J Michael Gaziano

Harvard University, Cambridge, Massachusetts, United States

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Publications (519)5332.09 Total impact

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    ABSTRACT: Background: High-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, may promote atherosclerosis, particularly among adults with elevated blood pressure; however, data are sparse. We examined the association between hsCRP concentrations and risk of total stroke by hypertension status (normotension, prehypertension, and hypertension) among men in the Physicians' Health Study (PHS). Methods and results: Blood samples were collected (1996-1997) and assayed for hsCRP among 10 456 initially healthy men from PHS I and PHS II and followed from 1997 to 2012. Self-reported hypertension status, cardiovascular risk factors, lifestyle, and alcohol consumption were obtained from the baseline questionnaire prior to randomization in PHS II. Strokes were updated approximately annually and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models were used. We observed 395 incident total strokes over 115 791 person-years. In analyses adjusted for potential confounders and stroke risk factors, clinically elevated hsCRP (>3 mg/L) was associated with a 40% significantly greater hazard of total stroke compared with hsCRP <1 mg/L (hazard ratio 1.40, 95% CI 1.06 to 1.87; Ptrend=0.01). Additional adjustment for blood pressure and biomarkers associated with cardiovascular risk marginally attenuated the estimates. Results were similar by hypertension status, although not statistically significant among normotensive and prehypertensive participants due to limited events. Conclusions: Elevated hsCRP levels were associated with a greater risk of total stroke, even after adjustment for potential confounders and cardiovascular risk factors. Risk of total stroke was significantly higher among hypertensive men with elevated hsCRP compared with normotensive men with low hsCRP.
    Journal of the American Heart Association 09/2015; 4(9). DOI:10.1161/JAHA.115.002073 · 4.31 Impact Factor
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    ABSTRACT: Background: Several cross-sectional, but few prospective, studies suggest that inflammation may be involved in the development of hypertension. We examined markers of inflammation-high-sensitivity C-reactive protein, interleukin-6, and soluble intercellular adhesion molecule-1-and a marker of fibrinolysis, D-dimer, for their associations with incident hypertension in the Physicians' Health Study. Methods and results: Baseline blood values and information on hypertension-related risk factors were collected in 1982. Incident hypertension was defined as self-reported initiation of antihypertensive treatment, systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg during follow-up. With use of a nested case-control design, 396 cases of incident hypertension and controls free of hypertension were matched 1:1 on age (mean 47.4 years) and follow-up time. In crude matched-pair analyses, the conditional relative risks of hypertension in the second through fourth versus the lowest quartiles for plasma high-sensitivity C-reactive protein were 1.27, 1.73, and 1.81 (Ptrend=0.01); for interleukin-6, 1.22, 1.02, and 1.51 (Ptrend=0.06); for soluble intercellular adhesion molecule-1, 1.00, 0.80, and 1.26 (Ptrend=0.37); and for D-dimer, 1.61, 1.81, and 1.52 (Ptrend=0.46). Multivariable adjustment attenuated the estimates. The multivariable relative risks of hypertension in the second through fourth compared to the lowest quartiles of high-sensitivity C-reactive protein were 1.24, 1.60, and 1.47 (Ptrend=0.20); for interleukin-6, 1.08, 0.92, and 1.36 (Ptrend=0.16); for soluble intercellular adhesion molecule-1, 0.89, 0.79, and 1.18 (Ptrend=0.55); and for D-dimer, 1.48, 1.68, and 1.38 (Ptrend=0.63). Conclusions: Elevated plasma inflammatory markers and D-dimer were nonsignificantly associated with a higher risk of hypertension among initially healthy men.
