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Articles by J. E Manson
Total Records ( 10 ) for J. E Manson
  S. L Gray , A. Z LaCroix , J Larson , J Robbins , J. A Cauley , J. E Manson and Z. Chen
 

Background  Proton pump inhibitor (PPI) medications have been inconsistently shown to be associated with osteoporotic fractures. We examined the association of PPI use with bone outcomes (fracture, bone mineral density [BMD]).

Methods  This prospective analysis included 161 806 postmenopausal women 50 to 79 years old, without history of hip fracture, enrolled in the Women's Health Initiative (WHI) Observational Study and Clinical Trials with a mean (SD) follow-up of 7.8 (1.6) years. Analyses were conducted for 130 487 women with complete information. Medication information was taken directly from drug containers during in-person interviews (baseline, year 3). The main outcome measures were self-reported fractures (hip [adjudicated], clinical spine, forearm or wrist, and total fractures) and for a subsample (3 densitometry sites), 3-year change in BMD.

Results  During 1 005 126 person-years of follow-up, 1500 hip fractures, 4881 forearm or wrist fractures, 2315 clinical spine fractures, and 21 247 total fractures occurred. The multivariate-adjusted hazard ratios for current PPI use were 1.00 (95% confidence interval [CI], 0.71-1.40) for hip fracture, 1.47 (95% CI, 1.18-1.82) for clinical spine fracture, 1.26 (95% CI, 1.05-1.51) for forearm or wrist fracture, and 1.25 (95% CI, 1.15-1.36) for total fractures. The BMD measurements did not vary between PPI users and nonusers at baseline. Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip (P = .05) but not at other sites.

Conclusion  Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures.

  A. A Arslan , K. J Helzlsouer , C Kooperberg , X. O Shu , E Steplowski , H. B Bueno de Mesquita , C. S Fuchs , M. D Gross , E. J Jacobs , A. Z LaCroix , G. M Petersen , R. Z Stolzenberg Solomon , W Zheng , D Albanes , L Amundadottir , W. R Bamlet , A Barricarte , S. A Bingham , H Boeing , M. C Boutron Ruault , J. E Buring , S. J Chanock , S Clipp , J. M Gaziano , E. L Giovannucci , S. E Hankinson , P Hartge , R. N Hoover , D. J Hunter , A Hutchinson , K. B Jacobs , P Kraft , S. M Lynch , J Manjer , J. E Manson , A McTiernan , R. R McWilliams , J. B Mendelsohn , D. S Michaud , D Palli , T. E Rohan , N Slimani , G Thomas , A Tjonneland , G. S Tobias , D Trichopoulos , J Virtamo , B. M Wolpin , K Yu , A Zeleniuch Jacquotte and A. V. Patel
 

Background  Obesity has been proposed as a risk factor for pancreatic cancer.

Methods  Pooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, <18.5; normal weight, 18.5-24.9; overweight, 25.0-29.9; obese, 30.0-34.9; and severely obese, ≥35.0). Models were adjusted for potential confounders.

Results  In all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI quartile, 1.33; 95% CI, 1.12-1.58; Ptrend < .001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% CI, 1.04-1.69; Ptrend < .03), and in women it was 1.34 (95% CI, 1.05-1.70; Ptrend = .01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% CI, 1.31-2.69; Ptrend = .003) but less so in men.

Conclusions  These findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women.

  R Clarke , J Halsey , S Lewington , E Lonn , J Armitage , J. E Manson , K. H Bonaa , J. D Spence , O Nygard , R Jamison , J. M Gaziano , P Guarino , D Bennett , F Mir , R Peto , R Collins and for the B Vitamin Treatment Trialists' Collaboration
 

Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.

  A Pan , M Lucas , Q Sun , R. M van Dam , O. H Franco , J. E Manson , W. C Willett , A Ascherio and F. B. Hu
 

Background  Although it has been hypothesized that the diabetes-depression relation is bidirectional, few studies have addressed this hypothesis in a prospective setting.

Methods  A total of 65 381 women aged 50 to 75 years in 1996 were observed until 2006. Clinical depression was defined as having diagnosed depression or using antidepressants, and depressed mood was defined as having clinical depression or severe depressive symptoms, ie, a 5-item Mental Health Index (MHI-5) score of 52 or less. Self-reported type 2 diabetes mellitus was confirmed by means of a supplementary questionnaire validated by medical record review.

