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Vascular protective effects of statin-related increase in serum 25-hydroxyvitamin D among high-risk cardiac patients
Yap-Hang Chan1, Kui-Kai Lau, Kai-Hang Yiu
1aDivision 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.
Insights
Statin use in cardiovascular patients increases serum 25-hydroxyvitamin D (25(OH)D), which is linked to reduced atherosclerosis, more endothelial progenitor cells (EPCs), and better glycemic control, potentially explaining statins' broader effects.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- Statins are widely used for cardiovascular disease prevention.
- Serum 25-hydroxyvitamin D (25(OH)D) levels may influence vascular health.
- The relationship between statin-induced 25(OH)D changes and vascular function is not fully understood.
Purpose of the Study:
- To investigate the protective effects of statin-associated increases in serum 25(OH)D on vascular function in high-risk cardiovascular patients.
- To explore the association between serum 25(OH)D levels and markers of atherosclerosis and endothelial progenitor cells (EPCs).
Main Methods:
- A cohort of 443 high-risk cardiovascular patients was studied.
- Serum 25(OH)D, carotid intima-media thickness (IMT), brachial flow-mediated dilatation, and circulating EPCs (CD34KDR, CD133KDR) were measured.
- Statistical analyses, including multivariable adjustments, were performed to assess associations.
Main Results:
- Statin users had significantly higher serum 25(OH)D levels compared to nonusers.
- Serum 25(OH)D was independently associated with reduced carotid IMT, increased circulating EPCs (CD34KDR and CD133KDR), and improved glycemic control (lower HbA1c).
- No significant association was found between serum 25(OH)D and brachial flow-mediated dilatation.
Conclusions:
- Statin use is associated with increased serum 25(OH)D in cardiovascular patients.
- Elevated serum 25(OH)D is independently linked to reduced atherosclerotic burden, enhanced EPCs, and better glycemic control.
- These findings suggest that increased 25(OH)D may contribute to the pleiotropic effects of statins.
Aim:
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).
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.
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