Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk
An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)
Background—Lipoprotein(a) [Lp(a)] is a low-density lipoprotein–like particle largely independent of known risk factors and predictive of cardiovascular disease. Statins may offset the risk associated with elevated Lp(a), but it is unknown whether Lp(a) is a determinant of residual risk in the setting of low low-density lipoprotein cholesterol after potent statin therapy.
Methods and Results—Baseline and on-treatment Lp(a) concentrations were assessed in 9612 multiethnic participants in the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) before and after random allocation to rosuvastatin 20 mg/d or placebo, with outcomes reported for whites (n=7746). Lp(a) concentrations (median [25th–75th percentile], in nmol/L) were highest in blacks (60 [34–100]), then Asians (38 [18–60]), Hispanics (24 [11–46]), and whites (23 [10–50]; P<0.001). Although the median change in Lp(a) with rosuvastatin and placebo was zero, rosuvastatin nonetheless resulted in a small but statistically significant positive shift in the overall Lp(a) distribution (P<0.0001). Baseline Lp(a) concentrations were associated with incident cardiovascular disease (adjusted hazard ratio per 1-SD increment in Ln[Lp(a)], 1.18; 95% confidence interval, 1.03–1.34; P=0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of cardiovascular disease (adjusted hazard ratio, 1.27; 95% confidence interval, 1.01–1.59; P=0.04), which was independent of low-density lipoprotein cholesterol and other factors. Rosuvastatin significantly reduced incident cardiovascular disease among participants with baseline Lp(a) greater than or equal to the median (hazard ratio, 0.62; 95% confidence interval, 0.43–0.90) and Lp(a) less than the median (hazard ratio, 0.46; 95% confidence interval, 0.30–0.72), with no evidence of interaction. Similar results were obtained when analyses included nonwhites.
Conclusion—Among white JUPITER participants treated with potent statin therapy, Lp(a) was a significant determinant of residual risk. The magnitude of relative risk reduction with rosuvastatin was similar among participants with high or low Lp(a).
- Received June 12, 2013.
- Accepted October 24, 2013.
- © 2013 American Heart Association, Inc.