{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:25:54Z","timestamp":1784280354657,"version":"3.55.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,4,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Subclinical rheumatic heart disease (SCRHD) is the precursor to symptomatic disease, yet the cytokine profile of its earliest borderline stage remains uncharacterized. It is unknown whether inflammatory markers persist longitudinally in subclinical rheumatic heart disease. This study characterized the cytokine profile in borderline SCRHD at baseline and evaluated its longitudinal evolution over a 2\u2010year period in the combined SCRHD (borderline and definitive).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In a prospective cohort study, 1026 children (5\u201315\u2009years) from disadvantaged areas of S\u00e3o Paulo, Brazil, underwent echocardiographic screening. Participants were classified as normal, borderline SCRHD, or definite SCRHD according to World Health Organization criteria. Plasma levels of interleukin\u20106 (IL\u20106), tumor necrosis factor\u2010alpha, and other cytokines were measured at baseline (T0) and after 2\u2009years (T1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The prevalence of SCRHD was 7.6% (95% CI, 6.0%\u20139.2%), with 6.7% borderline (95% CI, 5.2%\u20138.2%) and 0.9% as definite (95% CI, 0.3%\u20131.5%). At baseline, IL\u20106 levels were significantly higher in the borderline SCRHD group compared with controls (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.048), while tumor necrosis factor\u2010alpha showed a trend toward elevation (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.067). No significant differences were observed for interleukin\u20102 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.067), interleukin\u20104 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =1.000), interleukin\u201010 (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.690), interleukin\u201017A (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.067), or interferon\u2010gamma (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.456). Among 44 participants followed for 2\u2009years, IL\u20106 and tumor necrosis factor\u2010alpha levels remained persistently elevated, with no significant change over time (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.626 and\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.144, respectively), indicating ongoing inflammatory activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Borderline SCRHD is marked by elevated IL\u20106 levels that last for at least 2\u2009years, indicating a sustained proinflammatory state from the earliest detectable stage of the disease. These findings identify interleukin\u20106 as a potential early biomarker and therapeutic target to prevent the progression of SCRHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.042405","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:07:16Z","timestamp":1775556436000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Elevated Interleukin\u20106 Levels in Socioeconomically Disadvantaged Children With Borderline Subclinical Rheumatic Heart Disease in S\u00e3o Paulo, Brazil: A\u00a0Prospective Cohort Study Highlighting Early Detection and Treatment Opportunities"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-5058","authenticated-orcid":false,"given":"Carlos Eduardo","family":"de Barros Branco","sequence":"first","affiliation":[{"name":"University of S\u00e3o Paulo Medical School","place":["S\u00e3o Paulo, 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