title: Vascular protective effects of statin-related increase in serum 25-hydroxyvitamin D among high-risk cardiac patients.
abstract: OBJECTIVE
  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 CD34KDR and CD133KDR 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 CD34KDR EPC (R = 0.13, P = 0.030) and CD133KDR 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 CD34KDR EPC [B = 0.006, 95% CI 0.002 to 0.009, P = 0.001, log, unit (×10/ml)] and CD133KDR EPC [B = 0.004, 95% CI 0.001 to 0.008, P = 0.016, log, unit (×10/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDivision of Cardiology, Queen Mary Hospital bSchool of Public Health, The University of Hong Kong cDivision of Neurology, Queen Mary Hospital, The University of Hong Kong dDepartment of Medicine, Tung Wah Hospital eDepartment of Clinical Biochemistry Unit, Queen Mary Hospital fDivision of Clinical Pharmacology, Queen Mary Hospital gResearch Center of Heart, Brain, Hormone and Healthy Ageing, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yap-Hang
authors.initials: YH
authors.lastname: Chan
authors.forename: Kui-Kai
authors.initials: KK
authors.lastname: Lau
authors.forename: Kai-Hang
authors.initials: KH
authors.lastname: Yiu
authors.forename: Sheung-Wai
authors.initials: SW
authors.lastname: Li
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Tai-Hing
authors.initials: TH
authors.lastname: Lam
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
authors.forename: Chung-Wah
authors.initials: CW
authors.lastname: Siu
authors.forename: Bernard M Y
authors.initials: BM
authors.lastname: Cheung
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020520:Brain Infarction / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D059168:Carotid Intima-Media Thickness; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D066026:Endothelial Progenitor Cells; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000097:blood*
chemical_list: D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014807:Vitamin D; C517652:hemoglobin A1c protein, human