Results  During 10 years of follow-up (531 097 person-years), 2844 incident cases of type 2 diabetes mellitus were documented. Compared with referents (MHI-5 score of 86-100) who had the best depressive symptom scores, participants with increased severity of symptoms (MHI-5 scores of 76-85 or 53-75, or depressed mood) showed a monotonic elevated risk of developing type 2 diabetes (P for trend = .002 in the multivariable-adjusted model). The relative risk for individuals with depressed mood was 1.17 (95% confidence interval [CI], 1.05-1.30) after adjustment for various covariates, and participants using antidepressants were at a particularly higher relative risk (1.25; 95% CI, 1.10-1.41). In a parallel analysis, 7415 cases of incident clinical depression were documented (474 722 person-years). Compared with nondiabetic subjects, those with diabetes had a relative risk (95% CI) of developing clinical depression after controlling for all covariates of 1.29 (1.18-1.40), and it was 1.25 (1.09-1.42), 1.24 (1.09-1.41), and 1.53 (1.26-1.85) in diabetic subjects without medications, with oral hypoglycemic agents, and with insulin therapy, respectively. These associations remained significant after adjustment for diabetes-related comorbidities.

Conclusion  Our results provide compelling evidence that the diabetes-depression association is bidirectional.

  W. G Christen , R. J Glynn , H. D Sesso , T Kurth , J MacFadyen , V Bubes , J. E Buring , J. E Manson and J. M. Gaziano
 

Objective  To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men.

Methods  In a randomized, double-masked, placebo-controlled trial, 11 545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily.

Main Outcome Measure  Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review.

Application to Clinical Practice  Long-term use of vitamin E and C supplements has no appreciable effect on cataract.

Results  After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E–treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).

Conclusion  Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract.

Trial Registration  clinicaltrials.gov Identifier: NCT00270647

  J. H Page , J Ma , S. E Chiuve , M. J Stampfer , J Selhub , J. E Manson and E. B. Rimm
 

Background— We prospectively evaluated the relationships between fasting plasma levels of vitamin B6, as pyridoxal phosphate, and subsequent myocardial infarction risk in women.

Methods and Results— Among 32 826 women who provided blood samples between 1989 and 1990 (27% of the original 1976 cohort), 239 were diagnosed with incident myocardial infarction (fatal and nonfatal) after blood collection but before July 1998. Of these women, 144 had provided a sample after fasting >10 hours. Cases were matched 1:2 by age, cigarette smoking status, and month of and fasting status at the time of blood collection with controls from the same cohort. Conditional logistic regression was used to adjust for potential confounders, including traditional coronary risk factors, anthropometric factors, dietary intake, and selected biomarkers. Median age at blood collection was 63 years. Plasma levels of pyridoxal phosphate were inversely associated with risk of myocardial infarction; the multivariable-adjusted rate ratio for the highest compared with the lowest quartiles (>70 versus <27.9 pmol/mL) was 0.22 (95% confidence interval, 0.09 to 0.55; P for trend=0.05). The association varied by age: among women who were <60 years of age at blood sampling, the rate ratio comparing the highest and lowest quartiles was 0.05 (95% confidence interval, 0.004 to 0.61), whereas among older women, the corresponding rate ratio was 0.36 (95% confidence interval, 0.13 to 1.02).

Conclusions— Fasting plasma concentration of pyridoxal phosphate was inversely associated with myocardial infarction risk, an effect that was in part independent of dietary B6 intake. In addition to dietary vitamin B6 intake, there are other determinants of plasma vitamin B6 status, and these factors warrant further research.

  H. A Tindle , Y. F Chang , L. H Kuller , J. E Manson , J. G Robinson , M. C Rosal , G. J Siegle and K. A. Matthews
 

Background— Trait optimism (positive future expectations) and cynical, hostile attitudes toward others have not been studied together in relation to incident coronary heart disease (CHD) and mortality in postmenopausal women.

