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Association of BAX hypermethylation with coronary heart disease is specific to individuals aged over 70.

ABSTRACT: INTRODUCTION:As a member of B-cell lymphoma-2 (BCL-2) gene family, BCL-2 associated X (BAX) is important for cell apoptosis. In this work, we investigated the association of BAX promoter DNA methylation with coronary heart disease (CHD) in Han Chinese. METHODS:A SYBR green-based quantitative methylation specific PCR (qMSP) was used to test BAX methylation levels in 959 CHD cases and 514 controls. RESULTS:Although BAX methylation was not associated with CHD in the total samples, further breakdown analysis by age showed that BAX hypermethylation was significantly associated with CHD for individuals aged over 70 (median percentage of methylation ratio [PMR], 10.70% in cases versus (vs) 2.25% in controls, P =.046). Moreover, BAX methylation was associated with smoking and lipoprotein A (Lp(a)) for individuals aged over 70 (CHD: smoking P?=?.012, Lp(a) P?=?.001; non-CHD: smoking P?=?.051, Lp(a) P?=?.004). Further analysis of Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data showed BAX expression was upregulated by 5-aza-2'-deoxycytidine demethylation agent (fold?=?1.66, P?=?.038) and inversely correlated with BAX methylation (r?=?-0.428, P?=?8E-05). CONCLUSIONS:Our study supported that BAX hypermethylation might contribute to CHD risk via downregulation of BAX expression for individuals aged over 70.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6358363 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Association of BAX hypermethylation with coronary heart disease is specific to individuals aged over 70.

Zhang Limei L Ji Huihui H Huang Yi Y Hu Haochang H Li Bin B Yang Yong Y Yu Hang H Chen Xiaoying X Li Wenxia W Liu Fang F Wang Shi S Wang Chunming C Chen Ke K Bao Yingchun Y Liu Haibo H Duan Shiwei S

Medicine 20190101 4

<h4>Introduction</h4>As a member of B-cell lymphoma-2 (BCL-2) gene family, BCL-2 associated X (BAX) is important for cell apoptosis. In this work, we investigated the association of BAX promoter DNA methylation with coronary heart disease (CHD) in Han Chinese.<h4>Methods</h4>A SYBR green-based quantitative methylation specific PCR (qMSP) was used to test BAX methylation levels in 959 CHD cases and 514 controls.<h4>Results</h4>Although BAX methylation was not associated with CHD in the total samp ...[more]

PMID: 30681575

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Project description:BackgroundThe use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events.MethodsWe used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years.ResultsAt baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], P=0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, P=0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28).ConclusionA PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Project description:ImportanceCoronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults.ObjectiveTo determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up.Design, setting, and participantsThe Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.Main outcomes and measuresIncident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years.ResultsAt year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2.Conclusions and relevanceThe presence of CAC among individuals aged between 32 and 46 years was associated with increased risk of fatal and nonfatal CHD during 12.5 years of follow-up. A CAC score of 100 or more was associated with early death. Adults younger than 50 years with any CAC, even with very low scores, identified on a computed tomographic scan are at elevated risk of clinical CHD, CVD, and death. Selective use of screening for CAC might be considered in individuals with risk factors in early adulthood to inform discussions about primary prevention.

Project description:ObjectivesThe AHA/ACC-2017 hypertension guideline recommends an age-independent target blood pressure (BP) of less than 130/80 mmHg. In an elderly cohort without established cardiovascular disease (CVD) at baseline, we determined the impact of this guideline on the prevalence of hypertension and associated CVD risk.MethodsNineteen thousand, one hundred and fourteen participants aged at least 65 years from the ASPirin in Reducing Events in the Elderly (ASPREE) study were grouped by baseline BP: 'pre-2017 hypertensive' (BP ≥140/90 mmHg and/or on antihypertensive drugs); 'reclassified hypertensive' (normotensive by pre-2017 guidelines; hypertensive by AHA/ACC-2017 guideline), and 'normotensive' (BP <130 and <80 mmHg). For each group, we evaluated CVD risk factors, predicted 10-year CVD risk using the Atherosclerotic Cardiovascular Disease (ASCVD) risk equation, and reported observed CVD event rates during a median 4.7-year follow-up.ResultsOverall, 74.4% (14 213/19 114) were 'pre-2017 hypertensive'; an additional 12.3% (2354/19 114) were 'reclassified hypertensive' by the AHA/ACC-2017 guideline. Of those 'reclassified hypertensive', the majority (94.5%) met criteria for antihypertensive treatment although 29% had no other traditional CVD risk factors other than age. Further, a relatively lower mean 10-year predicted CVD risk (18% versus 26%, P < 0.001) and lower CVD rates (8.9 versus 12.1/1000 person-years, P = 0.01) were observed in 'reclassified hypertensive' compared with 'pre-2017 hypertensive'. Compared with 'normotensive', a hazard ratio (95% confidence interval) for CVD events of 1.60 (1.26-2.02) for 'pre-2017 hypertensive' and 1.26 (0.93-1.71) for 'reclassified hypertensive' was observed.ConclusionApplying current CVD risk calculators in the elderly 'reclassified hypertensive', as a result of shifting the BP threshold lower, increases eligibility for antihypertensive treatment but documented CVD rates remain lower than hypertensive patients defined by pre2017 BP thresholds.

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Association of BAX hypermethylation with coronary heart disease is specific to individuals aged over 70.

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Association of BAX hypermethylation with coronary heart disease is specific to individuals aged over 70.

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