title: Traditional Risk Factors Versus Biomarkers for Prediction of Secondary Events in Patients With Stable Coronary Heart Disease: From the Heart and Soul Study.
abstract: BACKGROUND
  Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD.
  
  
  RESULTS
  We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort.
  
  
  CONCLUSIONS
  Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) Cardiology Section, Veterans Affairs Puget Sound Health Care System, Seattle, WA (A.L.B.) Department of Medicine, University of Washington, Seattle, WA (A.L.B.).
authors.forename: Alexis L
authors.initials: AL
authors.lastname: Beatty
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) San Francisco General Hospital, San Francisco, CA (I.A.K., K.B.D., P.G.) Department of Cardiology, Kaiser Permanente Medical Center, San Francisco, CA (I.A.K., M.T.).
authors.forename: Ivy A
authors.initials: IA
authors.lastname: Ku
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (K.B.D., M.G.S., E.V., M.A.W.) San Francisco General Hospital, San Francisco, CA (I.A.K., K.B.D., P.G.).
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bibbins-Domingo
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore, MD (R.H.C.).
authors.forename: Robert H
authors.initials: RH
authors.lastname: Christenson
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (C.R.D.F.).
authors.forename: Christopher R
authors.initials: CR
authors.lastname: DeFilippi
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) San Francisco General Hospital, San Francisco, CA (I.A.K., K.B.D., P.G.).
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA (J.H.I.) Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA (J.H.I.) Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California San Diego, San Diego, CA (J.H.I.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Preventive Medicine and Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (D.L.J.) Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (D.L.J.).
authors.forename: Donald
authors.initials: D
authors.lastname: Lloyd-Jones
authors.affiliation: Division of Medicine, Akershus University Hospital and University of Oslo, Lørenskog, Norway (T.O.).
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (M.S.S.) Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.S.S., H.S.).
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.).
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Schiller
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (K.B.D., M.G.S., E.V., M.A.W.) Section of General Internal Medicine, Veterans Affairs Medical Center, San Francisco, CA (M.G.S., M.A.W.).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.S.S., H.S.).
authors.forename: Hicham
authors.initials: H
authors.lastname: Skali
authors.affiliation: Department of Cardiology, Kaiser Permanente Medical Center, San Francisco, CA (I.A.K., M.T.).
authors.forename: Madoka
authors.initials: M
authors.lastname: Takeuchi
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (K.B.D., M.G.S., E.V., M.A.W.).
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA (A.L.B., I.A.K., K.B.D., P.G., N.B.S., M.G.S., M.A.W.) Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA (K.B.D., M.G.S., E.V., M.A.W.) Section of General Internal Medicine, Veterans Affairs Medical Center, San Francisco, CA (M.G.S., M.A.W.).
authors.forename: Mary A
authors.initials: MA
authors.lastname: Whooley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015897:Comorbidity; D003327:Coronary Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism / Q000401:mortality; D003404:Creatinine / Q000652:urine*; D003661:Decision Support Techniques; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology* / Q000401:mortality; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000378:metabolism / Q000401:mortality; D013997:Time Factors; D020107:Troponin T / Q000097:blood*; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D003404:Creatinine
keywords: coronary disease; epidemiology; prevention; risk prediction