JoAnn E Manson

University of Minnesota Duluth, Duluth, Minnesota, United States

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Publications (775)8085.9 Total impact

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    ABSTRACT: We sought to evaluate the relationship between delayed conception and type 2 diabetes risk, given that there are plausible underlying mechanisms linking the two, including inflammation and insulin resistance. Participants of the Nurses' Health Study II prospective cohort were included if they were free of chronic disease (cardiovascular disease, type 2 diabetes, cancer) at baseline. Biennial questionnaires updated information on infertility status (>12 months attempted pregnancy), lifestyle characteristics and several health-related outcomes. Self-reported cases of diabetes were confirmed using a follow-up questionnaire. Multivariable Cox proportional hazards models were used to compute the HRs and 95% CIs. Incident type 2 diabetes occurred in 5,993 of the 112,106 participants over 24 years of follow-up (1989-2013). A history of infertility was reported in 27,774 (24.8%) women and was associated with a 20% greater risk of developing diabetes, compared with those never reporting infertility (HR 1.20 [95% CI 1.14, 1.28]), after adjusting for age, lifestyle factors, marital status, oral contraceptive use, family history of diabetes and BMI. Compared with women without a history of infertility, the causes of infertility associated with a higher diabetes risk were ovulation disorders (HR 1.43 [95% CI 1.29, 1.58]) and tubal factor (HR 1.34 [95% CI 1.13, 1.58]). Cervical factor (HR 1.06 [95% CI 0.81, 1.40]) and endometriosis (HR 1.06 [95% CI 0.89, 1.27]) were not associated, while male factor infertility was associated with a modestly higher diabetes risk (HR 1.15 [95% CI 1.00, 1.33]). These novel findings suggest a history of infertility, particularly that related to ovulation disorders and tubal blockage, is significantly associated with a higher risk of type 2 diabetes.
    Diabetologia 01/2015; · 6.88 Impact Factor
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    ABSTRACT: Background Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression. Aims To test whether long-term B-vitamin/folate supplementation reduces depression risk. Method Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms. Results There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86-1.21, P = 0.81), despite significant homocysteine level reduction. Conclusions Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women. Royal College of Psychiatrists.
    The British journal of psychiatry: the journal of mental science 01/2015; · 6.62 Impact Factor
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    ABSTRACT: Although multivitamins are widely used, there are limited prospective studies investigating their association with both long- and short-term risk of cardiovascular disease (CVD). The objective was to investigate how multivitamin use is associated with the long- and short-term risk of CVD. A prospective cohort study was conducted of 37,193 women from the Women's Health Study aged ≥45 y and free of CVD and cancer at baseline who were followed for an average of 16.2 y. At baseline, women self-reported a wide range of lifestyle, clinical, and dietary factors. Women were categorized into 1) no current use and 2) current use of multivitamins. Duration and updated measures over the course of the follow-up to address short-term effects were also considered. Women were followed for major CVD events, including myocardial infarction (MI), stroke, and CVD death. During the follow-up, 1493 incident cases of CVD [defined as myocardial infarction (MI), stroke, and CVD death] occurred. In multivariable analyses, multivitamin use compared with no use was not associated with major CVD events (HR: 1.01; 95% CI: 0.89, 1.15), MI (HR: 1.04; 95% CI: 0.84, 1.27), stroke (HR: 0.99; 95% CI: 0.83, 1.18), or CVD death (HR: 1.10; 95% CI: 0.84, 1.45). A nonsignificant inverse association was observed between baseline multivitamin use and major CVD events among women aged ≥70 y (P-interaction = 0.04) and those consuming <3 servings/d of fruit and vegetables (P-interaction = 0.01). When updating information on multivitamin use during the course of follow-up, no associations were observed for major CVD events (HR: 0.91; 95% CI: 0.82, 1.02), MI (HR: 0.89; 95% CI: 0.74, 1.06), stroke (HR: 0.91; 95% CI: 0.78, 1.06), and CVD death (HR: 0.91; 95% CI: 0.71, 1.16). In this study of middle-aged and elderly women, neither baseline nor time-varying multivitamin use was associated with the long-term risk of major CVD events, MI, stroke, cardiac revascularizations, or CVD death. Additional studies are needed to clarify the role of multivitamins on CVD. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):144-52. · 6.50 Impact Factor
