Current opinion in lipidology最新文献

Purpose of review: The study of naturally occurring genetic variation in human populations has laid the foundation for proprotein converts subtilisin/kexin type 9 inhibitors, and more recently new classes of lipid-lowering drugs such as lipoprotein(a) inhibitors and lipoprotein lipase pathway activators. These emerging therapies lower plasma lipoprotein-lipid levels that are not adequately managed by traditional low-density lipoprotein (LDL) cholesterol-lowering medications. By targeting different risk factors, these therapies could help manage the important residual cardiovascular risk of LDL cholesterol medications.

Recent findings: We review the latest insights into the pharmacological and genetic modulation of these new therapeutic targets. We highlight that the drugs remarkably recapitulate the lipid effects observed in genetic studies. In addition to lowering lipoprotein-lipid levels, robust genetic evidence support that these drugs may prevent cardiometabolic outcomes.

Summary: Emerging lipid-lowering therapies could launch a new era for preventive medicine in which treatments are optimally tailored to patient's lipoprotein-lipid profiles.

Purpose of review: Hypertriglyceridemia (HTG), which arises from defects in triglyceride-rich lipoprotein (TRL) metabolism, is associated with increased morbidity and mortality from pancreatitis and atherosclerotic cardiovascular disease. Traditional therapies, including fibrates and omega-3 fatty acids, have shown limited efficacy in controlling triglyceride (TG) levels and cardiovascular risk. This review explores the role of emerging therapies that target TG and TRL metabolism via novel biochemical pathways.

Recent findings: Apolipoprotein C-III inhibitors appear most effective for patients with variants of severe HTG, particularly multifactorial and familial chylomicronemia syndromes, by enhancing TRL metabolism through both lipoprotein lipase-dependent and independent mechanisms. Angiopoeitin-like proteins 3 and 4 inhibitors appear most useful for mixed hyperlipidemia, with favorable effects across the entire spectrum of apoB-containing atherogenic lipoproteins. For patients with HTG and concomitant complications of insulin resistance, including metabolic associated steatotic liver disease and type 2 diabetes mellitus, fibroblast growth factor-21 analogs may provide significant benefit.

Summary: HTG is a diverse condition. Apolipoprotein C-III inhibitors, angiopoeitin-like proteins 3 and 4 inhibitors, and fibroblast growth factor-21 analogs represent significant advancements in the treatment of HTG, offering new hope for effectively managing this condition across its full spectrum of disease.

Purpose of review: Cognitive decline and late-onset dementia pose significant challenges in aging societies, and many dementia cases could be prevented or delayed through modification of associated risk factors, many of which are tied to cardiovascular and metabolic dysfunction. As individuals age, the blood-brain barrier becomes more permeable, easing the exchange of molecules between the bloodstream and the brain. Consequently, blood-based biological markers (so-called biomarkers) provide a minimally invasive and accessible means of accessing molecular changes associated with aging and neurodegeneration.

Recent findings: Circulating free fatty acids, also called nonesterified fatty acids (NEFAs), and sphingolipids are associated with cardiovascular disease, insulin resistance, and diabetes; thus, could be promising candidates as biomarkers for cognitive decline and dementia.

Summary: The opportunity to study such minimally invasive biomarkers further opens up potential new avenues for improved understanding of the underlying biology of diseases of the brain.

Purpose of review: Despite reductions in low-density lipoprotein (LDL) cholesterol (LDLc), residual cardiovascular risk remains due to factors beyond lipoprotein levels, such as LDL particle count, size, electronegativity and modifications. Technological advances allow detailed profiling of LDL particles, offering potential biomarkers for diagnosis, prognosis, and treatment of cardiovascular disease (CVD). The aim of this review is to provide an updated overview of the state of knowledge in the field of LDL atherosclerotic role, which is evolving rapidly due to technological advances in biomarker measurement and applications.

Recent findings: While small dense LDL has been linked to increased CVD risk, current approaches favor a comprehensive evaluation of all lipoprotein subtypes, as this is a more feasible and standardized method. The atherogenic potential of circulating oxidized LDL (oxLDL) may be the key factor in the onset and progression of atherosclerosis. Thus, elevated oxLDL levels are recognized as a marker of increased CVD risk in both general and high-risk populations, although further research is needed to clarify some conflicting findings. The oxidized LDL receptor 1 (LOX-1) has emerged as a promising target for immunotherapy and innovative drug delivery strategies to modulate atherosclerosis.

Summary: A panel of biomarkers related to LDL atherogenicity may help predict future ischemic events. An atheroprotective diet and increased physical activity could improve LDL oxidation. OxLDL has become a target for immunomodulatory antiatherosclerosis therapy and delivering LDL-based nanocarriers holds promise for both imaging and therapeutics.

Purpose of review: The aim of this review is to explore a possible link between immunological candidate proteins, identified through modern proteomic techniques, and preeclampsia (PE) and fetal growth restriction (FGR).

