Current opinion in lipidology最新文献

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: Universal Screening programmes to identify subjects with familial hypercholesterolaemia (FH) have been the subject of much recent interest. However, any screening programme can cause harm as well as having potential benefits. Here we review recent papers using different ages and strategies to identify subjects with FH, and examine to what extent the publications provide quantitative or qualitative evidence of benefit or harm to children and adults.

Recent findings: Three studies have been published over the last 2 years where Universal Screening for FH has been carried out in infancy, at the time of routine vaccinations, or at preschool age. Next-generation sequencing of all known FH-causing genes has been used to determine the proportion of screened individuals, who have total or low-density lipoprotein cholesterol (LDL-C) concentrations above a predetermined threshold (such as >95th percentile), with genetically confirmed FH.

Summary: While we fully support the concept of Universal Screening for FH, which appears feasible and of potential clinical utility at all of the different ages examined, there is little data to document potential benefit or how to mitigate potential harms. Future study protocols should include collection of such data to strengthen the case of roll out of Universal Screening programmes.

Purpose of review: Familial hypercholesterolemia (FH) registries can capture unique data on FH concerning real-world practice, clinic epidemiology, natural history, cascade testing, cardiovascular consequences of late diagnosis, and use of healthcare resources. Such registries are also valuable for identifying and bridging the gaps between guidelines and clinical practice. We reviewed recent findings from the principal FH registries.

Recent findings: Most adult patients with heterozygous FH (HeFH) are diagnosed late, undertreated, and do not reach guideline-recommended low density lipoprotein-cholesterol (LDL-C) goals. In children and adolescents with HeFH, detection relies principally on genetic testing and measurement of LDL-C levels. Similarly, the majority of patients with homozygous FH (HoFH) receive sub-optimal cholesterol-lowering treatments and do not attain recommended LDL-C goals, gaps being wider in lower income than higher income countries. In HeFH patients, men have a higher risk of atherosclerotic cardiovascular disease than women.

Summary: The evolving data from FH registries provide real-world evidence for developing implementation strategies to address gaps across the continuum of care of FH worldwide.

Purpose of review: Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.

Recent findings: To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events.

Summary: Inclisiran has been evaluated in numerous trials, primarily the ORION 9 26 , ORION 10 27 and ORION 11 28 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.

Purpose of review: To review the development of oral agents to lower Lp(a) levels as an approach to reducing cardiovascular risk, with a focus on recent advances in the field.

Recent findings: Extensive evidence implicates Lp(a) in the causal pathway of atherosclerotic cardiovascular disease and calcific aortic stenosis. There are currently no therapies approved for lowering of Lp(a). The majority of recent therapeutic advances have focused on development of injectable agents that target RNA and inhibit synthesis of apo(a). Muvalaplin is the first, orally administered, small molecule inhibitor of Lp(a), which acts by disrupting binding of apo(a) and apoB, in clinical development. Nonhuman primate and early human studies have demonstrated the ability of muvalaplin to produce dose-dependent lowering of Lp(a). Ongoing clinical trials will evaluate the impact of muvalaplin in high cardiovascular risk and will ultimately need to determine whether this strategy lowers the rate of cardiovascular events.

Summary: Muvalaplin is the first oral agent, developed to lower Lp(a) levels. The ability of muvalaplin to reduce cardiovascular risk remains to be investigated, in order to determine whether it will be a useful agent for the prevention of cardiovascular disease.