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.


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.


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).
http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
Division of Preventive Medicine (A.V.K., B.M.E., P.M.R., S.M.) and Division of Cardiovascular Medicine (B.M.E., P.M.R., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Quest Diagnostics Nichols Institute, San Juan Capistrano, CA (M.P.C., F.M.H., J.W.).
Amit V
AV
Khera
Brendan M
BM
Everett
Michael P
MP
Caulfield
Feras M
FM
Hantash
Jay
J
Wohlgemuth
Paul M
PM
Ridker
Samia
S
Mora
D000368:Aged; D044383:Black People / Q000706:statistics & numerical data; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000208:ethnology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015994:Incidence; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011743:Pyrimidines / Q000008:administration & dosage*; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D044465:White People / Q000706:statistics & numerical data
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium
lipoproteins; risk factors; statins, HMG-CoA