Low vitamin D associated with early sign of cardiovascular disease in patients with HIV

Low levels of vitamin D are associated with an important early-warning sign of cardiovascular disease in patients with HIV, US investigators report in the April 1^st edition of Clinical Infectious Diseases.

The research showed a significant relationship between vitamin D insufficiency and thickening of the carotid artery.

“To our knowledge, this study is the first to report the association between vitamin D status and atherosclerotic vascular disease, measured by cIMT [carotid intima-media thickness], in HIV-infected persons,” comment the authors.

A number of studies have already shown that large numbers of HIV-positive patients have low levels of vitamin D. In the general population, vitamin D insufficiency has been associated with cardiovascular disease.

Investigators from the University of California-San Francisco Study of the Consequences of the Protease Inhibitor Era cohort therefore sought to establish the prevalence and risk factors for low vitamin D levels in patients with HIV, and the relationship between vitamin D deficiency and sub-clinical atherosclerosis (hardening of the arteries), measured by cIMT.

Their cross-sectional, or “snap-shot” study involved 139 patients, whose average age was 45.  The majority (84%) were male, 54% were white and 32% were black. Three-quarters of patients were taking antiretroviral therapy and 71% of these individuals had a viral load below 1000 copies/ml. The median CD4 cell count was 336 cells/mm³.

Between a fifth and a third of patients had traditional risk factors for cardiovascular disease such as smoking, high blood pressure, or elevated cholesterol.

Over half (52%) of patients had vitamin D deficiency (below 30 ng/ml). Factors associated with insufficient levels of the vitamin included black race (relative risk [RR] = 2.62; 95% CI, 1.80-3.82) and a higher body mass index, or BMI (RR = 1.25 per BMI increase of 5; 95% CI, 1.03-1.51). Both of these risk factors have been observed in other research.

Taking vitamin D supplements reduced the risk of insufficiency by almost a third (RR = 0.70; 95% CI, 0.52-0.95).

During the first six months of HIV therapy, patients treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI) were 2.5 times more likely than patients taking a protease inhibitor to have low levels of vitamin D. The investigators call for this finding “to be re-evaluated in other cohorts with longer NNRTI exposure.”

Further analysis showed that patients with vitamin D deficiency were more likely to have increased cIMT.

The relationship between vitamin D insufficiency and increased cIMT remained significant (p = 0.021) even after adjustment for traditional risk factors for hardening of the arteries, HIV-related factors such as viral load and duration of antiretroviral therapy, and lipid levels.

“We found that HIV-infected persons with vitamin D insufficiency had a mean cIMT that was 0.13 mm greater than the mean cIMT for those with normal vitamin D levels, even after extensive risk adjustment,” comment the authors.

They note that increased cIMT is “a strong predictor of future clinical events.” In the general population, an increase of 0.13 mm in cIMT is associated with an 18% increase in the relative risk of stroke and 15% increase in the relative risk of heart attack.

“We found that vitamin D insufficiency was common, and it was significantly associated with cIMT independent of traditional and HIV-related risk factors,” write the authors.

But they emphasise that “vitamin D insufficiency is a readily modifiable risk factor” which can be diagnosed using simple blood tests and treated with high-dose supplements.

The authors conclude that their findings “provide the basis for future studies that prospectively examine the risk of clinical cardiovascular disease associated with vitamin D status over time and the effects of high-dose vitamin D supplementation on cIMT.”