Home LiteratureArticle Details
PMID: 18413554 Published · ppublish English Journal Article Randomized Controlled Trial Research Support, N.I.H., Extramural

Reduction in blood pressure with statins: results from the UCSD Statin Study, a randomized trial.

Archives of internal medicine ·Vol. 168 ·No. 7 ·2008-04-14 ·Pages 721-7

Golomb BA, Dimsdale JE, White HL, Ritchie JB, Criqui MH

Abstract

Some studies have suggested reductions in blood pressure (BP)with statin treatment, particularly in persons with hypertension. Randomized trial evidence is limited. We performed a randomized, double-blind, placebo-controlled trial with equal allocation to simvastatin, 20 mg; pravastatin sodium,40 mg; or placebo for 6 months. Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus, with low-density lipoprotein cholesterol screening levels of 115 to 190 mg/dL, had assessment of systolic and diastolic BP (SBP and DBP, respectively). Blood pressure values were compared for placebo vs statins by intention-to-treat (ITT) analysis. Additional analyses were performed that (1) were confined to subjects with neither high baseline BP (SBP>140 mm Hg or DBP>90 mm Hg) nor receiving BP medications, to exclude groups in whom BP medications or medication changes may have influenced results, and (2) separately evaluated simvastatin and pravastatin (vs placebo). The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined. Statins modestly but significantly reduced BP relative to placebo,by 2.2 mm Hg for SBP (P=.02) and 2.4 mm Hg for DBP (P<.001) in ITT analysis. Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin, in those subjects with full follow-up, and without potential for influence by BP medications (ie, neither receiving nor meriting BP medications). Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects. These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins. Trial Registration clinicaltrials.gov Identifier: NCT00330980.

