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.

Tree nut consumption and prevalence of carotid artery plaques: The National Heart, Lung, and Blood Institute Family Heart Study.

PURPOSE: While tree nut consumption has been shown to be cardioprotective, a few studies have examined the relationship between tree nut consumption and carotid atherosclerosis. We tested the hypothesis that tree nut consumption would be inversely related with carotid atherosclerosis in adults. METHODS: We cross-sectionally analyzed data from 4536 participants of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study conducted in the United States. Dietary patterns among participants were variable, tree nut consumption was self-reported using the Food Frequency Questionnaire (FFQ), and B-mode ultrasound of the carotid arteries was used to assess for the presence of carotid artery plaques (primary outcome) and carotid intima media thickness (cIMT). Multivariable logistic regression was used to estimate odds ratio (95% confidence interval) of prevalent carotid artery plaques and linear regression was used to estimate adjusted mean cIMT across categories of nut consumption. RESULTS: The mean age was 52.3 years (SD = 13.6), 95.6% of the participants were white, and 54% were female. The median tree nut intake was 1-3 servings/month. Odds ratios (95% CI) for prevalent carotid artery plaques were 1.0 (reference), 1.03 [0.86, 1.4], 0.89 [0.70, 1.13], and 0.96 [0.73, 1.26] for tree nut consumption of almost never, 1-3 times/month, 1/week, and 2+/week, respectively, adjusting for age, sex, race, field center, BMI, smoking status, alcohol consumption, creatinine, energy intake, fruit and vegetable consumption, exercise, and education. In secondary analysis, there was a suggestive inverse association of tree nut consumption with cIMT in the internal carotid artery, but not the common carotid or bifurcation. CONCLUSION: Our data showed no association between tree nut consumption and prevalence of carotid artery plaques in adults.

Dietary Protein and Preservation of Physical Functioning Among Middle-Aged and Older Adults in the Framingham Offspring Study.

Dietary protein may help prevent age-related declines in strength and functional capacity. This study examines the independent relationship between dietary protein and longitudinal changes in physical functioning among adults participating in the Framingham Offspring Study from examination 5 (1991-1995) to examination 8 (2005-2008). Protein intakes were derived from 3-day diet records during examinations 3 and 5; functional status was determined over 12 years using 7 items selected from standardized questionnaires. Multivariable models adjusted for age, sex, education, physical activity, smoking, height, and energy intake. Functional tasks that benefitted most from a higher-protein diet (≥1.2 g/kg/day vs. <0.8 g/kg/day) were doing heavy work at home, walking 1/2 mile (0.8 km), going up and down stairs, stooping/kneeling/crouching, and lifting heavy items. Those with higher protein intakes were 41% less likely (95% CI: 0.43, 0.82) to become dependent in 1 or more of the functional tasks over follow-up. Higher physical activity and lower body mass index were both independently associated with less functional decline. The greatest risk reductions were found among those with higher protein intakes combined with either higher physical activity, more skeletal muscle mass, or lower body mass index. This study demonstrates that dietary protein intakes above the current US Recommended Daily Allowance may slow functional decline in older adults.

Walking and Calcified Atherosclerotic Plaque in the Coronary Arteries: The National Heart, Lung, and Blood Institute Family Heart Study.

OBJECTIVE: Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification. APPROACH AND RESULTS: In a cross-sectional design, we studied 2971 participants of the National Heart, Lung, and Blood Institute Family Heart Study without a history of myocardial infarction, coronary artery bypass grafting, or percutaneous transluminal angioplasty. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute walking metabolic equivalent hours. CAC was measured by cardiac computed tomography. We defined prevalent CAC and aortic calcification using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios. Mean age was 55 years, and 60% of participants were women. Compared with the ≤3.75-Met-h/wk group, prevalence ratios for CAC after adjusting for age, sex, race, smoking, alcohol use, total physical activity (excluding walking), and familial clustering were 0.53 (95% confidence interval, 0.35-0.79) for >3.75 to 7.5 Met-h/wk, 0.72 (95% confidence interval, 0.52-0.99) for >7.5 to 15 Met-h/wk, and 0.54 (95% confidence interval, 0.36-0.81) for >15 to 22.5 Met-h/wk, (P trend=0.01). The walking-CAC relationship remained significant for those with body mass index ≥25 (P trend=0.02) and persisted with CAC cutoffs of 300, 200, 150, and 50 but not 0. When examined as a continuous variable, a J-shaped association between walking and CAC was found. The walking-aortic calcification association was not significant. CONCLUSIONS: Our findings suggest that walking is associated with lower prevalent CAC (but not aortic calcification) in adults without known heart disease.

