Skip to main content
Top
Published in: Clinical Research in Cardiology 4/2013

01-04-2013 | Original Paper

25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment

Authors: Christian Ott, Ulrike Raff, Markus P. Schneider, Stephanie I. Titze, Roland E. Schmieder

Published in: Clinical Research in Cardiology | Issue 4/2013

Login to get access

Abstract

Background

Vitamin D deficiency is nowadays considered as a potential cardiovascular and renal risk factor. We tested the hypotheses that vitamin D deficiency impairs the endothelial function of renal vasculature and whether vitamin D levels and endothelial function can be improved by the treatment with statins.

Methods

In a double-blind, randomized study of 31 hypercholesterolemic patients with vitamin D insufficiency (<30 ng/ml) were randomly assigned to rosuvastatin (10 mg/d) and placebo for 6 weeks. Basal nitric oxide (NO) activity of the renal vasculature was assessed both before and after the blockade of NO synthases with systemic infusion of N(G)-monomethyl-l-arginine (l-NMMA). In parallel, 25(OH)D was measured.

Results

Multiple regression analysis revealed that at baseline 25(OH)D is an independent determinant of basal NO activity as assessed by the decrease in RPF, in response to l-NMMA (β = −0.446, r = 0.015). Compared to placebo treatment, rosuvastatin increased 25(OH)D levels (21.6 ± 4.0 vs. 24.1 ± 8.1 ng/ml, p = 0.039). Basal NO activity was significantly more increased after 6-week therapy with rosuvastatin than with placebo (−94.8 ± 70 vs. −68.2 ± 32 ml/min, p = 0.044), indicating increased basal NOS activity after 6 weeks of rosuvastatin treatment. Basal NO activity in the placebo phase was correlated inversely with 25(OH)D (r = −0.385; p = 0.027).

