Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy.
Research Center in Epidemiology and Preventive Medicine (EPIMED), Department of Medicine and Surgery, University of Insubria, Varese, Italy.
PLoS One. 2022 Sep 19;17(9):e0271663. doi: 10.1371/journal.pone.0271663. eCollection 2022.
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.
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.
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).
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.
血栓形成在患有心血管疾病（CVD）和癌症的患者中很常见。高凝状态在血栓形成的病理生理学中起着关键作用。因此，凝血关键酶——凝血酶的失活受到抗凝血酶（AT）的严格调节。AT 缺乏与血栓形成和心血管死亡有关。在这项研究中，我们调查了一般人群中 AT 水平与死亡率的关系，特别是心血管相关和癌症相关死亡。
我们研究了来自意大利一般人群的前瞻性队列中 AT 水平与死亡率的关系（n=19676）。在基线样本中测量 AT 水平，并在中位随访 8.2 年期间记录死亡率。Cox 回归用于研究 AT 水平与全因、CVD 相关和癌症相关死亡率的关系。
在随访期间，共有 989 例患者死亡，其中 373 例死于 CVD，353 例死于癌症相关原因。Cox 分析显示，在调整年龄、性别、当前吸烟、BMI、糖尿病、高血压、高胆固醇血症、心血管疾病史、癌症史、维生素 K 拮抗剂、抗血小板药物、肝素和口服避孕药后，AT 水平与全因死亡率无关（HRQ1vsQ5：0.92，95%CI：0.74-1.15）。有趣的是，在调整年龄和性别以及其他混杂因素后，与较高 AT 水平相比，低 AT 水平的患者 CVD 相关死亡率降低，但该关联并未改变（HRQ1vsQ5：0.64，95%CI：0.44-0.91）。此外，在完全调整模型中，低 AT 水平与癌症死亡率升高相关（HRQ1vsQ2-5：1.26，95%CI：0.88-1.81）。
低 AT 水平与一般人群致命心血管事件风险降低相关，无论年龄、性别和用药情况如何。相反，低 AT 水平与癌症存活率降低相关。我们首次表明，即使在癌症发生或诊断之前，一般人群中低于正常范围的 AT 水平与癌症死亡风险升高相关。
