Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk

Subha Subramanian; Chunyu Liu; Abraham Aviv; Jennifer E Ho; Paul Courchesne; Pieter Muntendam; Martin G Larson; Susan Cheng; Thomas J Wang; Nehal N Mehta; Daniel Levy

doi:10.1161/ATVBAHA.114.303579

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Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk

Journal article

Open access

Peer reviewed

Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk

Subha Subramanian, Chunyu Liu, Abraham Aviv, Jennifer E Ho, Paul Courchesne, Pieter Muntendam, Martin G Larson, Susan Cheng, Thomas J Wang, Nehal N Mehta, …

Arteriosclerosis, thrombosis, and vascular biology, Vol.34(9), pp.2100-2105

09/2014

DOI: https://doi.org/10.1161/ATVBAHA.114.303579

PMCID: PMC4142677

PMID: 25060794

Abstract

Blood Pressure

Myocardial Infarction - epidemiology

Follow-Up Studies

Smoking - blood

Humans

Middle Aged

Risk Factors

Kaplan-Meier Estimate

Proportional Hazards Models

Male

Heart Failure - blood

Telomere Homeostasis

Waist Circumference

Chemokine CXCL12 - blood

Female

Polymorphism, Single Nucleotide

Heart Failure - mortality

Biomarkers

CXCL12 encodes stromal cell-derived factor 1α (SDF-1), which binds to the receptor encoded by CXCR4. Variation at the CXCL12 locus is associated with coronary artery disease and endothelial progenitor cell numbers, whereas variation at the CXCR4 locus is associated with leukocyte telomere length, which has been shown to be associated with coronary artery disease. Therefore, we examined the relationships of plasma SDF-1 levels to cardiovascular disease (CVD)-related outcomes, risk factors, leukocyte telomere length, and endothelial progenitor cells. SDF-1 was measured in 3359 Framingham Heart Study participants. We used Cox regression to examine relationships of SDF-1 to new-onset CVD, myocardial infarction, heart failure, and all-cause mortality; we used linear regression to evaluate associations of SDF-1 with risk factors, leukocyte telomere length, and CD34+ cell phenotypes. In multivariable models, higher SDF-1 levels were associated with older age, lower levels of high-density lipoprotein-cholesterol and cigarette smoking. Higher SDF-1 levels were associated with lower CD34+ cell frequency (P=0.02) but not with leukocyte telomere length. During follow-up (median, 9.3 years), there were 263 new-onset CVD events, 160 myocardial infarctions, 200 heart failure events, and 385 deaths. After adjusting for clinical risk factors, SDF-1 levels were associated with heart failure (P=0.04) and all-cause mortality (P=0.003) but not with CVD (P=0.39) or myocardial infarction (P=0.10). The association of SDF-1 levels with myocardial infarction was attenuated after adjustment for high-density lipoprotein-cholesterol. After adjusting for traditional CVD risk factors, SDF-1 is associated with heart failure and all-cause mortality risk. Additional studies are needed to determine whether measurement of SDF-1 levels has clinical use.

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Title: Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk
Creators: Subha Subramanian - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Chunyu Liu - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Abraham Aviv - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Jennifer E Ho - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Paul Courchesne - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Pieter Muntendam - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Martin G Larson - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Susan Cheng - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Thomas J Wang - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Nehal N Mehta - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.)
Daniel Levy - From the Framingham Heart Study, MA (S.S., C.L., J.E.H., P.C., M.G.L., S.C., D. L.); Population Sciences Branch (S.S., C.L., P.C., D.L.) and Division of Intramural Research (S.S., C.L., P.C., N.N.M., D. L.), National Heart, Lung, and Blood Institute, Bethesda, MD; The Center of Human Development and Aging, New Jersey Medical School, Rutgers University, Newark, NJ (A.A.); Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, MA (J.E.H., D.L.); Formerly of BG Medicine, Inc, Waltham, MA (P.M.); Department of Mathematics and Statistics, Boston University, MA (M.G.L.); Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston (S.C.); and Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.). levyd@nih.gov
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.34(9), pp.2100-2105
Date published: 09/2014
Grant note: N01HC25195 / NHLBI NIH HHS Z99 HL999999 / Intramural NIH HHS N01-HC-25195 / NHLBI NIH HHS R01 HD071180 / NICHD NIH HHS R01 AG030678 / NIA NIH HHS R01HD071180 / NICHD NIH HHS R01AG030678 / NIA NIH HHS
Academic Unit: Pediatrics - Developmental-Behavioral Pediatrics (NJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031654454604646