Lipids in Health and Disease最新文献

{"title":"Integrating frailty and cumulative lipid burden for stroke risk stratification: a machine learning-guided Athero-Frailty Score from the CHARLS cohort.","authors":"Jingxian Sun, Daikang Xu, Guangyu Du, Tongyu Jia, Xing Han, Yi Yu, Jianpeng Wang, Zhiyong Yan, Shifang Li, Chao Wang, Shusheng Che","doi":"10.1186/s12944-026-02931-4","DOIUrl":"10.1186/s12944-026-02931-4","url":null,"abstract":"<p><p>BACKGROUND: Traditional lipid indices, such as the cumulative Atherogenic Index of Plasma (cumAIP), demonstrate inconsistent predictive performance for stroke in older adults, likely due to the modifying effects of complex medication regimens. We hypothesized that incorporating the Frailty Index (FI)—a measure of cumulative physiological deficits—could capture the residual risk missed by lipid markers alone. We developed and evaluated a novel Athero-Frailty Score (AFS) to address these limitations. METHODS: We analyzed 3,690 participants from the China Health and Retirement Longitudinal Study (CHARLS) using a landmark analysis design (baseline: 2015). An exploratory XGBoost model with SHAP analysis was used for variable screening. Based on the orthogonality of lipid and frailty metrics, AFS was constructed as an additive composite score of cumAIP and FI. Associations with incident stroke were assessed using Cox proportional hazards models and restricted cubic splines (RCS). Clinical utility was evaluated via C-statistics, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: SHAP analysis identified FI as having a larger average SHAP contribution than cumAIP and medication indicators. Survival analyses suggested that the association between cumAIP and stroke was attenuated after adjustment for antihypertensive and lipid-lowering therapies (HR 1.20, P = 0.042), and RCS indicated a non-linear pattern with an apparent plateau at higher cumAIP levels. In contrast, AFS was associated with an approximately linear dose–response relationship independent of medication use. In the fully adjusted model, each 1-SD increase in AFS was associated with a higher risk of stroke (HR = 2.75, P < 0.001). Crucially, the addition of AFS yielded significant improvement in reclassification (NRI = 15.4%, P < 0.001), while the improvement in integrated discrimination was modest (IDI = 0.007, P = 0.088). CONCLUSION: The AFS effectively addresses the predictive limitations of traditional metabolic markers in medicated older adults. By integrating metabolic burden with systemic vulnerability, this novel composite score offers a linear and robust predictive approach for stroke, supporting a multidimensional approach to vascular risk stratification in aging populations. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial expression of concern: In silico profiling of nonsynonymous SNPs of fat mass and obesity-associated gene: possible impacts on the treatment of non-alcoholic fatty liver disease.","authors":"Damini Patnaik, Atala Bihari Jena, Rout George Kerry, Asim K Duttaroy","doi":"10.1186/s12944-026-02934-1","DOIUrl":"10.1186/s12944-026-02934-1","url":null,"abstract":"","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The modified cardiometabolic index as a risk factor for mortality after percutaneous coronary intervention in acute myocardial infarction.","authors":"Tingting Xiao, Xiaoming Zhu, Shengjue Xiao, Jiandong Ding","doi":"10.1186/s12944-026-02935-0","DOIUrl":"10.1186/s12944-026-02935-0","url":null,"abstract":"<p><p>OBJECTIVE: The cardiometabolic index (CMI) serves as an integrative measure of both obesity and dyslipidemia. This study aimed to evaluate whether an elevated modified cardiometabolic index (MCMI) is related to the risk of all-cause mortality (ACM) and cardiovascular mortality (CVM) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: This large-scale retrospective cohort study utilized data from 2,688 participants with AMI undergoing PCI between June 2015 and June 2020 at Zhongda Hospital Southeast University and conducted follow-up. The MCMI, integrating high-density lipoprotein cholesterol, waist circumference, triglycerides, and fasting blood glucose, was used as a composite marker of cardiometabolic risk. After adjusting for potential confounding, restricted cubic splines (RCS), subgroup analyses, and Cox