OC 44.5 - High α2-macroglobulin levels are a risk factor for cardiovascular events

Monday, July 11, 2022

3:45 PM – 4:00 PM

Location: ExCel Center, ICC Capital Suite Room 14-16

Presentation Format: In-Person

Presenting Author(s)

Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

SC

Simona Constanzo

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Varese, Lombardia, Italy
QY

Qiuting Yan

.
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
AD

Augusto Di Castelnuovo

.
Mediterranea Cardiocentro, Napoli, Italy
Varese, Lombardia, Italy
AD

Amalia De Curtis

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Varese, Lombardia, Italy
CC

Chiara Cerletti

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Varese, Lombardia, Italy
MD

Maria Benedetta Donati

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Varese, Lombardia, Italy
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
LI

Licia Iacoviello

.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy
Varese, Lombardia, Italy

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.