Journal of clinical lipidology最新文献

Objective: Beyond glucose-lowering, sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects with unclear mechanisms. We examined changes in an extensive panel of plasma lipids, lipoproteins, and apolipoproteins and whether these changes were independent of weight loss, hemoglobin A1c, and hematocrit in patients treated with empagliflozin versus placebo to better understand the observed cardioprotective effects.

Methods: Post-hoc analyses of two double-blind, placebo-controlled trials, the Empire HF trial including 190 patients with heart failure and reduced ejection fraction and the SIMPLE trial including 90 patients with type 2 diabetes randomized to, respectively, 10 mg and 25 mg empagliflozin daily or placebo for 12 weeks.

Results: In studies combined, empagliflozin reduced age and sex adjusted body weight by 1.40 kg (SEM: 0.10; p < 0.001) and hemoglobin A1c by 2.71 mmol/mol (SEM: 0.24; p < 0.001); and increased hematocrit by 1.9% (SEM: 0.12; p < 0.001) compared to placebo. No mean changes were seen in concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, small dense LDL cholesterol, very low-density lipoprotein cholesterol, triglyceride rich lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, lipoprotein(a), HDL cholesterol, and triglycerides adjusted for body weight, hemoglobin A1c, and hematocrit with empagliflozin compared to placebo.

Conclusion: Empagliflozin treatment reduced body weight and hemoglobin A1c; and increased hematocrit. No changes were seen in concentrations of lipids and lipoproteins with empagliflozin compared to placebo. This suggests that the cardioprotective effects of SGLT2 inhibitors are independent of lipid and lipoprotein concentrations.

Background: Familial chylomicronemia syndrome (FCS) is diagnosed by genetic or non-genetic criteria.

Objective: To assess responses to treatment of apolipoprotein (apo)C-III, triglycerides, and pancreatitis events in patients with FCS-based diagnostic methods.

Methods: APPROACH enrolled 66 patients with FCS randomized to volanesorsen or placebo for 12 months. In 50 participants, genetic confirmation of FCS was based on the presence of pathogenic bi-allelic variants in LPL, APOC2, APOA5, GPIHBP1, or LMF1 genes. In 16 participants without a genetic diagnosis, FCS was diagnosed using clinical criteria and post-heparin lipoprotein lipase activity ≤20 % of normal. Plasma levels of apoC-III, triglycerides and related variables were measured at 3, 6 and 12 months.

Results: No significant differences were present in mean apoC-III reductions with volanesorsen at 3, 6 or 12 months in patients with FCS diagnosed either genetically or non-genetically. In contrast, the triglyceride reductions were statistically less robust in patients with genetic diagnosis at each timepoint, with mean (95 % confidence interval) percent reduction in triglycerides of -68.7 % (-78.7, -58.6) vs. -84.0 % (-99.4, -68.6), p = 0.014 at Month 3; -58.2 % (-78.1, -38.2) vs. -84.5 % (-122.4, -46.7), p = 0.009 at Month 6; and -35.6 % (-57.7, -13.4) vs. -69.0 % (-105.0, -33.1), p = 0.005 at Month 12. Patients with a genetic diagnosis had significantly lower response rates for achieved triglycerides <500 mg/dL, <750 mg/dL, <880 mg/dL and <1000 mg/dL than patients with a non-genetic diagnosis. All 5 episodes of acute pancreatitis occurred in patients with a genetic diagnosis.

Conclusions: For a similar reduction in apoC-III in response to volanesorsen, triglyceride reduction is attenuated in patients with genetically versus non-genetically diagnosed FCS.

This pilot study explores the feasibility of large-scale non-fasting triglyceride level screening at blood donation centers. Hypertriglyceridemia is a risk factor for cardiovascular disease and acute pancreatitis. Triglyceride levels were measured in 10,176 blood donors at Carter BloodCare North Texas and found 39.2% with moderate and 2.4% with severe hypertriglyceridemia. Predictors of elevated triglycerides included age, male gender, blood pressure, and body mass index, with increased odds in Hispanic and Asian individuals compared to White individuals. Survey results from 50 donors with severe hypertriglyceridemia showed 69% had positive intent to seek medical care. The study highlights the potential of blood donation centers to serve as platforms for public health screening, and scaling low-cost, non-fasting triglyceride screening is feasible. This approach provides an opportunity for early intervention and disease prevention.

