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 ∼48 g/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. Key messages   • Serum albumin may be associated with future risk of venous thromboembolism (VTE); however, the shape, nature, magnitude and consistency of the association is uncertain.   • In a population-based prospective cohort study, low serum albumin was associated with an increased risk of VTE in a linear dose-response manner and this association was independent of and not modified by inflammation.   • Serum albumin concentrations may play a role in the development of VTE.