NHLBI Family Heart Study Research Articles

Association of potato consumption with calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study

Background and aimsWhile the association of potato consumption with risk factors for coronary artery disease has been inconsistent, no data are available in the literature on the influence of potato consumption on subclinical disease. Thus, we sought to examine whether baked/mashed potato consumption is associated with calcified atherosclerotic plaques in the coronary arteries. Methods and ResultsIn a cross-sectional design, we studied 2208 participants of the NHLBI Family Heart Study. These subjects were selected based on their elevated cardiovascular disease risk compared to the general population. Potato consumption was assessed by a semi-quantitative food frequency questionnaire. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age at initial clinic visit was 58.2 years and 55% were female. Median consumption of potatoes was 2–4/week. There was no statistically significant association between frequency of potato consumption and prevalent CAC: odds ratios (95% CI) for CAC were 1.0 (reference), 0.85 (0.56–1.30), 0.85 (0.58–1.26), and 0.95 (0.60–1.53) among subjects reporting potato consumption of <1/week, 1/week, 2–4/week, and 5+/week, respectively (p for linear trend 0.83), adjusting for age, sex, BMI, smoking, exercise, diabetes, hypertension, total calories, prevalent coronary heart disease, income, education, and daily red meat intake. ConclusionsWe found no significant association between baked/mashed potato consumption and CAC in older adults. Study registration numberNCT00005136. Study registration date: 5/25/2000.

Dairy product consumption and calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study.

Diet modification is a major component of non-pharmacological coronary heart disease (CHD) prevention. Few studies have examined the association between consumption of different dairy products with subclinical coronary artery disease. We sought to examine whether milk, yogurt, or cheese consumption is associated with calcified atherosclerotic plaques in the coronary arteries. We cross-sectionally examined 2278 participants from the National Heart, Lung, and Blood Institute Family Heart Study. Dairy consumption was assessed by a semiquantitative food frequency questionnaire. Coronary artery calcium (CAC) was estimated by cardiac computed tomography. We used an Agatston score of ≥100 to indicate prevalent CAC and fitted multivariable logistic regression to calculate adjusted odds ratios. Mean age was 58±13 years and 45% were male. The frequency of milk (≤1/week, 2-4/week, and ≥5/week; 22%, 14%, and 64%, respectively), yogurt (almost never, <1/week, and ≥1/week; 54%, 20%, and 26%, respectively), and cheese consumption (<1/week, 1/week, 2-4/week, and ≥5/week; 15%, 17%, 41%, and 27%, respectively) varied in the cohort. We observed an inverse association of cheese consumption with prevalent CAC: odds ratio (95% CI) of 0.63 (0.42-0.94) when comparing cheese intake of ≥5 servings/week with <1/week, adjusting for sex, age, body mass index, cigarette pack years, presence of CHD, family income, and education (p for linear trend 0.007). In contrast, there was no association between yogurt or milk consumption and CAC (p for linear trend 0.51 and 0.87, respectively). Our data suggest that cheese consumption but not yogurt or milk is associated with a lower odds of CAC in men and women.

Coffee consumption and calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study

While a recent meta-analysis of prospective studies reported that coffee consumption is associated with a lower risk of cardiovascular disease mortality, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Thus, the aim of the present study was to see the association of coffee consumption with the prevalence of atherosclerotic plaque in the coronary arteries in NHLBI Family Heart Study. In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC as an Agatston score of ≥100 and used generalized estimating equations to calculate prevalence ratios of CAC as well as a sensitivity analysis at a range of cutpoints for CAC. Mean age was 56.7 years and 59% of the study subjects were female. In adjusted analysis for age, sex, BMI, smoking, alcohol, physical activity, field center, and energy intake, prevalence ratio (95% CI) for CAC was 1.0 (reference), 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64) for coffee consumption of almost never, <1/day, 1/day, 2-3/day, and ≥4 cups/day, respectively. In a sensitivity analysis, there was no evidence of association between coffee consumption and prevalent CAC when CAC cut points of 0, 50, 150, 200, and 300 were used. These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.

