Key result
Circulating metabolites, including C5 carnitine (OR 1.25; 95% CI 1.10-1.41), were initially associated with incident VTE risk, but no associations remained significant after adjusting for BMI.
Why the study?
Venous thromboembolism is a complex thrombotic disorder causing substantial mortality and morbidity, and improved understanding of its cause was needed.
Are specific circulating metabolites associated with the risk of incident venous thromboembolism?
Case-Control (n=7,203)
Yes
Are specific circulating metabolites associated with the risk of incident venous thromboembolism?
Effect estimate: OR 1.25 (95% CI 1.10-1.41)
p-value: p=0.03
Circulating metabolites initially associated with incident VTE risk were found to be confounded by body mass index, highlighting the need for larger studies with broader metabolomic coverage.
No independent metabolite-VTE associations after BMI adjustment; leaves open causal roles in larger prospective metabolomic studies.
Background Venous thromboembolism ( VTE ) is a complex thrombotic disorder that constitutes a major source of mortality and morbidity. To improve understanding of the cause of VTE , we conducted a metabolomic analysis in a case‐control study including 240 incident VTE cases and 6963 controls nested within 3 large prospective population‐based cohorts, the Nurses’ Health Study, the Nurses’ Health Study II , and the Health Professionals Follow‐Up Study. Methods and Results For each individual, we measured 211 metabolites and collected detailed information on lifestyle factors. We performed logistic regression and enrichment analysis to identify metabolites and biological categories associated with incident VTE risk, accounting for key confounders, such as age, sex, smoking, alcohol consumption, body mass index, and comorbid diseases (eg, cancers). We performed analyses of all VTEs and separate analyses of pulmonary embolism. Using the basic model controlling for age, sex, and primary disease, we identified 60 nominally significant VTE ‐ or pulmonary embolism–associated metabolites ( P <0.05). These metabolites were enriched for diacylglycerols ( P permutation <0.05). However, after controlling for multiple testing, only 1 metabolite (C5 carnitine; odds ratio, 1.25; 95% confidence interval, 1.10–1.41; P corrected =0.03) remained significantly associated with VTE . After further adjustment for body mass index, no metabolites were significantly associated with disease after accounting for multiple testing, and no metabolite classes were enriched for nominally significant associations. Conclusions Although our findings suggest that circulating metabolites may influence the risk of incident VTE , the associations we observed were confounded by body mass index. Larger studies involving additional individuals and with broader metabolomics coverage are needed to confirm our findings.
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Jiang et al. (2018) conducted a case-control in Incident Venous Thromboembolism (VTE) (n=7,203). Metabolomic profile (211 metabolites) vs. Controls without incident VTE was evaluated on Incident VTE risk associated with metabolites (OR 1.25, 95% CI 1.10-1.41, p=0.03). Circulating metabolites, including C5 carnitine (OR 1.25; 95% CI 1.10-1.41), were initially associated with incident VTE risk, but no associations remained significant after adjusting for BMI.
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