Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease. Song Ci,Burgess Stephen,Eicher John D,O'Donnell Christopher J,Johnson Andrew D Journal of the American Heart Association BACKGROUND:Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. METHODS AND RESULTS:To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. CONCLUSIONS:Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction. 10.1161/JAHA.116.004918

Iron status and its association with coronary heart disease: systematic review and meta-analysis of prospective studies. Das De Sudeep,Krishna Sreedhar,Jethwa Ankeet Atherosclerosis BACKGROUND:Observations in the past have hypothesized an association between body iron status and coronary heart disease (CHD). Epidemiological studies to date have however been inconclusive without the existence of strongly positive or strongly negative associations between iron status and coronary heart disease. OBJECTIVES:To investigate the association between iron status and coronary heart disease. DATA SOURCES:A systematic review was performed using the databases PubMed and Cochrane Library. Search terms included iron, ferritin, transferrin, total iron binding capacity, coronary heart disease and angina. STUDY SELECTION:Only prospective studies investigating the association of body iron status and coronary heart disease were included. All participants were free from coronary heart disease at baseline. There were no language or geographic restrictions imposed on the search strategy. DATA EXTRACTION:Independent extraction of articles by 2 authors using predefined data fields. DATA SYNTHESIS:All pooled analyses were based on random-effects models. A total of 17 studies were identified for analysis, involving a total of 9236 cases of coronary heart disease and 156,427 participants. Several studies reported more than 1 marker of iron status. For serum ferritin, comparison of individuals in the top third versus the bottom third of baseline measurements yielded a combined risk ratio of 1.03 (95%CI, 0.87-1.23) for CHD/MI. For transferrin saturation, the combined risk ratio for CHD/MI was 0.82 (95% CI, 0.75-0.89) for individuals in the top third versus the bottom third of baseline measurements. Comparison of individuals in top and bottom thirds of baseline measurements yielded non-significant risk ratios of studies involving total iron-binding capacity (combined risk ratio, 0.99; 95% CI 0.86-1.13) and serum iron (combined risk ratio, 0.87; 95% CI 0.73-1.04). For serum iron, the combined risk ratio for CHD/MI after excluding the study by Morrisson et al. [1] was 0.80 (95% CI, 0.73-0.87). CONCLUSIONS:The results suggest that there is a negative association of transferrin levels and coronary heart disease with high transferrin saturations being associated with a lower risk of CHD/MI. There was also a negative association of serum iron and CHD/MI after one study [1] was excluded. There is no significant association between the other markers of iron status and CHD. It is however difficult to infer causality from these findings due to limitations in terms of reverse causality bias and residual confounding. 10.1016/j.atherosclerosis.2014.12.018

Coronary heart disease and risk for cognitive impairment or dementia: Systematic review and meta-analysis. Deckers Kay,Schievink Syenna H J,Rodriquez Maria M F,van Oostenbrugge Robert J,van Boxtel Martin P J,Verhey Frans R J,Köhler Sebastian PloS one AIMS/HYPOTHESIS:Accumulating evidence suggests an association between coronary heart disease and risk for cognitive impairment or dementia, but no study has systematically reviewed this association. Therefore, we summarized the available evidence on the association between coronary heart disease and risk for cognitive impairment or dementia. METHODS:Medline, Embase, PsycINFO, and CINAHL were searched for all publications until 8th January 2016. Articles were included if they fulfilled the inclusion criteria: (1) myocardial infarction, angina pectoris or coronary heart disease (combination of both) as predictor variable; (2) cognition, cognitive impairment or dementia as outcome; (3) population-based study; (4) prospective (≥1 year follow-up), cross-sectional or case-control study design; (5) ≥100 participants; and (6) aged ≥45 years. Reference lists of publications and secondary literature were hand-searched for possible missing articles. Two reviewers independently screened all abstracts and extracted information from potential relevant full-text articles using a standardized data collection form. Study quality was assessed with the Newcastle-Ottawa Scale. We pooled estimates from the most fully adjusted model using random-effects meta-analysis. RESULTS:We identified 6,132 abstracts, of which 24 studies were included. A meta-analysis of 10 prospective cohort studies showed that coronary heart disease was associated with increased risk of cognitive impairment or dementia (OR = 1.45, 95%CI = 1.21-1.74, p<0.001). Between-study heterogeneity was low (I2 = 25.7%, 95%CI = 0-64, p = 0.207). Similar significant associations were found in separate meta-analyses of prospective cohort studies for the individual predictors (myocardial infarction, angina pectoris). In contrast, meta-analyses of cross-sectional and case-control studies were inconclusive. CONCLUSION/INTERPRETATION:This meta-analysis suggests that coronary heart disease is prospectively associated with increased odds of developing cognitive impairment or dementia. Given the projected worldwide increase in the number of people affected by coronary heart disease and dementia, insight into causal mechanisms or common pathways underlying the heart-brain connection is needed. 10.1371/journal.pone.0184244

