{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:47Z","timestamp":1786516307523,"version":"build-2736575974"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular calcification (VC) is a multifactorial process associated with adverse cardiovascular outcomes. The uric acid to high-density lipoprotein cholesterol ratio (UHR) has been proposed as a composite metabolic biomarker that reflects the balance between pro-oxidative and anti-inflammatory processes. However, its association with VC and the underlying mechanisms remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study integrated clinical association analysis, Mendelian randomization (MR), and network-based approaches. A retrospective cross-sectional analysis was conducted in 627 clinically stable cardiology inpatients, with aortic arch calcification (AoAC) assessed using chest radiographs. Multivariable logistic regression and restricted cubic spline analyses were used to examine the association between UHR and AoAC. Two-sample MR was performed to assess the potential causal effects of uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) on abdominal aortic calcification (AAC), a macrovascular calcification phenotype. Network-based analysis was conducted to explore potential molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher UHR levels were significantly associated with greater AoAC severity, which remained after adjusting for standard cardiovascular risk factors. MR analysis showed no significant genetic association between genetically predicted UA and AAC, whereas genetically predicted HDL-C showed an inverse association with AAC in the primary IVW analysis, but this was not consistently supported across sensitivity methods. Network-based analyses identified enrichment in inflammation- and remodeling-related pathways, including MAPK and PI3K\u2013Akt signaling, with key hub targets such as TNF, AKT1, and EGFR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher UHR levels were associated with greater VC burden in clinically stable cardiology inpatients. The clinical, genetic, and network-based findings provide complementary evidence suggesting that UHR may reflect the combined influence of multiple metabolic and inflammatory processes associated with VC, rather than the direct effect of any single component.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1877627","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:59:56Z","timestamp":1786514396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the relationship between uric acid-to-HDL cholesterol ratio and vascular calcification: evidence from clinical, genetic, and network-based analyses"],"prefix":"10.3389","volume":"13","author":[{"given":"Xinyi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Red Cross Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Red Cross Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZiQin","family":"Xiao","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Red Cross Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Red Cross Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Guangzhou Red Cross Hospital of Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Third Affiliated Hospital of Southern Medical University","place":["Guangzhou, China"]},{"name":"Department of Anesthesiology, Linzhi People\u2019s Hospital","place":["Linzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital)","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e682","DOI":"10.1002\/ctm2.682","article-title":"Osteomodulin attenuates smooth muscle cell osteogenic transition in vascular calcification","volume":"12","author":"Skenteris","year":"2022","journal-title":"Clin Transl Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1161\/ATVBAHA.122.317332","article-title":"Molecular mechanisms of vascular health: insights from vascular aging and calcification","volume":"43","author":"Sutton","year":"2023","journal-title":"ATVB"},{"key":"B3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.atherosclerosis.2009.11.012","article-title":"Aortic arch calcification detectable on chest x-ray is a strong independent predictor of cardiovascular events beyond traditional risk factors","volume":"210","author":"Iijima","year":"2010","journal-title":"Atherosclerosis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"100500","DOI":"10.1016\/j.lanwpc.2022.100500","article-title":"Aortic arch calcification: a simple but powerful marker of subclinical cardiovascular disease","volume":"23","author":"Qazi","year":"2022","journal-title":"Lancet Reg Health West Pac"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e200","DOI":"10.1002\/mco2.200","article-title":"Vascular calcification: molecular mechanisms and therapeutic interventions","volume":"4","author":"Pan","year":"2020","journal-title":"MedComm"},{"key":"B6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cca.2021.04.012","article-title":"Oxidative stress in vascular calcification","volume":"519","author":"Hu","year":"2021","journal-title":"Clin Chim Acta"},{"key":"B7","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/HJH.0b013e3282f240bf","article-title":"Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system","volume":"26","author":"Corry","year":"2008","journal-title":"J Hypertens"},{"key":"B8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s10753-020-01357-z","article-title":"The role of NLRP3 inflammasome activities in bone diseases and vascular calcification","volume":"44","author":"Yu","year":"2021","journal-title":"Inflammation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s11906-013-0344-5","article-title":"Potential role of uric acid in metabolic syndrome, hypertension, kidney injury, and cardiovascular diseases: is it time for reappraisal?","volume":"15","author":"Soltani","year":"2013","journal-title":"Curr Hypertens Rep"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.3390\/ijms24043132","article-title":"Inflammatory, metabolic, and coagulation effects on medial arterial calcification in patients with peripheral arterial disease","volume":"24","author":"Nikolajevi\u0107","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.3390\/ijms27031364","article-title":"The role and mechanism of gut microbiota and metabolites in vascular calcification","volume":"27","author":"Cao","year":"2026","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1056\/NEJMoa1409065","article-title":"HDL cholesterol efflux capacity and incident cardiovascular events","volume":"371","author":"Rohatgi","year":"2014","journal-title":"N Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1097\/MOL.0000000000000194","article-title":"How HDL protects LDL against atherogenic modification: paraoxonase 1 and other dramatis personae","volume":"26","author":"Soran","year":"2015","journal-title":"Curr Opin Lipidol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"S1933287425003071","DOI":"10.1016\/j.jacl.2025.05.017","article-title":"Association between uric acid to high-density lipoprotein cholesterol ratio and abdominal aortic calcification: a cross-sectional