    Journal of the American Heart Association 09/2015; 4(9). DOI:10.1161/JAHA.115.001802 · 4.31 Impact Factor
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    ABSTRACT: Background: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g., waist circumference; n=647,478; 1,947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n=1,096,492; 3,223 pancreatic cancer deaths). Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models. Results: Higher waist-to-hip ratio (HR=1.09, 95% CI: 1.02-1.17 per 0.1 increment) and waist circumference (HR=1.07, 95% CI: 1.00-1.14 per 10 cm) was associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR=1.18, 95% CI: 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight or obese individuals (compared with BMI of 21.0-<23 kg/m(2), HR=1.36, 95% CI: 1.20-1.55 for BMI 25.0<27.5 kg/m(2), HR=1.48, 95% CI: 1.20-1.84 for BMI 27.5-<30 kg/m(2), HR=1.43, 95% CI: 1.11-1.85 for BMI >30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR=1.05, 95% CI: 1.01-1.10 per 5kg/m(2)). Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.
    Annals of Oncology 09/2015; DOI:10.1093/annonc/mdv355 · 7.04 Impact Factor
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    ABSTRACT: Recent large clinical trials show lower rates of late cardiovascular events by extending clopidogrel >12 months after percutaneous coronary revascularization (PCI). However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients. The aim of this analysis was to determine the effect of prolonging clopidogrel therapy >12 months versus ≤12 months after PCI on very late outcomes in patients with diabetes mellitus (DM). Using the Veterans Health Administration, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into 3 groups: 1) 16,332 without DM; 2) 9,905 with DM treated with oral medications or diet; and 3) 2,612 with DM treated with insulin. Clinical outcomes, stratified by stent type, ≤4 years after PCI were determined from the Veterans Health Administration and Medicare databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or myocardial infarction (MI). In patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42 to 0.82) and death or MI (HR: 0.67; 95% CI: 0.49 to 0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48 to 0.77) and death or MI (HR: 0.61; 95% CI: 0.5 to 0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents. Extending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 09/2015; 66(10):1091-101. DOI:10.1016/j.jacc.2015.06.1339 · 16.50 Impact Factor
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    ABSTRACT: Soya proteins and isoflavones have been reported to exert beneficial effects on the serum lipid profile. More recently, this claim is being challenged. The objective of this study was to comprehensively examine the effects of soya consumption on the lipid profile using published trials. A detailed literature search was conducted via MEDLINE (from 2004 through February 2014), CENTRAL (The Cochrane Controlled Clinical Trials Register) and ClinicalTrials.gov for randomised controlled trials assessing the effects of soya on the lipid profile. The primary effect measure was the difference in means of the final measurements between the intervention and control groups. In all, thirty-five studies (fifty comparisons) were included in our analyses. Treatment duration ranged from 4 weeks to 1 year. Intake of soya products resulted in a significant reduction in serum LDL-cholesterol concentration, –4·83 (95 % CI –7·34, –2·31) mg/dl, TAG, –4·92 (95 % CI –7·79, –2·04) mg/dl, and total cholesterol (TC) concentrations, –5·33 (95 % CI –8·35, –2·30) mg/dl. There was also a significant increase in serum HDL-cholesterol concentration, 1·40 (95 % CI 0·58, 2·23) mg/dl. The I 2 statistic ranged from 92 to 99 %, indicating significant heterogeneity. LDL reductions were more marked in hypercholesterolaemic patients, –7·47 (95 % CI –11·79, –3·16) mg/dl, than in healthy subjects, –2·96 (95 % CI –5·28, –0·65) mg/dl. LDL reduction was stronger when whole soya products (soya milk, soyabeans and nuts) were used as the test regimen, –11·06 (95 % CI –15·74, –6·37) mg/dl, as opposed to when ‘processed’ soya extracts, –3·17 (95 % CI –5·75, –0·58) mg/dl, were used. These data are consistent with the beneficial effects of soya proteins on serum LDL, HDL, TAG and TC concentrations. The effect was stronger in hypercholesterolaemic subjects. Whole soya foods appeared to be more beneficial than soya supplementation, whereas isoflavone supplementation had no effects on the lipid profile.
