Vitamin D heritability and effect of pregnancy status in Vervet monkeys ( Chlorocebus aethiops sabaeus ) under conditions of modest and high dietary supplementation: Vitamin D, Pregnancy, Diet Interaction in Vervets

The two objectives of the current study were to: 1) investigate the genetic contributions to variations in serum vitamin D concentrations under two dietary conditions (a standard monkey biscuit diet vs. a diet designed to model typical American consumption) and; 2) explore the interaction of vitamin D with pregnancy status using a cohort of pedigreed female vervet/African green monkeys

A systematic review and meta-regression analysis to examine the ‘timing hypothesis’ of hormone replacement therapy on mortality, coronary heart disease, and stroke

Background: The ‘Timing Hypothesis’ states that the benefits and harms of hormone replacement therapy (HRT) are related to the proximity with which it is begun following the onset of menopause. The primary aim of this analysis was to test for heterogeneity of treatment effect for HRT using Chi2 and I2 tests for younger versus older initiators of HRT. The secondary aim was to perform a meta-regression with mean age at trial baseline as the covariate for various outcomes. Methods: Younger initiation trials were defined as those with mean age of participants 60 years. The primary endpoints included all-cause mortality, cardiac mortality, coronary heart disease (CHD) events (a composite of cardiac mortality and nonfatal myocardial (MI)), and a composite of stroke, transient ischemic attack (TIA) and systemic embolism. Results: Thirty-one RCTs were identified comparing HRT users to nonusers (n = 40,521). There was significant heterogeneity of treatment effect between younger versus older HRT initiators for all-cause mortality (Chi2 = 9.74, p = 0.002, I2 = 89.7%), cardiac mortality (Chi2 = 4.04, p = 0.04, I2 = 75.2%), and CHD events (Chi2 = 3.06, p = 0.08, I2 = 67.3%). Both groups experienced an increase in stroke, TIA and systemic embolism (1112/18,774 in the HRT group versus 734/18,070 in the control group; OR = 1.52; 95% confidence interval (CI) = 1.38–1.67). When performing the meta-regression, as age increased the treatment effect of HRT was increased for stroke, TIA and systemic embolism (point estimate 0.006 with a standard error of 0.002) (p = 0.0003). Conclusion: Younger initiation of HRT may be effective in reducing death and cardiac events. However, younger HRT initiators remained at an increased risk of stroke, TIA and systemic embolism and this risk increased as average age increased. Younger menopausal women using HRT to treat vasomotor symptoms do not appear to be at an increased risk of dying or experiencing CHD events

The association between incidentally found breast arterial calcification on routine screening mammography and the development of coronary artery disease and stroke: results of a 10-year prospective study.

OBJECTIVE: The objective of this study is to assess whether the presence of breast arterial calcifications (BACs) found on routine mammography is prospectively associated with the development of cardiovascular disease (CVD) events after 10 years of follow-up. METHODS: Women presenting for screening mammography were enrolled in this prospective cohort. Baseline data were collected including history of CVD and CVD risk factors. Mammograms were assessed for the presence or absence of BAC. Participants completed questionnaires 10 years after baseline that assessed the development of CVD (coronary artery disease [CAD] and stroke) and CVD risk factors. RESULTS: Of the 1,995 participants who enrolled at baseline, complete 10-year follow-up data were available for 1,039; of those, 114 (11.0%) were BAC-positive and 925 (89.0%) were BAC-negative at baseline. After controlling for age, BAC-positive women were more likely to develop CAD (odds ratio, 3.14; 95% confidence interval, 1.86-5.27; P \u3c 0.001) compared with BAC-negative women after 10 years of follow-up. After controlling for age, BAC-positive women were more likely to have had a stroke (odds ratio, 5.10; 95% CI, 1.82-14.30) compared with BAC-negative women after 10 years. CONCLUSIONS: The presence of BAC on routine screening mammography was associated with a significantly increased risk of developing CAD and stroke after 10 years of follow-up. Additional large prospective, population-based studies are needed to confirm BAC as a predictor of future CVD events and its utility in stratifying a woman\u27s risk of CVD

Vitamin D and conjugated equine estrogen: the association with coronary artery atherosclerosis in cynomolgus monkeys.