Abstract P243: Sugar-sweetened Beverage Consumption is Not Associated with Calcified Atherosclerotic Plaques in the Coronary Arteries: The NHLBI Family Heart Study

Background: Sugar-sweetened beverage (SSB) intake is associated with higher risk of weight gain, diabetes, hypertension, cardiovascular disease and cardiovascular mortality. However, the association of SSB with subclinical atherosclerosis in the general population is unknown. Hypothesis: Our primary hypothesis is that higher intake of SSB is associated with a higher prevalence of atherosclerotic plaque in coronary arteries in NHLBI Family Heart Study. Methods: In a cross-sectional design, we studied 1990 participants of the NHLBI Family Heart Study without known coronary heart disease. SSB was assessed through a semi-quantitative food frequency questionnaire by asking how often participants consumed 1 glass of regular soda, diet soda, and fruit punch/kool-aid. Coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios of CAC in SAS 9.3 software. Results: Mean age and BMI were 55.0 years and 29.5 kg/m2 respectively, and 60% were female. In adjusted analysis for age, sex, BMI, smoking, alcohol use, physical activity, total calories, and field center, higher SSB consumption was not associated with higher prevalence of CAC (Table1). In a sensitivity analysis, there was no evidence of association between SSB and prevalent CAC when CAC cut points of 0, 50, 150, 200, and 300 were used. Conclusions: These data do not provide evidence for an association between SSB consumption and prevalent CAC in adult men and women.

Abstract MP15: Physical Activity is Inversely Associated with Calcified Atherosclerotic Plaque in the Coronary Arteries: The NHLBI Family Heart Study

Background: Physical activity is integral to the primary prevention of cardiovascular diseases. However, studies have reported mixed findings on the association between physical activity and coronary artery calcification (CAC). Hypothesis: Our primary hypothesis is that physical activity is inversely associated with prevalent CAC. Methods: In a cross-sectional design, we studied 2,971 participants of the NHLBI Family Heart Study without a history of MI, CABG or PTCA. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute block metabolic equivalent hours per week. CAC was measured by cardiac CT, and we defined prevalent CAC using an Agatston score of at least 100. Generalized estimating equations were used to calculate adjusted prevalence ratios of CAC. Results: Mean age was 55 (±12.7) years and 60.3% of participants were women. Compared to 0-4 blocks/d, prevalence ratios for CAC after adjusting for age, sex, race, BMI, hyperlipidemia, hypertension, diabetes, smoking, and alcohol abuse were 0.73, 95% CI: 0.55-0.97 for &gt;4-8 blocks/d, 0.72, 95% CI: 0.58-0.89 for &gt;8-20 blocks/d, and 0.82, 95% CI: 0.62-1.1 for &gt;20 blocks/d, p for trend 0.02. Corresponding values for total block activity were 0.84, 95% CI: 0.53-1.30 for 1-4 met-hrs/wk, 0.50, 95% CI: 0.31- 0.81 for &gt;4-7 met-hrs/wk, 0.68, 95% CI: 0.47-1.00 for &gt;7-14 met-hrs/wk, and 0.54, 95% CI: 0.33-0.88 for &gt;14-22 met-hrs/wk, p for trend 0.04 (Table 1). In a secondary analysis stratified by BMI (&lt;25 and ≥25 kg/m2), the results remained statistically significant for those with BMI ≥ 25 (p=0.01). The number of participants with BMI &lt; 25 was too small for analysis. The inverse association persisted when we repeated the main analyses using CAC cutoffs of 150 and 200, but not 50. Conclusion: The Family Heart Study data are consistent with an inverse association of mild to moderate physical activity with coronary artery calcification in adult men and women.

A Framework for Interpreting Type I Error Rates from a Product-Term Model of Interaction Applied to Quantitative Traits.

