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)

Circulation. 2014 Feb 11;129(6):635-42. doi: 10.1161/CIRCULATIONAHA.113.004406. Epub 2013 Nov 17.

Abstract

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).

Clinical trials registration url: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Keywords: lipoproteins; risk factors; statins, HMG-CoA.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group / statistics & numerical data
  • Aged
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / ethnology
  • Cardiovascular Diseases* / prevention & control
  • Double-Blind Method
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Fluorobenzenes / administration & dosage*
  • Follow-Up Studies
  • Hispanic Americans / statistics & numerical data
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Incidence
  • Lipoprotein(a) / blood*
  • Male
  • Middle Aged
  • Placebos
  • Pyrimidines / administration & dosage*
  • Risk Factors
  • Rosuvastatin Calcium
  • Sulfonamides / administration & dosage*
  • Treatment Outcome

Substances

  • Fluorobenzenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoprotein(a)
  • Placebos
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium

Associated data

  • ClinicalTrials.gov/NCT00239681