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    Association of Metabolic Syndrome and Its Components With Risk of Stroke Recurrence and Mortality: A Meta-analysis. Zhang Fangfang,Liu Lili,Zhang Chundong,Ji Shiliang,Mei Zubing,Li Tian Neurology OBJECTIVE:Because metabolic syndrome is a significant risk factor for cardio-cerebrovascular diseases and the relationship between metabolic syndrome (including its components) and the prognosis of stroke is controversial, this study was conducted to evaluate whether metabolic syndrome is associated with a high recurrence and mortality of stroke. METHODS:This study was registered in the PROSPERO database (CRD42020177118). We searched for relevant observational cohort studies published from inception to April 23, 2020, using PubMed, Embase, and the Cochrane Library. Effect estimates with 95% confidence intervals (CIs) were pooled using the random-effects model. The primary and secondary outcomes were stroke recurrence and all-cause mortality, respectively. Leave-one-out sensitivity analyses and nonparametric trim-and-fill method were used to identify the stability of the results. RESULTS:Thirteen cohort studies comprising 59,919 participants >60 years of age were included for analysis. Overall, metabolic syndrome was significantly associated with stroke recurrence (relative risk [RR] 1.46, 95% CI 1.07-1.97, = 0.02). Among the metabolic syndrome components, low levels of high-density lipoprotein cholesterol (HDL-C) (RR 1.32, 95% CI 1.11-1.57, = 0.002) and ≥2 metabolic syndrome components (RR 1.68, 95% CI 1.44-1.94, < 0.001) significantly predicted stroke recurrence, whereas elevated triglycerides, elevated waist circumference, hyperglycemia, and hypertension failed to account for risk factors for stroke recurrence. Moreover, metabolic syndrome, not its components, was significantly associated with all-cause mortality (RR 1.27, 95% CI 1.18-1.36, < 0.001). The stability of these results was further confirmed by the leave-one-out sensitivity analyses and nonparametric trim-and-fill method. CONCLUSIONS:The present study indicates that metabolic syndrome and some of its components (low HDL-C and number of metabolic syndrome components) seem to be risk factors for stroke recurrence. Although metabolic syndrome is also associated with all-cause mortality, the role of its components in predicting all-cause mortality deserves further study. 10.1212/WNL.0000000000012415
    Elevated C-reactive Protein and Depressed High-density Lipoprotein Cholesterol are Associated with Poor Function Outcome After Ischemic Stroke. Zheng Xiaowei,Zeng Nimei,Wang Aili,Zhu Zhengbao,Zhong Chongke,Xu Tan,Xu Tian,Peng Yanbo,Peng Hao,Li Qunwei,Ju Zhong,Geng Deqin,Zhang Yonghong,He Jiang Current neurovascular research AIMS:C-reactive protein is an established marker of inflammation that can impair the protective function of High Density Lipoprotein Cholesterol (HDL-C). The combined effect of Creactive protein and HDL-C on long-term outcomes in patients with stroke remains uncertain. METHODS:A total of 3124 acute ischemic stroke subjects from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) were included in this analysis. Participants were divided into four groups according to CRP and HDL-C levels on admission. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at one year after stroke. RESULTS:Compared to participants with low CRP/ high HDL-C, adjusted odd ratios for primary outcome for those with low CRP /low HDL-C, high CRP /high HDL-C and high CRP /low HDL-C were 1.06(0.81-1.39),1.78(1.31-2.41) and 2.03(1.46-2.80), respectively, after multiple adjustments. Adding serum CRP and HDL-C status to a model containing conventional stroke risk factors significantly improve risk reclassification for the combined outcome of death and major disability (NRI: 6.85%, P=0.005; IDI: 2.57%, P=0.002). Moreover, no interaction was observed between CRP and HDL-C in relation to stroke outcomes (P-interaction >0.05 for all). CONCLUSIONS:High CRP with low HDL-C levels was associated with death and major disability within one year after ischemic stroke. The findings suggest that the ischemic patients with both high CRP and low HDL-C should be treated with reducing CRP and promoting HDL-C levels. 10.2174/1567202615666180712100440