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    ABSTRACT: Context: Vasomotor symptoms (VMS) are common. Whether VMS are associated with fracture incidence or bone mineral density (BMD) levels is unknown. Objective: This study aimed to examine associations of baseline VMS with fracture incidence and BMD. Design: This was a prospective observational study with mean (SD) followup of 8.2 (1.7) years (1993-2005). Setting: Forty United States clinical centers. Participants: We examined data from Women's Health Initiative Clinical Trial participants (n = 23 573) age 50-79 years not using menopausal hormone therapy, and 4,867 participants of the BMD sub-study. Interventions: None. Main Outcome Measures: We measured baseline VMS, incident adjudicated fractures, and BMD (baseline, annual visits 1, 3, 6, and 9). Results: After adjustment for baseline age, body mass index, race/ethnicity, smoking, and education, the hazard ratio for hip fracture among women with baseline moderate/severe VMS (vs no VMS) was 1.78 (95% confidence interval [CI], 1.20-2.64; P = .01). There was no association between VMS and vertebral fracture. VMS severity was inversely associated with BMD during followup (P = .004 for femoral neck, P = .045 for lumbar spine). In repeated measures models, compared with women who reported no VMS, women with moderate/severe VMS had 0.015 g/cm(2) lower femoral neck BMD (95% CI, -0.025--0.005) and 0.016 g/cm(2) lower lumbar spine BMD (95% CI, -0.032--0.004). Conclusions: Women with moderate/severe VMS have lower BMD and increased hip fracture rates. Elucidation of the biological mechanisms underlying these associations may inform the design of preventive strategies for at-risk women prior to occurrence of fracture.
    Journal of Clinical Endocrinology &amp Metabolism 12/2014; · 6.31 Impact Factor
  • Elizabeth R Bertone-Johnson, JoAnn E Manson
    Menopause (New York, N.Y.) 12/2014; · 3.08 Impact Factor
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    ABSTRACT: Positive associations between dog ownership and physical activity in older adults have been previously reported. The objective of this study was to examine cross-sectional associations between dog ownership and physical activity measures in a well-characterized, diverse sample of postmenopausal women. Analyses included 36,984 dog owners (mean age: 61.5years), and 115,645 non-dog owners (mean age: 63.9years) enrolled in a clinical trial or the observational study of the Women's Health Initiative between 1993 and 1998. Logistic regression models were used to test for associations between dog ownership and physical activity, adjusted for potential confounders. Owning a dog was associated with a higher likelihood of walking ≥150min/wk (Odds Ratio, 1.14; 95% Confidence Interval, 1.10-1.17) and a lower likelihood of being sedentary ≥8h/day (Odds Ratio, 0.86; 95% Confidence Interval, 0.83-0.89) as compared to not owning a dog. However, dog owners were less likely to meet ≥7.5MET-h/wk of total physical activity as compared to non-dog owners (Odds Ratio, 1.03; 95% Confidence Interval, 1.00-1.07). Dog ownership is associated with increased physical activity in older women, particularly among women living alone. Health promotion efforts aimed at older adults should highlight the benefits of regular dog walking for both dog owners and non-dog owners. Copyright © 2014 Elsevier Inc. All rights reserved.
    Preventive Medicine 11/2014; 70C:33-38. · 2.93 Impact Factor
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    ABSTRACT: This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind, placebo-controlled, randomized trial of low-dose oral 17β-E2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical placebo, was conducted among 339 women (aged 40-62 y) experiencing two or more vasomotor symptoms (VMS) per day (mean [SD], 8.07 [5.29]) who were recruited at three clinical sites from November 2011 to October 2012. The primary trial outcome, as reported previously, was frequency of VMS at 8 weeks. Here, we report on secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and from measures of pain (Pain, Enjoyment in life, and General activity scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and perceived stress (Perceived Stress Scale). Treatment with both E2 and venlafaxine resulted in significantly greater improvement in quality of life, as measured by total MENQOL scores, compared with placebo (E2: mean difference at 8 wk, -0.4; 95% CI, -0.7 to -0.2; P < 0.001; venlafaxine: mean difference at 8 wk, -0.2; 95% CI, -0.5 to 0.0; P = 0.04). Quality-of-life domain analyses revealed that E2 had beneficial treatment effects on all domains of the MENQOL except for the psychosocial domain, whereas venlafaxine benefits were observed only in the psychosocial domain. Neither E2 nor venlafaxine improved pain, anxiety, or depressive symptoms, although baseline symptom levels were low. Modest benefits were observed for perceived stress with venlafaxine. Both low-dose E2 and venlafaxine are effective pharmacologic agents for improving menopause-related quality of life in healthy women with VMS.