MeSH Terms
Antihypertensive Agents/therapeutic use Blood Pressure/drug effects Cardiovascular Diseases/prevention & control Diastole Double-Blind Method Female Follow-Up Studies Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use Hypertension/drug therapy Male Pravastatin/therapeutic use Simvastatin/therapeutic use Stroke/prevention & control Systole Treatment Outcome
Chemicals
Antihypertensive Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Simvastatin Pravastatin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Golomb Beatrice A
Department of Medicine, University of California, San Diego,9500 Gilman Dr, No. 0995, La Jolla, CA 92093-0995, USA. [email protected]
Dimsdale Joel E
White Halbert L
Ritchie Janis B
Criqui Michael H
References (48)
48 references, click to expand
  1. Non-lipid effects of statins: emerging new indications.
    Curr Vasc Pharmacol. 2004 Oct;2(4):309-18 PMID: 15320810
  2. Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project.
    Circulation. 2001 Jan 23;103(3):387-92 PMID: 11157690
  3. Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension.
    J Am Coll Cardiol. 2002 Mar 20;39(6):1020-5 PMID: 11897445
  4. Lowering of elevated ambulatory blood pressure by HMG-CoA reductase inhibitors.
    J Cardiovasc Pharmacol. 2005 Sep;46(3):310-5 PMID: 16116336
  5. Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina.
    Int J Cardiol. 2005 May 11;101(1):65-70 PMID: 15860385
  6. The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes.
    Control Clin Trials. 2004 Apr;25(2):178-202 PMID: 15020036
  7. Statin therapy helps to control blood pressure levels in hypertensive dyslipidemic patients.
    Ren Fail. 2005;27(3):297-303 PMID: 15957546
  8. Randomized trial of atorvastatin in improving endothelial function in diabetics without prior coronary disease and having average cholesterol level.
    J Med Assoc Thai. 2005 Mar;88(3):399-406 PMID: 15962651
  9. Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH).
    Curr Med Res Opin. 2005 Sep;21(9):1469-76 PMID: 16197666
  10. [Hypotensive effect of an inhibitor of cholesterol synthesis (fluvastatin). A pilot study].
    Schweiz Med Wochenschr. 1998 Feb 14;128(7):272-7 PMID: 9540154
  11. Statin-sensitive dysregulated AT1 receptor function and density in hypercholesterolemic men.
    Circulation. 1999 Nov 23;100(21):2131-4 PMID: 10571970
  12. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV.
    J Hum Hypertens. 2004 Mar;18(3):139-85 PMID: 14973512
  13. The effect of statin therapy on endothelial function in type 2 diabetes without manifest cardiovascular disease.
    Diabetes Care. 2005 Jul;28(7):1668-74 PMID: 15983318
  14. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials.
    JAMA. 1997 Jul 23-30;278(4):313-21 PMID: 9228438
  15. Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia.
    Am J Hypertens. 2001 Nov;14(11 Pt 1):1096-8 PMID: 11724206
  16. Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia.
    Hypertension. 1999 Dec;34(6):1281-6 PMID: 10601131
  17. Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation.
    Clin Cardiol. 2004 Apr;27(4):199-203 PMID: 15119693
  18. Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry.
    Arch Intern Med. 2004 Jan 26;164(2):153-62 PMID: 14744838
  19. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
    N Engl J Med. 1996 Oct 3;335(14):1001-9 PMID: 8801446
  20. Improvement of serum oxidation by pravastatin might be one of the mechanisms by which endothelial function in dilated coronary artery segments is ameliorated.
    Atherosclerosis. 2003 Aug;169(2):309-15 PMID: 12921983
  21. The rule of 5 and the rule of 7 in lipid-lowering by statin drugs.
    Am J Cardiol. 1997 Jul 1;80(1):106-7 PMID: 9205036
  22. Effect of pravastatin on blood pressure in people with cardiovascular disease.
    J Hum Hypertens. 2006 Aug;20(8):560-5 PMID: 16625234
  23. Do statins lower blood pressure?
    J Cardiovasc Pharmacol Ther. 2007 Jun;12(2):112-23 PMID: 17562781
  24. HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease.
    Atherosclerosis. 1999 Dec;147(2):237-42 PMID: 10559508
  25. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles.
    Atherosclerosis. 2003 Oct;170(2):315-23 PMID: 14612213
  26. High-dose atorvastatin after stroke or transient ischemic attack.
    N Engl J Med. 2006 Aug 10;355(6):549-59 PMID: 16899775
  27. [Effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, lipid peroxidation, and aortic atherosclerosis in hypercholesterolemic rabbits].
    Arq Bras Cardiol. 2005 Apr;84(4):314-9 PMID: 15880205
  28. Effect of statin therapy added to ACE-inhibitors on blood pressure control and endothelial functions in normolipidemic hypertensive patients.
    Anadolu Kardiyol Derg. 2003 Dec;3(4):331-7 PMID: 14675884
  29. Use of statins and blood pressure control in treated hypertensive patients with hypercholesterolemia.
    J Cardiovasc Pharmacol. 2000 Apr;35(4):549-55 PMID: 10774784
  30. Blood pressure reduction with HMG-CoA reductase inhibitors in renal transplant recipients.
    Kidney Int. 2003 Jan;63(1):360-4 PMID: 12472804
  31. [Does statin therapy reduce the risk of stroke? A meta-analysis].
    Ann Med Interne (Paris). 2001 Apr;152(3):188-93 PMID: 11431579
  32. Prehypertension and cardiovascular morbidity.
    Ann Fam Med. 2005 Jul-Aug;3(4):294-9 PMID: 16046560
  33. Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients.
    Blood Press. 1994 Nov;3(6):404-6 PMID: 7704289
  34. Prehypertension and cardiovascular disease risk in the Women's Health Initiative.
    Circulation. 2007 Feb 20;115(7):855-60 PMID: 17309936
  35. Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease.
    Am J Med. 2006 Feb;119(2):133-41 PMID: 16443415
  36. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
    JAMA. 2003 May 21;289(19):2560-72 PMID: 12748199
  37. Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both an anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet.
    Clin Ther. 2003 Apr;25(4):1107-22 PMID: 12809960
  38. Statins and blood pressure: is there an effect or not?
    J Clin Hypertens (Greenwich). 2007 Jun;9(6):460-7 PMID: 17541332
  39. Statin therapy and stroke prevention.
    Curr Opin Cardiol. 2001 Jul;16(4):219-24 PMID: 11574782
  40. Fluvastatin reduces oxidative stress, decreases serum monocyte chemotactic protein-1 level and improves endothelial function in patients with hypercholesterolemia.
    J Formos Med Assoc. 2004 Dec;103(12):914-20 PMID: 15624040
  41. Stroke, statins, and cholesterol. A meta-analysis of randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors.
    Stroke. 1997 May;28(5):946-50 PMID: 9158630
  42. Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients.
    Am Heart J. 2005 Mar;149(3):473 PMID: 15864218
  43. Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans.
    Circulation. 2005 May 10;111(18):2356-63 PMID: 15867181
  44. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials.
    Hypertension. 2007 Apr;49(4):792-8 PMID: 17309949
  45. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.
    Stroke. 2001 Apr;32(4):980-6 PMID: 11283400
  46. Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril).
    Am J Cardiol. 1999 May 15;83(10):1497-9, A8 PMID: 10335771
  47. Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions.
    J Am Coll Cardiol. 1999 Jan;33(1):234-41 PMID: 9935036
  48. Early vascular benefits of statin therapy.
    Curr Med Res Opin. 2003;19(6):540-56 PMID: 14594527
Article Info
Journal
Archives of internal medicine
Abbr.
Arch Intern Med
ISSN
0003-9926
Published
2008-04-14
Pages
721-7
Language
English
Region
United States
NLM ID
0372440
PMCID
PMC4285458
Subset
IM
Grants
NCRR NIH HHS · M01 RR000827 · United States
NHLBI NIH HHS · R01 HL063055 · United States
NCRR NIH HHS · M01 RR00827 · United States
NHLBI NIH HHS · R01 HL63055-05 · United States
Databases
ClinicalTrials.gov
NCT00330980
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]