Conclusions

Thus, vitamin D insufficiency is associated with impaired endothelial function in the renal vasculature and both were beneficially influenced by the treatment with rosuvastatin.
Literature
1.
go back to reference Dobnig H, Pilz S, Scharnagl H et al (2008) Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 168:1340–1349PubMedCrossRef Dobnig H, Pilz S, Scharnagl H et al (2008) Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 168:1340–1349PubMedCrossRef
2.
go back to reference Wang TJ, Pencina MJ, Booth SL et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511PubMedCrossRef Wang TJ, Pencina MJ, Booth SL et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511PubMedCrossRef
3.
go back to reference Kendrick J, Targher G, Smits G et al (2009) 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third national health and nutrition examination survey. Atherosclerosis 205:255–260PubMedCrossRef Kendrick J, Targher G, Smits G et al (2009) 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third national health and nutrition examination survey. Atherosclerosis 205:255–260PubMedCrossRef
4.
go back to reference Deanfield J, Donald A, Ferri C et al (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the working group on endothelin and endothelial factors of the European society of hypertension. J Hypertens 23:7–17PubMedCrossRef Deanfield J, Donald A, Ferri C et al (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the working group on endothelin and endothelial factors of the European society of hypertension. J Hypertens 23:7–17PubMedCrossRef
5.
go back to reference Sugden JA, Davies JI, Witham MD et al (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 25:320–325PubMedCrossRef Sugden JA, Davies JI, Witham MD et al (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 25:320–325PubMedCrossRef
6.
go back to reference Tarcin O, Yavuz DG, Ozben B et al (2009) Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 94:4023–4030PubMedCrossRef Tarcin O, Yavuz DG, Ozben B et al (2009) Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 94:4023–4030PubMedCrossRef
7.
go back to reference Jablonski KL, Chonchol M, Pierce GL et al (2011) 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 57:63–69PubMedCrossRef Jablonski KL, Chonchol M, Pierce GL et al (2011) 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 57:63–69PubMedCrossRef
8.
go back to reference Mancia G, Laurent S, Agabiti-Rosei E et al (2009) Reappraisal of European guidelines on hypertension management: a European Society of hypertension task force document. J Hypertens 27:2121–2158PubMedCrossRef Mancia G, Laurent S, Agabiti-Rosei E et al (2009) Reappraisal of European guidelines on hypertension management: a European Society of hypertension task force document. J Hypertens 27:2121–2158PubMedCrossRef
9.
go back to reference Wierema TK, Houben AJ, Kroon AA et al (2001) Nitric oxide dependence of renal blood flow in patients with renal artery stenosis. J Am Soc Nephrol 12:1836–1843PubMed Wierema TK, Houben AJ, Kroon AA et al (2001) Nitric oxide dependence of renal blood flow in patients with renal artery stenosis. J Am Soc Nephrol 12:1836–1843PubMed
10.
go back to reference Jacobi J, Schneider MP, John S et al (2002) Impact of NO-synthase inhibition on renal hemodynamics in normotensive and hypertensive subjects. J Hypertens 20:525–530PubMedCrossRef Jacobi J, Schneider MP, John S et al (2002) Impact of NO-synthase inhibition on renal hemodynamics in normotensive and hypertensive subjects. J Hypertens 20:525–530PubMedCrossRef
11.
go back to reference Delles C, Jacobi J, John S et al (2002) Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension. Kidney Int 61:1462–1468PubMedCrossRef Delles C, Jacobi J, John S et al (2002) Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension. Kidney Int 61:1462–1468PubMedCrossRef
12.
go back to reference Schaufele TG, Schlaich MP, Delles C et al (2006) Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress. Kidney Int 70:1177–1181PubMedCrossRef Schaufele TG, Schlaich MP, Delles C et al (2006) Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress. Kidney Int 70:1177–1181PubMedCrossRef
13.
go back to reference (1998) Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 97:1440–1445 (1998) Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 97:1440–1445
14.
go back to reference (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389 (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383–1389
15.
go back to reference Sacks FM, Pasternak RC, Gibson CM et al (1994) Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard atherosclerosis reversibility project (HARP) group. Lancet 344:1182–1186PubMedCrossRef Sacks FM, Pasternak RC, Gibson CM et al (1994) Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard atherosclerosis reversibility project (HARP) group. Lancet 344:1182–1186PubMedCrossRef
16.
go back to reference Shepherd J, Cobbe SM, Ford I et al (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333:1301–1307PubMedCrossRef Shepherd J, Cobbe SM, Ford I et al (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333:1301–1307PubMedCrossRef
17.
go back to reference Egashira K, Hirooka Y, Kai H et al (1994) Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 89:2519–2524PubMedCrossRef Egashira K, Hirooka Y, Kai H et al (1994) Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 89:2519–2524PubMedCrossRef
