Journal of clinical lipidology最新文献

Background: National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments.

Objective: We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events.

Results: Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS).

Conclusion: Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+.

Background: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder associated with extreme hypertriglyceridemia and high risk of acute pancreatitis. Olezarsen-an antisense oligonucleotide targeting hepatic apolipoprotein C3 (APOC3) messenger RNA-reduces triglycerides and may decrease pancreatitis risk. Olezarsen 80 mg once monthly is approved in the United States as an adjunct to diet to reduce triglycerides in adults with FCS.

Objective: To assess the effect of olezarsen on all-cause healthcare resource utilization (HCRU) and overall experience of patients with genetically identified FCS enrolled in the Balance trial (NCT04568434).

Methods: Prespecified exploratory endpoints included yearly all-cause hospitalization, total inpatient days, and emergency room visits for patients treated with olezarsen (80 or 50 mg) vs placebo, as well as Patient Global Impression of Change (PGIC). Ad hoc outcomes included length of hospital stay, intensive care unit (ICU) admissions, reasons for HCRU, and all-cause HCRU according to patients' history of acute pancreatitis and for individual olezarsen doses vs placebo.

Results: Treatment with olezarsen vs placebo for 1 year was associated with an 84% reduction in all-cause hospitalizations (mean rate ratio [95% CI], 0.16 [0.05, 0.50]), 6.3 fewer total inpatient days (95% CI, -11.09, -1.53), better PGIC scores, shorter length of stay, and numerically fewer ICU admissions. Acute pancreatitis was the most frequent cause of hospitalization. Reduction in all-cause inpatient service utilization was consistent for individual dose groups and in patients with a history of acute pancreatitis.

Conclusion: In the Balance study, olezarsen reduced all-cause inpatient service utilization and improved the experience of patients with FCS.

Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by mutations in genes regulating lipoprotein lipase activity, typically manifesting early in life.

Case presentation: We describe a 70-year-old man with severe refractory hypertriglyceridemia, chronic hyperCKemia, and protein-energy malnutrition, ultimately diagnosed with FCS due to a homozygous pathogenic LPL variant (c.844G>T; p.Glu282*). Despite long-standing disease and comorbidities, treatment with volanesorsen, an antisense oligonucleotide targeting apoC-III mRNA, produced a 74% reduction in triglyceride levels and marked clinical improvement. This case underscores that FCS may remain undetected until late adulthood, particularly when confounded by diabetes or chronic kidney disease.

Conclusion: Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life.

In the recent ApoA-I Event Reducing in Ischemic Syndromes II trial, a plasma-derived apolipoprotein A-I (apoA-I) infusion (CSL112) demonstrated no significant reduction in major cardiovascular events in the overall postmyocardial infarction population. However, exploratory analyses revealed benefits in subgroups with both elevated low-density lipoprotein cholesterol (LDL-C) and systemic inflammation, suggesting that biologic context may be critical to therapeutic efficacy. Building on these trial findings, we highlight that the efficacy of CSL112 may depend on the coexistence of elevated LDL-C and systemic inflammation. We integrate ATP-binding cassette transporter A1 (ABCA1) biology with subgroup trial findings to propose a precision-stratification framework for future apoA-I infusion trials. We focus on the interaction of lipid burden and inflammation on ABCA1 transporter function, the impact of statin-induced transporter downregulation, and strategies for patient selection, including ex vivo efflux assays and molecular transporter profiling, and the therapeutic promise of combination therapies (apoA-I infusion with liver X receptor agonists) in patients with impaired transporter function.

Background: Omega-3 polyunsaturated fatty acid (PUFA) administration has been associated with a reduced risk of developing cardiovascular diseases. Some studies have explored the potential effect of omega-3 PUFA on lipoprotein-associated phospholipase A2 (Lp-PLA2) levels with conflicting results; while some have shown no effect, others have found reduced levels of Lp-PLA2 with omega-3 supplementation. This meta-analysis of randomized controlled trials aims to clarify the impact of omega-3 supplementation on Lp-PLA2 mass and activity.

Sources of material: The Medical Subject Headings (MeSH) terms and keywords were searched in Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases. The random- or fixed-effects model and the generic inverse variance weighting method were applied for quantitative data. The influence of each study on the overall effect size was determined using the leave-one-out method.

Abstract of findings: The meta-analysis of 16 randomized controlled trials showed a significant reduction in Lp-PLA2 mass with omega-3 intervention (weighted mean difference [WMD]: -24.05 ng/mL, 95% CI: -27.63, -20.47, P < .0001) but no significant changes in Lp-PLA2 activity (WMD: -8.54 nmol/mL/min, 95% CI: -27.25, 10.18, P = .37). A subgroup analysis by type of omega-3 supplementation revealed that either icosapent ethyl (WMD: -32.67 ng/mL, 95% CI: -34.36, -30.98, P < .00001) or other omega-3 formulations (WMD: -17.05 ng/mL, 95% CI: -22.93, -11.18, P < .00001) significantly decreased the Lp-PLA2 mass.

Conclusion: Omega-3 supplementation significantly reduces circulating levels of Lp-PLA2 mass without affecting its activity.