Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.
BACKGROUND
Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF).


RESULTS
We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes).


CONCLUSIONS
In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay.
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
João Pedro
JP
Ferreira
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Nicolas
N
Girerd
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Kevin
K
Duarte
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Stefano
S
Coiro
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
John J V
JJ
McMurray
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Henry J
HJ
Dargie
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Bertram
B
Pitt
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Kenneth
K
Dickstein
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Jeffrey M
JM
Testani
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT.
Faiez
F
Zannad
From the INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, F-CRIN INI-CRCT, France (J.P.F., N.G., K.D., S.C., F.Z., P.R.); Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Portugal (J.P.F.); Division of Cardiology, School of Medicine, University of Perugia, Italy (S.C.); British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and Institute of Cardiovascular and Medical Sciences (H.J.D.), University of Glasgow, United Kingdom; Department of Medicine, University of Michigan School of Medicine, Ann Arbor (B.P.); Department of Cardiology, Stavanger University Hospital, University of Bergen, Norway (K.D.); and Program of Applied Translational Research (J.M.T.) and Department of Internal Medicine (J.M.T.), Yale University School of Medicine, New Haven, CT. p.rossignol@chru-nancy.fr.
Patrick
P
Rossignol
D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002712:Chlorides / Q000097:blood*; D015897:Comorbidity; D016208:Databases, Factual; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D017711:Nonlinear Dynamics; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012964:Sodium / Q000097:blood*; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D016277:Ventricular Function, Left
D015415:Biomarkers; D002712:Chlorides; D012964:Sodium
alkalosis; anion; attention; heart failure; myocardial infarction