study","volume":"19","author":"Li","year":"2025","journal-title":"J Clin Lipidol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"6065","DOI":"10.2147\/IJGM.S482440","article-title":"Correlation between uric acid\/high density lipoprotein cholesterol ratio and postoperative AKI in patients with CABG","volume":"17","author":"Jiang","year":"2024","journal-title":"Int J Gen Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1186\/s12872-025-05386-0","article-title":"The uric acid to high density lipoprotein cholesterol ratio as a new indicator for predicting coronary slow flow phenomenon","volume":"25","author":"Zhang","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"key":"B17","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s12944-025-02780-7","article-title":"Relationship of admission uric acid to high density lipoprotein cholesterol ratio with unfavorable prognosis among acute ischemic stroke patients","volume":"24","author":"Kong","year":"2025","journal-title":"Lipids Health Dis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1007\/s12265-018-9843-8","article-title":"Serum uric acid is independently associated with coronary calcification in an asymptomatic population","volume":"12","author":"Kiss","year":"2019","journal-title":"J Cardiovasc Transl Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s12933-022-01726-y","article-title":"High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong diabetes biobank","volume":"21","author":"Jin","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s43586-021-00056-9","article-title":"Genome-wide association studies","volume":"1","author":"Uffelmann","year":"2021","journal-title":"Nat Rev Methods Primers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"s13742-015-0047\u20138","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"B23","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int J Epidemiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1007\/s12672-025-03358-6","article-title":"Causal relationships between immune cell traits and HER2 subtypes in breast cancer: a Mendelian randomization study","volume":"16","author":"Gu","year":"2025","journal-title":"Discov Oncol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/aje\/kwt084","article-title":"Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators","volume":"178","author":"Pierce","year":"2013","journal-title":"Am J Epidemiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5870","DOI":"10.2174\/1381612820666140212210451","article-title":"Mechanisms of medial arterial calcification in diabetes","volume":"20","author":"Chistiakov","year":"2014","journal-title":"Curr Pharm Des"},{"key":"B27","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s12933-025-02807-4","article-title":"Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study","volume":"24","author":"Xie","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e20230680","DOI":"10.36660\/abc.20230680","article-title":"Inflammation burden and atrial fibrillation burden: a bidirectional relationship","volume":"121","author":"Naser","year":"2024","journal-title":"Arq Bras Cardiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"E248","DOI":"10.1210\/jc.2011-1846","article-title":"LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in 54,500 individuals","volume":"97","author":"Haase","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1161\/ATVBAHA.123.319742","article-title":"Understanding HDL metabolism and biology through in vivo tracer kinetics","volume":"44","author":"Andraski","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"154351","DOI":"10.1016\/j.metabol.2020.154351","article-title":"High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study","volume":"112","author":"Prats-Uribe","year":"2020","journal-title":"Metab Clin Exp"},{"key":"B32","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1016\/j.amjcard.2015.01.015","article-title":"Relation of black race between high density lipoprotein cholesterol content, high density lipoprotein particles and coronary events (from the Dallas heart study)","volume":"115","author":"Chandra","year":"2015","journal-title":"Am J Cardiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s12967-024-05032-x","article-title":"ANGPTL3 Is a novel HDL component that regulates HDL function","volume":"22","author":"Yang","year":"2024","journal-title":"J Transl Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1161\/HYPERTENSIONAHA.120.16547","article-title":"Urate, blood pressure, and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials","volume":"77","author":"Gill","year":"2021","journal-title":"Hypertension"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1782658","DOI":"10.3389\/fphar.2026.1782658","article-title":"Finerenone is associated with pronounced uric acid reduction in hyperuricemic diabetic kidney disease: a real-world analysis","volume":"17","author":"Lin","year":"2026","journal-title":"Front Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-026-07866-7","article-title":"The nonlinear relationship between serum uric acid and cardiovascular disease risk: mechanistic insights and clinical implications","author":"Hou","year":"2026","journal-title":"Cardiovasc Drugs Ther"},{"key":"B37","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.cca.2014.08.034","article-title":"Vascular calcification: from pathophysiology to biomarkers","volume":"438","author":"Evrard","year":"2015","journal-title":"Clin Chim Acta Int J Clin Chem"},{"key":"B38","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1080\/10799893.2016.1203941","article-title":"Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44\/42 MAPK and PDGFR\u03b2","volume":"37","author":"K\u0131r\u00e7a","year":"2017","journal-title":"J Recept Signal Transduct Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1007\/s00210-024-03358-3","article-title":"Metformin and the PI3\u2005K\/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases","volume":"398","author":"Ashayeri Ahmadabad","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41401-021-00704-6","article-title":"Activating BK channels ameliorates vascular smooth muscle calcification through akt signaling","volume":"43","author":"Ning","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"B41","doi-asserted-by":"publisher","first-page":"982","DOI":"10.18632\/aging.204442","article-title":"Identification of cellular heterogeneity and key signaling pathways associated with vascular remodeling and calcification in young and old primate aortas based on single-cell analysis","volume":"15","author":"Yin","year":"2022","journal-title":"Aging (Albany NY)"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1877627\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:59:57Z","timestamp":1786514397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1877627\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":41,"alternative-id":["10.3389\/fcvm.2026.1877627"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1877627","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"1877627"}}