    Menopause (New York, N.Y.) 11/2014; · 3.08 Impact Factor
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    ABSTRACT: -Vitamin D supplementation may be an inexpensive intervention to reduce heart failure (HF) incidence. However, there are insufficient data to support this hypothesis. This study evaluates whether vitamin D plus calcium (CaD) supplementation is associated with lower rates of HF in post-menopausal women and whether the effects differ between those at high versus low risk for HF.
    Circulation Heart Failure 11/2014; · 5.95 Impact Factor
  • Shari S. Bassuk, JoAnn E. Manson
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    ABSTRACT: To summarize the relative risks (RR) and attributable risks (AR) of major health outcomes associated with use of combined oral contraceptives (OCs) and menopausal hormone therapy (HT).Methods For OCs, measures of association are from meta-analyses of observational studies. For HT, these measures are from the Women’s Health Initiative (WHI), a large randomized trial of HT for chronic disease prevention in postmenopausal women aged 50-79.ResultsCurrent OC use increases risks of venous thromboembolism and ischemic stroke. However, women of reproductive age are at low baseline risk, so the AR are small. OC use also increases risk of breast and liver cancer and reduces risk of ovarian, endometrial, and colorectal cancer; the net effect is a modest reduction in total cancer. The WHI results show that HT does not prevent coronary events or overall chronic disease in postmenopausal women as a whole. Subgroup analyses suggest that timing of HT initiation influences the relation between such therapy and coronary risk, as well as its overall risk-benefit balance, with more favorable effects (on a relative scale) in younger or recently menopausal women than in older women or those further past the menopausal transition. However, even if the RR do not vary by these characteristics, the low absolute baseline risks of younger or recently menopausal women translate into low ARs in this group.ConclusionOC and HT can safely be used for contraception and treatment of vasomotor symptoms, respectively, by healthy women at low baseline risk for CVD and breast cancer.
    Annals of Epidemiology 11/2014; · 2.15 Impact Factor
  • Robert A Wild, JoAnn E Manson
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    ABSTRACT: Identifying appropriate candidates for menopausal hormone therapy (HT) is challenging given the complex profile of risks and benefits associated with treatment. Most professional societies agree that HT should not be used for chronic disease prevention. Recent findings from the Women's Health Initiative and other randomized trials suggest that a woman's age, proximity to menopause, underlying cardiovascular risk factor status, and various biological characteristics may modify health outcomes with HT. An emerging body of evidence suggests that it may be possible to assess individual risk and therefore better predict who is more likely to have favorable outcomes versus adverse effects when taking HT. Thus, once a woman is identified as a potential candidate for HT due to moderate-to-severe menopausal symptoms or other indications, risk stratification may be an important tool for minimizing patient risk. This individualized approach holds great promise for improving the safety of HT. We review here the evidence for this approach, focusing on vascular health because of limited data on other outcomes. The ultimate goal of this research is to develop a personalized risk/benefit prediction model to be used when a woman seeks therapy for symptom management. Patient centered outcomes including quality of life and sense of well-being should also be incorporated and will directly impact the benefit: risk ratio and compliance. Additional research on hormone dose, formulation, and route of delivery will be important for improving this model.
    Seminars in Reproductive Medicine 11/2014; 32(6):433-437. · 3.21 Impact Factor
  • JoAnn E Manson, Shari S Bassuk
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    ABSTRACT: Cardiovascular disease (CVD), including coronary heart disease and stroke, is the leading cause of death among U.S. women and men. Established cardiovascular risk factors such as smoking, diabetes, hypertension, and elevated total cholesterol, and risk prediction models based on such factors, perform well but do not perfectly predict future risk of CVD. Thus, there has been much recent interest among cardiovascular researchers in identifying novel biomarkers to aid in risk prediction. Such markers include alternative lipids, B-type natriuretic peptides, high-sensitivity troponin, coronary artery calcium, and genetic markers. This article reviews the role of traditional cardiovascular risk factors, risk prediction tools, and selected novel biomarkers and other exposures in predicting risk of developing CVD in women. The predictive role of novel cardiovascular biomarkers for women in primary prevention settings requires additional study, as does the diagnostic and prognostic utility of cardiac troponins for acute coronary syndromes in clinical settings. Sex differences in the clinical expression and physiology of metabolic syndrome may have implications for cardiovascular outcomes. Consideration of exposures that are unique to, or more prevalent in, women may also help to refine cardiovascular risk estimates in this group. Copyright © 2014 Elsevier Inc. All rights reserved.
