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1.
Am J Epidemiol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33025002

RESUMO

The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy post-menopausal women aged 50-79 at 40 U.S. clinical centers during 1993-1998, including 10,739 post-hysterectomy participants in a trial of conjugated equine estrogens, and 16,608 participants with uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over an 18-year (median) follow-up period (1993-2016) risk for a global index, defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all-cause mortality, is reduced with conjugated equine estrogens with hazard ratio (95% confidence interval) of 0.82 (0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture and all-cause mortality. Corresponding global index hazard ratio estimates of 1.06 (0.95, 1.19) were non-significant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50-59, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.

2.
Am J Epidemiol ; 189(9): 972-981, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32314781

RESUMO

Dual-outcome intention-to-treat hazard rate analyses have potential to complement single-outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes to obtain further insight into influences of menopausal hormone therapy on chronic disease. As part of the Women's Health Initiative, randomized, placebo-controlled hormone therapy trials of conjugated equine estrogens (CEE) among posthysterectomy participants and of these same estrogens plus medroxyprogesterone acetate (MPA) among participants with an intact uterus were carried out at 40 US clinical centers (1993-2016). These data provide the context for analyses covering the trial intervention periods and a nearly 20-year (median) cumulative duration of follow-up. The rates of multiple outcome pairs were significantly influenced by hormone therapy, especially over cumulative follow-up, providing potential clinical and mechanistic insights. For example, among women randomized to either regimen, hazard ratios for pairs defined by fracture during intervention followed by death from any cause were reduced and hazard ratios for pairs defined by gallbladder disease followed by death were increased, though these findings may primarily reflect single-outcome associations. In comparison, hazard ratios for diabetes followed by death were reduced with CEE but not with CEE + MPA, and those for hypertension followed by death were increased with CEE + MPA but not with CEE.


Assuntos
Terapia de Reposição de Estrogênios , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , Doenças Cardiovasculares/epidemiologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Fraturas Ósseas/epidemiologia , Doenças da Vesícula Biliar/epidemiologia , Humanos , Incidência , Análise de Intenção de Tratamento , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Estados Unidos/epidemiologia
4.
Ann Intern Med ; 171(6): 406-414, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31499528

RESUMO

Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Estrogen-Alone Trial. (ClinicalTrials.gov: NCT00000611). Setting: 40 U.S. clinical centers. Participants: 9939 women aged 50 to 79 years with prior hysterectomy and known oophorectomy status. Intervention: Conjugated equine estrogens (CEE) (0.625 mg/d) or placebo for a median of 7.2 years. Measurements: Incidence of coronary heart disease and invasive breast cancer (the trial's 2 primary end points), all-cause mortality, and a "global index" (these end points plus stroke, pulmonary embolism, colorectal cancer, and hip fracture) during the intervention phase and 18-year cumulative follow-up. Results: The effects of CEE alone did not differ significantly according to BSO status. However, age modified the effect of CEE in women with prior BSO. During the intervention phase, CEE was significantly associated with a net adverse effect (hazard ratio for global index, 1.42 [95% CI, 1.09 to 1.86]) in older women (aged ≥70 years), but the global index was not elevated in younger women (P trend by age = 0.016). During cumulative follow-up, women aged 50 to 59 years with BSO had a treatment-associated reduction in all-cause mortality (hazard ratio, 0.68 [CI, 0.48 to 0.96]), whereas older women with BSO had no reduction (P trend by age = 0.034). There was no significant association between CEE and outcomes among women with conserved ovaries, regardless of age. Limitations: The timing of CEE in relation to BSO varied; several comparisons were made without adjustment for multiple testing. Conclusion: The effects of CEE did not differ by BSO status in the overall cohort, but some findings varied by age. Among women with prior BSO, in those aged 70 years or older, CEE led to adverse effects during the treatment period, whereas women randomly assigned to CEE before age 60 seemed to derive mortality benefit over the long term. Primary Funding Source: The WHI program is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and U.S. Department of Health and Human Services. Wyeth Ayerst donated the study drugs.


