Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis from the JUPITER Trial
Background—Lipoprotein(a) [Lp(a)] is an LDL-like particle largely independent of known risk factors and predictive of cardiovascular disease (CVD). Statins may offset the risk associated with elevated Lp(a), but it is unknown if Lp(a) is a determinant of residual risk in the setting of low LDL-cholesterol after potent statin therapy.
Methods and Results—Baseline and on-treatment Lp(a) concentrations were assessed in 9,612 multiethnic JUPITER trial participants before and after random allocation to rosuvastatin 20 mg/day or placebo, with outcomes reported for whites (N=7,746). Lp(a) concentrations (nmol/L) were highest in blacks (median [25th-75th percentile] 60 [34-100]), then Asians (38 [18-60]), hispanics (24 [11-46]), and whites (23 [10-50]); p<0.001. While 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 CVD: adjusted hazard ratio (HR) per 1-SD increment in Ln[Lp(a)] 1.18 (95%CI 1.03 - 1.34; p=0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of CVD: adjusted HR 1.27 (95%CI 1.01 - 1.59; p=0.04), which was independent of LDL-cholesterol and other factors. Rosuvastatin significantly reduced incident CVD among participants with baseline Lp(a)≥median (HR 0.62, 0.43-0.90) and Lp(a)<median (HR 0.46, 0.30-0.72), with no evidence of interaction. Similar results were obtained when analyses included non-whites.
Conclusions—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).
Clinical Trials Registration Information—clinicaltrial.gov. Identifier: NCT00239681.
- Received June 12, 2013.
- Revision received October 23, 2013.
- Accepted October 24, 2013.