Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study

Abstract

Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE.Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54–0.89, p = 4.7 × 10−3) and 0.76 (CI 0.61–0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80–0.99, p = 0.031) and 0.85 (CI 0.78–0.94, p = 9.92 × 10−4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE.Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE.

Risk factors for incident venous thromboembolism in patients with renal tumor and inferior vena cava tumor thrombus: a retrospective case–control study

“…They found that decreased serum albumin levels in cancer patients were significantly associated with an increased risk of VTE and mortality 29 . Another two-sample mendelian randomization study also indicated that genetic liability to low-serum albumin and total protein levels is associated with a higher risk of VTE 41 . Additionally, hepatic dysfunction, from obstruction of the suprahepatic IVC, or Budd-Chiari syndrome, is known to occur in some RT patients who have advanced IVCTT 42 , leading to serum albumin synthesis disorder and facilitating the vicious circle further.…”

Association between uric acid and risk of venous thromboembolism in East Asian populations: a cohort and Mendelian randomization study

“…We utilized two large genetic datasets of the SUA to establish robust causal effects, which provided sufficient power to attain a causal inference. Compared to the previous MR analysis in SUA and VTE, 36 our study is unique and specific as it was restricted to individuals of East Asian descent, reducing the potential bias from population stratification. The use of exposure and outcome data from different populations and differences in the instrumental variables may have contributed to the lack of significant causal effect observed in the previous MR study.…”

A nomogram to predict left atrial appendage thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients

“…However, our study showed that hs-CRP level was not an important predictor of LAAT/SEC. Previous data has shown that reduction in albumin concentration and the plasma CRP level are inflammatory markers that might result in thrombosis [ 21 – 23 ]. These contradictory findings showed that besides inflammation, ALB was another major contributor to the LAAT/SEC.…”