    Isolated low levels of high-density lipoprotein cholesterol and stroke incidence: JMS Cohort Study. Watanabe Jun,Kakehi Eiichi,Kotani Kazuhiko,Kayaba Kazunori,Nakamura Yosikazu,Ishikawa Shizukiyo Journal of clinical laboratory analysis BACKGROUND:The cardiovascular relevance of isolated low levels of high-density lipoprotein cholesterol (HDL-C) is yet to be determined. Stroke often leads to long-term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL-C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. METHODS:In the Jichi Medical School cohort study, 11 025 community-living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non-isolated low HDL-C levels were calculated relative to those for normal HDL-C levels in stroke patients using Cox's regression models. RESULTS:During the mean follow-up period of 10.7 years, 412 residents had their first-ever stroke. The multivariable-adjusted HRs for the levels of isolated and non-isolated low HDL-C were 1.11 (95% confidence interval, 0.85-1.44) and 1.35 (1.01-1.81), respectively, when compared to that for normal HDL-C. CONCLUSION:Low HDL-C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL-C. 10.1002/jcla.23087
    Impact of Mean and Variability of High-Density Lipoprotein-Cholesterol on the Risk of Myocardial Infarction, Stroke, and Mortality in the General Population. Han Byung-Hun,Han Kyungdo,Yoon Kun-Ho,Kim Mee Kyoung,Lee Seung-Hwan Journal of the American Heart Association Background A low level of high-density lipoprotein-cholesterol (HDL-C) is a well-known risk factor for cardiovascular events. Recent studies have also suggested that HDL-C variability has a predictive role in patients with coronary artery disease. We investigated the combined effect of the mean and variability of HDL-C on the risk of myocardial infarction (MI), stroke, and mortality in the general population. Methods and Results We selected 5 433 098 subjects in the Korean National Health Insurance System cohort who had no history of MI or stroke and who underwent ≥3 health examinations between 2009 and 2013. Visit-to-visit HDL-C variability was calculated using the coefficient of variation, variability independent of the mean and average real variability. The low-mean and high-variability groups were defined as the lowest and highest quartiles of HDL-C mean and variability, respectively. There were 27 605 cases of MI, 31 162 cases of stroke, and 50 959 deaths during the median follow-up of 5.1±0.6 years. A lower mean or higher variability (coefficient of variation) of HDL-C was associated with a higher risk of adverse outcomes, and the 2 measures had an additive effect. In the multivariable-adjusted model, the hazard ratios (95% CIs) of the low-mean/high-variability group compared with the high-mean/low-variability group were 1.47 (1.41-1.54) for MI, 1.23 (1.18-1.28) for stroke, and 1.41 (1.36-1.45) for all-cause mortality. Results were consistent when variability was modeled using variability independent of the mean or average real variability, and in various sensitivity and subgroup analyses. Conclusions Low mean and high variability of HDL-C is associated with an increased risk of MI, stroke, and mortality. 10.1161/JAHA.119.015493
    Non-High-Density Lipoprotein Cholesterol Predicts Adverse Outcomes in Acute Ischemic Stroke. Wang Guangyao,Jing Jing,Wang Anxin,Zhang Xiaoli,Zhao Xingquan,Li Zixiao,Wang Chunjuan,Li Hao,Liu Liping,Wang Yongjun,Wang Yilong, Stroke Background and Purpose:Non–high-density lipoprotein cholesterol (non–HDL-C) was significantly related to adverse outcomes in patients with cardiovascular disease. We aim to investigate the associations of non-HDL-C and adverse outcomes in acute ischemic stroke. Methods:Among 19 604 patients with acute ischemic stroke admitted to the China National Stroke Registry II, 16 113 with both total cholesterol and HDL-C were analyzed. Patients were classified into 5 groups by quintiles of non-HDL-C. The outcomes included recurrent ischemic stroke, intracranial hemorrhage, and all-cause death within 1 