JoAnn E Manson

Harvard Medical School, Boston, Massachusetts, United States

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Publications (970)11033.21 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
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    ABSTRACT: Over the past decade, an emerging clinical research focus on cardiovascular (CV) disease (CVD) risk in women has highlighted sex-specific factors that are uniquely important in the prevention and early detection of coronary atherosclerosis in women. Concurrently, a 30% decrease in the number of female deaths from CVD has been observed. Despite this, CVD continues to be the leading cause of death in women, outnumbering deaths from all other causes combined. Clinical practice approaches that focus on the unique aspects of CV care for women are needed to provide necessary resources for the prevention, diagnosis, and treatment of CVD in women. In addition to increasing opportunities for women to participate in CV research, Women's Heart Clinics offer unique settings in which to deliver comprehensive CV care and education, ensuring appropriate diagnostic testing, while monitoring effectiveness of treatment. This article reviews the emerging need and role of focused CV care to address sex-specific aspects of diagnosis and treatment of CVD in women.
    Full-text · Article · Feb 2016
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    ABSTRACT: Purpose: To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12. Methods: In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial. Results: During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04). Conclusions: In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.
    No preview · Article · Jan 2016 · Ophthalmic epidemiology
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    ABSTRACT: Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial—the VITamin D and OmegA-3 TriaL (VITAL)—to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1 g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥ 50 and ≥ 55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review.
    No preview · Article · Jan 2016 · Contemporary clinical trials
  • Shari S. Bassuk · JoAnn E. Manson
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    ABSTRACT: The Women's Health Initiative (WHI), a landmark randomized trial of menopausal hormone therapy (HT) for prevention of chronic disease in postmenopausal women aged 50–79, established that such therapy neither prevents coronary heart disease (CHD) nor yields a favorable balance of benefits and risks in such women as a whole. However, a nuanced look at the data from this trial, considered alongside other evidence, suggests that timing of HT initiation affects the relation between such therapy and coronary risk, as well as its overall benefit–risk balance. Estrogen may have a beneficial effect on the heart if started in early menopause, when a woman's arteries are likely to be relatively healthy, but a harmful effect if started in late menopause, when those arteries are more likely to show signs of atherosclerotic disease. However, even if HT-associated relative risks are constant across age or time since menopause onset, the low absolute risk of CHD in younger or recently menopausal women translates into low attributable risks in this group. Thus, HT initiation for relief of moderate to severe vasomotor symptoms in early menopausal patients who have a favorable coronary profile remains a viable option.
    No preview · Article · Jan 2016
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    ABSTRACT: Evidence for a role of supplemental vitamin D and marine omega-3 fatty acids in preventing cancer and cardiovascular disease (CVD) remains inconclusive and insufficient to inform nutritional recommendations for primary prevention. The VITamin D and Omega-A 3 TriaL (VITAL) is an ongoing nationwide, randomized, double-blind, placebo-controlled clinical trial designed to fill this knowledge gap. The study population consists of 25,874 U.S. adults without cancer or CVD at baseline, who were selected only on age (men aged ≥ 50 and women aged ≥ 55), with an oversampling of African Americans (n = 5107). In a 2 × 2 factorial design, participants were randomized to one of four supplement groups: [1] active vitamin D3 (cholecalciferol; 2000 IU/d) and active marine omega-3 fatty acids (Omacor® fish oil, eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA], 1 g/d); [2] active vitamin D and omega-3 placebo; [3] vitamin D placebo and active marine omega-3 fatty acids; or [4] vitamin D placebo and omega-3 placebo. The mean length of the randomized treatment period will be 5 years. The randomization was successful, as evidenced by similar distributions of baseline demographic, health, and behavioral characteristics across treatment groups. The similar distribution of known potential confounders across treatment groups strongly suggests that unmeasured or unknown potential confounders are also equally distributed. VITAL is expected to provide important information on the benefit–risk balance of vitamin D and omega-3 fatty acid supplementation when taken for the primary prevention of cancer and CVD.
    No preview · Article · Jan 2016 · Contemporary clinical trials
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    ABSTRACT: Background: Self-reported physical activity measures continue to be validated against accelerometers; however, the absence of standardized, accelerometer moderate-to-vigorous physical activity (MVPA) definitions has made comparisons across studies difficult. Furthermore, recent accelerometer models assess accelerations in three axes, instead of only the vertical axis, but validation studies have yet to take incorporate triaxial data. Methods: Participants (n = 10 115) from the Women's Health Study wore a hip-worn accelerometer (ActiGraph GT3X+) for seven days during waking hours (2011-2014). Women then completed a physical activity questionnaire. We compared self-reported with accelerometer-assessed MVPA, using four established cutpoints for MVPA: three using only vertical axis data (760, 1041 and 1952 counts per minute (cpm)) and one using triaxial data (2690 cpm). Results: According to self-reported physical activity, 66.6% of women met the US federal physical activity guidelines, engaging in ≥150 minutes per week of MVPA. The percent of women who met guidelines varied widely depending on the accelerometer MVPA definition (760 cpm: 50.0%, 1041 cpm: 33.0%, 1952 cpm: 13.4%, and 2690 cpm: 19.3%). Conclusions: Triaxial count data do not substantially reduce the difference between self-reported and accelerometer-assessed MVPA.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Objective: To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and results: Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions: Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
    No preview · Article · Dec 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: Background Several studies have investigated the association of tobacco use with infertility and age at natural menopause, yet few have explored secondhand smoke (SHS) exposure with these outcomes. This study offers a comprehensive, quantified secondary data analysis of these issues using the Women's Health Initiative Observational Study (WHI OS). Purpose This study examines associations between lifetime tobacco exposure—active smoking and SHS—and infertility and natural menopause (before age 50). Methods Information on smoking, lifetime fertility status, and age at natural menopause was collected and available from 93 676 postmenopausal women aged 50–79 enrolled in the WHI OS from 1993 to 1998 at 40 centres in the USA. Multivariate-adjusted regression models were used to estimate ORs and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. Results Overall, 15.4% of the 88 732 women included in the analysis on infertility met criteria for the condition. 45% of the 79 690 women included in the analysis on natural menopause (before age 50) met criteria for the condition. Active-ever smokers had overall OR's of 1.14 (95% CI 1.03 to 1.26) for infertility, and 1.26 (95% CI 1.16 to 1.35) for earlier menopause than never-smoking women. Never-smoking women with the highest levels of lifetime SHS exposure had adjusted OR's of 1.18 (95% CI 1.02 to 1.35) for infertility, and 1.18 (95% CI 1.06 to 1.31) for earlier menopause. Active-ever smokers reached menopause 21.7 months earlier than the mean of 49.4 years for never-smokers not exposed to SHS, and women exposed to the highest level of SHS reached menopause 13.0 months earlier. Conclusions Active smoking and SHS exposure are associated with increased risk of infertility and natural menopause occurring before the age of 50 years.
    No preview · Article · Dec 2015 · Tobacco Control
  • Kathy Berra · James Rippe · JoAnn E. Manson

