Vitamin D and Cardiovascular Health

Abstract and Commentary

By David Kiefer, MD, Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; Adjunct Faculty, Bastyr University, Seattle. Dr. Kiefer reports no financial relationships relevant to this field of study.

Synopsis: Both vitamin D deficiency and supplementation with vitamin D are significantly associated with several cardiovascular outcomes, including mortality.

Source: Vacek JL, et al. Vitamin D deficiency and supplementation and relation to cardiovascular health. Am J Cardiology 2012;109:359-363.

To evaluate the relationship between cardiovascular morbidity and mortality, and overall survival, and both vitamin D deficiency and supplementation, the researchers of this analysis set up an observational retrospective study on a cohort of 10,899 people. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured and analyzed both as a continuous variable, and as either deficient (< 30 ng/mL) or normal (≥ 30 ng/mL). Patient diagnoses were determined from the problem lists as documented in the electronic medical record, and vitamin D supplementation was established from active prescriptions or patient self-reporting. Serum 25(OH)D and vitamin D supplementation were then compared to a variety of health outcomes, including coronary artery disease, atrial fibrillation, diabetes mellitus, cardiomyopathy, hypertension, and death, over 5 years, 8 months.

The mean age of the cohort was 58 years, 71% were women, and 70.3% were deficient (mean serum 25(OH)D was 24.1 ng/mL). According to the researchers, not all vitamin D doses were reported, but those that were reported ranged from 1000 IU daily to 50,000 IU biweekly, resulting in a mean vitamin D intake of 2254 IU per day ± 316 IU.

When serum 25(OH)D was analyzed as a dichotomous variable, deficiency was significantly associated with an increased risk of all of the above diagnoses except for atrial fibrillation, which actually had a decreased risk (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.693-0.984). Vitamin D supplementation improved overall survival (OR 0.44; CI 0.335-0.589) but only in people who were vitamin D deficient. Interestingly, the statistical significance of the association between vitamin D deficiency and risk of death disappeared in those people receiving vitamin D supplementation.

Alternatively, when serum 25(OH)D was analyzed as a continuous variable, it was negatively associated with body mass index and low-density lipoprotein, and positively associated with high-density lipoprotein.

Commentary

The results of this observational study dovetail with many prior research findings documenting effects of vitamin D deficiency and supplementation on cardiovascular conditions and risk factors1,2 (see the article's introduction for references to some of this important research). The authors expand on existing vitamin D mortality data by showing a benefit from vitamin D supplementation on overall mortality, but only for people who are vitamin D deficient. This, regardless of possible criticisms of this study (see below), is absolutely eye-opening and critical to patient care. Our patients may achieve better survival rates simply by supplementing with vitamin D if they are deficient — a very important finding. As the authors discuss, omnipresent vitamin D receptors make these global findings no surprise. Undoubtedly, research will continue to find connections between vitamin D and many diverse organ systems.

There are many details to criticize in any retrospective, observational study. Clearly, ultimate clinical recommendations need to be based on prospective, randomized controlled trials, rather than simply on proven associations; this fact is mentioned by other recent research reviews on the topic of vitamin D, some of which are more optimistic than others over the gap in current knowledge and clinical applicability.3,4 Research is beginning in this arena,5 so it will be exciting to see the results of vitamin D intervention trials.

It is interesting to muse over the use of the definition of vitamin D deficiency here (serum 25(OH)D < 30 ng/mL), considered by many clinicians to be on the low side of what is necessary to avoid various disease states. Perhaps the associations seen would have been stronger with a dichotomous analysis with deficiency defined as 25(OH)D less than 40 or 50 ng/mL. In addition, the method of calculating vitamin D supplementation (from patient reporting or electronic records) seems fraught with important problems. It is well documented that patients underreport their dietary supplement use, likely skewing the data in this study in ways that might be hard to predict. Also, the researchers document that the vitamin D dose for some patients was unlisted, but we don't know how many, so the average intake listed is really just a gross estimate. And the type of vitamin D (D2 or D3) used is not clarified, which, depending on the source or expert consulted, may make a difference.

References

1. van Ballegooijen AJ, et al. Vitamin D in relation to myocardial structure and function after eight years of follow-up: The Hoorn Study. Ann Nutr Metab 2012;60: 69-77.

2. Muscogiuri G, et al. Can vitamin D deficiency cause diabetes and cardiovascular diseases? Present evidence and future perspectives. Nutr Metab Cardiovasc Dis 2012;22:81-87.

3. Reid IR, Bolland MJ. Role of vitamin D deficiency in cardiovascular disease. Heart 2012; Feb 28 [Epub ahead of print].

4. McGreevy C, Williams D. New insights about vitamin D and cardiovascular disease: A narrative review. Ann Intern Med 2011;155:820-826.

5. Salehpour A, et al. Vitamin D3 and the risk of CVD in overweight and obese women: A randomised controlled trial. Br J Nutr 2012;Feb 9:1-8.