Journal of clinical lipidology最新文献

{"title":"Expanding the LDL-C criterion for suspected homozygous familial hypercholesterolemia to include treated and imputed elevations.","authors":"G B John Mancini, Frederick J Raal","doi":"10.1016/j.jacl.2026.09.015","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.015","url":null,"abstract":"<p><p>Homozygous familial hypercholesterolemia (HoFH) remains underdiagnosed worldwide. Cases may not be suspected when family history, physical manifestations, and untreated low-density lipoprotein-cholesterol (LDL-C) levels are unknown or when treated LDL-C levels do not meet current accepted criteria. The latter can be overcome through the application of a validated algorithm for the calculation of an imputed, pretreatment LDL-C based on treated LDL-C considered in the context and the drugs/dosages used to achieve that value. A study of this approach recently provides justification for expansion of the LDL-C criterion for suspected HoFH to be altered to include treated, untreated, or imputed LDL-C >10 mmol/L.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110391","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":"Need for population-specific lipid guidelines for South Asians: Focus on the Indian population and its distinct cardiometabolic risk profile.","authors":"Raman Puri, Vimal Mehta, Prasant Kumar Sahoo, Jamal Yusuf","doi":"10.1016/j.jacl.2026.09.010","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.010","url":null,"abstract":"<p><strong>Background: </strong>South Asian individuals bear a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD), characterized by earlier onset, greater severity, and higher mortality compared with Western populations. This is despite lower average low-density lipoprotein cholesterol (LDL-C) levels and is driven by a distinctive cardiometabolic phenotype, including adverse lifestyle factors, high prevalence of insulin resistance and diabetes, hypertriglyceridemia, increased small dense LDL particles, elevated lipoprotein(a), and low high-density lipoprotein cholesterol (HDL-C) levels.</p><p><strong>Objective: </strong>To review the cardiometabolic risk profile of South Asians and the rationale for population-specific lipid management strategies, with a focus on contemporary evidence and recommendations from the Lipid Association of India (LAI).</p><p><strong>Methods: </strong>The relevant evidence was identified from published prospective cohort studies, randomized controlled trials, meta-analyses, and international and Indian guidelines with emphasis on studies evaluating South Asian/ Indian populations. The literature was evaluated with specific attention to differences in ASCVD burden, age at disease onset, cardiometabolic risk factors, lipid and lipoprotein profiles, and treatment responses between South Asian/Indian and Western populations. Evidence supporting intensive LDL-C lowering and combination lipid-lowering therapy was reviewed.</p><p><strong>Results: </strong>South Asians demonstrate a high prevalence of atherogenic dyslipidemia characterized by hypertriglyceridemia, low HDL-C, elevated non-HDL-C, and increased apolipoprotein B (apo B) containing particles, often with relatively modest LDL-C levels. Western risk prediction models and lipid thresholds may therefore underestimate ASCVD risk in this population. LAI guidelines recommend lower LDL-C targets than Western counterparts, refined ASCVD risk stratification including extreme-risk group categories, and the use of non-HDL-C and apo B as complementary therapeutic targets. Combination lipid-lowering therapy with statins, ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors is often required to achieve recommended goals and address residual lipid-related risk.</p><p><strong>Conclusion: </strong>Given the distinctive cardiometabolic profile and high ASCVD burden, population-specific lipid guidelines are essential. Intensive LDL-C and non-HDL-C lowering, comprehensive risk stratification, and early combination therapy, alongside sustained lifestyle modification and optimal management of comorbidities, are key strategies to mitigate the growing epidemic of ASCVD in South Asian populations.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182175","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":"Safety and tolerability of nonstatin LDL-cholesterol-lowering therapies: A systematic review and pairwise meta-analysis of randomized controlled trials.","authors":"Andrea Matteucci, Michela Bonanni, Stefania Angela Di Fusco, Alessandro Aiello, Stefano Aquilani, Silvio Fedele, Federico Nardi, Furio Colivicchi","doi":"10.1016/j.jacl.2026.09.012","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.012","url":null,"abstract":"<p><strong>Background: </strong>Nonstatin low-density lipoprotein (LDL)-cholesterol-lowering therapies are increasingly used in secondary prevention, familial hypercholesterolemia, and statin-intolerant patients, but adverse-event reporting is heterogeneous, and harmonized safety evidence remains limited.