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

BACKGROUND AND AIMS: While 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 RESULTS: In 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. CONCLUSIONS: We found no significant association between baked/mashed potato consumption and CAC in older adults. STUDY REGISTRATION NUMBER: NCT00005136. Study registration date: 5/25/2000.

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

BACKGROUND & AIMS: 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. 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 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. RESULTS: 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. CONCLUSIONS: These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.

Future translational applications from the contemporary genomics era: a scientific statement from the American Heart Association.

The field of genetics and genomics has advanced considerably with the achievement of recent milestones encompassing the identification of many loci for cardiovascular disease and variable drug responses. Despite this achievement, a gap exists in the understanding and advancement to meaningful translation that directly affects disease prevention and clinical care. The purpose of this scientific statement is to address the gap between genetic discoveries and their practical application to cardiovascular clinical care. In brief, this scientific statement assesses the current timeline for effective translation of basic discoveries to clinical advances, highlighting past successes. Current discoveries in the area of genetics and genomics are covered next, followed by future expectations, tools, and competencies for achieving the goal of improving clinical care.

Genome-wide interaction of genotype by erythrocyte n-3 fatty acids contributes to phenotypic variance of diabetes-related traits.

BACKGROUND: Little is known about the interplay between n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level. The present study aimed to examine variance contributions of genotype by environment (GxE) interactions for different erythrocyte n-3 fatty acids and genetic variants for diabetes-related traits at the genome-wide level in a non-Hispanic white population living in the U.S.A. (n = 820). A tool for Genome-wide Complex Trait Analysis (GCTA) was used to estimate the genome-wide GxE variance contribution of four diabetes-related traits: HOMA-Insulin Resistance (HOMA-IR), fasting plasma insulin, glucose and adiponectin. A GxE genome-wide association study (GWAS) was conducted to further elucidate the GCTA results. Replication was conducted in the participants of the Boston Puerto Rican Health Study (BPRHS) without diabetes (n = 716). RESULTS: In GOLDN, docosapentaenoic acid (DPA) contributed the most significant GxE variance to the total phenotypic variance of both HOMA-IR (26.5%, P-nominal = 0.034) and fasting insulin (24.3%, P-nominal = 0.042). The ratio of arachidonic acid to eicosapentaenoic acid + docosahexaenoic acid contributed the most significant GxE variance to the total variance of fasting glucose (27.0%, P-nominal = 0.023). GxE variance of the arachidonic acid/eicosapentaenoic acid ratio showed a marginally significant contribution to the adiponectin variance (16.0%, P-nominal = 0.058). None of the GCTA results were significant after Bonferroni correction (P < 0.001). For each trait, the GxE GWAS identified a far larger number of significant single-nucleotide polymorphisms (P-interaction ≤ 10E-5) for the significant E factor (significant GxE variance contributor) than a control E factor (non-significant GxE variance contributor). In the BPRHS, DPA contributed a marginally significant GxE variance to the phenotypic variance of HOMA-IR (12.9%, P-nominal = 0.068) and fasting insulin (18.0%, P-nominal = 0.033). CONCLUSION: Erythrocyte n-3 fatty acids contributed a significant GxE variance to diabetes-related traits at the genome-wide level.

Polyunsaturated Fatty Acids Modulate the Association between PIK3CA-KCNMB3 Genetic Variants and Insulin Resistance.

BACKGROUND: Neighboring genes PIK3CA and KCNMB3 are both important for insulin signaling and ß-cell function, but their associations with glucose-related traits are unclear. OBJECTIVE: The objective was to examine associations of PIK3CA-KCNMB3 variants with glucose-related traits and potential interaction with dietary fat. DESIGN: We first investigated genetic associations and their modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820). Nine single-nucleotide polymorphisms (SNPs) were selected for analysis, covering more than 80% of the SNPs in the region. We then sought to replicate the findings in the Boston Puerto Rican Health Study (BPRHS) (n = 844). RESULTS: For KCNMB3 missense mutation rs7645550, meta-analysis indicated that homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower in minor allele T homozygotes compared with major allele C carriers (pooled P-value = 0.004); for another SNP rs1183319, which is in moderate LD with rs7645550, minor allele G carriers had higher HOMA-IR compared with non-carriers in both populations (pooled P-value = 0.028). In GOLDN, rs7645550 T allele homozygotes had lower HOMA-IR only when dietary n-3: n-6 PUFA ratio was low (≤0.11, P = 0.001), but not when it was high (>0.11, P-interaction = 0.033). Similar interaction was observed between rs1183319 and n-3: n-6 PUFA ratio on HOMA-IR (P-interaction = 0.001) in GOLDN. Variance contribution analyses in GOLDN confirmed the genetic association and gene-diet interaction. In BPRHS, dietary n-3: n-6 PUFA ratio significantly modulated the association between rs1183319 and HbA1c (P-interaction = 0.034). CONCLUSION: PIK3CA-KCNMB3 variants are associated with insulin resistance in populations of different ancestries, and are modified by dietary PUFA.

