Combined Effect of Hemoglobin Levels and Obesity on the Risk of Incident Venous Thromboembolism: The Tromsø Study

Abstract Red blood cells (RBCs) are key determinants of blood viscosity, which is related to thrombosis risk. Obesity is a well-recognized risk factor for venous thromboembolism (VTE). Whether the combination of these two risk factors synergistically increases VTE risk has not been studied. We aimed to investigate the joint effect of high hemoglobin and obesity on the risk of VTE in a population-based cohort. We included 35,801 participants from the Tromsø 4–7 surveys (1994–2016). All first-lifetime VTEs were validated and recorded from enrollment throughout 2020. Hemoglobin levels were categorized as low (women: <13.2 g/dL, men: <14.7 g/dL), medium (women: 13.2–14.0 g/dL, men: 14.7–15.5 g/dL), and high (women: ≥14.1 g/dL, men: ≥15.6 g/dL). Body mass index (BMI) was categorized as normal weight (<25 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Hazard ratios (HRs) for VTE with 95% confidence intervals (CIs) were estimated according to combined categories of hemoglobin and BMI in models adjusted for age, sex, cancer, arterial cardiovascular disease, and smoking. During 17.3 years of median follow-up, 1,040 cases of VTE occurred. In normal weight individuals, the HR of VTE according to high hemoglobin levels was 1.22 (95% CI: 0.90–1.66). The HR of VTE in obese individuals with low hemoglobin was 1.81 (95% CI: 1.35–2.43), while the HR of VTE in obese individuals with high hemoglobin levels was 1.71 (95% CI: 1.30–2.25), compared with those with normal weight and low hemoglobin. Combination of high hemoglobin and obesity did not yield excess VTE risk, suggesting no evidence of biological interaction between these factors in the pathogenesis of VTE.