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Should Vitamin D Measurement Be Routine in All Cardiovascular Disease Patients?
Abstract & commentary
By Harold L. Karpman, MD, FACC, FACP, Clinical Professor of Medicine, UCLA School of Medicine. Dr. Karpman reports no financial relationship to this field of study.
Synopsis: Hypovitaminosis D was found to be highly prevalent in U.S. adults with CVD, particularly those with both coronary heart disease and heart failure.
Source: Kim DH, et al. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol 2008;102:1540-1544.
Vitamin D deficiency occurs in one-third to one-half of otherwise healthy middle-aged and elderly adults in the United States and worldwide. There is a growing body of evidence that hypovitaminosis D is highly prevalent in patients with various cardiovascular diseases (CVDs)1-4 and, in fact, it may actually play a role in the pathogenesis of these illnesses.5-9 Inadequate exposure to sunlight and/or inadequate vitamin D intake will result in abnormally low serum vitamin D levels, which have been found to be associated with cardiovascular risk factors such as hypertension, diabetes mellitus, obesity, and dyslipidemia;10,11 however, it must be recognized that many of these observations were from the results of relatively small studies.
Because the degree of occurrence of hypovitaminosis D in adults in the United States with a diagnosis of CVD was largely unknown, Kim and his colleagues examined its prevalence in U.S. adults with CVDs using data from the National Health and Nutrition Examination Surveys (NHANES) from 2001 to 2004.12 Hypovitaminosis D was found to be present in 74% of the 8351 adults who had 25-hydroxyvitamin D (25-OH D) blood levels measured. Among CVD patients it was more common in blacks than it was in Hispanic or Caucasian patients and it did not differ by gender. However, although it was found to be present in 68% of persons at low risk for CVDs, it was more prevalent in high-risk patients (75%), in patients with coronary heart disease (77%), and in subjects with both coronary heart disease and heart failure (89%) after controlling for age, race, and gender.
Several lines of evidence have suggested that hypovitaminosis D may contribute to CVDs by stimulating renin expression,13 proliferation of cardiomyocytes14 and smooth muscle cells,15 and by producing secondary hyperparathyroidism16 and inflammation.17 Although the higher prevalence of hypovitaminosis D in patients with coronary heart disease and heart failure may have been caused by limited physical activity and sunlight exposure, studies have demonstrated that patients with heart failure compared to healthy controls differed in their lifestyle factors even in their earlier years, suggesting that hypovitaminosis D may occur earlier in life and precede the onset of CVDs.18
In conclusion, the Kim observational study revealed that hypovitaminosis D was highly prevalent in U.S. adults with CVDs, particularly those with both coronary heart disease and heart failure.12 In addition, the study results raise the clinical possibility that treatment of vitamin D deficiency with vitamin D supplements and/or lifestyle measures might be able to reduce the frequency of CVDs; however, it must be clearly recognized that treatment strategies suggested by observational data are not always supported by randomized trials. Despite the positive results in small clinical trials in which vitamin D supplementation has promoted reductions in blood pressure,19,20 left ventricular hypertrophy21 and inflammatory cytokines,22 vitamin D supplementation was not associated with a reduction in cardiovascular events in the Woman's Health Initiative,23 although it should be noted that that particular trial was not designed to evaluate cardiovascular risk.24 Obviously, although well conducted, randomized, double-blind clinical studies are needed to conclusively determine whether correction of vitamin D deficiency is able to contribute to the prevention and treatment of CVDs, at the present time there seems to be little risk for clinicians to recommend at least 800 IU of vitamin D daily for their adult (and especially elderly) patients and to consider prescribing even higher doses of vitamin D if needed to correct persistently abnormally low vitamin D blood levels, especially for those patients whose lifestyle and/or illnesses prevent them from being outdoors.
1. Fahrleitner A, et al. Vitamin D deficiency and secondary hyperparathyroidism are common complications in patients with peripheral arterial disease. J Gen Intern Med 2002;17:663-669.
2. Poole KE, et al. Reduced vitamin D in acute stroke. Stroke 2006;37:243-245.
3. Scragg R, et al. Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: A community-based study. Int J Epidemiol 1990;19: 559-563.
4. Zittermann A, et al. Low vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-112.
5. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81: 353-373.
6. Malabanan A, et al. Redefining vitamin D insufficiency. Lancet 1998;351:805-806.
7. Chapuy MC, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporosis Int 1997;7:439-443.
8. Nesby-O'Dell S, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr 2002;76:187-192.
9. Zittermann A. Vitamin D in preventive medicine: Are we ignoring the evidence? Br J Nutr 2003;89:552-572.
10. Lind L, et al. Vitamin D is related to blood pressure and other cardiovascular risk factors in middle-aged men. Am J Hypertens 1995;8:894-901.
11. Martins D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: Data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159-1165.
12. Kim DH, et al. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol 2008;102:1540-1544.
13. Li YC, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002;110:229-238.
14. O'Connell TD, et al. 1,25-dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. Am J Physiol 1997;27(4 pt 2):H1751-H1758.
15. Mitsuhashi T, et al. 1,25-dihydroxyvitamin D3 modulates growth of smooth muscle cells. J Clin Invest 1991;87:1889-1895.
16. Perkovic V, et al. Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells. Kidney Blood Press Res 2003;26:27-33.
17. Rigby WF, et al. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest 1987;79:1659-1664.
18. Zittermann A, et al. Patients with congestive heart failure and healthy controls differ in vitamin D-associated lifestyle factors. Int J Vitam Nutr Res 2007;77:280-288.
19. Lind L, et al. Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status; a double-blind placebo-controlled study. Am J Hypertens 1989;2:20-25.
20. Pfeifer M, et al. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrin Metab 2001;86:1633-1637.
21. Park CW, et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 1999;33:73-81.
22. Schleithoff SS, et al. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006;83:754-759.
23. Hsia J, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007;115:846-854.
24. Michos ED, et al. Vitamin D supplementation and cardiovascular disease risk. Circulation 2007;115:827-828.