title: Atherogenic dyslipidemia and residual cardiovascular risk in statin-treated patients.
abstract: OBJECTIVE
  Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high triglycerides (triglycerides≥150 mg/dL).
  
  
  METHODS
  We studied subjects with stroke or transient ischemic attack in the Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM; n=19,100) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL; n=4731) trials who were treated with a statin and who had high-density lipoprotein cholesterol and triglycerides measurements 3 months after randomization (n=10,498 and 2900, respectively). The primary outcome measure for this exploratory analysis was the occurrence of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). We also performed a time-varying analysis to account for all available high-density lipoprotein cholesterol and triglyceride measurements.
  
  
  RESULTS
  A total of 10% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06-1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95% confidence interval, 1.03-1.48 in PERFORM and hazard ratio, 1.24; 95% confidence interval, 0.93-1.65 in SPARCL). Time-varying analysis confirmed these findings.
  
  
  CONCLUSIONS
  The presence of atherogenic dyslipidemia was associated with higher residual cardiovascular risk in PERFORM and SPARCL subjects with stroke or transient ischemic attack receiving statin therapy. Specific therapeutic interventions should now be trialed to address this residual risk.
authors.affiliation: From the INSERM U698 and Paris-Diderot University, Sorbonne Paris Cité, Paris, France (G.S., J.L., P.A.); Department of Neurology and Stroke Centre, Bichat University Hospital, Paris, France (G.S., P.A.); Department of Biostatistics, EA2694, UDSL, University of Lille Nord de France, CHU Lille, Lille, France (J.L.); Department of Endocrinology, Pitié-Salpêtrière University Hospital, Paris, France (E.B.); Department of Neurology, Duke Comprehensive Stroke Center, Durham VAMC, Durham, NC (L.B.G.); NHLI Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom (K.M.F.); and Stroke Prevention Research Unit, NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, United Kingdom (P.M.R.).
authors.forename: Gaia
authors.initials: G
authors.lastname: Sirimarco
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.forename: Larry B
authors.initials: LB
authors.lastname: Goldstein
authors.forename: Kim M
authors.initials: KM
authors.lastname: Fox
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood; D015897:Comorbidity; D050171:Dyslipidemias / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides
keywords: HMG-CoA reductase inhibitors; cardiovascular diseases; lipids; stroke