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1.
Clin Chem ; 65(12): 1508-1521, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31699704

RESUMO

BACKGROUND: Observational studies suggest vitamin D and marine ω-3 fatty acid (n-3 FA) supplements are associated with lower systemic inflammation. However, past trials have been inconsistent. METHODS: The randomized, double-blind, placebo-controlled VITamin D and OmegA-3 TriaL (VITAL) tested vitamin D (2000 IU/day) and/or n-3 FA (1 g/day) supplementation in a 2 × 2 factorial design among women ≥55 and men ≥50 years of age. We assessed changes in interleukin (IL)-6, tumor necrosis factor receptor 2 (TNFR2), and high-sensitivity C-reactive protein (hsCRP) concentrations from baseline to 1 year among participants randomized to vitamin D + n-3 FA (392), vitamin D (392), n-3 FA (392), or placebo only (385). Geometric means and percent changes were compared, adjusting for baseline factors. RESULTS: Baseline characteristics were well balanced. In the active arms, 25-OH vitamin D rose 39% and n-3 FA rose 55% vs minimal change in placebo arms. Neither supplement reduced biomarkers at 1 year. Vitamin D resulted in 8.2% higher IL-6 (95% CI, 1.5%-15.3%; adjusted P = 0.02), but TNFR2 and hsCRP did not. Among 784 receiving vitamin D, hsCRP increased 35.7% (7.8%-70.9%) in those with low (<20 ng/mL) but not with higher baseline serum 25(OH) vitamin D [0.45% (-8.9% to 10.8%); P interaction = 0.02]. Among 777 randomized to n-3 FA, hsCRP declined [-10.5% (-20.4% to 0.8%)] in those with baseline low (<1.5 servings/week), but not with higher fish intake [6.4% (95% CI, -7.11% to 21.8%); P interaction = 0.06]. CONCLUSIONS: In this large sample from a population-based randomized controlled trial, neither vitamin D nor n-3 FA supplementation over 1 year decreased these biomarkers of inflammation. CLINICALTRIALSGOV IDENTIFIER: NCT01169259; NCT01351805.

2.
BMJ ; 367: l6204, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776125

RESUMO

OBJECTIVE: To examine the association of consumption of dairy foods with risk of total and cause specific mortality in women and men. DESIGN: Three prospective cohort studies with repeated measures of diet and lifestyle factors. SETTING: Nurses' Health Study, Nurses' Health Study II, and the Health Professionals Follow-up Study, in the United States. PARTICIPANTS: 168 153 women and 49 602 men without cardiovascular disease or cancer at baseline. MAIN OUTCOME MEASURE: Death confirmed by state vital records, the national death index, or reported by families and the postal system. During up to 32 years of follow-up, 51 438 deaths were documented, including 12 143 cardiovascular deaths and 15 120 cancer deaths. Multivariable analysis further adjusted for family history of cardiovascular disease and cancer, physical activity, overall dietary pattern (alternate healthy eating index 2010), total energy intake, smoking status, alcohol consumption, menopausal status (women only), and postmenopausal hormone use (women only). RESULTS: Compared to the lowest category of total dairy consumption (average 0.8 servings/day), the multivariate pooled hazard ratio for total mortality was 0.98 (95% confidence interval 0.96 to 1.01) for the second category of dairy consumption (average 1.5 servings/day), 1.00 (0.97 to 1.03) for the third (average 2.0 servings/day), 1.02 (0.99 to 1.05) for the fourth (average 2.8 servings/day), and 1.07 (1.04 to 1.10) for highest category (average 4.2 servings/day; P for trend <0.001). For the highest compared to the lowest category of total dairy consumption, the hazard ratio was 1.02 (0.95 to 1.08) for cardiovascular mortality and 1.05 (0.99 to 1.11) for cancer mortality. For subtypes of dairy products, whole milk intake was significantly associated with higher risks of total mortality (hazard ratio per 0.5 additional serving/day 1.11, 1.09 to 1.14), cardiovascular mortality (1.09, 1.03 to 1.15), and cancer mortality (1.11, 1.06 to 1.17). In food substitution analyses, consumption of nuts, legumes, or whole grains instead of dairy foods was associated with a lower mortality, whereas consumption of red and processed meat instead of dairy foods was associated with higher mortality. CONCLUSION: These data from large cohorts do not support an inverse association between high amount of total dairy consumption and risk of mortality. The health effects of dairy could depend on the comparison foods used to replace dairy. Slightly higher cancer mortality was non-significantly associated with dairy consumption, but warrants further investigation.