Assuntos
Terapia de Reposição de Estrogênios/métodos , Estrogênios Conjugados (USP)/uso terapêutico , Ovariectomia , Fatores Etários , Idoso , Neoplasias da Mama/epidemiologia , Causas de Morte , Neoplasias Colorretais/epidemiologia , Doença das Coronárias/epidemiologia , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Menopausa , Pessoa de Meia-Idade , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Estados Unidos/epidemiologia
5.
Nutrients ; 11(7)2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31330892

RESUMO

BACKGROUND AND AIMS: The association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less likely to be endogenously synthesized, are good biomarkers of dietary fatty acids. Thus, PL-FA profiles may better predict CHD risk with less measurement error. METHODS: We performed a matched case-control study of 2428 postmenopausal women nested in the Women's Health Initiative Observational Study. Plasma PL-FA were measured using gas chromatography and expressed as molar percentage (moL %). Multivariable conditional logistic regression was used to calculate odds ratios (95% CIs) for CHD associated with 1 moL % change in PL-FA. RESULTS: Higher plasma PL long-chain saturated fatty acids (SFA) were associated with increased CHD risk, while higher n-3 polyunsaturated fatty acids (PUFA) were associated with decreased risk. No significant associations were observed for very-long-chain SFA, monounsaturated fatty acids (MUFA), PUFA n-6 or trans fatty acids (TFA). Substituting 1 moL % PUFA n-6 or TFA with an equivalent proportion of PUFA n-3 were associated with lower CHD risk. CONCLUSIONS: Higher plasma PL long-chain SFA and lower PUFA n-3 were associated with increased CHD risk. A change in diet by limiting foods that are associated with plasma PL long-chain SFA and TFA while enhancing foods high in PUFA n-3 may be beneficial in CHD among postmenopausal women.


Assuntos
Doença das Coronárias/etiologia , Hiperlipidemias/complicações , Fosfolipídeos/sangue , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
6.
J Nutr ; 149(9): 1565-1574, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31175807

RESUMO

BACKGROUND: The preferred macronutrient dietary composition, and the health consequences of dietary fat reduction specifically, have been debated for decades. Here we provide a comprehensive overview of long-term health outcomes in the Women's Health Initiative Dietary Modification (DM) trial. OBJECTIVE: The DM trial aimed to examine whether a low-fat dietary pattern would reduce the risk of invasive breast cancer, colorectal cancer, and, secondarily, coronary heart disease (CHD), with various other health outcomes also considered. METHODS: The DM trial is a randomized controlled trial conducted at 40 centers in the US, among 48,835 postmenopausal women aged 50-79 y with baseline intake of ≥32% energy from fat. Participants were randomly assigned to a low-fat dietary pattern intervention group or to a usual-diet comparison group, during 1993-1998. Intervention goals were to reduce fat intake from ∼35% to 20% of total energy, in conjunction with increasing vegetables and fruit to 5 servings/d and grains to 6 servings/d. RESULTS: Over an 8.5-y (median) intervention period, intervention and comparison group differences included lower fat by 8-10%, and higher carbohydrate by 8-10%, of total energy, in conjunction with higher consumption of vegetables, fruit, and grains. Time-to-outcome analyses did not show significant differences between intervention and comparison groups for invasive breast cancer, colorectal cancer, or CHD, either over the intervention period or over longer-term cumulative follow-up. Additional analyses showed significant intervention group benefits related to breast cancer, CHD, and diabetes, without adverse effects. Over a 19.6-y (median) follow-up period, HRs (95% CIs) were 0.84 (0.74, 0.96) for breast cancer followed by death, and 0.87 (0.77, 0.98) for diabetes requiring insulin. CONCLUSIONS: Reduction in dietary fat with corresponding increase in vegetables, fruit, and grains led to benefits related to breast cancer, CHD, and diabetes, without adverse effects, among healthy postmenopausal US women.This trial was registered at clinicaltrials.gov as NCT00000611.


Assuntos
Neoplasias da Mama/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Doença das Coronárias/prevenção & controle , Diabetes Mellitus/terapia , Dieta com Restrição de Gorduras , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Saúde da Mulher
7.
JAMA Intern Med ; 178(9): 1231-1240, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30039172

