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.

Dietary ω-3 fatty acids and the incidence of atrial fibrillation in the Million Veteran Program.

BACKGROUND: Although recent large randomized clinical trials have reported an increased risk of atrial fibrillation (AF) with marine ω-3 fatty acid supplements, it is unclear whether dietary marine ω-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. OBJECTIVES: We sought to test the hypothesis that dietary eicosapentaenoic acid/docosahexaenoic acid/docosapentaecnoic acid (EPA/DHA/DPA) is associated with a higher risk of AF in a large prospective cohort of US Veterans. METHODS: We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multivariable Cox regression to estimate the HRs of AF across quintiles of ω-3 fatty acid consumption and a cubic spline analysis to assess the dose-response relations between ω-3 fatty acids and AF. RESULTS: Of the 301,294 veterans studied, the median intake of ω-3 fatty acids (EPA/DHA/DPA) was 219 mg/d (IQR: 144-575), and the mean age was 64.9 y (SD: 12.0); 91% were men, and 84% were White. Consumption of EPA/DHA/DPA exhibited a nonlinear inverse relation with incident AF characterized by an initial decline to 11% at 750 mg/d of marine ω-3 fatty acid intake followed by a plateau. CONCLUSIONS: Contrary to our hypothesis, dietary EPA/DHA/DPA was not associated with a higher risk of AF but was inversely related to AF risk in a nonlinear manner.

Effect of Vitamin D3 and Omega-3 Fatty Acid Supplementation on Risk of Frailty: An Ancillary Study of a Randomized Clinical Trial.

Importance: Preventive strategies for frailty are needed. Whether supplements with anti-inflammatory properties, such as vitamin D3 or marine omega-3 fatty acids, are useful for frailty prevention is unknown. Objective: To test the effects of vitamin D3 and omega-3 supplements on change in frailty in older individuals. Design, Setting, and Participants: This study was conducted in 2021, as a prespecified ancillary to the Vitamin D and Omega-3 (VITAL) trial, a 2 × 2 factorial randomized clinical trial. A total of 25 871 individuals (men aged ≥50 years and women aged ≥55 years), without cancer or cardiovascular disease and with data on frailty, were recruited across all 50 US states from November 2011 to March 2014 and followed up through December 31, 2017. Data analysis for the ancillary study was conducted from December 1, 2019, to March 30, 2022. Interventions: Vitamin D3, 2000 IU/d, and marine omega-3 fatty acids, 1 g/d. Main Outcomes and Measures: Frailty was measured using a validated 36-item frailty index that includes measures of function, cognition, mood, and comorbidities from annual questionnaires. Change in frailty score from baseline to year 5, according to randomization, using an intention-to-treat protocol, was assessed using repeated measures. Cox proportional hazards regression models assessed incident frailty. In subgroup analysis, an alternative frailty definition, the physical phenotype, was used as a sensitivity analysis. Results: Of 25 871 VITAL trial participants randomized, 25 057 had sufficient data to calculate a frailty index. Baseline mean (SD) age was 67.2 (7.0) years, and 12 698 (50.7.%) were women. Mean (SD) frailty score was 0.109 (0.090) (range, 0.00-0.685), and 3174 individuals (12.7%) were frail. During a median 5-year follow-up, mean (SD) frailty scores increased to 0.121 (0.099) (range, 0.00-0.792). Neither vitamin D3 nor omega-3 fatty acid supplementation affected mean frailty scores over time (mean difference at year 5: vitamin D3, -0.0002; P = .85; omega-3 fatty acid, -0.0001; P = .90) or rate of change in mean frailty score (interaction with time: vitamin D3; P = .98; omega-3 fatty acid; P = .13) Incident frailty remained similar over time (interaction with time: vitamin D3, P = .90; omega-3 fatty acid; P = .32). Results were unchanged using the frailty physical phenotype. Conclusions and Relevance: In this ancillary study of the VITAL randomized clinical trial, treatment with vitamin D3 or omega-3 fatty acid supplementation, compared with placebo, did not affect the rate of frailty change or incidence over time. These results do not support routine use of either vitamin D3 or omega-3 fatty acid supplementation for frailty prevention in generally healthy community-dwelling older adults not selected for vitamin D3 deficiency. Trial Registration: ClinicalTrials.gov Identifier: NCT01169259.

Diabetes Mellitus, Race, and Effects of Omega-3 Fatty Acids on Incidence of Heart Failure Hospitalization.