Lipoprotein(a) [Lp(a)] has been established as an independent risk factor for cardiovascular diseases. However, its role in cardiac allograft vasculopathy (CAV) development remains controversial. In a retrospective cohort study of 385 patients who underwent heart transplant between 2001 and 2023, Lp(a) concentrations were compared between patients with and without clinically significant CAV (grade 0-1 vs 2-3). Preoperative Lp(a) concentrations were not significantly different between patients with and without CAV (14.0 vs 12.0 mg/dL, P = .42). High (≥50 mg/dL) Lp(a) values were not associated with CAV development on univariable or multivariable analysis (hazard ratio [HR] 1.009, 95 % confidence interval [CI]: 0.47-2.14, P = .9). A history of graft rejection was the only independent factor associated with CAV (HR 2.88, 95 % CI: 1.50-5.52, P = .001). Elevated Lp(a) levels were not associated with increased risk of CAV. The lack of a significant association between traditional risk factors and CAV underscores that CAV is not purely an atherosclerotic process and different pathophysiological mechanisms are involved.

Background: Dyslipidemia is recognized as a contributing factor to peripheral artery disease (PAD). However, the influence of lipoprotein subfractions as compared to traditional serum lipid levels is not well-understood.

Objective: This study explores the association between lipoprotein subfractions and the occurrence of PAD in patients with coronary heart disease (CHD).

Methods: In the CORDIOPREV study, 981 patients were categorized based on PAD diagnosis, determined by an ankle-brachial index (ABI) ≤0.9. Those with ABI >0.9 and <1.4 were considered PAD-free, while patients with ABI ≥1.4 were excluded. We employed high-throughput nuclear magnetic resonance (NMR) spectroscopy to analyze the concentration and lipid content of lipoprotein subfractions.

Results: PAD patients exhibited significantly lower levels of medium high-density lipoprotein (HDL) particles and reduced concentrations of associated lipids within these subfractions except for triglycerides. A higher concentration of large or medium HDL particles correlated with a lower PAD prevalence (OR: 0.61, 95% CI, 0.44-0.84; OR: 0.59, 95% CI, 0.43-0.81, respectively). In multivariate logistic regression, medium HDL particle levels inversely associated with PAD presence (OR: 0.69, 95% CI, 0.48-0.99, P = .044) after adjustment for confounding factors.

Conclusions: The presence of PAD among CHD patients inversely correlates with medium HDL particle concentrations as determined by NMR. These insights could advance our understanding of PAD pathophysiology and HDL metabolism.

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) are clearly associated with atherosclerotic cardiovascular disease (ASCVD), but the risk curve is not well defined, especially at very high and low HDL-C levels. Current proportional hazards prediction models assume inverse linearity of effect, which may not accurately represent risk at these levels.

Sources of material: Clinical inattention to risk associated with low HDL-C may derive from randomized controlled trials (RCTs) aimed at raising HDL-C, though most failed to reduce ASCVD events when combined with statin-based therapy. However, these prior trials enrolled patients with HDL-C levels largely in the 35-45 mg/dL range.

Abstract of findings: Mounting post hoc evidence from RCTsß as well as new genetic and observational data suggests that very low HDL-C (less than 30 or 35 mg/dL) may signal a further increase in incident cardiovascular events. Moreover, when HDL-C exceeds 90 mg/dL, monotonic reduction of ASCVD risk appears to reverse. Because a pervasively agnostic view of the importance of both very low and high levels of HDL-C now exists, consideration should be given to incorporating nonlinear effects of HDL-C into future risk prediction models such that very low HDL-C and/or very high HDL-C levels could be considered as new risk-enhancing factors to promote more optimal risk stratification.