Hepatitis B virus and the risk of coronary heart disease: A comprehensive systematic review and meta-analyses of observational studies. Wang Yaqin,Xiong Jianping,Niu Meng,Xu Weiyu,Xu Ke,Zhong Hongshan International journal of cardiology BACKGROUND:Several studies have reported that hepatitis B virus (HBV) infection affects the risk of coronary heart disease. However, its association is controversial. Thus, we conducted a systematic review and meta-analysis to better understand it. METHODS:Relevant studies published before October 2017 were identified by searching PubMed, EMBASE, and ISI Web of Science. The relationships between HBV and the risk of coronary heart disease were assessed using Relative risk (RR) values and the corresponding 95% confidence intervals (CIs). We used the random effects model proposed by DerSimonian and Laird to quantify the relationship. RESULTS:Nine articles, including 65,058 HBV-infected patients and 534,998 uninfected controls, were included in the meta-analysis. The present study does not support that HBV infection is associated with the risk of coronary heart disease (RR = 0.99, CI = 0.76-1.22; I = 68.9%). Sensitivity analysis and 'trim and fill' method yielded similar results. No evidence of publication bias was observed. CONCLUSIONS:HBV infection does not increase the risk of coronary heart disease. The associations were not significant both in cohort studies and in case-control studies. 10.1016/j.ijcard.2018.04.059

Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease. Dong Yan,Chen Hengwen,Gao Jialiang,Liu Yongmei,Li Jun,Wang Jie Journal of molecular and cellular cardiology Coronary heart disease (CHD) is a common heart disease and the leading cause of cardiovascular death. Apoptosis and autophagy are two forms of programmed cell deaths which participate in the pathogenesis, development and prognosis of CHD. They are activated by several different pathways respectively and can interact with each other through the Beclin 1-Bcl-2/Bcl-xL complex, mTOR, TRAIL, TNF-α, ER stress and nucleus p53 pathways. Excessive apoptosis can promote myocardial ischemia, ischemia/reperfusion (I/R) injury, post-ischemia cardiac remodeling and coronary atherosclerosis except for VSMC-induced atherosclerosis progress. In contrast, activated autophagy protects heart from myocardial ischemia injury and post-ischemia cardiac remodeling, but can exert controversial effects on I/R injury and coronary atherosclerosis. Therefore, considering the pathological significance and mechanisms of apoptosis and autophagy underlying CHD, therapeutic implication of targeting apoptosis and autophagy is obvious. Fortunately, some therapeutic drugs and pharmacologic compounds involving mTOR inhibitor and AMPK activator have been reported to regulate apoptosis and autophagy. Although recent studies are limited and insufficient, they have pointed out the complex interplay between apoptosis and autophagy and further provided treatment concept for CHD by balancing the switch between the two responses. 10.1016/j.yjmcc.2019.09.001