Serum 25-hydroxyvitamin D concentration in subclinical carotid atherosclerosis.

OBJECTIVE: Vitamin D deficiency has been implicated in cardiovascular disease and is associated with multiple cardiovascular risk factors. We investigated the serum 25-hydroxyvitamin D (25(OH)D) concentration in relation to latitude, baseline carotid intima-media thickness (IMT), and IMT progression, the carotid IMT measures being surrogate markers of subclinical atherosclerosis and cardiovascular disease risk. APPROACH AND RESULTS: Serum 25(OH)D concentration was related to high-resolution carotid IMT measures in 3430 middle-aged and elderly subjects with high cardiovascular risk but no prevalent disease, who were recruited at 7 centers in Finland, Sweden, The Netherlands, France, and Italy. Participants underwent carotid ultrasound examination at baseline and at months 15 and 30 after entry into the study, whereas blood samples, clinical data, and information about lifestyle were collected at baseline. Serum 25(OH)D levels were positively associated with latitude (Jonckheere-Terpstra χ=166.643; P<0.001) and, as previously reported, associated with a range of cardiovascular risk factors. There were no independent relationships between 25(OH)D and segment-specific or composite IMT measures in the entire cohort. In analyses stratified by sex, diabetes mellitus, and statin treatment, weak associations with some baseline and progression measures of carotid IMT were observed in males, diabetics, and nonstatin-treated individuals. CONCLUSIONS: Levels of 25(OH)D differed across Europe, were highest in the North, showed multiple associations with established and emerging cardiovascular risk factors but were not consistently, independently related to measures of carotid IMT. This argues against a protective role of vitamin D against subclinical atherosclerosis in high-risk individuals.

Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular risk factors and risk of myocardial infarction before the age of 60 years.

OBJECTIVE: We examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to established and emerging cardiovascular risk factors and risk of myocardial infarction (MI) in a population-based case-control study of MI before the age of 60 years. METHODS: A total of 387 survivors of a first MI and 387 sex- and age-matched controls were included. Fasting blood samples drawn three months after the MI in cases and at the same time in the matched controls were used for biochemical analyses. RESULTS: Serum concentrations of 25(OH)D, adjusted for seasonal variation, were lower in cases than controls (55.0 (40.0-71.0) nmol/L vs 60.5 (47.0-75.0) nmol/L; median (interquartile range); standardized odds ratio (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69-0.93); p = 0.003). The 25(OH)D association with MI disappeared after adjustment for established and emerging risk factors (OR: 1.01 (0.82-1.25)). Current smoking and plasma levels of proinsulin and PAI-1 activity were independently associated with 25(OH)D in controls, whereas waist circumference, plasma triglycerides, proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no systematic differences between sampling times. CONCLUSION: Vitamin D insufficiency, which is associated with a multitude of metabolic, procoagulant and inflammatory perturbations, is not independently related to premature MI. This suggests that vitamin D insufficiency either constitutes an epiphenomenon or increases the risk of MI by promoting established risk factor mechanisms that predispose to atherothrombosis.