Teresa K Chen1, Lawrence J Appel2, Morgan E Grams2, Adrienne Tin2, Michael J Choi2, Michael S Lipkowitz2, Cheryl A Winkler2, Michelle M Estrella2. 1. From the Divisions of Nephrology (T.K.C., M.E.G., M.J.C.) and General Internal Medicine (L.J.A.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (L.J.A., M.E.G., A.T.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.T.); Division of Nephrology and Hypertension, Department of Medicine, Georgetown University School of Medicine, Washington, DC (M.S.L.); Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health and Leidos Biomedical, Frederick National Laboratory, MD (C.A.W.); and Kidney Health Research Collaborative, Department of Medicine, San Francisco VA Medical Center and University of California (M.M.E.). tchen39@jhmi.edu. 2. From the Divisions of Nephrology (T.K.C., M.E.G., M.J.C.) and General Internal Medicine (L.J.A.), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD (L.J.A., M.E.G., A.T.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (A.T.); Division of Nephrology and Hypertension, Department of Medicine, Georgetown University School of Medicine, Washington, DC (M.S.L.); Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health and Leidos Biomedical, Frederick National Laboratory, MD (C.A.W.); and Kidney Health Research Collaborative, Department of Medicine, San Francisco VA Medical Center and University of California (M.M.E.).
Abstract
OBJECTIVE: Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m2) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality. CONCLUSIONS: Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.
RCT Entities:
OBJECTIVE: Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes. We adjusted for age, sex, ancestry, smoking, heart disease history, body mass index, cholesterol, randomized treatment groups, and baseline and longitudinal estimated glomerular filtration rate, systolic blood pressure, and proteinuria. Among 693 participants with APOL1 genotyping available (23% high risk), the high-risk group had lower mean estimated glomerular filtration rate (44.7 versus 50.1 mL/min per 1.73 m2) and greater proteinuria (median 0.19 versus 0.06) compared with the low-risk group at baseline. There was no significant association between APOL1 genotypes and the composite cardiovascular disease outcome in both unadjusted (hazard ratio=1.23; 95% confidence interval: 0.83-1.81) and fully adjusted (hazard ratio=1.16; 95% confidence interval: 0.77-1.76) models; however, in using an additive model, APOL1 high-risk variants were associated with increased cardiovascular mortality. CONCLUSIONS: Among African Americans with hypertension-attributed chronic kidney disease, APOL1 risk variants were not associated with an overall risk for cardiovascular disease although some signals for cardiovascular mortality were noted.
Authors: P N Duchateau; C R Pullinger; R E Orellana; S T Kunitake; J Naya-Vigne; P M O'Connor; M J Malloy; J P Kane Journal: J Biol Chem Date: 1997-10-10 Impact factor: 5.157
Authors: Kunihiro Matsushita; Marije van der Velde; Brad C Astor; Mark Woodward; Andrew S Levey; Paul E de Jong; Josef Coresh; Ron T Gansevoort Journal: Lancet Date: 2010-05-17 Impact factor: 79.321
Authors: Marije van der Velde; Kunihiro Matsushita; Josef Coresh; Brad C Astor; Mark Woodward; Andrew Levey; Paul de Jong; Ron T Gansevoort; Marije van der Velde; Kunihiro Matsushita; Josef Coresh; Brad C Astor; Mark Woodward; Andrew S Levey; Paul E de Jong; Ron T Gansevoort; Andrew Levey; Meguid El-Nahas; Kai-Uwe Eckardt; Bertram L Kasiske; Toshiharu Ninomiya; John Chalmers; Stephen Macmahon; Marcello Tonelli; Brenda Hemmelgarn; Frank Sacks; Gary Curhan; Allan J Collins; Suying Li; Shu-Cheng Chen; K P Hawaii Cohort; Brian J Lee; Areef Ishani; James Neaton; Ken Svendsen; Johannes F E Mann; Salim Yusuf; Koon K Teo; Peggy Gao; Robert G Nelson; William C Knowler; Henk J Bilo; Hanneke Joosten; Nanno Kleefstra; K H Groenier; Priscilla Auguste; Kasper Veldhuis; Yaping Wang; Laura Camarata; Beverly Thomas; Tom Manley Journal: Kidney Int Date: 2011-02-09 Impact factor: 10.612
