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Should we forget about vitamin D in cardiovascular disease prevention?

Comment by Stefan Busnatu, EAPC Young Ambassador from Romania

Risk Factors and Prevention


During the past years, there have been numerous reports suggesting a high prevalence of vitamin D deficiency or inadequate vitamin D status throughout Europe. Coupled with the growing concern related to the health risks associated with low vitamin D status, this has conducted to an increased interest in the topic of vitamin D from healthcare professionals, the media and the public [1].

Vitamin D is synthesised in the skin as a pro-hormone in response to ultraviolet light and is also absorbed from the gastrointestinal tract. The vitamin D receptor is expressed in cells throughout the vascular system [2]. Many cell types such as vascular smooth muscle cells, endothelial cells, and cardiomyocytes, produce 1α-hydroxylase, which converts 25-hydroxyvitamin D to calcitriol, the natural ligand of the vitamin D receptor. Calcitriol has been shown to inhibit vascular smooth muscle cell proliferation, regulate the renin-angiotensin system, decrease coagulation, and exhibit anti-inflammatory properties [3].

That is why vitamin D received increased attention for its potential role in preventing cardiovascular disease (CVD). Several epidemiological studies have ended even suggesting that individuals with low blood levels of vitamin D have increased risks of heart disease, stroke, hypertension, and diabetes[4].

This widespread mirage with vitamin D as a panacea for many illnesses, including cardiovascular diseases (CVD), became responsible for nearly a 100-fold increase in vitamin D testing and oral supplementation over the last decade, surprisingly in populations at low risk for vitamin D deficiency[5].

In a recent meta-analysis that appeared in JAMA Cardiology, Mahmoud Barbarawi et al. [6] analysed all randomised clinical trials published in PubMed, Cochrane Library, and Embase, that reported on the effects of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality.

They have identified twenty-one randomised clinical trials published before 15 December 2018 that included in total 83,291 patients, of whom 41,669 received vitamin D and 41,622 received placebos.

The mean age of the participants within the trials was approximatively 65 years, consisting of 61,943 (74.4%) females. Mean follow-up varied from 1 to 12 years. At the end of the follow-up, no significant differences emerged. Within the trials a total of 6,243 cases of MACE occurred, but the incidence did not vary significantly based on vitamin D supplementation vs placebo (relative risk, 1.0; 95% confidence interval [CI], 0.95 - 1.06; P = .85).

Vitamin D supplementation compared with placebo has not been found to be associated with any reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23).

The results were generally consistent in terms of the participant’s gender, baseline 25-hydroxyvitamin D level, vitamin D dosage, administration (daily vs bolus dosing), and their relation with the presence or absence of concurrent calcium administration [6]. In the end, the authors stated that vitamin D supplementation does not confer cardiovascular protection but they still left a door open for vitamin D by specifying that one of the limitations of the report is that many of the included studies did not prespecify cardiovascular outcomes.

Although the results of this report are clear, we should not forget that in specific situations, for example in patients with chronic kidney disease and hyperparathyroidism, vitamin D therapy is definitely indicated, and such therapy has established cardiovascular benefits[7].

Note: The content of this article reflects the personal opinion of the author and is not necessarily the official position of the European Society of Cardiology. 

References

References:

1. Spiro, A, and J L Buttriss. “Vitamin D: An overview of vitamin D status and intake in Europe.” Nutrition bulletin vol. 39,4 (2014): 322-350. doi:10.1111/nbu.12108

2. Anthony W Norman, From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health, The American Journal of Clinical Nutrition, Volume 88, Issue 2, August 2008, Pages 491S–499S, https://doi.org/10.1093/ajcn/88.2.491S

3. Danik, Jacqueline S, and Joann E Manson. “Vitamin d and cardiovascular disease.” Current treatment options in cardiovascular medicine vol. 14,4 (2012): 414-24. doi:10.1007/s11936-012-0183-8

4. A. Catharine Ross, JoAnn E. Manson, Steven A. Abrams, John F. Aloia, Patsy M. Brannon, Steven K. Clinton, Ramon A. Durazo-Arvizu, J. Christopher Gallagher, Richard L. Gallo, Glenville Jones, Christopher S. Kovacs, Susan T. Mayne, Clifford J. Rosen, Sue A. Shapses, The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 1, 1 January 2011, Pages 53–58, https://doi.org/10.1210/jc.2010-2704

5. Arshed A. Quyyumi, MD; Ibhar Al Mheid, MD. "The Demise of Vitamin D for Cardiovascular Prevention." JAMA Cardiology. June 19, 2019. DOI:10.1001/jamacardio.2019.1906

6. Barbarawi M, Kheiri B, Zayed Y, et al. Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis. JAMA Cardiol. Published online June 19, 20194(8):765–775. doi:10.1001/jamacardio.2019.1870

7. Keung, Lisa, and Farzana Perwad. “Vitamin D and kidney disease.” Bone reports vol. 9 93-100. 25 Jul. 2018, doi:10.1016/j.bonr.2018.07.002