Skip to main content
Erschienen 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

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

Erschienen in: Clinical Research in Cardiology | Ausgabe 4/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat (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.
Zurück zum Zitat (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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
25-Hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment
verfasst von
Christian Ott
Ulrike Raff
Markus P. Schneider
Stephanie I. Titze
Roland E. Schmieder
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
Clinical Research in Cardiology / Ausgabe 4/2013
Print ISSN: 1861-0684
Elektronische ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-012-0534-1

Weitere Artikel der Ausgabe 4/2013

Clinical Research in Cardiology 4/2013 Zur Ausgabe

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.