EClinicalMedicine最新文献

{"title":"Comparative effectiveness of GLP-1 receptor agonists versus mineralocorticoid receptor antagonists as fourth-line pharmacological therapy in patients with resistant hypertension and overweight or obesity: a retrospective multicenter cohort study in the USA.","authors":"Zhejia Tian, Jonas M Willerding, Kai M Schmidt-Ott, Anette Melk, Bernhard M W Schmidt","doi":"10.1016/j.eclinm.2026.104176","DOIUrl":"10.1016/j.eclinm.2026.104176","url":null,"abstract":"<p><strong>Background: </strong>Mineralocorticoid receptor antagonists (MRAs) are the guideline-recommended therapy for resistant hypertension. Resistant hypertension is particularly common in individuals with overweight or obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce substantial weight loss and reduce cardiovascular and renal events, with modest reductions in blood pressure. Whether GLP-1RAs provide benefit as an alternative therapeutic strategy in patients with resistant hypertension and overweight or obesity is unknown. We compared the effectiveness of GLP-1RAs and MRAs as fourth-line pharmacologic therapy in this population.</p><p><strong>Methods: </strong>In this retrospective multicenter cohort study using the TriNetX US Collaborative Network including 67 healthcare organizations, female and male adults with overweight or obesity and resistant hypertension (uncontrolled blood pressure despite ACE-inhibitors/angiotensin receptor blockers, calcium antagonists and diuretics) initiating a fourth-line pharmacological therapy between 01 June 2017 and 31 March 2025 were identified and included. Patients initiating GLP-1RAs (semaglutide or tirzepatide) were compared with those initiating MRAs (spironolactone or eplerenone). The primary outcome was major adverse cardiovascular events (MACE) during 2-year follow-up. Secondary outcomes included all-cause mortality, cardiovascular events, kidney outcomes, and blood pressure changes. Propensity score matching balanced baseline characteristics. Outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models.</p><p><strong>Findings: </strong>Among 213,309 eligible patients, 22,694 initiated GLP-1RAs and 5673 initiated MRAs. After propensity score matching, 4153 patients remained in each group. During a median follow-up of 1.4 years, GLP-1RA therapy was associated with lower risks of MACE (HR 0.63, 95% CI 0.52-0.78), all-cause mortality (HR 0.34, 95% CI 0.21-0.55), cardiovascular events (HR 0.74, 95% CI 0.59-0.92), major adverse kidney events (HR 0.64, 95% CI 0.46-0.88), and acute kidney injury (HR 0.62, 95% CI 0.46-0.83) compared with MRAs. Systolic blood pressure reductions at 12 weeks were similar (-5.7 [95% CI -4.0 to -7.4] mmHg versus -6.3 [95% CI -4.7 to -8.0] mmHg).</p><p><strong>Interpretation: </strong>In our retrospective study, among adults with resistant hypertension and overweight or obesity, GLP-1RA was associated with lower cardiovascular and kidney risk compared with MRAs despite smaller blood pressure reductions. GLP-1RAs may represent a potential alternative or complementary therapeutic option in this population. Prospective studies are needed to determine whether GLP-1RAs should be incorporated into treatment strategies for resistant hypertension in patients with overweight or obesity.</p><p><strong>Funding: </strong>None.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104176"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian and behavioral timing in MASLD: a systematic review of human observational studies.","authors":"Arunkumar Subramanian, Raja Affendi Raja Ali, Gavin Stewart Dawe, Vetriselvan Subramaniyan","doi":"10.1016/j.eclinm.2026.104187","DOIUrl":"10.1016/j.eclinm.2026.104187","url":null,"abstract":"<p><strong>Background: </strong>Circadian disruption may affect metabolism through altered timing of sleep, activity, light exposure, hormonal rhythms, and food intake. However, its relationship with metabolic dysfunction-associated steatotic liver disease (MASLD), including fibrosis and cirrhosis remains unclear. To evaluate associations between circadian and behavioural timing exposures and MASLD in observational studies.</p><p><strong>Methods: </strong>PubMed, Embase, and Scopus were searched from inception to 14 July 2026. Eligible studies examined naturally occurring timing-related exposures in adults and reported steatosis, fibrosis, cirrhosis, or quantitative liver-fat outcomes. Findings were synthesized narratively because heterogeneity precluded pooling. Risk of bias was assessed using AXIS or the Newcastle-Ottawa Scale, and certainty using an adapted domain-level GRADE approach (PROSPERO Registration number: CRD420261381636).