ABSTRACTAdequate control of type I error rates will be necessary in the increasing genome‐wide search for interactive effects on complex traits. After observing unexpected variability in type I error rates from SNP‐by‐genome interaction scans, we sought to characterize this variability and test the ability of heteroskedasticity‐consistent standard errors to correct it. We performed 81 SNP‐by‐genome interaction scans using a product‐term model on quantitative traits in a sample of 1,053 unrelated European Americans from the NHLBI Family Heart Study, and additional scans on five simulated datasets. We found that the interaction‐term genomic inflation factor (lambda) showed inflation and deflation that varied with sample size and allele frequency; that similar lambda variation occurred in the absence of population substructure; and that lambda was strongly related to heteroskedasticity but not to minor non‐normality of phenotypes. Heteroskedasticity‐consistent standard errors narrowed the range of lambda, with HC3 outperforming HC0, but in individual scans tended to create new P‐value outliers related to sparse two‐locus genotype classes. We explain the lambda variation as a result of non‐independence of test statistics coupled with stochastic biases in test statistics due to a failure of the test to reach asymptotic properties. We propose that one way to interpret lambda is by comparison to an empirical distribution generated from data simulated under the null hypothesis and without population substructure. We further conclude that the interaction‐term lambda should not be used to adjust test statistics and that heteroskedasticity‐consistent standard errors come with limitations that may outweigh their benefits in this setting.

Abstract 19899: Coffee Consumption is Not Associated With Calcified Atherosclerotic Plaques in the Coronary Arteries: The NHLBI Family Heart Study

Introduction: The average consumption of coffee per day in the United States is 3.2 cups. While in a recent meta-analysis of 21 prospective studies, coffee consumption was associated with a lower risk of cardiovascular disease mortality, with the lowest risk observed among consumers of 4 cups/day, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Hypothesis: Our primary hypothesis is that coffee consumption is inversely associated with the prevalence of atherosclerotic plaque in coronary arteries in NHLBI Family Heart Study Methods: In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Results: Mean age and BMI were 56.7 years and 28.8 kg/m2 respectively, and 59% were male. In crude analysis, higher coffee consumption was associated with higher prevalence of CAC. Odds ratio (95%CI) for CAC were 1.0 (reference), 1.34 (0.92-1.94), 2.48 (1.81-3.40), 2.45 (1.82-3.30), and 1.81 (1.29-2.56) for coffee consumption of almost never, &lt;1/day, 1/day, 2-3/day, and ≥4 cups/day. However, controlling for potential confounding factors eliminated such association [Corresponding odds ratio (95%CI) for CAC: 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64), respectively, adjusting for age, sex, BMI, smoking, alcohol, physical activity, field center, and total calories]. Conclusions: These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.

Admixture mapping of coronary artery calcification in African Americans from the NHLBI family heart study.

BackgroundCoronary artery calcification (CAC) is an imaging biomarker of coronary atherosclerosis. In European Americans, genome-wide association studies (GWAS) have identified several regions associated with coronary artery disease. However, few large studies have been conducted in African Americans. The largest meta-analysis of CAC in African Americans failed to identify genome-wide significant variants despite being powered to detect effects comparable to effects identified in European Americans. Because CAC is different in prevalence and severity in African Americans and European Americans, admixture mapping is a useful approach to identify loci missed by GWAS.ResultsWe applied admixture mapping to the African American cohort of the Family Heart Study and identified one genome-wide significant region on chromosome 12 and three potential regions on chromosomes 6, 15, and 19 that are associated with CAC. Follow-up studies using previously reported GWAS meta-analysis data suggest that the regions identified on chromosome 6 and 15 contain variants that are possibly associated with CAC. The associated region on chromosome 6 contains the gene for BMP-6, which is expressed in vascular calcific lesions.ConclusionsOur results suggest that admixture mapping can be a useful hypothesis-generating tool to identify genomic regions that contribute to complex diseases in genetically admixed populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0196-x) contains supplementary material, which is available to authorized users.

Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: The NHLBI Family Heart Study

Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries. In a cross-sectional design, we studied 1848 participants of the NHLBI Family Heart Study without known CHD. Egg consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age was 56.5 years and 41% were male. Median consumption of eggs was 1/week. There was no association between frequency of egg consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.95 (0.66-1.38), 0.94 (0.63-1.40), and 0.90 (0.57-1.42) for egg consumption of almost never, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.66), adjusting for age, sex, BMI, smoking, alcohol, physical activity, income, field center, total calories, and bacon. Additional control for hypertension and diabetes mellitus, or restricting the analysis to subjects with diabetes mellitus or fasting glucose >126 mg/dL did not alter the findings. These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women.