Recent findings: Proteomics has become a promising tool in the search for disease pathways, drug targets, and biomarkers. PE and FGR are adverse pregnancy complications with supposed immunological involvement in their pathogenesis, but no circulating immunological biomarkers are currently established for diagnosis and risk stratification. Several proteomic studies have aimed to identify PE and FGR biomarkers - often with varying results across studies. However, proteomics has revealed altered expression of human leukocyte antigen-I in PE cases, which is supported in Genome-wide association study (GWAS) studies. Proteomic results support the heterogeneous nature of PE by identification of molecular subgroups - including subgroups characterized by immune-related proteins e.g. CXCL10. No specific immunological markers are found on FGR, but differences in overall plasma proteomic signature have been suggested.

Summary: Proteomics certainly holds great potential. The immunological component in PE and FGR are still unclarified, but improvements in proteomic technologies may provide both definition of disease subgroups and subsequent discovery of biomarkers and targeted analysis within each subgroup.

Purpose of review: Cardiometabolic diseases are a major global health concern, with diet playing a crucial role in their prevention and management. Recent advancements in the identification of metabolic signatures related to dietary patterns offer a more objective assessment of individualized dietary exposure and provide deeper insights into diet-disease associations.

Recent findings: Recent studies have shown that distinct metabolic signatures are associated with the adherence to various dietary patterns. These signatures show even stronger associations with cardiometabolic disease incidence, independent of traditional risk factors and self-reported adherence to such dietary patterns. Emerging dietary approaches, such as sustainable diets, health outcome-focused diets, and population data-driven dietary patterns, also hold promise for improving cardiometabolic health. Additionally, metabolic signatures could offer insights into diet-disease associations in underrepresented populations, addressing genetic and lifestyle differences.

Summary: Application of metabolomics provides a more precise understanding of how dietary patterns influence cardiometabolic health. Although the number of studies remains limited, and current evidence is inconsistent, the approach has significant potential for improving clinical and public health strategies. Future research should prioritize prospective studies and address population- and outcome-specific dietary needs to enable targeted interventions that optimize cardiometabolic health.

Purpose of review: Cardiometabolic diseases (CMDs) increasingly contribute to the cumulative burden of morbidity and mortality worldwide. Here, we reviewed intervention studies using a randomized controlled trial (RCT) design as well as meta-analyses of RCTs aimed at testing the effectiveness of different dietary approaches for CMD prevention.

Recent findings: Recent studies testing dietary approaches for CMD prevention were summarized narratively, with a focus on interventions based on caloric restriction and fasting, healthy dietary patterns and food-based dietary modifications. Evidence supports intermittent fasting, Mediterranean, Nordic, DASH, low-carbohydrate/ketogenic and plant-based diets as effective strategies for improving cardiometabolic health. However, the benefits observed with some of these dietary patterns are linked to energy restriction, and the independent effects beyond weight loss remain unclear. The effectiveness of some strategies may also depend on the overall dietary quality and adherence to the programme.

Summary: Recent findings highlight the importance of focusing on overall dietary patterns, rather than isolated nutrients, for preventing CMD. Future research should prioritize long-term intervention studies to assess the sustained effects of these dietary patterns on CMD outcomes.

Purpose of review: For many years, inflammation has been a major concept in basic research on atherosclerosis and in the development of potential diagnostic tools and treatments. The purpose of this review is to assess the performance of this concept with an emphasis on recent clinical trials. In addition, contemporary literature may help identify new therapeutic targets, particularly in the context of the treatment of early, rather than end-stage, arterial disease.

Recent findings: Newly reported clinical trials cast doubt on the efficacy of colchicine, the sole anti-inflammatory agent currently approved for use in patients with atherosclerotic cardiovascular disease (ASCVD). New analyses also challenge the hypothesis that residual ASCVD event risk after optimal management of lipids, blood pressure, and smoking arises primarily from residual inflammatory risk. Current clinical practice to initiate interventions so late in the course of atherosclerotic arterial disease may be a better explanation. Lipid-lowering therapy in early atherosclerosis, possibly combined with novel add-on agents to specifically accelerate resolution of maladaptive inflammation, may be more fruitful than the conventional approach of testing immunosuppressive strategies in end-stage arterial disease. Also discussed is the ongoing revolution in noninvasive technologies to image the arterial wall. These technologies are changing screening, diagnosis, and treatment of atherosclerosis, including early and possibly reversable disease.

Summary: The burden of proof that the Big Idea of inflammation in atherosclerosis has clinical value remains the responsibility of its advocates. This responsibility requires convincing trial data but still seems largely unmet. Unfortunately, the focus on inflammation as the source of residual ASCVD event risk has distracted us from the need to screen and treat earlier.

Purpose of review: Genetic testing has become an integral component of clinical care when an inherited condition is suspected. However, the interpretation of variants identified with this testing can be nuanced. Variants of uncertain significance (VUS) are variants for which there is not enough data currently available to determine if the variant is causal for disease (i.e. pathogenic) or is benign. VUS can exist on a spectrum with some leaning towards suspected pathogenicity and others leaning towards likely benign. Clinician understanding of variant interpretation can improve clinical care by providing more context around how suspicious a VUS is, determining whether additional steps should be taken to further evaluate the variant in question, and ensuring patient understanding of these results.

Recent findings: Research on this topic highlights the complexities around VUS interpretation and counseling. VUS are not static: interpretations of pathogenicity change as new information is uncovered.

Summary: This review aims to summarize this literature and provide insight into variant interpretation, practical steps clinicians can take to further assess a VUS, and considerations when counseling patients on these results.