Effect of simvastatin and ezetimibe on suPAR levels and outcomes. (May 2018)

• Record Type: Journal Article
• Authors: Hodges, Gethin W.; Bang, Casper N.; Forman, Julie L.; Olsen, Michael H.; Boman, Kurt; Ray, Simon; Kesäniemi, Y. Antero; Eugen-Olsen, Jesper; Greve, Anders M.; Jeppesen, Jørgen L.; Wachtell, Kristian
• Is Part Of: Atherosclerosis. Volume 272(2018)
• Page Start: 129
• Page End: 136
• Publication Date: 2018-05
• Subjects: Atherosclerosis -- Biomarker -- Cardiovascular disease -- Cardiovascular risk -- Inflammation -- Statins -- SuPAR; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2018.03.030
• Languages: English
• ISSNs: 0021-9150

Abstract

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). Highlights: Simvastatin/Ezetimibe treatment is associated with a slower progression of the time-related increase in suPAR levels. SuPAR predicts adverse outcomes in patients with mild-moderate asymptomatic aortic stenosis. Change in suPAR levels are of prognostic value in this cohort.