proportional hazards models were utilized to evaluate the associations of MCMI with ACM and CVM. Receiver operating characteristic (ROC) curve analysis was used to assess its diagnostic value. RESULTS: In total, 2,688 participants with AMI were enrolled (mean age 54.47 ± 18.41 years, 50.9% male). The RCS plot revealed a positive linear association between MCMI and the risk of ACM and CVM in participants after AMI (all P for overall < 0.001). After adjusting for known confounders, compared with the lowest MCMI quartile, the hazard ratios (95% CIs) for ACM in the second, third, and fourth quartiles were 1.40 (1.07, 1.83), 1.53 (1.18, 1.99) and 1.55 (1.18, 2.03), respectively. The corresponding values for CVM were 1.32 (1.03, 2.06), 1.53 (1.15, 2.18) and 1.73 (1.21, 2.24). Finally, MCMI demonstrated better predictive ability for ACM and CVM in patients with AMI after PCI (AUC = 0.811; AUC = 0.828). CONCLUSIONS: In conclusion, this study demonstrates that among AMI patients, high MCMI was independently related to a greater risk of ACM and CVM. This finding establishes MCMI as a significant prognostic marker, which can aid in risk stratification and guide more aggressive secondary prevention strategies for high-risk individuals. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Integrative analysis of serum lipids and chronic gastritis: causal insights from mendelian randomization and experimental models.","authors":"Xinqiao Chu, Yaning Biao, Hongzheng Li, Jian Chen, Jixiong Yin, Xingxing Gao, Shaoli Wang, Jizheng Ma, Liufeng Yi, Yixin Zhang, Muqing Zhang, Zhen Liu","doi":"10.1186/s12944-026-02933-2","DOIUrl":"10.1186/s12944-026-02933-2","url":null,"abstract":"","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":"25 1","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13023184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147520625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint association of weekend catch-up sleep and triglyceride-glucose index on bone loss and all-cause mortality in employed U.S. adults aged 18-60 with diabetes.","authors":"Cong Ma, Jingcheng Li, Ronghui Yu, Junhong Li, Zhen'ai Liang, Kangwei Wang, Hongxiang Feng, Ping Liu, Xiaodong Wang, Yuxiong Weng","doi":"10.1186/s12944-026-02936-z","DOIUrl":"10.1186/s12944-026-02936-z","url":null,"abstract":"<p><p>BACKGROUND: The increasing prevalence of younger-onset type 2 diabetes mellitus (T2DM) has resulted in an increased risk of bone loss and mortality among employed adults aged 18–60 years. Weekend catch-up sleep (WCS) index, reflecting irregularity in sleep duration, and triglyceride-glucose (TyG) index, reflecting glucolipid metabolism, may be interrelated in the assessment of diabetes pathophysiology. This study developed a composite WCS + TyG index to yield an incremental effect, improving predictive performance of bone loss risk and all-cause mortality in employed U.S. adults aged 18–60 years with T2DM. METHODS: A cohort analysis included 4,185 employed adults aged 18–60 with T2DM from the NHANES database. Receiver operating characteristic (ROC) curves, logistic regression, and Cox models were used to evaluate predictive performance of the WCS + TyG combination on bone loss risk and all-cause mortality. RESULTS: Logistic regression and Cox models provided preliminary evidence that the WCS + TyG combination was an independent risk factor for bone loss and all-cause mortality; among patients with T2DM, those with high levels of both indices had the highest risk (full adjusted Model 3: bone loss risk OR = 1.480, 95% CI = 1.195–1.833, P < 0.001; all-cause mortality HR = 2.600, 95% CI = 1.957–3.454, P < 0.001). These findings suggest an association, but causal conclusions cannot be drawn, and further prospective research is needed to confirm these results. CONCLUSIONS: This study confirmed that the WCS + TyG combination can provide an incremental effect in predicting risk of bone loss and all-cause mortality in employed U.S. adults aged 18–60 with T2DM. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the structural diversity and distribution pattern of gangliosides and sulfatides in mouse brain tissues and biomarkers for Parkinson's Disease.","authors":"Ming-Yang Liu, Juan Wang, Xiong-Yu Meng, Jia-Ru Liu, Xiao-Jun Yao, Yu-Wei Wang, Lee-Fong Yau, An-Ran Sun, Jia-Ning Mi, Liang Liu, Wen-Jing Ren, Yue Kang, Jing-Rong Wang","doi":"10.1186/s12944-026-02918-1","DOIUrl":"10.1186/s12944-026-02918-1","url":null,"abstract":"<p><p>BACKGROUND: Acidic glycosphingolipids (GSLs), including gangliosides (GAs) and sulfatides (STs), play key roles in intercellular signalling and neurodegenerative diseases. However, their comprehensive characterization remains challenging because of structural complexity, abundance variation, and interference from isomers and isotopes. This study aimed to systematically profile GAs and STs in mouse brain tissues and explore their potential as biomarkers in a Parkinson’s disease (PD) model. METHODS: Prefractionation in combination with UHPLC-Q-TOF MS was employed for high-resolution MS and MS/MS analysis of acidic GSLs. Quantitative structure–retention relationship (QSRR) models were constructed from identified structures and retention times (RTs) to predict RTs and provide complementary support for MS/MS-based annotation. Dynamic multiple reaction monitoring (dMRM) on UHPLC-QQQ MS was applied to quantify GSLs, followed by a comparative analysis of PD and control mouse brain tissues. RESULTS: A total of 220 acidic GSLs were characterized, including 173 GAs (21 subclasses) and 47 STs (3 subclasses), representing the most extensive profile reported from mouse brain tissues, among which 75 GAs and 29 STs are, to the best of the authors’ knowledge, newly reported here. The QSRR model provided retention time predictions supporting the tentative annotation of eight rare acidic GSLs with insufficient MS/MS data. Among the identified species, Monosialogangliosides (GM) were the most abundant subclass, with GM1 and GM3 predominant. GD1a was the major disialoganglioside (GD) species, and the trisialoganglioside (GT), tetrasialoganglioside (GQ), and pentasialoganglioside (GP) subclasses were identified as GT1b, GQ1b, and GP1c, respectively. The STs were mainly of the SulfoHex type. O-acetylation was frequent in GQ species, while fucosylation and GalNAc attachment were primarily associated with GM and GD species. The sphingoid bases were mainly d18:0, d18:1, d20:0, and d20:1, while the N-acyl chains spanned C16:0–C24:0. For quantification, a method covering 17 subclasses enabled the simultaneous measurement of 89 GAs and 27 STs, representing the broadest quantification coverage in PD mouse brain studies to date. Further analysis revealed significant alterations in 20 GAs and 7 STs in PD, with GQ1b reported for the first time as a potential PD-related biomarker, and pathway analysis indicated disruption of b-series GA biosynthesis. CONCLUSIONS: This study provides a comprehensive profile of acidic GSLs in mouse brain tissues and reveals GQ alterations with pathway disruptions in PD, offering molecular evidence linking acidic GSL metabolism to this disease. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess apolipoprotein B predicts long-term survival in statin-treated CAD irrespective of achieved LDL-C levels: a pooled cohort analysis.","authors":"Wei Pan, Xiaozhao Lu, Ziwei Zhou, Jin Liu, Shaozhao Zhang, Haozhang Huang, Yibo He, Jingru Deng, Yihang Ling, Xianlin Ruan, Ling Jing, Weipeng Zhang, Shiqun Chen, Xinxue Liao, Jiyan Chen, Xiaodong Zhuang, Yong Liu","doi":"10.1186/s12944-026-02928-z","DOIUrl":"10.1186/s12944-026-02928-z","url":null,"abstract":"<p><p>BACKGROUND: Residual cardiovascular risk persists in statin-treated patients with coronary artery disease (CAD), even when low-density lipoprotein cholesterol (LDL-C) targets are met. Excess apolipoprotein B (apoB), defined as measured apoB minus LDL-C-predicted apoB, may capture atherogenic particle burden beyond LDL-C, but its prognostic value for long-term mortality in secondary prevention remains uncertain. METHODS: We conducted a pooled analysis of two nationwide Chinese cohorts (CIN-II and RED-CARPET) comprising 68,616 statin-treated CAD patients. Excess apoB was calculated using an internal reference population (triglycerides ≤ 1.0 mmol/L). Associations with all-cause and cardiovascular mortality were assessed using multivariable Cox models, with adjustment for clinical covariates including nutritional status. External validation was performed in 13,702 participants from the UK Biobank. RESULTS: Over a median follow-up of 5.2 years, 