</p><p><strong>Objective: </strong>To evaluate the tolerability and safety profile of non-statin LDL-cholesterol-lowering treatments.</p><p><strong>Methods: </strong>We performed a systematic review and pairwise meta-analysis of randomized, double-blind, placebo-controlled trials of ezetimibe, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies, bempedoic acid, and inclisiran. Prespecified tolerability outcomes were any adverse event, serious adverse event, discontinuation because of adverse events, and investigator-attributed drug-related adverse events. Safety outcomes included myalgia, muscle-related and hepatic adverse events, aminotransferase elevation greater than 3 times the upper limit of normal, and neurocognitive adverse events. Random-effects Mantel-Haenszel models estimated risk ratios (RRs) with 95% CIs using restricted maximum likelihood and Hartung-Knapp adjustment.</p><p><strong>Results: </strong>The primary synthesis included 41 trial-level comparisons and 104,672 participants. Nonstatin LDL-cholesterol-lowering therapy was not associated with any adverse event (RR 1.003, 95% CI 0.991-1.015) or serious adverse event (RR 0.980, 0.946-1.015), but discontinuation because of adverse events (RR 1.084, 1.020-1.152) and investigator-attributed drug-related adverse events (RR 1.227, 1.120-1.344) were modestly increased. No significant pooled associations were observed for myalgia, muscle-related, hepatic, aminotransferase, or neurocognitive adverse events. The only class-specific finding remaining significant after false-discovery-rate correction was lower myalgia risk in adenosine triphosphate citrate lyase-inhibitor trials (RR 0.845, 0.769-0.927), attenuated after excluding CLEAR outcomes.</p><p><strong>Conclusion: </strong>Nonstatin LDL-cholesterol-lowering therapies were not associated with excess total or serious adverse events or consistent muscle, hepatic, or neurocognitive safety signals. Modest excesses were confined to tolerability-related outcomes (discontinuation because of adverse events and investigator-attributed drug-related adverse events) rather than major toxicity.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127709","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":"Does the evidence support the ACC/AHA multisociety recommendation to measure apoB only after LDL-C and non-HDL-C are at target?","authors":"Justine Cole, Line Dufresne, Peter P Toth, Michel Langlois, George Thanassoulis, Allan D Sniderman","doi":"10.1016/j.jacl.2026.09.009","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.009","url":null,"abstract":"<p><strong>Background: </strong>The American College of Cardiology (ACC)/American Heart Association (AHA) multisociety guidelines, state that discordance between apolipoprotein B (apoB) and Martin/Hopkins (MH) low-density lipoprotein cholesterol (LDL-C) is minimal at LDL-C targets of 100 and 70 mg/dL, citing studies that did not use the guideline's apoB targets.</p><p><strong>Objective: </strong>We aimed to quantify discordance at the recommended apoB targets, which correspond to values from uncited studies, and at population-equivalent values, and to determine the clinical significance of that discordance.</p><p><strong>Methods: </strong>Variance between LDL-C estimated by MH, modified-Sampson (mS), or Friedewald (F) and apoB was examined in the National Health and Nutrition Examination Survey (NHANES) database. Differences between achieving guideline targs of MH LDL-C, mS LDL-C, and F LDL-C vs guideline target levels of apoB (90, 70, and 55 mg/dL) or the percentile equivalent values of apoB in the untreated NHANES-based population (79, 58, and 46 mg/dL) were calculated. Clinical significance of discordance of MH-LDL-C was determined in the UK Biobank overall and at the 3 target levels of MH LDL-C.</p><p><strong>Results: </strong>Significant discordance was present between LDL-C, however estimated, and apoB in the NHANES participants. Substantial differences between apoB and LDL-C at target levels were evident using guideline target values of apoB and even greater using population equivalent values of apoB. In the UK Biobank, residual discordance analysis demonstrated apoB was a more precise marker of cardiovascular risk than MH LDL-C overall and at MH LDL-C target levels of LDL-C of 100 and 70 mg/dL.