OBJECTIVES: The primary aim was to evaluate whether prevalent type 2 diabetes (T2D) modifies the effects of omega-3 supplementation on heart failure (HF) hospitalization. The secondary aim was to examine if race modifies the effects of omega-3 supplements on HF risk. BACKGROUND: It is unclear whether race and T2D modify the effects of omega-3 supplementation on the incidence of HF. METHODS: In this ancillary study of the parent VITAL (Vitamin D and Omega-3 Trial)-a completed randomized trial testing the efficacy of vitamin D and omega-3 fatty acids on cardiovascular diseases and cancer, we assessed the role of T2D and race on the effects of omega-3 supplements on the incidence of HF hospitalization (adjudicated by a review of medical records and supplemented with a query of Centers for Medicare and Medicaid Services data). RESULTS: When omega-3 supplements were compared with placebo, the HR for first HF hospitalization was 0.69 (95% CI: 0.50-0.95) in participants with prevalent T2D and 1.09 (95% CI: 0.88-1.34) in those without T2D (P for interaction = 0.019). Furthermore, prevalent T2D modified the effects of omega-3 fatty acids on the incidence of recurrent HF hospitalization (HR: 0.53; 95% CI: 0.41-0.69 in participants with prevalent T2D vs HR: 1.07; 95% CI: 0.89-1.28 in those without T2D; P interaction <0.0001). In our secondary analysis, omega-3 supplementation reduced recurrent HF hospitalization only in Black participants (P interaction race × omega-3 = 0.0497). CONCLUSIONS: Our data show beneficial effects of omega-3 fatty acid supplements on incidence of HF hospitalization in participants with T2D but not in those without T2D, and such benefit appeared to be stronger in Black participants with T2D. (Intervention With Vitamin D and Omega-3 Supplements and Incident Heart Failure; NCT02271230; Vitamin D and Omega-3 Trial [VITAL]; NCT01169259 [parent study]).

Serum Nonesterified Fatty Acids and Incident Stroke: The CHS.

Background Significant associations between total nonesterified fatty acid (NEFA) concentrations and incident stroke have been reported in some prospective cohort studies. We evaluated the associations between incident stroke and serum concentrations of nonesterified saturated, monounsaturated, polyunsaturated, and trans fatty acids. Methods and Results CHS (Cardiovascular Health Study) participants (N=2028) who were free of stroke at baseline (1996-1997) and had an archived fasting serum sample were included in this study. A total of 35 NEFAs were quantified using gas chromatography. Cox proportional hazards regression models were used to evaluate associations of 5 subclasses (nonesterified saturated, monounsaturated, omega (n)-6 polyunsaturated, n-3 polyunsaturated, and trans fatty acids) of NEFAs and individual NEFAs with incident stroke. Sensitivity analysis was conducted by excluding cases with hemorrhagic stroke (n=45). A total of 338 cases of incident stroke occurred during the median 10.5-year follow-up period. Total n-3 (hazard ratio [HR], 0.77 [95% CI, 0.61-0.97]) and n-6 (HR, 1.32 [95% CI, 1.01-1.73]) subclasses of NEFA were negatively and positively associated with incident stroke, respectively. Among individual NEFAs, dihomo-γ-linolenic acid (20:3n-6) was associated with higher risk (HR, 1.29 [95% CI, 1.02-1.63]), whereas cis-7-hexadecenoic acid (16:1n-9c) and arachidonic acid (20:4n-6) were associated with a lower risk (HR, 0.67 [95% CI, 0.47-0.97]; HR, 0.81 [95% CI. 0.65-1.00], respectively) of incident stroke per standard deviation increment. After the exclusion of cases with hemorrhagic stroke, these associations did not remain significant. Conclusions A total of 2 NEFA subclasses and 3 individual NEFAs were associated with incident stroke. Of these, the NEFA n-3 subclass and dihomo-γ-linolenic acid are diet derived and may be potential biomarkers for total stroke risk.

Effect of Long-Term Marine É·-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine É·-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related. METHODS: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine É·-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of É·-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model. RESULTS: Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of É·-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine É·-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; P=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; P=0.024; P for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of É·-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; P=0.001). CONCLUSIONS: In RCTs examining cardiovascular outcomes, marine É·-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.

Chocolate consumption and risk of coronary artery disease: the Million Veteran Program.

