Lipidology

Editorial introduction No abstract available

Non-HDL cholesterol should not generally replace LDL cholesterol in the management of hyperlipidaemia Purpose of review Non-HDL cholesterol was originally conceived as a therapeutic target for statin treatment in hypertriglyceridaemia when apolipoprotein B100 assays were not widely available. Recently non-HDL cholesterol has been recommended to replace LDL cholesterol in the clinical management of dyslipidaemia routinely in general medical practice. This is misguided. Recent findings Non-HDL cholesterol is heterogeneous, constituting a mixture of triglyceride-rich VLDL, intermediate density lipoprotein and LDL in which small dense LDL is poorly represented and to which VLDL cholesterol contributes increasingly as triglyceride levels rise. This makes it unsuitable as a goal of lipid-lowering treatment or as an arbiter of who should receive such treatment. Results of trials designed to lower LDL cholesterol are not easily translated to non-HDL cholesterol. Fasting is no longer thought essential for screening the general population for raised LDL cholesterol. ApoB100 measurement also does not require fasting even in rarer more extreme lipoprotein disorders encountered in the Lipid Clinic, provides greater precision and specificity and overcomes the problems posed by LDL and non-HDL cholesterol. It is more easily interpreted both in diagnosis and as a therapeutic goal and it includes SD-LDL. Summary If we are to discourage use of LDL cholesterol, it should be in favour of apoB100 not non-HDL cholesterol.

Update on low-density lipoprotein cholesterol quantification Purpose of review β-Quantification is considered the reference measurement procedure for low-density lipoprotein cholesterol (LDL-C). However, this technique is time-consuming and thus is inappropriate for routine clinical practice. Therefore, the Friedewald equation or homogeneous assays have been widely utilized. As several pitfalls exist with these two methods, a novel method for estimating LDL-C was developed by Martin et al. Recent findings Martin's method uses a strata-specific median for the triglycerides/very low-density lipoprotein cholesterol (VLDL-C) ratio on the basis of triglycerides and non-HDL-C concentrations. Recent studies show that Martin's method better correlates with β-quantification or homogeneous assays compared with the Friedewald equation, especially with values of triglycerides at least 150 mg/dl and/or LDL-CD less than 70 mg/dl. Such findings have also been demonstrated in other ethnic groups (Japanese and Korean) and disease populations, including diabetes and cardiovascular disease, in which the triglycerides/VLDL-C ratio can be affected. Summary For the current therapeutic goal of LDL-C values below 70 mg/dl in high-risk patients, accurate assessment of LDL-C levels at very low levels is required. Martin's method could overcome pitfalls such as underestimation of the Friedewald equation at this level. Further evaluation of the triglycerides/VLDL-C ratio in participants with diverse ethnic backgrounds or clinical conditions would expand the implementation of this novel method.

Recent developments in lipodystrophy Purpose of review Lipodystrophy syndromes have an estimated prevalence of 1.3–4.7 cases per million and as with other rare diseases conducting research can be challenging. The present review highlights recently published work that has provided insights into the field of non-HIV--associated lipodystrophy syndromes. Recent findings Lipodystrophies are a heterogenous group of disorders, as such research is often focused on specific subtypes of the condition. The identification of children carrying LMNA mutations has provided insights into the natural history of FPLD2, specifically that the adipose tissue phenotype predates the onset of puberty. Recent reports of PLIN1 heterozygous null variant carriers and the apparent absence of a lipodystrophy phenotype challenges our understanding of the molecular biology of perilipin 1 and its role in the pathogenesis of FPLD4. With a focus on therapeutics, studies delineating the differential responsiveness of PPARγ mutants to endogenous and synthetic ligands has illustrated the potential for pharmacogenetics to inform therapeutic decisions in lipodystrophy related to PPARG mutations, whereas robust human studies have provided insight into the food independent metabolic effects of leptin in lipodystrophy. Finally, rare syndromes of lipodystrophy continue to serve as an exemplar for the contribution of genetically determined adipose tissue expandability to metabolic disease in the general population. Summary Lipodystrophy research continues to illuminate our understanding of this rare disease and the possibility that lipodystrophy syndromes and the metabolic syndrome may have shared pathophysiology.

Is hypertriglyceridemia atherogenic? Purpose of review Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as 'bystanders' for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases. Recent findings The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death. Summary For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.

Monogenic, polygenic, and oligogenic familial hypercholesterolemia Purpose of review Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease. Recent findings Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia. Summary Familial hypercholesterolemia is a relatively common 'genetic' disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.

