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High α2-macroglobulin levels are a risk factor for cardiovascular events

1Synapse Research Institute, Maastricht, Limburg, Netherlands, 2Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy, Varese, Lombardia, Italy, 3Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands;, Maastricht, Limburg, Netherlands, 4Mediterranea Cardiocentro, Napoli, Italy, Varese, Lombardia, Italy, 5Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands

Abstract Number: OC 44.5

Meeting: ISTH 2022 Congress

Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors

Background: α2-macroglobulin (α2M) is a very versatile endopeptidase inhibitor that plays a role in growth, inflammation and coagulation. Hypercoagulability is a risk factor for thrombotic events. Therefore, the inactivation of thrombin, the key coagulation enzyme, is tightly regulated via antithrombin and α2M. Antithrombin deficiency has been related to thrombosis and cardiovascular events, while this is still unknown for α2M.

Aims: We analyzed the association of α2M levels with the occurrence of cardiovascular events in a large sample of general Italian population (n=19,688).

Methods: We determined α2M levels in the baseline samples of the prospective Moli-sani cohort and analyzed the association of α2M levels with cardiovascular events in the 4.3 years follow-up period. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated by multivariable cox regression based on α2M quintiles and adjusted for age and sex, BMI, smoking and oral contraceptive use.

Results: 432 subjects suffered from a cardiovascular disease (CVD) event (2.2%); most events were non-fatal (82%) and 18% were fatal. The percentage of CVD events was 2.2-fold higher in subjects in the highest α2M quintile compared to the lowest quintile. The highest quintile of α2M (α2MQ5) was significantly associated with overall CVD events (HRQ1-4vs5=1.93; CI=1.57-2.38; p < 0.001) in the crude model and after adjustment for age, sex, current smoking, BMI, and oral contraceptive use (HRQ1-4vs5=1.30; CI=1.04-1.62; p=0.019). α2MQ5 was especially associated with the risk of fatal CVD (HRQ1-4vs5=1.84; CI=1.13-2.99; p=0.015). From all CVD events, 368 were classified as coronary heart disease (CHD) events. α2MQ5 was significantly associated with fatal CHD events in the crude model (ORQ5vsQ1-4=3.95 (2.31-6.77); p < 0.001), and after adjustment for age, sex, BMI, smoking and oral contraceptive use (ORQ5vsQ1-4=1.88; (1.07-3.29); p=0.027).

Conclusion(s): We showed for the first time in a prospective cross-sectional cohort that α2M in the highest quintile of the normal range is a marker for CVD-related death.

To cite this abstract in AMA style:

de Laat-Kremers R, Constanzo S, Yan Q, Di Castelnuovo A, De Curtis A, Cerletti C, Donati M, de Laat B, Iacoviello L. High α2-macroglobulin levels are a risk factor for cardiovascular events [abstract]. https://abstracts.isth.org/abstract/high-%ce%b12-macroglobulin-levels-are-a-risk-factor-for-cardiovascular-events/. Accessed October 1, 2023.

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