MONW subjects, there is still no specialized treatment, and the therapies are the same as those used in obese subjects. 10.1007/s13105-020-00781-x
    Metabolic abnormalities, but not obesity per se, associated with chronic kidney disease in a Taiwanese population. Chen Hung-Yu,Lu Feng-Hwa,Chang Chih-Jen,Wang Ruh-Sueh,Yang Yi-Ching,Chang Yin-Fan,Wu Jin-Shang Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIMS:It is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults. METHODS AND RESULTS:This study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables. CONCLUSIONS:Metabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults. 10.1016/j.numecd.2019.09.029
    Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis. Lassale Camille,Tzoulaki Ioanna,Moons Karel G M,Sweeting Michael,Boer Jolanda,Johnson Laura,Huerta José María,Agnoli Claudia,Freisling Heinz,Weiderpass Elisabete,Wennberg Patrik,van der A Daphne L,Arriola Larraitz,Benetou Vassiliki,Boeing Heiner,Bonnet Fabrice,Colorado-Yohar Sandra M,Engström Gunnar,Eriksen Anne K,Ferrari Pietro,Grioni Sara,Johansson Matthias,Kaaks Rudolf,Katsoulis Michail,Katzke Verena,Key Timothy J,Matullo Giuseppe,Melander Olle,Molina-Portillo Elena,Moreno-Iribas Concepción,Norberg Margareta,Overvad Kim,Panico Salvatore,Quirós J Ramón,Saieva Calogero,Skeie Guri,Steffen Annika,Stepien Magdalena,Tjønneland Anne,Trichopoulou Antonia,Tumino Rosario,van der Schouw Yvonne T,Verschuren W M Monique,Langenberg Claudia,Di Angelantonio Emanuele,Riboli Elio,Wareham Nicholas J,Danesh John,Butterworth Adam S European heart journal Aims:The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. Methods and results:We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Conclusion:Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity. 10.1093/eurheartj/ehx448
    Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women. Caleyachetty Rishi,Thomas G Neil,Toulis Konstantinos A,Mohammed Nuredin,Gokhale Krishna M,Balachandran Kumarendran,Nirantharakumar Krishnarajah Journal of the American College of Cardiology BACKGROUND:Previous studies have been unclear about the cardiovascular risks for metabolically healthy obese individuals. OBJECTIVES:This study examined the associations among metabolically healthy obese individuals and 4 different presentations of incident cardiovascular disease in a contemporary population. METHODS:We used linked electronic health records (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years of age or older and initially free of cardiovascular disease. We created body size phenotypes defined by body mass index categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of 1 of 4 cardiovascular presentations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and peripheral vascular disease). RESULTS:During a mean follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.45 to 1.54), cerebrovascular disease (HR: 1.07; 95% CI: 1.04 to 1.11), and heart failure (HR: 1.96; 95% CI: 1.86 to 2.06) compared with normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease, and heart failure in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities. CONCLUSIONS:Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities and similar risks for cardiovascular disease events. 10.1016/j.jacc.2017.07.763
    Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications. Physiological reviews The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to the rapidly increased prevalence of overweight and obesity. To this point, epidemiological, clinical, and experimental evidence supports the existence of a unique disease entity termed "obesity cardiomyopathy," which develops independent of hypertension, coronary heart disease, and other heart diseases. Our contemporary review evaluates the evidence for this pathological condition, examines putative responsible mechanisms, and discusses therapeutic options for this disorder. Clinical findings have consolidated the presence of left ventricular dysfunction in obesity. Experimental investigations have uncovered pathophysiological changes in myocardial structure and function in genetically predisposed and diet-induced obesity. Indeed, contemporary evidence consolidates a wide array of cellular and molecular mechanisms underlying the etiology of obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover of free fatty acids, lipotoxicity, and amino acid derangement), altered intracellular especially mitochondrial Ca homeostasis, oxidative stress, autophagy/mitophagy defect, myocardial fibrosis, dampened coronary flow reserve, coronary microvascular disease (microangiopathy), and endothelial impairment. Given the important role of obesity in the increased risk of heart failure, especially that with preserved systolic function and the recent rises in COVID-19-associated cardiovascular mortality, this review should provide compelling evidence for the presence of obesity cardiomyopathy, independent of various comorbid conditions, underlying mechanisms, and offer new insights into potential therapeutic approaches (pharmacological and lifestyle modification) for the clinical management of obesity cardiomyopathy. 10.1152/physrev.00030.2020
    Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Powell-Wiley Tiffany M,Poirier Paul,Burke Lora E,Després Jean-Pierre,Gordon-Larsen Penny,Lavie Carl J,Lear Scott A,Ndumele Chiadi E,Neeland Ian J,Sanders Prashanthan,St-Onge Marie-Pierre, Circulation The global obesity epidemic is well established, with increases in obesity prevalence for most countries since the 1980s. Obesity contributes directly to incident cardiovascular risk factors, including dyslipidemia, type 2 diabetes, hypertension, and sleep disorders. Obesity also leads to the development of cardiovascular disease and cardiovascular disease mortality independently of other cardiovascular risk factors. More recent data highlight abdominal obesity, as determined by waist circumference, as a cardiovascular disease risk marker that is independent of body mass index. There have also been significant advances in imaging modalities for characterizing body composition, including visceral adiposity. Studies that quantify fat depots, including ectopic fat, support excess visceral adiposity as an independent indicator of poor cardiovascular outcomes. Lifestyle modification and subsequent weight loss improve both metabolic syndrome and associated systemic inflammation and endothelial dysfunction. However, clinical trials of medical weight loss have not demonstrated a reduction in coronary artery disease rates. In contrast, prospective studies comparing patients undergoing bariatric surgery with nonsurgical patients with obesity have shown reduced coronary artery disease risk with surgery. In this statement, we summarize the impact of obesity on the diagnosis, clinical management, and outcomes of atherosclerotic cardiovascular disease, heart failure, and arrhythmias, especially sudden cardiac death and atrial fibrillation. In particular, we examine the influence of obesity on noninvasive and invasive diagnostic procedures for coronary artery disease. Moreover, we review the impact of obesity on cardiac function and outcomes related to heart failure with reduced and preserved ejection fraction. Finally, we describe the effects of lifestyle and surgical weight loss interventions on outcomes related to coronary artery disease, heart failure, and atrial fibrillation. 10.1161/CIR.0000000000000973
