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Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort From the Women's Health Initiative.
Mora, S, Wenger, NK, Cook, NR, Liu, J, Howard, BV, Limacher, MC, Liu, S, Margolis, KL, Martin, LW, Paynter, NP, et al
JAMA internal medicine. 2018;(9):1231-1240
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Abstract
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.
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Cocoa Flavanol Intake and Biomarkers for Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Lin, X, Zhang, I, Li, A, Manson, JE, Sesso, HD, Wang, L, Liu, S
The Journal of nutrition. 2016;(11):2325-2333
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Abstract
BACKGROUND Cocoa flavanols may improve cardiometabolic health. Evidence from small short-term randomized clinical trials (RCTs) remains inconsistent, and large long-term RCTs testing the efficacy of cocoa flavanols are still lacking. OBJECTIVE We performed a systematic review and meta-analysis of RCTs to quantify the effect of cocoa flavanol intake on cardiometabolic biomarkers. METHODS We searched PubMed, Web of Science, and the Cochrane Library for RCTs that evaluated the effects of cocoa flavanols on biomarkers relevant to vascular disease pathways among adults. Data were extracted following a standardized protocol. We used DerSimonian and Laird random-effect models to compute the weighted mean differences (WMDs) and 95% CIs. We also examined potential modification by intervention duration, design, age, sex, comorbidities, and the form and amount of cocoa flavanol intake. RESULTS We included 19 RCTs that comprised 1131 participants, and the number of studies for a specific biomarker varied. The amount of cocoa flavanols ranged from 166 to 2110 mg/d, and intervention duration ranged from 2 to 52 wk. Cocoa flavanol intake significantly improved insulin sensitivity and lipid profile. The WMDs between treatment and placebo were -0.10 mmol/L (95% CI: -0.16, -0.04 mmol/L) for total triglycerides, 0.06 mmol/L (95% CI: 0.02, 0.09 mmol/L) for HDL cholesterol, -2.33 μIU/mL (95% CI: -3.47, -1.19 μIU/mL) for fasting insulin, -0.93 (95% CI: -1.31, -0.55) for the homeostatic model assessment of insulin resistance, 0.03 (95% CI: 0.01, 0.05) for the quantitative insulin sensitivity check index, 2.54 (95% CI: 0.63, 4.44) for the insulin sensitivity index, -0.83 mg/dL (95% CI: -0.88, -0.77 mg/dL) for C-reactive protein, and 85.6 ng/mL (95% CI: 16.0, 155 ng/mL) for vascular cell adhesion molecule 1. No significant associations were found for other biomarkers. None of the modifiers seemed to qualitatively modify the effects of cocoa flavanol intake. CONCLUSIONS Our study suggests that cocoa flavanol intake has favorable effects on select cardiometabolic biomarkers among adults. These findings support the need for large long-term RCTs to assess whether cocoa flavanol intake reduces the risk of diabetes and cardiovascular events.
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Serum 25-hydroxyvitamin D concentrations in relation to cardiometabolic risk factors and metabolic syndrome in postmenopausal women.
Chacko, SA, Song, Y, Manson, JE, Van Horn, L, Eaton, C, Martin, LW, McTiernan, A, Curb, JD, Wylie-Rosett, J, Phillips, LS, et al
The American journal of clinical nutrition. 2011;(1):209-17
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Abstract
BACKGROUND Low concentrations of serum 25-hydroxyvitamin D [25(OH)D] may be associated with cardiometabolic disorders; however, little is known about their relation to intermediate metabolic and lipid markers. OBJECTIVE We investigated the relation of serum 25(OH)D concentrations to fasting insulin, glucose, dyslipidemia, adiposity, and prevalent metabolic syndrome. DESIGN We conducted this cross-sectional analysis in 292 postmenopausal women aged 50-79 y in the Women's Health Initiative Calcium-Vitamin D (WHI-CaD) trial. Data were collected from 3 nested case-control studies that measured baseline serum 25(OH)D concentrations. Inverse probability weighting was used to approximate parameter estimates for the WHI-CaD population. RESULTS In weighted linear regression models adjusted for age, race-ethnicity, month of blood draw, region, case-control status, smoking, alcohol, physical activity, and history of cardiometabolic risk factors, there was an inverse association of serum 25(OH)D with adiposity [body mass index (BMI): β = -1.12 ± 0.30, P = 0.0002; waist circumference: β = -3.57 ± 0.49, P < 0.0001; waist-hip ratio: β = -0.01 ± 0.002, P < 0.0001], triglycerides (β = -0.10 ± 0.02, P < 0.0001), and triglyceride:HDL-cholesterol ratio (β = -0.11 ± 0.03, P = 0.0003). The multivariable-adjusted odds ratio for metabolic syndrome for the highest (≥52 nmol/L) compared with the lowest (<35 nmol/L) tertile of serum 25(OH)D concentrations was 0.28 (95% CI: 0.14, 0.56). Significant associations remained after adjustment for BMI. We observed no significant associations with LDL cholesterol, HDL cholesterol, insulin, glucose, homeostatic model assessment of insulin resistance (HOMA-IR), or homeostatic model assessment of β cell function (HOMA-β). CONCLUSION Higher serum 25(OH)D concentrations may be inversely associated with adiposity, triglycerides, triglyceride:HDL-cholesterol ratio, and metabolic syndrome but are not associated with LDL and HDL cholesterol, insulin, glucose, HOMA-IR, or HOMA-β in postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.