    No preview · Article · Dec 2015 · JAMA The Journal of the American Medical Association
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    ABSTRACT: Background: The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial. Objective: We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Women's Health Initiative Observational Study. Design: In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2-3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension. Results: During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all). Conclusion: In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women.
    No preview · Article · Dec 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p<0.001), and of several site-specific cancers (HR, 1.2-1.4, and up to over 2-fold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p<0.001). There was no overall difference in cancer incidence by diabetes therapy (p=0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 versus 1.45; p=0.007) and for breast cancer (HRs, 0.50 versus 1.29; p=0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · International Journal of Cancer
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    ABSTRACT: The prevalence of hypertension is increasing among younger women, and new strategies are needed to identify high-risk women who should be targets for early intervention. Several mechanisms underlying hypertension might also contribute to premenstrual syndrome (PMS), but whether women with PMS have a higher risk of subsequently developing hypertension has not been assessed. We prospectively evaluated this possibility in a substudy of the Nurses' Health Study II. Participants were 1,257 women with clinically significant PMS (1991–2005) and 2,463 age-matched comparison women with few menstrual symptoms. Participants were followed for incident hypertension until 2011. Over 6–20 years, hypertension was reported by 342 women with PMS and 541 women without. After adjustment for age, smoking, body mass index, and other risk factors for hypertension, women with PMS had a hazard ratio for hypertension of 1.4 (95% confidence interval: 1.2, 1.6) compared with women without PMS. Risk was highest for hypertension that occurred before 40 years of age (hazard ratio = 3.3; 95% confidence interval: 1.7, 6.5; P for interaction = 0.0002). The risk associated with PMS was not modified by use of oral contraceptives or antidepressants but was attenuated among women with high intakes of thiamine and riboflavin (P < 0.05). These results suggest that PMS might be associated with future development of hypertension and that this risk may be modifiable.
    No preview · Article · Nov 2015 · American Journal of Epidemiology
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    ABSTRACT: Background: The effectiveness of low-fat diets for long-term weight loss has been debated for decades, with many randomised controlled trials (RCTs) and recent reviews giving mixed results. We aimed to summarise the large body of evidence from RCTs to determine whether low-fat diets contribute to greater weight loss than participants' usual diet, low-carbohydrate diets, and other higher-fat dietary interventions. Methods: We did a systematic review and random effects meta-analysis of RCTs comparing the long-term effect (≥1 year) of low-fat and higher-fat dietary interventions on weight loss by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews to identify eligible trials published from database inception up until July 31, 2014. We excluded trials if one intervention group included a non-dietary weight loss component but the other did not, and trials of dietary supplements or meal replacement drink interventions. Data including the main outcome measure of mean difference in weight change between interventions, and whether interventions were intended to lead to weight loss, weight maintenance, or neither, were extracted from published reports. We estimated the pooled weighted mean difference (WMD) with a DerSimonian and Laird random effects method. Findings: 3517 citations were identified by the search and 53 studies met our inclusion criteria, including 68 128 participants (69 comparisons). In weight loss trials, low-carbohydrate interventions led to significantly greater weight loss than did low-fat interventions (18 comparisons; WMD 1·15 kg [95% CI 0·52 to 1·79]; I(2)=10%). Low-fat interventions did not lead to differences in weight change compared with other higher-fat weight loss interventions (19 comparisons; WMD 0·36 kg [-0·66 to 1·37; I(2)=82%), and led to a greater weight decrease only when compared with a usual diet (eight comparisons; -5·41 kg [-7·29 to -3·54]; I(2)=68%). Similarly, results of non-weight-loss trials and weight maintenance trials, for which no low-carbohydrate comparisons were made, showed that low-fat versus higher-fat interventions have a similar effect on weight loss, and that low-fat interventions led to greater weight loss only when compared with usual diet. In weight loss trials, higher-fat weight loss interventions led to significantly greater weight loss than low-fat interventions when groups differed by more than 5% of calories obtained from fat at follow-up (18 comparisons; WMD 1·04 kg [95% CI 0·06 to 2·03]; I(2)=78%), and when the difference in serum triglycerides between the two interventions at follow-up was at least 0·06 mmol/L (17 comparisons; 1·38 kg [0·50 to 2·25]; I(2)=62%). Interpretation: These findings suggest that the long-term effect of low-fat diet intervention on bodyweight depends on the intensity of the intervention in the comparison group. When compared with dietary interventions of similar intensity, evidence from RCTs does not support low-fat diets over other dietary interventions for long-term weight loss. Funding: National Institutes of Health and American Diabetes Association.
    No preview · Article · Nov 2015