    Association of Obesity or Weight Change With Coronary Heart Disease Among Young Adults in South Korea. Choi Seulggie,Kim Kyuwoong,Kim Sung Min,Lee Gyeongsil,Jeong Su-Min,Park Seong Yong,Kim Yeon-Yong,Son Joung Sik,Yun Jae-Moon,Park Sang Min JAMA internal medicine Importance:Previous studies have shown a U- or J-shaped association of body mass index (BMI) or change in BMI with coronary heart disease (CHD) among middle-aged and elderly adults. However, whether a similar association exists among young adults is unclear. Objective:To determine whether an association exists between BMI or BMI change with CHD among young adults. Design, Setting, and Participants:This population-based longitudinal study used data obtained by the Korean National Health Insurance Service from 2002 to 2015. The study population comprised 2 611 450 men and women aged between 20 and 39 years who underwent 2 health examinations, the first between 2002 and 2003 and the second between 2004 and 2005. Exposures:World Health Organization Western Pacific Region guideline BMI categories of underweight, normal weight, overweight, obese grade 1, and obese grade 2 derived during the first health examination and change in BMI calculated during the second health examination. Main Outcomes and Measures:Body mass index (calculated as weight in kilograms divided by height in meters squared). Absolute risks (ARs), adjusted hazard ratios (aHRs), and 95% CIs for acute myocardial infarction or CHD during follow-up from 2006 to 2015. Results:Data from 1 802 408 men with a mean (SD) age of 35.1 (4.8) years and 809 042 women with a mean (SD) age of 32.5 (6.3) years were included. The mean (SD) BMI was 23.2 (3.2) for the total population, 24.0 (3.0) for men, and 21.4 (2.9) for women. Compared with normal weight men, overweight (AR, 1.38%; aHR, 1.18 [95% CI, 1.14-1.22]), obese grade 1 (AR, 1.86%; aHR, 1.45 [95% CI, 1.41-1.50]), and obese grade 2 (AR, 2.69%; aHR, 1.97 [95% CI, 1.86-2.08]) men had an increased risk of CHD (P < .001 for trend). Similarly, compared with normal weight women, overweight (AR, 0.77%; aHR, 1.34 [95% CI, 1.24-1.46]), obese grade 1 (AR, 0.95%; aHR, 1.52 [95% CI, 1.39-1.66]), and obese grade 2 (AR, 1.01%; aHR, 1.64 [95% CI, 1.34-2.01]) women had an increased risk of CHD (P < .001 for trend). Compared with participants who maintained their weight at normal levels, those who became obese had elevated CHD risk among men (0.35% increase in AR; aHR, 1.35 [95% CI, 1.17-1.55]) and women (0.13% increase in AR; aHR, 1.31 [95% CI, 0.95-1.82]). Weight loss to normal levels among obese participants was associated with reduced CHD risk for men (0.58% decrease in AR; aHR, 0.77 [95% CI, 0.64-0.94]) and women (0.57% decrease in AR; aHR, 0.66 [95% CI, 0.45-0.98]). Conclusions and Relevance:Obesity and weight gain were associated with elevated risk of CHD among young adults in this study. Studies that prospectively determine the association between weight change and CHD risk are needed to validate these findings. 10.1001/jamainternmed.2018.2310
    The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE. Lee Alexandra K,Woodward Mark,Wang Dan,Ohkuma Toshiaki,Warren Bethany,Sharrett A Richey,Williams Bryan,Marre Michel,Hamet Pavel,Harrap Stephen,Mcevoy John W,Chalmers John,Selvin Elizabeth The Journal of clinical endocrinology and metabolism CONTEXT:Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes. OBJECTIVE:To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes. DESIGN AND SETTING:The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit. RESULTS:Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication. CONCLUSIONS:In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes. 10.1210/clinem/dgz045
    Associations of Weight Gain From Early to Middle Adulthood With Major Health Outcomes Later in Life. Zheng Yan,Manson JoAnn E,Yuan Changzheng,Liang Matthew H,Grodstein Francine,Stampfer Meir J,Willett Walter C,Hu Frank B JAMA IMPORTANCE:Data describing the effects of weight gain across adulthood on overall health are important for weight control. OBJECTIVE:To examine the association of weight gain from early to middle adulthood with health outcomes later in life. DESIGN, SETTING, AND PARTICIPANTS:Cohort analysis of US women from the Nurses' Health Study (1976-June 30, 2012) and US men from the Health Professionals Follow-Up Study (1986-January 31, 2012) who recalled weight during early adulthood (at age of 18 years in women; 21 years in men), and reported current weight during middle adulthood (at age of 55 years). EXPOSURES:Weight change from early to middle adulthood (age of 18 or 21 years to age of 55 years). MAIN OUTCOMES AND MEASURES:Beginning at the age of 55 years, participants were followed up to the incident disease outcomes. Cardiovascular disease, cancer, and death were confirmed by medical records or the National Death Index. A composite healthy aging outcome was defined as being free of 11 chronic diseases and major cognitive or physical impairment. RESULTS:A total of 92 837 women (97% white; mean [SD] weight gain: 12.6 kg [12.3 kg] over 37 years) and 25 303 men (97% white; mean [SD] weight gain: 9.7 kg [9.7 kg] over 34 years) were included in the analysis. For type 2 diabetes, the adjusted incidence per 100 000 person-years was 207 among women who gained a moderate amount of weight (≥2.5 kg to <10 kg) vs 110 among women who maintained a stable weight (weight loss ≤2.5 kg or gain <2.5 kg) (absolute rate difference [ARD] per 100 000 person-years, 98; 95% CI, 72 to 127) and 258 vs 147, respectively, among men (ARD, 111; 95% CI, 58 to 179); hypertension: 3415 vs 2754 among women (ARD, 662; 95% CI, 545 to 782) and 2861 vs 2366 among men (ARD, 495; 95% CI, 281 to 726); cardiovascular disease: 309 vs 248 among women (ARD, 61; 95% CI, 38 to 87) and 383 vs 340 among men (ARD, 43; 95% CI, -14 to 109); obesity-related cancer: 452 vs 415 among women (ARD, 37; 95% CI, 4 to 73) and 208 vs 165 among men (ARD, 42; 95% CI, 0.5 to 94). Among those who gained a moderate amount of weight, 3651 women (24%) and 2405 men (37%) achieved the composite healthy aging outcome. Among those who maintained a stable weight, 1528 women (27%) and 989 men (39%) achieved the composite healthy aging outcome. The multivariable-adjusted odds ratio for the composite healthy aging outcome associated with moderate weight gain was 0.78 (95% CI, 0.72 to 0.84) in women and 0.88 (95% CI, 0.79 to 0.97) in men. Higher amounts of weight gain were associated with greater risks of major chronic diseases and lower likelihood of healthy aging. CONCLUSIONS AND RELEVANCE:In these cohorts of health professionals, weight gain during adulthood was associated with significantly increased risk of major chronic diseases and decreased odds of healthy aging. These findings may help counsel patients regarding the risks of weight gain. 10.1001/jama.2017.7092
    Risk of stroke and coronary heart disease among various levels of blood pressure in diabetic and nondiabetic Chinese patients. Zhang Yuqing,Jiang Xueli,Bo Jian,Yin Lu,Chen Hui,Wang Yang,Yu Hongwei,Wang Xingyu,Li Wei, Journal of hypertension OBJECTIVE:To compare the risk of stroke and coronary heart disease (CHD) among various blood pressure (BP) levels in diabetic and people without diabetes Chinese patients. METHODS:This cross-sectional study was part of Prospective Urban Rural Epidemiology China study. Patients aged 35 to70 years were recruited from 12 provinces of China between 2005 and 2009. The participants were classified into three groups: hypertension (HTN), high normal BP, and normal BP, and also into SBP and DBP quintiles. RESULTS:A total of 42 959 patients were analyzed with 38 975 (90.7% of total population) people without diabetes and 3984 (9.3% of total population) diabetic patients. Among diabetic patients, the HTN group was associated with an increased risk of stroke (odds ratio, 3.03; 95% confidence interval, 1.47-6.25) and CHD (odds ratio, 2.21; 95% confidence interval, 1.45-3.38), when compared with normal BP group. Similar results were drawn in nondiabetic patients. However, no significant difference in risk of stroke or CHD was found between high normal BP and normal BP groups in either diabetic or nondiabetic patients. Risk of CHD and stroke increased significantly when SBP was above 125 mmHg or DBP above 72 mmHg in people without diabetes, whereas this trend was attenuated in diabetic patients. CONCLUSION:HTN was associated with a two-fold increased risk of CHD and a three-fold increased risk of stroke compared with normotension irrespective of diabetes status. For diabetic patients with HTN, a more comprehensive method is essential for assessing cardiovascular risk. 10.1097/HJH.0000000000001528