Association of dietary omega-3 fatty acids with prevalence of metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study.

BACKGROUND & AIMS: Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. Omega-3 fatty acids have been relatively well studied in relation to many individual cardiovascular risk factors; however, their effects on MetS are not well established. METHODS: We conducted a cross-sectional study consisting of 4941 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of dietary omega-3 fatty acids with the prevalence of MetS. Omega-3 intake was assessed using a food frequency questionnaire and we used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS. RESULTS: Our study population had a mean age (SD) of 52.1 (13.9) years and 45.9% were men. The mean (SD) of dietary omega-3 fatty acids was 0.25 g/day (0.27). From the lowest to the highest quintile of dietary omega-3 fatty acids, multivariable adjusted ORs (95% CI) for MetS were 1.00 (ref), 0.90 (0.72-1.13), 1.03 (0.82-1.28), 0.94 (0.74-1.18), and 0.99 (0.77-1.25), respectively. In a secondary analysis, neither fish consumption nor dietary alpha-linolenic acid was associated with MetS. CONCLUSIONS: Our findings do not support an association between dietary omega-3 fatty acids and MetS in a large US population.

ADIPOQ polymorphisms, monounsaturated fatty acids, and obesity risk: the GOLDN study.

Serum adiponectin levels have been positively associated with insulin sensitivity and are decreased in type 2 diabetes (T2D) and obesity. Genetic and environmental factors influence serum adiponectin and may contribute to risk of metabolic syndrome and T2D. Therefore, we investigated the effect of ADIPOQ single-nucleotide polymorphisms (SNPs), -11377C>G and -11391G>A, on metabolic-related traits, and their modulation by dietary fat in white Americans. Data were collected from 1,083 subjects participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Mean serum adiponectin concentration was higher for carriers of the -11391A allele (P = 0.001) but lower for the -11377G allele carriers (P = 0.017). Moreover, we found a significant association with obesity traits for the -11391G>A SNP. Carriers of the -11391A allele had significantly lower weight (P = 0.029), BMI (P = 0.019), waist (P = 0.003), and hip circumferences (P = 0.004) compared to noncarriers. Interestingly, the associations of the -11391G>A with BMI and obesity risk were modified by monounsaturated fatty acids (MUFAs) intake (P-interaction = 0.021 and 0.034 for BMI and obesity risk, respectively). In subjects with MUFA intake above the median (> or =13% of energy intake), -11391A carriers had lower BMI (27.1 kg/m(2) for GA+AA vs. 29.1 kg/m(2) for GG, P = 0.002) and decreased obesity risk (odds ratio for -11391A = 0.52, 95% confidence interval (CI); 0.28-0.96; P = 0.031). However, we did not detect genotype-related differences for BMI or obesity in subjects with MUFA intake <13%. Our findings support a significant association between the -11391G>A SNPs and obesity-related traits and the potential to moderate such effects using dietary modification.

Polyunsaturated fatty acids modulate the effect of TCF7L2 gene variants on postprandial lipemia.

The transcription factor 7-like 2 (TCF7L2) has been recently associated with diabetes risk, and it may exert its effect through metabolic syndrome (MetS)-related traits and be subjected to modification by environmental factors. We investigated the effect of single nucleotide polymorphisms (SNP), rs7903146 and rs12255372, within the TCF7L2 locus on postprandial lipemia and other MetS-related traits and their modulation by dietary fat. Data were collected from 1083 European Americans participating in the Genetics of Lipid Lowering Drugs and Diet Network Study. Carriers of the minor T allele at the C/T rs7903146 SNP had higher fasting plasma glucose (P = 0.012), lower homeostasis model assessment of beta cell function (P = 0.041), higher plasma VLDL (P = 0.035), and lower large LDL particle (P = 0.007) concentrations and higher risk of MetS (P = 0.011) than CC individuals. Moreover, we identified significant interactions between this SNP and PUFA intake modulating fasting VLDL particle concentrations (P = 0.016) and postprandial triglycerides (TG) (P = 0.028), chylomicrons (P = 0.025), total VLDL (P = 0.026), and large VLDL (P = 0.018) concentrations. Thus, only T allele carriers with a PUFA intake > or = 7.36% of energy had elevated fasting plasma VLDL concentrations and postprandial TG-rich lipoproteins. These variables did not differ in T allele carriers and noncarriers in the low-PUFA intake group. Moreover, these significant interactions were due exclusively to (n-6) PUFA intake. In summary, high (n-6) PUFA intakes (> or = 6.62% of energy intake) were associated with atherogenic dyslipidemia in carriers of the minor T allele at the TCF7L2 rs7903146 SNP and may predispose them to MetS, diabetes, and cardiovascular disease.

VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.

BACKGROUND: Although the influence of VKORC1 and CYP2C9 polymorphisms on warfarin response has been studied, variability in dose explained by CYP2C9 and VKORC1 is lower among African-Americans compared with European-Americans. This has lead investigators to hypothesize that assessment of VKORC1 haplotypes may help capture a greater proportion of the variability in dose for this under-represented group. However, the inadequate representation of African-Americans and the assessment of a few VKORC1 polymorphisms have hindered this effort. METHODS: To determine if VKORC1 haplotypes or haplotype groups explain a higher variability in warfarin dose, we comprehensively assessed VKORC1 polymorphisms in 273 African-Americans and 302 European-Americans. The influence of VKORC1 polymorphisms, race-specific haplotypes and haplotype groups on warfarin dose was evaluated in race-stratified multivariable analyses after accounting for CYP2C9 (*2, *3, *5, *6 and *11) and clinical covariates. RESULTS: VKORC1 explained 18% (30% with CYP2C9) variability in warfarin dose among European-Americans and 5% (8% with CYP2C9) among African-Americans. Four common haplotypes in European-Americans and twelve in African-Americans were identified. In each race VKORC1 haplotypes emerged into two groups: low-dose (Group A) and high-dose (Group B). African-Americans had a lower frequency of Group A haplotype (10.6%) compared with European-Americans (35%, p < 0.0001).The variability in dose explained by VKORC1 haplotype or haplotype groups was similar to that of a single informative polymorphism. CONCLUSIONS: Our findings support the use of CYP2C9, VKORC1 polymorphisms (rs9934438 or rs9923231) and clinical covariates to predict warfarin dose in both African- and European-Americans. A uniform set of common polymorphisms in CYP2C9 and VKORC1, and limited clinical covariates can be used to improve warfarin dose prediction for a racially diverse population.

Interleukin1beta genetic polymorphisms interact with polyunsaturated fatty acids to modulate risk of the metabolic syndrome.

Chronic inflammation has been identified as an important component of the metabolic syndrome (MetS). Therefore, environmental and genetic factors contributing to the variation of inflammatory responses could affect individuals' susceptibility to MetS. We investigated the association between common IL1beta genetic polymorphisms, inflammation, and the MetS, and the modulation of diet-related variables (i.e., erythrocyte membrane fatty acid composition) in a white U.S. population. IL1beta single nucleotide polymorphisms (SNP) (-1473G > C, -511G > A, -31T > C, 3966C > T, 6054G > A), clinical and biochemical measurements were characterized in a total of 1120 subjects (540 males and 580 females) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. The 6054 G > A SNP was significantly associated with plasma C-reactive protein (P = 0.054), adiponectin (P = 0.021), and the prevalence of MetS (P = 0.004). Moreover, there was a significant interaction between the 6054G > A SNP and erythrocyte membrane (n-3) PUFA (P = 0.019). Among subjects with low (n-3) PUFA content (below the median), the 6054 G allele was associated with increased risk of the MetS (OR = 3.29, 95%CI = 1.49-7.26 for GG and OR = 1.95, 95%CI = 0.85-4.46 for GA, P < 0.001) compared with the AA genotype, but there were no significant genotype associations among subjects with high (n-3) PUFA content (above the median). Further analyses supported a significant haplotype global effect on the MetS (P = 0.017) among subjects with low (n-3) PUFA content. These results suggested that IL1beta genetic variants were associated with measures of chronic inflammation and the MetS risk, and that genetic influences were more evident among subjects with low (n-3) PUFA intake.

Use of nonprescription medications for perceived cardiovascular health.

