Journal of clinical lipidology最新文献

{"title":"Rapid lipid-lowering response in two cases of autosomal recessive hypercholesterolemia","authors":"Havva Yazıcı,&nbsp;Fehime Erdem,&nbsp;Ebru Canda,&nbsp;Sema Kalkan Uçar,&nbsp;Mahmut Çoker","doi":"10.1016/j.jacl.2024.09.003","DOIUrl":"10.1016/j.jacl.2024.09.003","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Autosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the <em>LDLRAP1</em> gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH).</div></div><div><h3>CASE</h3><div>We present the cases of 2 siblings diagnosed with ARH caused by <em>LDLRAP1</em> gene c.617-14C &gt; A splicing homozygous variant. Over a 5-year treatment period, the older sibling experienced an 81% reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75% reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis.</div></div><div><h3>CONCLUSION</h3><div>Our findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C &gt; A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 167-172"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extreme LDL-C concentration is associated with increased cardiovascular disease in women with homozygous familial hypercholesterolemia","authors":"Martine Paquette MSc ,&nbsp;Isabelle Ruel PhD ,&nbsp;Simon-Pierre Guay MD, PhD ,&nbsp;Zobaida Al-Baldawi MSc ,&nbsp;Diane Brisson PhD ,&nbsp;Daniel Gaudet MD, PhD ,&nbsp;Patrick Couture MD, PhD ,&nbsp;Jean Bergeron MD, MSc ,&nbsp;Robert A Hegele MD ,&nbsp;Gordon A Francis MD ,&nbsp;Mark H Sherman MD ,&nbsp;Ruth McPherson MD, PhD ,&nbsp;Thomas Ransom MD, MSc ,&nbsp;Liam R Brunham MD, PhD ,&nbsp;GB John Mancini MD ,&nbsp;Brian W McCrindle MD MPH ,&nbsp;Lulia Latan MD, PhD ,&nbsp;Jacques Genest MD ,&nbsp;Alexis Baass MD, MSc","doi":"10.1016/j.jacl.2024.10.008","DOIUrl":"10.1016/j.jacl.2024.10.008","url":null,"abstract":"<div><h3>BACKGROUND</h3><div>Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied.</div></div><div><h3>OBJECTIVE</h3><div>To investigate the univariate and multivariate predictors of ASCVD in HoFH patients.</div></div><div><h3>METHODS</h3><div>Patients from the Canadian HoFH Registry were included in the present retrospective longitudinal study. Data for these patients were collected using a standardized questionnaire between 2019 and 2022 in 19 academic sites across Canada. Predictors of ASCVD were evaluated using Cox proportional hazards models.</div></div><div><h3>RESULTS</h3><div>Among 48 HoFH patients, 26 (54%) of them had at least 1 ASCVD event. The average age at baseline was 19 ± 15 years and women represented 56% of the cohort. The independent predictors of ASCVD events were male sex (HR 2.57 [1.13–5.84]), diabetes (HR 16.22 [3.38–77.97]), and LDL-C above the median of 14.45 mmol/L (559 mg/dL) (HR 3.10 [1.24–7.76]). When performing subgroup analysis according to sex, the presence of LDL-C above the median was associated with a significantly higher probability of ASCVD (88% vs 43%, <em>P</em> = .005) in women, but not in men (100% at age 40 in both groups, <em>P</em> = .98).</div></div><div><h3>CONCLUSION</h3><div>This study reported for the first time the univariate and multivariate predictors of ASCVD in HoFH patients. We demonstrate that predictors of ASCVD in HoFH differ in males and females with respect to LDL-C levels.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 1","pages":"Pages 105-113"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-lowering efficacy of obicetrapib: A comprehensive systematic review and meta-analysis.","authors":"Walter Masson, Leandro Barbagelata, Martin Lobo, Juan Patricio Nogueira, Yehuda Handelsman","doi":"10.1016/j.jacl.2024.12.016","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.016","url":null,"abstract":"<p><strong>Background: </strong>Obicetrapib is a next-generation, oral, selective cholesteryl ester transfer protein inhibitor known to significantly affect atherogenic lipoproteins, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (Non-HDL-C), and lipoprotein(a) [Lp(a)].</p><p><strong>Objective: </strong>To evaluate the lipid-lowering efficacy of obicetrapib based on available evidence.</p><p><strong>Methods: </strong>This systematic review was drafted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted to identify randomized clinical trials assessing the lipid-lowering effects of obicetrapib compared to placebo. Fixed- and random-effects models were used.</p><p><strong>Results: </strong>Five randomized clinical trials (n = 288 patients) were included in this analysis. Patients treated with obicetrapib exhibited significantly greater reductions in LDL-C (mean difference [MD]: 41.4% [95% CI: 45.7 to -37.1]; I²: 6%), ApoB (MD: 26.5% [95% CI: 31.3 to -21.6]; I²: 45%) and Non-HDL-C (MD: 34.5% [95% CI: 37.0 to -31.6]; I²: 80%) compared to those receiving a placebo. Additionally, HDL-C levels were significantly higher in the obicetrapib group (MD: 157.4% [95% CI: 142.2 to 172.6]; I²: 69%). While triglyceride levels did not differ significantly between the 2 groups, Lp(a) levels were notably reduced with obicetrapib treatment (MD: 39.5% [95% CI: 54.6 to -24.3]; I²: 67%).</p><p><strong>Conclusion: </strong>Obicetrapib is associated with significant reductions in key atherogenic lipoproteins, including LDL-C, ApoB, Non-HDL-C and Lp(a). Further investigation is needed to assess its impact on cardiovascular risk.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and outcomes of patients with and without statin-associated muscle symptoms treated with bempedoic acid in the CLEAR Outcomes trial.","authors":"Ulrich Laufs, A Michael Lincoff, Stephen J Nicholls, Na Li, LeAnne Bloedon, William J Sasiela, Heather A Powell, Peter M Herout, Paul D Thompson, Steven E Nissen","doi":"10.1016/j.jacl.2024.12.014","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.014","url":null,"abstract":"<p><strong>Background: </strong>Cholesterol Lowering via bEmpedoic Acid Regimen (CLEAR) outcomes, a randomized, double-blind, placebo-controlled cardiovascular outcomes trial, and the largest prospective database of patients with statin intolerance (SI), demonstrated that bempedoic acid reduces low-density lipoprotein cholesterol and cardiovascular risk in patients at high cardiovascular risk.