Correction

HomeCirculation: Cardiovascular ImagingVol. 7, No. 2Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published1 Mar 2014https://doi.org/10.1161/HCI.0000000000000003Circulation: Cardiovascular Imaging. 2014;7:415This article corrects the followingAdult Height and Prevalence of Coronary Artery CalciumA correction was needed to an article by Miedema et al, which published online December 11, 2013, and appeared in the January 2014 issue of this journal (Miedema MD, Petrone AB, Arnett DK, Dodson JA, Carr JJ, Pankow JS, Hunt SC, Province MA, Kraja A, Gaziano JM, Djousse L. Adult Height and Prevalence of Coronary Artery Calcium: The National Heart, Lung, and Blood Institute Family Heart Study. Circ Cardiovasc Imaging. 2014;7:).The Sources of Funding statement was revised and now appears as follows:The NHLBI Family Heart Study was supported by the NHLBI cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, and U01 HL67902. Dr Dodson performed this work while on a T32 training grant from the National Institutes of Health/National Institute on Aging (T32 AG000158).This correction has been made to the current online version of the article, which is available at: http://circimaging.ahajournals.org/content/7/1/52.full Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesAdult Height and Prevalence of Coronary Artery CalciumMichael D. Miedema, et al. Circulation: Cardiovascular Imaging. 2014;7:52-57 March 2014Vol 7, Issue 2 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/HCI.0000000000000003 Originally publishedMarch 1, 2014 PDF download Advertisement

α(1,3)-Fucosyltransferases FUT4 and FUT7 Control Murine Susceptibility to Thrombosis

The α(1,3)-fucosyltransferases, types IV and VII (FUT4 and FUT7, respectively), are required for the synthesis of functional selectin-type leukocyte adhesion molecule ligands. The selectins and their ligands modulate leukocyte trafficking, and P-selectin and its ligand, P-selectin glycoprotein ligand-1, can modulate hemostasis and thrombosis. Regulation of thrombosis by FUT4 and/or FUT7 activity was examined in mouse models of carotid artery thrombosis and collagen/epinephrine-induced thromboembolism. Mice lacking both FUT4 and FUT7 (Fut(-/-) mice) had a shorter time to occlusive thrombus formation in the injured carotid artery and a higher mortality due to collagen/epinephrine-induced pulmonary thromboemboli. Mice lacking P-selectin or P-selectin glycoprotein ligand-1 did not have a prothrombotic phenotype. Whole blood platelet aggregation was enhanced, and plasma fibrinogen content, clot weight, and clot strength were increased in Fut(-/-) mice, and invitro clot lysis was reduced compared with wild type. Fut4(-/-), but not Fut7(-/-), mice had increased pulmonary thromboembolism-induced mortality and decreased thromboemboli dissolution invivo. These data show that FUT4 and FUT7 activity regulates thrombosis in a P-selectin- and P-selectin glycoprotein ligand-1-independent manner and suggest that FUT4 activity is important for thrombolysis.

