Korean Circ J.  2020 Dec;50(12):1095-1110. 10.4070/kcj.2020.0412.

Sex-based Approach for the Clinical Impact of the Increased Hemoglobin on Incident AF in the General Population

• Kim IS
• Lee BK
• Yang PS
• Joung B
• Kim JY

• KMID: 2509029
• DOI: http://doi.org/10.4070/kcj.2020.0412

Abstract

Background and Objectives
Although the adverse cardiovascular effect of anemia has been well described, the effect of polycythemia on the incident atrial fibrillation (AF) remain unclear. The objective of this study is to identify the association between increased hemoglobin and incident AF.
Methods
This was a retrospective-cohort study with 434,269 subjects who underwent national health examinations from the Korean National Sample Cohort. We estimated the risk of incident AF according to hemoglobin-based four-categories.
Results
During 3.9-year of follow-up, polycythemia group showed higher incidences of AF (hazard ratio[HR] with 95% confidence interval[CI], 1.50 [1.28–1.76] and 1.69 [1.13–2.56]; in men and women, respectively) than normal hemoglobin group (each p<0.001). In the normal hemoglobin and polycythemia groups, a 1 g/dL increase in hemoglobin level was associated with increased risks of incident AF (1.12 [1.07–1.17] and 1.18 [1.10–1.26] in men and women, each p<0.001). To investigate the specific hemoglobin concentration related to greater AF incidence, we analyzed the sensitivity/specificity of different hemoglobin levels: ≥16.0 g/dL in men and ≥14.5 g/dL in women showed the highest Youden's index, with c-indices of 0.83 and 0.82, respectively. Kaplan-Meier cumulative-event curves according to these specific hemoglobin levels (≥16.0 g/dL in men and ≥14.5 g/dL in women) also showed consistent results in both sexes (each p<0.05).
Conclusions
Even in the Korean general population, increased hemoglobin was significantly associated with higher rate of incident AF. Especially, subjects with hemoglobin levels ≥14.5 g/ dL in women and ≥16.0 g/dL among men were associated with increased risk of incident AF.

Keyword

Hemoglobins; Polycythemia; Sex; Atrial fibrillation

Figure

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  Figure 1 Study cohort and included subjects from the NHIS-NSC (overall general population).NHIS-NSC = National Health Insurance Service-National Sample Cohort.*A total of 67,306 were excluded owing to invalid data in health examination items including baseline characteristics blood test results, and smoking and alcohol history.

• 

  Figure 2 Concentration-responsive U-shaped relationships between Hb level and incident AF tested by log-linear model with a thin-plate spline (age, body mass index, serum creatinine, history of hypertension, diabetes, and dyslipidemia, socioeconomic status, and smoking and alcohol intake habits-adjusted HRs). It also showed the specific Hb level (lower 95% CI more than 1.0 of HR) associated with increased risk of incident AF in both sexes.AF = atrial fibrillation; CI = confidence interval; Hb = hemoglobin; HR = hazard ratio.

• 

  Figure 3 (A) ROC curves of specific Hb level for predicting incident AF among normal Hb and polycythemia subjects (among female subjects with Hb ≥13.9 g/dL and male subjects with Hb ≥15.2 g/dL who had linearly increasing relationships between Hb and incident AF as they were shown in Figure 2). The c-indices on the basis of the AUC for Hb in predicting incident AF were 0.82 and 0.83 in women and men, respectively. Hb levels above 14.5 g/dL in women and above 16.0 g/dL in men showed the highest Youden's index (sensitivity + specificity - 1). (B and C) Kaplan-Meier curves (B, women; C, men) about the time-dependent incident AF cases according to Hb cutoff (≥14.5 g/dL in women and ≥16.0 g/dL in men) among these subjects (all long-rank p<0.05).AF = atrial fibrillation; AUC = area of receiver operating characteristic curve; Hb = hemoglobin; ROC = receiver operating characteristics curve.

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