Comparison of coronary heart disease genetic assessment with conventional cardiovascular risk assessment in primary care: reflections on a feasibility study

This study assesses the feasibility of collecting genetic samples and self-reported outcome measures after cardiovascular risk assessment, and presenting the genetic test results to participants. Coronary heart disease (CHD) genetic tests are increasingly available through direct-to-consumer marketing, but their potential clinical impact on cardiovascular risk assessment is unclear. Observational study in 10 British general practices in Central England. A total of 320 individuals, who had completed conventional cardiovascular risk assessment, were offered CHD genetic test, with follow-up outcome questionnaire at eight months for lifestyle change and State-Trait Anxiety. A total of 119 (37%) participants returned genetic test specimens, with over a third reporting family history of CHD in a specified relative; 79 (66.4%) were categorized above-average risk on conventional cardiovascular risk assessment, 65 of whom (82.3%) were only average risk on genetic assessment. The dietary fat questionnaire was poorly completed while study participation was not associated with increased anxiety (mean increase in anxiety score=2.1; 95% CI −0.1–4.3; P=0.06). As a feasibility study, over a third of individuals offered genetic testing in primary care, as part of CVD risk assessment, took up the offer. Although intervention did not appear to increase anxiety, this needs further evaluation. To improve generalizability and effect size, future studies should actively engage individuals from wider socio-economic backgrounds who may not have already contemplated lifestyle change. The current research suggests general practitioners will face the clinical challenge of patients presenting with direct-to-consumer genetic results that are inconsistent with conventional cardiovascular risk assessment

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe

The S447X variant of lipoprotein lipase gene is associated with metabolic syndrome and lipid levels among Turks.

Background: We evaluated the relationship of the lipoprotein lipase (LPL) S447X variant with serum lipid levels and the metabolic syndrome (MS) in the Turkish Adult Risk Factor (TARF) study. This is the first study examining this LPL variant in the Turkish population

Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

<div><p>Background</p><p>The association of <i>APOE</i> genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention.</p><p>Methods and Findings</p><p>To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, <i>p <</i> 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both <i>p <</i> 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both <i>p <</i> 0.001), high-density lipoprotein (correlation coefficient 0.16 and −0.14, respectively; both <i>p <</i> 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both <i>p <</i> 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, <i>p =</i> 0.001) and lipoprotein(a) (correlation coefficient −0.11, <i>p <</i> 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect.</p><p>Conclusions</p><p>In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of <i>APOE</i> genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.</p></div

Baseline characteristics of studies included.

<p>Baseline characteristics of studies included.</p

Summary estimates for the association of log ApoE concentration with cardiovascular events from the three studies.

<p>Summary estimates for the association of log ApoE concentration with cardiovascular events from the three studies.</p

Bivariate associations of circulating ApoE with measured markers in the population-based studies, ELSA and NPHSII.

<p>Bivariate associations of circulating ApoE with measured markers in the population-based studies, ELSA and NPHSII.</p