    Primary Prevention of Cardiovascular Disease in Diabetes Mellitus. Newman Jonathan D,Schwartzbard Arthur Z,Weintraub Howard S,Goldberg Ira J,Berger Jeffrey S Journal of the American College of Cardiology Type 2 diabetes mellitus (T2D) is a major risk factor for cardiovascular disease (CVD), the most common cause of death in T2D. Yet, <50% of U.S. adults with T2D meet recommended guidelines for CVD prevention. The burden of T2D is increasing: by 2050, approximately 1 in 3 U.S. individuals may have T2D, and patients with T2D will comprise an increasingly large proportion of the CVD population. The authors believe it is imperative that we expand the use of therapies proven to reduce CVD risk in patients with T2D. The authors summarize evidence and guidelines for lifestyle (exercise, nutrition, and weight management) and CVD risk factor (blood pressure, cholesterol and blood lipids, glycemic control, and the use of aspirin) management for the prevention of CVD among patients with T2D. The authors believe appropriate lifestyle and CVD risk factor management has the potential to significantly reduce the burden of CVD among patients with T2D. 10.1016/j.jacc.2017.07.001
    Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks. Sattar Naveed,Rawshani Araz,Franzén Stefan,Rawshani Aidin,Svensson Ann-Marie,Rosengren Annika,McGuire Darren K,Eliasson Björn,Gudbjörnsdottir Soffia Circulation BACKGROUND:Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by the age at T2DM diagnosis, but few population studies have analyzed mortality and CVD outcomes associations across the full age range. METHODS:With use of the Swedish National Diabetes Registry, everyone with T2DM registered in the Registry between 1998 and 2012 was included. Controls were randomly selected from the general population matched for age, sex, and county. The analysis cohort comprised 318 083 patients with T2DM matched with just <1.6 million controls. Participants were followed from 1998 to 2013 for CVD outcomes and to 2014 for mortality. Outcomes of interest were total mortality, cardiovascular mortality, noncardiovascular mortality, coronary heart disease, acute myocardial infarction, stroke, heart failure, and atrial fibrillation. We also examined life expectancy by age at diagnosis. We conducted the primary analyses using Cox proportional hazards models in those with no previous CVD and repeated the work in the entire cohort. RESULTS:Over a median follow-up period of 5.63 years, patients with T2DM diagnosed at ≤40 years had the highest excess risk for most outcomes relative to controls with adjusted hazard ratio (95% CI) of 2.05 (1.81-2.33) for total mortality, 2.72 (2.13-3.48) for cardiovascular-related mortality, 1.95 (1.68-2.25) for noncardiovascular mortality, 4.77 (3.86-5.89) for heart failure, and 4.33 (3.82-4.91) for coronary heart disease. All risks attenuated progressively with each increasing decade at diagnostic age; by the time T2DM was diagnosed at >80 years, the adjusted hazard ratios for CVD and non-CVD mortality were <1, with excess risks for other CVD outcomes substantially attenuated. Moreover, survival in those diagnosed beyond 80 was the same as controls, whereas it was more than a decade less when T2DM was diagnosed in adolescence. Finally, hazard ratios for most outcomes were numerically greater in younger women with T2DM. CONCLUSIONS:Age at diagnosis of T2DM is prognostically important for survival and cardiovascular risks, with implications for determining the timing and intensity of risk factor interventions for clinical decision making and for guideline-directed care. These observations amplify support for preventing/delaying T2DM onset in younger individuals. 10.1161/CIRCULATIONAHA.118.037885
    Risk Factors for First and Subsequent CVD Events in Type 1 Diabetes: The DCCT/EDIC Study. Bebu Ionut,Schade David,Braffett Barbara,Kosiborod Mikhail,Lopes-Virella Maria,Soliman Elsayed Z,Herman William H,Bluemke David A,Wallia Amisha,Orchard Trevor,Lachin John M, Diabetes care OBJECTIVE:The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events. RESEARCH DESIGN AND METHODS:CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes. RESULTS:Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]). CONCLUSIONS:Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained. 10.2337/dc19-2292
    Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries. Rajan Selina,McKee Martin,Rangarajan Sumathy,Bangdiwala Shrikant,Rosengren Annika,Gupta Rajeev,Kutty Vellappillil Raman,Wielgosz Andreas,Lear Scott,AlHabib Khalid F,Co Homer U,Lopez-Jaramillo Patricio,Avezum Alvaro,Seron Pamela,Oguz Aytekin,Kruger Iolanthé M,Diaz Rafael,Nafiza Mat-Nasir,Chifamba Jephat,Yeates Karen,Kelishadi Roya,Sharief Wadeia Mohammed,Szuba Andrzej,Khatib Rasha,Rahman Omar,Iqbal Romaina,Bo Hu,Yibing Zhu,Wei Li,Yusuf Salim, JAMA psychiatry Importance:Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective:To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants:This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures:Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures:Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results:Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance:In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide. 10.1001/jamapsychiatry.2020.1351
    Plasma protein patterns as comprehensive indicators of health. Williams Stephen A,Kivimaki Mika,Langenberg Claudia,Hingorani Aroon D,Casas J P,Bouchard Claude,Jonasson Christian,Sarzynski Mark A,Shipley Martin J,Alexander Leigh,Ash Jessica,Bauer Tim,Chadwick Jessica,Datta Gargi,DeLisle Robert Kirk,Hagar Yolanda,Hinterberg Michael,Ostroff Rachel,Weiss Sophie,Ganz Peter,Wareham Nicholas J Nature medicine Proteins are effector molecules that mediate the functions of genes and modulate comorbidities, behaviors and drug treatments. They represent an enormous potential resource for personalized, systemic and data-driven diagnosis, prevention, monitoring and treatment. However, the concept of using plasma proteins for individualized health assessment across many health conditions simultaneously has not been tested. Here, we show that plasma protein expression patterns strongly encode for multiple different health states, future disease risks and lifestyle behaviors. We developed and validated protein-phenotype models for 11 different health indicators: liver fat, kidney filtration, percentage body fat, visceral fat mass, lean body mass, cardiopulmonary fitness, physical activity, alcohol consumption, cigarette smoking, diabetes risk and primary cardiovascular event risk. The analyses were prospectively planned, documented and executed at scale on archived samples and clinical data, with a total of ~85 million protein measurements in 16,894 participants. Our proof-of-concept study demonstrates that protein expression patterns reliably encode for many different health issues, and that large-scale protein scanning coupled with machine learning is viable for the development and future simultaneous delivery of multiple measures of health. We anticipate that, with further validation and the addition of more protein-phenotype models, this approach could enable a single-source, individualized so-called liquid health check. 10.1038/s41591-019-0665-2