</p><p><strong>Conclusion: </strong>This report identifies an apparent consequential error in the ACC/AHA multisociety guidelines and further supports the view that apoB should have at least equal priority to LDL-C and non-high-density lipoprotein cholesterol in routine clinical care.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127723","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":"Fatty liver index and atherogenic risk determined by lipoprotein particle subclasses: A cross-sectional study of middle- to older-aged adults.","authors":"Seán R Millar, Ivan J Perry, Catherine M Phillips","doi":"10.1016/j.jacl.2026.09.007","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.007","url":null,"abstract":"<p><strong>Background: </strong>The fatty liver index (FLI) provides a cost-effective way to screen for metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is associated with preclinical atherosclerosis, with cardiovascular disease (CVD) mortality being the leading cause of death among MASLD patients.</p><p><strong>Objective: </strong>Lipoprotein particles can provide better CVD risk prediction than traditional lipid measures. Yet, FLI associations with intermediate disease markers remain under-researched. This study addressed this gap by investigating FLI relationships with lipoprotein particle subclass concentrations.</p><p><strong>Methods: </strong>This was a cross-sectional study of 1713 middle-aged to older-aged men and women randomly selected from a large primary care center. The FLI was calculated using triglyceride, body mass index, waist circumference, and gamma-glutamyl transferase levels. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Linear regression analyses examined FLI associations with lipoprotein biomarkers.</p><p><strong>Results: </strong>In fully adjusted models, higher FLI scores were associated with larger very low-density lipoprotein (VLDL) and smaller low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size, more large and medium VLDL, small LDL, and less large HDL particle concentrations, and greater lipoprotein-related insulin resistance (all P <.001). In models that examined these variable associations across FLI quintiles, significant dose-response relationships were observed (P trend <.001 for all).</p><p><strong>Conclusion: </strong>These findings support the clinical utility of the FLI as a marker of atherogenic risk and as a tool for identifying at-risk individuals. Incorporating the FLI into CVD risk assessment may help improve risk prediction in individuals with liver disease and guide targeted interventions.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136898","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":"Estimated small dense low-density lipoprotein cholesterol in predicting atherosclerotic cardiovascular disease: Longitudinal evidence from over 1 million Japanese adults.","authors":"Koki Ono, Aya Hirata, Tomonori Okamura","doi":"10.1016/j.jacl.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.005","url":null,"abstract":"<p><strong>Background: </strong>Small dense low-density lipoprotein cholesterol (sdLDL-C) is an atherogenic LDL-C subfraction associated with atherosclerotic cardiovascular disease (ASCVD). Although sdLDL-C integration into major routine risk assessments remains limited, partly because of requiring additional lipid tests, a more implementable estimated sdLDL-C equation was recently developed.</p><p><strong>Objective: </strong>This study aimed to evaluate the association between estimated sdLDL-C and incident ASCVD in a health checkup population of Japanese adults.</p><p><strong>Methods: </strong>Using the DeSC database in Japan, this study included adults aged 40 to 74 years who underwent health checkups between April 2014 and March 2023. Estimated sdLDL-C was calculated via the Sampson formula, and the primary outcome was the first incident ASCVD hospitalization via claims data. Estimated sdLDL-C was categorized into quartiles, and associations with incident ASCVD were evaluated using Cox regression models adjusted for sex, age, body mass index, hypertension, diabetes, smoking, alcohol, low HDL-C, high LDL-C, lipid-lowering medication, and fasting time. Subgroup analyses were conducted by LDL-C, sex, age, and ASCVD subtypes.</p><p><strong>Results: </strong>Among 1884,758 participants, 22,596 incident ASCVD events were observed. The Cox model showed ASCVD risk increased across estimated sdLDL-C quartiles, with a hazard ratio of 1.25 (1.20-1.31) for Q4. This association largely continued across sex, age, LDL-C, and ASCVD subtype subgroups, with stronger associations observed in male participants for coronary artery disease (CAD) than ischemic stroke, among younger individuals, and those with higher LDL-C.