3.
JAMA Oncol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750855

RESUMO

Importance: Marine ω-3 fatty acid has been suggested to protect against colorectal cancer. Objective: To assess the effect of daily marine ω-3 fatty acid supplementation on the risk of colorectal cancer precursors, including conventional adenomas and serrated polyps. Design, Setting, and Participants: This study was a prespecified ancillary study of the placebo-controlled randomized clinical trial VITAL (Vitamin D and Omega-3 Trial). An intention-to-treat analysis was used to examine the effect of daily marine ω-3 supplements among 25 871 adults in the US general population (including 5106 African American persons) free of cancer and cardiovascular disease at enrollment. Randomization was from November 2011 to March 2014, and intervention ended as planned on December 31, 2017. Interventions: Marine ω-3 fatty acid, 1 g daily (which included eicosapentaenoic acid, 460 mg, and docosahexaenoic acid, 380 mg) and vitamin D3 (2000 IU daily) supplements. Main Outcomes and Measures: Risk of conventional adenomas (including tubular adenoma, tubulovillous adenoma, villous adenoma, and adenoma with high-grade dysplasia) or serrated polyps (including hyperplastic polyp, traditional serrated adenoma, and sessile serrated polyp). In a subset of participants who reported receiving a diagnosis of polyp on follow-up questionnaires, endoscopic and pathologic records were obtained to confirm the diagnosis. Odds ratios (ORs) and 95% CIs were calculated using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. Secondary analyses were performed according to polyp features and participants' characteristics. Results: The demographic characteristics of participants at randomization were well balanced between the treatment and placebo groups; for example, 50.6% vs 50.5% were women, and 19.7% vs 19.8% were African American persons were included in each group. The mean (SD) age was 67.1 (7.1) years in the placebo group and 67.2 (7.1) in the ω-3 treatment group. During a median follow-up of 5.3 years (range, 3.8-6.1 years), 294 cases of conventional adenomas were documented in the ω-3 group and 301 in the control group (multivariable OR, 0.98; 95% CI, 0.83-1.15) (1:1 ratio between number of cases and number of participants). In addition, 174 cases of serrated polyps were documented in the ω-3 group and 167 in the control group (OR, 1.05; 95% CI, 0.84-1.29). Null associations were found for polyp subgroups according to size, location, multiplicity, or histology. In secondary analyses, marine ω-3 treatment appeared to be associated with lower risk of conventional adenomas among individuals with low plasma levels of ω-3 index at baseline (OR, 0.76; 95% CI, 0.57-1.02; P = .03 for interaction by ω-3 index). A beneficial association of supplementation was also noted in the African American population (OR, 0.59; 95% CI, 0.35-1.00) but not in other racial/ethnic groups (P = .11 for interaction). Conclusions and Relevance: Supplementation with marine ω-3 fatty acids, 1 g per day, was not associated with reduced risk of colorectal cancer precursors. A potential benefit of this supplementation for individuals with low baseline ω-3 levels or for African American persons requires further confirmation. Trial Registration: ClinicalTrials.gov identifier: NCT01169259.

4.
Brain ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746986

RESUMO

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 µg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

