{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:45:25Z","timestamp":1782992725872,"version":"3.54.5"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Heart failure (HF) is associated with inflammation, but its specific immunophenotypic characteristics and relevant prognostic relationships are poorly established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In the HRS (Health and Retirement Study; N=9566), we used multivariable logistic regression, linear regression, and Cox proportional hazard models to describe cross\u2010sectional relationships between HF, plasma biomarkers, leukocyte levels, lymphocyte subsets enumerated by flow cytometry, and all\u2010cause survival. We then analyzed real\u2010world lymphocyte levels, incident HF, and death among outpatients within the US Veterans Affairs Health System (N=38\u2009565).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      HF was accompanied by elevated inflammatory cytokine levels as well as relative lymphopenia. This lymphopenia was due to marked reduction in the reservoir of na\u00efve CD4+ T cells, whereas total CD8+ T\u2010cell numbers were not reduced, and the CD4+ effector memory niche was expanded. Importantly, among those without HF, total lymphocytes and na\u00efve CD4+ T cells were each inversely related to aminoterminal pro\u2010B\u2010type natriuretic peptide levels and signaled a higher mortality rate. Linkages between lymphocyte deficiency, HF, and survival were robust to adjustment for low physical activity and a variety of inflammatory biomarkers. In the Veterans Affairs system, real\u2010world lymphopenia (absolute lymphocyte count &lt;1.2: \u224811.5% of outpatient complete blood cell counts) is associated with incident HF (adjusted hazard ratio [aHR], 1.60 [95% CI, 1.38\u20131.86];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001) and also portends a poor subsequent prognosis (aHR, 1.43 [95% CI, 1.20\u20131.70];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">HF is associated with total lymphopenia due to a specific deficiency of na\u00efve CD4+ T lymphocytes. Crude lymphopenia among the general ambulatory population can herald incident HF and poor subsequent survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.042475","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:33:54Z","timestamp":1773138834000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Specific Deficiency of Na\u00efve CD4+ T Lymphocytes Characterizes Heart Failure and Heightens Mortality Risk in the HRS"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-3986","authenticated-orcid":false,"given":"David A.","family":"Zidar","sequence":"first","affiliation":[{"name":"Cleveland Clinic Foundation","place":["Cleveland, USA"]},{"name":"Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"name":"Louis Stokes Cleveland Veterans Affairs Medical Center","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7690-5258","authenticated-orcid":false,"given":"Michael L.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Case Western Reserve University School of Medicine","place":["Cleveland, USA"]},{"name":"Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-2940","authenticated-orcid":false,"given":"Brigid M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Veterans Affairs Medical Center","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1122-7695","authenticated-orcid":false,"given":"Sadeer","family":"Al\u2010kindi","sequence":"additional","affiliation":[{"name":"Houston Methodist DeBakey Heart and Vascular Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-6045","authenticated-orcid":false,"given":"Mina K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation","place":["Cleveland, USA"]},{"name":"Case Western Reserve University School of Medicine","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-8578","authenticated-orcid":false,"given":"Douglas D.","family":"Gunzler","sequence":"additional","affiliation":[{"name":"Case Western Reserve University at MetroHealth","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0551-5885","authenticated-orcid":false,"given":"Sahil A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center","place":["New York, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9444-7046","authenticated-orcid":false,"given":"Ashish A.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-1246","authenticated-orcid":false,"given":"Carey L.","family":"Shive","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Veterans Affairs Medical Center","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0975-4760","authenticated-orcid":false,"given":"Mukesh","family":"Jain","sequence":"additional","affiliation":[{"name":"The Warren Alpert Medical School of Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-5733","authenticated-orcid":false,"given":"Jacek","family":"Skarbinski","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Northern California","place":["Oakland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-735X","authenticated-orcid":false,"given":"W. 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