RESUMO

Importance: Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for overestimation are unclear. Objective: We evaluated the predictive accuracy of the PCE in the Women's Health Initiative (WHI), a multiethnic cohort of contemporary US postmenopausal women. We evaluated the effects of time-varying treatments such as aspirin and statins, and ascertainment of additional ASCVD events by linkage with the Centers for Medicare and Medicaid Services (CMS) claims. Design, Setting, and Participants: The WHI recruited the largest number of US women (n = 161 808) with the racial/ethnic, geographic, and age diversity of the general population (1993-1998). For this study, we included women aged 50 to 79 (n = 19 995) participating in the WHI with data on the risk equation variables at baseline and who met the guideline inclusion and exclusion criteria. Median follow-up was 10 years. Main Outcomes and Measures: For this study, ASCVD was defined as myocardial infarction, stroke, or cardiovascular death. Results: Among the 19 995 women (mean [SD] age, 64 [7.3] years; 8305 [41.5%] white, 7688 [38.5%] black, 3491 [17.5%] Hispanic, 103 [0.5%] American Indian, 321 [1.6%] Asian/Pacific Islander, and 87 [0.4%] other/unknown), a total of 1236 ASCVD events occurred in 10 years and were adjudicated through medical record review by WHI investigators. The WHI-adjudicated observed risks were lower than predicted. The observed (predicted) risks for baseline 10-year risk categories less than 5%, 5% to less than 7.5%, 7.5% to less than 10%, and 10% or more were 1.7 (2.8), 4.4 (6.2), 5.3 (8.7), and 12.4 (18.2), respectively. Small changes were noted after adjusting for time-dependent changes in statin and aspirin use. Among women 65 years or older enrolled in Medicare, WHI-adjudicated risks were also lower than predicted, but observed (predicted) risks became aligned after including events ascertained by linkage with CMS for additional surveillance for events: 3.8 (4.3), 7.1 (6.4), 8.3 (8.7), and 18.9 (18.7), respectively. Similar results were seen across ethnic/racial groups. Overall, the equations discriminated risk well (C statistic, 0.726; 95% CI, 0.714-0.738). Conclusions and Relevance: Without including surveillance for ASCVD events using CMS, observed risks in the WHI were lower than predicted by PCE as noted in several other US cohorts, but risks were better aligned after including CMS events. Trial Registration: ClinicalTrials.gov identifier: NCT00000611.


Assuntos
Doenças Cardiovasculares/etnologia , Grupos Étnicos , Pós-Menopausa , Medição de Risco/métodos , Saúde da Mulher , Idoso , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
11.
JAMA ; 318(10): 927-938, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28898378

RESUMO

Importance: Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality. Objective: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials. Design, Setting, and Participants: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. Interventions: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median). Main Outcomes and Measures: All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization. Results: Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. Conclusions and Relevance: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. Trial Registration: clinicaltrials.gov Identifier: NCT00000611.


Assuntos
Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/uso terapêutico , Medroxiprogesterona/uso terapêutico , Mortalidade , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Método Duplo-Cego , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/efeitos adversos , Feminino , Seguimentos , Humanos , Medroxiprogesterona/efeitos adversos , Pessoa de Meia-Idade , Neoplasias/mortalidade , Pós-Menopausa , Risco
12.
Am J Epidemiol ; 186(9): 1035-1043, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28633342

RESUMO

Studies of the associations of sodium and potassium intakes with cardiovascular disease incidence often rely on self-reported dietary data. In the present study, self-reported intakes from postmenopausal women at 40 participating US clinical centers are calibrated using 24-hour urinary excretion measures in cohorts from the Women's Health Initiative, with follow-up from 1993 to 2010. The incidence of hypertension was positively related to (calibrated) sodium intake and to the ratio of sodium to potassium. The sodium-to-potassium ratio was associated with cardiovascular disease incidence during an average follow-up period of 12 years. The estimated hazard ratio for a 20% increase in the sodium-to-potassium ratio was 1.13 (95% confidence interval (CI): 1.04, 1.22) for coronary heart disease, 1.20 (95% CI: 1.01, 1.42) for heart failure, and 1.11 (95% CI: 1.04, 1.19) for a composite cardiovascular disease outcome. The association with total stroke was not significant, but it was positive for ischemic stroke and inverse for hemorrhagic stroke. Aside from hemorrhagic stroke, corresponding associations of cardiovascular disease with sodium and potassium jointly were positive for sodium and inverse for potassium, although some were not statistically significant. Specifically, for coronary heart disease, the hazard ratios for 20% increases were 1.11 (95% CI: 0.95, 1.30) for sodium and 0.85 (95% CI: 0.73, 0.99) for potassium; and corresponding values for heart failure were 1.36 (95% CI: 1.02, 1.82) for sodium and 0.90 (95% CI: 0.69, 1.18) for potassium.