Background: Although previous studies have suggested cocoa products may promote cardiovascular health in the general population, no public data are available from patients receiving care in a national integrated health care system. Objectives: We tested the hypothesis that regular chocolate consumption is associated with a lower risk of coronary artery disease (CAD) events among participants of the Million Veteran Program (MVP). Secondary analysis examined if the main hypothesis was observed among participants with type 2 diabetes. Methods: We analyzed data from MVP participants who completed the food frequency section of the MVP Lifestyle Survey and were free of CAD at the time of survey completion. CAD events during follow-up (International Statistical Classification of Diseases Ninth Revision codes 410-411 and 413-414, and Tenth Revision codes I20-I25 except I25.2) were assessed using electronic health records. We fitted a Cox proportional hazard model to estimate the RR of CAD. Results: Of 188,447 MVP enrollees with survey data, mean ± SD age was 64 ± 12.0 y and 90% were men. For regular chocolate (28.3 g/serving) consumption of <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk, crude incidence rates (per 1000 person-years) for fatal and nonfatal CAD events or coronary procedures were 20.2, 17.5, 16.7, 17.1, and 16.9, respectively, during a mean follow-up of 3.2 y. After adjusting for age, sex, race, and lifestyle factors, the corresponding HRs (95% CIs) were 1.00 (ref), 0.92 (0.87, 0.96), 0.88 (0.83, 0.93), 0.89 (0.84, 0.95), and 0.89 (0.84, 0.96), respectively (P for linear trend < 0.0001). In a secondary analysis of 47,265 diabetics, we did not observe a decreasing trend in CAD mortality among those who consumed ≥1 serving of chocolate a month compared with those who consumed <1 serving/mo. Conclusions: Regular chocolate consumption was associated with a lower risk of CAD among veterans, but was not associated with cardiovascular disease risk in veterans with type 2 diabetes.

Omega-3 supplementation and heart failure: A meta-analysis of 12 trials including 81,364 participants.

Heart failure (HF) remains a leading cause of hospitalization and mortality. Marine omega-3 fatty acid supplements (omega-3 s) have shown efficacy in decreasing sudden cardiac death and improving the left ventricle ejection fraction percent (LVEF%). In this review, we evaluated the effect of marine omega-3 fatty acid supplements (omega-3 s) on HF hospitalization, recurrent HF hospitalization, and cardiovascular mortality in patients with heart failure. We found that omega-3 supplementation did not reduce first HF hospitalization or cardiovascular mortality but did significantly reduce recurrent HF hospitalizations, as compared with placebo.

Consumption of potatoes and incidence rate of coronary artery disease: The Million Veteran Program.

BACKGROUND: Potato consumption is highly prevalent around the world. Previous studies have reported a positive association of potato intake with hypertension and type 2 diabetes. However, data are scarce on potato consumption and risk of coronary artery disease (CAD). OBJECTIVE: We hypothesized that potato consumption is positively associated with the incidence of CAD among US veterans. DESIGN: We prospectively studied 148,671 participants from Million Veteran Program (MVP). We used a semi-quantitative food frequency questionnaire to assess consumption of baked, boiled, and mashed potatoes. The incidence of CAD was assessed through electronic health record. We used Cox Proportional hazard model to compute hazard ratios (HR) and 95% confidence intervals (95% CI) for CAD events across categories of potato intake. RESULT: The average age of participants was 64 years at the time of potato assessment. A total of 6309 new cases of CAD occurred during a mean follow up of 2.7 ± 1.4 y. Median potato consumption was 1 cup/week. The crude incidence of CAD from lowest to highest category of potato consumption was 14.5, 15.0, 15.2, 16.1, and 18.9 per 1000 person-years, respectively. Hazard ratios (95% CI) of CAD were 1.00 (reference), 1.02 (0.93-1.11), 1.02 (0.93-1.12), 1.04 (0.95-1.15), and 1.21 (1.07-1.37) for potato intake of <1 cup/month, 1-3 cups/month, 1 cup/week, 2-4 cups/week, and 5+ cups/week respectively, adjusting for age, gender, race, body mass index (BMI), alcohol consumption, exercise, smoking, DASH (Dietary Approaches to Stop Hypertension) score, and education. The observed relation of potato consumption with CAD was not modified by age, BMI, gender, and ethnicity in a secondary analysis. In a sensitivity analysis, exclusion of CAD events occurred during the first year of follow up did not alter the findings. CONCLUSION: Frequent (5+ cups/week) but not infrequent potato consumption was associated with a higher risk of CAD among MVP participants.

Coffee consumption and risk of heart failure in the Physicians' Health Study.

