{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:16:35Z","timestamp":1778134595402,"version":"3.51.4"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011176","name":"Peking Union Medical College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004912","name":"Sichuan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004912","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The increasing frequency and intensity of heatwaves threaten global cardiovascular (CV) health. While the link between acute heatwaves and clinical CV events is known, the effect of cumulative heat exposure on early, subclinical CV injury is poorly understood. We investigated the dose\u2013response relation between sustained thermal burden and subclinical CV damage and identified the main metabolic-inflammatory pathways involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this large-scale, population-based retrospective cross-sectional study of 64,088 adults from Sichuan, China, we quantified cumulative heat exposure using new Cumulative Excess Heat Wave Index (CEHWI) based on apparent temperature (AT). Subclinical CV injury was assessed using a progressive cascade of biomarkers, including lipid remodeling markers (RC), Atherogenic Index of Plasma (AIP) and myocardial injury enzymes (AST), Lactate Dehydrogenase (LDH). We used multivariable generalized linear models and causal mediation analysis to evaluate 10 candidate metabolic-inflammatory mediators in metabolic, lipid and inflammation domains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Higher CEHWI is associated with a dose-dependent increase in subclinical CV injury markers. Each unit increase of CEHWI was associated with elevated RC (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f0.088\u202fmmol\/L), AIP (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f0.019) and LDH (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u202f=\u202f2.069\u202fU\/L; all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Mediation analysis showed Uric Acid-to-HDL Cholesterol Ratio (UHR) to be the most important mediator explaining 73.7% of the total effect of cumulative heat on AIP (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01) and revealing a previously unknown metabolic\u2013inflammatory axis. Subgroup analyses supported the Double-Hit hypothesis, indicating heightened vulnerability among older adults and hypertensive individuals. Hypertension acted as a \u201cpriming factor\u201d that reduced the threshold of heat-induced metabolic collapse even for active clinical treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Short-term cumulative heat exposure(7-day CEHWI) is strongly associated with subclinical CV injury, with the association largely mediated through a UHR-related metabolic-inflammatory nexus. These findings underscore the necessity of transitioning toward cumulative intensity monitoring in climate-health monitoring. Integrating UHR as a \u201cbiological thermometer\u201d in early warning systems and precision prevention strategies for metabolically vulnerable populations, such as metabolic monitoring during extreme heat periods, are public health imperatives in warming world.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1825331","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:43:34Z","timestamp":1778132614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["UHR as a systemic sensor of cumulative heat exposure and subclinical cardiovascular injury: evidence from 64,088 adults"],"prefix":"10.3389","volume":"14","author":[{"given":"Tao","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui-Chen","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiu-Lin","family":"Guo","sequence":"additional","affiliation":[{"name":"Information Center, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Kun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian-Shan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1056\/nejmra2210769","article-title":"Climate change, extreme heat, and health","volume":"390","author":"Bell","year":"2024","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"ITC97","DOI":"10.7326\/annals-25-01958","article-title":"Heat-related illnesses","volume":"178","author":"O\u2019Connor","year":"2025","journal-title":"Ann Intern 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