Assuntos
Doenças Cardiovasculares/epidemiologia , Potássio na Dieta/urina , Sódio na Dieta/urina , Idoso , Biomarcadores/urina , Índice de Massa Corporal , Calibragem , Doenças Cardiovasculares/urina , Registros de Dieta , Feminino , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Razão de Chances , Pós-Menopausa/urina , Potássio na Dieta/administração & dosagem , Potássio na Dieta/efeitos adversos , Modelos de Riscos Proporcionais , Análise de Regressão , Medição de Risco , Sódio na Dieta/administração & dosagem , Sódio na Dieta/efeitos adversos , Estados Unidos/epidemiologia
13.
Am J Clin Nutr ; 106(1): 35-43, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28515068

RESUMO

Background: The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest.Objective: This report evaluates low-fat dietary pattern influences on cardiovascular disease (CVD) incidence and mortality during the intervention and postintervention phases of the Women's Health Initiative Dietary Modification Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y; 40% were randomly assigned to a low-fat dietary pattern intervention (target of 20% of energy from fat), and 60% were randomly assigned to a usual diet comparison group. The 8.3-y intervention period ended in March 2005, after which >80% of surviving participants consented to additional active follow-up through September 2010; all participants were followed for mortality through 2013. Breast and colorectal cancer were the primary trial outcomes, and coronary heart disease (CHD) and overall CVD were additional designated outcomes.Results: Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period. However, CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status. Participants without prior CVD had an intervention period CHD HR of 0.70 (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk. Corresponding HRs in the postintervention period were close to null. Participants with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61 (95% CI: 1.02, 2.55) in the intervention and postintervention periods, respectively. However, various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postrandomization use of cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and, among healthy women, includes both CHD benefit and stroke risk. This trial was registered at clinicaltrials.gov as NCT00000611.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Dieta com Restrição de Gorduras , Gorduras na Dieta/farmacologia , Comportamento Alimentar , Acidente Vascular Cerebral , Idoso , Neoplasias da Mama , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Neoplasias Colorretais , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Gorduras na Dieta/administração & dosagem , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Incidência , Pessoa de Meia-Idade , Pós-Menopausa , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Saúde da Mulher
14.
Thromb Res ; 150: 78-85, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28063368

RESUMO

INTRODUCTION: Our objective was to compare Medicare claims to physician review and adjudication of medical records for identifying venous thromboembolism (VTE), and to assess VTE incidence, recurrence, and mortality in a large national cohort of post-menopausal women followed up to 19years. MATERIALS AND METHODS: We used detailed clinical data from the Women's Health Initiative (WHI) linked to Medicare claims. Agreement between data sources was evaluated among 16,003 women during 1993-2010. A claims-based definition was selected to analyze VTE occurrence and impact among 71,267 women during 1993-2012. RESULTS: Our VTE definition had 83% sensitivity. Positive predictive value was 69% when all records were included, and 94% after limiting Medicare records to those with a WHI hospitalization adjudicated. Annualized VTE incidence was 4.06/1000person-years (PY), recurrence was 5.30/100PY, and both rates varied by race/ethnicity. Post-VTE mortality within 1year was 22.49% from all causes, including 1.01% from pulmonary embolism, 10.40% from cancer, and 11.08% from other causes. Cancer-related VTE compared to non-cancer VTE had significantly (p<0.001) higher recurrence (9.86/100PY vs. 4.43/100PY) and mortality from all causes (45.89% vs. 12.28%), but not from pulmonary embolism (0.40% vs. 1.27%). CONCLUSIONS: Medicare claims compared reasonably well to physician adjudication. The combined data sources provided new insights about VTE burden and prognosis in older women.


Assuntos
Tromboembolia Venosa/epidemiologia , Demandas Administrativas em Assistência à Saúde , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Registros Médicos , Medicare , Pessoa de Meia-Idade , Neoplasias/complicações , Recidiva , Estados Unidos/epidemiologia , Tromboembolia Venosa/complicações , Tromboembolia Venosa/mortalidade , Saúde da Mulher
15.
Menopause ; 24(4): 360-370, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27922933

RESUMO

OBJECTIVE: Vasomotor symptoms (VMS) may be a marker of cardiovascular risk. We aimed to evaluate the cross-sectional association of VMS presence and severity with hemostatic parameter levels measured at baseline among Women's Health Initiative (WHI) Hormone Therapy trial postmenopausal participants. METHODS: This cross-sectional analysis included 2,148 postmenopausal women with measures of VMS presence and severity reported in the 4 weeks before WHI baseline, who were not using warfarin or hormone therapy and for whom the following baseline hemostatic parameters were measured within the WHI Cardiovascular Disease Biomarker Case-Control Study: antithrombin, plasminogen activator inhibitor-1, protein C antigen, total and free protein S antigen, total and free tissue factor pathway inhibitor, D-dimer, normalized activated protein C sensitivity ratio, and thrombin generation. Using multiple linear regression, we estimated the adjusted average difference in each hemostatic parameter associated with VMS presence and severity. A multiple comparisons-corrected P value was computed using the P-min procedure to determine statistical significance of our smallest observed P value. RESULTS: Women were 67 years of age on average and 33% reported VMS presence at baseline. There was some suggestion that VMS presence may be associated with a -0.34 adjusted difference in normalized activated protein C sensitivity ratio compared with no VMS (95% CI, -0.60 to -0.087; P = 0.009), but this association was not significant after correction for multiple comparisons (P = 0.073). VMS presence or severity was not significantly associated with the other hemostatic parameters. CONCLUSIONS: We found no convincing evidence that VMS presence or severity was associated with levels of hemostatic parameters among postmenopausal women.