    The British journal of nutrition 08/2015; 114:1-13. DOI:10.1017/S0007114515002603 · 3.45 Impact Factor
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    ABSTRACT: Patients with chronic kidney disease (CKD) are at high risk of death or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We assessed whether prolonged dual antiplatelet therapy beyond the recommended 12 months may prevent adverse outcomes in patients with CKD receiving drug-eluting stents (DES) or bare-metal stents (BMS). We studied all Veterans receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA) Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular filtration rate <60 mL/min) or normal renal function. We used landmark analyses from 12 months after PCI with Cox proportional hazards multivariable and propensity-adjusted models to assess the effect of prolonged clopidogrel (more than 12 months) versus 12 months or less after PCI on clinical outcomes from 1 year to 4 years after PCI. Of 23 042 eligible subjects receiving PCI, 4880 (21%) had CKD. Compared with normal renal function, patients with CKD had higher risks of death or MI 1-4 years after DES (21% vs 12%, HR=1.75; 95% CI 1.51 to 2.04) or BMS (28% vs 15%, HR=2.10; 95% CI 1.90 to 2.32). In patients with CKD receiving DES, clopidogrel use of more than 12 months after PCI was associated with lower risks of death or MI (18% vs 24%, HR=0.74; 95% CI 0.58 to 0.95), and death (15% vs 23%, HR=0.61; 95% CI 0.47 to 0.80), but had no effect on repeat revascularisation 1-4 years after PCI. In patients with CKD, prolonging clopidogrel beyond 12 months after PCI may decrease the risk of death or MI only in patients receiving first-generation DES. These results support a patient-tailored approach to prolonging clopidogrel after PCI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Heart (British Cardiac Society) 07/2015; 101(19). DOI:10.1136/heartjnl-2014-307168 · 5.60 Impact Factor
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    ABSTRACT: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC n=860, ICC n=260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; ptrend cups/day=<0.0001). More notable reduced risk was seen among women than men (pinteraction=0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71, 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no relationship between coffee consumption and ICC. These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Copyright © 2015, American Association for Cancer Research.
    Cancer Epidemiology Biomarkers & Prevention 06/2015; DOI:10.1158/1055-9965.EPI-15-0137 · 4.13 Impact Factor
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    ABSTRACT: Background: Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%). Methods: 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. Results: Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002). Conclusions: Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.
    Journal of Diabetes Research 06/2015; 2015:1-13. DOI:10.1155/2015/157698 · 2.16 Impact Factor
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    ABSTRACT: Associations between anthropometry and head and neck cancer (HNC) risk are inconsistent. We aimed to evaluate these associations while minimizing biases found in previous studies. We pooled data from 1 941 300 participants, including 3760 cases, in 20 cohort studies and used multivariable-adjusted Cox proportional hazard regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of anthropometric measures with HNC risk overall and stratified by smoking status. Greater waist circumference (per 5 cm: HR = 1.04, 95% CI 1.03-1.05, P-value for trend = <0.0001) and waist-to-hip ratio (per 0.1 unit: HR = 1.07, 95% CI 1.05-1.09, P-value for trend = <0.0001), adjusted for body mass index (BMI), were associated with higher risk and did not vary by smoking status (P-value for heterogeneity = 0.85 and 0.44, respectively). Associations with BMI (P-value for interaction = <0.0001) varied by smoking status. Larger BMI was associated with higher HNC risk in never smokers (per 5 kg/m(2): HR = 1.15, 95% CI 1.06-1.24, P-value for trend = 0.0006), but not in former smokers (per 5 kg/m(2): HR = 0.99, 95% CI 0.93-1.06, P-value for trend = 0.79) or current smokers (per 5 kg/m(2): HR = 0.76, 95% CI 0.71-0.82, P-value for trend = <0.0001). Larger hip circumference was not associated with a higher HNC risk. Greater height (per 5 cm) was associated with higher risk of HNC in never and former smokers, but not in current smokers. Waist circumference and waist-to-hip ratio were associated positively with HNC risk regardless of smoking status, whereas a positive association with BMI was only found in never smokers. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    International Journal of Epidemiology 06/2015; 44(2). DOI:10.1093/ije/dyv059 · 9.18 Impact Factor
  • Philip Greenland · Eric D. Peterson · J. Michael Gaziano
    JAMA The Journal of the American Medical Association 05/2015; 313(17):1718. DOI:10.1001/jama.2015.3049 · 35.29 Impact Factor
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    ABSTRACT: We confirmed strong association of rs78378222:A>C (per allele odds ratio = 3.14; P = 6.48×10(-11) ), a germline rare single nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study (GWAS) of glioma (1856 cases and 4955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with ∼3kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Human Mutation 04/2015; 36(7). DOI:10.1002/humu.22799 · 5.14 Impact Factor
  • Jeremy Robbins · Andrew B Petrone · J.Michael Gaziano · Luc Djoussé
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    ABSTRACT: 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. 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). 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. Published by Elsevier Ltd.
