S-EPMC5081270 - Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study. - OmicsDI

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Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study.

ABSTRACT: Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary heart disease (CHD) and incident cardiovascular disease (CVD) in a primary prevention cohort.8127 participants from the ARIC study (4th visit, 1996-1998) were stratified as having minimal, mild, or substantial atherosclerosis by cIMT. Levels of C-reactive protein, lipoprotein-associated phospholipase A2, cardiac troponin T, N-terminal pro-brain natriuretic peptide, lipoprotein(a), cystatin C, and urine albumin to creatinine ratio were measured in each participant. Hazard ratios were used to determine the relationship between the biomarkers and incident CHD, stroke, and CVD in each category of atherosclerosis.While each of the biomarkers was significantly associated with risk of events overall, we found no significant differences noted in the strength of association of biomarkers with CHD, stroke, and CVD when analyzed by degree of atherosclerosis.These findings suggest that the level of atherosclerosis does not significantly influence the association between biomarkers and CVD.

SUBMITTER: Agarwala A

PROVIDER: S-EPMC5081270 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Biomarkers and degree of atherosclerosis are independently associated with incident atherosclerotic cardiovascular disease in a primary prevention cohort: The ARIC study.

Agarwala Anandita A Virani Salim S Couper David D Chambless Lloyd L Boerwinkle Eric E Astor Brad C BC Hoogeveen Ron C RC Coresh Joe J Sharrett A Richey AR Folsom Aaron R AR Mosley Tom T Ballantyne Christie M CM Nambi Vijay V

Atherosclerosis 20160825

<h4>Background and aims</h4>Biomarkers and atherosclerosis imaging have been studied individually for association with incident cardiovascular disease (CVD); however, limited data exist on whether the biomarkers are associated with events with a similar magnitude in the presence of atherosclerosis. In this study, we assessed whether the presence of atherosclerosis as measured by carotid intima media thickness (cIMT) affects the association between biomarkers known to be associated with coronary ...[more]

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Project description:Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (?7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.

Project description:AimsThe total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol.MethodsWe studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach.ResultsMean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively.ConclusionClinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.

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Project description:ImportanceThe Million Hearts initiative emphasizes ABCS (aspirin for high-risk patients, blood pressure [BP] control, cholesterol level management, and smoking cessation). Evidence of the effects of drugs used to achieve ABCS has not been synthesized comprehensively in the prevention of primary atherosclerotic cardiovascular disease (ASCVD).ObjectiveTo compare the efficacy and safety of aspirin, BP-lowering therapy, statins, and tobacco cessation drugs for fatal and nonfatal ASCVD outcomes in primary ASCVD prevention.Evidence reviewStructured search of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, EMBASE, and PROSPERO International Prospective Systematic Review Trial Register to identify systematic reviews published from January 1, 2005, to June 17, 2015, that reported the effect of aspirin, BP-lowering therapy, statin, or tobacco cessation drugs on ASCVD events in individuals without prevalent ASCVD. Additional studies were identified by searching the reference lists of included systematic reviews, meta-analyses, and health technology assessment reports. Reviews were selected according to predefined criteria and appraised for methodologic quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (range, 0-11). Studies were independently reviewed for key participant and intervention characteristics. Outcomes that were meta-analyzed in each included review were extracted. Qualitative synthesis was performed, and data were analyzed from July 2 to August 13, 2015.FindingsFrom a total of 1967 reports, 35 systematic reviews of randomized clinical trials were identified, including 15 reviews of aspirin, 4 reviews of BP-lowering therapy, 12 reviews of statins, and 4 reviews of tobacco cessation drugs. Methodologic quality varied, but 30 reviews had AMSTAR ratings of 5 or higher. Compared with placebo, aspirin (relative risk [RR], 0.90; 95% CI, 0.85-0.96) and statins (RR, 0.75; 95% CI, 0.70-0.81) reduced the risk for ASCVD. Compared with placebo, BP-lowering therapy reduced the risk for coronary heart disease (RR, 0.84; 95% CI, 0.79-0.90) and stroke (RR, 0.64; 95% CI, 0.56-0.73). Tobacco cessation drugs increased the odds of continued abstinence at 6 months (odds ratio range, 1.82 [95% CI, 1.60-2.06] to 2.88 [95% CI, 2.40-3.47]), but the direct effects on ASCVD were poorly reported. Aspirin increased the risk for major bleeding (RR, 1.54; 95% CI, 1.30-1.82), and statins did not increase overall risk for adverse effects (RR, 1.00; 95% CI, 0.97-1.03). Adverse effects of BP-lowering therapy and tobacco cessation drugs were poorly reported.Conclusions and relevanceThis overview demonstrates high-quality evidence to support aspirin, BP-lowering therapy, and statins for primary ASCVD prevention and tobacco cessation drugs for smoking cessation. Treatment effects of each drug can be used to enrich discussions between health care professionals and patients in primary ASCVD prevention.

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Project description:ObjectivesThis study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population.BackgroundAortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals.MethodsWe performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis.ResultsOver a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21).ConclusionsIn this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).