10,835 deaths occurred (5,090 cardiovascular). Each 1-standard deviation (15.4 mg/dL) increase in excess apoB was associated with a 12% higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.12, 95% CI 1.06–1.18) and a 24% higher risk of cardiovascular mortality (aHR 1.24, 95% CI 1.15–1.34). Patients in the highest excess apoB quartile (≥ 11.5 mg/dL) had significantly worse survival. Notably, these associations persisted consistently across all achieved LDL-C strata (< 2.0 to > 4.0 mmol/L). These findings were robustly confirmed in the external validation cohort. CONCLUSIONS: Excess apoB is an independent predictor of long-term mortality in statin-treated CAD patients, even among those with well-controlled LDL-C. Its incorporation into risk assessment could improve prognostic stratification and guide personalized management in secondary prevention. TRIAL REGISTRATION: CIN-II: ClinicalTrials.gov, NCT05050877 (Retrospectively registered, 21 September 2021); RED-CARPET: Chinese Clinical Trial Registry, ChiCTR2000039901 (Prospectively registered, 14 November 2020). The UK Biobank study is covered by generic ethical approval from the NHS National Research Ethics Service (Ref: 99231). </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma complex lipids in relation to cortical thickness and brain volumes: results from the population-based Rhineland study.","authors":"Elvire N Landstra, Valerie Lohner, Juliana F Tavares, Kersten Diers, Alexandra Koch, Monique M B Breteler","doi":"10.1186/s12944-026-02930-5","DOIUrl":"10.1186/s12944-026-02930-5","url":null,"abstract":"<p><p>BACKGROUND: The brain is man’s second-fattiest organ and shows a remarkable lipid diversity. Despite recent advances in lipidomics, much remains unknown about the connection between blood lipids and the brain. Therefore, we investigated the relation between circulating lipid levels and cortical thickness and brain volumes. METHODS: We related blood levels of ~ 1000 lipid species and fatty acid composite measures to cortical thickness, and total brain, white matter and grey matter volume in the Rhineland Study (n = 3,248) using linear regression models, adjusting for sex, age and low-density and high-density lipoprotein cholesterol. To assess region-specific effects in the relation between lipids and cortical thickness, we performed a cortex-wide vertex-based analysis on our top hits. RESULTS: Chain length and degree of saturation influenced a lipid’s effect across different markers of brain health (cortical thickness, brain volumes). Specifically, odd-chained and 18-carbon carrying lipids were mostly associated with a thicker cortex and larger total, grey and white matter volume, whereas 16-carbon carrying and highly unsaturated (> 4 bonds) lipids were associated with a thinner cortex and smaller brain volumes. Furthermore, we found that lipids were mainly associated with regions outside of the pre-frontal cortex and related to the two hemispheres asymmetrically. CONCLUSIONS: Investigation of within-class relative lipid concentrations suggested that higher levels of odd-chained and 18-carbon carrying lipids and lower levels of polyunsaturated and 16-carbon carrying lipids could be crucial for brain structure. Our research highlights potential targets to improve brain health and underscores that lipid profiles, rather than total lipid concentrations, are critical. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the atherogenic index of plasma combined with obesity indices with cardiovascular disease and mortality.","authors":"Xinran Wang, Sirun Qin, Hong Xiang, Ye Tao, Shuhua Chen, Hongwei Lu","doi":"10.1186/s12944-026-02932-3","DOIUrl":"10.1186/s12944-026-02932-3","url":null,"abstract":"<p><p>BACKGROUND: Both the atherogenic index of plasma (AIP) and obesity have been implicated in cardiovascular disease (CVD) risk. This study aimed to investigate the associations of AIP and AIP-obesity indices (AIP-WC, AIP-BMI, AIP-WHtR, AIP-WWI, and AIP-BRI) with CVD and mortality. METHODS: This study enrolled 21,944 individuals from the National Health and Nutrition Examination Survey (NHANES) fielded during the years 1999–2018. Cox and logistic regression modeling, along with restricted cubic splines (RCS), served to assess the associations of AIP and AIP-obesity indices with all-cause