    Metabolism: clinical and experimental 10/2014; · 3.61 Impact Factor
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    ABSTRACT: Background The impact of a healthy lifestyle on risk of heart failure (HF) is not well known. Objectives The objectives of this study were to evaluate the effect of a combination of lifestyle factors on incident HF and to further investigate whether weighting each lifestyle factor has additional impact. Methods Participants were 84,537 post-menopausal women from the WHI (Women’s Health Initiative) observational study, free of self-reported HF at baseline. A healthy lifestyle score (HL score) was created wherein women received 1 point for each healthy criterion met: high-scoring Alternative Healthy Eating Index, physically active, healthy body mass index, and currently not smoking. A weighted score (wHL score) was also created in which each lifestyle factor was weighted according to its independent magnitude of effect on HF. The incidence of hospitalized HF was determined by trained adjudicators using standardized methodology. Results There were 1,826 HF cases over a mean follow-up of 11 years. HL score was strongly associated with risk of HF (multivariable-adjusted hazard ratio [HR] [95% confidence interval (CI)] 0.49 [95% CI: 0.38 to 0.62], 0.36 [95% CI: 0.28 to 0.46], 0.24 [95% CI: 0.19 to 0.31], and 0.23 [95% CI: 0.17 to 0.30] for HL score of 1, 2, 3, and 4 vs. 0, respectively). The HL score and wHL score were similarly associated with HF risk (HR: 0.46 [95% CI: 0.41 to 0.52] for HL score; HR: 0.48 [95% CI: 0.42 to 0.55] for wHL score, comparing the highest tertile to the lowest). The HL score was also strongly associated with HF risk among women without antecedent coronary heart disease, diabetes, or hypertension. Conclusions An increasingly healthy lifestyle was associated with decreasing HF risk among post-menopausal women, even in the absence of antecedent coronary heart disease, hypertension, and diabetes. Weighting the lifestyle factors had minimal impact.
    Journal of the American College of Cardiology 10/2014; 64(17):1777–1785. · 15.34 Impact Factor
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    ABSTRACT: Background Although N-terminal pro–B-type natriuretic peptide (NT-proBNP) has a strong relationship with incident cardiovascular disease (CVD), few studies have examined whether NT-proBNP adds to risk prediction algorithms, particularly in women. Objectives This study sought to evaluate the relationship between NT-proBNP and incident CVD in women. Methods Using a prospective case-cohort within the WHI (Women’s Health Initiative) observational study, we selected 1,821 incident cases of CVD (746 myocardial infarctions, 754 ischemic strokes, 160 hemorrhagic strokes, and 161 other cardiovascular [CV] deaths) and a randomly selected reference cohort of 1,992 women without CVD at baseline. Results Median levels of NT-proBNP were higher at study entry among incident cases (120.3 ng/l [interquartile range (IQR): 68.1 to 219.5 ng/l]) than among control subjects (100.4 ng/l [IQR: 59.7 to 172.6 ng/l]; p < 0.0001). Women in the highest quartile of NT-proBNP (≥140.8 ng/l) were at 53% increased risk of CVD versus those in the lowest quartile after adjusting for traditional risk factors (1.53 [95% confidence interval (CI): 1.21 to 1.94]; p for trend <0.0001). Similar associations were observed after adjustment for Reynolds Risk Score covariables (1.53 [95% CI: 1.20 to 1.95]; p for trend <0.0001); the association remained in separate analyses of CV death (2.66 [95% CI: 1.48 to 4.81]; p for trend <0.0001), myocardial infarction (1.39 [95% CI: 1.02 to 1.88]; p for trend = 0.008), and stroke (1.60 [95% CI: 1.22 to 2.11]; p for trend <0.0001). When added to traditional risk covariables, NT-proBNP improved the c-statistic (0.765 to 0.774; p = 0.0003), categorical net reclassification (0.08; p < 0.0001), and integrated discrimination (0.0105; p < 0.0001). Similar results were observed when NT-proBNP was added to the Reynolds Risk Score. Conclusions In this multiethnic cohort of women with numerous CV events, NT-proBNP modestly improved measures of CVD risk prediction.
    Journal of the American College of Cardiology 10/2014; 64(17):1789–1797. · 15.34 Impact Factor
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    ABSTRACT: Clinical practice focuses on the primary prevention of cardiovascular (CV) disease (CVD) through the modification and pharmacological treatment of elevated risk factors. Prediction models based on established risk factors are available for use in the primary prevention setting. However, the prevention of risk factor development through healthy lifestyle behaviors, or primordial prevention, is of paramount importance to achieve optimal population-wide CV health and minimize long-term CVD risk.