    Clinical Nutrition 04/2015; DOI:10.1016/j.clnu.2015.04.011 · 4.48 Impact Factor
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    ABSTRACT: ω3 and ω6 fatty acids (FA) may have divergent effects on the development of obesity. We examined the association of baseline erythrocyte ω3 and ω6 FA composition with body weight change and the risk of becoming overweight or obese in the Women's Health Study (WHS) participants. We identified 534 women who had baseline erythrocyte FA measured and a baseline body mass index (BMI) of 18.5-<25 kg/m(2). Body weight was updated at a total of six time points during follow-up. Weight gain during a mean of 10.4-year follow-up increased with increasing quartiles of baseline erythrocyte cis ω6 FA, ω6/ω3 ratio, and trans FA while decreased with increasing cis ω3 FA. After multivariable adjustment including total energy intake and physical activity, the weight gain (kg) in the highest versus the lowest quartile was 3.08 versus 2.32 for erythrocyte cis ω6 FA (p trend 0.04), 2.07 versus 2.92 for cis ω3 FA (p trend 0.08), 2.93 versus 2.05 for ω6/ω3 ratio (p trend 0.046), and 3.03 versus 2.27 for trans FA (p trend 0.06). Among individual FA, the associations were significant for 18:2ω6, 18:3ω6, and trans 18:1 and marginally significant for 20:3ω6 and trans 18:2. The risk of becoming overweight or obese (defined as BMI ≥25 kg/m(2) at any follow-up time point) increased across increasing ω6/ω3 ratio (multivariable model p trend 0.04). In this prospective study, we found suggestive evidence that erythrocyte cis ω6 FA may be positively associated, and cis ω3 FA inversely associated with weight gain in initially normal-weight women.
    European Journal of Nutrition 03/2015; DOI:10.1007/s00394-015-0889-y · 3.47 Impact Factor
  • Luc Djoussé · Andrew B Petrone · J Michael Gaziano
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    ABSTRACT: Consumption of fried foods is highly prevalent in the Western dietary pattern. Though limited studies have reported a positive association between frequency of fried food intake and risk of coronary artery disease, diabetes, or hypertension, other investigators failed to report such an association. It is unclear whether intake of fried foods is associated with a higher risk of heart failure (HF). Hence, we sought to examine the association between the frequency of fried food consumption and the risk of HF. This was a prospective cohort study of 15 362 participants from the Physicians' Health Study. Fried food intake frequency was assessed by a food frequency questionnaire (1997-2001), and incident HF was captured by annual questionnaires. We used Cox regression to calculate hazard ratios (HRs) of HF. After an average follow-up of 9.6±2.4 years, a total of 632 new HF cases occurred in this cohort. Compared to subjects who reported fried food consumption of <1 per week, HRs (95% CI) for HF were 1.24 (1.04 to 1.48), 1.28 (1.00 to 1.63), and 2.03 (1.37 to 3.02) for fried food intake of 1 to 3/week, 4 to 6/week, and 7+/week, respectively, after adjustment for age, energy intake, alcohol use, exercise, smoking, and overall diet score (P linear trend, 0.0002). Similar results were obtained for intake of fried foods at home or away from home and among subjects with higher dietary score or HF without antecedent myocardial infarction. Our data are consistent with a positive association of fried food intake frequency with incident HF in male physicians. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 03/2015; 4(4). DOI:10.1161/JAHA.114.001740 · 4.31 Impact Factor
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    ABSTRACT: Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 03/2015; 96(3):487-97. DOI:10.1016/j.ajhg.2015.01.011 · 10.93 Impact Factor
