A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk

Treatment of Obstructive Sleep Apnea in Young and Middle-Aged Adults: Effects of Positive Airway Pressure and Compliance on Arterial Stiffness, Endothelial Function, and Cardiac Hemodynamics.

BackgroundThe cardiovascular effects of positive airway pressure (PAP) therapy in obstructive sleep apnea (OSA) patients are not clear because of confounding by comorbid conditions.Methods and resultsProspective interventional study of PAP therapy and withdrawal. Apnea Hypopnea Index (AHI; events/hour of sleep) was determined from polysomnography. Central aortic blood pressures (BPs), Aortic Augmentation Index (AAIx), and central (PWVc-f) and peripheral pulse wave (PWVc-r) velocities were determined by applanation tonometry. Echocardiography and brachial artery reactivity testing were performed at baseline, after 4 and 12 weeks of PAP therapy, and 1 week after PAP withdrawal. The 84 participants were mean (SD) 41.1 (7.6) years old and had 39.8 (24.5) AHI events/hour. After 4 weeks post-PAP initiation and sustained after 12 weeks, subjects experienced decreases in central systolic BP (P=0.008), diastolic BP, mean BP, AAIx, and PWVc-r, and brachial artery dilation (all P&lt;0.001), as well as improvements in left ventricular diastolic function and systemic and pulmonary vascular resistance. In adjusted models, PAP use (hours/night) predicted reductions in diastolic BP (β=-0.65 [SE, 0.32] mm Hg/hour; P=0.045), AAIx (β=-0.53 [0.27] %/hour; P=0.049) and PWVc-r (β=-0.13 [0.05] m·s(-1)/hour; P=0.007), and improved brachial artery flow-mediated dilation (β=0.31 [0.14] %/hour use; P=0.015). After 1 week of PAP withdrawal, brachial diameter, diastolic BP, mean BP, AAIx, and heart rate increased (P≤0.05).ConclusionsPAP therapy reduces arterial tone and improves endothelial and diastolic function in young to middle-aged adults. This positive effect is observed after 4 weeks and depends on hours of use, but reverts quickly with PAP withdrawal.Clinical trial registrationURL: https://clinicaltrials.gov/. Unique identifier: NCT01317329

Effects of HIV Infection on Arterial Endothelial Function

ObjectiveTo determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV- controls. Approach and Results: We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV- controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV- serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV- controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=-1.59% [95% CI, -2.58% to -0.60%], P=0.002), even after covariate adjustment (β=-1.36% [95% CI, -2.46% to -0.47%], P=0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=-1.90% [95% CI, -2.58% to -1.21%], P&lt;0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD.ConclusionsThe significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease

Carotid Artery Longitudinal Displacement, Cardiovascular Disease and Risk Factors: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND:Associations between carotid artery longitudinal displacement, cardiovascular disease risk factors, and events were evaluated in a large, multi-ethnic cohort. MATERIALS AND METHODS:A novel, reproducible protocol was developed for measuring right common carotid artery longitudinal displacement using ultrasound speckle-tracking. Total longitudinal displacement was measured in 389 randomly selected participants from the Multi-Ethnic Study of Atherosclerosis that were free of cardiovascular disease at baseline. Univariate analyses and Pearson Correlations were used to define relationships between longitudinal displacement with traditional cardiovascular risk factors and traditional measures of arterial stiffness. Hazard ratios of longitudinal displacement for cardiovascular disease and coronary heart disease events were compared using Cox proportional hazards models. RESULTS:Participants were a mean (standard deviation) 59.0 (8.7) years old, 48% female, 39% White, 26% Black, 22% Hispanic, and 14% Chinese. They had 19 (4.9%) cardiovascular disease and 14 (3.6%) coronary heart disease events over a mean 9.5 years of follow-up. Less longitudinal displacement was associated with Chinese (β = -0.11, p = 0.02) compared to White race/ethnicity and greater longitudinal displacement was associated with higher carotid intima-media thickness (β = 0.26, p = 0.004). Longitudinal displacement was not associated with other cardiovascular disease risk factors or markers of arterial stiffness. After adjustment for age and sex, and heart rate, Chinese race/ethnicity (β = -0.10, p = 0.04) and carotid intima-media thickness (β = 0.30 p = 0.003) were associated independently with longitudinal displacement. Longitudinal displacement predicted coronary heart disease (Hazard ratio [HR] 3.3, 95% Confidence intervals [CI] 0.96-11.14, p = 0.06) and cardiovascular disease (HR 2.1, 95% CI 0.6-7.3, p = 0.23) events. CONCLUSIONS:Less longitudinal displacement is associated with Chinese ethnicity and greater carotid artery longitudinal displacement is associated with thicker intima-media thickness. Longitudinal displacement may predict adverse coronary heart disease and cardiovascular disease events