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)
Lipoprotein(a) [Lp(a)] is a low-density lipoprotein–like particle largely independent of known risk factors and predictive of cardiovascular disease (CVD). Is Lp(a) a determinant of residual risk in the setting of low levels of low-density lipoprotein cholesterol (LDL-C) after potent statin therapy?
Baseline and on-treatment Lp(a) concentrations were assessed in 9,612 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 = 7,746). Lp(a) in mg/dl = nmol/L ÷ 2.8.
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). Baseline Lp(a) concentrations were associated with incident CVD (adjusted hazard ratio [HR] per 1-standard deviation increment in Ln[Lp(a)], 1.18; 95% confidence interval [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-C and other factors. Rosuvastatin significantly reduced incident CVD among participants with baseline Lp(a) greater than or equal to the median (HR, 0.62; 95% CI, 0.43–0.90) and Lp(a) less than the median (HR, 0.46; 95% CI, 0.30–0.72), with no evidence of interaction. Similar results were obtained when analyses included nonwhites.
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).
Lp(a) is both proatherogenic and prothrombotic and has been associated with premature myocardial infarction, strokes, deep-vein thrombosis/pulmonary embolism, and thrombosis of saphenous grafts. Many trials have demonstrated it remains a risk factor in persons with coronary disease on statins. This is the first to demonstrate it remains an important risk predictor in low-risk persons in whom the statin-treated LDL-C is very low. New developments in lipid therapy include a drug that directly targets Lp(a) (RNA anti-sense), which will clarify the attributable risk.
Keywords: Fluorobenzenes, Myocardial Infarction, Stroke, Pulmonary Embolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors, RNA, Antisense, Coronary Disease, Pyrimidines, Hispanic Americans, Cholesterol, Dyslipidemias, Cardiology, Cardiovascular Diseases, Venous Thrombosis, Confidence Intervals, Sulfonamides
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