year. The relationship of non-HDL-C with the risk of outcomes was analyzed by Cox regression models. Results:Among the 16 113 patients, the median (interquartile range) of non-HDL-C was 3.41 (2.78–4.10) mmol/L. After adjustment for confounding variables, patients in the top quintile of non-HDL-C were associated with higher risk of recurrent ischemic stroke within 1 year (adjusted hazard ratio, 1.46 [95% CI, 1.20–1.77]), compared with those in the third quintile. Patients in the bottom and top quintile of non-HDL-C were associated with higher risk of all-cause death within 1 year (adjusted hazard ratio, 1.22 [95% CI, 1.01–1.47] and adjusted hazard ratio, 1.40 [95% CI, 1.15–1.70], respectively), compared with those in the third quintile. However, non-HDL-C levels were not significantly predictive in intracranial hemorrhage. Conclusions:Non-HDL-C may be a qualified predictor for recurrent ischemic stroke and all-cause death within 1 year in patients with acute ischemic stroke. 10.1161/STROKEAHA.120.030783
    Association of Lipids With Ischemic and Hemorrhagic Stroke: A Prospective Cohort Study Among 267 500 Chinese. Gu Xiaoying,Li Yunzhi,Chen Shuohua,Yang Xueli,Liu Fangchao,Li Ying,Li Jianxin,Cao Jie,Liu Xiaoqing,Chen Jichun,Shen Chong,Yu Ling,Huang Jianfeng,Lam Tai-Hing,Fang Xianghua,He Yao,Zhang Xinhua,Lu Xiangfeng,Wu Shouling,Gu Dongfeng Stroke Background and Purpose- Previous results on the association between lipids and stroke were controversial. We investigated the association of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C ), high-density lipoprotein cholesterol (HDL-C), and triglyceride with stroke. Methods- Six cohort studies in China with 267 500 participants were included. Cox proportional hazards regression models and restricted cubic spline analyses were used to estimate hazard ratios and 95% CIs and explore linear and nonlinear relationships of lipids and stroke, respectively. Results- The median follow-up duration ranged from 6 to 19 years. During 2 295 881 person-years, 8072 people developed stroke. Multivariable adjusted hazard ratios (95% CIs) per 1 mmol/L increase in TC, LDL-C, triglyceride were 1.08 (1.05-1.11), 1.08 (1.04-1.11), 1.07 (1.05-1.09) for ischemic stroke, respectively. Compared with participants with TC 160-199.9 mg/dL, hazard ratios (95% CIs) were 1.43 (1.11-1.85) for hemorrhagic stroke in those with TC <120 mg/dL. Compared with participants with HDL-C 50 to 59.9 mg/dL, hazard ratios (95% CIs) were 1.23 (1.12-1.35), 1.13 (1.04-1.22) for ischemic stroke, and 1.28 (1.10-1.49), 1.17 (1.03-1.33) for hemorrhagic stroke in those with HDL-C <40 and 40 to 49.9 mg/dL, respectively. Restricted cubic spline analyses showed linear relationships of TC and LDL-C, and nonlinear relationships of HDL-C and triglyceride with ischemic stroke (all <0.001). Hemorrhagic stroke showed linear relationships with TC and HDL-C (=0.029 and <0.001 respectively), but no relationship with LDL-C and triglyceride (all >0.05). Conclusions- TC, LDL-C, and triglyceride showed positive associations with ischemic stroke. The risk of hemorrhagic stroke was higher when TC was lower than 120 mg/dL. LDL-C and triglyceride showed no association with hemorrhagic stroke. The risks of ischemic and hemorrhagic stroke might be higher when HDL-C was lower than 50 mg/dL. 10.1161/STROKEAHA.119.026402
    U-Shaped Relationship of High-Density Lipoprotein Cholesterol and Incidence of Total, Ischemic and Hemorrhagic Stroke: A Prospective Cohort Study. Stroke BACKGROUND:We aimed to investigate the association between serially measured HDL-C (high-density lipoprotein cholesterol) levels and stroke risk in a prospective cohort study. METHODS:We included 96 258 individuals (79.6% men, mean age 51.5 years) without a history of stroke, myocardial infarction, or cancer at baseline from the Kailuan Study, with repeated measurements of HDL-C in 2006, 2008, 2010, 2012, 2014, and 2016. Cumulatively, averaged HDL-C concentrations were calculated using all available HDL-C measurements before incidence stroke or end of follow-up (December 31, 2017). Incident stroke cases were confirmed by review of medical records and further subclassified