No abstract

Hypercholesterolemia, particularly an increase in low-density lipoprotein cholesterol (LDL-C) levels, contributes substantially to the development of coronary artery disease and the risk for cardiovascular events. As the first-line pharmacotherapy, statins have been shown to reduce both LDL-C levels and cardiovascular events. However, despite intensive statin therapy, a sizable proportion of statin-treated patients are unable to achieve the recommended target LDL-C levels, and not all patients can avoid future cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis by enhancing the degradation of hepatic low-density lipoprotein receptor (LDLR). Owing to its importance in lipid metabolism, PCSK9 has emerged as a novel pharmacological target for lowering LDL-C levels. In this review, the potential role of circulating PCSK9 as a new biomarker of lipid metabolism is described. Next, previous studies evaluating the effects of lipid-modifying pharmacological agents, particularly statins, on circulating PCSK9 concentrations are summarized. Statins decrease hepatic intracellular cholesterol, resulting in increased LDLRs as well as increased PCSK9 protein. There is a clear dose-response effect of statin treatment on PCSK9 level, as increasing doses of statins also increase the level of circulating PCSK9. Finally, the available therapeutic strategies to inhibit PCSK9 are present. Monoclonal antibodies against PCSK9, in combination with statins, are one of the most promising and novel approaches to achieve further reduction of LDL-C levels and reduce the risk of cardiovascular events.

No abstract

The CMV/eGFR ratio could be a useful predictor of CIN developing after elective PCI.

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein (LDL) cholesterol levels, and sortilin is linked to lipoprotein metabolism. Although statin therapy increases PCSK9 levels, effects of this therapy on plasma sortilin levels have not been evaluated. The purpose of the present study was to examine the effects of statins on plasma PCSK9 and sortilin levels, and association of statin-induced increase in PCSK9 levels with sortilin. Methods: Serum lipid levels and plasma PCSK9 and sortilin levels were measured at baseline and 8 months after statin therapy in 90 statin-naive patients with coronary artery disease (CAD). Pitavastatin 4 mg/day was used to treat 44 patients and pravastatin 20 mg/day to treat the remaining 46 patients. Results: For both statin groups, significant increases in hetero-dimer PCSK9 levels (pitavastatin: 31%, p 0.0001; pravastatin: 34%, p 0.03) and decreases in sortilin levels (pitavastatin: 8%, p 0.02; pravastatin: 16%, p 0.002) were observed. Although a reduction in LDL cholesterol was greater in the pitavastatin group than in the pravastatin group, no significant differences were observed in percentage changes in hetero-dimer PCSK9 and sortilin levels. A significant positive correlation was observed between percentage changes in hetero-dimer PCSK9 levels and those in sortilin levels (pitavastatin: r 0.359, p 0.02; pravastatin: r 0.276, p 0.06). Conclusions: Use of pitavastatin and pravastatin increased plasma PCSK9 and decreased sortilin levels. Statin-induced increases in PCSK9 were associated with changes in sortilin in statin-naive patients with CAD. J Atheroscler Thromb, 2016; 23: 848-856.