The paradox of diabetes, obesity and cardiovascular risk

Weight loss to reduce cardiovascular risk is encouraged in both healthy overweight individuals and those at high cardiovascular risk, including patients with diabetes. However, a large body of studies suggest that, in comparison to overweight and even obese subjects, cardiovascular events may be more common among patients who lose weight or who fall into lower body mass index categories. In contrast, other studies confirm the traditional concept that weight loss and maintenance of a healthy body weight is not only associated with improvement in cardiovascular risk factors, such as blood pressure, lipid profile and blood glucose control, but also with a reduction in cardiovascular morbidity and mortality. Possible reasons for the difference in outcomes between these two groups of studies include differences in study design, bias and statistics, the health status of the study participants and differential treatment afforded to different patient groups. This article reviews studies supporting both pointsof view and describes potential explanations for the observed differences in outcomes according to body weight

Novel approaches to lipid-lowering therapy

Cardiovascular disease (CVD) remains a major cause of death worldwide, with dyslipidaemia playing a significant role in the disease process. It is clinically useful to demarcate hypercholesterolaemia from hypertriglyceridaemia, with an increased serum low-density lipoprotein (LDL) cholesterol being the most powerful predictor of CVD morbidity and mortality, and a significant elevation in triglyceride levels increasing the risk of acute pancreatitis. Statins (with or without ezetimibe) and fibrates are the current first-line therapy in the management of dyslipidaemia. Although these medications have shown effectiveness in reducing CVD complications, there are patients who require a greater modification in lipid profile or are intolerant of first-line therapy. Novel agents are on the horizon, which have shown to lead to a significant decrease in serum LDL cholesterol. These include the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (which have shown a reduction in CVD morbidity), mipomersen, cholesterol ester transfer protein (CETP) inhibitors and bempedoic acid. Further studies of the clinical benefit of these medications are ongoing. Drugs such as pemfibrate, angiopoietin-like protein 3 (ANGPTL3) inhibitors, apolipoprotein C3 (apo C3) inhibitors and diacylglycerol acyltransferase-1 (DGAT 1) inhibitors have shown promising results in the management of hypertriglyceridaemia. It is hoped that these exciting new technological advancements in the future management of dyslipidaemia will result in clinical benefit for patients

Prevention of Cardiovascular Burden in COVID-19 Patients Suffering from Familial Hypercholesterolemia : A Global Challenge

A recent meta-analysis of over 20,000 individuals showed that hospitalized COVID-19 patients with acute myocardial injury had more than fourfold higher mortality than those without such injury. Since the COVID-19 pandemic exacerbates already existing health inequalities, there is an urgent need to create measures to protect the most vulnerable patient groups, including those with a pre-existing increased risk of atherosclerotic cardiovascular disease (ASCVD). A typical example is familial hypercholesterolemia (FH), a common genetic disease affecting over 30 million individuals worldwide. If left untreated or undertreated, FH patients suffer from complications of premature ASCVD, such as acute coronary syndromes, resulting in acute myocardial injury/infarction. A recent population-based analysis provided strong evidence suggesting that COVID-19 poses an even higher risk for myocardial injury in FH patients. From the long-term preventive point of view, it is important to note that, in addition to the acutely elevated risk of myocardial injury, an elevated risk of ASCVD and its complications will persist after COVID-19. The decline in outpatient preventive care during the pandemic is likely to influence ASCVD risk and outcomes, particularly in high-risk patients, such as those with FH. This commentary aims to raise global awareness of the challenges that clinicians treating FH patients continue to face during the COVID-19 pandemic, with two low- to middle-income countries, South Africa and Brazil, serving as examples.Non peer reviewe

Mipomersen preferentially reduces small low-density lipoprotein particle number in patients with hypercholesterolemia

AbstractBackgroundBecause of variability in lipoprotein cholesterol content, low-density lipoprotein (LDL) cholesterol frequently underrepresents or overrepresents the number of LDL particles. Mipomersen is an antisense oligonucleotide that reduces hepatic production of apolipoprotein B–100, the sole apolipoprotein of LDL.ObjectiveTo characterize the effects of mipomersen on lipoprotein particle numbers as well as subclass distribution using nuclear magnetic resonance (NMR) spectroscopy.MethodsWe compared the tertiary results for the direct measurement of LDL particle numbers by NMR among 4 placebo-controlled, phase 3 studies of mipomersen that had similar study designs but different patient populations: homozygous familial hypercholesterolemia (HoFH), severe hypercholesterolemia, heterozygous familial hypercholesterolemia with established coronary artery disease, or hypercholesterolemia with high risk for coronary heart disease (HC-CHD).ResultsHoFH patients had the highest median total LDL particles at baseline compared with HC-CHD patients, who had the lowest. At baseline, the HoFH population uniquely had a greater mean percentage of large LDL particles (placebo, 60.2%; mipomersen, 54.9%) compared with small LDL particles (placebo, 33.1%; mipomersen, 38.9%). In all 4 studies, mipomersen was associated with greater reductions from baseline in the concentrations of small LDL particles compared with those of large LDL particles, and both total LDL particles and small LDL particles were statistically significantly reduced.ConclusionsMipomersen consistently reduced all LDL particle numbers and preferentially reduced the concentration of small LDL particles in all 4 phase 3 studies