The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study

ObjectivesNonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to hepatic inflammation to cirrhosis. We sought to identify common genetic variants contributing to NAFLD, using CT measured fatty liver (FL), and alanine aminotransferase levels (ALT), as a biochemical marker of hepatic inflammation. MethodsWe employed a correlated meta-analysis (CMA) to test whether combining FL and ALT genomewide association (GWA) results, using ∼2.5 million imputed SNPs, could enhance ability to detect variants influencing both traits. ResultsVariants of the ERLIN1-CHUK-CWF19L1 gene cluster were associated with concomitant variation of FL and ALT. Nine variants (rs2862954, rs1408579, rs10883451, rs11597086, rs11591741, rs17729876, rs17668255, rs17668357, rs12784396) displayed genomewide significant associations at loci concomitantly influencing FL and ALT (2.47 × 10−9 ≤ CMA-p ≤ 4.29 × 10−10) as compared with the suggestive significance of marginal tests (4.11 × 10−5 ≤ GWA-p ≤ 2.34 × 10−6). For example, the missense variant in ERLIN1-rs2862954 was genomewide significant (CMA-p = 4.88 × 10−10) for the combination of FL and ALT, while the respective univariate associations were suggestive (FL:p = 5.74 × 10−6, ALT:p = 3.71 × 10−6). Further we investigated whether the concomitant associations were driven mainly by ALT levels. When we adjusted FL by ALT, the correlated associations diminished but did not vanish (CMA-p ≤ 3.3 × 10−7). Our findings suggest ERLIN1-CHUK-CWF19L1 variants are associated with early stage of FL accumulation (measured by CT) to hepatic inflammation (ALT levels), and the association enhances when accounting for the correlations between their scans. ConclusionsCMA approach enhanced the ability to identify novel variants of the ERLIN1-CHUK-CWF19L1 influencing both simple steatosis and hepatic steatosis with inflammation, which suggest that this gene cluster may regulate the susceptibility of NAFLD in a wide spectrum of disease.

The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study

The ERLIN1-CHUK-CWF19L1 gene cluster influences liver fat deposition and hepatic inflammation in the NHLBI Family Heart Study

PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: The NHLBI Family Heart Study

PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: The NHLBI Family Heart Study

PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: the NHLBI family heart study.

BackgroundFatty liver disease (FLD) is characterized by increased intrahepatic triglyceride content with or without inflammation and is associated with obesity, and features of the metabolic syndrome. Several recent GWAS have reported an association between SNP rs738409 in the PNPLA3 gene and FLD. Liver attenuation (Hounsfield Units, HU) by computed tomography is a non-invasive measure of liver fat, with lower values of HU indicating higher liver fat content. Clinically, a liver attenuation (LA) value of ≤ 40 HU indicates moderate-to-severe hepatic steatosis.ObjectiveWe investigated whether missense rs738409 PNPLA3 interacted with abdominal visceral adipose tissue volume (cm3) to reduce liver attenuation (i.e. increased liver fat) in 1,019 European American men and 1,238 European American women from the Family Heart Study.MethodsWe used linear regression to test the additive effect of genotype, abdominal visceral adipose tissue (VAT), and their multiplicative interaction on LA adjusted for age, BMI, HDL-cholesterol, insulin resistance, serum triglycerides, abdominal subcutaneous adipose tissue, and alcohol intake.ResultsIn men and women combined, the interaction between each copy of the rs738409 variant allele (MAF 0.23) and 100cm3/150mm slice VAT decreased LA by 2.68±0.35 HU (p < 0.01). The interaction of 100cm3 VAT and the variant allele was associated with a greater decrease in LA in women than men (−4.8±0.6 and −2.2±0.5 HU, respectively).ConclusionsThe interaction between genotype and VAT volume suggest key differences in the role of PNPLA3 genotype in conjunction with abdominal VAT in liver fat accrual. The stronger association of the PNPLA3 genotype and liver fat in women suggests that women may be more sensitive to liver fat accumulation in the setting of increased visceral fat, compared to men. The presence of the PNPLA3 variant genotype, particularly in the context of high visceral adipose tissue content may play an important role in FLD.

Sex and race differences in the prevalence of fatty liver disease as measured by computed tomography liver attenuation in European American and African American participants of the NHLBI family heart study