18.
go back to reference John S, Schlaich M, Langenfeld M et al (1998) Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 98:211–216PubMedCrossRef John S, Schlaich M, Langenfeld M et al (1998) Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 98:211–216PubMedCrossRef
19.
go back to reference Perticone F, Ceravolo R, Maio R et al (2000) Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients. Atherosclerosis 152:511–518PubMedCrossRef Perticone F, Ceravolo R, Maio R et al (2000) Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients. Atherosclerosis 152:511–518PubMedCrossRef
20.
go back to reference Edwards CJ, Hart DJ, Spector TD (2000) Oral statins and increased bone-mineral density in postmenopausal women. Lancet 355:2218–2219PubMedCrossRef Edwards CJ, Hart DJ, Spector TD (2000) Oral statins and increased bone-mineral density in postmenopausal women. Lancet 355:2218–2219PubMedCrossRef
21.
go back to reference Ott C, Schlaich MP, Schmidt BM et al (2008) Rosuvastatin improves basal nitric oxide activity of the renal vasculature in patients with hypercholesterolemia. Atherosclerosis 196:704–711 Ott C, Schlaich MP, Schmidt BM et al (2008) Rosuvastatin improves basal nitric oxide activity of the renal vasculature in patients with hypercholesterolemia. Atherosclerosis 196:704–711
22.
go back to reference Cole BR, Giangiacomo J, Ingelfinger JR et al (1972) Measurement of renal function without urine collection. A critical evaluation of the constant-infusion technic for determination of inulin and para-aminohippurate. N Engl J Med 287:1109–1114PubMedCrossRef Cole BR, Giangiacomo J, Ingelfinger JR et al (1972) Measurement of renal function without urine collection. A critical evaluation of the constant-infusion technic for determination of inulin and para-aminohippurate. N Engl J Med 287:1109–1114PubMedCrossRef
23.
go back to reference Schlaich MP, Jacobi J, John S et al (2000) Is l-arginine infusion an adequate tool to assess endothelium-dependent vasodilation of the human renal vasculature? Clin Sci (Lond) 99:293–302CrossRef Schlaich MP, Jacobi J, John S et al (2000) Is l-arginine infusion an adequate tool to assess endothelium-dependent vasodilation of the human renal vasculature? Clin Sci (Lond) 99:293–302CrossRef
25.
go back to reference Looker AC, Dawson-Hughes B, Calvo MS et al (2002) Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30:771–777PubMedCrossRef Looker AC, Dawson-Hughes B, Calvo MS et al (2002) Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III. Bone 30:771–777PubMedCrossRef
26.
go back to reference Verbeke FH, Pannier B, Guerin AP et al (2011) Flow-mediated vasodilation in end-stage renal disease. Clin J Am Soc Nephrol 6:2009–2015PubMedCrossRef Verbeke FH, Pannier B, Guerin AP et al (2011) Flow-mediated vasodilation in end-stage renal disease. Clin J Am Soc Nephrol 6:2009–2015PubMedCrossRef
27.
go back to reference Al Mheid I, Patel R, Murrow J et al (2011) Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol 58:186–192PubMedCrossRef Al Mheid I, Patel R, Murrow J et al (2011) Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol 58:186–192PubMedCrossRef
28.
go back to reference Yavuz B, Ertugrul DT, Cil H et al (2009) Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther 23:295–299PubMedCrossRef Yavuz B, Ertugrul DT, Cil H et al (2009) Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther 23:295–299PubMedCrossRef
29.
go back to reference Perez-Castrillon JL, Vega G, Abad L et al (2007) Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 99:903–905PubMedCrossRef Perez-Castrillon JL, Vega G, Abad L et al (2007) Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 99:903–905PubMedCrossRef
31.
go back to reference London GM, Guerin AP, Verbeke FH et al (2007) Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 18:613–620PubMedCrossRef London GM, Guerin AP, Verbeke FH et al (2007) Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 18:613–620PubMedCrossRef
32.
go back to reference Rezai MR, Wallace AM, Sattar N et al (2011) Ethnic differences in aortic pulse wave velocity occur in the descending aorta and may be related to vitamin D. Hypertension 58:247–253PubMedCrossRef Rezai MR, Wallace AM, Sattar N et al (2011) Ethnic differences in aortic pulse wave velocity occur in the descending aorta and may be related to vitamin D. Hypertension 58:247–253PubMedCrossRef
33.
go back to reference Gupta A, Thompson PD (2011) The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis 215:23–29PubMedCrossRef Gupta A, Thompson PD (2011) The relationship of vitamin D deficiency to statin myopathy. Atherosclerosis 215:23–29PubMedCrossRef
34.
go back to reference Wu-Wong JR, Nakane M, Ma J et al (2007) Statins do not directly activate vitamin D receptor. J Thromb Haemost 5:415–416PubMedCrossRef Wu-Wong JR, Nakane M, Ma J et al (2007) Statins do not directly activate vitamin D receptor. J Thromb Haemost 5:415–416PubMedCrossRef
Metadata
Title
25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment
Authors
Christian Ott
Ulrike Raff
Markus P. Schneider
Stephanie I. Titze
Roland E. Schmieder
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Clinical Research in Cardiology / Issue 4/2013
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-012-0534-1

Other articles of this Issue 4/2013

Clinical Research in Cardiology 4/2013 Go to the issue