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APOL1 renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial.

ABSTRACT: Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, 2,568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including non-fatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non-fatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality.Cox proportional hazards regression models were employed adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg versus <140 mm Hg).Fourteen percent of participants had two APOL1 RRVs; these individuals also had lower baseline estimated GFR and higher levels of albuminuria and BMI. After a median follow-up of 39 months, no significant association was observed between APOL1 RRVs and the primary composite CVD outcome, any of its components, or all-cause mortality (recessive or additive genetic models). APOL1 demonstrated a trend toward association with sustained 30% reduction in estimated GFR to <60 ml/min/1.73m2 in those with normal kidney function at baseline (hazard ratio [95% CI] 1.64 [0.85-2.93]; p=0.114, recessive model).APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, non-diabetic African American participants in SPRINT.

SUBMITTER: Freedman BI

PROVIDER: S-EPMC5527675 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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<i>APOL1</i> renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial.

Freedman Barry I BI Rocco Michael V MV Bates Jeffrey T JT Chonchol Michel M Hawfield Amret T AT Lash James P JP Papademetriou Vasilios V Sedor John R JR Servilla Karen K Kimmel Paul L PL Wall Barry M BM Pajewski Nicholas M NM

Kidney international reports 20170331 4

<h4>Introduction</h4>Relationships between apolipoprotein L1 gene (<i>APOL1</i>) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between <i>APOL1</i> and CVD, 2,568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including non-fatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non-fa ...[more]

PMID: 28758155

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Project description:Rationale and objectiveAlthough low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality.Study designLongitudinal analysis of clinical trial participants.Settings and participants7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors.PredictorseGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits.OutcomesThe SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up.Analytical approachCox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18.ResultsMean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up.LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded.ConclusionsIn trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Project description:Rational & objectiveMany drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain.Study designLongitudinal subgroup analysis of clinical trial participants.Setting & participants2,089 Systolic Blood Pressure Intervention Trial participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline.ExposureSummary score incorporating urine-to-plasma ratios of 10 endogenous secretion markers measured in paired urine and plasma samples at baseline.OutcomeThe primary outcome was longitudinal change in eGFR. Secondary outcomes included chronic kidney disease (CKD) progression (≥50% eGFR decline or incident kidney failure requiring dialysis or kidney transplantation), a cardiovascular disease (CVD) composite (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes), and mortality.Analytical approachLinear mixed-effect models were used to evaluate the association between the secretion score and change in eGFR, and Cox proportional hazards models were used to evaluate associations with CKD progression, CVD, and mortality.ResultsAt baseline, mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. During a median follow-up of 3.3 years, mean change in eGFR was -1.44% per year, and 72 CKD progression events, 272 CVD events, and 144 deaths occurred. In multivariable analyses, lower secretion score was associated with faster eGFR decline and greater risk of CKD progression, CVD, and mortality. After further adjustment for baseline eGFR and albuminuria, each 1-standard deviation lower secretion score was associated with faster eGFR decline (-0.65% per year; 95% CI, -0.84% to -0.46%), but not CKD progression (HR, 1.23; 95% CI, 0.96-1.58), CVD (HR, 1.02; 95% CI, 0.89-1.18), or mortality (HR, 0.90; 95% CI, 0.74-1.09). The secretion score association with eGFR decline appeared stronger in participants with baseline eGFR <45 mL/min/1.73 m2 (P for interaction < 0.001).LimitationsPersons with diabetes and proteinuria >1 g/d were excluded.ConclusionsAmong SPRINT participants with CKD, lower estimated tubular secretion was associated with faster eGFR decline, independent of baseline eGFR and albuminuria, but not with CKD progression, CVD, or mortality.

Dataset Information

APOL1 renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial.

Publications

<i>APOL1</i> renal-risk variants do not associate with incident cardiovascular disease or mortality in the Systolic Blood Pressure Intervention Trial.

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