Genetic loci associated with ideal cardiovascular health: A meta-analysis of genome-wide association studies.

BACKGROUND: Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. METHODS AND RESULTS: We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50±5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 × 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. CONCLUSION: A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.

Health behavior modification after electron beam computed tomography and physician consultation.

This study aimed to determine whether participants reported altering health behaviors (physical activity, diet, and alcohol consumption) after seeing results from an electron-beam computed tomography (EBCT) scan for coronary artery calcium and reviewing these results with a physician. Clinicians attempt to motivate patients to control cardiovascular risk factors by adopting healthy behaviors and reducing harmful actions. Asymptomatic patients (N = 510) were evaluated by EBCT for the extent of coronary artery calcium. Information pertaining to demographics, health history, and lifestyle/health behaviors was obtained from each participant at the time of the EBCT scan. Patients were given their numerical calcium score, shown images of their coronary arteries, and counseled by a physician for lifestyle and medical risk modification based on their coronary artery calcium score. Approximately 6 years after the scan, participants completed a follow-up questionnaire related to lifestyle modifications. In multivariable analysis, the presence and extent of coronary artery calcium was significantly associated with beneficial health behavior modifications. Specifically, the greater a patient's coronary artery calcium score, the more likely they were to report increasing exercise (odds ratio = 1.34, P = 0.02), changing diet (odds ratio = 1.40, P < 0.01), and changing alcohol intake (odds ratio = 1.46, P = 0.05). This study suggests that seeing and being counseled on the presence and extent of coronary artery calcium is significantly associated with behavior change.

Association between IL-6 and the extent of coronary atherosclerosis in the veterans affairs diabetes trial (VADT).

AIMS: The aim of the present study was to investigate the association of high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with the extent of calcified coronary atherosclerosis in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND RESULTS: This is a cross-sectional study of 306 subjects aged 40years or older who were enrolled into the veterans affairs diabetes trial (VADT). Calcified coronary atherosclerosis was assessed using electron beam computed tomography scored by the Agatston method. Clinical parameters, traditional cardiovascular risk factors and plasma levels of CRP, IL-6 and Lp-PLA2 were measured at the time of the scan. Coronary artery calcium (CAC) scores increased stepwise across increasing categories of IL-6, but did not change across increasing categories of CRP and Lp-PLA2. After adjustment for traditional cardiovascular risk factors, IL-6 was significantly associated with CAC scores (p=0.05). The association between IL-6 and CAC was largely in those with lower (below the median) abdominal artery calcium (AAC) levels (p=0.04). CONCLUSIONS: Despite a generally higher level of systemic inflammation in T2DM, the inflammatory marker IL-6 remained significantly associated with CAC score, particularly in those subjects with lower AAC scores.