Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes

Marco Colombo, Helen C Looker, Bassam Farran, Felix Agakov, M Julia Brosnan, Paul Welsh, Naveed Sattar, Shona Livingstone, Paul N Durrington, D John Betteridge, Paul M McKeigue, Helen M Colhoun

    Research output: Contribution to journalArticle

    2 Citations (Scopus)
    63 Downloads (Pure)

    Abstract

    BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded.

    METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction.

    RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745.

    CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.

    Original languageEnglish
    Pages (from-to)182-190
    Number of pages9
    JournalAtherosclerosis
    Volume274
    Early online date21 May 2018
    DOIs
    Publication statusPublished - Jul 2018

    Fingerprint

    Apolipoprotein C-III
    Natriuretic Peptides
    Type 2 Diabetes Mellitus
    Cardiovascular Diseases
    Brain Natriuretic Peptide
    Biomarkers
    Troponin T
    Confidence Intervals
    ROC Curve
    Interleukin-15
    Proportional Hazards Models
    Coronary Disease
    Interleukin-6
    Stroke
    Placebos
    Clinical Trials

    Keywords

    • Apolipoprotein
    • Cardiovascular disease
    • Epidemiology
    • Type 2 diabetes mellitus

    Cite this

    Colombo, Marco ; Looker, Helen C ; Farran, Bassam ; Agakov, Felix ; Brosnan, M Julia ; Welsh, Paul ; Sattar, Naveed ; Livingstone, Shona ; Durrington, Paul N ; Betteridge, D John ; McKeigue, Paul M ; Colhoun, Helen M. / Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes. In: Atherosclerosis. 2018 ; Vol. 274. pp. 182-190.
    @article{d46d044fd7cf4f13a3e8eb6e228a72da,
    title = "Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes",
    abstract = "BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded.METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction.RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95{\%} Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95{\%} CI 1.12, 1.60) and hsTnT (1.40, 95{\%} CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745.CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.",
    keywords = "Apolipoprotein, Cardiovascular disease, Epidemiology, Type 2 diabetes mellitus",
    author = "Marco Colombo and Looker, {Helen C} and Bassam Farran and Felix Agakov and Brosnan, {M Julia} and Paul Welsh and Naveed Sattar and Shona Livingstone and Durrington, {Paul N} and Betteridge, {D John} and McKeigue, {Paul M} and Colhoun, {Helen M}",
    note = "This work was funded by the Innovative Medicine Initiative under grant agreement n° IMI/115006 (the SUMMIT consortium). The original CARDS Trial was funded by Diabetes UK, the UK Department of Health, Pfizer UK and Pfizer Inc. (manufacturers of atorvastatin).",
    year = "2018",
    month = "7",
    doi = "10.1016/j.atherosclerosis.2018.05.014",
    language = "English",
    volume = "274",
    pages = "182--190",
    journal = "Atherosclerosis",
    issn = "0021-9150",
    publisher = "Elsevier",

    }

    Colombo, M, Looker, HC, Farran, B, Agakov, F, Brosnan, MJ, Welsh, P, Sattar, N, Livingstone, S, Durrington, PN, Betteridge, DJ, McKeigue, PM & Colhoun, HM 2018, 'Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes', Atherosclerosis, vol. 274, pp. 182-190. https://doi.org/10.1016/j.atherosclerosis.2018.05.014

    Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes. / Colombo, Marco; Looker, Helen C; Farran, Bassam; Agakov, Felix; Brosnan, M Julia; Welsh, Paul; Sattar, Naveed; Livingstone, Shona; Durrington, Paul N; Betteridge, D John; McKeigue, Paul M; Colhoun, Helen M.

    In: Atherosclerosis, Vol. 274, 07.2018, p. 182-190.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes

    AU - Colombo, Marco

    AU - Looker, Helen C

    AU - Farran, Bassam

    AU - Agakov, Felix

    AU - Brosnan, M Julia

    AU - Welsh, Paul

    AU - Sattar, Naveed

    AU - Livingstone, Shona

    AU - Durrington, Paul N

    AU - Betteridge, D John

    AU - McKeigue, Paul M

    AU - Colhoun, Helen M

    N1 - This work was funded by the Innovative Medicine Initiative under grant agreement n° IMI/115006 (the SUMMIT consortium). The original CARDS Trial was funded by Diabetes UK, the UK Department of Health, Pfizer UK and Pfizer Inc. (manufacturers of atorvastatin).

    PY - 2018/7

    Y1 - 2018/7

    N2 - BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded.METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction.RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745.CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.

    AB - BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded.METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction.RESULTS: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745.CONCLUSIONS: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score.

    KW - Apolipoprotein

    KW - Cardiovascular disease

    KW - Epidemiology

    KW - Type 2 diabetes mellitus

    U2 - 10.1016/j.atherosclerosis.2018.05.014

    DO - 10.1016/j.atherosclerosis.2018.05.014

    M3 - Article

    VL - 274

    SP - 182

    EP - 190

    JO - Atherosclerosis

    JF - Atherosclerosis

    SN - 0021-9150

    ER -