    Influence of Lifestyle on Incident Cardiovascular Disease and Mortality in Patients With Diabetes Mellitus. Liu Gang,Li Yanping,Hu Yang,Zong Geng,Li Shanshan,Rimm Eric B,Hu Frank B,Manson JoAnn E,Rexrode Kathryn M,Shin Hyun Joon,Sun Qi Journal of the American College of Cardiology BACKGROUND:Evidence is limited regarding the impact of healthy lifestyle practices on the risk of subsequent cardiovascular events among patients with diabetes. OBJECTIVES:The purpose of this study was to examine the associations of an overall healthy lifestyle, defined by eating a high-quality diet (top two-fifths of Alternative Healthy Eating Index), nonsmoking, engaging in moderate- to vigorous-intensity physical activity (≥150 min/week), and drinking alcohol in moderation (5 to 15 g/day for women and 5 to 30 g/day for men), with the risk of developing cardiovascular disease (CVD) and CVD mortality among adults with type 2 diabetes (T2D). METHODS:This prospective analysis included 11,527 participants with T2D diagnosed during follow-up (8,970 women from the Nurses' Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of CVD and cancer at the time of diabetes diagnosis. Diet and lifestyle factors before and after T2D diagnosis were repeatedly assessed every 2 to 4 years. RESULTS:There were 2,311 incident CVD cases and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment of covariates, the low-risk lifestyle factors after diabetes diagnosis were each associated with a lower risk of CVD incidence and CVD mortality. The multivariate-adjusted hazard ratios for participants with 3 or more low-risk lifestyle factors compared with 0 were 0.48 (95% confidence interval [CI]: 0.40 to 0.59) for total CVD incidence, 0.53 (95% CI: 0.42 to 0.66) for incidence of coronary heart disease, 0.33 (95% CI: 0.21 to 0.51) for stroke incidence, and 0.32 (95% CI: 0.22 to 0.47) for CVD mortality (all p trend <0.001). The population-attributable risk for poor adherence to the overall healthy lifestyle (<3 low-risk factors) was 40.9% (95% CI: 28.5% to 52.0%) for CVD mortality. In addition, greater improvements in healthy lifestyle factors from pre-diabetes to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and CVD mortality. For each number increment in low-risk lifestyle factors there was a 14% lower risk of incident total CVD, a 12% lower risk of coronary heart disease, a 21% lower risk of stroke, and a 27% lower risk of CVD mortality (all p < 0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis. CONCLUSIONS:Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and CVD mortality among adults with T2D. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in patients with T2D. 10.1016/j.jacc.2018.04.027
    Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. Roth Gregory A,Mensah George A,Johnson Catherine O,Addolorato Giovanni,Ammirati Enrico,Baddour Larry M,Barengo Noël C,Beaton Andrea Z,Benjamin Emelia J,Benziger Catherine P,Bonny Aimé,Brauer Michael,Brodmann Marianne,Cahill Thomas J,Carapetis Jonathan,Catapano Alberico L,Chugh Sumeet S,Cooper Leslie T,Coresh Josef,Criqui Michael,DeCleene Nicole,Eagle Kim A,Emmons-Bell Sophia,Feigin Valery L,Fernández-Solà Joaquim,Fowkes Gerry,Gakidou Emmanuela,Grundy Scott M,He Feng J,Howard George,Hu Frank,Inker Lesley,Karthikeyan Ganesan,Kassebaum Nicholas,Koroshetz Walter,Lavie Carl,Lloyd-Jones Donald,Lu Hong S,Mirijello Antonio,Temesgen Awoke Misganaw,Mokdad Ali,Moran Andrew E,Muntner Paul,Narula Jagat,Neal Bruce,Ntsekhe Mpiko,Moraes de Oliveira Glaucia,Otto Catherine,Owolabi Mayowa,Pratt Michael,Rajagopalan Sanjay,Reitsma Marissa,Ribeiro Antonio Luiz P,Rigotti Nancy,Rodgers Anthony,Sable Craig,Shakil Saate,Sliwa-Hahnle Karen,Stark Benjamin,Sundström Johan,Timpel Patrick,Tleyjeh Imad M,Valgimigli Marco,Vos Theo,Whelton Paul K,Yacoub Magdi,Zuhlke Liesl,Murray Christopher,Fuster Valentin, Journal of the American College of Cardiology Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases. 10.1016/j.jacc.2020.11.010
    Ideal Cardiovascular Health Metrics and Major Cardiovascular Events in Patients With Prediabetes and Diabetes. Wang Tiange,Lu Jieli,Su Qing,Chen Yuhong,Bi Yufang,Mu Yiming,Chen Lulu,Hu Ruying,Tang Xulei,Yu Xuefeng,Li Mian,Xu Min,Xu Yu,Zhao Zhiyun,Yan Li,Qin Guijun,Wan Qin,Chen Gang,Dai Meng,Zhang Di,Gao Zhengnan,Wang Guixia,Shen Feixia,Luo Zuojie,Qin Yingfen,Chen Li,Huo Yanan,Li Qiang,Ye Zhen,Zhang Yinfei,Liu Chao,Wang Youmin,Wu Shengli,Yang Tao,Deng Huacong,Li Donghui,Lai Shenghan,Bloomgarden Zachary T,Shi Lixin,Ning Guang,Zhao Jiajun,Wang Weiqing, JAMA cardiology Importance:Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective:To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants:The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures:Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures:The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results:Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHMs and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58; 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance:Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation. 10.1001/jamacardio.2019.2499
    Association between prediabetes and risk of all cause mortality and cardiovascular disease: updated meta-analysis. Cai Xiaoyan,Zhang Yunlong,Li Meijun,Wu Jason Hy,Mai Linlin,Li Jun,Yang Yu,Hu Yunzhao,Huang Yuli BMJ (Clinical research ed.) OBJECTIVE:To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease. DESIGN:Updated meta-analysis. DATA SOURCES:Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020. REVIEW METHODS:Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke. RESULTS:A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10). CONCLUSIONS:Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease. 10.1136/bmj.m2297
    Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. Roth Gregory A,Johnson Catherine,Abajobir Amanuel,Abd-Allah Foad,Abera Semaw Ferede,Abyu Gebre,Ahmed Muktar,Aksut Baran,Alam Tahiya,Alam Khurshid,Alla François,Alvis-Guzman Nelson,Amrock Stephen,Ansari Hossein,Ärnlöv Johan,Asayesh Hamid,Atey Tesfay Mehari,Avila-Burgos Leticia,Awasthi Ashish,Banerjee Amitava,Barac Aleksandra,Bärnighausen Till,Barregard Lars,Bedi Neeraj,Belay Ketema Ezra,Bennett Derrick,Berhe Gebremedhin,Bhutta Zulfiqar,Bitew Shimelash,Carapetis Jonathan,Carrero Juan Jesus,Malta Deborah Carvalho,Castañeda-Orjuela Carlos Andres,Castillo-Rivas Jacqueline,Catalá-López Ferrán,Choi Jee-Young,Christensen Hanne,Cirillo Massimo,Cooper Leslie,Criqui Michael,Cundiff David,Damasceno Albertino,Dandona Lalit,Dandona Rakhi,Davletov Kairat,Dharmaratne Samath,Dorairaj Prabhakaran,Dubey Manisha,Ehrenkranz Rebecca,El Sayed Zaki Maysaa,Faraon Emerito Jose A,Esteghamati Alireza,Farid Talha,Farvid Maryam,Feigin Valery,Ding Eric L,Fowkes Gerry,Gebrehiwot Tsegaye,Gillum Richard,Gold Audra,Gona Philimon,Gupta Rajeev,Habtewold Tesfa Dejenie,Hafezi-Nejad Nima,Hailu Tesfaye,Hailu Gessessew Bugssa,Hankey Graeme,Hassen Hamid Yimam,Abate Kalkidan Hassen,Havmoeller Rasmus,Hay Simon I,Horino Masako,Hotez Peter J,Jacobsen Kathryn,James Spencer,Javanbakht Mehdi,Jeemon Panniyammakal,John Denny,Jonas Jost,Kalkonde Yogeshwar,Karimkhani Chante,Kasaeian Amir,Khader Yousef,Khan Abdur,Khang Young-Ho,Khera Sahil,Khoja Abdullah T,Khubchandani Jagdish,Kim Daniel,Kolte Dhaval,Kosen Soewarta,Krohn Kristopher J,Kumar G Anil,Kwan Gene F,Lal Dharmesh Kumar,Larsson Anders,Linn Shai,Lopez Alan,Lotufo Paulo