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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. In addition, recent advances in lipid-modifying therapies, such as the development of proprotein convertase subtilisin/kexin type 9 inhibitors, have further improved cardiovascular outcomes in patients with hypercholesterolemia. However, despite significant progress in the treatment of dyslipidemia, there is still considerable residual risk of recurring cardiovascular events. Furthermore, in some cases, an effective therapy for the identified primary cause of a specific dyslipidemia has not been found up to date. Thus, a number of novel pharmacological interventions are under early human trials, targeting different molecular pathways of lipid formation, regulation and metabolism. This editorial aims to discuss the current clinical and scientific data on new promising lipid-modifying therapies addressing unmet needs in CVD, which may prove beneficial in the near future.
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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. Aspirin, niacin, estrogens, and statins, which act on different molecular pathways, may be prescribed to patients with mild or modest elevations of Lp(a) levels. Other therapeutic interventions, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, Lp(a) apheresis, and the novel antisense oligonucleotides APO(a)-Rx and APO(a)-LRx, which are being evaluated in ongoing clinical trials, have provided some promising results and can potentially be used in severe cases of hyperlipoproteinemia (a). This review aims to present and discuss the current clinical and scientific data pertaining to the therapeutic options for the management of hyperlipoproteinemia (a).
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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 ï¬rst line of therapy for obesity, these are often insufï¬cient in attaining weight loss goals. Orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion, and liraglutide are agents that have been approved for the treatment of obesity but their effects on cardiometabolic risk factors and outcomes have not been clearly elucidated. Given the detrimental repercussions of obesity on cardiometabolic health, there is a pressing clinical need to fully understand the effects of these agents beyond weight loss alone. Certain previous weight loss drugs have been withdrawn due to safety concerns and this underlines the need for more careful assessment of the effects of the various pharmacologic agents currently used for the treatment of obesity. This review aims to provide an overview of the mechanisms, efficacy, safety and cardiometabolic effects of the currently available pharmacologic agents for weight loss.
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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. Our review aims to provide the clinical and scientific data pertaining to the effects of different anti-inflammatory agents administered in patients with CVD.
RESUMEN
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. 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.
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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. However, further larger studies are needed for a more definitive assessment of the short- and long-term patient adherence rates to evolocumab. In addition, reductions in the price of evolocumab may also be necessary to improve cost-effectiveness of the drug.
RESUMEN
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.
RESUMEN
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.
RESUMEN
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. The small interfering RNA (siRNA) molecules have been used recently to target the hepatic production of PCSK9. siRNA interferes with the expression of specific genes with complementary nucleotide sequences by affecting the degradation of mRNA post-transcription, thus preventing translation. Inclisiran is a long-acting, synthetic siRNA directed against PCSK9 and it has been shown to significantly decrease hepatic production of PCSK9 and cause a marked reduction in LDL-C levels. This review aims to present and discuss the current clinical and scientific evidence pertaining to inclisiran, which is a new promising agent in the management of hypercholesterolemia.
RESUMEN
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. HDL cholesterol efflux capacity (CEC) from macrophages is a key metric of HDL functionality and exhibits a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease (CAD), independent of the HDL-C level. Thus, extensive research is being conducted to identify new agents with a favorable side effect profile, which would be able to enhance CEC, improve HDL functionality and potentially decrease cardiovascular risk. This review aims to present and discuss the current clinical and scientific evidence pertaining to the significance of HDL functionality over the actual HDL-C concentration in mediating the favorable effects on the cardiovascular system. Thus, we conducted a PubMed search until December 2017 through the English literature using the search terms 'HDL function/functionality', 'HDL properties', 'cardiovascular risk' and 'cholesterol efflux capacity'. We also included references from the articles identified and publications available in the authors' libraries.
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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. Spironolactone antagonizes the effect of aldosterone and can lead to a reduction in fibrosis and an improvement in left ventricular (LV) function. Furthermore, spironolactone decreases extracellular matrix turnover and myocardial collagen content and improves endothelial vasomotor dysfunction, mechanisms known to influence the progression of HF. Thus, given the aforementioned beneficial actions of spironolactone, extensive research has been conducted to explore the effects of spironolactone on HFpEF. Our review aims to present and discuss the clinical and scientific data pertaining to the role of spironolactone in the treatment of patients with HFpEF.
RESUMEN
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.