Abstract
Part of the efficacy of statins in the prevention of cardiovascular events can be attributed to their blood pressure-lowering effect, but clinical trials primarily designed to investigate this effect are scarce. In a double-blind parallel placebo-controlled clinical trial with ambulatory blood pressure (ABP) monitoring, 79 hypertensive patients were randomly assigned to 40 mg of simvastatin (n=40) or placebo (n=39) taken in the morning for 2 months. Between-group deltas of ABP change, adjusted for the corresponding baseline BP, were 2.8 mm Hg (95% CI: 0.4–5.1; P=0.02) for 24-h diastolic blood pressure (DBP), 4.2 mm Hg (95% CI: 0.1–8.4; P=0.04) for daytime systolic BP and 3.1 mm Hg (95% CI: 0.4–5.9; P=0.02) for daytime DBP. There was no effect on nighttime BP. There was an interaction between baseline cholesterol levels and treatment effect, which was restricted to patients with cholesterol above the median of the whole sample. There was no significant change in office BP. In conclusion, simvastatin lowers ABP in patients with hypertension, particularly in the presence of higher levels of cholesterol. This effect may contribute to the beneficial effects of statins in the prevention of cardiovascular disease.
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04 December 2013
This article has been corrected since online publication and a corrigendum is also printed in this issue.
References
Downs JR, Clearfield MDO, Weis SDO, Whitney E, Shapiro DR, Beere PA et al for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998; 279: 1615–1621.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW et al West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301–1307.
Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–1389.
The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349–1357.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22.
Robinson JG, Smith B, Maheshwari N, Schrott H . Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 2005; 46: 1855–1862.
McFarlane SI, Muniyappa R, Francisco R, Sowers JR . Pleiotropic effects of statins: lipid reduction and beyond. Clin Endocrinol Metab 2002; 87: 1451–1458.
Bonetti PO, Lerman LO, Napoli C, Lerman A . Statin effects beyond lipid lowering—are they clinically relevant? Eur Heart J 2003; 24: 225–248.
Koh KK, Quon MJ, Waclawiw MA . Are statins effective for simultaneously treating dyslipidemias and hypertension? Atherosclerosis 2008; 196: 1–8.
Corrêa V Jr, Gus M, Fuchs FD . Does the blood pressure-lowering effect of statins contribute to their beneficial cardiovascular effects? Expert Rev Cardiovasc Ther 2010; 8: 775–779.
Mancia G, Parati G, Revera M, Bilo G, Giuliano A, Veglia F et al. Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: evidence from PHYLLIS randomised double blind trial. Br Med J 2010; 340: c1197.
Kanaki AI, Sarafidis PA, Georgianos PI, Stafylas PC, Kanavos K, Tziolas IM et al. Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild hypertension and hypercholesterolaemia: a double-blind, randomized, placebo-controlled study. J Hum Hypertens 2011; 26: 577–584.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL et al. The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.
Friedewald WT, Levy RI, Fredrickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.
Sociedade Brasileira de Cardiologia; Sociedade Brasileira de Hipertensão; Sociedade Brasileira de Nefrologia. (VI Brazilian Guidelines on Hypertension). Arq Bras Cardiol 2010; 95 (1 Suppl): 1–51.
Lennernäs H, Fager G . Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences. Clin Pharmacokinet 1997; 32: 403–425.
Law MR, Morris JK, Wald NJ . Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analyses of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.
Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J et al Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007; 370: 1829–1839.
Fuchs FD, Fuchs SC, Moreira LB, Gus M . Proof of concept in cardiovascular risk: the paradoxical findings in blood pressure and lipid abnormalities. Vasc Health and Risk Manag 2012; 8: 437–442.
ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT). JAMA 2002; 288: 2998–3007.
Glorioso N, Troffa C, Filigheddu F, Dettori F, Soro A, Parpaglia PP et al. Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia. Hypertension 1999; 34: 1281–1286.
Ikeda T, Sakurai J, Nakayama D, Takahashi Y, Matsuo K, Shibuya Y et al. Pravastatin has an additional depressor effect in patients undergoing long-term treatment with antihypertensive drugs. Am J Hypertens 2004; 17: 502–506.
Calvo C, Hermida RC, Ayala DE, Covelo M, Lopez JE . Atorvastatin reduces ambulatory blood pressure in hyperlipidemic patients with untreated grade 1 essential hypertension. Am J Hypertens 2005; 18 (Suppl 1): A2.
Terzoli L, Mircoli L, Raco R, Ferrari U . Lowering of elevated ambulatory blood pressure by HMG-CoA reductase Inhibitors. J Cardiovasc Pharmacol 2005; 46: 310–315.
Kanbay M, Yildirir A, Bozbas H, Ulus T, Bilgi M, Muderrisoglu H et al. Statin therapy helps to control blood pressure levels in hypertensive dyslipidemic patients. Ren Fail 2005; 27: 297–303.
Golomb BA, Dimsdale JE, White HL, Richie JB, Criqui MH . Reduction in blood pressure with statins. Results from the UCSD statin study, a randomized trial. Arch Intern Med 2008; 168: 721–727.
Borghi C, Dormi A, Veronesi M, Sangiorgi Z, Gaddi A and Brisighella Heart Study Working Party. Association between different lipid-lowering treatment strategies and blood pressure control in the Brisighella Heart Study. Am Heart J 2004; 148: 285–292.
Lopau K, Spindler K, Wanner C . Effects of pravastatin treatment on blood pressure regulation after renal transplantation. Kidney Blood Press Res 2006; 29: 329–337.
Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim HS et al. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 2005; 45: 1088–1093.
Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 2004; 110: 3687–3692.
Strazzullo O, Kerry SM, Barbato A, Versiero M, D’elia L, Cappuccio FP . Do statins reduce blood pressure? A meta-analysis of randomized, controlled trials. Hypertension 2007; 49: 792–798.
Williams B, Lacy PS, Cruickshank K, Collier D, Hughes AD, Stanton A et al The CAFE and ASCOT Investigators. Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study. Circulation 2009; 119: 53–61.
Laufs U, La Fata V, Plutzky J, Liao JK . Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998; 97: 1129–1135.
Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz et al. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 2001; 32: 980–986.
Laufs U, Wassmann S, Hilgers S, Ribaudo N, Böhm M, Nickenig G . Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men. Am J Cardiol 2001; 88: 1306–1307.
Nickenig G, Bäumer AT, Temur Y, Kebben D, Jockenhövel F, Böhm M . Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men. Circulation 1999; 100: 2131–2134.
Hernández-Perera O, Pérez-Sala D, Soria E, Lamas S . Involvement of Rho GTPases in the transcriptional inhibition of preproendothelin-1 gene expression by simvastatin in vascular endothelial cells. Circ Res 2000; 87: 616–622.
Acknowledgements
This study was supported in part by FIPE (Fundo de Incentivo de Pesquisa e Eventos/Hospital de Clínicas de Porto Alegre).
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Correa, V., Fuchs, F., Moreira, L. et al. Blood pressure-lowering effect of simvastatin: a placebo-controlled randomized clinical trial with 24-h ambulatory blood pressure monitoring. J Hum Hypertens 28, 62–67 (2014). https://doi.org/10.1038/jhh.2013.35
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DOI: https://doi.org/10.1038/jhh.2013.35
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