A,El Razek Hassan Magdy Abd,Malekzadeh Reza,Mazidi Mohsen,Meier Toni,Meles Kidanu Gebremariam,Mensah George,Meretoja Atte,Mezgebe Haftay,Miller Ted,Mirrakhimov Erkin,Mohammed Shafiu,Moran Andrew E,Musa Kamarul Imran,Narula Jagat,Neal Bruce,Ngalesoni Frida,Nguyen Grant,Obermeyer Carla Makhlouf,Owolabi Mayowa,Patton George,Pedro João,Qato Dima,Qorbani Mostafa,Rahimi Kazem,Rai Rajesh Kumar,Rawaf Salman,Ribeiro Antônio,Safiri Saeid,Salomon Joshua A,Santos Itamar,Santric Milicevic Milena,Sartorius Benn,Schutte Aletta,Sepanlou Sadaf,Shaikh Masood Ali,Shin Min-Jeong,Shishehbor Mehdi,Shore Hirbo,Silva Diego Augusto Santos,Sobngwi Eugene,Stranges Saverio,Swaminathan Soumya,Tabarés-Seisdedos Rafael,Tadele Atnafu Niguse,Tesfay Fisaha,Thakur J S,Thrift Amanda,Topor-Madry Roman,Truelsen Thomas,Tyrovolas Stefanos,Ukwaja Kingsley Nnanna,Uthman Olalekan,Vasankari Tommi,Vlassov Vasiliy,Vollset Stein Emil,Wakayo Tolassa,Watkins David,Weintraub Robert,Werdecker Andrea,Westerman Ronny,Wiysonge Charles Shey,Wolfe Charles,Workicho Abdulhalik,Xu Gelin,Yano Yuichiro,Yip Paul,Yonemoto Naohiro,Younis Mustafa,Yu Chuanhua,Vos Theo,Naghavi Mohsen,Murray Christopher Journal of the American College of Cardiology BACKGROUND:The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES:The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS:CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS:In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS:CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD. 10.1016/j.jacc.2017.04.052
    Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Zhou Maigeng,Wang Haidong,Zeng Xinying,Yin Peng,Zhu Jun,Chen Wanqing,Li Xiaohong,Wang Lijun,Wang Limin,Liu Yunning,Liu Jiangmei,Zhang Mei,Qi Jinlei,Yu Shicheng,Afshin Ashkan,Gakidou Emmanuela,Glenn Scott,Krish Varsha Sarah,Miller-Petrie Molly Katherine,Mountjoy-Venning W Cliff,Mullany Erin C,Redford Sofia Boston,Liu Hongyan,Naghavi Mohsen,Hay Simon I,Wang Linhong,Murray Christopher J L,Liang Xiaofeng Lancet (London, England) BACKGROUND:Public health is a priority for the Chinese Government. Evidence-based decision making for health at the province level in China, which is home to a fifth of the global population, is of paramount importance. This analysis uses data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to help inform decision making and monitor progress on health at the province level. METHODS:We used the methods in GBD 2017 to analyse health patterns in the 34 province-level administrative units in China from 1990 to 2017. We estimated all-cause and cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), summary exposure values (SEVs), and attributable risk. We compared the observed results with expected values estimated based on the Socio-demographic Index (SDI). FINDINGS:Stroke and ischaemic heart disease were the leading causes of death and DALYs at the national level in China in 2017. Age-standardised DALYs per 100 000 population decreased by 33·1% (95% uncertainty interval [UI] 29·8 to 37·4) for stroke and increased by 4·6% (-3·3 to 10·7) for ischaemic heart disease from 1990 to 2017. Age-standardised stroke, ischaemic heart disease, lung cancer, chronic obstructive pulmonary disease, and liver cancer were the five leading causes of YLLs in 2017. Musculoskeletal disorders, mental health disorders, and sense organ diseases were the three leading causes of YLDs in 2017, and high systolic blood pressure, smoking, high-sodium diet, and ambient particulate matter pollution were among the leading four risk factors contributing to deaths and DALYs. All provinces had higher than expected DALYs per 100 000 population for liver cancer, with the observed to expected ratio ranging from 2·04 to 6·88. The all-cause age-standardised DALYs per 100 000 population were lower than expected in all provinces in 2017, and among the top 20 level 3 causes were lower than expected for ischaemic heart disease, Alzheimer's disease, headache disorder, and low back pain. The largest percentage change at the national level in age-standardised SEVs among the top ten leading risk factors was in high body-mass index (185%, 95% UI 113·1 to 247·7]), followed by ambient particulate matter pollution (88·5%, 66·4 to 116·4). INTERPRETATION:China has made substantial progress in reducing the burden of many diseases and disabilities. Strategies targeting chronic diseases, particularly in the elderly, should be prioritised in the expanding Chinese health-care system. FUNDING:China National Key Research and Development Program and Bill & Melinda Gates Foundation. 10.1016/S0140-6736(19)30427-1
    Reducing the Global Burden of Cardiovascular Disease, Part 1: The Epidemiology and Risk Factors. Joseph Philip,Leong Darryl,McKee Martin,Anand Sonia S,Schwalm Jon-David,Teo Koon,Mente Andrew,Yusuf Salim Circulation research Current global health policy goals include a 25% reduction in premature mortality from noncommunicable diseases by 2025. In this 2-part review, we provide an overview of the current epidemiological data on cardiovascular diseases (CVD), its risk factors, and describe strategies aimed at reducing its burden. In part 1, we examine the global epidemiology of cardiac conditions that have the greatest impact on CVD mortality; the predominant risk factors; and the impact of upstream, societal health determinants (eg, environmental factors, health policy, and health systems) on CVD. Although age-standardized mortality from CVD has decreased in many regions of the world, the absolute number of deaths continues to increase, with the majority now occurring in middle- and low-income countries. It is evident that multiple factors are causally related to CVD, including traditional individual level risk factors (mainly tobacco use, lipids, and elevated blood pressure) and societal level health determinants (eg, health systems, health policies, and barriers to CVD prevention and care). Both individual and societal risk factors vary considerably between different regions of the world and economic settings. However, reliable data to estimate CVD burden are lacking in many regions of the world, which hampers the establishment of nationwide prevention and management strategies. A 25% reduction in premature CVD mortality globally is feasible but will require better implementation of evidence-based policies (particularly tobacco control) and integrated health systems strategies that improve CVD prevention and management. In addition, there is a need for better health information to monitor progress and guide health policy decisions. 10.1161/CIRCRESAHA.117.308903
    Reducing the Global Burden of Cardiovascular Disease, Part 2: Prevention and Treatment of Cardiovascular Disease. Leong Darryl P,Joseph Philip G,McKee Martin,Anand Sonia S,Teo Koon K,Schwalm Jon-David,Yusuf Salim Circulation research In this second part of a 2-part series on the global burden of cardiovascular disease, we review the proven, effective approaches to the prevention and treatment of cardiovascular disease. We specifically review the management of acute cardiovascular diseases, including acute coronary syndromes and stroke; the care of cardiovascular disease in the ambulatory setting, including medical strategies for vascular disease, atrial fibrillation, and heart failure; surgical strategies for arterial revascularization, rheumatic and other valvular heart disease, and symptomatic bradyarrhythmia; and approaches to the prevention of cardiovascular disease, including lifestyle factors, blood pressure control, cholesterol-lowering, antithrombotic therapy, and fixed-dose combination therapy. We also discuss cardiovascular disease prevention in diabetes mellitus; digital health interventions; the importance of socioeconomic status and universal health coverage. We review building capacity for conduction cardiovascular intervention through strengthening healthcare systems, priority setting, and the role of cost effectiveness. 10.1161/CIRCRESAHA.117.311849
    Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study. Islam Nazrul,Krajden Mel,Shoveller Jean,Gustafson Paul,Gilbert Mark,Buxton Jane A,Wong Jason,Tyndall Mark W,Janjua Naveed Zafar, The lancet. Gastroenterology & hepatology BACKGROUND:People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. METHODS:We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). FINDINGS:5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). INTERPRETATION:The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. FUNDING:The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research. 10.1016/S2468-1253(16)30182-0
    Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Walli-Attaei Marjan,Joseph Philip,Rosengren Annika,Chow Clara K,Rangarajan Sumathy,Lear Scott A,AlHabib Khalid F,Davletov Kairat,Dans Antonio,Lanas Fernando,Yeates Karen,Poirier Paul,Teo Koon K,Bahonar Ahmad,Camilo Felix,Chifamba Jephat,Diaz Rafael,Didkowska Joanna A,Irazola Vilma,Ismail Rosnah,Kaur Manmeet,Khatib Rasha,Liu Xiaoyun,Mańczuk Marta,Miranda J Jaime,Oguz Aytekin,Perez-Mayorga Maritza,Szuba Andrzej,Tsolekile Lungiswa P,Prasad Varma Ravi,Yusufali Afzalhussein,Yusuf Rita,Wei Li,Anand Sonia S,Yusuf Salim Lancet (London, England) BACKGROUND:Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies. METHODS:In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death. FINDINGS:From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease. INTERPRETATION:Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men. FUNDING:Full funding sources are listed at the end of the paper (see Acknowledgments). 10.1016/S0140-6736(20)30543-2
    Prevention and Control of Cardiovascular Disease in the Rapidly Changing Economy of China. Wu Yangfeng,Benjamin Emelia J,MacMahon Stephen Circulation With one-fifth of the world's total population, China's prevention and control of cardiovascular disease (CVD) may affect the success of worldwide efforts to achieve sustainable CVD reduction. Understanding China's current cardiovascular epidemic requires awareness of the economic development in the past decades. The rapid economic transformations (industrialization, marketization, urbanization, globalization, and informationalization) contributed to the aging demography, unhealthy lifestyles, and environmental changes. The latter have predisposed to increasing cardiovascular risk factors and the CVD pandemic. Rising CVD rates have had a major economic impact, which has challenged the healthcare system and the whole society. With recognition of the importance of health, initial political steps and national actions have been taken to address the CVD epidemic. Looking to the future, we recommend that 4 priorities should be taken: pursue multisectorial government and nongovernment strategies targeting the underlying causes of CVD (the whole-of-government and whole-of-society policy); give priority to prevention; reform the healthcare system to fit the nature of noncommunicable diseases; and conduct research for evidence-based, low-cost, simple, sustainable, and scalable interventions. By pursuing the 4 priorities, the pandemic of CVD and other major noncommunicable diseases in China will be reversed and the global sustainable development goal achieved. 10.1161/CIRCULATIONAHA.115.008728
    Potential Impact of Time Trend of Life-Style Factors on Cardiovascular Disease Burden in China. Li Yanping,Wang Dong D,Ley Sylvia H,Howard Annie Green,He Yuna,Lu Yuan,Danaei Goodarz,Hu Frank B Journal of the American College of Cardiology BACKGROUND:Cardiovascular disease (CVD) is a leading cause of death in China. Evaluation of risk factors and their impacts on disease burden is important for future public health initiatives and policy making. OBJECTIVES:The study used data from a cohort of the China Health and Nutrition Survey to estimate time trends in cardiovascular risk factors from 1991 to 2011. METHODS:We applied the comparative risk assessment method to estimate the number of CVD events attributable to all nonoptimal levels (e.g., theoretical-minimum-risk exposure distribution [TMRED]) of each risk factor. RESULTS:In 2011, high blood pressure, high low-density lipoprotein cholesterol, and high blood glucose were associated with 3.1, 1.4, and 0.9 million CVD events in China, respectively. Increase in body mass index was associated with an increase in attributable CVD events, from 0.5 to 1.1 million between 1991 and 2011, whereas decreased physical activity was associated with a 0.7-million increase in attributable CVD events. In 2011, 53.4% of men used tobacco, estimated to be responsible for 30.1% of CVD burden in men. Dietary quality improved, but remained suboptimal; mean intakes were 5.4 (TMRED: 2.0) g/day for sodium, 67.7 (TMRED: 300.0) g/day for fruits, 6.2 (TMRED: 114.0) g/day for nuts, and 25.0 (TMRED: 250.0) mg/day for marine omega-3 fatty acids in 2011. CONCLUSIONS:High blood pressure remains the most important individual risk factor related to CVD burden in China. Increased body mass index and decreased physical activity were also associated with the increase in CVD burden from 1991 to 2011. High rates of tobacco use in men and unhealthy dietary factors continue to contribute to the burden of CVD in China. 10.1016/j.jacc.2016.06.011
    Time Trends in Cardiovascular Disease Mortality Across the BRICS: An Age-Period-Cohort Analysis of Key Nations With Emerging Economies Using the Global Burden of Disease Study 2017. Zou Zhiyong,Cini Karly,Dong Bin,Ma Yinghua,Ma Jun,Burgner David P,Patton George C Circulation BACKGROUND:Brazil, Russia, India, China, and South Africa (BRICS) are emerging economies making up almost half the global population. We analyzed trends in cardiovascular disease (CVD) mortality across the BRICS and associations with age, period, and birth cohort. METHODS:Mortality estimates were derived from the Global Burden of Disease Study 2017. We used age-period-cohort modeling to estimate cohort and period effects in CVD between 1992 and 2016. Period was defined as survey year, and period effects reflect population-wide exposure at a circumscribed point in time. Cohort effects are defined as differences in risks across birth cohort. Net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks were calculated. RESULTS:In 2016, there were 8.4 million CVD deaths across the BRICS. Between 1992 and 2016, the reduction in CVD age-standardized mortality rate in BRICS (-17%) was less than in North America (-39%). Eighty-eight percent of the increased number of all-cause deaths resulted from the increase in CVD deaths. The age-standardized mortality rate from stroke and hypertensive heart disease declined by approximately one-third across the BRICS, whereas ischemic heart disease increased slightly (2%). Brazil had the largest age-standardized mortality rate reductions across all CVD categories, with improvement both over time and in recent birth cohorts. South Africa was the only country where the CVD age-standardized mortality rate increased. Different age-related CVD mortality was seen in those ≥50 years of age in China, ≤40 years of age in Russia, 35 to 60 years of age in India, and ≥55 years of age in South Africa. Improving period and cohort risks for CVD mortality were generally found across countries, except for worsening period effects in India and greater risks for ischemic heart disease in Chinese cohorts born in the 1950s and 1960s. CONCLUSIONS:Except for Brazil, reductions of CVD mortality across the BRICS have been less than that in North America, such that China, India, and South Africa contribute an increasing proportion of global CVD deaths. Brazil's example suggests that prevention policies can both reduce the risks for younger birth cohorts and shift the risks for all age groups over time. 10.1161/CIRCULATIONAHA.119.042864