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Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study.
Ding, EL, Song, Y, Manson, JE, Rifai, N, Buring, JE, Liu, S
Diabetologia. 2007;(10):2076-84
Abstract
AIMS/HYPOTHESIS Prospective data directly investigating the role of endogenous sex hormones in diabetes risk have been scant, particularly in women. We aimed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women. METHODS We conducted a prospective, nested case-control study of plasma oestradiol, testosterone and dehydroepiandrosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause. Among women not using hormone therapy and free of baseline cardiovascular disease, cancer and diabetes, 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years. RESULTS Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes. After adjustment for BMI, family history, lifestyle and reproductive variables, the multivariable relative risks (95% CI) comparing the highest vs lowest quintile were 12.6 (2.83-56.3) for total oestradiol (p = 0.002 for trend), 13.1 (4.18-40.8) for free oestradiol (p < 0.001 for trend), 4.15 (1.21-14.2) for total testosterone (p = 0.019 for trend) and 14.8 (4.44-49.2) for free testosterone (p < 0.001 for trend). These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA(1c) levels. CONCLUSIONS/INTERPRETATION In postmenopausal women, higher plasma levels of oestradiol and testosterone were strongly and prospectively related to increased risk of developing type 2 diabetes. These prospective data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes. ClinicalTrials.gov ID no.: NCT00000479.
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[The changing trend of serum total cholesterol in Beijing population aged 25 - 64 years during 1984 - 1999].
Sun, JY, Zhao, D, Wang, W, Liu, J, Li, Y, Liu, S, Jia, YN, Wu, ZS
Zhonghua nei ke za zhi. 2006;(12):980-4
Abstract
OBJECTIVE To describe the changing trend of serum total cholesterol (TC) in Beijing population aged 25 - 64 years old from 1984 to 1999 and to explore the distributions of hypercholesterolemia in different subgroups. METHODS From 1984 to 1999, five independent cardiovascular diseases (CVD) risk factors surveys with the same protocol were conducted in Beijing population aged 25 - 64 years. Stratified-random sampling was used. RESULTS (1) In the period from 1984 to 1999, the mean level of TC increased 1.058 mmol/L (25.1%) in Beijing population aged 25 - 64. The mean level of TC showed increase trends in different genders and age groups, with the greatest increase of 0.998 mmol/L (25.9%) being in the 25 - 34 age group. The mean level of TC was higher in urban subjects than in rural subjects, whereas the increment of TC level was higher in the rural subjects (32.8%) than in urban subjects (26.3%). (2) The prevalence of hypercholesterolemia increased from 6.1% in 1984 to 29.9% in 1999, with 23.8% of the increase during the 15 years. Among different subgroups, both the lowest prevalence of hypercholesterolemia and the greatest increase of hypercholesterolemia prevalence were shown in men aged 25 - 34 years old, with a 16.4 fold increase in 15 years. CONCLUSION The increase trends of mean TC level and hypercholesterolemia prevalence were observed in Beijing population during 1984 - 1999, especially in rural subjects and men aged 25 - 34 years old.
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Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study.
McKeown, NM, Meigs, JB, Liu, S, Wilson, PW, Jacques, PF
The American journal of clinical nutrition. 2002;(2):390-8
Abstract
BACKGROUND The influence of whole grains on cardiovascular disease risk may be mediated through multiple pathways, eg, a reduction in blood lipids and blood pressure, an enhancement of insulin sensitivity, and an improvement in blood glucose control. OBJECTIVE The objective was to examine the association between diets rich in whole- or refined-grain foods and several metabolic markers of disease risk in the Framingham Offspring Study cohort. DESIGN Whole-grain intake and metabolic risk markers were assessed in a cross-sectional study of 2941 subjects. RESULTS After adjustment for potential confounding factors, whole-grain intake was inversely associated with body mass index (: 26.9 in the lowest and 26.4 in the highest quintile of intake; P for trend = 0.06), waist-to-hip ratio (0.92 and 0.91, respectively; P for trend = 0.005), total cholesterol (5.20 and 5.09 mmol/L, respectively; P for trend = 0.06), LDL cholesterol (3.16 and 3.04 mmol/L, respectively; P for trend = 0.02), and fasting insulin (205 and 199 pmol/L, respectively; P for trend = 0.03). There were no significant trends in metabolic risk factor concentrations across quintile categories of refined-grain intake. The inverse association between whole-grain intake and fasting insulin was most striking among overweight participants. The association between whole-grain intake and fasting insulin was attenuated after adjustment for dietary fiber and magnesium. CONCLUSION Increased intakes of whole grains may reduce disease risk by means of favorable effects on metabolic risk factors.