title: Strict blood pressure control associates with decreased mortality risk by APOL1 genotype.
abstract: Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001. This included 682 participants with known APOL1 genotype (157 with high-risk genotype) previously assigned to either strict (mean arterial pressure [MAP] 92 mm Hg or less) versus usual blood pressure control (MAP 102-107 mm Hg) during the trial. During a median follow-up of 14.5 years, risk of death did not differ between individuals with high- versus low-risk APOL1 genotypes (unadjusted hazard ratio 1.00 [95% confidence interval 0.76-1.33]). However, a significant interaction was detected between the APOL1 risk group and blood pressure control strategy. In the APOL1 high-risk group, the risk of death was 42% lower comparing strict versus usual blood pressure control (0.58 [0.35-0.97]). In the APOL1 low-risk group, the risk of death comparing strict versus usual blood pressure control was not significantly different (1.09 [0.84-1.43]). Thus, strict blood pressure control during CKD associates with a lower risk of death in blacks with the high-risk CKD APOL1 genotype. Knowledge of APOL1 status could inform selection of blood pressure treatment targets in black CKD patients.
authors.affiliation: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA; Division of Pediatric Nephrology, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA. Electronic address: elaine.ku@ucsf.edu.
authors.forename: Elaine
authors.initials: E
authors.lastname: Ku
authors.affiliation: Division of Nephrology, Department of Medicine, Georgetown University, Washington, DC, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lipkowitz
authors.affiliation: Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Appel
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland, Baltimore, Maryland, USA; Department of Medicine, Baltimore VA Medical Center, Baltimore, Maryland, USA.
authors.forename: Afshin
authors.initials: A
authors.lastname: Parsa
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gassman
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Smogorzewski
authors.affiliation: Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Hsu
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D062186:Arterial Pressure / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D065840:Protective Factors; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C108666:APOL1 protein, human; D000959:Antihypertensive Agents; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: APOL1 genotype; CKD; mortality