Archna Bajaj1, Scott M Damrauer2, Amanda H Anderson2, Dawei Xie2, Matthew J Budoff2, Alan S Go2, Jiang He2, James P Lash2, Akinlolu Ojo2, Wendy S Post2, Mahboob Rahman2, Muredach P Reilly2, Danish Saleheen2, Raymond R Townsend2, Jinbo Chen2, Daniel J Rader2. 1. From the Division of General Internal Medicine, Department of Medicine (A.B.), Division of Vascular Surgery (S.M.D.), Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics (A.H.A., D.X., D.S., J.C.), Department of Genetics (D.S., D.J.R.), Department of Medicine (D.J.R.), Department of Pediatrics (D.J.R.), The Penn Cardiovascular Institute (D.J.R.), and Institute for Translational Medicine and Therapeutics (D.J.R.), University of Pennsylvania, Philadelphia; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA (S.M.D.); Department of Medicine, Los Angeles Biomedical Research Institute at Harbor, University of California-Los Angles (M.J.B.); Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.S.G.); Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H.); Division of Nephrology, Department of Medicine, University of Illinois at Chicago (J.P.L.); Department of Medicine, University of Michigan, Ann Arbor (A.O.); Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (W.S.P.); Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD (W.S.P.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); Division of Cardiology, Department of Medicine, (M.P.R.) and Irving Institute for Clinical and Translational Research (M.P.R.), Columbia University, New York, NY; and Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (R.R.T.). bajaja@mail.med.upenn.edu. 2. From the Division of General Internal Medicine, Department of Medicine (A.B.), Division of Vascular Surgery (S.M.D.), Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics (A.H.A., D.X., D.S., J.C.), Department of Genetics (D.S., D.J.R.), Department of Medicine (D.J.R.), Department of Pediatrics (D.J.R.), The Penn Cardiovascular Institute (D.J.R.), and Institute for Translational Medicine and Therapeutics (D.J.R.), University of Pennsylvania, Philadelphia; Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA (S.M.D.); Department of Medicine, Los Angeles Biomedical Research Institute at Harbor, University of California-Los Angles (M.J.B.); Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.S.G.); Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H.); Division of Nephrology, Department of Medicine, University of Illinois at Chicago (J.P.L.); Department of Medicine, University of Michigan, Ann Arbor (A.O.); Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (W.S.P.); Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD (W.S.P.); Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH (M.R.); Division of Cardiology, Department of Medicine, (M.P.R.) and Irving Institute for Clinical and Translational Research (M.P.R.), Columbia University, New York, NY; and Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (R.R.T.).
Abstract
OBJECTIVE: To investigate the effect of LPA gene variants and renal function on lipoprotein(a) [Lp(a)] levels in people with chronic kidney disease and determine the association between elevated Lp(a) and myocardial infarction and death in this setting. APPROACH AND RESULTS: The CRIC Study (Chronic Renal Insufficiency Cohort) is an ongoing prospective study of 3939 participants with chronic kidney disease. In 3635 CRIC participants with genotype data, carriers of the rs10455872 or rs6930542 variants had a higher median Lp(a) level (mg/dL) compared with noncarriers (73 versus 23; P<0.001 and 56 versus 22; P<0.001, respectively). The 3744 participants (55% male and 41% non-Hispanic White) with available baseline Lp(a) levels were stratified into quartiles of baseline Lp(a) (mg/dL): <9.8, 9.8 to 26.0, 26.1 to 61.3, and >61.3. There were 315 myocardial infarctions and 822 deaths during a median follow-up of 7.5 years. The second quartile had the lowest event rate. After adjusting for potential confounders and using a Cox proportional hazards model, the highest quartile of Lp(a) was associated with increased risk of myocardial infarction (hazard ratio, 1.49; 95% confidence interval, 1.05-2.11), death (hazard ratio, 1.28; 95% confidence interval, 1.05-1.57), and the composite outcome (hazard ratio, 1.29; 95% confidence interval, 1.07-1.56) compared with the second quartile of Lp(a). CONCLUSIONS: Among adults with chronic kidney disease, elevated Lp(a) is independently associated with myocardial infarction and death. Future studies exploring pharmacological Lp(a) reduction in this population are warranted.