into ischemic or hemorrhagic stroke. Cox proportional hazards regression and restricted cubic splines were used to examine these associations. RESULTS:During a median follow-up of 10.7 years, 5012 incident stroke cases occurred. Restricted cubic splines analysis suggested a U-shaped association between concentrations of cumulatively averaged HDL-C and risk of stroke ( <0.001), with the nadir of risk at 1.29 mmol/L. After adjustment for cardiovascular risk factors, individuals with cumulatively averaged HDL-C ≤1.06 mmol/L or ≥2.05 mmol/L had hazard ratios for total stroke of 1.31 (95% CI, 1.15-1.49) and 1.85 (1.63-2.09) compared with those with HDL-C of 1.26 to 1.39 mmol/L. Corresponding hazard ratios were 1.29 (1.11-1.48) and 1.84 (1.60-2.11) for ischemic stroke and 1.54 (1.12-2.12) and 2.29 (1.73-3.04) for hemorrhagic stroke, respectively. CONCLUSIONS:Both low and high cumulatively averaged HDL-C were associated with an increased risk of ischemic and hemorrhagic strokes. 10.1161/STROKEAHA.121.034393
    Serum TG/HDL-C level at the acute phase of ischemic stroke is associated with post-stroke cognitive impairment. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology BACKGROUND:The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) bears a relation with poor outcomes of acute ischemic stroke (AIS), but the impact of serum TG/HDL-C level on post-stroke cognitive impairment (PSCI) remains unknown. We conducted this prospective study to explore the association between TG/HDL-C and PSCI. METHODS:Consecutive AIS patients from the Stroke Units of our hospital were prospectively enrolled between July 1, 2020, and June 30, 2021. Blood samples were collected within 24 h after admission. Cognition function was evaluated by the Montreal Cognitive Assessment (MoCA) at 3 months after stroke. We used logistic regression analyses to explore the relationship between TG/HDL-C and PSCI, and then used a receiver operating characteristic (ROC) analysis to assess the ability of acute TG/HDL-C for predicting PSCI. RESULTS:A total of 227 AIS patients were recruited. Compared with patients without PSCI, those with PSCI had a higher level of TG/HDL-C at admission (P < 0.01). The multivariate logistic regression analyses showed that TG/HDL-C level was independently associated with PSCI (P < 0.01). The area under the curve of the ROC for TG/HDL-C as predictor of PSCI was 0.701 (95%CI 0.635-0.768). The optimal cutoff value of TG/HDL-C to indicate PSCI was 1.564, which gave a sensitivity of 55.2% and specificity of 80.6%. CONCLUSIONS:Our study demonstrated that a higher level of TG/HDL-C at the acute phase of ischemic stroke predicted the presence of PSCI at 3 months after stroke. 10.1007/s10072-022-06267-6
    HDL-C, ApoA1 and VLDL-TG as biomarkers for the carotid plaque presence in patients with metabolic syndrome. Abi-Ayad Meryem,Abbou Amine,Abi-Ayad Fatima Zahra,Behadada Omar,Benyoucef Mohamed Diabetes & metabolic syndrome AIM:Hypercholesterolemia and hyper LDL-C are associated with the atherosclerosis (AS). The current study was performed to evaluate the implication of the others lipoproteins (HDL, LDL, VLDL) and apolipoproteins (ApoA1, ApoB100) with subclinical atherosclerosis (carotid plaque) in patients with metabolic syndrome (MetS) free from cardiovascular disease (CVD). METHODS:Prospective transversal study was conducted in patients with MetS free from cardiovascular disease (CVD). The lipids, lipoproteins and apolipoproteins were measured. The lipoproteins (HDL, LDL, VLDL) were obtained by the precipitation method. The carotid plaque (CP) was evaluated by ultrasonography, method for assessing AS. Logistic regression and analysis tree were used to look for the association and the incrimination of the lipoproteins with the presence of CP. RESULTS:The CP incidence was 60% among the participants, 34.29% on the right and the left plaque against 25.71% for only one plaque. The HDL-C was the only lipoprotein associated with the CP after adjustment of the age, the sex and BMI (OR: 0.007 P: 0.046) with the logistic regression analysis, HDL-C (<0.35 g/l), ApoA1 (<1.43 g/l) and VLDL-TG (>0.656 g/l) are implicated in the presence of CP with the analysis tree analysis. CONCLUSION:Lower level of HDL-C is associated with CP, HDL-C, ApoA1, and high level VLDL-TG but not total cholesterol, and LDL-Care useful parameters in the assessment of initial atherosclerosis in metabolic syndrome. 10.1016/j.dsx.2017.12.017
