title: Multimodality Strategy for Cardiovascular Risk Assessment: Performance in 2 Population-Based Cohorts.
abstract: Current strategies for cardiovascular disease (CVD) risk assessment among adults without known CVD are limited by suboptimal performance and a narrow focus on only atherosclerotic CVD (ASCVD). We hypothesized that a strategy combining promising biomarkers across multiple different testing modalities would improve global and atherosclerotic CVD risk assessment among individuals without known CVD.
  
  
  
  We included participants from MESA (Multi-Ethnic Study of Atherosclerosis) (n=6621) and the Dallas Heart Study (n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein. Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction, stroke, coronary or peripheral revascularization, incident heart failure, or atrial fibrillation) and ASCVD (fatal or nonfatal myocardial infarction or stroke) were assessed over >10 years of follow-up. Multivariable analyses for the primary global CVD end point adjusted for traditional risk factors plus statin use and creatinine (base model).
  
  
  
  Each test result was independently associated with global composite CVD events in MESA after adjustment for the components of the base model and the other test results (P<0.05 for each). When the 5 tests were added to the base model, the c-statistic improved from 0.74 to 0.79 (P=0.001), significant integrated discrimination improvement (0.07, 95% confidence interval [CI] 0.06-0.08,P<0.001) and category free net reclassification improvement (0.47; 95% CI, 0.38-0.56;P=0.003) were observed, and the model was well calibrated (χ2=12.2,P=0.20). Using a simple integer score counting the number of abnormal tests, compared with those with a score of 0, global CVD risk was increased among participants with a score of 1 (adjusted hazard ratio, 1.9; 95% CI, 1.4-2.6), 2 (hazard ratio, 3.2; 95% CI, 2.3-4.4), 3 (hazard ratio, 4.7; 95% CI, 3.4-6.5), and ≥4 (hazard ratio, 7.5; 95% CI, 5.2-10.6). Findings replicated in the Dallas Health Study were similar for the ASCVD outcome.
  
  
  
  Among adults without known CVD, a novel multimodality testing strategy using left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein significantly improved global CVD and ASCVD risk assessment.
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.). james.delemos@utsouthwestern.edu.
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Levine
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Christopher R
authors.initials: CR
authors.lastname: deFilippi
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Hundley
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Jarett D
authors.initials: JD
authors.lastname: Berry
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: From Departments of Medicine (J.A.d.L., B.L., J.P.B., D.K.M., M.H.D., A.K.) and Clinical Sciences (C.R.A., J.D.B., D.K.M.), University of Texas Southwestern Medical Center, Dallas; Institute for Exercise and Environmental Medicine, Texas Health Presbyterian, Dallas (B.L.); Inova Heart and Vascular Institute, Fall Church, VA (C.R.d.); Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (T.J.W.); Departments of Medicine and Radiological Sciences, Wake Forest Health Sciences, Winston-Salem, NC (W.G.H.); Department of Medicine, University of Maryland School of Medicine, Baltimore (S.L.S.); The Johns Hopkins University School of Medicine, Baltimore, MD (P.O.); Los Angeles Biomedical Research Institute, CA (M.B.); Departments of Preventive Medicine and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (P.G.); and Baylor College of Medicine, Houston, TX (G.M.B.).
authors.forename: Amit
authors.initials: A
authors.lastname: Khera
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D018570:Risk Assessment; D013781:Texas / Q000208:ethnology
chemical_list: D015415:Biomarkers
keywords: C-reactive protein; NT-proBNP; biomarker; coronary calcium; risk prediction; troponin T