Multiple thrombogenic and atherogenic markers were involved in premature coronary artery disease

Abstract

Atherogenic and thrombogenic factors are implicated in the pathogenesis of coronary artery disease (CAD). Polymorphisms in the lymphotoxin-alfa (LTA) gene, a pro-inflammatory cytokine, have been also associated with susceptibility to myocardial infarction, but results in different studies are conflicting. We examined the association of atherothrombotic markers and the LTA promoter A252G polymorphism with risk of premature CAD. Methods: A case-control study was conducted in 336 patients with documented premature CAD and 189 unrelated health controls both with less than 50 years old. Clinical characteristics and laboratorial data which included thrombogenic factors (fibrinogen, protein C, protein S and antithrombin III); and atherogenic factors (fasting glucose, lipid profile; lipoprotein (a), apolipoproteins AI and B fractions) were evaluated. Genetic variability of LTA was determined by polymerase chain reaction. Results: Male, history of premature CAD, smoking status, diabetes, hypertension and dyslipidemia were significantly more prevalent in the CAD group. Compared with controls, CAD cases had significantly lower mean concentrations of apolipoprotein AI (1.34±0.21 vs 1.23±0.22 mg/dL;<0.01), HDL-cholesterol (46.4±11.9 vs 41.1±11.2 mg/dL; p<0.01) and antithrombin III(100±12.7 vs 94.2±17.8%; p=0.02), and higher plasma concentration of fasting glucose (103.3±26.9 vs 112.1±45.3 mg/dL; p<0.01) and Lipoprotein (a) levels(32.8±32.6 vs 50.1±49.2 mg/dL; p<0.01). The LTA A252G polymorphism frequency for AA, AG and GG was respectively 55.0%, 37,6%, and 7.4% for control group and 42.7%, 46.0% and 11.3% for patients group (p=0.02). A multivariable logistic regression analysis showed that hypertension (OR 2.19 95% CI 1.290-3.716), smoker (OR 2.18; 95% CI 1.455-3.277), dyslipidemia (OR 1.94; 95% CI1.233-3.072), family history (OR 7.13; 95% CI 4.383-11.606) and LTA polymorphism (OR 1.88; 95% CI 1.193-2.972) were independent risk factors for susceptibility to CAD. LTA mutant was risk marker for CAD only in male without the traditional risk factors. Conclusions: Worse traditional risk factors profile and atherothrombogenic markers were associated with susceptibility to premature CAD. LTA mutant allelic was independently associated with premature CAD in male in the absence of traditional risk factors. Premature CAD was associated with worse clinical and laboratory multimarkers.