Low Molecular Weight Apolipoprotein(a) Phenotype Rather Than Lipoprotein(a) Is Associated With Coronary Atherosclerosis and Myocardial Infarction.

Background and Aims: Current evidence suggests that lipoprotein(a) [Lp(a)] level above 50 mg/dL is associated with increased cardiovascular risk. Our study aim was to determine the relationship of apolipoprotein(a) [apo(a)] phenotypes and Lp(a) concentration below and above 50 mg/dL with coronary atherosclerosis severity and myocardial infarction (MI). Material and Methods: The study population consisted of 540 patients (mean age 54.0 ± 8.8 years, 82% men) who passed through coronary angiography. The number of diseased major coronary arteries assessed atherosclerosis severity. Lipids, glucose, Lp(a) levels and apo(a) phenotypes were determined in all patients. All patients were divided into four groups: with Lp(a) <50 mg/dL [ "normal" Lp(a)] or ≥50 mg/dL [hyperLp(a)], and with low-molecular (LMW) or high-molecular weight (HMW) apo(a) phenotypes. Results: Baseline clinical and biochemical characteristics were similar between the groups. In groups with LMW apo(a) phenotypes, the odds ratio (OR; 95% confidence interval) of multivessel disease was higher [10.1; 3.1-33.5, p < 0.005 for hyperLp(a) and 2.2; 1.0-4.9, p = 0.056 for normal Lp(a)], but not in the group with HMW apo(a) and hyperLp(a) [1.1; 0.3-3.3, p = 0.92] compared with the reference group with HMW apo(a) and normal Lp(a). Similarly, MI was observed more often in patients with LMW apo(a) phenotype and hyperLp(a) and normal Lp(a) than in groups with HMW apo(a) phenotype. Conclusion: The LMW apo(a) phenotype is associated with the severity of coronary atherosclerosis and MI even when Lp(a) level is below 50 mg/dL. The combination of Lp(a) level above 50 mg/dL and LMW apo(a) phenotype increases the risk of severe coronary atherosclerosis, regardless of other risk factors.

Matrix Metalloproteinase 9 as a Predictor of Coronary Atherosclerotic Plaque Instability in Stable Coronary Heart Disease Patients with Elevated Lipoprotein(a) Levels.

We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.

Association of lipoprotein(a) level with short- and long-term outcomes after CABG: The role of lipoprotein apheresis.

OBJECTIVE: To evaluate the association of lipoprotein(a) [Lp(a)] level with short- and long-term outcomes after coronary artery bypass grafting (CABG) and to assess the effect of a 12 month course of weekly lipoprotein apheresis on vein graft patency and coronary atherosclerosis course in post-CABG patients with hyperlipidemia. METHODS: This study was performed in patients after successful CABG and consisted of three parts: a) a retrospective part with computed tomography assessment of vein graft patency in patients with first-year recurrence of chest pain after CABG (n = 102); b) a prospective trial with evaluation of cardiovascular outcomes during follow up time up to 15 years in relation to baseline Lp(a) levels (n = 356); c) an 12-months interventional controlled study in 50 patients with low-density lipoprotein cholesterol (LDL-C) levels >2.6 mmol/L prior to the operation despite statin treatment that allocated into 2 groups: active (n = 25, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 25, atorvastatin alone). RESULTS: Patients subjected to computed tomography were divided in two groups: 66 (65%) with at least one vein graft occlusion and 36 (35%) without occlusions. Lp(a) levels were significantly higher in patients with occluded grafts with a median (95% confidence intervals (CI)) of 24 (17-42) mg/dL vs. 12 (6-24) mg/dL in patients with patent grafts, p < 0.01. Over a mean of 8.5 ± 3.5 years (range 0.9-15.0 years), the primary and secondary endpoints were registered in 46 (13%) and 107 (30%) patients, respectively. Patients with Lp(a) ≥30 mg/dL were at significantly greater risk for the primary endpoint (hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.76-5.03, p < 0.001) and secondary endpoint (HR 3.47, 95%CI 2.48-4.85, p < 0.001) than patients with Lp(a) values <30 mg/dL. During the CPF procedure LDL-C levels decreased by 59 ± 14%, Lp(a) levels by 49 ± 15. The frequency of vein graft occlusions at study end was 14.3% (11 of 77) in the apheresis group and 27.4% (23 of 84) in the control group, p < 0.05. Progression of atherosclerosis was obtained in 26 (14.2%) segments of native coronary arteries in the apheresis group and in 50 (25.0%) segments of the control group. Regression signs were found in 30 (16.4%) and 19 (9.5%) segments, stabilization in 127 (69.4%) and 131 (65.5%) segments, respectively (χ2 = 9.37, p < 0.01). A Lp(a) level higher than 30 mg/dL was associated with a three-fold increased risk of vein grafts occlusion during first year after CABG, p < 0.001. CONCLUSION: Our data suggest that elevated Lp(a) is associated with a significantly increasing rate of one-year vein graft occlusions and adverse long-term cardiovascular outcomes whereas the use of lipoprotein apheresis improves vein graft patency during the first year after CABG.