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    ABSTRACT: To assess the prevalence and changes over time of ideal Life's Simple Seven (LSS) in African-Americans. Prospective cohort of 5301 African-Americans from the Jackson Heart Study (JHS) from 2000 to 2013. Each of the LSS metrics was categorized as poor, intermediate, or ideal. Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal LSS was 3.3%, 23.0%, 33.5%, 24.7%, 11.6%, 3.6%, 0.3%, and 0%, respectively. Corresponding values for women were 1.7%, 26.3%, 33.1%, 22.8%, 11.9%, 3.7%, 0.6%, and 0%. Prevalence of ideal diet was 0.9%. The proportions of those meeting LSS ideal recommendations for cholesterol and fasting glucose declined from the first through third JHS visits across all age groups, whereas prevalence of ideal BMI declined only in participants <40years at a given visit. Prevalence of ideal blood pressure did not change over time and being ideal on physical activity improved from the first [18.3% (95% CI: 17.3% to 19.3%)] to third visit [24.8% (95% CI: 23.3% to 26.3%)]. Our data show a low prevalence of ideal LSS (especially diet, physical activity, and obesity) in the JHS and a slight improvement in adherence to physical activity recommendations over time. Copyright © 2015. Published by Elsevier Inc.
    Preventive Medicine 02/2015; 74. DOI:10.1016/j.ypmed.2015.02.006 · 3.09 Impact Factor
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    ABSTRACT: Previous studies reported beneficial effects of cocoa or chocolate on insulin resistance, oxidative stress, and inflammation, which are important risk factors of type 2 diabetes mellitus (DM). However, it is unclear whether chocolate consumption is associated with risk of DM. We tested the hypothesis that chocolate consumption is inversely associated with incident DM in the Physicians' Health Study (PHS). We prospectively analyzed data on 18,235 PHS participants who were free of DM at baseline (1997-2001). Chocolate consumption was obtained from a baseline food-frequency questionnaire. Incident DM was ascertained via annual follow-up questionnaires and validated in a subsample by a review of medical records. We used Cox proportional hazards models to estimate HRs and 95% CIs of DM. The mean (±SD) age at baseline was 66.3 ± 9.2 y. During a mean follow up of 9.2 y, 1123 men (6.2%) developed DM. For self-reported chocolate consumption of none, 1-3 servings/mo, 1 serving/wk, and ≥2 servings/wk, multivariable-adjusted HRs (95% CIs) of DM adjusted for lifestyle, clinical, and dietary risk factors including total energy intake were 1.00 (referent), 0.93 (0.79, 1.09), 0.86 (0.72, 1.04), and 0.83 (0.69, 0.99), respectively (P-trend = 0.047). In secondary analyses, the inverse association of chocolate consumption and risk of DM was slightly stronger in subjects without a history of cardiovascular disease or heart failure (P-trend = 0.023). In addition, both age and BMI modified the chocolate-DM relation (P < 0.05 each). Our data support an inverse relation of chocolate intake with incident DM, which appears only to apply in younger and normal-body weight men after controlling for comprehensive life styles including total energy consumption. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 02/2015; 101(2):362-7. DOI:10.3945/ajcn.114.092221 · 6.77 Impact Factor
  • Tammy T Hshieh · Andrew B Petrone · J Michael Gaziano · Luc Djoussé
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    ABSTRACT: Previous studies have suggested that nut consumption is associated with beneficial cardiovascular outcomes. However, limited data are available on the association between nut intake and all-cause mortality. Our aim was to test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality. In this prospective cohort study in 20,742 male physicians, we assessed nut intake between 1999 and 2002 via a food-frequency questionnaire and ascertained deaths through an endpoint committee. We used Cox regression to estimate multivariable-adjusted HRs for death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality. During a mean follow-up of 9.6 y, there were 2732 deaths. The mean (±SD) age at baseline was 66.6 ± 9.3 y. Median nut consumption was 1 serving/wk. Multivariable-adjusted HRs (95% CIs) were 1.0 (reference), 0.92 (0.83, 1.01), 0.85 (0.76, 0.96), 0.86 (0.75, 0.98), and 0.74 (0.63, 0.87) for nut consumption of never or <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk, respectively (P-linear trend < 0.0001), after adjustment for age, body mass index, alcohol use, smoking, exercise, prevalent diabetes and hypertension, and intakes of energy, saturated fat, fruit and vegetables, and red meat. In a secondary analysis, results were consistent for cardiovascular disease mortality but only suggestive and non-statistically significant for coronary artery disease and cancer mortality. Our data are consistent with an inverse association between nut consumption and the risk of all-cause and cardiovascular disease mortality in US male physicians. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 02/2015; 101(2):407-12. DOI:10.3945/ajcn.114.099846 · 6.77 Impact Factor
