title: Non-HDL Cholesterol and Triglycerides: Implications for Coronary Atheroma Progression and Clinical Events.
abstract: Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume.
  
  
  
  Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (ΔPAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) </≥70 mg/dL and C-reactive protein </≥2 mg/L and in patients with or without diabetes mellitus. On-treatment non-HDLC levels linearly associated with ΔPAV. Overt PAV progression (ΔPAV>0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ΔPAV were more strongly influenced by changes in non-HDLC (β=0.62; P<0.001) compared with changes in LDLC (β=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve.
  
  
  
  Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC. Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk.
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Rishi
authors: R
authors: Puri
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.). nissens@ccf.org.
authors: Steven E
authors: SE
authors: Nissen
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Mingyuan
authors: M
authors: Shao
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Mohamed B
authors: MB
authors: Elshazly
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Yu
authors: Y
authors: Kataoka
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Samir R
authors: SR
authors: Kapadia
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: E Murat
authors: EM
authors: Tuzcu
authors: From the Cleveland Clinic Coordinating Center for Clinical Research (C5R) (R.P., S.E.N., M.S.), and Department of Cardiovascular Medicine (R.P., S.E.N., M.B.E., S.R.K., E.M.T.), Cleveland Clinic, OH; Department of Medicine, University of Adelaide, Australia (R.P., S.J.N.); and South Australian Health and Medical Research Institute, Adelaide, Australia (Y.K., S.J.N.).
authors: Stephen J
authors: SJ
authors: Nicholls
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*; D018084:Ultrasonography, Interventional
chemical_list: D015415:Biomarkers; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol
keywords: atherosclerosis; low-density lipoprotein; non-HDL; residual risk; triglycerides