mortality, CVD mortality, and CVD prevalence. The incremental predictive value of AIP and AIP-obesity indices was further assessed. RESULTS: Throughout an average follow-up period of 116 months, 3,326 all-cause deaths were documented, among which 1,042 were CVD deaths. AIP, AIP-WC, AIP-BMI, AIP-WHtR, AIP-WWI, and AIP-BRI were significantly associated with all-cause mortality, CVD mortality, and CVD prevalence. In the fully adjusted model, relative to the lowest-tertile participants, the highest-tertile participants of these indices had an elevated risk of 17.7–20.3% for all-cause mortality, an elevated risk of 30.3–33.8% for CVD mortality, and a 103.7–122.2% increase in the odds of CVD. RCS analyses indicated non-linear associations of AIP, AIP-WC, AIP-BMI, AIP-WHtR, AIP-WWI, and AIP-BRI with all-cause mortality and CVD prevalence, whereas linear associations were observed with CVD mortality. Incremental predictive value analyses showed that compared with AIP alone, AIP-WC, AIP-BMI, AIP-WHtR, AIP-WWI, and AIP-BRI provided superior risk reclassification and discrimination across all outcomes. CONCLUSIONS: AIP and AIP-obesity indices were significantly associated with CVD and mortality risk. AIP combined with obesity-related indices, particularly BRI, provides additional value for the stratification of CVD and mortality risk. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SdLDL‑C/LDL‑C discordance as a practical surrogate for triglyceride‑associated cardiovascular risk: identification of at‑risk lipid phenotypes in the CHARLS prospective cohort.","authors":"Yaya Xue, Jing Luo, Xinyu Yang, Zhaoyu Ren, Hongxuan Fan, Wei Luo, Bin Liang","doi":"10.1186/s12944-026-02925-2","DOIUrl":"10.1186/s12944-026-02925-2","url":null,"abstract":"<p><p>BACKGROUND: Discordance between small dense low-density lipoprotein cholesterol (sdLDL-C) and low-density lipoprotein cholesterol (LDL-C) levels is common. Whether this easily calculated parameter, derived from routine lipid profiles using the triglyceride (TG)-dependent Sampson equation, can serve as a practical surrogate for TG-associated cardiovascular disease (CVD) risk and improve risk stratification remains unclear. METHODS: This prospective analysis included 7736 CVD-free participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS). The sdLDL-C level was estimated using the Sampson equation and discordance was defined as a ≥ 10 percentile difference. Cox proportional hazards models were used to evaluate associations with incident CVD. Net reclassification improvement (NRI) was used to assess the incremental predictive value, and risk stratification was performed using clinically relevant cutoff points. RESULTS: During a median follow-up of 84 months, 1390 incident CVD events were documented. After multivariable adjustment, elevated sdLDL-C was associated with an increased CVD risk (hazard ratio [HR] = 1.392, 95% confidence interval [CI]:1.175–1.649). The high-discordance group exhibited a higher CVD risk (HR = 1.158, 95% CI: 1.007–1.332); this association was fully attenuated in the TG-stratified analyses, indicating that discordance mainly reflects TG-related risk. Notably, 13.3% of individuals with normal TG levels (< 150 mg/dL) showed high discordance, corresponding to a high-normal TG phenotype. Including sdLDL-C into traditional risk factors yielded a significant NRI (0.103, P < 0.05). Using paired clinical thresholds (LDL-C 130 mg/dL; sdLDL-C 40 mg/dL), individuals with dual-high LDL-C and sdLDL-C levels had the highest CVD risk (HR = 1.215, 95% CI: 1.067–1.384), whereas isolated high LDL-C level was not associated with an elevated risk. CONCLUSIONS: In this Chinese cohort, the sdLDL-C/LDL-C discordance derived from routine lipid measurements represented a significant CVD risk marker consistent with TG-associated atherogenic dyslipidaemia. This parameter provides a modest incremental prognostic value without additional costs and identifies two clinically actionable high-risk subgroups: the high-normal TG phenotype and the dual-high phenotype. Evaluating the sdLDL-C/LDL-C discordance may help refine CVD risk stratification as an auxiliary tool in current lipid management strategies. </p>","PeriodicalId":18073,"journal":{"name":"Lipids in Health and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}