</p><p><strong>Findings: </strong>Twenty-four independent MASLD-related evidence sources were included in the primary synthesis; two additional mixed-aetiology cirrhosis studies were considered contextually. Shift work showed the most consistent associations and most longitudinal evidence. Chronotype was generally associated with disease occurrence but inconsistently with advanced outcomes: intermediate or late chronotype was associated with fibrosis in one clinical cohort, whereas morning chronotype was not independently associated with incident cirrhosis in a prospective cohort. Later sleep timing was associated with prevalent MASLD and, in one NHANES analysis, fibrosis. Evidence for objective rest-activity rhythms, light exposure, meal timing, and melatonin phase remained limited or heterogeneous. Mixed-aetiology cirrhosis studies suggested that advanced liver disease may itself disrupt circadian physiology.</p><p><strong>Interpretation: </strong>Circadian and behavioural timing exposures showed trends associated with MASLD-related outcomes, with the most consistent evidence for shift work. Residual confounding, cross-sectional designs, self-reported exposures, heterogeneous outcomes, and reverse causality preclude causal conclusions. Prospective studies using objective circadian phenotyping and standardized fibrosis outcomes are needed.</p><p><strong>Funding: </strong>This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104187"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risks of adverse respiratory outcomes in adults with cancer over the course of survivorship compared with cancer-free individuals: a matched cohort study using linked English electronic health records.","authors":"Kirsty Andresen, Helena Carreira, Harriet Forbes, Liza Bowen, Jennifer K Quint, Elizabeth Williamson, Krishnan Bhaskaran","doi":"10.1016/j.eclinm.2026.104173","DOIUrl":"10.1016/j.eclinm.2026.104173","url":null,"abstract":"<p><strong>Background: </strong>We aimed to compare the risks of developing new chronic respiratory conditions, or exacerbating existing ones in survivors of 20 common cancers vs. cancer-free individuals.</p><p><strong>Methods: </strong>We conducted a population-based matched cohort study using English electronic primary care records, linked to cancer registry, hospital admissions, and death records data from 1999 to 2019. Adults aged ≥ 18 years with incident cancer were matched 1:10 to cancer-free individuals on age, sex and general practice. Outcomes included new-onset and exacerbations of asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and interstitial lung disease (ILD) ascertained from electronic health record (EHR) data throughout follow-up. Relative risks were estimated using Cox models, adjusted for confounders, like smoking. Absolute risks were estimated using adjusted incident rate differences and standardised cumulative incidence curves for new-onset disease and mean cumulative count for exacerbations.</p><p><strong>Findings: </strong>789,254 adults with incident cancer were included. Compared with cancer-free individuals, ILD risk was raised in 18 cancers (adjusted hazard ratio [adjHR] > 5 in CNS, oesophageal and lung cancers, and adjHR > 2 in seven further cancers); raised risks persisted beyond five years after diagnosis in 11 cancers. Elevated risks of developing COPD were observed in 11 cancers (adjHR 4.69 increased risk for lung cancer; other adjHRs 1.08-1.71); for seven of these cancers, raised risks persisted beyond five years. New-onset bronchiectasis risk was increased in oesophageal, lung and haematological cancers while new-onset asthma risk was raised in non-Hodgkin lymphoma only. Exacerbations rates of pre-existing respiratory diseases were raised in survivors of oesophageal, liver, lung, pancreatic, central nervous system, and haematological cancers.</p><p><strong>Interpretation: </strong>Survivors of most types of cancer had substantial and sometimes prolonged raised risk of a range of respiratory conditions. Future research should explore the mechanisms underlying these associations, including the roles of post-cancer tobacco use and specific anti-cancer treatments. Targeted management, smoking cessation, and vaccination may be warranted for those at highest risk.