J Michael Gaziano

Harvard University, Cambridge, Massachusetts, United States

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Publications (549)5499.12 Total impact

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    ABSTRACT: Background: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. Methods: We measured 82 metabolites by liquid chromatography–mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year. After multiple-hypothesis testing correction, a P value of .0006 or less (.05/82) was considered statistically significant. Based on the results, we evaluated 33 tagging single-nucleotide polymorphisms (SNPs) in the ACO1 gene, requiring a P value of less than .002 (.05/33) for statistical significance. All statistical tests were two-sided. Results: Two metabolites in the tricarboxylic acid (TCA) cycle—isocitrate and aconitate—were statistically significantly associated with survival. Participants in the highest vs lowest quintile had hazard ratios (HRs) for death of 1.89 (95% confidence interval [CI] = 1.06 to 3.35, P trend < .001) for isocitrate and 2.54 (95% CI = 1.42 to 4.54, P trend < .001) for aconitate. Isocitrate is interconverted with citrate via the intermediate aconitate in a reaction catalyzed by the enzyme aconitase 1 (ACO1). Therefore, we investigated the citrate to aconitate plus isocitrate ratio and SNPs in the ACO1 gene. The ratio was strongly associated with survival (P trend < .001) as was the SNP rs7874815 in the ACO1 gene (hazard ratio for death per minor allele = 1.37, 95% CI = 1.16 to 1.61, P < .001). Patients had an approximately three-fold hazard for death when possessing one or more minor alleles at rs7874851 and high aconitate or isocitrate. Conclusions: Prediagnostic circulating levels of TCA cycle intermediates and inherited ACO1 genotypes were associated with survival among patients with pancreatic cancer.
    No preview · Article · Jun 2016 · JNCI Journal of the National Cancer Institute
  • Luc Djoussé · Bing Lu · J. Michael Gaziano
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    ABSTRACT: The aim of this study was to obtain preliminary data to test the hypothesis that (1) a 12-week intervention with 28 g/day of walnuts improves endothelial function in people with type 2 diabetes mellitus (DM) and (2) intake of walnuts improves plasma adipokines after 12 weeks of intervention. In this pilot randomized, single-blinded, controlled trial of 26 adult subjects with prevalent DM, each subject was randomized to a usual diet with 28 g of walnuts per day or usual diet without walnuts (control group). Reactive hyperemia index (RHI), a measure of endothelial function, was measured non-invasively at baseline and after 12 weeks using Endo-PAT2000. We used linear regression to examine the effects of the intervention on RHI. The mean age at baseline was 64.8 ± 11.6 years; 61.5 % of participants were female, and 15.4 % had coronary artery disease. The standard error of RHI was 0.19. The difference in change in RHI during the intervention between the two groups was −0.029 (95 % confidence interval (CI) −0.52, 0.46, p = 0.23). Walnut intervention led to a suggestive increase in adiponectin, albeit non-statistically significant (difference 0.50 μg/ml (95 % CI −0.10, 1.09), p = 0.65). We demonstrated the feasibility of the proposed randomized trial and obtained needed standard deviations to calculate the required sample size to test proposed hypotheses in an efficacy trial.
    No preview · Article · Jan 2016
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    ABSTRACT: Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: In this large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women), we investigated thyroid cancer incidence associated with greater height, body mass index (BMI) at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2,996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: HRs (95% CIs) for height (per 5 cm)=1.07 (1.04-1.10), BMI (per 5 kg/m2)=1.06 (1.02-1.10), waist circumference (per 5 cm)=1.03 (1.01-1.05), young-adult BMI (per 5 kg/m2)=1.13 (1.02-1.25), and adulthood BMI gain (per 5 kg/m2)=1.07 (1.00-1.15). Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (P-interaction=0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: Our results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but most aggressive form, anaplastic carcinoma, and higher thyroid cancer mortality. Potential underlying biological mechanisms should be explored in future studies.
