Investigations into the link between vitamin D and cardiovascular disease (CVD) have yielded inconsistent results. The vitamin D metabolite ratio (VMR), the ratio of 24,25(OH)2D to 25(OH)D, has shown stronger associations with fracture and mortality than 25(OH)D alone. Our study assessed the association between the VMR and CVD outcomes. We evaluated a cohort of 6,313 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), without pre-existing CVD, over 15 years. Utilizing Cox regression, we examined the associations of both the VMR and 25-hydroxyvitamin D [25(OH)D] with various cardiovascular events. Over the study, 800 participants developed CVD, including conditions such as myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death, and stroke death. Heart failure (HF) was observed in 398 participants, and 413 experienced cardiovascular mortality. Models were adjusted for factors including demographics, lifestyle, clinical conditions and medications, biomarkers, and kidney function.
Participants averaged 62 years (range 44-84), with 53% females. The mean (SD) 25(OH)D level was 22.7 (11.0) ng/mL, and the mean VMR was 15.2 (5.0). In fully adjusted models, a two-fold increase in VMR was associated with a 24% reduction in incident CVD (HR: 0.76, 95% CI: 0.65-0.88). However, there was no association between the VMR and HF (0.98, 0.78-1.24), or cardiovascular mortality (0.96, 0.77-1.21). 25(OH)D was not significantly associated with any CVD outcome.
In a diverse cohort, VMR was significantly associated with reduced incident CVD, but not HF or cardiovascular mortality. The results suggest that VMR may provide greater insight into vitamin D metabolism, compared with 25(OH)D alone.