APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial

SPRINT Research Group

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Abstract

Introduction Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results Of the participants, 14% had 2 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/1.73 m2 in those with normal kidney function at baseline (hazard ratio 1.64; 95% confidence interval = 0.85−2.93; P = 0.114, recessive model). Discussion APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT.

Original languageEnglish (US)
Pages (from-to)713-720
Number of pages8
JournalKidney International Reports
Volume2
Issue number4
DOIs
StatePublished - Jul 1 2017

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Apolipoproteins
Cardiovascular Diseases
Blood Pressure
Kidney
Mortality
Genes
African Americans
Myocardial Infarction
Albuminuria
Genetic Models
Acute Coronary Syndrome
Proportional Hazards Models
Heart Diseases
Heart Failure
Stroke
Confidence Intervals
Incidence

All Science Journal Classification (ASJC) codes

  • Nephrology

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APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial. / SPRINT Research Group.

In: Kidney International Reports, Vol. 2, No. 4, 01.07.2017, p. 713-720.

Research output: Contribution to journalArticle

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abstract = "Introduction Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results Of the participants, 14{\%} had 2 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/1.73 m2 in those with normal kidney function at baseline (hazard ratio 1.64; 95{\%} confidence interval = 0.85−2.93; P = 0.114, recessive model). Discussion APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT.",
author = "{SPRINT Research Group} and Freedman, {Barry I.} and Rocco, {Michael V.} and Bates, {Jeffrey T.} and Michel Chonchol and Hawfield, {Amret T.} and Lash, {James P.} and Vasilios Papademetriou and Sedor, {John R.} and Karen Servilla and Kimmel, {Paul L.} and Barry Wall and Pajewski, {Nicholas M.}",
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T1 - APOL1 Renal-Risk Variants Do Not Associate With Incident Cardiovascular Disease or Mortality in the Systolic Blood Pressure Intervention Trial

AU - SPRINT Research Group

AU - Freedman, Barry I.

AU - Rocco, Michael V.

AU - Bates, Jeffrey T.

AU - Chonchol, Michel

AU - Hawfield, Amret T.

AU - Lash, James P.

AU - Papademetriou, Vasilios

AU - Sedor, John R.

AU - Servilla, Karen

AU - Kimmel, Paul L.

AU - Wall, Barry

AU - Pajewski, Nicholas M.

PY - 2017/7/1

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N2 - Introduction Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results Of the participants, 14% had 2 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/1.73 m2 in those with normal kidney function at baseline (hazard ratio 1.64; 95% confidence interval = 0.85−2.93; P = 0.114, recessive model). Discussion APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT.

AB - Introduction Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, a total of 2568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including nonfatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality. Methods Cox proportional hazards regression models were used, adjusting for age, sex, African ancestry proportion, and treatment group (systolic blood pressure target of <120 mm Hg vs. <140 mm Hg). Results Of the participants, 14% had 2 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/1.73 m2 in those with normal kidney function at baseline (hazard ratio 1.64; 95% confidence interval = 0.85−2.93; P = 0.114, recessive model). Discussion APOL1 RRVs were not associated with incident CVD in high-risk hypertensive, nondiabetic African American participants in SPRINT.

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