Assuntos
Fogachos/sangue , Pós-Menopausa/sangue , Sudorese , Idoso , Antígenos/sangue , Proteínas Antitrombina/metabolismo , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemostasia , Humanos , Lipoproteínas/sangue , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteína C/imunologia , Proteína S/imunologia , Índice de Gravidade de Doença , Avaliação de Sintomas , Trombina/biossíntese
16.
Circulation ; 135(1): 7-16, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27831499

RESUMO

BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.


Assuntos
Tromboembolia Venosa/etiologia , Fatores Etários , Pressão Sanguínea , Índice de Massa Corporal , Complicações do Diabetes , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Lipídeos/sangue , Modelos de Riscos Proporcionais , Estudos Prospectivos , Embolia Pulmonar/etiologia , Fatores de Risco , Fatores Sexuais , Fumar , Trombose Venosa/etiologia
17.
Epidemiology ; 28(1): 145-156, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27648593

RESUMO

BACKGROUND: Several recent articles have called into question the deleterious effects of high animal fat diets due to mixed results from epidemiologic studies and the lack of clinical trial evidence in meta-analyses of dietary intervention trials. We were interested in examining the theoretical effects of substituting plant-based fats from different types of margarine for animal-based fat from butter on the risk of atherosclerosis-related cardiovascular disease (CVD). METHODS: We prospectively studied 71,410 women, aged 50-79 years, and evaluated their risk for clinical myocardial infarction (MI), total coronary heart disease (CHD), ischemic stroke, and atherosclerosis-related CVD with an average of 13.2 years of follow-up. Butter and margarine intakes were obtained at baseline and year 3 by means of a validated food frequency questionnaire. Cox proportional hazards regression using a cumulative average diet method was used to estimate the theoretical effect of substituting 1 teaspoon/day of three types of margarine for the same amount of butter. RESULTS: Substituting butter or stick margarine with tub margarine was associated with lower risk of MI (HRs = 0.95 and 0.91). Subgroup analyses, which evaluated these substitutions among participants with a single source of spreadable fat, showed stronger associations for MI (HRs = 0.92 and 0.87). Outcomes of total CHD, ischemic stroke, and atherosclerosis-related CVD showed wide confidence intervals but the same trends as the MI results. CONCLUSIONS: This theoretical dietary substitution analysis suggests that substituting butter and stick margarine with tub margarine when spreadable fats are eaten may be associated with reduced risk of myocardial infarction.


Assuntos
Manteiga/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Dieta/estatística & dados numéricos , Margarina/estatística & dados numéricos , Idoso , Aterosclerose/epidemiologia , Isquemia Encefálica/epidemiologia , Doença das Coronárias/epidemiologia , Gorduras na Dieta , Gorduras Insaturadas na Dieta , Ácidos Graxos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Ácidos Graxos Trans
18.
Nat Genet ; 48(10): 1162-70, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27618448

RESUMO

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.


Assuntos
Pressão Sanguínea/genética , Variação Genética , Exoma , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hipertensão/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único
19.
Am J Hypertens ; 29(2): 202-16, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26137952

RESUMO

BACKGROUND: To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS: Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS: Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS: Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056.


Assuntos
Cognição , Disfunção Cognitiva/etiologia , Demência/etiologia , Hipertensão/complicações , Sódio na Dieta/efeitos adversos , Idoso , Anti-Hipertensivos/uso terapêutico , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Demência/epidemiologia , Demência/prevenção & controle , Feminino , Humanos , Hipertensão/tratamento farmacológico , Incidência , Memória , Estudos Prospectivos , Estados Unidos/epidemiologia
20.
Arterioscler Thromb Vasc Biol ; 36(2): 418-24, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26681757

RESUMO

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.


Assuntos
Resistência à Proteína C Ativada/complicações , Doença das Coronárias/induzido quimicamente , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/efeitos adversos , Lipoproteínas/metabolismo , Progestinas/efeitos adversos , Resistência à Proteína C Ativada/sangue , Resistência à Proteína C Ativada/diagnóstico , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Pós-Menopausa , Estudos Prospectivos , Medição de Risco , Fatores de Risco
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