Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease.

BACKGROUND: Lipoprotein (a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). Recent studies have indicated that statins tend to increase Lp(a) levels by 10-20%. However, the association of statin-mediated increases in Lp(a) levels with CAD has not been determined.  METHODS: This study included 488 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Lp(a) levels were measured at baseline and 1 month after statin therapy. The study endpoints were major adverse cardiovascular events (MACE). Hazard ratios for the MACE were adjusted for potential confounder using Cox regression. RESULTS: After statin therapy, the mean level of Lp(a) increased by 19.3% from baseline. Lp(a) levels increased in 307 patients (62.9%) with a median elevation of 4.1 mg/dL. Patients with an increase in Lp(a) were at higher risk for MACE than those without an increase in Lp(a) (p = 0.044). Subgroup analyses revealed that a mild-to-moderate increase in Lp(a) was not associated with MACE, whereas there was a strong correlation between the highest quartile increase in Lp(a) (≥ 10.1 mg/dL) and MACE (HR = 2.29, 95%CI = 1.36-3.84, p = 0.002). This correlation was independent of baseline Lp(a) levels but not independent of on-statin Lp(a) levels. CONCLUSIONS: Severe increases in Lp(a) following statin therapy raise the risk of MACE, but a mild-to-moderate increase in Lp(a) may not affect the cardiovascular prognosis of CAD patients. Even if the baseline Lp(a) levels are low, it is necessary to continue testing for Lp(a) concentration at least once after statin.

Prostaglandin E1 protects coronary microvascular function via the glycogen synthase kinase 3ß-mitochondrial permeability transition pore pathway in rat hearts subjected to sodium laurate-induced coronary microembolization.

Prostaglandin E1 (PGE1) is used as a pretreatment for ischemia reperfusion injury in many biological systems. However, its value as a pretreatment for coronary microembolization (CME) is unknown. The goal of this study was to determine whether PGE1 would protect against CME. In a CME rat model, we observed microthrombi and early myocardial ischemia, with endothelium appearing exfoliated and mitochondria having irregular morphology and decreased internal complexity. The level of fibrinogen-like protein 2 prothrombinase was increased and superoxide dismutase and catalase levels were decreased. Moreover, mitochondria copy number and mitochondrial permeability transition pore (mPTP) opening were increased. Pretreatment with PGE1 (1 or 2 µg/kg) significantly improved these cardiological deficits, acting via the glycogen synthase kinase 3ß (GSK-3ß)-mPTP pathway. Unexpectedly, the phosphorylation of Akt at Ser473 decreased in the PGE1 at high dose. Overall, our findings suggested an important role for PGE1 in pretreatment of coronary microvascular dysfunction.