Hemoglobin Concentration and Risk of Incident Stroke in Community-Living Adults

Abstract

Background and Purpose In prior observational studies, hemoglobin concentrations have been associated with an increased risk of stroke. However, these studies were limited by a relatively low number of stroke events, making it difficult to determine whether the association of hemoglobin and stroke differed by demographic or clinical factors. Methods Using Cox proportional hazards analysis and Kaplan-Meier plots, we examined the association of baseline hemoglobin concentrations with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults ≥45 years of age. Results A total of 518 participants developed stroke over a mean 7±2 years of follow-up. There was a statistically significant interaction between hemoglobin and sex (P=0.05) on the risk of incident stroke. In Cox regression models adjusted for demographic and clinical variables, there was no association of baseline hemoglobin concentration with incident stroke in men, whereas in women, the lowest (<12.4 g/dL) and highest (>14.0 g/dL) quartiles of hemoglobin were associated with higher risk of stroke as compared to the second quartile (12.4 – 13.2 g/dL) (Quartile 1, HR 1.59, 95%CI 1.09,2.31; Quartile 2 referent; Quartile 3, HR 0.91, 95%CI 0.59,1.38; Quartile 4, HR 1.59, 95%CI 1.08,2.35). Similar results were observed in models stratified by hemoglobin and sex and when hemoglobin was modeled as a continuous variable using restricted quadratic spline regression. Conclusions Lower and higher hemoglobin concentrations were associated with a higher risk of incident stroke in women. No such associations were found in men.

Ancestry-specific associations identified in genome-wide combined-phenotype study of red blood cell traits emphasize benefits of diversity in genomics

“…The possibility that combined-phenotype methods could benefit the study of other correlated polygenic traits still merits further investigation, particularly with groups of traits that may overlap in genetic architecture, but have not been previously examined in concert. Over the past three decades, RBC traits have been associated with cardiovascular disease outcomes like heart failure and stroke, highlighting the potential for identifying novel pleiotropic loci [6,[57][58][59][60][61][62]. Indeed, combinedphenotype approaches that examine the shared genetic architecture underlying intermediate phenotypes and clinical events may be particularly powerful for outcomes like stroke and heart failure, given that phenotypic heterogeneity of these phenotypes has complicated locus identification and characterization.…”

Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome

“…Some forms are easy to treat once recognized, but many patients with chronic anemia go untreated or partially treated because it is thought to generally be well tolerated. However, anemia has been associated with increased prevalence of stroke and cognitive morbidity . Anemia increases risk of white matter strokes 1.8‐fold in the elderly and worsens the severity of ischemic strokes .…”

Association Between Changes in Hemoglobin Concentration and Cardiovascular Risks and All‐Cause Mortality Among Young Women

“…The associations between hemoglobin (Hb) concentrations and cardiocerebrovascular diseases have been well investigated, primarily among high‐risk groups, including patients with chronic kidney disease or cardiovascular disease and older adults 1, 2, 3, 4, 5, 6, 7, 8. However, it is possible that an abnormal Hb concentration is a consequence of preclinical cardiocerebrovascular disease rather than a predisposing factor.…”

“…Thus, Hb concentration has not been considered as a risk factor in calculating cardiovascular disease risks. Additionally, in prior studies,1, 2, 3, 4, 5, 6 Hb has generally been examined only once, making it possible to misclassify a patient's Hb status and making it difficult to estimate the duration of an abnormal Hb status.…”