CETP Inhibition: Past Failures and Future Hopes

The atheroprotective role of high-density lipoprotein cholesterol (HDL-C) in cardiovascular disease has been unequivocally established, and epidemiological data have clearly demonstrated a strong inverse relationship between HDL-C levels and the risk of cardiovascular events, which is independent of the low-density lipoprotein cholesterol (LDL-C) levels. Thus, it would be logical to hypothesize that raising HDL-C might potentially lead to a reduction of cardiovascular risk. Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from HDL to very low-density lipoprotein and LDL. Therefore, CETP inhibition raises HDL-C levels and decreases LDL-C levels. The first trials with CETP inhibitors failed to show a reduction in cardiovascular events. However, newer CETP inhibitors with more favorable effects on lipids are presently being tested in clinical trials with the hope that their use may lead to a reduction in cardiovascular risk. This review aims to provide the current evidence regarding CETP inhibition, as well as the clinical and scientific data pertaining to the new CETP inhibitors in development

Dysfunctional high-density lipoprotein and atherogenesis

High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport (RCT) but also exhibits, anti-inflammatory, endothelial/vasodilatory, anti-thrombotic, antioxidant, anti-aggregating, anticoagulant and cytoprotective functions, which enhance its protective effect against cardiovascular disease. However, the function of HDL is dependent upon genetic, environmental and lifestyle factors. Modification of the protein or lipid components of HDL in certain conditions may convert the HDL particles from anti-inflammatory to pro-inflammatory and pro-atherogenic by limiting their ability to promote RCT and to prevent LDL modification. In our review, we will present the clinical and scientific data pertaining to the factors and conditions that impair HDL functionality and we will discuss the effects of dysfunctional HDL on atherogenesis

Complications of Continuous-Flow Mechanical Circulatory Support Devices

Left ventricular assist devices (LVADs), more importantly the continuous-flow subclass, have revolutionized the medical field by improving New York Heart Association (NYHA) functional class status, quality of life, and survival rates in patients with advanced systolic heart failure. From the first pulsatile device to modern day continuous-flow devices, LVADs have continued to improve, but they are still associated with several complications. These complications include infection, bleeding, thrombosis, hemolysis, aortic valvular dysfunction, right heart failure, and ventricular arrhythmias. In this article, we aim to review these complications to understand the most appropriate approach for their prevention and to discuss the available therapeutic modalities

Impact of lipid-lowering therapy on glycemic control and the risk for new-onset diabetes mellitus

Lipid-lowering therapy is used very commonly nowadays not only for the optimization of the lipid profile but also to reduce cardiovascular risk. However, some studies have linked the use of certain lipid-lowering agents with an increased risk for impaired glycemic control and new-onset diabetes mellitus, a condition well established as an important risk factor for cardiovascular disease. On the other hand, some other lipidlowering agents have been shown to have a beneficial effect on glucose metabolism. Profound knowledge of these differences would enable the clinician to choose the right lipid-lowering medication for each individual patient, so that the benefits would outweigh the risk of side effects. This review aims to present and discuss the clinical and scientific data pertaining to the impact of lipid-lowering therapy on glycemic control and the risk for new-onset diabetes mellitus

Effects of Statins on Cardiovascular Outcomes in Patients With Chronic Kidney Disease

Statins are the standard of care in the treatment of hypercholesterolemia, and their use is supported by extensive evidence demonstrating their effectiveness in primary and secondary cardiovascular risk reduction. However, clinical and epidemiologic data have clearly demonstrated that patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease. However, the efficacy of statins in the reduction of cardiovascular risk has not been definitively confirmed in patients with CKD and especially those with stage 5 CKD or on dialysis. This review aims to provide the current clinical and scientific data pertaining to the effects of statins on cardiovascular outcomes in patients with CKD

Primary genetic disorders affecting high density lipoprotein (HDL)

There is extensive evidence demonstrating that there is a clear inverse correlation between plasma high density lipoprotein cholesterol (HDL-C) concentration and cardiovascular disease (CVD). On the other hand, there is also extensive evidence that HDL functionality plays a very important role in atheroprotection. Thus, genetic disorders altering certain enzymes, lipid transfer proteins, or specific receptors crucial for the metabolism and adequate function of HDL, may positively or negatively affect the HDL-C levels and/or HDL functionality and subsequently either provide protection or predispose to atherosclerotic disease. This review aims to describe certain genetic disorders associated with either low or high plasma HDL-C and discuss their clinical features, associated risk for cardiovascular events, and treatment options

Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): an emerging chapter in lipid-lowering therapy

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is mainly expressed in the liver but can also be found in the intestine and kidneys. PCSK9 promotes the degradation of low density lipoprotein receptors (LDLR) by reducing their recycling and targeting the receptors for lysosomal destruction, thereby decreasing the rate of removal of LDL-cholesterol from the circulation. Thus, interventions targeting PCSK9 by reducing its expression may lead to significant reductions of LDL-cholesterol and possibly decrease cardiovascular risk. The present review aims to present and discuss the current clinical and scientific data pertaining to lipid-lowering interventions targeting PCSK9

The Impact of Insulin Resistance and Chronic Kidney Disease on Inflammation and Cardiovascular Disease

There is extensive evidence showing that insulin resistance (IR) is associated with chronic low-grade inflammation. Furthermore, IR has been shown to increase the risk for cardiovascular disease (CVD), even in nondiabetic patients, and is currently considered as a “nontraditional” risk factor contributing to CVD by promoting hypertension, oxidative stress, endothelial dysfunction, dyslipidemia, and type 2 diabetes mellitus. However, chronic kidney disease (CKD) is also considered a state of low-grade inflammation. In addition, CKD is considered an IR state and has been described as an independent risk factor for the development of CVD, as even early-stage CKD is associated with an estimated 40% to 100% increase in CVD risk. There is also strong evidence indicating that inflammation per se plays a crucial role in both the initiation and progression of CVD. Given the above, the combined effect of IR and CKD may significantly increase the risk of inflammation and CVD. This review aims to focus on the complex interplay between IR, CKD, inflammation, and CVD and will present and discuss the current clinical and scientific data pertaining to the impact of IR and CKD on inflammation and CVD