Association of ideal cardiovascular health and calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study.

BACKGROUND: The American Heart Association (AHA) established recommendations based on 7 ideal health behaviors and factors with the goal of improving cardiovascular health (CVH) and reducing both morbidity and mortality from cardiovascular disease by 20% by 2020. Few studies have investigated their association with subclinical coronary heart disease. We sought to examine whether the 7 AHA CVH metrics were associated with calcified atherosclerotic plaque in the coronary arteries. METHODS: In a cross-sectional design, we studied 1,731 predominantly white men and women from the National Heart, Lung, and Blood Institute Family Heart Study without prevalent coronary heart disease. Diet was assessed by a semiquantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac computed tomography. We defined prevalent CAC using an Agatston score of 100+ and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. RESULTS: Mean age was 56.8 years, and 41% were male. The median number of ideal CVH metrics was 3, and no participant met all 7. There was a strong inverse relationship between number of ideal CVH metrics and prevalent CAC. Odds ratios (95% CI) for CAC of 100+ were 1.0 (reference), 0.37 (0.29-0.45), 0.35 (0.26-0.44), and 0.27 (0.20-0.36) among subjects with 0 to 1, 2, 3, and 4+ ideal CVH metrics, respectively (P = .0001), adjusting for sex, age, field center, alcohol, income, education, and energy consumption. CONCLUSIONS: These data demonstrate a strong and graded inverse relationship between AHA ideal CVH metrics and prevalent CAC in adult men and women.

Lack of association of apolipoprotein E (Apo E) polymorphism with the prevalence of metabolic syndrome: the National Heart, Lung and Blood Institute Family Heart Study.

OBJECTIVE: Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidaemia, elevated blood pressure and insulin resistance, is a major public health concern in the United States. The effects of apolipoprotein E (Apo E) polymorphism on MetS are not well established. METHODS: We conducted a cross-sectional study consisting of 1551 participants from the National Heart, Lung and Blood Institute Family Heart Study to assess the relation of Apo E polymorphism with the prevalence of MetS. MetS was defined according to the American Heart Association-National Heart, Lung and Blood Institute-International Diabetes Federation-World Health Organization harmonized criteria. We used generalized estimating equations to estimate adjusted odds ratios (ORs) for prevalent MetS and the Bonferroni correction to account for multiple testing in the secondary analysis. RESULTS: Our study population had a mean age (standard deviation) of 56.5 (11.0) years, and 49.7% had MetS. There was no association between the Apo E genotypes and the MetS. The multivariable adjusted ORs (95% confidence interval) were 1.00 (reference), 1.26 (0.31-5.21), 0.89 (0.62-1.29), 1.13 (0.61-2.10), 1.13 (0.88-1.47) and 1.87 (0.91-3.85) for the Ɛ3/Ɛ3, Ɛ2/Ɛ2, Ɛ2/Ɛ3, Ɛ2/Ɛ4, Ɛ3/Ɛ4 and Ɛ4/Ɛ4 genotypes, respectively. In a secondary analysis, Ɛ2/Ɛ3 genotype was associated with 41% lower prevalence odds of low high-density lipoprotein [multivariable adjusted ORs (95% confidence interval) = 0.59 (0.36-0.95)] compared with Ɛ3/Ɛ3 genotype. CONCLUSIONS: Our findings do not support an association between Apo E polymorphism and MetS in a multicentre population-based study of predominantly White US men and women.

Integrative Mendelian randomization reveals the soluble receptor for advanced glycation end products as protective in relation to rheumatoid arthritis.