    Journal of the American Heart Association. 10/2014; 3(6).
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    ABSTRACT: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes.
    Sleep 10/2014; · 5.06 Impact Factor
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    ABSTRACT: We evaluated the within-person variability of urinary BPA levels over two samples collected three years apart in 90 Women's Health Initiative participants. The intraclass correlation coefficient was 0.09 (95% CI 0.01–0.44), indicating high within-participant variability relative to the between-person variation. Concordance of BPA quartile over time was low (31.7%) and was unrelated to demographic, behavioral, or dietary factors. A single, or even several, measurements of BPA may not adequately classify long-term exposure in human studies.
    Environmental Research 10/2014; 135:285–288. · 3.95 Impact Factor
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    Menopause (New York, N.Y.) 10/2014; · 3.08 Impact Factor
  • Shilpa N Bhupathiraju, JoAnn E Manson
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    ABSTRACT: Objective: This review provides a comprehensive overview of the most recent findings from the Women's Health Initiative (WHI) hormone therapy (HT) trials and highlights the role of age and other clinical risk factors in risk stratification.Methods: We review the findings on cardiovascular disease, cancer outcomes, all-cause mortality, and other major endpoints in the two WHI HT trials (conjugated equine estrogens [CEE: 0.625 mg/d] with or without medroxyprogesterone acetate [MPA: 2.5 mg/d]).Results: The hazard ratio (HR) for coronary heart disease (CHD) was 1.18 (95% confidence interval (CI): 0.95-1.45) in the CEE+MPA trial and 0.94 (95% CI: 0.78-1.14) in the CEE-alone trial. In both HT trials, there was an increased risk of stroke and deep vein thrombosis, and a lower risk of hip fractures and diabetes. The HT regimens had divergent effects on breast cancer. CEE+MPA increased breast cancer risk (cumulative HR=1.28, 95% CI: 1.11-1.48) while CEE-alone had a protective effect (cumulative HR=0.79, 95% CI: 0.65-0.97). The absolute risks of HT were low in younger women (ages 50-59) and those who were within 10 years of menopause onset. Further, for CHD, the risks were elevated for women with metabolic syndrome or high LDL-C concentrations, but not in women without these risk factors. Factor V Leiden genotype was associated with elevated risk of venous thromboembolism on HT.Conclusion: HT has a complex pattern of benefits and risks. Women in early menopause have low absolute risks of chronic disease outcomes on HT. Use of HT for management of menopausal symptoms remains appropriate, and risk stratification will help to identify women in whom benefits would be expected to outweigh risks.
    Endocrine Practice 10/2014; 1(-1):1-24. · 2.59 Impact Factor
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    ABSTRACT: Background: The Women's Health Initiative (WHI) low fat (20% kcal) diet modification (DM) trial (1993-2005) demonstrated a non-significant reduction in breast cancer, a nominally significant reduction in ovarian cancer and no effect on other cancers (mean 8.3 years intervention). Consent to non-intervention follow-up was 83% (n=37,858). This analysis was designed to assess post-intervention cancer risk in women randomized to the low-fat diet (40%) versus usual diet comparison (60%). Methods: Randomized, controlled low fat diet intervention for prevention of breast and colorectal cancers conducted in 48,835 postmenopausal U.S. women, aged 50-79 years at 40 U.S. sites. Outcomes included total invasive cancer, breast and colorectal cancer, cancer-specific and overall mortality. Results: There were no intervention effects on invasive breast 1.08 (0.94, 1.24) or colorectal cancer, other cancers, cancer-specific or overall mortality during the post-intervention period or the combined intervention and follow-up periods. For invasive breast cancer, the HRs were 0.92 (0.84, 1.01) during intervention, during the post-intervention period, and 0.97 (0.89, 1.05) during cumulative follow up. A reduced risk for estrogen receptor positive/progesterone receptor negative tumors was demonstrated during follow-up. Women with higher baseline fat intake (quartile), point estimates of breast cancer risk were HR-0.76; 0.62, 0.92 during intervention versus HR-1.11; 0.84, 1.4 during post-intervention follow-up (p-diff=.03). Conclusions: Dietary fat intake rose post-intervention in intervention women; no long-term reduction in cancer risk or mortality was shown in the WHI DM trial. Impact: Dietary advisement to reduce fat for cancer prevention after menopause generally was not supported by the WHI DM trial.