    No preview · Article · Jan 2016 · Thyroid: official journal of the American Thyroid Association
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    Luc Djoussé · Owais A Khawaja · J Michael Gaziano
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    ABSTRACT: Background: Observational data on the association between egg consumption and risk of type 2 diabetes mellitus (DM) have been inconsistent. Because eggs are a good source of protein and micronutrients and are inexpensive, it is important to clarify their role in the risk of developing DM. Objective: We conducted a meta-analysis of published prospective cohort studies to evaluate the relation of egg consumption with the risk of DM. Design: We searched PubMed, Ovid, Cochrane, and Google Scholar (up to October 2015) to retrieve published studies. We used RRs from extreme categories of egg consumption for the main analysis but also evaluated dose response by using cubic splines and generalized least squares regression. Results: We identified 12 cohorts for a total of 219,979 subjects and 8911 cases of DM. When comparing the highest with the lowest category of egg intake, pooled multivariate RRs of DM were 1.09 (95% CI: 0.99, 1.20) using the fixed-effect model and 1.06 (95% CI: 0.86, 1.30) using the random-effect model. There was evidence for heterogeneity (I(2) = 73.6%, P < 0.001). When stratified by geographic area, there was a 39% higher risk of DM (95% CI: 21%, 60%) comparing highest with lowest egg consumption in US studies (I(2) = 45.4%, P = 0.089) and no elevated risk of DM with egg intake in non-US studies (RR = 0.89; 95% CI: 0.79, 1.02 using the fixed-effect model, P < 0.001 comparing US with non-US studies). In a dose-response assessment using cubic splines, elevated risk of DM was observed in US studies among people consuming ≥3 eggs/wk but not in non-US studies. Conclusions: Our meta-analysis shows no relation between infrequent egg consumption and DM risk but suggests a modest elevated risk of DM with ≥3 eggs/wk that is restricted to US studies.
    Preview · Article · Jan 2016 · American Journal of Clinical Nutrition
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    ABSTRACT: Objective: Impairments in cognition and everyday functioning are common in schizophrenia and bipolar disorder (BPD). In this article, we present factor analyses of cognitive and functional capacity (FC) measures based on 2 studies of schizophrenia (SCZ) and bipolar I disorder (BPI) using similar methods. The overall goal of these analyses was to determine whether performance-based assessments should be examined individually, or aggregated on the basis of the correlational structure of the tests, as well as to evaluate the similarity of factor structures of SCZ and BPI. Method: Veterans Affairs Cooperative Studies Program Study #572 (Harvey et al., 2014) evaluated cognitive and FC measures among 5,414 BPI and 3,942 SCZ patients. A 2nd study evaluated similar neuropsychological (NP) and FC measures among 368 BPI and 436 SCZ patients. Principal components analysis, as well as exploratory and CFAs, were used to examine the data. Results: Analyses in both datasets suggested that NP and FC measures were explained by a single underlying factor in BPI and SCZ patients, both when analyzed separately or as in a combined sample. The factor structure in both studies was similar, with or without inclusion of FC measures; homogeneous loadings were observed for that single factor across cognitive and FC domains across the samples. Conclusion: The empirically derived factor model suggests that NP performance and FC are best explained as a single latent trait applicable to people with SCZ and BPD. This single measure may enhance the robustness of the analyses relating genomic data to performance-based phenotypes. (PsycINFO Database Record
    No preview · Article · Dec 2015 · Neuropsychology
  • J Michael Gaziano · Eric D Peterson · Philip Greenland