BACKGROUND: Previous studies have reported the benefits of coffee consumption on diabetes, stroke, hyperlipidemia, and coronary artery disease (CAD). However, no large-scale long-term prospective study has evaluated the relation between coffee consumption and heart failure (HF) among US population. OBJECTIVE: To test the hypothesis that coffee consumption is associated with risk of HF among male physicians. METHODS: We prospectively studied 20,433 middle-aged and older men from the Physicians' Health Study (PHS). Coffee consumption was assessed using a semi-quantitative food frequency questionnaire. The incidence of HF was assessed based on self-reports on annual questionnaires which were validated in a subsample using by review of medical records. We used Cox proportional hazard models to compute the hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). RESULTS: The mean (SD) age of men was 66.4 (9.2) years. During a mean follow-up of 9.3 years, 901 new cases of HF were reported. In a multivariable Cox model adjusting for age, alcohol, smoking, and exercise, the HR (95% CI) of HF were 1.00 (reference), 1.04 (0.84-1.28), 0.90 (0.73-1.11), and 1.09 (0.91-1.30) for coffee consumption of almost never, <1 cup/day, 1 cup/day, and ≥2 cups/day, respectively (P for linear trend - 0.47). In a secondary analysis, dietary caffeine intake was not associated with HF risk: multivariable adjusted HR (95% CI) were 1.00 (reference), 1.07 (0.87-1.31), 0.95 (0.77-1.18), 1.06 (0.86-1.31), and 1.15 (0.92-1.44) across consecutive quintiles of dietary caffeine (P for linear trend - 0.34). CONCLUSIONS: We found no association between either coffee consumption or dietary caffeine intake with HF risk among US male physicians.

Omega-3 supplement use, fish intake, and risk of non-fatal coronary artery disease and ischemic stroke in the Million Veteran Program.

BACKGROUND & AIMS: Observational and clinical trial evidence suggests an inverse association of omega-3 polyunsaturated fatty acids with coronary artery disease (CAD) mortality, although relationships with non-fatal CAD and stroke are less clear. We investigated whether omega-3 fatty acid supplement use and fish intake were associated with incident non-fatal CAD and ischemic stroke among US Veterans. METHODS: The Million Veteran Program (MVP) is an ongoing nation-wide longitudinal cohort study of US Veterans with self-reported survey, biospecimen, and electronic health record data. Regular use of omega-3 supplements (yes/no) and frequency of fish intake within the past year were assessed using a food frequency questionnaire. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of omega-3 supplement use and fish intake with incident non-fatal CAD and ischemic stroke, defined from electronic health records using validated algorithms. Multivariable models included demographics, body mass index, education, smoking status, alcohol intake, and exercise frequency. RESULTS: Among 197,761 participants with food frequency data (mean age: 66 ± 12 years, 92% men), 21% regularly took omega-3 supplements and median fish intake was 1 (3-5 ounce) serving/week. Over a median follow-up of 2.9 years for non-fatal CAD and 3.3 years for non-fatal ischemic stroke, we observed 6265 and 4042 incident cases of non-fatal CAD and non-fatal ischemic stroke, respectively. Omega-3 fatty acid supplement use was independently associated with a lower risk of non-fatal ischemic stroke [HR (95% CI): 0.88 (0.81, 0.95)] but not non-fatal CAD [0.99 (0.93, 1.06)]. Fish intake was not independently associated with non-fatal CAD [1.01 (0.94, 1.09) for 1-3 servings/month, 1.03 (0.98, 1.11) for 1 serving/week, 1.02 (0.93, 1.11) for 2-4 servings/week, and 1.15 (0.98, 1.35) for ≥5 servings/week, reference = <1 serving/month, linear p-trend = 0.09] or non-fatal ischemic stroke [0.92 (0.84, 1.00) for 1-3 servings/month, 0.93 (0.85, 1.02) for 1 serving/week, 0.96 (0.86, 1.07) for 2-4 servings/week, and 1.13 (0.93-1.38) for ≥5 servings/week, linear p-trend = 0.16]. CONCLUSIONS: Neither omega-3 supplement use, nor fish intake, was associated with non-fatal CAD among US Veterans. While omega-3 supplement use was associated with lower risk of non-fatal ischemic stroke, fish intake was not. Randomized controlled trials are needed to confirm whether omega-3 supplementation is protective against ischemic stroke in a US population.

Coffee Consumption and Risk of Atrial Fibrillation in the Physicians' Health Study.