BACKGROUND: Nonprescription products (over-the-counter drugs; vitamins/minerals; and nonvitamin, nonmineral supplements) are promoted or advertised for cardiovascular health. The extent of nonprescription products used specifically for perceived cardiovascular health (NONRX-CVH) is unknown. This study aimed to (1) determine prevalence and types of nonprescription medications used for NONRX-CVH, (2) compare the demographics of NONRX-CVH users to persons using nonprescription medications in general, and (3) determine the prevalence of use of NONRX-CVH among those taking a prescription medication for a cardiovascular reason. METHODS: A cross-sectional survey comprised the probability sample of 3128 adults in the Minneapolis-St. Paul area in the 2000-2002 Minnesota Heart Survey. Trained interviewers collected medication information from participants using a structured medication inventory approach. RESULTS: Analysis in 2005 shows that 10% of participants (n=315) self-reported taking one or more nonprescription medications in the past 2 weeks for a perceived cardiovascular health purpose. Among these individuals, prevalence of use of vitamin/mineral supplements, nonvitamin/nonmineral supplements, and over-the-counter products for a cardiovascular purpose was 37.5%, 21.3%, and 54.6%, respectively. Popular NONRX-CVHs were aspirin (52.1%), vitamin E (24.4%), garlic (9.8%), and omega-3/fish oils/fatty acids (3.8%). NONRX-CVH users were older than general nonprescription users (p<0.001). Of 613 people using a prescription drug for cardiovascular reasons, 135 (22%) reported using one or more NONRX-CVH medications. CONCLUSIONS: Use of NONRX-CVHs, especially aspirin, vitamin E, and herbals, is common, and older patients may use aspirin or dietary supplements for this purpose. Physicians having patients with cardiovascular disease should ask about nonprescription medication usage, as some NONRX-CVHs may be inappropriate.

Dietary linolenic acid and adjusted QT and JT intervals in the National Heart, Lung, and Blood Institute Family Heart study.

OBJECTIVES: The goal of this study was to examine whether higher consumption of total linolenic acid was associated with rate-adjusted QT and JT intervals (QTrr and JTrr, respectively). BACKGROUND: Higher intake of fish omega-3 fatty acids and plant omega-3 such as alpha-linolenic acid is associated with lower risk of myocardial infarction. While long-chain omega-3 can inhibit ventricular arrhythmia, it is not known whether alpha-linolenic acid influences ventricular repolarization. METHODS: We studied 3,642 subjects from the National Heart, Lung, and Blood Institute Family Heart study who were free of myocardial infarction, left ventricular hypertrophy, pacemaker, and with QRS <120 ms. We used the 95th percentile of the gender-specific distribution of QTrr and JTrr to define abnormally prolonged repolarization. Within each gender, we created age- and energy-adjusted tertiles of linolenic acid and used regression models for analyses. RESULTS: Mean age was 50 years, and average intake of total linolenic acid was 0.74 g/day. There was an inverse association between consumption of linolenic acid and QTrr and JTrr (p for trend 0.001 and 0.0005, respectively). From the lowest (reference) to the highest gender-, age-, and energy-adjusted tertile of linolenic acid, multivariable adjusted odds ratios for prolonged QTrr were 1.0, 0.74 (95% confidence interval [CI] 0.57 to 0.96), and 0.59 (95% CI 0.44 to 0.77), respectively (p for trend 0.0003). Corresponding values for JTrr were 1.0, 0.73 (95% CI 0.52 to 1.03), and 0.59 (95% CI 0.40 to 0.87), respectively (p for trend 0.009). Exclusion of subjects taking drugs known to influence QT did not influence this association. CONCLUSIONS: Higher intake of dietary linolenic acid might be associated with a reduced risk of abnormally prolonged repolarization in men and women.

Trends in the trans-fatty acid composition of the diet in a metropolitan area: the Minnesota Heart Survey.

OBJECTIVE: In this study, we examine trends in dietary intake of trans-fatty acids from 1980-1982 to 1995-1997 using data collected as part of the Minnesota Heart Survey (MHS). DESIGN: The MHS is an ongoing observational epidemiologic study among independent cross-sectional probability samples of adults. Twenty-four-hour dietary recalls were collected on a subset of participants. To obtain trans-fatty acid intake estimates, the dietary recall records were recalculated using the University of Minnesota Nutrition Coordinating Center Food and Nutrient Database. Subjects/setting The survey population included noninstitutionalized adults aged 25 to 74 years residing in the Minneapolis-St. Paul, MN, metropolitan area. Statistical analysis Mean intake estimates were generated for each survey, and a generalized linear mixed model was used to test the null hypothesis of no difference in the age-adjusted sex-specific means between 1980-1982, 1985-1987, 1990-1992, and 1995-1997. RESULTS: Downward trends in dietary intake of trans-fatty acids were found between 1980-1982 and 1995-1997. For example, for men mean intake of total trans-fatty acids declined from 8.3 g per day in 1980-1982 to 6.2 g per day in 1995-1997 (P<.001). Represented as a percentage of energy, similar declines were seen with mean intake of total trans-fatty acids decreasing from 3.0% of total energy in 1980-1982 to 2.2% of total energy in 1995-1997 (P<.001). APPLICATIONS/CONCLUSIONS: It seems that intake of trans-fatty acids is on the decline. Consideration should be given to additional changes in the food supply and consumer food choices that may result in further reduction in consumption of trans-fatty acids.