Lipoprotein(a) and Risk of Myocardial Infarction and Death in Chronic Kidney Disease: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort)

Archna Bajaj; Scott M Damrauer; Amanda H Anderson; Dawei Xie; Matthew J Budoff; Alan S Go; Jiang He; James P Lash; Akinlolu Ojo; Wendy S Post; Mahboob Rahman; Muredach P Reilly; Danish Saleheen; Raymond R Townsend; Jinbo Chen; Daniel J Rader; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators*

doi:10.1161/ATVBAHA.117.309920

Lipoprotein(a) and Risk of Myocardial Infarction and Death in Chronic Kidney Disease: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort)

Arterioscler Thromb Vasc Biol. 2017 Oct;37(10):1971-1978. doi: 10.1161/ATVBAHA.117.309920. Epub 2017 Aug 24.

Authors

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; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators*

Affiliations

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.

Keywords: chronic kidney disease; genotype; lipoprotein(a); myocardial infarction.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Female
Genotype
Humans
Lipoprotein(a) / blood*
Lipoprotein(a) / genetics
Male
Middle Aged
Myocardial Infarction / blood*
Myocardial Infarction / epidemiology*
Myocardial Infarction / mortality
Proportional Hazards Models
Renal Insufficiency, Chronic / blood*
Renal Insufficiency, Chronic / epidemiology*
Risk Factors
United States / epidemiology

Substances

Lipoprotein(a)

Abstract

Publication types

MeSH terms

Substances

Grants and funding