Sex-based approach for the clinical impact of polycythaemia on cardiovascular outcomes in the general population

Abstract

Aims: Although the adverse cardiovascular effect of anaemia has been well described, the effect of polycythaemia on the cardiovascular outcomes of the general population remain unclear. The primary objective is to identify the association between polycythaemia and major adverse cardiovascular events (MACE), and the secondary objective is to identify the specific haemoglobin concentration more associated with an increased risk for MACE.

Methods and results: This was a retrospective cohort study, 451 107 subjects were enrolled who underwent national health examinations from the Korean National Sample Cohort. We estimated the risk of MACE, a composite of cardiovascular mortality, incident myocardial infarction (MI), and stroke according to haemoglobin-based four categories. During 3.8-year of follow-up, polycythaemia group showed higher MACE [hazard ratio (HR) = 1.27 (1.13-1.44) and HR = 1.76 (1.08-2.88); in men and women, respectively], incident MI [HR = 1.37 (1.05-1.79) and HR = 3.46 (1.06-14.00)], and incident ischaemic stroke [HR = 1.27 (1.10-1.46) and HR = 1.72 (1.02-2.91)] than normal haemoglobin group (P < 0.001 in all cases). In the normal haemoglobin and polycythaemia groups, a 1 g/dL increase in haemoglobin level was associated with increased risks of MACE [HR = 1.04 (1.01-1.07) and HR = 1.05 (1.01-1.10) in men and women, each P < 0.05]. To investigate the specific haemoglobin concentration related to greater MACE incidence, we analysed the sensitivity/specificity of different haemoglobin levels: ≥16.5 g/dL in men and ≥15.0 g/dL in women showed the highest Youden's index (sensitivity + specificity - 1), with c-indices of 0.82 (0.81-0.83) and 0.83 (0.82-0.84), respectively.

Conclusion: Even in the Korean general population, polycythaemia was significantly associated with higher rates of MACE, incident MI, and incident ischaemic stroke. Especially, subjects with haemoglobin levels ≥15.0 g/dL in women and ≥16.5 g/dL among men were associated with increased risks of MACE.

Keywords: Cardiovascular event; Haemoglobin; Mortality; Polycythaemia; Sex.