Abstract
Objectives
Low levels of 25-hydroxyvitamin D are associated with higher risk of cardiovascular morbidity and mortality. Large trials demonstrated that statins significantly decrease cardiovascular morbidity and mortality. 7-dehydrocholesterol is the precursor of both cholesterol and vitamin D. The aim of this study was to investigate the possible effect of rosuvastatin on vitamin D metabolism.
Methods
The study was performed in a prospective cohort design. The study group consisted of 91 hyperlipidemic patients who had not been treated with lipid lowering medications. Lipid parameters, 25 hydroxyvitamin-D, 1,25-dihydroxyvitamin D, and bone alkaline phosphatase were obtained at baseline and after 8 weeks of rosuvastatin treatment.
Results
None of the subjects withdrew from the study because of the adverse effects. The mean age was 59.9 ± 12.5 years. The majority of the patients were male (55, 60%). Seventeen patients were diabetic, and 43 patients had systemic hypertension. There was a significant increase in 25-hydroxyvitamin D, from mean 14.0 (range 3.7– 67) to mean 36.3 (range 3.8 –117) ng/ml (p < 0.001), and also an increase of 1,25-dihydroxyvitamin D from mean 22.9 ± 11.2 to 26.6 ± 9.3 pg/dl (p = 0.023). Bone alkaline phosphatase decreased after 8 weeks of rosuvastatin treatment, mean 17.7 (range 2.6–214) to mean 9.5 (range 2.3–19.1) u/l (p < 0.001) rosuvastatin treatment.
Conclusion
This study has shown an effect of rosuvastatin on vitamin D metabolism, with an increase in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. This may be an important pleiotropic effect whereby rosuvastatin reduces mortality in patients with coronary artery disease. Further studies are needed to clarify the relationship between statins and vitamin D metabolism.
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References
Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.2.
Grimes DS, Hindle E, Dyer T. Sunlight, cholesterol and coronary heart disease. Q J Med. 1996;89:579–89.
Mortimer EA, Monson RR, MacMahon B. Reduction in mortality from coronary heart disease in men residing at high altitude. N EngI J Med. 1977;296:581–85.
Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989;3342:757–61.
Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:1205–1209.
Shepherd J, Cobbe SM, Ford I, for the West of Scotland Coronary Prevention Study Group, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N EngI J Med. 1995;333:1301–7.
Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4 S). Lancet. 1994;344:1383–9.
Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc NatI Acad Sci USA. 2003;100:14754–14759.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc. 2001;285:2486–97.
Wilczek H, Sobra J, Justova V, Ceska R, Juzova Z, Prochazkova R, et al. latropathogenic effect of mevacor on vitamin D metabolism. Cas Lek Cesk. 1989;128:1254–1256.
Wilzcek H, Sobra J, Ceska R, Justota V, Juzova Z, Prochazkova R, et al. Monitoring plasma levels of vitamin D metabolites in simvastatin therapy in patients with familial hypercholesterolemia. Cas Lek Cesk. 1994;133:727–729.
Perez-Castrillon JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, et al. Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol. 2007;99:903–5.
Bonetti PO, Lerman LO, Napoli C, Lerman A. Statin effects beyond lipid lowering — are they clinically relevant? Eur Heart J. 2003;24:225–48.
Grimes DS. Are statins analogues of vitamin D? Lancet. 2006;368:83–6.
Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.
Hatzigeorgiou C, Jackson JL. Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta-analysis. Osteoporos Int. 2005;16:990–998.
Safaei H, Janghorbani M, Aminorroaya A, Amini M. Lovastatin effects on bone mineral density in postmenopausal women with type 2 diabetes mellitus. Acta Diabetol. 2007;44:76–82.
Uysal AR, Delibasi T, Erdogan MF, et al. Effect of simvastatin use on bone mineral density in women with type 2 diabetes. Endocr Pract. 2007;13:114–6.
Svejda P, Soska V, Soucek M. The impact of statin therapy on bone density changes in postmenopausal women. Vnitr Lek. 2007;53:1064–70.
Rosenson RS, Tangney CC, Langman CB, Parker TS, Levine DM. Gordon BR. Short-term reduction in bone markers with high-dose simvastatin. Osteoporos Int. 2005;16:1272–1276.
Rejnmark L, Buus NH, Vestergaard P, Andreasen F, Larsen ML, Mosekilde L. Statins decrease bone turnover in postmenopausal women: A cross-sectional study. Eur J Clin Invest. 2002;32:581–589.
Kajinami K, Takekoshi N, Matsui S, Kanemitsu S, Okubo S, Kanayama S, et al. Effect of pretreatment vitamin D levels on in vivo effects of atorvastatin on bone metabolism in patients with heterozygous familial hypercholesterolemia. Am J Cardiol. 2003;92:1113–1116.
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Yavuz, B., Ertugrul, D.T., Cil, H. et al. Increased Levels of 25 Hydroxyvitamin D and 1,25-Dihydroxyvitamin D After Rosuvastatin Treatment: A Novel Pleiotropic Effect of Statins?. Cardiovasc Drugs Ther 23, 295–299 (2009). https://doi.org/10.1007/s10557-009-6181-8
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DOI: https://doi.org/10.1007/s10557-009-6181-8