Key result
Low antithrombin levels were associated with a reduced risk of cardiovascular disease-related mortality but an increased risk of cancer mortality in the general population.
Why the study?
Antithrombin deficiency is related to thrombosis and cardiovascular death, but the association between antithrombin levels and mortality, particularly cardiovascular-related and cancer-related death, in the general population was unestablished.
Are low antithrombin levels associated with reduced cardiovascular mortality and increased cancer mortality in the general population?
Cohort (n=19,676)
No
Are low antithrombin levels associated with reduced cardiovascular mortality and increased cancer mortality in the general population?
In the general population, low antithrombin levels are paradoxically associated with a lower risk of cardiovascular death but a higher risk of cancer mortality.
Answers are grounded in this paper and cite their sources.
Should not change practice; leaves open paradoxical antithrombin-mortality links for prospective validation.
BACKGROUND: Thrombosis is common in subjects suffering from cardiovascular diseases (CVD) and cancer. Hypercoagulation plays a pivotal role in the pathophysiology of thrombosis. Therefore, the inactivation of thrombin, the key enzyme in coagulation, is tightly regulated via antithrombin (AT). AT deficiency is related to thrombosis and cardiovascular death. In this study we investigated the association between AT levels and mortality, in particularly cardiovascular-related and cancer-related death in the general population. METHODS: We studied the association of AT levels and mortality in a prospective cohort sampled from the general Italian population (n = 19,676). AT levels were measured in the baseline samples, and mortality was recorded during a median follow-up period of 8.2 years. Cox regression was performed to investigate the association of all-cause, CVD-related and cancer-related mortality with variations in AT levels. RESULTS: In total, 989 subjects died during follow-up, of which 373 subjects of CVD and 353 of cancer-related causes. Cox analysis revealed that, after adjustment for age, sex, current smoking, BMI, diabetes, hypertension, hypercholesterolemia, history of cardiovascular disease, history of cancer, vitamin K antagonists, antiplatelet medication, heparin and oral contraceptives AT levels were not associated with all-cause mortality (HRQ1vsQ5: 0.92, 95% CI:0.74-1.15). Interestingly, the risk of CVD-related mortality was reduced in subjects with low AT levels compared to subjects with higher AT levels, after adjustment for age and sex and other confounders did not change the association (HRQ1vsQ5: 0.64, 95% CI:0.44-0.91). Moreover, low AT levels were associated with increased cancer mortality in a fully adjusted model (HRQ1vsQ2-5: 1.26, 95% CI:0.88-1.81). CONCLUSIONS: Low AT levels are associated to a lower risk of fatal cardiovascular events in the general population, regardless of age, sex and medication use. In contrast, low AT levels are associated with lower cancer survival. For the first time we show that AT levels lower than the normal range in the general population, even before the development or diagnosis of cancer, are associated with an elevated risk of cancer death.
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Iacoviello et al. (2022) conducted a cohort in General population (n=19,676). Low antithrombin levels vs. High antithrombin levels was evaluated on Cardiovascular disease-related mortality (HR 0.64, 95% CI 0.44-0.91). Low antithrombin levels were associated with a reduced risk of cardiovascular disease-related mortality but an increased risk of cancer mortality in the general population.
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