5.
JAMA ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703120

RESUMO

Importance: Chronic kidney disease (CKD) is a common complication of type 2 diabetes that can lead to end-stage kidney disease and is associated with high cardiovascular risk. Few treatments are available to prevent CKD in type 2 diabetes. Objective: To test whether supplementation with vitamin D3 or omega-3 fatty acids prevents development or progression of CKD in type 2 diabetes. Design, Setting, and Participants: Randomized clinical trial with a 2 × 2 factorial design conducted among 1312 adults with type 2 diabetes recruited between November 2011 and March 2014 from all 50 US states as an ancillary study to the Vitamin D and Omega-3 Trial (VITAL), coordinated by a single center in Massachusetts. Follow-up was completed in December 2017. Interventions: Participants were randomized to receive vitamin D3 (2000 IU/d) and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid; 1 g/d) (n = 370), vitamin D3 and placebo (n = 333), placebo and omega-3 fatty acids (n = 289), or 2 placebos (n = 320) for 5 years. Main Outcomes and Measures: The primary outcome was change in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) from baseline to year 5. Results: Among 1312 participants randomized (mean age, 67.6 years; 46% women; 31% of racial or ethnic minority), 934 (71%) completed the study. Baseline mean eGFR was 85.8 (SD, 22.1) mL/min/1.73 m2. Mean change in eGFR from baseline to year 5 was -12.3 (95% CI, -13.4 to -11.2) mL/min/1.73 m2 with vitamin D3 vs -13.1 (95% CI, -14.2 to -11.9) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.5] mL/min/1.73 m2). Mean change in eGFR was -12.2 (95% CI, -13.3 to -11.1) mL/min/1.73 m2 with omega-3 fatty acids vs -13.1 (95% CI, -14.2 to -12.0) mL/min/1.73 m2 with placebo (difference, 0.9 [95% CI, -0.7 to 2.6] mL/min/1.73 m2). There was no significant interaction between the 2 interventions. Kidney stones occurred among 58 participants (n = 32 receiving vitamin D3 and n = 26 receiving placebo) and gastrointestinal bleeding among 45 (n = 28 receiving omega-3 fatty acids and n = 17 receiving placebo). Conclusions and Relevance: Among adults with type 2 diabetes, supplementation with vitamin D3 or omega-3 fatty acids, compared with placebo, resulted in no significant difference in change in eGFR at 5 years. The findings do not support the use of vitamin D or omega-3 fatty acid supplementation for preserving kidney function in patients with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT01684722.

7.
Contemp Clin Trials ; 87: 105854, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31669447

RESUMO

BACKGROUND: The VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D3 (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors. METHODS: Baseline 25(OH)D was measured in 15,804 participants (mean age 68 years.; 50.8% women; 15.7% African Americans) and in 1660 1-year follow-up samples using liquid chromatography-tandem mass spectrometry and chemiluminescence. Calcium and parathyroid hormone (iPTH) were measured by chemiluminescence and spectrophotometry respectively. RESULTS: Mean baseline total 25(OH)D (ng/mL ±â€¯SD) was 30.8 ±â€¯10.0 ng/mL, and correlated inversely with iPTH (r = -0.28), p < .001. After adjusting for clinical factors, 25(OH)D (ng/mL ±â€¯SE) was lower in men vs women (29.7 ±â€¯0.30 vs 31.4 ±â€¯0.30, p < .0001) and in African Americans vs whites (27.9 ±â€¯0.29 vs 32.5 ±â€¯0.22, p < .0001). It was also lower with increasing BMI, smoking, and latitude, and varied by season. Mean 1-year 25(OH)D increased by 11.9 ng/mL in the active group and decreased by 0.7 ng/mL in placebo. The largest increases were noted among individuals with low baseline and African Americans. Results were similar for chemiluminescent immunoassay. Mean calcium was unchanged, and iPTH decreased with treatment. CONCLUSION: In VITAL, baseline 25(OH)D varied by clinical subgroups, was lower in men and African Americans. Concentrations increased with vitamin D supplementation, with the greatest increases in those with lower baseline 25(OH)D. The seasonal trends in 25(OH)D, iPTH, and calcium may be relevant when interpreting 25(OH)D levels for clinical treatment decisions. CLINICAL TRIAL REGISTRATION: VITAL ClinicalTrials.gov number NCT01169259.

8.
J Am Coll Cardiol ; 74(21): 2623-2634, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31727422

RESUMO

BACKGROUND: Sudden cardiac death occurs in ∼220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection. OBJECTIVES: This study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population. METHODS: The authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death. RESULTS: Among the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death-corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p < 0.0001). Among the 4,525 participants of the prospective cohort study, 41 (0.9%) carried a pathogenic or likely pathogenic variant and these individuals had 3.24-fold higher risk of cardiovascular death over a median follow-up of 14.3 years (p = 0.02). CONCLUSIONS: Gene sequencing identifies a pathogenic or likely pathogenic variant in a small but potentially important subset of adults experiencing sudden cardiac death; these variants are present in ∼1% of asymptomatic adults.