  • No preview · Conference Paper · Nov 2015
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    ABSTRACT: Background: Evidence for the effect of weight loss on coronary heart disease (CHD) or mortality has been mixed. The effect estimates can be confounded due to undiagnosed diseases that may affect weight loss. Methods: We used data from the Nurses' Health Study to estimate the 26-year risk of CHD under several hypothetical weight loss strategies. We applied the parametric g-formula and implemented a novel sensitivity analysis for unmeasured confounding due to undiagnosed disease by imposing a lag time for the effect of weight loss on chronic disease. Several sensitivity analyses were conducted. Results: The estimated 26-year risk of CHD did not change under weight loss strategies using lag times from 0 to 18 years. For a 6-year lag time, the risk ratios of CHD for weight loss compared with no weight loss ranged from 1.00 (0.99, 1.02) to 1.02 (0.99, 1.05) for different degrees of weight loss with and without restricting the weight loss strategy to participants with no major chronic disease. Similarly, no protective effect of weight loss was estimated for mortality risk. In contrast, we estimated a protective effect of weight loss on risk of type 2 diabetes. Conclusion: We estimated that maintaining or losing weight after becoming overweight or obese does not reduce the risk of CHD or death in this cohort of middle-aged US women. Unmeasured confounding, measurement error, and model misspecification are possible explanations but they did not prevent us from estimating a beneficial effect of weight loss on diabetes. Copyright
    No preview · Article · Nov 2015 · Epidemiology
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    ABSTRACT: Background: Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n=606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. Methods: The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in same KEEPS participants four years after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β estradiol (50 µg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Results: Twenty SNPs within the innate immunity pathway most related with CIMT after 4 years were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, SNPs within the innate immunity pathway were found to alter the treatment effect on 4-year change in CIMT (i.e. significant interaction between treatment and genetic variation in the innate immunity pathway; p<0.001). No SNPs by treatment effects were observed with changes of CAC >5 Agatston Units after 4 years. Conclusion: Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT. Key words: atherosclerosis, candidate genes, estrogen, innate immunity, thrombosis.
    Preview · Article · Oct 2015 · Physiological Genomics
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    ABSTRACT: Objective: In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes. Research design and methods: The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, ages 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia). Results: Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions: interactions P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens. Conclusions: These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose based energy sources in the brain may explain this interaction.
    No preview · Article · Oct 2015 · Diabetes care

