Blood Institute Family Heart Research Articles

Is Bitter Better? The Benefits of Chocolate for the Cardiovascular System

Background and Aims: Cocoa, particularly dark chocolate, is rich in flavonoids, and recent studies have demonstrated blood pressure lowering effects of dark chocolate. Because limited data are available on the association of chocolate consumption and the risk of coronary heart disease (CHD), the investigators examined the association between chocolate consumption and prevalence of CHD. Methods: Using a cross-sectional design, 4,970 participants 25to 93years ofage were studiedintheNationalHeart, Lung, and Blood Institute (NHLBI) Family Heart Study. Chocolate intakewasassessedthroughasemiquantitativefoodfrequency questionnaire. The workers generalized estimating equations to assess adjusted odds ratios. Results: Compared with subjects who did not report any chocolate intake at all, the odds ratios for CHD were 1.01 (95% CI, 0.76–1.37), 0.74 (95% CI, 0.56–0.98), and 0.43 (95% CI, 0.28–0.67) in subjects consuming chocolate 1–3 times per month, 1–4 times per week, or 5+ times per week, respectively (P for trend <0.0001), adjusting for age, sex, family CHD risk group, and a large number of other confounders. Interestingly, subjects who consumed nonchocolate candy 5+ times per week had a 49% higher prevalence of CHD than those with no such consumption (OR, 1.49; 95% CI, 0.96–2.32). Discussion: The authors suggest that consumption of chocolate is inversely related with prevalent CHD in a general United States population.

Association of Coronary Artery Calcified Plaque With Clinical Coronary Heart Disease in the National Heart, Lung, and Blood Institute’s Family Heart Study

The presence of calcified coronary artery plaque has shown variable association with clinical coronary heart disease (CHD), particularly after adjustment for other risk factors. From 2002 to 2004, as part of the National Heart, Lung, and Blood Institute's Family Heart Study, coronary artery calcium (CAC) scans by 4-slice multidetector computed tomography were performed in 3,359 subjects, including 389 with clinically diagnosed CHD. Among these was a cohort of 2,254 patients who had been asymptomatic at an initial examination 7 to 9 years previously (1994 to 1996), with 111 who had developed newly diagnosed, nonfatal CHD since the initial examination. In cross-sectional analyses, we examined associations between CAC and CHD in the entire group and in the subgroup seen at the initial examination. In the 2 sets of analyses, odds ratios for CHD ranged from approximately 4 in those with CAC scores of 100 to 199 (p <0.01) to >20 in those with CAC scores >/=1,000 (p <0.0001) compared with those with no measurable CAC. This steep gradient of risk persisted after adjustment for risk factors. A quantitative CHD family history score was significantly associated with CHD even after adjusting for all standard risk factors and including CAC in the model. In conclusion, CAC was strongly associated with CHD even after adjustment for standard risk factors and family history contributed independently to CHD risk.

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD=3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD=3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD=3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD=3.05) and on chromosome 5 in the entire group of families (LOD=2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD=4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD=3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI Family Heart Study

To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. A population-based cross-sectional study. Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. The prevalence of examined mutations by Lewis phenotype. The examined mutations were common and strongly associated with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.