</p><p><strong>Conclusion: </strong>Higher estimated sdLDL-C was associated with increased ASCVD risk, including among individuals with low LDL-C. Estimated sdLDL-C may improve ASCVD risk stratification beyond LDL-C and inform further primary prevention strategies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110339","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":"Association between lipoprotein(a) and structural degeneration of bioprosthetic aortic valves: A systematic review and meta-analysis.","authors":"Ermilo Echeverría-Ortegón, Mario César Torres-Chávez, Alfredo Pérez-Tagle Tejeda, Paulina Caballero, Juan Pastor-Cervantes","doi":"10.1016/j.jacl.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.003","url":null,"abstract":"<p><strong>Background: </strong>Structural valve degeneration (SVD) remains a major limitation of bioprosthetic aortic valves (bAVs). Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor implicated in native aortic valve calcification, but its role in bioprosthetic valve degeneration remains incompletely understood.</p><p><strong>Objective: </strong>To systematically evaluate the association between elevated Lp(a) levels and structural degeneration of bAVs.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EBSCOhost, and Cochrane Library databases were searched for studies evaluating Lp(a) and structural degeneration of bAVs in patients undergoing surgical or transcatheter aortic valve replacement. Random-effects models were used to pool effect estimates. Cross-sectional outcomes were summarized using odds ratios (ORs), and longitudinal outcomes were pooled using hazard ratios (HRs), both with 95% CIs.</p><p><strong>Results: </strong>Five observational cohort studies, including 1227 patients, were included. In cross-sectional analyses (2 studies), elevated Lp(a) levels were significantly associated with SVD (OR 2.09, 95% CI 1.02-4.28; I² = 0%). In longitudinal analyses (3 studies), elevated Lp(a) was associated with a higher risk of incident SVD or valve-related reintervention (HR 3.49, 95% CI 2.18-5.59; I² = 0%).</p><p><strong>Conclusion: </strong>Elevated Lp(a) levels are associated with an increased risk of structural degeneration in bAVs. Lp(a) may represent a useful biomarker for identifying patients at higher risk of valve deterioration and may have implications for surveillance strategies and emerging Lp(a)-lowering therapies.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081015","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":"LDL-C equation disagreement as a threshold-integrity flag for orthogonal lipid confirmation.","authors":"Ronald Doku, Nana Yaw A Osafo, John Kwagyan, William M Southerland","doi":"10.1016/j.jacl.2026.09.004","DOIUrl":"10.1016/j.jacl.2026.09.004","url":null,"abstract":"<p><strong>Background: </strong>Multiple low-density lipoprotein cholesterol (LDL-C) equations can be applied to every standard lipid panel. Disagreement across a treatment threshold may indicate unstable classification.</p><p><strong>Objective: </strong>To test LDL-C equation disagreement as a calculation-only threshold-integrity flag and as a trigger for orthogonal lipid confirmation.</p><p><strong>Methods: </strong>We analyzed decontaminated All of Us lipid panels with same-day standard lipids and direct homogeneous LDL-C, recognizing that direct LDL-C is a clinical reference assay rather than beta-quantification. Friedewald, Sampson/National Institutes of Health (NIH), and Martin-Hopkins were evaluated at LDL-C thresholds of 70, 100, and 130 mg/dL; 55 mg/dL was added in the temporal audit. The 3-equation disagreement flag was compared against triglyceride (TG)-based reflex rules. Medical Information Mart for Intensive Care IV (MIMIC-IV) was used for external stress testing.</p><p><strong>Results: </strong>Equation agreement identified a high-stability majority: in the primary All of Us cohort, equations agreed for 86% to 92% of panels with 92% to 95% threshold accuracy. In the temporal audit, future clean panels showed 3-equation disagreement in 10.2%, 11.4%, 9.2%, and 5.8% of rows at LDL-C thresholds of 55, 70, 100, and 130 mg/dL. Disagreement-subgroup accuracy was lower for all 3 equations. The 3-equation straddle outperformed TG ≥200 mg/dL for detecting apparent at-goal discordance at all 4 thresholds. Sparse apolipoprotein B (ApoB) analyses supported ApoB as an independent witness.</p><p><strong>Conclusion: </strong>LDL-C equation disagreement is a threshold-integrity flag, not proof that any equation is wrong. When equations disagree near a treatment goal, clinicians should avoid treating the LDL-C threshold result as unqualified and consider orthogonal confirmation, preferably ApoB, when particle burden is the clinical question.