{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:00:51Z","timestamp":1780657251919,"version":"3.54.1"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Cardiometabolic risk factors frequently cluster and substantially increase the risk of cardiovascular disease. While high-density lipoprotein cholesterol (HDL-C) and systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), are independently associated with cardiometabolic risk, whether systemic inflammation modifies the association between HDL-C and cardiometabolic risk clustering (CMRC) remains unclear. This study aimed to examine the independent associations of HDL-C and hs-CRP with CMRC and to evaluate the multiplicative product interaction between HDL-C and natural log-transformed hs-CRP in relation to CMRC among middle-aged adults. Materials and Methods: This cross-sectional study used data from 2283 adults aged 40\u201364 years who participated in the 2024 Korea National Health and Nutrition Examination Survey. CMRC was defined as the presence of \u22652 cardiometabolic risk factors. HDL-C and hs-CRP were analyzed as continuous variables. Complex sample logistic regression analyses were performed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), including a multiplicative product interaction term calculated as HDL-C \u00d7 ln hs-CRP. Results: The prevalence of CMRC was 46.4%. HDL-C was inversely associated with CMRC (OR = 0.946, 95% CI = 0.937\u20130.956, p &lt; 0.001), whereas ln hs-CRP was positively associated with CMRC (OR = 1.224, 95% CI = 1.020\u20131.468, p = 0.030). The HDL-C \u00d7 ln hs-CRP product interaction term was significantly associated with CMRC (OR = 1.005, 95% CI = 1.001\u20131.009, p = 0.008). This finding indicates that the association between HDL-C and CMRC may vary across levels of ln hs-CRP, but it does not indicate a direct association between HDL-C and ln hs-CRP. Conclusions: HDL-C and ln hs-CRP were independently associated with CMRC. The significant HDL-C \u00d7 ln hs-CRP product interaction term suggests possible statistical effect modification of the HDL-C\u2013CMRC association by systemic inflammatory status. These findings should be interpreted cautiously and do not establish a causal or mechanistic relationship.<\/jats:p>","DOI":"10.3390\/medicina62061096","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:43:04Z","timestamp":1780648984000},"page":"1096","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interactive Effects of HDL Cholesterol and hs-CRP in Relation to Cardiometabolic Risk Clustering Among Middle-Aged Adults"],"prefix":"10.3390","volume":"62","author":[{"given":"Heeyoung","family":"Hwang","sequence":"first","affiliation":[{"name":"Myongji St. Mary\u2019s Hospital, Seoul 07417, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5837-3971","authenticated-orcid":false,"given":"Gitak","family":"Bae","sequence":"additional","affiliation":[{"name":"Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-4183","authenticated-orcid":false,"given":"Kyeongmin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Nursing, College of Health Sciences, Daejin University, Pocheon-si 11159, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: Update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J. 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