Functional foods with added plant sterols for treatment of hypercholesterolaemia and prevention of ischaemic heart disease

Background. A spread with added plant sterols, Pro-activ, is marketed in South Africa as an adjunct to low-fat diets for lowering of total and low-density lipoprotein (LDL) cholesterol concentrations and to decrease risk of ischaemic heart disease (IHD). Objectives. The need for this functional food in South Africa, its efficacy, safety and target market, are evaluated in this review. Results. The high, and probably increasing incidence of hypercholesterolaemia and cardiovascular disease in South Africa motivates the need for appropriate functional foods. There is convincing evidence in the literature that an average daily intake of about 2 g plant sterols in about 20 g of spread significantly lowers total and LDL cholesterol concentrations by approximately 10 - 15%, without influencing high-density lipoprotein (HDL) cholesterol and triglyceride concentrations. There is some concern about the effects on absorption of lipid-soluble vitamins and pro-vitamins, but safety tests lasting for up to 3 years found no serious adverse effects. Conclusions. The target market for this spread should be nonpregnant, non-lactating adults with hypercholesterolaemia and/or increased risk of IHD. If it is considered for use in hypercholesterolaemic children, fat-soluble vitamin status should be monitored. It is recommended that post-marketing surveillance should be established to determine long-term effects and safety

Familial hypercholesterolemia and COVID-19 : A menacing but treatable vasculopathic condition

Publisher Copyright: © 2021 The AuthorsSARS-CoV-2 infection continues to cause increased morbidity and mortality, and due to the slow pace of vaccination COVID-19 will probably remain a global burden to health systems for a long time. Unfortunately, the necessary prevention and treatment strategies of COVID-19 have led to restriction measures that are hampering the routine care of common chronic metabolic conditions like hypercholesterolemia. It is of particular concern that during the acute phase of COVID-19, the control of pre-existing metabolic diseases tends to get worse which again increases the risk for complications and a poor outcome in these patients. A significant contributor to these complications is endothelial dysfunction which is associated with COVID-19. This Commentary will discuss the impact of COVID-19 on endothelial function particularly in patients with familial hypercholesterolemia (FH), a metabolic inherited disease known to in itself adversely affect endothelial function. There should be no hesitation to continue with statin therapy in severe hypercholesterolemic patients with COVID-19. We argue that in FH patients with COVID-19 the clinicians need even consider intensifying statin therapy as well as the addition of other lipid-lowering agents, such as proprotein convertase subtilisin/kexin type 9(PCSK9) inhibitors. In contrast to statins, the PCSK9 inhibitors lower lipoprotein(a) [Lp(a)] level, and, accordingly, these latter drugs need to be considered particularly in FH patients with an elevated level of Lp(a). This call applies to the in-hospital stay and also beyond. When considering that the vasculopathic effects of COVID-19 may persist, a long-term follow-up of individualized therapies in FH patients is warranted.Peer reviewe

Familial hypercholesterolemia and COVID-19 : A menacing but treatable vasculopathic condition

Publisher Copyright: © 2021 The AuthorsSARS-CoV-2 infection continues to cause increased morbidity and mortality, and due to the slow pace of vaccination COVID-19 will probably remain a global burden to health systems for a long time. Unfortunately, the necessary prevention and treatment strategies of COVID-19 have led to restriction measures that are hampering the routine care of common chronic metabolic conditions like hypercholesterolemia. It is of particular concern that during the acute phase of COVID-19, the control of pre-existing metabolic diseases tends to get worse which again increases the risk for complications and a poor outcome in these patients. A significant contributor to these complications is endothelial dysfunction which is associated with COVID-19. This Commentary will discuss the impact of COVID-19 on endothelial function particularly in patients with familial hypercholesterolemia (FH), a metabolic inherited disease known to in itself adversely affect endothelial function. There should be no hesitation to continue with statin therapy in severe hypercholesterolemic patients with COVID-19. We argue that in FH patients with COVID-19 the clinicians need even consider intensifying statin therapy as well as the addition of other lipid-lowering agents, such as proprotein convertase subtilisin/kexin type 9(PCSK9) inhibitors. In contrast to statins, the PCSK9 inhibitors lower lipoprotein(a) [Lp(a)] level, and, accordingly, these latter drugs need to be considered particularly in FH patients with an elevated level of Lp(a). This call applies to the in-hospital stay and also beyond. When considering that the vasculopathic effects of COVID-19 may persist, a long-term follow-up of individualized therapies in FH patients is warranted.Peer reviewe