    Epidemic of Cardiovascular Disease in China: Current Perspective and Prospects for the Future. Shen Chengxing,Ge Junbo Circulation 10.1161/CIRCULATIONAHA.118.033484
    Epidemiology of Cardiovascular Disease in China and Opportunities for Improvement: JACC International. Du Xin,Patel Anushka,Anderson Craig S,Dong Jianzeng,Ma Changsheng Journal of the American College of Cardiology The burden of cardiovascular (CV) disease is very high in China, due to highly prevalent and poorly controlled risk factors resulting from changing sociodemographic structure and lifestyles in its large population. Rapid economic development and urbanization have been accompanied by changing patterns, expression, and management of CV disease. However, the health care system in China lacks a hierarchical structure, with a focus on treating acute diseases in hospital while ignoring long-term management, and primary health care is too weak to effectively control CV risk factors. To address these challenges, the Chinese central government has ensured health is a national priority and has introduced reforms that include implementing policies for a healthy environment, strengthening primary care, and improving affordability and accessibility within the health system. Turning the inverted pyramid of the health care system is essential in the ongoing battle against CV disease. 10.1016/j.jacc.2019.04.036
    Epidemiology of cardiovascular disease in China: current features and implications. Zhao Dong,Liu Jing,Wang Miao,Zhang Xingguang,Zhou Mengge Nature reviews. Cardiology Cardiovascular disease (CVD) is the leading cause of death in China. To develop effective and timely strategies to cope with the challenges of CVD epidemics, we need to understand the current epidemiological features of the major types of CVD and the implications of these features for the prevention and treatment of CVD. In this Review, we summarize eight important features of the epidemiology of CVD in China. Some features indicate a transition in CVD epidemiology owing to interrelated changes in demography, environment, lifestyle, and health care, including the rising burden from atherosclerotic CVD (ischaemic heart disease and ischaemic stroke), declining mortality from haemorrhage stroke, varied regional epidemiological trends in the subtypes of CVD, increasing numbers of patients with moderate types of ischaemic heart disease and ischaemic stroke, and increasing ageing of patients with CVD. Other features highlight the problems that need particular attention, including the high proportion of out-of-hospital death of patients with ischaemic heart disease with insufficient prehospital care; the wide gaps between guideline-recommended goals and levels of lifestyle indicators; and the huge number of patients with undiagnosed, untreated, or uncontrolled hypertension, hypercholesterolaemia, or diabetes mellitus. 10.1038/s41569-018-0119-4
    Burden of Cardiovascular Diseases in China, 1990-2016: Findings From the 2016 Global Burden of Disease Study. Liu Shiwei,Li Yichong,Zeng Xinying,Wang Haidong,Yin Peng,Wang Lijun,Liu Yunning,Liu Jiangmei,Qi Jinlei,Ran Sha,Yang Shiya,Zhou Maigeng JAMA cardiology Importance:Cardiovascular disease (CVD) remains the top cause of death in China. To our knowledge, no consistent and comparable assessments of CVD burden have been produced at subnational levels, and little is understood about the spatial patterns and temporal trends of CVD in China. Objective:To determine the national and province-level burden of CVD from 1990 to 2016 in China. Design, Setting, and Participants:Following the methodology framework and analytical strategies used in the 2016 Global Burden of Disease study, the mortality, prevalence, and disability-adjusted life-years (DALYs) of CVD in the Chinese population were examined by age, sex, and year and according to 10 subcategories. Estimates were produced for all province-level administrative units of mainland China, Hong Kong, and Macao. Exposures:Residence in China. Main Outcomes and Measures:Mortality, prevalence, and DALYs of CVD. Results:The annual number of deaths owing to CVD increased from 2.51 million to 3.97 million between 1990 and 2016; the age-standardized mortality rate fell by 28.7%, from 431.6 per 100 000 persons in 1990 to 307.9 per 100 000 in 2016. Prevalent cases of CVD doubled since 1990, reaching nearly 94 million in 2016. The age-standardized prevalence rate of CVD overall increased significantly from 1990 to 2016 by 14.7%, as did rates for ischemic heart disease (19.1%), ischemic stroke (36.6%), cardiomyopathy and myocarditis (23.1%), and endocarditis (26.7%). Substantial reduction in the CVD burden, as measured by age-standardized DALY rate, was observed from 1990 to 2016 nationally, with a greater reduction in women (43.7%) than men (24.7%). There were marked differences in the spatial patterns of mortality, prevalence, and DALYs of CVD overall as well as its main subcategories, including ischemic heart disease, hemorrhagic stroke, and ischemic stroke. The CVD burden appeared to be lower in coastal provinces with higher economic development. The between-province gap in relative burden of CVD increased from 1990 to 2016, with faster decline in economically developed provinces. Conclusions and Relevance:Substantial discrepancies in the total CVD burden and burdens of CVD subcategories have persisted between provinces in China despite a relative decrease in the CVD burden. Geographically targeted considerations are needed to tailor future strategies to enhance CVD health throughout China and in specific provinces. 10.1001/jamacardio.2019.0295
    Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Yusuf Salim,Joseph Philip,Rangarajan Sumathy,Islam Shofiqul,Mente Andrew,Hystad Perry,Brauer Michael,Kutty Vellappillil Raman,Gupta Rajeev,Wielgosz Andreas,AlHabib Khalid F,Dans Antonio,Lopez-Jaramillo Patricio,Avezum Alvaro,Lanas Fernando,Oguz Aytekin,Kruger Iolanthe M,Diaz Rafael,Yusoff Khalid,Mony Prem,Chifamba Jephat,Yeates Karen,Kelishadi Roya,Yusufali Afzalhussein,Khatib Rasha,Rahman Omar,Zatonska Katarzyna,Iqbal Romaina,Wei Li,Bo Hu,Rosengren Annika,Kaur Manmeet,Mohan Viswanathan,Lear Scott A,Teo Koon K,Leong Darryl,O'Donnell Martin,McKee Martin,Dagenais Gilles Lancet (London, England) BACKGROUND:Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. METHODS:In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. FINDINGS:Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. INTERPRETATION:Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. FUNDING:Full funding sources are listed at the end of the paper (see Acknowledgments). 10.1016/S0140-6736(19)32008-2
    World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions. The Lancet. Global health BACKGROUND:To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS:In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS:Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION:We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING:World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research. 10.1016/S2214-109X(19)30318-3
