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Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study.

ABSTRACT: BACKGROUND AND AIMS:Lipoprotein(a) (Lp[a]) is a strong genetic risk factor for cardiovascular disease (CVD). The American Heart Association has prioritised seven cardiovascular health metrics to reduce the burden of CVD: body mass index, healthy diet, physical activity, smoking status, blood pressure, diabetes and cholesterol levels (together also known as ideal cardiovascular health). Our objective was to determine if individuals with high Lp(a) levels could derive cardiovascular benefits if characterized by ideal cardiovascular health. METHODS:A total of 14,051 participants of the EPIC-Norfolk study were stratified according to the cardiovascular health score (based on the number of health metrics with an ideal, intermediate or poor status). Of them, 1732 had a CVD event during a mean follow-up of 11.5 years. Cox proportional hazards models were used to describe the association between the cardiovascular health score and Lp(a) level or genotype (as estimated by the rs10455872 variant) with the risk of CVD. RESULTS:We observed little or no differences in serum Lp(a) levels across the seven cardiovascular health metric categories. Among participants with high serum Lp(a) levels ?50 mg/dl), those in the highest (i.e. healthiest) cardiovascular health score category (10-14) had an adjusted hazard ratio for cardiovascular disease of 0.33 (95% CI = 0.17-0.63, p = 0.001) compared to participants in the lowest (i.e. unhealthiest) cardiovascular health score category(0-4). Similar results were obtained when we replaced Lp(a) with rs10455872. CONCLUSIONS:Although Lp(a) levels are only slightly influenced by cardiovascular health metrics, an ideal cardiovascular health could substantially reduce CVD risk associated with high Lp(a) levels or genotype.

SUBMITTER: Perrot N

PROVIDER: S-EPMC5321848 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study.

Perrot Nicolas N Verbeek Rutger R Sandhu Manjinder M Boekholdt S Matthijs SM Hovingh G Kees GK Wareham Nicholas J NJ Khaw Kay-Tee KT Arsenault Benoit J BJ

Atherosclerosis 20161111

<h4>Background and aims</h4>Lipoprotein(a) (Lp[a]) is a strong genetic risk factor for cardiovascular disease (CVD). The American Heart Association has prioritised seven cardiovascular health metrics to reduce the burden of CVD: body mass index, healthy diet, physical activity, smoking status, blood pressure, diabetes and cholesterol levels (together also known as ideal cardiovascular health). Our objective was to determine if individuals with high Lp(a) levels could derive cardiovascular benefi ...[more]

PMID: 27998826

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Project description:OBJECTIVE:Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. APPROACH AND RESULTS:Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, (r=0.39), particle numbers of very-low-density lipoprotein (r=0.25), intermediate-density lipoprotein (r=0.23), small dense low-density lipoprotein (r=0.26), and high-sensitivity C-reactive protein (r=0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number (r=-0.11), P<0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein. CONCLUSIONS:ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association.

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Dataset Information

Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study.

Publications

Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study.

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