Abstract 13083: Lipoprotein(a) is a Residual Cardiovascular Risk Factor in Statin Treated Stroke Survivors - Insights From the SPARCL Trial

Abstract

Introduction: Elevated lipoprotein (a) [Lp(a)] plasma levels are causally associated with CAD. The association between Lp(a) and stroke is however less clear. The SPARCL trial has demonstrated the superiority of 80mg atorvastatin to placebo for the prevention of stroke in patients with recent stroke or TIA. The aim of the current study was to investigate if Lp(a) is predictive of recurrent cerebrovascular and incident coronary events in these patients. Methods: Lp(a) concentration and apolipoprotein(a) [apo(a)] isoform size, a strong determinant of Lp(a) plasma levels, were measured by LC-HRMS in samples collected at baseline from 2814 SPARCL participants (1418 randomized to atorvastatin & 1396 to placebo). Within each treatment arm, we compared patients in the highest quartile ( >84.0nmol/L ) with those in the lowest quartiles of Lp(a) concentrations and patients in the lowest quartile ( <25.9 KIV domains ) with those in the highest quartiles of apo(a) size distributions. The relationship between these parameters and subsequent events was established with a Cox proportional hazard model adjusted for age, sex, type of entry event, time since entry event, BMI, smoking, hypertension, non HDLC and DM. Results: In patients randomized to atorvastatin, elevated Lp(a) concentrations and shorter apo(a) isoforms were independently associated with an increased risk of coronary events [HR (95% CI) of 1.607 (1.007-2.563) p=0.047 & 2.052 (1.303-3.232) p=0.002 , respectively]. These associations were primarily driven by a significantly higher incidence of coronary revascularisation procedures, stable angina requiring hospitalization, and MI. No such association was found in patients randomized to placebo [0.925 (0.606-1.412) & 1.105 (0.735-1.659)]. We did not observe any significant association between elevated Lp(a) concentrations or short apo(a) isoforms and the risk of recurrent cerebrovascular events in patients randomized to atorvastatin [0.794 (0.586-1.076) & 1.114 (0.760-1.352)] or placebo [0.914 (0.688-1.214) & 0.940 (0.709-1.248)]. Conclusion: Lp(a) contributes to the residual CAD risk of statin-treated stroke/TIA survivors, paving the way for the use of novel therapies targeting Lp(a) in patients with a history of stroke and elevated Lp(a).