    The changing patterns of cardiovascular diseases and their risk factors in the states of India: the Global Burden of Disease Study 1990-2016. The Lancet. Global health BACKGROUND:The burden of cardiovascular diseases is increasing in India, but a systematic understanding of its distribution and time trends across all the states is not readily available. In this report, we present a detailed analysis of how the patterns of cardiovascular diseases and major risk factors have changed across the states of India between 1990 and 2016. METHODS:We analysed the prevalence and disability-adjusted life-years (DALYs) due to cardiovascular diseases and the major component causes in the states of India from 1990 to 2016, using all accessible data sources as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016. We placed states into four groups based on epidemiological transition level (ETL), defined using the ratio of DALYs from communicable diseases to those from non-communicable diseases and injuries combined, with a low ratio denoting high ETL and vice versa. We assessed heterogeneity in the burden of major cardiovascular diseases across the states of India, and the contribution of risk factors to cardiovascular diseases. We calculated 95% uncertainty intervals (UIs) for the point estimates. FINDINGS:Overall, cardiovascular diseases contributed 28·1% (95% UI 26·5-29·1) of the total deaths and 14·1% (12·9-15·3) of the total DALYs in India in 2016, compared with 15·2% (13·7-16·2) and 6·9% (6·3-7·4), respectively, in 1990. In 2016, there was a nine times difference between states in the DALY rate for ischaemic heart disease, a six times difference for stroke, and a four times difference for rheumatic heart disease. 23·8 million (95% UI 22·6-25·0) prevalent cases of ischaemic heart disease were estimated in India in 2016, and 6·5 million (6·3-6·8) prevalent cases of stroke, a 2·3 times increase in both disorders from 1990. The age-standardised prevalence of both ischaemic heart disease and stroke increased in all ETL state groups between 1990 and 2016, whereas that of rheumatic heart disease decreased; the increase for ischaemic heart disease was highest in the low ETL state group. 53·4% (95% UI 52·6-54·6) of crude deaths due to cardiovascular diseases in India in 2016 were among people younger than 70 years, with a higher proportion in the low ETL state group. The leading overlapping risk factors for cardiovascular diseases in 2016 included dietary risks (56·4% [95% CI 48·5-63·9] of cardiovascular disease DALYs), high systolic blood pressure (54·6% [49·0-59·8]), air pollution (31·1% [29·0-33·4]), high total cholesterol (29·4% [24·3-34·8]), tobacco use (18·9% [16·6-21·3]), high fasting plasma glucose (16·7% [11·4-23·5]), and high body-mass index (14·7% [8·3-22·0]). The prevalence of high systolic blood pressure, high total cholesterol, and high fasting plasma glucose increased generally across all ETL state groups from 1990 to 2016, but this increase was variable across the states; the prevalence of smoking decreased during this period in all ETL state groups. INTERPRETATION:The burden from the leading cardiovascular diseases in India-ischaemic heart disease and stroke-varies widely between the states. Their increasing prevalence and that of several major risk factors in every part of India, especially the highest increase in the prevalence of ischaemic heart disease in the less developed low ETL states, indicates the need for urgent policy and health system response appropriate for the situation in each state. FUNDING:Bill & Melinda Gates Foundation; and Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India. 10.1016/S2214-109X(18)30407-8
    The Burden of Cardiovascular Diseases Among US States, 1990-2016. ,Roth Gregory A,Johnson Catherine O,Abate Kalkidan Hassen,Abd-Allah Foad,Ahmed Muktar,Alam Khurshid,Alam Tahiya,Alvis-Guzman Nelson,Ansari Hossein,Ärnlöv Johan,Atey Tesfay Mehari,Awasthi Ashish,Awoke Tadesse,Barac Aleksandra,Bärnighausen Till,Bedi Neeraj,Bennett Derrick,Bensenor Isabela,Biadgilign Sibhatu,Castañeda-Orjuela Carlos,Catalá-López Ferrán,Davletov Kairat,Dharmaratne Samath,Ding Eric L,Dubey Manisha,Faraon Emerito Jose Aquino,Farid Talha,Farvid Maryam S,Feigin Valery,Fernandes João,Frostad Joseph,Gebru Alemseged,Geleijnse Johanna M,Gona Philimon Nyakauru,Griswold Max,Hailu Gessessew Bugssa,Hankey Graeme J,Hassen Hamid Yimam,Havmoeller Rasmus,Hay Simon,Heckbert Susan R,Irvine Caleb Mackay Salpeter,James Spencer Lewis,Jara Dube,Kasaeian Amir,Khan Abdur Rahman,Khera Sahil,Khoja Abdullah T,Khubchandani Jagdish,Kim Daniel,Kolte Dhaval,Lal Dharmesh,Larsson Anders,Linn Shai,Lotufo Paulo A,Magdy Abd El Razek Hassan,Mazidi Mohsen,Meier Toni,Mendoza Walter,Mensah George A,Meretoja Atte,Mezgebe Haftay Berhane,Mirrakhimov Erkin,Mohammed Shafiu,Moran Andrew Edward,Nguyen Grant,Nguyen Minh,Ong Kanyin Liane,Owolabi Mayowa,Pletcher Martin,Pourmalek Farshad,Purcell Caroline A,Qorbani Mostafa,Rahman Mahfuzar,Rai Rajesh Kumar,Ram Usha,Reitsma Marissa Bettay,Renzaho Andre M N,Rios-Blancas Maria Jesus,Safiri Saeid,Salomon Joshua A,Sartorius Benn,Sepanlou Sadaf Ghajarieh,Shaikh Masood Ali,Silva Diego,Stranges Saverio,Tabarés-Seisdedos Rafael,Tadele Atnafu Niguse,Thakur J S,Topor-Madry Roman,Truelsen Thomas,Tuzcu E Murat,Tyrovolas Stefanos,Ukwaja Kingsley Nnanna,Vasankari Tommi,Vlassov Vasiliy,Vollset Stein Emil,Wakayo Tolassa,Weintraub Robert,Wolfe Charles,Workicho Abdulhalik,Xu Gelin,Yadgir Simon,Yano Yuichiro,Yip Paul,Yonemoto Naohiro,Younis Mustafa,Yu Chuanhua,Zaidi Zoubida,Zaki Maysaa El Sayed,Zipkin Ben,Afshin Ashkan,Gakidou Emmanuela,Lim Stephen S,Mokdad Ali H,Naghavi Mohsen,Vos Theo,Murray Christopher J L JAMA cardiology Importance:Cardiovascular disease (CVD) is the leading cause of death in the United States, but regional variation within the United States is large. Comparable and consistent state-level measures of total CVD burden and risk factors have not been produced previously. Objective:To quantify and describe levels and trends of lost health due to CVD within the United States from 1990 to 2016 as well as risk factors driving these changes. Design, Setting, and Participants:Using the Global Burden of Disease methodology, cardiovascular disease mortality, nonfatal health outcomes, and associated risk factors were analyzed by age group, sex, and year from 1990 to 2016 for all residents in the United States using standardized approaches for data processing and statistical modeling. Burden of disease was estimated for 10 groupings of CVD, and comparative risk analysis was performed. Data were analyzed from August 2016 to July 2017. Exposures:Residing in the United States. Main Outcomes and Measures:Cardiovascular disease disability-adjusted life-years (DALYs). Results:Between 1990 and 2016, age-standardized CVD DALYs for all states decreased. Several states had large rises in their relative rank ordering for total CVD DALYs among states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana, Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and CVD burden increased for a small number of states in the most recent years. Cardiovascular disease DALYs remained twice as large among men compared with women. Ischemic heart disease was the leading cause of CVD DALYs in all states, but the second most common varied by state. Trends were driven by 12 groups of risk factors, with the largest attributable CVD burden due to dietary risk exposures followed by high systolic blood pressure, high body mass index, high total cholesterol level, high fasting plasma glucose level, tobacco smoking, and low levels of physical activity. Increases in risk-deleted CVD DALY rates between 2006 and 2016 in 16 states suggest additional unmeasured risks beyond these traditional factors. Conclusions and Relevance:Large disparities in total burden of CVD persist between US states despite marked improvements in CVD burden. Differences in CVD burden are largely attributable to modifiable risk exposures. 10.1001/jamacardio.2018.0385