Rheumatoid arthritis (RA) is a risk factor for atherosclerotic cardiovascular diseases (CVD). Given the critical roles of the immune system and inflammatory signals in the pathogenesis of CVD, we hypothesized that interrogation of CVD-related proteins using integrative genomics might provide new insights into the pathophysiology of RA. We utilized two-sample Mendelian randomization (MR) for causal inference between circulating protein levels and RA by incorporating genetic variants, followed by colocalization to characterize the causal associations. Genetic variants from three sources were obtained: those associated with 71 CVD-related proteins measured in nearly 7000 Framingham Heart Study participants, a published genome-wide association study (GWAS) of RA (19 234 cases, 61 565 controls), and GWAS of rheumatoid factor (RF) levels from the UK Biobank (n = 30 565). We identified the soluble receptor for advanced glycation end products (sRAGE), a critical inflammatory pathway protein, as putatively causal and protective for both RA (odds ratio per 1-standard deviation increment in inverse-rank normalized sRAGE level = 0.364; 95% confidence interval 0.342-0.385; P = 6.40 × 10-241) and RF levels (ß [change in RF level per sRAGE increment] = - 1.318; SE = 0.434; P = 0.002). Using an integrative genomic approach, we highlight the AGER/RAGE axis as a putatively causal and promising therapeutic target for RA.

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

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our data suggest that cheese consumption but not yogurt or milk is associated with a lower odds of CAC in men and women.

Apolipoprotein ε4 polymorphism does not modify the association between body mass index and high-density lipoprotein cholesterol: a cross-sectional cohort study.

BACKGROUND: We sought to examine whether ε4 carrier status modifies the relation between body mass index (BMI) and HDL. The National Heart, Lung, and Blood Institute Family Heart Study included 657 families with high family risk scores for coronary heart disease and 588 randomly selected families of probands in the Framingham, Atherosclerosis Risk in Communities, and Utah Family Health Tree studies. We selected 1402 subjects who had ε4 carrier status available. We used generalized estimating equations to examine the interaction between BMI and ε4 allele carrier status on HDL after adjusting for age, gender, smoking, alcohol intake, mono- and poly-unsaturated fat intake, exercise, comorbidities, LDL, and family cluster. RESULTS: The mean (standard deviation) age of included subjects was 56.4(11.0) years and 47% were male. Adjusted means of HDL for normal, overweight, and obese BMI categories were 51.2(± 0.97), 45.0(± 0.75), and 41.6(± 0.93), respectively, among 397 ε4 carriers (p for trend < 0.0001) and 53.6(± 0.62), 51.3(± 0.49), and 45.0(± 0.62), respectively, among 1005 non-carriers of the ε4 allele (p-value for trend < 0.0001). There was no evidence for an interaction between BMI and ε4 status on HDL(p-value 0.39). CONCLUSION: Our findings do not support an interaction between ε4 allele status and BMI on HDL.

Adherence to a Mediterranean-Style Dietary Pattern and Cancer Risk in a Prospective Cohort Study.

A Mediterranean-style diet is a healthy eating pattern that may benefit cancer risk, but evidence among Americans is scarce. We examined the prospective association between adherence to such a diet pattern and total cancer risk. A Mediterranean-style dietary pattern (MSDP) score was derived from a semi-quantitative food frequency questionnaire at exam 5 (1991-1995). Subjects included 2966 participants of the Framingham Offspring Study who were free of prevalent cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic, lifestyle, and anthropometric measures. Cox-models were also used to examine effect modification by lifestyle and anthropometric measures. During 18 years of median follow-up, 259 women and 352 men were diagnosed with cancer. Women with moderate or higher adherence to the MSDP had ≥25% lower risks of cancer than women with the lowest MSDP (HR (moderate vs. lowest): 0.71, 95% CI: 0.52-0.97 and HR (highest vs. lowest): 0.74; 95% CI: 0.55-0.99). The association between MSDP score and cancer risk in men was weaker except in non-smokers. Beneficial effects of the MSDP in women were stronger among those who were not overweight. In this study, higher adherence to MSDP was associated with lower cancer risk, especially among women.