OBJECTIVE: To investigate the effect of LPA gene variants and renal function on lipoprotein(a) [Lp(a)] levels in people with chronic kidney disease and determine the association between elevated Lp(a) and myocardial infarction and death in this setting. APPROACH AND RESULTS: The CRIC Study (Chronic Renal Insufficiency Cohort) is an ongoing prospective study of 3939 participants with chronic kidney disease. In 3635 CRIC participants with genotype data, carriers of the rs10455872 or rs6930542 variants had a higher median Lp(a) level (mg/dL) compared with noncarriers (73 versus 23; P<0.001 and 56 versus 22; P<0.001, respectively). The 3744 participants (55% male and 41% non-Hispanic White) with available baseline Lp(a) levels were stratified into quartiles of baseline Lp(a) (mg/dL): <9.8, 9.8 to 26.0, 26.1 to 61.3, and >61.3. There were 315 myocardial infarctions and 822 deaths during a median follow-up of 7.5 years. The second quartile had the lowest event rate. After adjusting for potential confounders and using a Cox proportional hazards model, the highest quartile of Lp(a) was associated with increased risk of myocardial infarction (hazard ratio, 1.49; 95% confidence interval, 1.05-2.11), death (hazard ratio, 1.28; 95% confidence interval, 1.05-1.57), and the composite outcome (hazard ratio, 1.29; 95% confidence interval, 1.07-1.56) compared with the second quartile of Lp(a). CONCLUSIONS: Among adults with chronic kidney disease, elevated Lp(a) is independently associated with myocardial infarction and death. Future studies exploring pharmacological Lp(a) reduction in this population are warranted.
Authors: Julio A Lamprea-Montealegre; A Richey Sharrett; Kunihiro Matsushita; Elizabeth Selvin; Moyses Szklo; Brad C Astor Journal: Atherosclerosis Date: 2014-02-20 Impact factor: 5.162
Authors: J Craig Longenecker; Michael J Klag; Santica M Marcovina; Yong-Mei Liu; Bernard G Jaar; Neil R Powe; Nancy E Fink; Andrew S Levey; Josef Coresh Journal: J Am Soc Nephrol Date: 2005-03-30 Impact factor: 10.121
Authors: Wensheng Lu; Yu-Ching Cheng; Keping Chen; Hong Wang; Glenn S Gerhard; Christopher D Still; Xin Chu; Rongze Yang; Ankita Parihar; Jeffrey R O'Connell; Toni I Pollin; Eduardo Angles-Cano; Michael J Quon; Braxton D Mitchell; Alan R Shuldiner; Mao Fu Journal: Hum Mol Genet Date: 2015-01-09 Impact factor: 6.150
Authors: Connor A Emdin; Amit V Khera; Pradeep Natarajan; Derek Klarin; Hong-Hee Won; Gina M Peloso; Nathan O Stitziel; Akihiro Nomura; Seyedeh M Zekavat; Alexander G Bick; Namrata Gupta; Rosanna Asselta; Stefano Duga; Piera Angelica Merlini; Adolfo Correa; Thorsten Kessler; James G Wilson; Matthew J Bown; Alistair S Hall; Peter S Braund; Nilesh J Samani; Heribert Schunkert; Jaume Marrugat; Roberto Elosua; Ruth McPherson; Martin Farrall; Hugh Watkins; Cristen Willer; Gonçalo R Abecasis; Janine F Felix; Ramachandran S Vasan; Eric Lander; Daniel J Rader; John Danesh; Diego Ardissino; Stacey Gabriel; Danish Saleheen; Sekar Kathiresan Journal: J Am Coll Cardiol Date: 2016-12-27 Impact factor: 24.094
Authors: Rahul C Deo; James G Wilson; Chao Xing; Kim Lawson; W H Linda Kao; David Reich; Arti Tandon; Ermeg Akylbekova; Nick Patterson; Thomas H Mosley; Eric Boerwinkle; Herman A Taylor Journal: PLoS One Date: 2011-01-24 Impact factor: 3.240
Authors: Sotirios Tsimikas; Sergio Fazio; Keith C Ferdinand; Henry N Ginsberg; Marlys L Koschinsky; Santica M Marcovina; Patrick M Moriarty; Daniel J Rader; Alan T Remaley; Gissette Reyes-Soffer; Raul D Santos; George Thanassoulis; Joseph L Witztum; Simhan Danthi; Michelle Olive; Lijuan Liu Journal: J Am Coll Cardiol Date: 2018-01-16 Impact factor: 24.094
Authors: Tariq E Farrah; Atul Anand; Peter J Gallacher; Robert Kimmitt; Edwin Carter; James W Dear; Nicholas L Mills; David J Webb; Neeraj Dhaun Journal: Hypertension Date: 2019-06-10 Impact factor: 10.190