{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:34:45Z","timestamp":1790555685208,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>The aim of this analysis was to determine the long-term prognostic value of lower serum chloride in patients with stable chronic heart failure. Electrolyte abnormalities are prevalent in patients with chronic heart failure. Little is known regarding the prognostic implications of lower serum chloride.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>\n                      Serum chloride was measured in 1673 consecutively consented stable patients with a history of heart failure undergoing elective diagnostic coronary angiography. All patients were followed for 5-year all-cause mortality, and survival models were adjusted for variables that confounded the chloride\u2013risk relationship. The average chloride level was 102\u00b14 mEq\/L. Over 6772 person-years of follow-up, there were 547 deaths. Lower chloride (per standard deviation decrease) was associated with a higher adjusted risk of mortality (hazard ratio 1.29, 95% confidence interval 1.12\u20131.49;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Chloride levels net-reclassified risk in 10.4% (\n                      <jats:italic>P<\/jats:italic>\n                      =0.03) when added to a multivariable model (with a resultant C-statistic of 0.70), in which sodium levels were not prognostic (\n                      <jats:italic>P<\/jats:italic>\n                      =0.30). In comparison to those with above first quartile chloride (\u2265101 mEq\/L) and sodium (\u2265138 meq\/L), subjects with first quartile chloride had a higher adjusted mortality risk, whether they had first quartile sodium (hazard ratio 1.35, 95% confidence interval 1.08\u20131.69;\n                      <jats:italic>P<\/jats:italic>\n                      =0.008) or higher (hazard ratio 1.43, 95% confidence interval 1.12\u20131.85;\n                      <jats:italic>P<\/jats:italic>\n                      =0.005). However, subjects with first quartile sodium but above first quartile chloride had no association with mortality (\n                      <jats:italic>P<\/jats:italic>\n                      =0.67).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Lower serum chloride levels are independently and incrementally associated with increased mortality risk in patients with chronic heart failure. A better understanding of the biological role of serum chloride is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.115.002453","type":"journal-article","created":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T23:03:11Z","timestamp":1451602991000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":100,"title":["Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure"],"prefix":"10.1161","volume":"9","author":[{"given":"Justin L","family":"Grodin","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik H","family":"Verbrugge","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G","family":"Ellis","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Mullens","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M","family":"Testani","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.H. Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, Heart and Vascular Institute (J.L.G., S.G.E., W.H.W.T.) and Department for Cellular and Molecular Medicine, Lerner Research Institute (W.H.W.T.), Cleveland Clinic, OH; Department of Cardiology, Ziekenhuis Oost-Limburg, Genk, Belgium (F.H.V., W.M.); and Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT (J.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005253422107"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(83)80040-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.5.1724"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.019"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01063938"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0388"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.35"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs099"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.12.1319"},{"issue":"4","key":"e_1_3_3_11_2","first-page":"R771","article-title":"Adaptations to chloride-depletion alkalosis.","volume":"261","author":"Galla JH","year":"1991","unstructured":"Galla JH, Gifford JD, Luke RG, Rome L. 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