Authors: Jeffrey B Kopp; George W Nelson; Karmini Sampath; Randall C Johnson; Giulio Genovese; Ping An; David Friedman; William Briggs; Richard Dart; Stephen Korbet; Michele H Mokrzycki; Paul L Kimmel; Sophie Limou; Tejinder S Ahuja; Jeffrey S Berns; Justyna Fryc; Eric E Simon; Michael C Smith; Howard Trachtman; Donna M Michel; Jeffrey R Schelling; David Vlahov; Martin Pollak; Cheryl A Winkler Journal: J Am Soc Nephrol Date: 2011-10-13 Impact factor: 10.121
Authors: Barry I Freedman; Crystal A Gadegbeku; R Nick Bryan; Nicholas M Pajewski; Jasmin Divers; Nicholette D Palmer; Pamela J Hicks; Lijun Ma; Michael V Rocco; S Carrie Smith; Jianzhao Xu; Christopher T Whitlow; Benjamin C Wagner; Carl D Langefeld; Amret T Hawfield; Jeffrey T Bates; Alan J Lerner; Dominic S Raj; Mohammad S Sadaghiani; Robert D Toto; Jackson T Wright; Donald W Bowden; Jeff D Williamson; Kaycee M Sink; Joseph A Maldjian Journal: Kidney Int Date: 2016-06-22 Impact factor: 10.612
Authors: Lijun Ma; Gregory S Shelness; James A Snipes; Mariana Murea; Peter A Antinozzi; Dongmei Cheng; Moin A Saleem; Simon C Satchell; Bernhard Banas; Peter W Mathieson; Matthias Kretzler; Ashok K Hemal; Lawrence L Rudel; Snezana Petrovic; Allison Weckerle; Martin R Pollak; Michael D Ross; John S Parks; Barry I Freedman Journal: J Am Soc Nephrol Date: 2014-07-10 Impact factor: 10.121
Authors: Carl D Langefeld; Jasmin Divers; Nicholas M Pajewski; Amret T Hawfield; David M Reboussin; Diane E Bild; George A Kaysen; Paul L Kimmel; Dominic S Raj; Ana C Ricardo; Jackson T Wright; John R Sedor; Michael V Rocco; Barry I Freedman Journal: Kidney Int Date: 2014-07-16 Impact factor: 10.612
Authors: Michael S Lipkowitz; Barry I Freedman; Carl D Langefeld; Mary E Comeau; Donald W Bowden; W H Linda Kao; Brad C Astor; Erwin P Bottinger; Sudha K Iyengar; Paul E Klotman; Richard G Freedman; Weijia Zhang; Rulan S Parekh; Michael J Choi; George W Nelson; Cheryl A Winkler; Jeffrey B Kopp Journal: Kidney Int Date: 2012-07-25 Impact factor: 10.612
Authors: Nora Franceschini; Jeffrey B Kopp; Ana Barac; Lisa W Martin; Yun Li; Huijun Qian; Alex P Reiner; Martin Pollak; Robert B Wallace; Wayne D Rosamond; Cheryl A Winkler Journal: JAMA Cardiol Date: 2018-08-01 Impact factor: 14.676
Authors: Alexander G Bick; Elvis Akwo; Cassianne Robinson-Cohen; Kyung Lee; Julie Lynch; Themistocles L Assimes; Scott DuVall; Todd Edwards; Huaying Fang; S Matthew Freiberg; Ayush Giri; Jennifer E Huffman; Jie Huang; Leland Hull; Rachel L Kember; Derek Klarin; Jennifer S Lee; Michael Levin; Donald R Miller; Pradeep Natarajan; Danish Saleheen; Qing Shao; Yan V Sun; Hua Tang; Otis Wilson; Kyong-Mi Chang; Kelly Cho; John Concato; J Michael Gaziano; Sekar Kathiresan; Christopher J O'Donnell; Daniel J Rader; Philip S Tsao; Peter W Wilson; Adriana M Hung; Scott M Damrauer Journal: Circulation Date: 2019-07-24 Impact factor: 29.690
Authors: Archna Bajaj; Andrea Ihegword; Chengxiang Qiu; Aeron M Small; Wei-Qi Wei; Lisa Bastarache; QiPing Feng; Rachel L Kember; Marjorie Risman; Roy D Bloom; David L Birtwell; Heather Williams; Christian M Shaffer; Jinbo Chen; Regeneron Genetics Center; Joshua C Denny; Daniel J Rader; C Michael Stein; Scott M Damrauer; Katalin Susztak Journal: Kidney Int Date: 2020-02-17 Impact factor: 10.612
Authors: Orlando M Gutiérrez; Marguerite R Irvin; Neil A Zakai; Rakhi P Naik; Ninad S Chaudhary; Michelle M Estrella; Sophie Limou; Suzanne E Judd; Mary Cushman; Jeffrey B Kopp; Cheryl A Winkler Journal: Am J Kidney Dis Date: 2019-09-26 Impact factor: 8.860
Authors: Orlando M Gutiérrez; Marguerite R Irvin; Ninad S Chaudhary; Mary Cushman; Neil A Zakai; Victor A David; Sophie Limou; Nathalie Pamir; Alex P Reiner; Rakhi P Naik; Michele M Sale; Monika M Safford; Hyacinth I Hyacinth; Suzanne E Judd; Jeffrey B Kopp; Cheryl A Winkler Journal: Circ Genom Precis Med Date: 2018-06