Thirty-year risk of ischemic stroke in individuals with sickle cell trait and modification by chronic kidney disease: The atherosclerosis risk in communities (ARIC) study

Am J Hematol. 2019 Dec;94(12):1306-1313. doi: 10.1002/ajh.25615. Epub 2019 Sep 10.

Abstract

Sickle cell trait (SCT) has been associated with hypercoagulability, chronic kidney disease (CKD), and ischemic stroke. Whether concomitant CKD modifies long-term ischemic stroke risk in individuals with SCT is uncertain. We analyzed data from 3602 genotyped black adults (female = 62%, mean baseline age = 54 years) who were followed for a median 26 years by the Atherosclerosis Risk in Communities Study. Ischemic stroke was verified by physician review. Associations between SCT and ischemic stroke were analyzed using repeat-events Cox regression, adjusted for potential confounders. SCT was identified in 236 (7%) participants, who more often had CKD at baseline than noncarriers (18% vs 13%, P = .02). Among those with CKD, elevated factor VII activity was more prevalent with SCT genotype (36% vs 22%; P = .05). From 1987-2017, 555 ischemic strokes occurred in 436 individuals. The overall hazard ratio of ischemic stroke associated with SCT was 1.31 (95% CI: 0.95-1.80) and was stronger in participants with concomitant CKD (HR = 2.18; 95% CI: 1.16-4.12) than those without CKD (HR = 1.09; 95% CI: 0.74-1.61); P for interaction = .04. The hazard ratio of composite ischemic stroke and/or death associated with SCT was 1.20 (95% CI: 1.01-1.42) overall, 1.44 (95% CI: 1.002-2.07) among those with CKD, and 1.15 (95% CI: 0.94-1.39) among those without CKD; P for interaction = .18. The long-term risk of ischemic stroke associated with SCT relative to noncarrier genotype appears to be modified by concomitant CKD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • African Americans / genetics
  • Atherosclerosis / blood
  • Atherosclerosis / epidemiology*
  • Biomarkers
  • Blood Proteins / analysis
  • Brain Ischemia / blood
  • Brain Ischemia / epidemiology*
  • Brain Ischemia / etiology
  • Brain Ischemia / genetics
  • Comorbidity
  • Diabetes Mellitus / epidemiology
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Glomerular Filtration Rate
  • Hemoglobin C / genetics
  • Hemoglobin, Sickle / genetics
  • Hospitalization / statistics & numerical data
  • Humans
  • Hyperlipidemias / epidemiology
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Population Surveillance
  • Principal Component Analysis
  • Proportional Hazards Models
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / epidemiology*
  • Risk Factors
  • Sickle Cell Trait / blood
  • Sickle Cell Trait / epidemiology*
  • Sickle Cell Trait / genetics
  • Smoking / epidemiology

Substances

  • Biomarkers
  • Blood Proteins
  • Hemoglobin, Sickle
  • Hemoglobin C