Coronary artery disease and the bad dual: homocysteine and lipoprotein (a)

Abstract Introduction High homocysteine (Hcy) and Lipoprotein (Lp) (a) levels are independent risk factors for coronary artery disease (CAD) through several mechanisms, such as endothelial dysfunction, increased permeability of lipids and inflammation. It promotes the release of free Apo(a) from Lp(a). Free Apo(a) has high fibrin affinity and inhibits plasminogen binding, altering fibrinolysis. Identifying individuals with the dual risk focus on preventive measures might decrease the risk of this atherothrombotic disease. Aim Evaluate Hcy and Lp(a) as independent risk factors for CAD in a Portuguese population, establishing the cut-off value for the appearance of CAD in our population. Finally, investigate whether there is a positive interaction between these two markers. Methods We performed a case-control study with 1722 coronary patients and 1435 controls (aged 53.0±7.8 years; 77.6% male) matched by sex and age. Hcy and Lp(a) levels were determined and stratified into deciles. Multivariate logistic regression adjusted for age and gender was performed using Hcy and Lp(a) deciles to investigate the independent risk of CAD. Our disease cut-off is the point along the deciles when the risk begins. Finally, a second regression analysis was performed with Hcy and Lp(a) combination and adjusted for age, sex, smoking, hypertension, diabetes, dyslipidemia, BMI≥30Kg/m², physical inactivity and CAD family history to evaluate their synergistic interaction. Results After a multivariate regression concerning Hcy, the first four deciles (lower values) presented CAD protection. From this point (fifth decile), the CAD risk begins, and as Hcy levels increase, CAD risk also increases. In the 10th decile, the CAD risk was 80% higher than the reference. In the case of Lp(a), the 6th decile was the reference, starting the significant risk below these. On the 10th, CAD risk was 200% higher than the reference. The combination of Hcy and Lp(a) higher values had an increased risk of 2.16 (95% CI: 1.73-2.69; p0.0001). Conclusion High levels of Lp(a) and Hcy were independent risk factors for CAD in our population. There was an interaction between Lp(a) and Hcy that significantly potentiates the CAD risk. These findings highlight the importance of identifying individuals with this dual risk factor of elevated Hcy and Lp(a) to focus on preventive measures that might decrease the CAD risk in our population. This interaction deserves to be investigated concerning other ethnicities.