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Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD.
Am J Kidney Dis. 2019 06; 73(6):827-836.AJ

Abstract

RATIONALE & OBJECTIVE

A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD.

STUDY DESIGN

Prospective cohort study.

SETTINGS & PARTICIPANTS

Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States.

PREDICTOR

Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles.

OUTCOME

A composite ASCVD event of myocardial infarction or ischemic stroke.

ANALYTIC APPROACH

Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor.

RESULTS

Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile).

LIMITATIONS

Associations based on observational data do not permit inferences about causal associations.

CONCLUSIONS

Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD.

Authors+Show Affiliations

Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA. Electronic address: bajaja@pennmedicine.upenn.edu.Department of Biostatistics and Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Division of Nephrology, Department of Medicine, University of Illinois College of Medicine at Chicago, Chicago, IL.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.Division of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine, New Orleans, LA.Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Biostatistics and Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Division of Research, Kaiser Permanente Northern California, Oakland, CA.Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.Division of Nephrology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH.Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.Division of Nephrology and Hypertension, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH.Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.Department of Biostatistics and Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; The Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30686529

Citation

Bajaj, Archna, et al. "Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 73, no. 6, 2019, pp. 827-836.
Bajaj A, Xie D, Cedillo-Couvert E, et al. Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD. Am J Kidney Dis. 2019;73(6):827-836.
Bajaj, A., Xie, D., Cedillo-Couvert, E., Charleston, J., Chen, J., Deo, R., Feldman, H. I., Go, A. S., He, J., Horwitz, E., Kallem, R., Rahman, M., Weir, M. R., Anderson, A. H., & Rader, D. J. (2019). Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 73(6), 827-836. https://doi.org/10.1053/j.ajkd.2018.11.010
Bajaj A, et al. Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD. Am J Kidney Dis. 2019;73(6):827-836. PubMed PMID: 30686529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD. AU - Bajaj,Archna, AU - Xie,Dawei, AU - Cedillo-Couvert,Esteban, AU - Charleston,Jeanne, AU - Chen,Jing, AU - Deo,Rajat, AU - Feldman,Harold I, AU - Go,Alan S, AU - He,Jiang, AU - Horwitz,Edward, AU - Kallem,Radhakrishna, AU - Rahman,Mahboob, AU - Weir,Matthew R, AU - Anderson,Amanda H, AU - Rader,Daniel J, AU - ,, Y1 - 2019/01/25/ PY - 2018/06/01/received PY - 2018/11/26/accepted PY - 2019/1/29/pubmed PY - 2020/3/12/medline PY - 2019/1/29/entrez KW - Lipids KW - apolipoprotein KW - atherosclerotic cardiovascular disease (ASCVD) KW - chronic kidney disease (CKD) KW - high-density lipoprotein cholesterol (HDL-C) KW - ischemic stroke KW - myocardial infarction (MI) KW - triglyceride KW - very low-density lipoprotein cholesterol (VLDL-C) SP - 827 EP - 836 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 73 IS - 6 N2 - RATIONALE & OBJECTIVE: A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States. PREDICTOR: Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles. OUTCOME: A composite ASCVD event of myocardial infarction or ischemic stroke. ANALYTIC APPROACH: Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor. RESULTS: Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile). LIMITATIONS: Associations based on observational data do not permit inferences about causal associations. CONCLUSIONS: Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/30686529/Lipids_Apolipoproteins_and_Risk_of_Atherosclerotic_Cardiovascular_Disease_in_Persons_With_CKD_ DB - PRIME DP - Unbound Medicine ER -