Low 25-hydroxyvitamin D [25(OH)D] concentrations when participants entered the SATURN-HIV trial of rosuvastatin diminished the impact of the statin on low-density lipoprotein cholesterol (LDL-C) and common carotid artery intima media thickness (cIMT) in a 96-week analysis. The SATURN investigators suggest that "[v]itamin D supplementation may be warranted for deficient patients initiating statin therapy."
HIV infection is associated with heightened risk of atherosclerosis and myocardial infarction. Statin therapy prevents cardiovascular disease in the general population and has antiinflammatory and immunomodulatory activity that may benefit people with HIV. Statins increase vitamin D in the general population. Because 7-dehydrocholesterol is a direct precursor of both vitamin D and cholesterol, SATURN-HIV investigators hypothesized that statins affect both cholesterol and vitamin D metabolism.
To explore interactions between rosuvastatin, vitamin D, lipids and other factors, SATURN-HIV investigators conducted this 96-week analysis of trial participants. SATURN-HIV randomized 147 HIV-positive adults with antiretroviral-controlled viremia and LDL-C ≤130 mg/dL to 10 mg of rosuvastatin daily or placebo.
Related: What Do Vitamin D Levels at HIV Treatment Initiation Have to Do With CD4 Cell Count Recovery?
Demographics and baseline clinical characteristics did not differ significantly between the 72 participants randomized to rosuvastatin and the 75 randomized to placebo. Three-quarters of participants (78%) were men, 68% were black, 76% had a viral load below 48 copies/mL (range 20 to 600 copies/mL) and age averaged 45.4 years. Through 96 weeks, rosuvastatin lowered LDL-C by an average of 21 mg/dL and slowed cIMT thickening.
Baseline 25(OH)D levels did not differ significantly between study arms. Overall, 23% of participants were vitamin D insufficient (<30 but ≥20 ng/mL), 53% deficient (<20 but ≥10 ng/mL) and 14% severely deficient (<10 ng/mL). Through 96 weeks of SATURN-HIV, 25(OH)D levels did not change significantly in the rosuvastatin group or the placebo group.
Participants with baseline 25(OH)D ≥20 ng/mL had a greater drop in LDL-C with rosuvastatin versus placebo at 96 weeks than did participants who started with lower 25(OH)D (P = .02 for interaction). Similarly, participants who started the trial with 25(OH)D ≥20 ng/mL had a more favorable change in cIMT with rosuvastatin versus placebo at 96 weeks than did people who started the trial with 25(OH)D <20 ng/mL (P < .01 for interaction).
Starting rosuvastatin versus placebo with 25(OH)D ≥20 ng/mL rather than <20 ng/mL also had positive impacts on levels of the vascular inflammation marker lipoprotein-associated phospholipase A2 (P = .02) and on proportion of monocytes expressing tissue factor (CD14dimCD16+TF+) (P = .04). Baseline 25(OH)D levels had no significant impact on other markers of inflammation or monocyte activation, on activated CD4 or CD8 cells or on insulin resistance (HOMA-IR).
The researchers conclude that vitamin D levels modify the impact of rosuvastatin on important outcomes including lowering LDL-C and slowing cIMT progression. Because vitamin D levels are often deficient in people with HIV, the SATURN-HIV team calls for further study to see whether vitamin D supplementation improves outcomes with statin therapy.