  • No preview · Article · Oct 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: Objectives This study examined the association of BMI repeatedly measured over 32 years and BMI during early and mid-adulthood with risk of sudden cardiac death (SCD) in the Nurses' Health Study. Background SCD is often the first manifestation of coronary heart disease among women. Data regarding body mass index (BMI) and risk of SCD are limited and conflicting. Methods We prospectively followed 72,484 women free of chronic disease from 1980 to 2012. We ascertained adult height, current weight, and weight at age 18 years at baseline, and updated weight biennially. The primary endpoint was SCD (n = 445). Results When updated biennially, higher BMI was associated with greater SCD risk after adjusting for confounders (p linear trend <0.001). Compared with a BMI of 21.0 to 22.9 kg/m2, the multivariate relative risk (RR) of SCD was 1.46 (95% confidence interval [CI]: 1.05 to 2.04) for BMI 25.0 to 29.9 kg/m2, 1.46 (95% CI: 1.00 to 2.13) for BMI 30.0 to 34.9 kg/m2, and 2.18 (95% CI: 1.44 to 3.28) for BMI >35.0 kg/m2. Among women with a BMI >35.0 kg/m2, SCD remained elevated even after adjustment for interim development of coronary heart disease and other mediators (RR: 1.72; 95% CI: 1.13 to 2.60). In contrast, the association between BMI and fatal coronary heart disease risk was completely attenuated after adjustment for mediators. The magnitude of the association between BMI and SCD was greater when BMI was assessed at baseline or at age 18 years, at which time SCD risk remained significantly elevated at BMI >30 kg/m2 after adjustment for mediators. Conclusions Higher BMI was associated with greater risk of SCD, particularly when assessed earlier in adulthood. Strategies to maintain a healthy weight throughout adulthood may minimize SCD incidence.
    No preview · Article · Oct 2015 · JACC Clinical Electrophysiology

Publication Stats

93k Citations
11,033.21 Total Impact Points

Institutions

  • 1990-2016
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2015
    • Indiana University-Purdue University Indianapolis
      • Division of Clinical Pharmacology
      Indianapolis, Indiana, United States
  • 2005-2015
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, California, United States
    • University of Pittsburgh
      • Division of General Internal Medicine
      Pittsburgh, PA, United States
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
    • Florida Atlantic University
      • Department of Biomedical Science
      Boca Raton, Florida, United States
  • 1991-2015
    • Brigham and Women's Hospital
      • • Division of Preventive Medicine
      • • Department of Medicine
      Boston, Massachusetts, United States
  • 1987-2015
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
  • 2013
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2011
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, CA, United States
  • 2000-2011
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York, New York, United States
    • University of Alaska Anchorage
      Anchorage, Alaska, United States
  • 2008
    • University of East Anglia
      • Norwich Medical School
      Norwich, England, United Kingdom
  • 2006-2008
    • Beth Israel Deaconess Medical Center
      • Division of Endocrinology, Diabetes and Metabolism
      Boston, Massachusetts, United States
    • University at Buffalo, The State University of New York
      • Department of Social and Preventive Medicine
      Buffalo, NY, United States
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • George Washington University
      • Department of Medicine
      Washington, D. C., DC, United States
  • 2007
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, CA, United States
  • 2004-2006
    • Columbia University
      New York, New York, United States
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
    • Wake Forest School of Medicine
      • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2004-2005
    • Simmons College
      • Program in Nutrition and Dietetics
      Boston, Massachusetts, United States
  • 2002-2004
    • Boston University
      Boston, Massachusetts, United States
    • Duke University
      Durham, North Carolina, United States
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 2003
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 1999
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1996
    • William Penn University
      Filadelfia, Pennsylvania, United States