Conclusion: When revision of the U.S. Cholesterol Guideline recommences, consideration should be directed to whether HDL-associated risk matches the assumptions of current statistical models. Thus, it may be both timely and opportune to revisit the "HDL Hypothesis" based on evolving scientific evidence.

Lipid goal attainment remains suboptimal due to patient, provider, and system level factors. We aimed to assess whether updated, guideline-based lipid reporting and clinical decision support was associated with different lipid-lowering therapy (LLT) prescription patterns. We conducted a retrospective study in our electronic health record (EHR) comparing prescriptions within 90 days of lab reporting both prior to the reporting change (21,417 patients in 2019-2020) and after (39,866 patients in 2020-2021). We found a significant increase in the initiation of LLT in patients > 40 years of age with LDL-C ≥ 100  mg/dL, with 2377 (11.6%) initiated prior to compared to 6205 (16.3%) after the reporting change (P < .001). Among 4469 adult patients with ASCVD and LDL-C ≥ 70 mg/dL prior to (n = 2040) and after (n = 3277) the reporting change, there was a significantly higher rate of LLT initiation, 444 (25.9%) prior to vs 875 (31.8%) after; P < .001. In conclusion, after implementation of updated guideline-based lipid test reporting, we observed higher initiation rates of LLT for indicated patients. Our study suggests that guideline-based reporting of lipid test results may aid in guideline implementation.

Background: Ezetimibe, a Niemann-Pick C1-like 1 inhibitor, is widely prescribed as a monotherapy or in combination with statins to reduce cholesterol levels. Although generally well-tolerated, concerns have emerged regarding the risk of rhabdomyolysis, particularly with combination therapies. This study aims to evaluate the association between ezetimibe and rhabdomyolysis using data from the United States Food and Drug Administration's Adverse Event Reporting System (USFDA AERS), case reviews, and a meta-analysis of clinical trials.

Methods: We analyzed reports from the USFDA AERS between Q1 2004 and Q2 2024, focusing on cases with rhabdomyolysis with ezetimibe alone or in combination with statins or bempedoic acid. Disproportionality analysis using both frequentist and Bayesian methods was conducted. We also reviewed published case reports and performed a meta-analysis of randomized clinical trials comparing ezetimibe monotherapy with placebo.

Results: Of 29,153,222 reports in AERS, 668 cases met the inclusion criteria. Frequentist and Bayesian analyses indicated an increased risk of rhabdomyolysis with ezetimibe alone and with statin combinations, particularly with simvastatin and atorvastatin. Interaction signal scores suggested statistically significant interactions between ezetimibe and certain statins (atorvastatin and rosuvastatin). Case reviews identified nine published cases, most of which involved ezetimibe in patients on a stable background therapy of statins. The meta-analysis of 3 trials did not show a significant risk for rhabdomyolysis with ezetimibe monotherapy.

Conclusion: This study suggests a potentially possible association between ezetimibe (monotherapy and in combination), and rhabdomyolysis risk. Clinicians should monitor patients closely, particularly those on combination therapies. Further prospective studies are needed to elucidate causality and inform safe prescribing practices.

Tangier disease is an extremely rare autosomal recessive monogenic disorder caused by mutations in the ATP binding cassette transporter A1 gene (ABCA1). It is characterized by severe deficiency or absence of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA1), with highly variable clinical presentations depending on cholesterol accumulation in macrophages across different tissues. We report a case of a 47-year-old man with very low HDL-C and very high triglyceride levels, initially attributed to the patient's metabolic syndrome, alcohol abuse, and splenomegaly. He had pancytopenia and splenomegaly for over fourteen years and developed premature myocardial infarction during his diagnostic workup. Suspecting of Tangier disease, we sequenced the ABCA1 gene, which revealed a homozygous new variant c.164A>G p (His5Arg) in the exon 4. Given the limited number of published cases, there are no reliable data on genotype-phenotype correlations in Tangier disease, highlighting the importance of reporting new variants and associated clinical features.