Pulmonary embolism and deep vein thrombosis: Similar but different

Wenger, Nicolas; Sebastian, Tim; Engelberger, Rolf P.; Kucher, Nils; Spirk, David

doi:10.1016/j.thromres.2021.08.015

Cited by 30 publications

(27 citation statements)

References 47 publications

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“…Furthermore, the percentage of DVT and PE overlap was low in the FinnGen study (9.1%), which means that the causal effect of varicose veins on PE via DVT may have been too small to be detected using MR methods. In fact, the difference between DVT and PE is more remarkable than previous thought ( 34 ). For example, patients carrying the factor V Leiden mutation are reported to have a substantially increased risk to develop DVT but only a mildly increased risk to acquire PE ( 35 ).…”

Section: Discussionmentioning

confidence: 74%

Varicose Veins and Risk of Venous Thromboembolic Diseases: A Two-Sample-Based Mendelian Randomization Study

Chen

Gui

et al. 2022

Front. Cardiovasc. Med.

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Background:Varicose veins are found to be associated with increased risk of venous thromboembolism (VTE) in many observational studies, but whether varicose veins are causally associated with VTE remains unclear. Therefore, we used a series of Mendelian randomization (MR) methods to investigate that association.Methods23 independent single-nucleotide polymorphisms (SNPs) for varicose veins were obtained from the Pan UK Biobank analysis. The outcomes datasets for deep vein thrombosis (DVT), pulmonary embolism (PE) and venous thromboembolism (VTE) were obtained from the FinnGen study. Before analysis, body mass index (BMI) and height were included as confounders in our MR model. Basic MR [inverse-variance weighted (IVW), weight-median, penalized weighted-median and MR-Egger methods] and MR-PRESSO were performed against each outcome using the whole SNPs and SNPs after excluding those associated with confounders. If causal associations were suggested for any outcome, a basic MR validation analysis, a multivariable MR analysis with BMI and height, a Causal Analysis Using Summary Effect estimates (CAUSE), and a two-step MR analysis with BMI and height, would follow.ResultsUsing 21 qualified SNPs, the IVW method (OR: 1.173, 95% CI: 1.070–1.286, p < 0.001, FDR = 0.002), the weighted median method (OR: 1.255, 95% CI: 1.106–1.423, p < 0.001, FDR = 0.001), the penalized weighted median method (OR: 1.299, 95% CI: 1.128–1.495, p < 0.001, FDR = 0.001) and the MR-PRESSO (OR: 1.165, 95% CI: 1.067–1.273, p = 0.003, FDR = 0.009) suggested potential causal effect of varicose veins on DVT, but no cause effect was found for PE and VTE. Excluding SNPs associated with confounders yielded similar results. The causal association with DVT was validated using a self-reported DVT cohort (IVW, OR: 1.107, 95% CI: 1.041–1.178, p = 0.001). The causal association maintained after adjustment for height (OR = 1.105, 95% CI: 1.028–1.188, p = 0.007), BMI (OR = 1.148, 95% CI: 1.059–1.244, p < 0.001) and them both (OR = 1.104, 95% CI: 1.035–1.177, p = 0.003). The causal association also survived the strict CAUSE (p = 0.018). Finally, in two-step MR, height and BMI were found to have causal effects on both varicose veins and DVT.ConclusionGenetically predicted varicose veins may have a causal effect on DVT and may be one of the mediators of obesity and taller height that predispose to DVT.

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Section: Discussionmentioning

confidence: 74%

Varicose Veins and Risk of Venous Thromboembolic Diseases: A Two-Sample-Based Mendelian Randomization Study

Chen

Gui

et al. 2022

Front. Cardiovasc. Med.

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“… 29 Although this is usual in trials conducted in oncological populations, our conclusions cannot be generalized to more severely ill patients with cancer-associated PE. We included only patients with PE in our analysis in light of their specific characteristics 30 ; therefore a future analysis encompassing patients with DVT alone may be of additional worth. Last, the number of patients in the different subgroups of cancer types was small; consequently, differences in prognostic outcomes across cancer types were not studied, as analysis power was limited.…”

Section: Discussionmentioning

confidence: 99%

Performance Status and Long-Term Outcomes in Cancer-Associated Pulmonary Embolism

Farmakis

Mavromanoli

Konstantinides

et al. 2022

JACC: CardioOncology

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“…Our separate PE and DVT analyses showed that genetically predicted UC was causally associated with DVT only, despite evidence for increased risk for both DVT and PE in IBD patients (DVT risk is nearly twice that of PE) ( 38 , 39 ). Since PE is mostly a secondary event following DVT, it is expected that there is no direct causal association between IBD and PE, which may explain this seemingly contradictory result ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study

Gao

et al. 2022

Front. Immunol.

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IntroductionImmune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE.MethodsWe collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness.ResultsIVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy.ConclusionThis MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.

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Pulmonary embolism and deep vein thrombosis: Similar but different

Cited by 30 publications

References 47 publications

Varicose Veins and Risk of Venous Thromboembolic Diseases: A Two-Sample-Based Mendelian Randomization Study

Varicose Veins and Risk of Venous Thromboembolic Diseases: A Two-Sample-Based Mendelian Randomization Study

Performance Status and Long-Term Outcomes in Cancer-Associated Pulmonary Embolism

Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study

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