{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:09:44Z","timestamp":1784113784608,"version":"3.55.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Inflammatory biomarkers, including immune cells appear associated with reduced heart rate variability (HRV), an indicator of cardiac autonomic nervous dysfunction. However, the influence of leukocytes on HRV and their relation across sex and glucose metabolism status remains unclear. Hence, we sought to investigate the cross\u2010sectional association between leukocytes and HRV indices and their association across sex and glucose metabolism status in a general population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We retrieved cross\u2010sectional data of 1888 participants of the Maastricht Study who completed the baseline survey between November 2010 and December 2017. Blood leukocyte numbers (including neutrophils, monocytes, basophils, eosinophils, and lymphocytes) were determined with an automated hematology analyzer. Qualitative changes within lymphocytes were assessed with flow cytometry. HRV indices were assessed using a 24\u2010hour ECG. Time\u2010domain and frequency\u2010domain HRV index average scores were calculated. We regressed HRV average scores on standardized leukocytes and adjusted the models for several covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In fully adjusted models, higher neutrophil (\u22120.07 [\u22120.11 to \u22120.03]; false discovery rate (FDR)\u2010corrected\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      value,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      =0.006) and monocyte (\u22120.05 [\u22120.09 to \u22120.02];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      =0.020) counts were associated with a lower time\u2010domain average score. Higher neutrophil (\u22120.07 [\u22120.11 to \u22120.03];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      =0.006) and monocyte (\u22120.05 [\u22120.09 to \u22120.01];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      =0.020) counts were also associated with a lower frequency\u2010domain HRV index average score. No effect modification by either sex or glucose metabolism status was found (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      <jats:sub>intFDR<\/jats:sub>\n                      &gt;0.05). There were no other associations between immune cells and HRV indices.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Higher neutrophil and monocyte counts were associated with lower HRV, irrespective of sex and glucose metabolism status. This suggests a role of these cells reflecting innate immune processes and inflammatory response in cardiac autonomic nervous dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043994","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T10:22:18Z","timestamp":1769077338000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Neutrophil and Monocyte Counts Are Inversely Associated With Heart Rate Variability Indices: The Maastricht Study"],"prefix":"10.1161","volume":"15","author":[{"given":"Haifa","family":"Maalmi","sequence":"first","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]},{"name":"German Center for Diabetes Research (DZD)","place":["Partner D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7127-6950","authenticated-orcid":false,"given":"Kristiaan","family":"Wouters","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Cardiovascular Research Institute Maastricht (CARIM)","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2128-8029","authenticated-orcid":false,"given":"Nicolaas C.","family":"Schaper","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3432-0593","authenticated-orcid":false,"given":"Anna","family":"Zhu","sequence":"additional","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]},{"name":"German Center for Diabetes Research (DZD)","place":["Partner D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1418-108X","authenticated-orcid":false,"given":"Jordi","family":"Heijman","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Gottfried Schatz Research Center, Medical University of Graz","place":["Graz, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1468-8793","authenticated-orcid":false,"given":"Carla J. H.","family":"van der Kallen","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Cardiovascular Research Institute Maastricht (CARIM)","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-1631","authenticated-orcid":false,"given":"Marleen M. J.","family":"van Greevenbroek","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Cardiovascular Research Institute Maastricht (CARIM)","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1767-8814","authenticated-orcid":false,"given":"Pieter C.","family":"Dagnelie","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Cardiovascular Research Institute Maastricht (CARIM)","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan E.","family":"de Galan","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre (MUMC)","place":["Maastricht, the Netherlands"]},{"name":"Cardiovascular Research Institute Maastricht (CARIM)","place":["Maastricht, the Netherlands"]},{"name":"Radboud University Medical Centre","place":["Nijmegen, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4474-9665","authenticated-orcid":false,"given":"Anke","family":"Wesselius","sequence":"additional","affiliation":[{"name":"Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University","place":["Maastricht, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-3552","authenticated-orcid":false,"given":"Dan","family":"Ziegler","sequence":"additional","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Michael","family":"Roden","sequence":"additional","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]},{"name":"German Center for Diabetes Research (DZD)","place":["Partner D\u00fcsseldorf, Germany"]},{"name":"Medical Faculty and University Hospital D\u00fcsseldorf","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-093X","authenticated-orcid":false,"given":"Christian","family":"Herder","sequence":"additional","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]},{"name":"German Center for Diabetes Research (DZD)","place":["Partner D\u00fcsseldorf, Germany"]},{"name":"Medical Faculty and University Hospital D\u00fcsseldorf","place":["D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-5970","authenticated-orcid":false,"given":"Kolade","family":"Oluwagbemigun","sequence":"additional","affiliation":[{"name":"German Diabetes Center (DDZ), Institute for Clinical Diabetology, Leibniz Center for Diabetes Research at Heinrich Heine Universit\u00e4t","place":["D\u00fcsseldorf, Germany"]},{"name":"German Center for Diabetes Research (DZD)","place":["Partner D\u00fcsseldorf, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen D. 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