9.
Circulation ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709816

RESUMO

Among older adults, heart failure (HF) is the leading cause of hospitalization in the US and is associated with high costs and mortality1. Vitamin D and marine omega-3 (n-3) fatty acids have each been associated with reduced risks of HF in observational studies, but randomized trial evidence is limited. The current ancillary study sought to investigate the effects of vitamin D and n-3 supplements on the incidence of HF hospitalization in a large multi-ethnic cohort. VITAL-HF is an ancillary study of the parent VITAL trial, which is a completed randomized trial with a two-by-two factorial design to examine the efficacy of vitamin D3 (2000 IU/d) and n-3 fatty acids (1 gram per day, including eicosapentaenoic acid [EPA, 460 mg] + docosahexaenoic acid [DHA, 380 mg]) for the prevention of cardiovascular disease and cancer in 25, 871 adults from 2011 to 2017. Detailed description of the VITAL design and main results has been published2. We excluded 36 participants with prevalent HF for current analyses. Each participant signed informed consent and the study protocol was approved by the Institutional Review Board of Brigham and Women's Hospital.

10.
Psychosom Med ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31688458

RESUMO

OBJECTIVE: Mounting evidence suggests that higher optimism is associated with reduced risk of age-related morbidities and premature mortality. Yet, possible biological mechanisms underlying these associations remain understudied. One hypothesized mechanism is a slower rate of cellular aging, which in turn delays age-related declines in health. METHODS: We used data from two large cohort studies to test the hypothesis that higher optimism is associated with longer leukocyte telomere length. Using cross-sectional data from the Health and Retirement Study (HRS; N=6,417; mean age=70 years) and the Women's Health Initiative (WHI; N=3,582; mean age=63 years), we used linear regression models to examine the association of optimism with relative telomere length (assessed in leukocytes from saliva [HRS] or plasma [WHI]). Models adjusted for sociodemographics, depression, health status, and health behaviors. RESULTS: Considering both optimism and telomere length as continuous variables, we found consistently null associations in both cohorts, regardless of which covariates were included in the models. In models adjusting for demographics, depression, co-morbidities, and health behaviors, optimism was not associated with mean relative telomere length (HRS: ß=-0.002; 95% CI:-0.014, 0.011; WHI: ß=-0.004; 95% CI:-0.017, 0.009). CONCLUSIONS: Findings do not support mean telomere length as a mechanism that explains observed relations of optimism with reduced risk of chronic disease in older adults. Future research is needed to evaluate other potential biological markers and pathways.

11.
J Steroid Biochem Mol Biol ; : 105522, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31733345

RESUMO

Whether supplemental vitamin D reduces risk of cancer or cardiovascular disease (CVD) is relatively unexplored in randomized trial settings. The VITamin D and OmegA-3 TriaL (VITAL) was a nationwide, randomized, placebo-controlled, 2 × 2 factorial trial of daily vitamin D3 (2000 IU) and marine omega-3 fatty acids (1 g) in the primary prevention of cancer and CVD among 25,871 U.S. men aged ≥50 and women aged ≥55, including 5,106 African Americans. Median treatment duration was 5.3 years. Vitamin D did not significantly reduce the primary endpoint of total invasive cancer incidence (hazard ratio [HR] = 0.96 [95% confidence interval 0.88-1.06]) but showed a promising signal for reduction in total cancer mortality (HR = 0.83 [0.67-1.02]), especially in analyses that accounted for latency by excluding the first year (HR = 0.79 [0.63-0.99]) or first 2 years (HR = 0.75 [0.59-0.96]) of follow-up. Vitamin D did not significantly reduce the co-primary endpoint of major CVD events (HR = 0.97 [0.85-1.12]), other cardiovascular endpoints, or all-cause mortality (HR = 0.99 [0.87-1.12]). Updated meta-analyses that include VITAL and other recent vitamin D trials indicate a significant reduction in cancer mortality but not in cancer incidence or CVD endpoints. Additional research is needed to determine which individuals may be most likely to derive a net benefit from vitamin D supplementation. (VITAL clinicaltrials.gov identifier: NCT01169259).

