Novel lipid-modifying therapies addressing unmet needs in cardiovascular disease.

Cardiovascular disease (CVD) remains a major cause of morbidity and mortality worldwide. Currently, it is well established that dyslipidemia is one of the major risk factors leading to the development of atherosclerosis and CVD. Statins remain the standard-of-care in the treatment of hypercholesterolemia and their use has significantly reduced cardiovascular morbidity and mortality.

Pharmacologic therapy of obesity: mechanisms of action and cardiometabolic effects.

Obesity is a chronic, relapsing, multifactorial disease, which has become a serious threat to public health globally, as the worldwide prevalence of obesity increases exponentially over time. It has been well established that obesity is associated with multiple adverse cardiometabolic effects. Although lifestyle changes are the first line of therapy for obesity, these are often insufficient in attaining weight loss goals.

Therapeutic management of hyperlipoproteinemia (a).

Cardiovascular disease (CVD) has consistently been the leading cause of death worldwide. Several clinical and epidemiological studies have demonstrated that an elevated plasma concentration of lipoprotein (a) [Lp(a)] is a causative and independent major risk factor for the development of CVD, as well as calcific aortic valve stenosis. Thus, the therapeutic management of hyperlipoproteinemia (a) has received much attention, as significant reductions in Lp(a) levels may, potentially, favorably affect cardiovascular risk.

Anti-inflammatory therapy for cardiovascular disease.

Chronic subclinical inflammation is a central process in the pathogenesis of cardiovascular disease (CVD) and it has been linked with both the initiation and progression of atherosclerosis. Several pro-inflammatory cytokines, such as the C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) have been described as independent risk factors for coronary heart disease and promoters of atherogenesis. Thus, extensive research is being conducted to assess the role of anti-inflammatory therapy in the primary and secondary prevention of CVD.

Role of spironolactone in the treatment of heart failure with preserved ejection fraction.

Heart failure (HF) is the leading cause of morbidity and mortality globally. Heart failure with preserved ejection fraction (HFpEF) is currently responsible for about half of the patients affected with HF and is associated with impaired functional capacity, as well as significant morbidity due to frequent hospitalizations. Unfortunately, despite its poor prognosis, the management of HFpEF is very controversial and no therapy has been so far shown to reduce mortality in HFpEF.

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 lipid-lowering agents have been shown to have a beneficial effect on glucose metabolism.

Patient adherence, compliance, and perspectives on evolocumab for the management of resistant hypercholesterolemia.

Evolocumab is a PCSK9 inhibitor which is administered subcutaneously, and when added to statin therapy it has been shown to cause a significant incremental LDL-C reduction, leading to a reduction of cardiovascular risk. Evolocumab has a favorable side effect profile, and its self-administration at home appears to be safe and effective with the appropriate training and instructions from a health care provider. Current studies are showing encouraging results regarding adherence to evolocumab in real-life settings, and adherence rates to evolocumab appear to be better than those to statins.

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.

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.

Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia.

The discovery of proprotein convertase subtilisin-kexin type 9 (PCSK9), a serine protease which binds to the low-density lipoprotein (LDL) receptors and targets the receptors for lysosomal degradation, offered an additional route through which plasma LDL-cholesterol (LDL-C) levels can be controlled. Initially, the therapeutic approaches to reduce circulating levels of PCSK9 were focused on the use of monoclonal antibodies. To that effect, evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9, given on a background of statin therapy, have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk.

High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease.

Several prospective epidemiological studies have shown that there is a clear inverse relationship between serum high-density lipoprotein-cholesterol (HDL-C) concentrations and risk for coronary heart disease (CHD), even at low-density lipoprotein-cholesterol (LDL-C) levels below 70 mg/dL. However, more recent evidence from genetic studies and clinical research has come to challenge the long-standing notion that higher HDL-C levels are always beneficial, while lower HDL-C levels are always detrimental. Thus, it becomes apparent that HDL functionality plays a much more important role in atheroprotection than circulating HDL-C levels.

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.