    Lipoproteins and cancer: The role of HDL-C, LDL-C, and cholesterol-lowering drugs. Patel Kush K,Kashfi Khosrow Biochemical pharmacology Cholesterol is an amphipathic sterol molecule that is vital for maintaining normal physiological homeostasis. It is a relatively complicated molecule with 27 carbons whose synthesis starts with 2-carbon units. This in itself signifies the importance of this molecule. Cholesterol serves as a precursor for vitamin D, bile acids, and hormones, including estrogens, androgens, progestogens, and corticosteroids. Although essential, high cholesterol levels are associated with cardiovascular and kidney diseases and cancer initiation, progression, and metastasis. Although there are some contrary reports, current literature suggests a positive association between serum cholesterol levels and the risk and extent of cancer development. In this review, we first present a brief overview of cholesterol biosynthesis and its transport, then elucidate the role of cholesterol in the progression of some cancers. Suggested mechanisms for cholesterol-mediated cancer progression are plentiful and include the activation of oncogenic signaling pathways and the induction of oxidative stress, among others. The specific roles of the lipoprotein molecules, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), in this pathogenesis, are also reviewed. Finally, we hone on the potential role of some cholesterol-lowering medications in cancer. 10.1016/j.bcp.2021.114654
    Association of LDL-C/HDL-C Ratio With Stroke Outcomes Within 1 Year After Onset: A Hospital-Based Follow-Up Study. Liu Li,Yin Ping,Lu Chong,Li Jingxin,Zang Zhaoxia,Liu Yongdan,Liu Shuang,Wei Yafen Frontiers in neurology Stroke remains a leading cause of death and disability. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C ratio) ratio has been confirmed to be a predictor of stroke. However, few studies have assessed the prognostic impact of the LDL-C/HDL-C ratio for stroke patients. We aimed to investigate the relationship between the LDL-C/HDL-C ratio and the prognosis following stroke in Chinese patients. A total of 3,410 patients who had experienced their first ischemic stroke was recruited to this study within 72 h of stroke onset. The patients were followed for at least 12 months. A multivariate regression analysis was used to assess the association between the LDL-C/HDL-C ratio and prognosis following stroke. We considered the LDL-C/HDL-C ratio as a continuous variable and stratified patients according to the LDL-C/HDL-C ratio quartile. A higher LDL-C/HDL-C ratio was associated with lower rates of death, recurrence, and moderate disability (defined as a modified Rankin scale score >2) at 3 months. Using group 1 as the reference group, the relative risk (RRs) at 3 months for death were 0.45 (95% confidence interval [CI]: 0.27, 0.77) for group 2, 0.58 (95% CI: 0.34, 0.98) for group 3, and 0.97 (95% CI: 0.60, 1.56) for group 4; for recurrence, the RRs were 0.75 (95% CI: 0.56, 0.99) for group 2, 0.65 (95% CI: 0.48, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.78) for group 4; and for moderate disability, the RRs were 0.74 (95% CI: 0.55, 0.99) for group 2, 0.65 (95% CI: 0.47, 0.89) for group 3, and 0.55 (95% CI: 0.39, 0.77) for group 4. At 12 months, patients in group 2 were the most protected against ischemic stroke death (RR: 0.57; 95% CI: 0.34, 0.95). However, there were no associations between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability. A higher LDL-C/HDL-C ratio was found to protect against death, recurrence, and moderate disability at 3 months. However, there was no significant association between the LDL-C/HDL-C ratio and stroke recurrence or moderate disability at 12 months. These results nonetheless suggest that a higher LDL-C/HDL-C ratio was associated with short-term stroke prognosis. 10.3389/fneur.2020.00408