Incorporating hyperhomocysteinemia into hyperlipoprotein(a)emia predicts adverse cardiovascular outcome in patients with coronary artery disease

초록

Objectives We sought to evaluate the incorporating prognostic value of hyperlipoprotein(a)emia and hyperhomocysteinemia in patients with coronary artery disease (CAD). Methods 5839 patients (60.4% male, mean age 61.3 ± 11.2 years) with CAD were enrolled. CAD was diagnosed by invasive coronary angiography. Laboratory values including Lp(a) and Hcy levels were obtained at the day of coronary angiography and analyses were done shortly after sampling. Elevation of Lp(a) and Hcy levels were defined as upper tertiles of these biomarkers. Patients were divided into four groups according to their Lp(a) and Hcy levels. Baseline risk factors, coronary angiographic findings, length of follow-up, and major adverse cardiovascular event (MACE) including cardiac death and non-fatal myocardial infarction (MI) were recorded. Results Over a mean follow-up period of 4.4 ± 2.5 years, there were 132 MACEs (75 cardiac death and 57 non-fatal MI) with an event rate of 2.3%. Mean Lp(a) level and Hcy levels were 21.4 ± 24.5 mg/dL and 9.9 ± 4.3 mg/dL, respectively. Of the 5839 patients, 2624 patients (44.9%) were allocated in group 1 [normal Lp(a) and Hcy group]; 1262 patients (21.6%) in group 2 [elevated Lp(a), but normal Hcy group]; 1256 patients (21.5%) in group 3 [elevated Hcy, but normal Lp(a)] and 697 patients (11.9%) in group 4 [elevated Lp(a) and Hcy]. Composite MACE rates were 1.3% (33/2624), 2.1% (27/1262), 2.8% (35/1256), and 5.3% (37/697) for group 1, 2, 3 and 4, respectively. Kaplan-Meier survival analysis revealed that elevated Lp(a) and Hcy was associated with adverse cardiac outcome (p<0.0001). Furthermore, multi-variate Cox regression analysis after adjustment of age, gender, diabetes, hypertension, hypercholesterolemia, smoking and extent of CAD revealed that elevated Lp(a) and Hcy was associated with worse prognosis. Conclusions Incorporating hyperhomocysteinemia into hyperlipoprotein(a)emia is associated with increased incidence of adverse cardiovascular events.