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Effect of simvastatin and ezetimibe on suPAR levels and outcomes.

Abstract：

BACKGROUND AND AIMS:Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown. METHODS:We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE). RESULTS:After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE. CONCLUSIONS:Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Hodges GW,Bang CN,Forman JL,Olsen MH,Boman K,Ray S,Kesäniemi YA,Eugen-Olsen J,Greve AM,Jeppesen JL,Wachtell K

doi

10.1016/j.atherosclerosis.2018.03.030

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

129-136

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(18)30155-2

journal_volume

272

pub_type

杂志文章,随机对照试验

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