Race, APOL1 Risk, and eGFR Decline in the General Population

Grams, Morgan E.; Rebholz, Casey M.; Chen, Yuan; Rawlings, Andreea M.; Estrella, Michelle M.; Selvin, Elizabeth; Appel, Lawrence J.; Tin, Adrienne; Coresh, Josef

doi:10.1681/asn.2015070763

Cited by 129 publications

(139 citation statements)

References 38 publications

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“…We found no association between the APOL1 risk variants and incident MI, coronary heart disease, or stroke. These findings are in accordance with results from the ARIC (Atherosclerosis Risk in Communities) study and SPRINT trial, which also reported no significant association between the APOL1 high‐risk variants and incident or prevalent CVD, respectively 20, 25. On the other hand, the JHS and WHI (Women's Health Initiative) both demonstrated a significantly increased risk for a major adverse cardiovascular event among people with 2 versus 0 APOL1 high‐risk alleles,21 whereas the CHS noted an increased risk of MI but not stroke or cardiovascular mortality 22.…”

Section: Discussionsupporting

confidence: 90%

“…On the other hand, the JHS and WHI (Women's Health Initiative) both demonstrated a significantly increased risk for a major adverse cardiovascular event among people with 2 versus 0 APOL1 high‐risk alleles,21 whereas the CHS noted an increased risk of MI but not stroke or cardiovascular mortality 22. The reasons for these discrepant findings are unclear, although differences in study populations likely contribute, including varying ages and comorbidities 20, 21, 22, 25…”

Section: Discussionmentioning

confidence: 99%

“…In longitudinal analyses of community‐based blacks, postmenopausal women, or older individuals, APOL1 risk variants have been associated with increased cardiovascular morbidity 21, 22. Other longitudinal analyses in the general population and among blacks with diabetes mellitus or hypertension, however, have reported either no association with clinical CVD or even reduced risk for subclinical CVD 23, 24, 25…”

Section: Introductionmentioning

confidence: 99%

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Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Chen

Katz

Estrella

et al. 2017

JAHA

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Background APOL1 genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by APOL1 genotypes among self‐identified black participants of MESA (Multi‐Ethnic Study of Atherosclerosis).Methods and ResultsCross‐sectional associations of APOL1 genotypes (high‐risk=2 alleles; low‐risk=0 or 1 allele) with coronary artery calcification, carotid‐intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of APOL1 genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with APOL1 genotyping (mean age 62 years, 55% women, mean cystatin C–based estimated glomerular filtration rate 89 mL/min per 1.73 m2, 12% with albuminuria), 12% had the high‐risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid‐intimal media thickness, or left ventricular mass by APOL1 genotypes. The APOL1 high‐risk group was 82% more likely to develop incident heart failure compared with the low‐risk group (95% confidence interval, 1.01–3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00–3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03–3.35) slightly attenuated this association. The APOL1 high‐risk genotypes were not significantly associated with other clinical CVD outcomes.ConclusionsAmong blacks without baseline CVD, the APOL1 high‐risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Chen

Katz

Estrella

et al. 2017

JAHA

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“…15,17 Some investigators have also described an increased risk of cardiovascular disease among individuals with two APOL1 high-risk alleles, though this finding has not been consistent across studies. 26–29 In addition, Skorecki and Wasser illustrated that the geographic distribution of APOL1 risk variants correlates with the distribution of hypertension prevalence rates in West Africa. 30 Finally, in APOL1 expression studies by Madhavan et al , de novo expression of APOL1 was found in arterial smooth muscle cells of diseased but not healthy kidneys.…”

Section: Discussionmentioning

confidence: 99%

APOL1 genetic variants are not associated with longitudinal blood pressure in young black adults