Methods and Results— Participants were 97 253 women (89 259 white, 7994 black) from the Women’s Health Initiative who were free of cancer and cardiovascular disease at study entry. Optimism was assessed by the Life Orientation Test–Revised and cynical hostility by the cynicism subscale of the Cook Medley Questionnaire. Cox proportional hazard models produced adjusted hazard ratios (AHRs) for incident CHD (myocardial infarction, angina, percutaneous coronary angioplasty, or coronary artery bypass surgery) and total mortality (CHD, cardiovascular disease, or cancer related) over 8 years. Optimists (top versus bottom quartile ["pessimists"]) had lower age-adjusted rates (per 10 000) of CHD (43 versus 60) and total mortality (46 versus 63). The most cynical, hostile women (top versus bottom quartile) had higher rates of CHD (56 versus 44) and total mortality (63 versus 46). Optimists (versus pessimists) had a lower hazard of CHD (AHR 0.91, 95% CI 0.83 to 0.99), CHD-related mortality (AHR 0.70, 95% CI 0.55 to 0.90), cancer-related mortality (blacks only; AHR 0.56, 95% CI 0.35 to 0.88), and total mortality (AHR 0.86, 95% CI 0.79 to 0.93). Most (versus least) cynical, hostile women had a higher hazard of cancer-related mortality (AHR 1.23, 95% CI 1.09 to 1.40) and total mortality (AHR 1.16, 95% CI 1.07 to 1.27; this effect was pronounced in blacks). Effects of optimism and cynical hostility were independent.

Conclusions— Optimism and cynical hostility are independently associated with important health outcomes in black and white women. Future research should examine whether interventions designed to change attitudes would lead to altered risk.

  C. M Albert , C. A MacRae , D. I Chasman , M VanDenburgh , J. E Buring , J. E Manson , N. R Cook and C. Newton Cheh
  Background—

Rare variants in cardiac ion channel genes are associated with sudden cardiac death in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to sudden cardiac death risk at the population level.

Methods and Results—

We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 noncoding SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched control subjects of European ancestry enrolled in 6 prospective cohort studies. After accounting for multiple testing, 2 SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (false discovery rate=0.01 and 0.03, respectively). Each increasing copy of the major T-allele of rs2283222 or the major C-allele of rs1172052 was associated with an odds ratio of 1.36 (95% confidence interval, 1.16 to 1.60; P=0.0002) and 1.30 (95% confidence interval, 1.12 to 1.51; P=0.0005), respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite sudden cardiac death did not significantly alter these relationships.

Conclusion—

In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in KCNQ1 and SCN5A were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.

  J Hsia , R. J Rodabough , J. E Manson , S Liu , M. S Freiberg , W Graettinger , M. C Rosal , B Cochrane , D Lloyd Jones , J. G Robinson , B. V Howard and for the Women's Health Initiative Research Group
 

Background— The 2007 update to the American Heart Association (AHA) guidelines for cardiovascular disease prevention in women recommend a simplified approach to risk stratification. We assigned Women’s Health Initiative participants to risk categories as described in the guideline and evaluated clinical event rates within and between strata.

Methods and Results— The Women’s Health Initiative enrolled 161 808 women ages 50 to 79 years and followed them prospectively for 7.8 years (mean). Applying the 2007 AHA guideline categories, 11% of women were high risk, 72% at-risk, and 4% at optimal risk; 13% of women did not fall into any category, that is, lacked risk factors but did not adhere to a healthy lifestyle (moderate intensity exercise for 30 minute most days and <7% of calories from saturated fat). Among high risk, at-risk, and optimal risk women, rates of myocardial infarction/coronary death were 12.5%, 3.1%, and 1.1% per 10 years (P for trend <0.0001); the event rate was 1.3% among women who could not be categorized. We observed a graded relationship between risk category and cardiovascular event rates for white, black, Hispanic, and Asian women, although event rates differed among ethnic groups (P for interaction=0.002). The AHA guideline predicted coronary events with accuracy similar to current Framingham risk categories (area under receiver operating characteristic curve for Framingham risk, 0.665; for AHA risk, 0.664; P=0.94) but less well than proposed Framingham 10-year risk categories of <5%, 5% to 20%, and >20% (area under receiver operating characteristic curve for Framingham risk, 0.724; for AHA risk, 0.664; P<0.0001).

Conclusions— Risk stratification as proposed in the 2007 AHA guideline is simple, accessible to patients and providers, and identifies cardiovascular risk with accuracy similar to that of the current Framingham algorithm.

Clinical Trial Registration— clinicaltrials.gov. Identifier: NCT00000611.

 
 
 
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