Background Although coffee consumption is often reported as a trigger for atrial fibrillation (AF) among patients with paroxysmal AF, prospective studies on the relation of coffee consumption with AF risk have been inconsistent. Hence, we sought to assess the association between coffee consumption and risk of AF in men. Methods and Results We prospectively studied men who participated in the Physicians' Health Study (N=18 960). Coffee consumption was assessed through self-reported food frequency questionnaires. The incidence of AF was assessed through annual questionnaires and validated through review of medical records in a subsample. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs of AF. The average age was 66.1 years. A total of 2098 new cases of AF occurred during a mean follow-up of 9 years. Hazard ratios (95% CI) of AF were 1.0 (reference), 0.85 (0.71-1.02), 1.07 (0.88-1.30), 0.93 (0.74-1.17), 0.85 (0.74-0.98), 0.86 (0.76-0.97), and 0.96 (0.80-1.14) for coffee consumption of rarely/never, ≤1 cup/week, 2 to 4 cups/week, 5 to 6 cups/week, 1 cup/day, 2 to 3 cups/day, and 4+ cups/day, respectively; adjusting for age, smoking, alcohol intake, and exercise (P for nonlinear trend=0.01). In a secondary analysis the multivariable adjusted hazard ratio (95% CI) of AF per standard deviation (149-mg) change in caffeine intake was 0.97 (0.92-1.02). Conclusions Our data suggest a lower risk of AF among men who reported coffee consumption of 1 to 3 cups/day.

Vitamin D supplements and prevention of cardiovascular disease.

PURPOSE OF REVIEW: The role of vitamin D supplementation for prevention of cardiovascular disease (CVD) outcomes has been rigorously studied only recently. This review briefly summarizes results from recent randomized controlled trials in the context of prior laboratory and epidemiologic data. RECENT FINDINGS: Randomized trials of vitamin D that included CVD outcomes, as well as two recently published large population-based trials that prespecified CVD as a primary endpoint (The Vitamin D Assessmentand The VITamin D and OmegA-3 TriaL), indicate that vitamin D supplementation does not decrease CVD incidence, when compared with placebo. SUMMARY: Evidence to date suggests that vitamin D supplementation in the general community does not reduce the risk of major cardiovascular events. Other trials are ongoing and future studies will explore additional CVD outcomes such as heart failure and assess high-risk populations such as those with chronic kidney disease.

Seafood Long-Chain n-3 Polyunsaturated Fatty Acids and Cardiovascular Disease: A Science Advisory From the American Heart Association.

Since the 2002 American Heart Association scientific statement "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease," evidence from observational and experimental studies and from randomized controlled trials continues to emerge to further substantiate the beneficial effects of seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease. A recent American Heart Association science advisory addressed the specific effect of n-3 polyunsaturated fatty acid supplementation on clinical cardiovascular events. This American Heart Association science advisory extends that review and offers further support to include n-3 polyunsaturated fatty acids from seafood consumption. Several potential mechanisms have been investigated, including antiarrhythmic, anti-inflammatory, hematologic, and endothelial, although for most, longer-term dietary trials of seafood are warranted to substantiate the benefit of seafood as a replacement for other important sources of macronutrients. The present science advisory reviews this evidence and makes a suggestion in the context of the 2015-2020 Dietary Guidelines for Americans and in consideration of other constituents of seafood and the impact on sustainability. We conclude that 1 to 2 seafood meals per week be included to reduce the risk of congestive heart failure, coronary heart disease, ischemic stroke, and sudden cardiac death, especially when seafood replaces the intake of less healthy foods.

Lack of Association Between Heart Failure and Incident Cancer.

BACKGROUND: Several recent studies have suggested an increased cancer risk among patients with heart failure (HF). However, these studies are constrained by limited size and follow-up, lack of comprehensive data on other health attributes, and adjudicated cancer outcomes. OBJECTIVES: This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality. METHODS: The study assembled a cohort from the Physicians' Health Studies I and II, 2 randomized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011, respectively, that included annual health evaluations and determination of cancer and HF diagnoses. In the primary analysis, the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer, modeling HF as a time-varying exposure. In a complementary analysis, the study used the landmark method and identified cancer-free participants at 70 years of age, distinguishing between those with and without HF, and likewise performed Cox regression. Sensitivity analyses were performed at 65, 75, and 80 years of age. RESULTS: Among 28,341 Physicians' Health Study participants, 1,420 developed HF. A total of 7,363 cancers developed during a median follow-up time of 19.9 years (25th to 75th percentile: 11.0 to 26.8 years). HF was not associated with cancer incidence in crude (hazard ratio: 0.92; 95% confidence interval: 0.80 to 1.08) or multivariable-adjusted analysis (hazard ratio: 1.05; 95% confidence interval: 0.86 to 1.29). No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment. Results were similar when using the landmark method at all landmark ages. CONCLUSIONS: HF is not associated with an increased risk of cancer among male physicians.