Liver attenuation (LA) [Hounsfield Units (HU)] by computed tomography is a validated quantitative measure that is inversely related to liver fat burden. We examined race and sex differences on the distribution of LA [one of the first stages of fatty liver disease (FLD)] and the predictors of these mean differences in European American (EA) and African American (AA) participants of the Family Heart Study. A total of 1242 (1064 EA, 178 AA) and 1477 (1150 EA, 327 AA) men and women, respectively, underwent computed tomography examination from which LA and abdominal adipose volume were measured. LA (adjusted for phantom and field center) was the dependent variable in linear mixed models (to control for family relatedness) that tested for mean differences by race and by sex. Independent explanatory variables included age, BMI, visceral adipose tissue volume (VAT), subcutaneous adipose tissue volume, alcohol consumption, triglyceride, HDL-cholesterol, and insulin resistance. Mean LA varied significantly by sex, [(men) 57.76±10.03 HU and (women) 60.03±10.91 HU, P=0.0002], but not by race. Higher LA was associated with older age, whereas higher values of VAT, triglycerides, and insulin resistance were associated with lower LA in men and women. In contrast, alcohol consumption and BMI were associated with lower LA only among men. In analyses stratified by race, LA was associated with alcohol consumption, VAT, and insulin resistance in both EA and AA and with age, BMI, and HDL-cholesterol in EA participants only. Our study findings confirm that there are important sex differences and race by sex interaction effects on the distribution of LA, the prevalence of FLD, and on the influence of metabolic risk factors on LA and FLD.

Sex and race differences in the prevalence of fatty liver disease as measured by computed tomography liver attenuation in European American and African American participants of the NHLBI family heart study

Sex and race differences in the prevalence of fatty liver disease as measured by computed tomography liver attenuation in European American and African American participants of the NHLBI family heart study

Evaluation of the gene–age interactions in HDL cholesterol, LDL cholesterol, and triglyceride levels: The impact of the SORT1 polymorphism on LDL cholesterol levels is age dependent

Several genes that influence HDL-C, LDL-C, and triglyceride levels have been identified. The effects of genetic polymorphisms on lipid levels may be age dependent. We replicated 17 of these previously identified associations and then used cross-sectional and longitudinal analysis to investigate age–SNP interaction effects. The rs646776 SNP at the SORT1 locus showed an age interaction that was significant in cross-sectional analyses of 1350 individuals from Utah (p=0.0003) and in 2977 individuals from the NHLBI Family Heart Study (p=0.007) as well as in longitudinal analysis of a subsample of 1099 individuals from the Utah cohort that had been followed for over 20years (p=0.0001). The rs646776 genotype-specific difference in LDL-C levels was significantly greater for younger individuals than for older individuals. These findings may help elucidate the mode of action of the SORT1 gene and impact potential therapeutic interventions targeting this pathway.

Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: The NHLBI Family Heart Study☆

Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: The NHLBI Family Heart Study☆

Serum Urate Is Not Associated with Coronary Artery Calcification: The NHLBI Family Heart Study

urate may have effects on vascular remodeling and atherosclerosis. We had shown an association between serum uric acid (SUA) and carotid atherosclerotic plaques. Inflammation and vascular remodeling in atherosclerosis promote coronary artery calcification (CAC), a preclinical marker for atherosclerosis. Here, we examined whether SUA is associated with CAC, using the same study sample and methods as for our previous carotid atherosclerosis study. the national Heart, Lung, and Blood Institute Family Heart Study is a multicenter study designed to assess risk factors for heart disease. Participants were recruited from population-based cohorts in the US states of Massachusetts, North Carolina, Minnesota, Utah, and Alabama. CAC was assessed with helical computed tomography (CT). We conducted sex-specific and family-cluster analyses, as well as additional analyses among persons without risk factors related to both cardiovascular disease and hyperuricemia, adjusting for potential confounders as we had in the previous study of carotid atherosclerosis. for the CAC study, 2412 subjects had both SUA and helical CT results available (55% women, age 58 ± 13 yrs, body mass index 27.6 ± 5.3). We found no association of SUA with CAC in men or women [OR in men: 1.0, 1.11, 0.86, 0.90; women: 1.0, 0.83, 1.00, 0.87 for increasing categories of SUA: < 5 (referent group), 5 to < 6, 6 to < 6.8, ≥ 6.8 mg/dl, respectively], nor in subgroup analyses. replicating the methods used to demonstrate an association of SUA with carotid atherosclerosis did not reveal any association between SUA and CAC, suggesting that SUA likely does not contribute to atherosclerosis through effects on arterial calcification. The possibility that urate has divergent pathophysiologic effects on atherosclerosis and artery calcification merits further study.