OBJECTIVE: To analyze vitamin D3 plasma concentrations among monkeys randomized to oral conjugated equine estrogen (CEE) versus control and the association with coronary artery atherosclerosis (CAA). METHODS: Surgically postmenopausal monkeys (N = 50) were fed an atherogenic diet containing a woman\u27s equivalent of 1000 IU/day of vitamin D3. The monkeys were randomized at baseline to receive CEE (equivalent of 0.45 mg/d, n = 25) or placebo (n = 25). 25-hydroxyvitamin D3 (25OHD3) was measured at baseline and 20 months later. At 20 months, CAA evidence of coronary artery remodeling, and American Heart Association (AHA) severity scores were assessed. RESULTS: The percent change in 25OHD3 concentrations from baseline to 20 months postrandomization was inversely correlated with plaque area of the right coronary artery (P = 0.048), left circumflex artery (P = 0.039), left anterior descending artery (P = 0.017), and AHA severity score (AHA LADmax) (P = 0.016). Those with increased 25OHD3 concentrations who were taking CEE also had significantly lower AHA scores compared with those who were not taking CEE and did not have an increase in 25OHD3 (P = 0.01). CONCLUSIONS: Monkeys with increases in 25OHD3 concentrations had significantly less severe CAA. Those with increases in 25OHD3 with CEE were associated with significantly decreased AHA lesion scores, decreased plaque, and greater coronary artery remodeling. If these findings are present in women, achieving higher 25OHD3 concentrations (or being a vitamin D supplementation responder ) may be associated with cardioprotection, and further studies to evaluate a synergistic effect with CEE and vitamin D on cardiovascular health are needed

Vitamin D deficiency and cardiovascular disease in postmenopausal women: contributions from human and nonhuman primate studies.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death among American postmenopausal women and all adult Americans. The medical community and the lay community have recently become intrigued with vitamin D and its potential role in reducing the risk of CVD. Research findings from multiple retrospective studies, few prospective studies, and recent nonhuman primate studies have been inconsistent and conflicting. The objective of this study is to review what is known about the topic, what questions remain unanswered, and where the research community should be focusing. METHODS: A literature search was conducted through PubMed and Google Scholar up to August 1, 2014. One hundred six articles, including 18 double-blind, placebo-controlled, randomized clinical trials, relevant to the study topic were identified. All studies were stratified based on study design and primary outcome. The effects of vitamin D on CVD were reviewed and summarized. RESULTS: Although there is an abundance of observational studies suggesting an association with CVD protection, the most well-controlled randomized human trial data available show no benefit of vitamin D on CVD. However, highly controlled nonhuman primate studies indicate a beneficial relationship. CONCLUSIONS: Well-designed research, with CVD as primary outcome, is needed to help bridge the gap in our knowledge on this topic. In the meantime, caution should be applied to avoid overdiagnosis and overtreatment of vitamin D deficiency

A Prospective Analysis of the Association Between Cardiovascular Disease and Depression in Middle-Aged Women.

OBJECTIVE: Experimental and clinical data demonstrate a close association between depression and coronary heart disease (CHD). Because no simple depression instrument for use by general practitioners has been shown to predict CHD, the objective of this study was to evaluate whether such a questionnaire could predict CHD. METHODS: The prevalence of CHD and CHD risk factors was assessed in women with depression, measured by a validated three-question depression screening instrument. Among 1,919 participants in the breast arterial calcification and CHD 5-year prospective study, 1,454 women (75.8%) completed a baseline depression inventory. RESULTS: Among the 1,454 women, 72.2% were postmenopausal, and the mean (SD) age at the conclusion of a 5-year prospective study was 61.3 (12.1) years. Among the women with no CHD risk factors at baseline and with one or less positive depression responses compared with those with two or more, 1.6% versus 3.8%, respectively, had at least one CHD risk factor (P = 0.004) by the 5th year of the study. In addition, 2.3% versus 6.0%, respectively, developed CHD (P = 0.005) by the 5th year of the study. Among all women with no positive depression responses compared with those with any positive depression responses, 2.1% versus 5.6%, respectively, had developed CHD by the 5th year of the study (P = 0.002). Finally, more positive depression responses were associated with a greater prevalence of CHD. CONCLUSIONS: In this prospective study, depression-detected by a validated three-item questionnaire-was able to predict those women more likely to develop CHD