12.
Int J Epidemiol ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31651959

RESUMO

BACKGROUND: Metabolomics profiling has shown promise in elucidating the biological pathways underpinning mortality, but there are limited data in female populations. METHODS: We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to EDTA-plasma to measure 470 metabolites at baseline in a discovery set of 943 postmenopausal women (including 417 incident deaths, median time to death of 10.6 years) with validation in an independent set of 1355 postmenopausal women (including 685 deaths, median time to death of 9.1 years) in the Women's Health Initiative. RESULTS: Eight new metabolites were discovered to be associated with all-cause mortality. Findings included protective effects of increased levels of three amino acids (asparagine, homoarginine and tryptophan) and docosatrienoic acid; and detrimental effects of increased levels of C4-OH-carnitine, hexadecanedioate and two purine/pyrimidines (N2, N2-dimethylguanosine and N4-acetylcytidine). In addition, a set of nine previously published metabolite associations were replicated. A metabolite score comprising 17 metabolites was associated with mortality (P < 10-8) after adjustment for risk factors, with a hazard ratio of 1.95 (95% CI: 1.46-2.62) for women in the highest quartile compared with the lowest quartile of metabolite score. The score was robust among younger women and older women, for both cardiovascular and non-cardiovascular mortality, and associated with both early deaths (within the first 10 years of baseline) and later deaths. CONCLUSIONS: Our study fills a gap in the literature by identifying eight novel metabolite associations with all-cause mortality in women, using a robust study design involving independent discovery and validation datasets.

13.
J Am Heart Assoc ; 8(15): e012763, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31652073

RESUMO

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17ß-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and <100 and annualized change in CAC score was ≥10. Of 727 KEEPS participants, 474 (mean age: 52.7 [SD: 2.6]; 78.1% white) had computed tomography-based heart fat and CAC measures at both baseline and 48 months. Compared with women on placebo, women on oral conjugated equine estrogens were less likely to have any increase in epicardial adipose tissue (odds ratio for oral conjugated equine estrogens versus placebo: 0.62 [95% CI, 0.40-0.97]; P=0.03). PAT did not change in any group. Changes in epicardial adipose tissue and PAT did not differ by treatment group. CAC increased in 14% of participants. The assigned treatment modified the association between PAT changes and CAC progression (P=0.02) such that PAT increases were associated with CAC increases only in the transdermal 17ß-estradiol group. Conclusions In recently menopausal women, oral conjugated equine estrogens may slow epicardial adipose tissue accumulation, whereas transdermal 17ß-estradiol may increase progression of CAC associated with PAT accumulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00154180.

14.
J Am Heart Assoc ; 8(19): e013543, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31567003

RESUMO

Background Whether marine omega-3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial. Methods and Results This meta-analysis included study-level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed-effect meta-analysis. A meta-regression was conducted to estimate the dose-response relationship between marine omega-3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), marine omega-3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE-IT while introducing statistically significant heterogeneity. Statistically significant linear dose-response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE-IT. Conclusions Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose.

16.
Diabetes Care ; 42(12): 2181-2189, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31582428

RESUMO

OBJECTIVE: We evaluated the associations of long-term changes in consumption of sugary beverages (including sugar-sweetened beverages and 100% fruit juices) and artificially sweetened beverages (ASBs) with subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed up 76,531 women in the Nurses' Health Study (1986-2012), 81,597 women in the Nurses' Health Study II (1991-2013), and 34,224 men in the Health Professionals' Follow-up Study (1986-2012). Changes in beverage consumption (in 8-ounce servings/day) were calculated from food frequency questionnaires administered every 4 years. Multivariable Cox proportional regression models were used to calculate hazard ratios for diabetes associated with changes in beverage consumption. Results of the three cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. RESULTS: During 2,783,210 person-years of follow-up, we documented 11,906 incident cases of type 2 diabetes. After adjustment for BMI and initial and changes in diet and lifestyle covariates, increasing total sugary beverage intake (including both sugar-sweetened beverages and 100% fruit juices) by >0.50 serving/day over a 4-year period was associated with a 16% (95% CI 1%, 34%) higher diabetes risk in the subsequent 4 years. Increasing ASB consumption by >0.50 serving/day was associated with 18% (2%, 36%) higher diabetes risk. Replacing one daily serving of sugary beverage with water, coffee, or tea, but not ASB, was associated with a 2-10% lower diabetes risk. CONCLUSIONS: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of type 2 diabetes, albeit the latter association may be affected by reverse causation and surveillance bias.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31663769