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    ABSTRACT: The present issue of Epidemiologic Reviews is dedicated to better understanding the health of men and women who have served in the military. There are 13 articles that discuss a range of physical and mental health concerns among both military personnel who are currently serving and those who served in the past. The corresponding research provides insight into issues that are directly relevant and of keen interest to clinicians and investigators. The articles illustrate some of the obstacles to conducting rigorous epidemiologic research when seeking to inform the health issues of those who serve in the military and of veterans. Within the United States, they point to opportunities for the Department of Defense and Department of Veterans Affairs (VA) to address existing gaps in knowledge. The VA in particular can take advantage of its research infrastructure, altruistic veteran population, and clinical and administrative databases. In the era of multinational military interventions, international counterparts of the Department of Defense and VA should collaborate in the collection of data on relevant military exposures and also in the characterization of short- and long-term health effects related to service to better inform health needs. The work included in this issue is a call to the global research community to continue to invest resources to better characterize military service and its impact on health. Finally, these articles serve as a testament to the additional health burden carried by many of the women and men who have provided service to their country. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.
    Epidemiologic Reviews 01/2015; 37(1). DOI:10.1093/epirev/mxu013 · 6.67 Impact Factor

Publication Stats

30k Citations
5,332.09 Total Impact Points


  • 1995–2015
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 1991–2015
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Preventive Medicine
      • • Division of Aging
      • • Massachusetts Veteran's Epidemiology Research and Information Center
      Boston, Massachusetts, United States
    • Harvard Medical School
      • • Department of Medicine
      • • Division of Nutrition
      Boston, Massachusetts, United States
  • 2013
    • McGill University
      • Department of Oncology
      Montréal, Quebec, Canada
  • 2012
    • University of Ioannina
      • Department of Hygiene and Epidemiology
      Yannina, Epirus, Greece
  • 2006–2012
    • Boston University
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2011
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
    • Brown University
      • Department of Epidemiology
      Providence, Rhode Island, United States
  • 2010
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
    • University of Oxford
      • Cancer Epidemiology Unit
      Oxford, England, United Kingdom
  • 1997–2010
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2009
    • Harvard Vanguard Medical Associates
      Cambridge, Massachusetts, United States
  • 2005–2008
    • Florida Atlantic University
      • Department of Biomedical Science
      Boca Raton, Florida, United States
    • Cornell University
      • Department of Nutritional Sciences
      Ithaca, NY, United States
  • 2007
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 2006–2007
    • Center for Information Services
      Miami, Florida, United States
  • 1996
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Tufts University
      Бостон, Georgia, United States