Rishi Puri1, Steven E Nissen2, Mingyuan Shao1, Mohamed B Elshazly1, Yu Kataoka1, Samir R Kapadia1, E Murat Tuzcu1, Stephen J Nicholls1. 1. 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.). 2. 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.
Abstract
OBJECTIVES: 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. APPROACH AND RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: 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. APPROACH AND RESULTS: 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. CONCLUSIONS: 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: Stephen J Nicholls; A Michael Lincoff; Dianna Bash; Christie M Ballantyne; Philip J Barter; Michael H Davidson; John J P Kastelein; Wolfgang Koenig; Darren K McGuire; Dariush Mozaffarian; Terje R Pedersen; Paul M Ridker; Kausik Ray; Björn W Karlson; Torbjörn Lundström; Kathy Wolski; Steven E Nissen Journal: Clin Cardiol Date: 2018-09-28 Impact factor: 2.882
Authors: Dirk Müller-Wieland; Lawrence A Leiter; Bertrand Cariou; Alexia Letierce; Helen M Colhoun; Stefano Del Prato; Robert R Henry; Francisco J Tinahones; Lisa Aurand; Jaman Maroni; Kausik K Ray; Maja Bujas-Bobanovic Journal: Cardiovasc Diabetol Date: 2017-05-25 Impact factor: 9.951