title: Stromal cell-derived factor 1 as a biomarker of heart failure and mortality risk.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.).
authors: Subha
authors: S
authors: Subramanian
authors: 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.).
authors: Chunyu
authors: C
authors: Liu
authors: 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.).
authors: Abraham
authors: A
authors: Aviv
authors: 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.).
authors: Jennifer E
authors: JE
authors: Ho
authors: 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.).
authors: Paul
authors: P
authors: Courchesne
authors: 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.).
authors: Pieter
authors: P
authors: Muntendam
authors: 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.).
authors: Martin G
authors: MG
authors: Larson
authors: 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.).
authors: Susan
authors: S
authors: Cheng
authors: 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.).
authors: Thomas J
authors: TJ
authors: Wang
authors: 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.).
authors: Nehal N
authors: NN
authors: Mehta
authors: 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.
authors: Daniel
authors: D
authors: Levy
mesh_terms: D015415:Biomarkers; D001794:Blood Pressure; D054377:Chemokine CXCL12 / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000097:blood; D059505:Telomere Homeostasis; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: cardiovascular diseases; chemokine CXCL12; epidemiology; heart failure; mortality; myocardial infarction; stem cells