Sugar-Sweetened Beverage Consumption and 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. OBJECTIVE: Our primary objective was to investigate the association between SSB intake and prevalence of atherosclerotic plaque in the coronary arteries in The National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. METHODS: We studied 1991 participants of the NHLBI Family Heart Study without known coronary heart disease. Intake of SSB was assessed through a semi-quantitative food frequency questionnaire. Coronary artery calcium (CAC) was measured by cardiac Computed Tomography (CT) and prevalent CAC was defined as an Agatston score ≥100. We used generalized estimating equations to calculate adjusted prevalence ratios of CAC. A sensitivity analysis was also performed at different ranges of cut points for CAC. RESULTS: Mean age and body mass index (BMI) were 55.0 years and 29.5 kg/m2, respectively, and 60% were female. In analysis adjusted for age, sex, BMI, smoking, alcohol use, physical activity, energy intake, and field center, higher SSB consumption was not associated with higher prevalence of CAC [prevalence ratio (95% confidence interval) of: 1.0 (reference), 1.36 (0.70-2.63), 1.69 (0.93-3.09), 1.21 (0.69-2.12), 1.05 (0.60-1.84), and 1.58 (0.85-2.94) for SSB consumption of almost never, 1-3/month, 1/week, 2-6/week, 1/day, and ≥2/day, respectively (p for linear trend 0.32)]. In a sensitivity analysis, there was no evidence of association between SSB and prevalent CAC when different 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.

Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome (MetS). Alanine aminotransferase (ALT) levels are used to detect NAFLD and have also been associated with increased risk for MetS, diabetes mellitus, and cardiovascular disease (CVD). We studied the relationship between ALT levels and these disorders in a long-term follow-up study. METHODS: Framingham Offspring Heart Study participants (n = 2812; mean age, 44 years; 56% women) were followed for the development of MetS, diabetes, CVD, and all-cause mortality using logistic regression (MetS, diabetes) or Cox proportional hazards models (CVD, all-cause mortality). RESULTS: Among individuals at baseline, per 1 standard deviation increase in log ALT level, there were increased odds of the development of MetS (odds ratio [OR] 1.21, P < .001) and diabetes (OR, 1.48; P < .0001) over 20 years of follow-up. These findings also applied to participants with ALT levels within the normal range (MetS OR, 1.17; P = .006; diabetes OR, 1.34; P =.002). There was an increased risk of CVD in age/gender-adjusted models (hazard ratio, 1.23; P < .0001), but this was attenuated in multivariable-adjusted models (hazard ratio 1.05; P = .27); no association was observed for all-cause mortality. Aspartate aminotransferase levels were found to be associated with an increased risk of only diabetes. CONCLUSIONS: Both normal and increased levels of ALT are associated with long-term development of multiple metabolic disorders. These results indicate the potential for ALT values as biomarkers for the risk of metabolic disease.

Parental obesity and offspring serum alanine and aspartate aminotransferase levels: the Framingham heart study.

BACKGROUND & AIMS: Obesity is an important correlate of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. We sought to examine the relations between parental obesity and the serum ALT and AST levels among offspring in a community-based sample. METHODS: Participants (n = 1732) of the Framingham Offspring Study (50% women; mean age, 42 years) who had serum ALT and AST measurements and both parents in the original Framingham cohort were studied. Study participants were grouped into early-onset parental obesity (n = 193) (at least one parent obese), later-onset parental obesity (n = 460), and no parental obesity (n = 1079) subgroups. The association between elevated ALT or AST levels and parental obesity was tested using generalized estimating equations to account for familial correlations. RESULTS: In multivariable analysis including adjustment for offspring obesity, significantly higher ALT levels were observed among individuals with paternal early-onset obesity as compared with those without paternal obesity (P = .02). Offspring with early-onset paternal obesity were more likely to have elevated ALT levels compared with those without paternal obesity (odds ratio, 1.75; 95% confidence interval, 1.06-2.89; P = .03). There was no association with elevated ALT levels among offspring with maternal early-onset obesity (odds ratio, 1.10; 95% confidence interval, 0.76-1.59; P = .61). There was no association between parental obesity and serum AST levels. CONCLUSIONS: Early-onset paternal obesity, but not maternal obesity, increases the odds of elevated serum ALT levels in offspring, suggesting a predisposition to developing elevated serum ALT levels that may be mediated through familial early-onset obesity.