</p><p><strong>Funding: </strong>Medical Research Council and Wellcome trust.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104173"},"PeriodicalIF":12.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Electroacupuncture for knee osteoarthritis: a multicentre randomised controlled trial assessing symptomatic and structural efficacy\".","authors":"Minghui Hang, Yubo Shao, Wang Lu, Xiaoyun Wang, Hao Xu, Shaohua Chen, Xiang Yu, Junjun Zhu, Xianggeng Luo, Honggang Yi, Jiabao Zhang, Yimeng Wang, Shiyong Xue, Shunchao Liu, Zheng Gong, Zhipeng Song, Lianbo Xiao, Zheng Xiang, Shiyan Yan, Ting Zhang, Ruoyu Yao, Tao Wang, Zhanying Tang, Lin Cong, Qiang Li, Haiyin Zhao, Weiwei Meng, Yibin Fan, Rongguang Ao, Bingli Liu, Liyuan Tao, Xiaohua Gu, Li Ding, Tao Wu, Yong Xu, Yongjun Wang, Qianqian Liang","doi":"10.1016/j.eclinm.2026.104161","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104161","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.eclinm.2026.103982.].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104161"},"PeriodicalIF":12.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From airways to arteries: cardiovascular and kidney risk in chronic obstructive pulmonary disease.","authors":"Inuk Tórsheim, Alexander G Mathioudakis, Pradeesh Sivapalan","doi":"10.1016/j.eclinm.2026.104165","DOIUrl":"10.1016/j.eclinm.2026.104165","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104165"},"PeriodicalIF":12.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection-triggered encephalopathy syndromes: a meta-analysis of clinical characteristics and outcomes in 1946 cases.","authors":"Michael Eyre, Velda X Han, Terrence Thomas, Hiroshi Sakuma, Shekeeb S Mohammad, Hannah F Jones, Takayuki Mori, Go Kawano, Vanessa W Lee, Stephen Malone, Carly Debinski, Hiroya Nishida, Margherita Nosadini, Ming Lim, Russell C Dale","doi":"10.1016/j.eclinm.2026.104163","DOIUrl":"10.1016/j.eclinm.2026.104163","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Infection-triggered encephalopathy syndromes (ITES) are acute, para-infectious disorders that can cause disability or death. Recognition is increasingly important in viral pandemics, but clinical features and outcomes remain poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed search (inception to 6 March 2024) identified studies with published individual patient data (raw data were not collected from authors). The search was updated on 14 May 2026 using the same terms to identify reports and cases published after the data extraction cutoff. Data were extracted by paediatric neurologists using a standardised proforma. Major syndromes included acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), acute necrotising encephalopathy (ANE), acute shock with encephalopathy and multiorgan failure (ASEM), hemiconvulsion-hemiplegia-epilepsy syndrome (HHE), febrile infection-related epilepsy syndrome (FIRES) and mild encephalopathy with reversible splenial lesion (MERS). We performed a pooled analysis of individual-level published data investigating patient characteristics, infections, and clinical outcomes measured by six-month modified Rankin Scale (mRS). Infection-syndrome associations were analysed with chi-square normalised residuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;1946 patients from 656 studies (by ascending age of onset) included 164 ASEM (median age 0.78 years), 217 AESD (1.3 years), 95 HHE (2 years), 414 ANE (3.4 years), 562 FIRES (9 years), and 422 MERS (9.25 years). An updated search identified 658 cases from 171 studies that could be eligible for inclusion. AESD was linked to human herpesvirus 6 (z = 12.87); ANE with influenza A (z = 11.1), SARS-CoV-2 (z = 9.1) and influenza B (z = 4.3); MERS with rotavirus infection (z = 7.48); and FIRES with absence of microbiological identification (z = 18.2) (all p &lt; 0.001).Neuroimaging was often delayed. Magnetic resonance imaging (MRI) brain restricted diffusion was the commonest finding, typically bilateral (except HHE). Characteristic patterns included thalamic involvement with or without haemorrhagic changes in ANE, corpus callosum involvement in MERS, and subcortical white matter involvement in AESD and HHE. Cerebrospinal fluid pleocytosis occurred mostly in FIRES and MERS, and elevated protein in ANE.Immunotherapy (commonly steroids, immunoglobulin) including biologics (anakinra, tocilizumab) was used most in ANE and FIRES. Acute mortality was 12% (227/1946), highest in ASEM (50%) and ANE (35%). There was good six-month outcome (mRS 0-2) in 52% (95% CI 50-55; 615/1174): MERS 99% (95% CI 97-100; 323/326), AESD 54% (95% CI 44-64; 50/93), FIRES 38% (95% CI 33-44; 120/314), ANE 33% (95% CI 27-38; 88/269), HHE 16% (95% CI 7-32; 5/32), and ASEM 15% (95% CI 9-24; 14/91).