    Cancer Epidemiology Biomarkers & Prevention 09/2014; 23(12). · 4.32 Impact Factor
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    ABSTRACT: Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9–6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06–1·18 in all trials; 1·11, 95% CI 1·03–1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04–1·22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. Funding The funding sources are cited at the end of the paper.
    The Lancet. 09/2014;

Publication Stats

53k Citations
8,085.90 Total Impact Points


  • 2012–2014
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • Brown University
      • Department of Epidemiology
      Providence, RI, United States
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
    • Medical College of Wisconsin
      • Department of Psychiatry and Behavioral Medicine
      Milwaukee, WI, United States
    • Columbia University
      New York City, New York, United States
    • University of Massachusetts Medical School
      • Division of Preventive and Behavioral Medicine
      Worcester, MA, United States
  • 1992–2014
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Preventive Medicine
      Boston, Massachusetts, United States
  • 1990–2014
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2013
    • University of Alabama at Birmingham
      • Department of Epidemiology
      Birmingham, AL, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2011–2013
    • Stanford University
      • • Department of Medicine
      • • Department of Dermatology
      Palo Alto, CA, United States
    • University of California, San Francisco
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      San Francisco, CA, United States
    • Washington Hospital Center
      Washington, Washington, D.C., United States
    • Pennsylvania State University
      • Department of Nutritional Sciences
      University Park, MD, United States
    • Rutgers, The State University of New Jersey
      • Department of Nutritional Sciences
      New Brunswick, NJ, United States
  • 2007–2013
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • Isfahan University of Medical Sciences
      • Epidemiology and Biostatistics Department
      Eşfahān, Ostan-e Esfahan, Iran
  • 2005–2013
    • University of Pittsburgh
      • • Department of Epidemiology
      • • Division of General Internal Medicine
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
  • 2011–2012
    • Alpert Medical School - Brown University
      Providence, Rhode Island, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2008–2012
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
    • Northwestern University
      • Feinberg School of Medicine
      Evanston, IL, United States
    • University of East Anglia
      • Norwich Medical School
      Norwich, England, United Kingdom
    • University of North Carolina at Chapel Hill
      • Department of Epidemiology
      Chapel Hill, NC, United States
    • The University of Tennessee Health Science Center
      • Department of Preventive Medicine
      Memphis, TN, United States
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
  • 2007–2012
    • CSU Mentor
      Long Beach, California, United States
  • 2005–2012
    • University of Massachusetts Amherst
      • • Division of Biostatistics and Epidemiology
      • • Department of Public Health
      Amherst Center, MA, United States
    • University of California, Los Angeles
      • • Department of Medicine
      • • Department of Epidemiology
      Los Angeles, CA, United States
  • 2003–2012
    • Fred Hutchinson Cancer Research Center
      • Division of Public Health Sciences
      Seattle, WA, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 1997–2012
    • Harvard University
      • • Department of Nutrition
      • • Department of Epidemiology
      Cambridge, Massachusetts, United States
  • 2009–2011
    • Drexel University
      • Department of Epidemiology and Biostatistics
      Philadelphia, PA, United States
  • 2004–2011
    • University of California, San Diego
      • Department of Family and Preventive Medicine
      San Diego, California, United States
  • 2002–2011
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
    • Partners HealthCare
      Boston, Massachusetts, United States
    • University of Zurich
      • Internal Medicine Unit
      Zürich, ZH, Switzerland
  • 2010
    • Kaiser Permanente
      Oakland, California, United States
    • University of Virginia
      • Division of Endocrinology and Metabolism
      Charlottesville, VA, United States
    • Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2009–2010
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2007–2010
    • George Washington University
      • Department of Medicine
      Washington, Washington, D.C., United States
  • 2006–2010
    • Tufts 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
    • Ben-Gurion University of the Negev
      Be'er Sheva`, Southern District, Israel
  • 2008–2009
    • John Wayne Cancer Institute
      Santa Monica, California, United States
  • 2004–2009
    • Massachusetts General Hospital
      • • Reproductive Endocrine Unit
      • • Department of Medicine
      Boston, MA, United States
    • Simmons College
      Boston, Massachusetts, United States
  • 2003–2009
    • Massachusetts Department of Public Health
      Boston, Massachusetts, United States
  • 2005–2008
    • Beth Israel Deaconess Medical Center
      • • Division of Endocrinology, Diabetes and Metabolism
      • • Department of Medicine
      Boston, Massachusetts, United States
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
  • 2005–2006
    • MedStar Health Research Institute
      Maryland, United States