Chen

Estrella

Vittinghoff

et al. 2017

Kidney International

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Whether APOL1 polymorphisms contribute to the excess risk of hypertension among blacks is unknown. To assess this we evaluated whether self-reported race and, in blacks, APOL1 risk variants (high-risk [2 risk alleles] versus low-risk [0–1 risk allele]) were associated with longitudinal blood pressure. Blood pressure trajectories were determined using linear mixed-effects (slope) and latent class models (5 distinct groups) during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults Study. Associations of race and APOL1 genotypes with blood pressure change, separately, using linear mixed-effects and multinomial logistic regression models, adjusting for demographic, socioeconomic, and traditional hypertension risk factors, anti-hypertensive medication use, and kidney function were evaluated. Among 1700 whites and 1330 blacks (13% APOL1 high-risk, mean age 25 years; 46% male) mean mid-, ([systolic + diastolic blood pressure]/2), systolic and diastolic blood pressures were 89, 110, 69 mmHg, respectively. One percent of participants used anti-hypertensive medications at baseline. Compared to whites, blacks, regardless of APOL1 genotype, had significantly greater increases in mid-blood pressure and were more likely to experience significantly increasing mid-blood pressure trajectories with adjusted relative risk ratios of 5.21 and 7.27 for moderate-increasing and elevated-increasing versus low-stable blood pressure, respectively. Among blacks, longitudinal mid-blood pressure changes and mid-blood pressure trajectory classification were similar by APOL1 risk status. Modeling systolic and diastolic blood pressure as outcomes yielded similar findings. From young adulthood to mid-life, blacks have greater blood pressure increases versus whites that are not fully explained by traditional risk factors. Thus APOL1 variants are not associated with longitudinal blood pressure in blacks.

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“…The decline of kidney function in the general population and the progression of CKD to ESRD are highly variable (1)(2)(3)(4). Some individuals may experience an unremitting decline in eGFR, whereas others maintain stable eGFR for an extended period (2,3).…”

Section: Introductionmentioning

confidence: 99%

Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK

Tin

Grams²,

Estrella³

et al. 2016

CJASN

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Background and objectives Trajectories of eGFR in patients with CKD are highly variable. Only a subset of patients with CKD experiences a steady decline in eGFR. The objective of our study was to investigate whether eGFR trajectory patterns differ by APOL1 risk status.Design, setting, participants, & measurements Our study was a longitudinal observational study of 622 participants in the African American Study of Kidney Disease and Hypertension with APOL1 genotyping and sufficient follow-up for estimating GFR trajectories. The predictor was APOL1 high-risk status (having two copies of the G1 or G2 risk alleles) versus low-risk status (zero or one copy of the risk alleles), and the outcome was four eGFR trajectory patterns on the basis of the joint probabilities of linearity and progression: steady decline, unsteady decline, steady stable, and unsteady stable.Results Over a median follow-up of 9 years, 24.0% of participants experienced steady eGFR decline, 25.9% had an unsteady decline, 25.6% were steady and stable, and 24.6% were unsteady but stable. Those experiencing steady decline had lower eGFR and higher urine protein-to-creatinine ratio at baseline than participants with the other eGFR trajectory patterns. The APOL1 high-risk group was associated with a greater odds for the steady decline pattern than the APOL1 low-risk group (unadjusted odds ratio, 2.45; 95% confidence interval, 1.62 to 3.69). This association remained significant after adjusting for demographic factors, baseline eGFR, urine proteinto-creatinine ratio, treatment assignment, and follow-up time (adjusted odds ratio, 1.59; 95% confidence interval, 1.00 to 2.52).Conclusions Among patients with CKD attributed to hypertension, those with the APOL1 high-risk genotype were more likely to experience a steady decline trajectory in eGFR than those without the APOL1 high-risk genotype. These findings suggest a persistent underlying pathophysiologic process in those patients with the APOL1 high-risk genotype.

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Race, APOL1 Risk, and eGFR Decline in the General Population

Cited by 129 publications

References 38 publications

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

Association Between APOL1 Genotypes and Risk of Cardiovascular Disease in MESA (Multi‐Ethnic Study of Atherosclerosis)

APOL1 genetic variants are not associated with longitudinal blood pressure in young black adults

Patterns of Kidney Function Decline Associated with APOL1 Genotypes: Results from AASK

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