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;ITES showed distinct demographic, clinico-radiological features and outcomes. This largest ITES cohort to date highlights the importance o","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104163"},"PeriodicalIF":12.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of referral strategies for patients with suspected axial spondyloarthritis: a systematic review with meta-analysis.","authors":"Daniel Feller, Roel Wingbermühle, Bart Koes, Sofia Ramiro, Alessandro Chiarotto","doi":"10.1016/j.eclinm.2026.104167","DOIUrl":"10.1016/j.eclinm.2026.104167","url":null,"abstract":"<p><strong>Background: </strong>Axial spondyloarthritis (axSpA) is a clinically important but often under-recognized condition, with substantial diagnostic delay. Structured referral strategies have been proposed to facilitate earlier identification of suspected cases; however, their diagnostic accuracy has not been comprehensively compared. We therefore conducted a systematic review to synthesize the diagnostic accuracy of referral strategies for identifying axSpA in patients with chronic back pain.</p><p><strong>Methods: </strong>We performed a systematic review of observational studies evaluating referral strategies for suspected axSpA. The review protocol was prospectively registered in PROSPERO (CRD42025634153). MEDLINE, Embase, Web of Science, CENTRAL, and CINAHL Plus were searched from inception to December 2025. Study selection, data extraction using the \"Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies\" (CHARMS), risk of bias assessment using the \"Prediction model Risk Of Bias Assessment Tool + Artificial Intelligence\" (PROBAST+AI), and certainty of evidence rating using an adapted \"Grading of Recommendations Assessment, Development and Evaluation\" (GRADE) approach were conducted by two independent reviewers.</p><p><strong>Findings: </strong>Twenty-four studies evaluating 40 referral strategies were included. Risk of bias was high across all strategies, resulting in low to very low certainty of evidence for most performance metrics. Meta-analysis was feasible for nine referral strategies. Statistically significant pooled likelihood ratios were observed for the negative likelihood ratio (LR-) of the ASAS referral criteria (0.18, 95% CI 0.04-0.81), and for both the positive and negative LRs of the Braun 2-step alternative strategy (LR+ 2.02, 95% CI 1.47-2.76; LR- 0.38, 95% CI 0.19-0.75), CaFaSpA ≥1 (LR+ 1.64, 95% CI 1.04-2.59; LR- 0.43, 95% CI 0.21-0.87), and RADAR 2/3 (LR+ 2.76, 95% CI 2.13-3.59; LR- 0.60, 95% CI 0.51-0.71). These results did not meet thresholds (e.g., LR+ >10, LR- <0.10) for strong diagnostic accuracy.</p><p><strong>Interpretation: </strong>Current referral strategies for axSpA have limited diagnostic impact and are supported by low to very low-certainty evidence. Future research should prioritize the development of new referral strategies, particularly for primary care settings.</p><p><strong>Funding: </strong>No specific funding was received for this work.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104167"},"PeriodicalIF":12.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Biofire FilmArray Meningitis/Encephalitis panel for the aetiological diagnosis of central nervous system infections: a systematic review and diagnostic test accuracy meta-analysis\".","authors":"Juliana Trujillo-Gomez, Sofía Tsokani, Catalina Arango-Ferreira, Santiago Atehortua-Muñoz, María José Jimenez-Villegas, Carolina Serrano-Tabares, Areti-Angeliki Veroniki, Ivan D Florez","doi":"10.1016/j.eclinm.2026.104160","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104160","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.eclinm.2026.104097.][This corrects the article DOI: 10.1016/j.eclinm.2026.104157.][This corrects the article DOI: 10.1016/j.eclinm.2022.101275.].</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104160"},"PeriodicalIF":12.