Glycoprotein Ibα Polymorphism T145M, Elevated Lipoprotein-Associated Phospholipase A2, and Hypertriglyceridemia Predict Risk for Recurrent Coronary Events in Diabetic Postinfarction Patients

Abstract

To explore altered platelet function in recurrent coronary event risk among diabetic postinfarction patients, we investigated a function-altering genetic polymorphism (T145M) in the von Willebrand factor binding region of the platelet glycoprotein Ib␣ (GPIb␣) subunit. The study comprised diabetic and nondiabetic patients of the Thrombogenic Factors and Recurrent Coronary Events postinfarction study. Cox proportional hazards multivariable modeling, adjusted for significant clinical covariates, was performed using the polymorphism and metabolic, inflammatory, and thrombogenic blood markers. Nondiabetic patients demonstrated risk for elevated lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ). In contrast, diabetic patients demonstrated significant and independent risk for the M allele of the T145M polymorphism (MT plus MM versus TT, hazard ratio [HR] 3.73, 95% CI 1.90 -7.33, P < 0.001), hypertriglyceridemia (2.91, 1.52-5.56, P ‫؍‬ 0.001), and elevated Lp-PLA 2 (2.78, 1.45-5.35, P ‫؍‬ 0.002). Joint risk (one, two, or three risk factors) expressed as relative outcome rates (compared with no risk factors) were 2.4, 4.0, and 8.2, respectively. We conclude that the M allele of the T145M polymorphism of the GPIb␣ subunit predicts risk for recurrent coronary events in diabetic postinfarction patients, but not in nondiabetic postinfarction patients, supportive of an important role for platelet hyperactivation in diabetic coronary heart disease.

Lipoprotein-Associated Phospholipase A2Mass Level Is Increased in Elderly Subjects with Type 2 Diabetes Mellitus

“…Our study shows statistically significant increased levels of Lp-PLA 2 mass in diabetic patients compared to nondiabetic (before any cardiac intervention). These observations were also shown in other studies [20, 21]. It is probable that significantly higher levels of total cholesterol, LDL, HDL, and triglycerides on diabetic subjects when compared to nondiabetic subjects were not found because many of the subjects (in both groups) were on statin therapy.…”

Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease

“…patients with very high baseline LDL-values, with diabetes mellitus or history of cardiovascular events [25]. To add to that, other studies show that elevated CRP and Lp-PLA2 levels correlate to increased circulating von Willebrand factor (vFW) [26]. vVF is an important regulator of systemic inflammation and thrombosis and its interplay with other inflammatory mediators like Lp-PLA2 may be of great significance in the progression of CAD [27,28].…”

The association of platelet GPIbα145Thr/Met (HPA-2a/2b) with myocardial infarction and coronary artery disease

“…Although the results, in our sample of Croatian population, presented here, do not suggest a strong relationship of the GPIba with CAD and/or MI, they nevertheless suggest that there might be an association of the CAD and/or MI with this genotype in bivariate analysis and also show the trend of increasing risk with the presence of Met in the GPIba locus. The results presented, however, need to rely on further investigation, most likely studies with larger sample sizes or meta-analytic studies of both published and unpublished material, in order to fully establish the role of this genetic marker for cardiovascular disease diagnostics and possibly even the disease prevention [3][4][5][6][7][8][9][10][11][12]. …”