</p><p><strong>Objective: </strong>Assess baseline differences in SI symptoms and whether these influenced the clinical course during CLEAR outcomes.</p><p><strong>Methods: </strong>Symptoms and impact of SI on daily living were recorded prior to randomization. This posthoc analysis grouped patients as reporting statin-associated muscle symptoms only (SAMS), nonmuscle adverse effects only (nonSAMS), or BOTH.</p><p><strong>Results: </strong>Of the 13,970 patients at baseline, 49% reported SAMS, 18% NonSAMS, and 33% BOTH. Moderate/severe impact on daily living was recorded for 62% SAMS, 48% NonSAMS, and 69% BOTH. Baseline lipid modifying treatment (LMT) was used in 43% SAMS, 36% nonSAMS, and 42% BOTH. Drop-in use of moderate/high-intensity statin at any time during the study was higher in the placebo group in all SI groups and higher in SAMS and BOTH vs. nonSAMS, but was not generally maintained at study end. SAMS and BOTH groups had more muscle symptoms and higher rates of treatment discontinuation vs. NonSAMS but there was no difference between treatments.</p><p><strong>Conclusion: </strong>Patients who reported SAMS, regardless of randomization to bempedoic acid or placebo, had higher rates of discontinuation, higher rates of skeletal muscle symptoms, and a greater percentage of patients to attempt statin rechallenge. These findings indicate patients with history of SAMS may have background factors impacting their tolerance to LMT and may require more focused clinical management.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT02993406.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of empagliflozin on plasma lipids and lipoproteins in type 2 diabetes and heart failure - Empire HF and SIMPLE.","authors":"Frida Emanuelsson, Jesper Jensen, Massar Omar, Mikkel Jürgens, Caroline Kistorp, Niels H Brandt-Jacobsen, Jacob Eifer Møller, Morten Schou, Louise Ellegaard Bechmann, Emil List Larsen, Børge G Nordestgaard, Marianne Benn","doi":"10.1016/j.jacl.2024.12.015","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.015","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of volanesorsen on apoC-III, triglycerides and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or non-genetic criteria.","authors":"Sotirios Tsimikas, Henry N Ginsberg, Veronica J Alexander, Ewa Karwatowska-Prokopczuk, Andy Dibble, Lu Li, Joseph L Witztum, Robert A Hegele","doi":"10.1016/j.jacl.2024.12.018","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.018","url":null,"abstract":"<p><strong>Background: </strong>Familial chylomicronemia syndrome (FCS) is diagnosed by genetic or non-genetic criteria.</p><p><strong>Objective: </strong>To assess responses to treatment of apolipoprotein (apo)C-III, triglycerides, and pancreatitis events in patients with FCS-based diagnostic methods.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>For a similar reduction in apoC-III in response to volanesorsen, triglyceride reduction is attenuated in patients with genetically versus non-genetically diagnosed FCS.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between lipoprotein(a) levels and the development of cardiac allograft vasculopathy.","authors":"Mohammed Tiseer Abbas, Kamal Awad, Juan M Farina, Ahmed K Mahmoud, Milagros Pereyra, Isabel G Scalia, Moaz A Kamel, Nima Baba Ali, Said Alsidawi, Steven J Lester, Vuyisile T Nkomo, Parag C Patel, Kristen A Sell-Dottin, Andrew N Rosenbaum, Grace Lin, Brian W Hardaway, D Eric Steidley, Robert L Scott, Lisa M LeMond, Julie L Rosenthal, Chadi Ayoub, Reza Arsanjani","doi":"10.1016/j.jacl.2024.12.011","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.011","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-fasting triglyceride screening in volunteer blood donors: A pilot program.","authors":"Caroline Abe, Emily Decicco, Stephen Eason, Frances Compton, Merlyn Sayers, Sukh Makhnoon, Michelle L Xing, Chao Xing, Amit Khera, Zahid Ahmad","doi":"10.1016/j.jacl.2024.12.013","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.013","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein particle profile in the presence of peripheral artery disease among patients with coronary heart disease: Data from the CORDIOPREV study.","authors":"Silvia de la Cruz-Ares, María Del Pilar Coronado-Carvajal, Oriol Alberto Rangel-Zúñiga, José David Torres-Peña, Antonio Pablo Arenas-de Larriva, Alejandro López-Moreno, Niki Katsiki, José María Ordovás, Javier Delgado-Lista, Pablo López-Martínez, Francisco Miguel Gutiérrez-Mariscal, José López-Miranda","doi":"10.1016/j.jacl.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.007","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>This study explores the association between lipoprotein subfractions and the occurrence of PAD in patients with coronary heart disease (CHD).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonlinearity of the inverse relationship between high-density lipoprotein (HDL) cholesterol and incident cardiovascular risk: Is it time to revisit the \"HDL hypothesis\"?","authors":"Carl Hashem, S Elissa Altin, John R Guyton, William E Boden","doi":"10.1016/j.jacl.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.12.009","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Sources of material: </strong>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.</p><p><strong>Abstract of findings: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}