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heatwaves and health system resilience in Europe.","authors":"eClinicalMedicine","doi":"10.1016/j.eclinm.2026.104168","DOIUrl":"https://doi.org/10.1016/j.eclinm.2026.104168","url":null,"abstract":"","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"98 ","pages":"104168"},"PeriodicalIF":12.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of lipidomic and polygenic risk scores within contemporary clinical cardiovascular risk assessment pathways: a multi-cohort development and validation study.","authors":"Aleksandar Dakic, Jingqin Wu, Tingting Wang, Thomas G Meikle, Kevin Huynh, Changyu Yi, Habtamu B Beyene, Agus Salim, Michelle Cinel, Nat Mellett, Thy Duong, Alexandra N Faulkner, Matilda van Buuren-Milne, Anjali Bhagwat, Jonathan E Shaw, Dianna J Magliano, Gerald F Watts, Joseph Hung, Jennie Hui, John P Beilby, John Blangero, Eric K Moses, Melissa C Southey, Roger L Milne, Allison M Hodge, John J McNeil, Paul Lacaze, Chenglong Yu, Rory Wolfe, Jean Yh Yang, Stuart M Grieve, Clara K Chow, Stephen T Vernon, Michael P Gray, Gemma A Figtree, Jedidiah I Morton, Paul Scuffham, Mark Woodward, Lisa Kalman, Ellie Paige, Melinda J Carrington, Michael Inouye, Corey Giles, Peter J Meikle","doi":"10.1016/j.eclinm.2026.104159","DOIUrl":"10.1016/j.eclinm.2026.104159","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Guideline-recommended clinical risk scores such as AusCVDRisk underestimate cardiovascular disease (CVD) risk in a substantial proportion of individuals who later experience events, with up to 65% initially classified as low or intermediate risk. This limitation is most consequential in the intermediate-risk group, where treatment decisions are uncertain and additional risk refinement could alter management. Circulating lipid species and inherited genetic variation capture complementary molecular aspects of atherosclerotic risk that are not fully reflected by conventional clinical variables, but are not routinely incorporated into primary-care risk assessment. We investigated whether selective integration of lipidomic and genomic risk signals into AusCVDRisk improves 5-year CVD prediction and reclassification, with a focus on individuals at intermediate clinical risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A lipidomic score comprising 689 lipid species measured by liquid chromatography-tandem mass spectrometry was derived using regularised Cox regression in 8082 participants from the Australian Diabetes, Obesity and Lifestyle Study (1999-2000). A genome-wide coronary artery disease polygenic score (PGS002048; 762,124 variants) was optimised in 3328 participants from the Busselton Health Study (1994-95). Each score was adjusted for AusCVDRisk predictors to isolate independent effects and incorporated into Cox models retaining the AusCVDRisk linear predictor as a fixed offset, generating lipidomic-enhanced (L.CVDRisk), genomic-enhanced (G.CVDRisk), and combined (LG.CVDRisk) scores. Internal and external validation was performed across five Australian cohorts totalling 13,521 adults without baseline CVD. Discrimination (Harrell's concordance index; C-statistic), calibration, categorical net reclassification improvement (NRI), and decision-curve analyses were assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;LG.CVDRisk showed modest gains in discrimination compared with AusCVDRisk (pooled ΔC among intermediate-risk individuals 0.071, 95% CI 0.033-0.109; overall 0.012, 95% CI 0.000-0.024). Risk classification improved substantially (pooled NRI in the intermediate-risk group 0.305, 95% CI 0.212-0.397; overall 0.080, 95% CI 0.031-0.129), with net event and non-event reclassification of 38.2% (95% CI 29.3-47.0%) and -6.8% (95% CI -9.3 to -4.2%) among intermediate-risk individuals. Decision-curve analysis showed the greatest net benefit when molecular profiling was selectively applied to individuals with intermediate AusCVDRisk (5-&lt;10%). In a coronary imaging cohort, LG.CVDRisk reclassified 17 (41%) of 41 intermediate-risk individuals with extensive coronary calcification into the high-risk category.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Selective augmentation of an established clinical risk algorithm with lipidomic and genomic information improves cardiovascular risk stratification among individuals at intermediate baseline risk. This ","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"99 ","pages":"104159"},"PeriodicalIF":12.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}