Inverse association between serum albumin and future risk of venous thromboembolism: interrelationship with high sensitivity C-reactive protein

Purpose: We aimed to assess the prospective association of serum albumin with venous thromboembolism (VTE) risk and evaluate if the association is independent of or modified by inflammation, as measured by high sensitivity C-reactive protein (hsCRP). Design: We analysed data of 2176 men aged 42-61 years free from VTE in the Kuopio Ischemic Heart Disease study, with serum albumin concentrations measured at baseline using Coulter's bromocresol purple colorimetric assays. Hazard ratios (HRs) (95% confidence intervals [CI]) were calculated for VTE. Results: There were 109 validated cases of VTE recorded during a median follow-up of 24.9 years. The risk of VTE increased linearly below a serum albumin concentration of similar to 48g/l. In Cox regression analysis adjusted for established risk factors and other potential confounders, the HR (95% CI) for VTE per 1 standard deviation lower serum albumin was 1.23 (1.02-1.47). The association remained persistent on further adjustment for hsCRP 1.22 (1.01-1.46). Furthermore, the association was not modified by hsCRP and persisted on exclusion of men with elevated hsCRP levels. Conclusions: In middle-aged Caucasian men, low serum albumin is associated with an increased risk of VTE, consistent with a linear dose-response relationship. The association is independent of and not modified by inflammation.