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Cardiovascular Risk Factors With HIV Infection: A Long and Motley List

Summer 2013

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Vitamin D and Hormonal Contraceptive Conundrums

Research links low vitamin D to cardiovascular disease in the general population, but so far studies of vitamin D and cardiovascular risk in people with HIV are small, rely on surrogate markers, and yield mixed results. All of these studies weigh vitamin D in relation to cIMT, a marker of atherosclerosis, and some examine other cardiovascular proxies.

The largest heart-related vitamin D study involved 139 HIV-positive adults in a San Francisco group, all of whom had vitamin D measured as 25-hydroxyvitamin D [25(OH)D], the standard way to measure this vitamin.110 The study group averaged 45 years in age, 84% were men, 54% white, and 32% black. Half of these people (52%) had vitamin D insufficiency, defined as a level at or below 30 ng/mL. A statistical model adjusted for classic heart risk factors and HIV variables determined that average cIMT increased (worsened) significantly from about 0.8 mm in people with normal vitamin D (above 30 ng/mL) to about 1.0 mm in those with deficient vitamin D (15 to 30 ng/mL) and to about 1.1 mm in those with vitamin D below 15 ng/mL (P = 0.021). cIMT was an average 0.13 mm greater in people with 25(OH)D below 30 ng/mL than in people with normal 25(OH)D. The authors observe that research in the general population links every 0.10-mm greater cIMT to a 15% higher MI risk and an 18% higher stroke risk. The study is limited by its cross-sectional nature and the inability to account for the possible impact of individual antiretrovirals. Other work, for example, links efavirenz to low vitamin D.

In three smaller cross-sectional analyses of vitamin D and cIMT, one study tied lower 25(OH)D to greater cIMT but two studies did not. The study that found a link involved 56 adults with HIV.111 Median age stood at 49, and most participants were men (85%) and white (52%). Although this analysis did not tie 25(OH)D to inflammatory or endothelial markers, lower 25(OH)D conferred a 10 times higher risk of common carotid IMT above the median for the study group (P < 0.01). The association was not significant for internal carotid IMT.

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An analysis in the Hawaii Aging With HIV-Cardiovascular Cohort Study involved 100 people with a median age of 52, most of them male (86%) and white (60%).112 Analysis of 50 cIMT measurements found a significant correlation between 25(OH)D and brachial artery flow-mediated dilation but not cIMT (r = -0.05, P = 0.76). A third cross-sectional study involved 30 HIV-positive children and young adults with a median age of 11, three quarters of them black and 37% male.113 These researchers found no significant correlation between 25(OH)D and cIMT, inflammatory markers, or lipids. But 25(OH)D correlated inversely with insulin resistance -- the lower the 25(OH)D, the greater the insulin resistance.

A recent review of randomized trials, meta-analyses, and other evidence in the general population concluded that adequate vitamin D may protect against cardiovascular disease -- as well as musculoskeletal maladies, infectious diseases, autoimmune diseases, type 1 and type 2 diabetes, several cancers, neurocognitive dysfunction, and mental illness.114 This mega-analysis also tied low vitamin D to all-cause mortality. With such a catalog of benefits-in-waiting, checking HIV-positive people for vitamin D and supplementing those deficient may seem a sensible hedge. But randomized trials in the general population -- and in people with HIV -- show that swallowing high doses of vitamin D3 does not ipso facto translate into sounder health. A double-blind, placebo-controlled trial of 45 HIV-positive adults who took 4000 IU of vitamin D daily or placebo for 12 weeks found that supplementation modestly improved vitamin D status and non-HDL cholesterol but did not change endothelial function and worsened insulin resistance.115

A Women's Interagency HIV Study of 885 HIV-positive and 408 HIV-negative women linked progestin-only hormonal contraceptives to lower HDL cholesterol (-3 mg/dL, 95% CI -5 to -1 with HIV, -6 mg/dL, -9 to -3 without HIV) and greater insulin resistance (HOMA-IR +0.86, 95% CI 0.51 to 1.22 with HIV, and +0.56, 95% CI 0.12 to 1.01 without HIV).116 Estrogen/progestin hormonal contraceptives were associated with higher HDL. The WIHS investigators suggested that combined hormonal contraceptives may be preferred for women with HIV, but they cautioned clinicians to check for interactions with antiretrovirals.

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This article was provided by The Center for AIDS. It is a part of the publication Research Initiative/Treatment Action!. Visit CFA's website to find out more about their activities and publications.
 

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