RESUMO

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of post-menopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45± 2.49 years of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE, n=109), transdermal 17ß-estradiol (t-E2, n=107), or placebo (n=146). Androstenedione, testosterone, 17ß-estradiol, estrone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum prior to (baseline) and 48 months after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE , t-E2, and placebo on these hormone levels at 48 months adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 months within treatment groups. As expected, at 48 months of treatment, hormone levels differed between women in the two active treatment groups compared to placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups as compared to placebo. Associations among testosterone, 17ß-estradiol, FSH and LH differed between the o-CEE group compared to t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and inter-hormonal associations in recently menopausal women. These interactions provide the basis for future studies investing the impact of hormonal modulation of aging including cognitive decline in women.

18.
Int J Cancer ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584193

RESUMO

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50-79 years without breast cancer at enrollment (1993-1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6-8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79-0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.

19.
Epidemiology ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31569119

RESUMO

BACKGROUND: Weight gain following smoking cessation reduces the incentive to quit, especially among women. Exercise and diet interventions may reduce post-cessation weight gain, but their long-term effect has not been estimated in randomized trials. METHODS: We estimated the long-term reduction in post-cessation weight gain among women under smoking cessation alone or combined with (1) moderate-to-vigorous exercise (15, 30, 45, 60 minutes/day), and (2) exercise and diet modification (≤2 servings/week of unprocessed red meat; ≥ 5 servings/day of fruits and vegetables; minimal sugar-sweetened beverages, sweets and desserts, potato chips or fried potatoes, and processed red meat). RESULTS: Among 10,087 eligible smokers in the Nurses' Health Study and 9,271 in the Nurses' Health Study II, the estimated 10-year mean weights under smoking cessation were 75.0 (95% CI: 74.7, 75.5) kg and 79.0 (78.2, 79.6) kg, respectively. In both cohorts, the estimated post-cessation mean weight gain was 4.9 (7.3, 2.6) kg lower under a hypothetical strategy of exercising at least 30 minutes/day and diet modification, and 5.9 (8.0, 3.8) kg lower under exercising at least 60 minutes/day and diet modification, compared with smoking cessation without exercising. CONCLUSIONS: In this study, substantial weight gain occurred in women after smoking cessation, but we estimate that exercise and dietary modifications averted most of it.

20.
Environ Int ; 132: 105113, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31473415

RESUMO

BACKGROUND: Fruit and vegetable (FV) intake is recommended for the prevention of coronary heart disease (CHD). FVs are also an important source of exposure to pesticide residues. Whether the relations of FV intake with CHD differ according to pesticide residue status is unknown. OBJECTIVE: To examine the associations of high- and low-pesticide-residue FVs with the risk of CHD. METHODS: We followed 145,789 women and 24,353 men free of cardiovascular disease and cancer (excluding non-melanoma skin cancer) at baseline and participating in three ongoing prospective cohorts: the Nurses' Health Study (NHS: 1998-2012), the NHS-II (1999-2013), and the Health Professionals Follow-up Study (HPFS: 1998-2012). FV intake was assessed via food frequency questionnaires. We categorized FVs as having high- or low-pesticide-residues using a validated method based on pesticide surveillance data from the US Department of Agriculture. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI) of CHD in relation to high- and low-pesticide-residue FV intake. RESULTS: A total of 3707 incident CHD events were identified during 2,241,977 person-years of follow-up. In multivariable-adjusted models, a greater intake of low-pesticide-residue FVs was associated with a lower risk of CHD whereas high-pesticide-residue FV intake was unrelated to CHD risk. Specifically, compared with individuals consuming <1 serving/day of low-pesticide-residue FVs, those consuming ≥4 servings/day had 20% (95CI: 4%, 33%) lower risk of CHD. The corresponding HR (comparing ≥4 servings/day to <1 serving/day) for high-pesticide-residue FV intake and CHD was 0.97 (95%CI: 0.72, 1.30). CONCLUSIONS: Our data suggested exposure to pesticide residues through FV intake may modify some cardiovascular benefits of FV consumption. Further confirmation of these findings, especially using biomarkers for assessment of pesticide exposure, is needed.

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