    No preview · Article · Nov 2015 · JAMA The Journal of the American Medical Association
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    ABSTRACT: Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
    Full-text · Article · Oct 2015 · JNCI Journal of the National Cancer Institute
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    Taraka V Gadiraju · Yash Patel · J Michael Gaziano · Luc Djoussé
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    ABSTRACT: Fried food consumption and its effects on cardiovascular disease are still subjects of debate. The objective of this review was to summarize current evidence on the association between fried food consumption and cardiovascular disease, diabetes, hypertension and obesity and to recommend directions for future research. We used PubMed, Google Scholar and Medline searches to retrieve pertinent publications. Most available data were based on questionnaires as a tool to capture fried food intakes, and study design was limited to case-control and cohort studies. While few studies have reported a positive association between frequencies of fried food intake and risk of coronary artery disease, heart failure, diabetes or hypertension, other investigators have failed to confirm such an association. There is strong evidence suggesting a higher risk of developing chronic disease when fried foods are consumed more frequently (i.e., four or more times per week). Major gaps in the current literature include a lack of detailed information on the type of oils used for frying foods, stratification of the different types of fried food, frying procedure (deep and pan frying), temperature and duration of frying, how often oils were reused and a lack of consideration of overall dietary patterns. Besides addressing these gaps, future research should also develop tools to better define fried food consumption at home versus away from home and to assess their effects on chronic diseases. In summary, the current review provides enough evidence to suggest adverse health effects with higher frequency of fried food consumption. While awaiting confirmation from future studies, it may be advisable to the public to consume fried foods in moderation while emphasizing an overall healthy diet.
    Preview · Article · Oct 2015 · Nutrients
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    ABSTRACT: Alzheimer's disease and related dementias (ADRD) comprise several progressive and incurable neurodegenerative disorders that some have classified as amyloidosis. With increased aging of the world's population, the prevalence of the sporadic form of ADRD, which comprises over 99% of cases, continues to rise at an alarming rate. The enormous societal burdens of ADRD already rival those of the many other major chronic diseases causing premature morbidity and mortality in the USA and worldwide such as cardiovascular disease and cancer. At present, there is an insufficient totality of evidence concerning the efficacy and safety of any pharmacologic agents to delay slow progression or reduce complications of ADRD. In this context, glutaminyl cyclase (QC) inhibitors have shown some early possible evidence of efficacy with a reassuring safety profile. To reliably test the glutaminyl cyclase (QC) and any other promising hypotheses will require cogent data from large-scale randomized trials of sufficient size and duration.
    Preview · Article · Oct 2015 · Expert Review of Neurotherapeutics
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    ABSTRACT: Objective: To describe the design and ongoing conduct of the Million Veteran Program (MVP), as an observational cohort study and mega-biobank in the Department of Veterans Affairs (VA) healthcare system. Study design and setting: Data are being collected from participants using questionnaires, the VA electronic health record, and a blood sample for genomic and other testing. Several ongoing projects are linked to MVP, both as peer-reviewed research studies and as activities to help develop an infrastructure for future, broad-based research uses. Results: Formal planning for MVP commenced in 2009; the protocol was approved in 2010, and enrollment began in 2011. As of 3 August 2015, and with a steady-state of ≈50 recruiting sites nationwide, N=397,104 Veterans have been enrolled. Among N=199,348 with currently available genotyping data, most participants (as expected) are male (92.0%) between the ages of 50 and 69 years (55.0%). Based on self-reported race, white (77.2%) and African-American (13.5%) populations are well represented. Conclusions: By helping to promote the future integration of genetic testing in health care delivery, including clinical decision-making, the Million Veteran Program is designed to contribute to the development of precision medicine.
    Full-text · Article · Oct 2015 · Journal of clinical epidemiology
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    ABSTRACT: Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC=679, ICC=225) from ten US-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Current aspirin use, versus nonuse, was inversely associated with HCC (HR=0.68, 95% CI=0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5 and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR=0.64, 95% CI=0.42-0.98) but not women (HR=1.34, 95% CI=0.89-2.01, pinteraction=0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggest the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.
    No preview · Article · Sep 2015 · Cancer Prevention Research
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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.
    Preview · Article · Sep 2015 · Journal of the American Heart Association
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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.
    Preview · Article · Sep 2015 · Journal of the American Heart Association
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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.
    No preview · Article · Sep 2015 · Journal of the American College of Cardiology
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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.
    Full-text · Article · Sep 2015 · Annals of Oncology
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    ABSTRACT: Chocolate consumption has been shown to protect against various cardiovascular end points; however, little is known about the association between chocolate consumption and incident atrial fibrillation (AF). Therefore, we prospectively examined the association between chocolate consumption and incident AF in a cohort of 18,819 US male physicians. Chocolate consumption was ascertained from 1999 to 2002 through a self-administered food frequency questionnaire. Incident AF was ascertained through yearly follow-up questionnaires. Cox regression was used to estimate relative risks of AF. The average age at baseline was 66 years (±9.1). During a mean follow-up of 9.0 years (±3.0), 2,092 cases of AF occurred. Using <1 per month of chocolate consumption as the reference group, multivariable adjusted hazard ratios (95% confidence interval) for AF were 1.04 (0.93 to 1.18), 1.10 (0.96 to 1.25), 1.14 (0.99 to 1.31), and 1.05 (0.89 to 1.25) for chocolate intake of 1 to 3 per month and 1, 2 to 4, and ≥5 per week (p for trend 0.25), respectively. In a secondary analysis, there was no evidence of effect modification by adiposity (p interaction = 0.71) or age (p interaction = 0.26). In conclusion, our data did not support an association between chocolate consumption and risk of AF in US male physicians.
    No preview · Article · Aug 2015 · The American Journal of Cardiology
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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.
    No preview · Article · Aug 2015 · The British journal of nutrition
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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.
    No preview · Article · Jul 2015 · Heart (British Cardiac Society)
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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.
    No preview · Article · Jun 2015 · Cancer Epidemiology Biomarkers & Prevention
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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.
    Full-text · Article · Jun 2015 · Journal of Diabetes Research

Publication Stats

34k Citations
5,499.12 Total Impact Points


  • 1995-2015
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1991-2015
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Preventive Medicine
      • • Division of Aging
      Boston, Massachusetts, United States
    • Harvard Medical School
      • • Department of Medicine
      • • Division of Nutrition
      Boston, Massachusetts, United States
  • 2012
    • University of Ioannina
      • Department of Hygiene and Epidemiology
      Yannina, Epirus, Greece
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 2009-2012
    • Boston University
      • Department of Medicine
      Boston, Massachusetts, United States
    • Harvard Vanguard Medical Associates
      Cambridge, Massachusetts, United States
  • 2011
    • Brown University
      • Department of Epidemiology
      Providence, Rhode Island, United States
  • 2010
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
  • 1997-2010
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2007
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 2006-2007
    • Center for Information Services
      Miami, Florida, United States
  • 2002
    • University of California, San Francisco
      San Francisco, California, United States
  • 1996-1998
    • Tufts University
      • Nutritional Immunology Research Laboratory
      Бостон, Georgia, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States