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.

Occurrence of hepatotoxicity with pazopanib and other anti-VEGF treatments for renal cell carcinoma: an observational study utilizing a distributed database network.

PURPOSE: To quantify the hepatic safety of pazopanib and comparator anti-vascular endothelial growth factor (VEGF) therapies in clinical practice among renal cell carcinoma (RCC) patients. METHODS: A population-based cohort study of new anti-VEGF users was conducted in two US healthcare databases, Department of Veterans Affairs (VA) and an oncology practice network (Altos), and the PHARMO Database Network in The Netherlands. A common protocol was used to collect liver chemistry (LC) data from anti-VEGF initiation through 4 years of follow-up. In the VA population, suspected drug-induced liver injury (DILI) outcomes were investigated via chart review, with adjudication by hepatologists. RESULTS: In Altos and VA, respectively, the total RCC patients were: pazopanib (156, 243), bevacizumab (122, 99), sorafenib (82, 249) and sunitinib (285, 751). PHARMO contained too few patients to be included. Few cases of alanine aminotransferase (ALT) ≥8× the upper limit of normal were seen across the anti-VEGF cohorts; incidence rates (per 100 person-years) ranged from 0 (sunitinib) to 8.2 (pazopanib) in Altos and from 0 (bevacizumab and sorafenib) to 2.1 (pazopanib) among VA patients. No cases of Hy's law identified by combination LC elevations were seen in patients treated with pazopanib or bevacizumab; one case was observed in those treated with sorafenib, and two cases were found among sunitinib users. One case of adjudicated DILI was observed in a sunitinib-treated patient; none were found among patients treated with pazopanib, bevacizumab or sorafenib. CONCLUSIONS: Severe liver injury occurred infrequently during exposure to pazopanib and other anti-VEGF therapies in a population-based setting.

ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies.

IMPORTANCE: The role of ω-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE: To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20:5ω-3), docosapentaenoic acid (DPA; 22:5ω-3), and docosahexaenoic acid (DHA; 22:6ω-3) and plant-derived α-linolenic acid (ALA; 18:3ω-3) for incident CHD. DATA SOURCES: A global consortium of 19 studies identified by November 2014. STUDY SELECTION: Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue ω-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS: Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, ω-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES: Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS: The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with ω-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the ω-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE: On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived ω-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

Dietary vitamin D and risk of heart failure in the Physicians' Health Study.

BACKGROUND: Experimental studies have demonstrated the role of vitamin D in key pathways related to cardiovascular health. While several studies have investigated the impact of vitamin D therapy on outcomes in subjects with prevalent heart failure, limited research exists on the relationship of dietary vitamin D consumption with the risk of heart failure. Thus, we sought to investigate whether dietary vitamin D consumption was associated with a lower risk of incident heart failure in a large prospective cohort of male physicians. METHODS AND RESULTS: We prospectively studied 19,635 males from the Physicians' Health Study. Dietary vitamin D information was obtained from a baseline food frequency questionnaire, and heart failure information was obtained by questionnaire and validated in a subsample. Mean age was 66.4 years. Median dietary vitamin D consumption was 200.4 IU and only 2.3% of the subjects used vitamin D supplements. After an average follow-up of 9.3 years, there were 858 new cases of heart failure identified. Higher intake of dietary vitamin D was not associated with incident heart failure in a multivariable adjusted model: hazard ratios (95% CI) of incident heart failure were 1.0 (reference), 1.29 (1.04-1.60), 1.17 (0.94-1.46), 1.22 (0.98-1.53), and 1.16 (0.92-1.46) from lowest to highest age- and energy-adjusted vitamin D quintile, respectively, after adjusting for age, BMI, race, exercise, alcohol use, smoking, calories, and prevalent atrial fibrillation (p for linear trend = 0.64). CONCLUSIONS: These data are consistent with a lack of an association between dietary vitamin D and incident heart failure in this population of professionally-employed middle-aged males.