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Severe diet-induced hypercholesterolemia mimicking familial hypercholesterolemia in atypical lean mass hyper-responders on ketogenic diets: A case series.","authors":"Benjamin Lechner, Katharina Lechner, German Rubinstein, Klaus G Parhofer, Anja Vogt","doi":"10.1016/j.jacl.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.09.002","url":null,"abstract":"<p><strong>Background: </strong>The lean mass hyper-responder (LMHR) phenotype describes marked increases in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) during carbohydrate-restricted ketogenic diets, usually in lean, metabolically healthy individuals with high high-density lipoprotein cholesterol and low triglycerides.</p><p><strong>Case presentations: </strong>We report 3 Western European patients referred for suspected familial hypercholesterolemia (FH) after severe hypercholesterolemia developed during ketogenic dieting. None consistently met all current LMHR laboratory criteria. One patient was overweight before diet initiation, 1 was on the low side of the normal body mass index (BMI) range upon referral, and 1 was within the normal weight BMI range and became markedly underweight during diet exposure. Peak LDL-C during ketogenic dieting ranged from 364 to 682 mg/dL. After modest carbohydrate reintroduction, LDL-C and ApoB decreased substantially without lipid-lowering pharmacotherapy.</p><p><strong>Conclusion: </strong>These cases suggest that ketogenic diet-associated severe hypercholesterolemia may extend beyond classical LMHR criteria and can closely mimic FH. Dietary patterns, weight trajectory, and secondary causes should be assessed before assigning an FH diagnosis. Because ApoB-containing lipoproteins are causal in atherosclerosis, severe diet-induced ApoB elevation should not be assumed to be benign.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024932","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":"Fish oil supplementation reduces the CERT2 risk score in adults with increased cardiometabolic risk: Findings from the MoKaRi trial.","authors":"Angelika Witoslawska, Christine Dawczynski, Mitja Lääperi, Reini Hurme, Michael Kiehntopf, Stefan Lorkowski, Winfried März, Reijo Laaksonen, Angela P Moissl-Blanke","doi":"10.1016/j.jacl.2026.08.013","DOIUrl":"https://doi.org/10.1016/j.jacl.2026.08.013","url":null,"abstract":"<p><strong>Background: </strong>Ceramides and phosphatidylcholines, key components of the Coronary Event Risk Test 2 (CERT2), are strong predictors of cardiovascular events beyond low-density lipoprotein cholesterol (LDL-C). Whether dietary strategies targeting lipidomic risk profiles can modify these biomarkers remains insufficiently explored.</p><p><strong>Objective: </strong>To investigate whether long-chain n-3 polyunsaturated fatty acid supplementation, within a structured cardioprotective dietary program, modifies ceramide- and phosphatidylcholine-associated cardiovascular risk in adults at increased cardiometabolic risk in a primary prevention setting.</p><p><strong>Methods: </strong>The MoKaRi trial was a 20-week, randomized, parallel-group dietary intervention followed by a 20-week follow-up. Adults aged 20-80 years with LDL-C ≥3.0 mmol/L, not receiving lipid-lowering medication, were included. Participants received either personalized cardioprotective menu plans (MP) or identical MP supplemented with 3 g/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (MP-fish oil [FO]). The exploratory endpoint was the change in the CERT2 risk score following the dietary intervention.</p><p><strong>Results: </strong>The MP-FO group demonstrated significantly greater reductions in the CERT2 score throughout the 20-week intervention when compared to the MP group (Week 10: -2.44, 95% CI -3.42--1.47; Week 20: -2.18, 95% CI -3.15--1.21). Although the effect attenuated after 40 weeks, it remained significant (-1.63, 95% CI -2.61--0.65). Only the FO-supplemented group displayed favorable changes in ceramide-phosphatidylcholine ratios.</p><p><strong>Conclusions: </strong>High-dose EPA + DHA supplementation embedded in a structured heart-healthy diet reduces CERT2 in adults with increased cardiometabolic risk, indicating that this lipidomic risk score is modifiable by nutritional intervention. CERT2 may therefore serve as a responsive biomarker for monitoring improvements in cardiovascular risk beyond LDL-C in preventive cardiology.</p>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920030","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}