Inheritance of high and low HDL: mechanisms and management Purpose of review The inverse association between plasma high-density lipoprotein cholesterol (HDL-C) concentration and the incidence of cardiovascular disease (CVD) has been unequivocally proven by many epidemiological studies. There are several genetic disorders affecting HDL-C plasma levels, either providing atheroprotection or predisposing to premature atherosclerosis. However, up to date, there has not been any pharmacological intervention modulating HDL-C levels, which has been clearly shown to prevent the progression of CVD. Thus, clarifying the exact underlying mechanisms of inheritance of these genetic disorders that affect HDL is a current goal of the research, as key roles of molecular components of HDL metabolism and function can be revealed and become targets for the discovery of novel medications for the prevention and treatment of CVD. Recent findings Primary genetic disorders of HDL can be either associated with longevity or, in contrast, may lead to premature CVD, causing high morbidity and mortality to their carriers. A large body of recent research has closely examined the genetic disorders of HDL and new promising therapeutic strategies have been developed, which may be proven beneficial in patients predisposed to CVD in the near future. Summary We have reviewed recent findings on the inheritance of genetic disorders associated with high and low HDL-C plasma levels and we have discussed their clinical features, as well as information about new promising HDL-C-targeted therapies that are under clinical trials.

High-density lipoprotein: our elusive friend Purpose of review Despite advances in the research on HDL composition (lipidomics and proteomics) and functions (cholesterol efflux and antioxidative capacities), the relationship between HDL compositional and functional properties is not fully understood. We have reviewed the recent literature on this topic and pointed out the difficulties which limit our understanding of HDL's role in cardiovascular disease (CVD). Recent findings Though current findings strongly support that HDL has a significant role in CVD, the underlying mechanisms by which HDL mitigates CVD risk are not clear. This review focuses on studies that investigate the cell-cholesterol efflux capacity and the proteomic and lipidomic characterization of HDL and its subfractions especially those that analyzed the relationship between HDL composition and functions. Summary Recent studies on HDL composition and HDL functions have greatly contributed to our understanding of HDL's role in CVD. A major problem in HDL research is the lack of standardization of both the HDL isolation and HDL functionality methods. Data generated by different methods often produce discordant results on the particle number, size, lipid and protein composition, and the various functions of HDL.

Role of serum amyloid A in atherosclerosis Purpose of review Acute phase serum amyloid A (SAA) is persistently elevated in chronic inflammatory conditions, and elevated levels predict cardiovascular risk in humans. More recently, murine studies have demonstrated that over-expression of SAA increases and deficiency/suppression of SAA attenuates atherosclerosis. Thus, beyond being a biomarker, SAA appears to play a causal role in atherogenesis. The purpose of this review is to summarize the data supporting SAA as a key player in atherosclerosis development. Recent findings A number of pro-inflammatory and pro-atherogenic activities have been ascribed to SAA. However, the literature is conflicted, as recombinant SAA, and/or lipid-free SAA, used in many of the earlier studies, do not reflect the activity of native human or murine SAA, which exists largely lipid-associated. Recent literatures demonstrate that SAA activates the NLRP3 inflammasome, alters vascular function, affects HDL function, and increases thrombosis. Importantly, SAA activity appears to be regulated by its lipid association, and HDL may serve to sequester and limit SAA activity. Summary SAA has many pro-inflammatory and pro-atherogenic activities, is clearly demonstrated to affect atherosclerosis development, and may be a candidate target for clinical trials in cardiovascular diseases.

The future of apolipoprotein E mimetic peptides in the prevention of cardiovascular disease Purpose of review This review aims to discuss the recent developments in the area of apolipoprotein E (apoE) mimetics and their therapeutic potential for treating cardiovascular disease, the leading cause of mortality worldwide. Recent findings Ongoing research efforts target the development of novel therapies that would not only reduce circulating levels of atherogenic lipoproteins, but could also increase high density lipoprotein cholesterol (HDL-C) levels and/or improve HDL function. Among them, synthetic peptides that mimic the structure of natural human apoE, a component of triglyceride-rich lipoproteins and HDL, have been designed and proven to be functionally similar to apoE. In specific, apoE mimetic peptides mediate hepatic clearance of circulating atherogenic lipoproteins, dramatically reduce plasma cholesterol, and lead to attenuation of atherosclerosis development in vivo. These peptides also exhibit pleiotropic antiatherogenic properties, such as macrophage cholesterol efflux capacity, as well as anti-inflammatory and antioxidative functions. Summary ApoE mimetics are undergoing preclinical and clinical evaluation with promising results to date that render them attractive candidates in cardiovascular disease prevention and treatment.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com