To investigate the protective effects of statin-related increase in serum 25-hydroxyvitamin D [25(OH)D] on vascular function among high-risk cardiovascular patients.Methods
We studied 443 high-risk cardiovascular patients (coronary disease 83%, ischemic stroke 21%; mean age 68 ± 10 years; men 77%). Serum 25(OH)D was measured by ELISA assay. Carotid intima-media thickness (IMT) and brachial flow-mediated dilatation were measured by high-resolution vascular ultrasound. Circulating CD34+KDR+ and CD133+KDR+ endothelial progenitor cells (EPCs) were measured by flow cytometry.Results
Three hundred and twenty-nine (74%) patients were statin users. Serum 25(OH)D was higher among statin users than nonusers (30.2 ± 12.8 versus 26.8 ± 8.5 ng/ml; P = 0.009), which remained significant after multivariable adjustment [B = +3.8, 95% confidence interval (CI) 0.6 to 6.9, P = 0.019). Serum 25(OH)D was associated with reduced carotid IMT (R = −0.11, P = 0.026), and increased circulating CD34+KDR+ EPC (R = 0.13, P = 0.030) and CD133+KDR+ EPC (R = 0.15, P = 0.012). Adjusted for potential confounders, serum 25(OH)D remained independently associated with reduced carotid IMT (B = −0.003, 95% CI −0.005 to 0.000, P = 0.017), and increased circulating CD34+KDR+ EPC [B = 0.006, 95% CI 0.002 to 0.009, P = 0.001, log, unit (×10−3/ml)] and CD133+KDR+ EPC [B = 0.004, 95% CI 0.001 to 0.008, P = 0.016, log, unit (×10−3/ml)]. Interaction test showed no multiplicative effect between statins and serum 25(OH)D on carotid IMT or EPCs. Serum 25(OH)D was negatively associated with HbA1c (B = −0.010, 95% CI −0.019 to −0.001, P = 0.035). There was no significant association between serum 25(OH)D and brachial flow-mediated dilatation (R = −0.045, P = 0.344).Conclusion
In patients with cardiovascular disease, statin use is associated with increased serum 25(OH)D, which is independently associated with reduced carotid atherosclerotic burden, increased circulating EPCs, and improved glycemic control. These may partially explain the pleotrophic effects of statins.