Adults with a serum 25-hydroxyvitamin D level of 55 nmol/L or lower are at increased risk for all-cause mortality, cardiovascular death and heart failure, according to a 20-year retrospective analysis of Australian patient data.
To date, randomized controlled trials of vitamin D supplementation have not shown a protective effect on CV events or death, Kun Zhu, PhD, of the department of endocrinology and diabetes at Sir Charles Gairdner Hospital in Newlands, Western Australia, and colleagues wrote in the study background. However, many trials have limitations that hamper interpretation, including a study design aimed at detecting musculoskeletal outcomes rather than CVD outcomes and heterogeneity in the supplementation dose and interval.
“It is also possible that vitamin D is more relevant to particular types of CVD, such as heart failure,” the researchers wrote. “The ‘dose-response’ relationship between serum 25-(OH)D level and CVD risk is also not well-characterized and threshold levels for risk uncertain.”
Zhu and colleagues analyzed data from 3,946 adults from the 1994-1995 Busselton Health Survey cohort, a population in the coastal area of Western Australia that has been regularly surveyed since 1966 (mean age, 52 years; 43% men). Participants completed health and lifestyle questionnaires and provided fasting blood samples to measure serum 25-(OH)D. Researchers linked patient data to data from the Hospital Morbidity Data Collection and Mortality Register to assess CV hospitalizations and deaths between January 1980 and June 2014. A history of CVD at baseline was based on any CVD hospital admission during the 15 years before the survey. Researchers analyzed time to death from any cause, time to death from CVD, time to first fatal or nonfatal CV event and time to first heart failure event. Researchers used Cox proportional hazard regression modeling to assess associations between vitamin D level and CV outcomes. Vitamin D level was examined both as a continuous variable and in categories corresponding to lower ( 50 nmol/L), medium (between 50 nmol/L and 75 nmol/L) and higher ( 75 nmol/L) levels, based on U.S. Institute of Medicine and Endocrine Society guidelines.
At baseline, 18% had a history of CVD. Mean vitamin D concentration for the cohort was 60.6 nmol/L; median concentration was 58.8 nmol/L. Fifty-four present of the cohort had a serum 25-(OH)D level between 50 nmol/L and 75 nmol/L, 28% had a serum 25-(OH)D level of 50 nmol/L or less, and 18% had a level of at least 75 nmol/L.
During 20 years of follow-up (excluding the first 2 years), 889 participants died, including 363 from CVD, and 944 experienced a CV event, including 242 with heart failure.
Researchers observed an inverse relationship between baseline vitamin D levels and risk for all-cause mortality, with a 17% reduction in risk per standard deviation (SD) increment in baseline vitamin D level (HR = 0.83; 95% CI, 0.77-0.9), after controlling for Framingham risk score variables. A similar relationship was observed for CV mortality, with an HR of 0.84 per SD increment of baseline vitamin D level (95% CI, 0.74-0.96), and for heart failure, with an HR of 0.82 per SD increment of baseline vitamin D level (95% CI, 0.7-0.95). Researchers did not observe an association between baseline vitamin D level (either as a continuous or categorical variable) and the risk for all CV events among either the full cohort or those without baseline CVD.
In restricted cubic spline regression models, participants with vitamin D level of 65 nmol/L or less had a higher risk for all-cause mortality vs. those with vitamin D level of 80 nmol/L, whereas those with a level of 55 nmol/L or less had a higher risk for CV death and heart failure vs. those who had a level of 80 nmol/L. Results persisted when restricted to those without CVD at baseline (n = 3,220), apart from CV death.
“Our findings suggest that maintaining serum 25-(OH)D level at least above 55 nmol/L could be associated with lower risk for mortality and heart failure in adults,” Zhu told Endocrine Today. “Large-scale, randomized controlled trials designed to test the benefit of vitamin D supplementation on mortality and CV outcomes in the general population are needed to demine the optimal level of serum 25-(OH)D for CV health.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.