A Multimodality Strategy for Cardiovascular Risk Assessment: Performance in Two Population-Based Cohorts

James A. de Lemos, Colby R. Ayers, Benjamin Levine, Christopher R. deFilippi, Thomas J. Wang, Gregory G. Hundley, Jarett D. Berry, Stephen L. Seliger, Darren K. McGuire, Pamela Ouyang, Mark H. Drazner, Matthew Budoff, Philip Greenland, Christie M. Ballantyne, Amit Khera

Research output: Contribution to journalArticle

Abstract

BACKGROUND—: 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. METHODS—: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA, n=6621) and Dallas Heart Study (DHS, n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by electrocardiogram (ECG-LVH), coronary artery calcium (CAC), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hs-CRP). Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction [MI], stroke, coronary or peripheral revascularization, incident heart failure or atrial fibrillation) and ASCVD (fatal or nonfatal MI or stroke) were assessed over > 10 years of follow-up. Multivariable analyses for the primary global CVD endpoint adjusted for traditional risk factors plus statin use and creatinine (base model). RESULTS—: 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 five 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% CI 0.06-0.08, p<0.001) and 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 HR 1.9, 95% CI 1.4-2.6), 2 (HR 3.2, 95% CI 2.3-4.4), 3 (HR 4.7, 95% CI 3.4, 6.5) and ≥4 (HR 7.5, 95% CI 5.2-10.6). Findings replicated in DHS and were similar for the ASCVD outcome. CONCLUSIONS—: Among adults without known CVD, a novel multimodality testing strategy using ECG-LVH, CAC, NT-proBNP, hs-cTnT and hs-CRP significantly improved global CVD and ASCVD risk assessment.

Original languageEnglish (US)
JournalCirculation
DOIs
StateAccepted/In press - Apr 21 2017

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Cardiovascular Diseases
Population
Electrocardiography
Troponin T
Brain Natriuretic Peptide
C-Reactive Protein
Coronary Vessels
Stroke
Myocardial Infarction
Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Left Ventricular Hypertrophy
Atrial Fibrillation
Creatinine
Atherosclerosis
Heart Failure
Biomarkers

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

de Lemos, J. A., Ayers, C. R., Levine, B., deFilippi, C. R., Wang, T. J., Hundley, G. G., ... Khera, A. (Accepted/In press). A Multimodality Strategy for Cardiovascular Risk Assessment: Performance in Two Population-Based Cohorts. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.117.027272

A Multimodality Strategy for Cardiovascular Risk Assessment : Performance in Two Population-Based Cohorts. / de Lemos, James A.; Ayers, Colby R.; Levine, Benjamin; deFilippi, Christopher R.; Wang, Thomas J.; Hundley, Gregory G.; Berry, Jarett D.; Seliger, Stephen L.; McGuire, Darren K.; Ouyang, Pamela; Drazner, Mark H.; Budoff, Matthew; Greenland, Philip; Ballantyne, Christie M.; Khera, Amit.

In: Circulation, 21.04.2017.

Research output: Contribution to journalArticle

de Lemos, JA, Ayers, CR, Levine, B, deFilippi, CR, Wang, TJ, Hundley, GG, Berry, JD, Seliger, SL, McGuire, DK, Ouyang, P, Drazner, MH, Budoff, M, Greenland, P, Ballantyne, CM & Khera, A 2017, 'A Multimodality Strategy for Cardiovascular Risk Assessment: Performance in Two Population-Based Cohorts', Circulation. https://doi.org/10.1161/CIRCULATIONAHA.117.027272
de Lemos, James A. ; Ayers, Colby R. ; Levine, Benjamin ; deFilippi, Christopher R. ; Wang, Thomas J. ; Hundley, Gregory G. ; Berry, Jarett D. ; Seliger, Stephen L. ; McGuire, Darren K. ; Ouyang, Pamela ; Drazner, Mark H. ; Budoff, Matthew ; Greenland, Philip ; Ballantyne, Christie M. ; Khera, Amit. / A Multimodality Strategy for Cardiovascular Risk Assessment : Performance in Two Population-Based Cohorts. In: Circulation. 2017.
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TY - JOUR

T1 - A Multimodality Strategy for Cardiovascular Risk Assessment

T2 - Performance in Two Population-Based Cohorts

AU - de Lemos, James A.

AU - Ayers, Colby R.

AU - Levine, Benjamin

AU - deFilippi, Christopher R.

AU - Wang, Thomas J.

AU - Hundley, Gregory G.

AU - Berry, Jarett D.

AU - Seliger, Stephen L.

AU - McGuire, Darren K.

AU - Ouyang, Pamela

AU - Drazner, Mark H.

AU - Budoff, Matthew

AU - Greenland, Philip

AU - Ballantyne, Christie M.

AU - Khera, Amit

PY - 2017/4/21

Y1 - 2017/4/21

N2 - BACKGROUND—: 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. METHODS—: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA, n=6621) and Dallas Heart Study (DHS, n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by electrocardiogram (ECG-LVH), coronary artery calcium (CAC), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hs-CRP). Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction [MI], stroke, coronary or peripheral revascularization, incident heart failure or atrial fibrillation) and ASCVD (fatal or nonfatal MI or stroke) were assessed over > 10 years of follow-up. Multivariable analyses for the primary global CVD endpoint adjusted for traditional risk factors plus statin use and creatinine (base model). RESULTS—: 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 five 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% CI 0.06-0.08, p<0.001) and 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 HR 1.9, 95% CI 1.4-2.6), 2 (HR 3.2, 95% CI 2.3-4.4), 3 (HR 4.7, 95% CI 3.4, 6.5) and ≥4 (HR 7.5, 95% CI 5.2-10.6). Findings replicated in DHS and were similar for the ASCVD outcome. CONCLUSIONS—: Among adults without known CVD, a novel multimodality testing strategy using ECG-LVH, CAC, NT-proBNP, hs-cTnT and hs-CRP significantly improved global CVD and ASCVD risk assessment.

AB - BACKGROUND—: 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. METHODS—: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA, n=6621) and Dallas Heart Study (DHS, n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by electrocardiogram (ECG-LVH), coronary artery calcium (CAC), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hs-CRP). Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction [MI], stroke, coronary or peripheral revascularization, incident heart failure or atrial fibrillation) and ASCVD (fatal or nonfatal MI or stroke) were assessed over > 10 years of follow-up. Multivariable analyses for the primary global CVD endpoint adjusted for traditional risk factors plus statin use and creatinine (base model). RESULTS—: 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 five 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% CI 0.06-0.08, p<0.001) and 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 HR 1.9, 95% CI 1.4-2.6), 2 (HR 3.2, 95% CI 2.3-4.4), 3 (HR 4.7, 95% CI 3.4, 6.5) and ≥4 (HR 7.5, 95% CI 5.2-10.6). Findings replicated in DHS and were similar for the ASCVD outcome. CONCLUSIONS—: Among adults without known CVD, a novel multimodality testing strategy using ECG-LVH, CAC, NT-proBNP, hs-cTnT and hs-CRP significantly improved global CVD and ASCVD risk assessment.

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