Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes

The SUMMIT VIP Study

SUMMIT Consortium, Angela C. Shore, Helen M. Colhoun, Andrea Natali, Carlo Palombo, Faisel Khan, Gerd Östling, Kunihiko Aizawa, Cecilia Kennbäck, Francesco Casanova, Margaretha Persson, Kim Gooding, Phillip E Gates, Helen Looker, Fiona Dove, Jill Belch, Silvia Pinnola, Elena Venturi, Michaela Kozakova, Isabel Goncalves & 3 others Jasmina Kravic, Harry Björkbacka, Jan Nilsson

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS: The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS: The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm 2 [16.1-92.2] vs. 19.5 mm 2 [9.5-40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS: Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.

Original languageEnglish
Pages (from-to)2212-2219
Number of pages8
JournalDiabetes Care
Volume41
Issue number10
Early online date30 Jul 2018
DOIs
Publication statusPublished - 1 Oct 2018

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Type 2 Diabetes Mellitus
Blood Vessels
Cardiovascular Diseases
Biomarkers
Vascular Stiffness
Ankle Brachial Index
Carotid Intima-Media Thickness
Carotid Artery Diseases
Hepatocyte Growth Factor
Mitogens
Chemokines
Vascular Endothelial Growth Factor A
Interleukin-6
Atherosclerosis
Cohort Studies
Research Design
Ligands
Inflammation
Pressure

Keywords

  • Aged
  • Ankle Brachial Index
  • Biomarkers/blood
  • Cardiovascular Diseases/blood
  • Carotid Intima-Media Thickness
  • Cohort Studies
  • Diabetes Mellitus, Type 2/blood
  • Endothelial Cells/physiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic/blood
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Vascular Stiffness/physiology

Cite this

SUMMIT Consortium, Shore, A. C., Colhoun, H. M., Natali, A., Palombo, C., Khan, F., ... Nilsson, J. (2018). Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study. Diabetes Care, 41(10), 2212-2219. https://doi.org/10.2337/dc18-0185
SUMMIT Consortium ; Shore, Angela C. ; Colhoun, Helen M. ; Natali, Andrea ; Palombo, Carlo ; Khan, Faisel ; Östling, Gerd ; Aizawa, Kunihiko ; Kennbäck, Cecilia ; Casanova, Francesco ; Persson, Margaretha ; Gooding, Kim ; Gates, Phillip E ; Looker, Helen ; Dove, Fiona ; Belch, Jill ; Pinnola, Silvia ; Venturi, Elena ; Kozakova, Michaela ; Goncalves, Isabel ; Kravic, Jasmina ; Björkbacka, Harry ; Nilsson, Jan. / Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes : The SUMMIT VIP Study. In: Diabetes Care. 2018 ; Vol. 41, No. 10. pp. 2212-2219.
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title = "Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study",
abstract = "OBJECTIVE: Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS: The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS: The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm 2 [16.1-92.2] vs. 19.5 mm 2 [9.5-40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS: Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.",
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SUMMIT Consortium, Shore, AC, Colhoun, HM, Natali, A, Palombo, C, Khan, F, Östling, G, Aizawa, K, Kennbäck, C, Casanova, F, Persson, M, Gooding, K, Gates, PE, Looker, H, Dove, F, Belch, J, Pinnola, S, Venturi, E, Kozakova, M, Goncalves, I, Kravic, J, Björkbacka, H & Nilsson, J 2018, 'Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study', Diabetes Care, vol. 41, no. 10, pp. 2212-2219. https://doi.org/10.2337/dc18-0185

Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes : The SUMMIT VIP Study. / SUMMIT Consortium; Shore, Angela C.; Colhoun, Helen M.; Natali, Andrea; Palombo, Carlo; Khan, Faisel; Östling, Gerd; Aizawa, Kunihiko; Kennbäck, Cecilia; Casanova, Francesco; Persson, Margaretha; Gooding, Kim; Gates, Phillip E; Looker, Helen; Dove, Fiona; Belch, Jill; Pinnola, Silvia; Venturi, Elena; Kozakova, Michaela; Goncalves, Isabel; Kravic, Jasmina; Björkbacka, Harry; Nilsson, Jan (Lead / Corresponding author).

In: Diabetes Care, Vol. 41, No. 10, 01.10.2018, p. 2212-2219.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes

T2 - The SUMMIT VIP Study

AU - SUMMIT Consortium

AU - Shore, Angela C.

AU - Colhoun, Helen M.

AU - Natali, Andrea

AU - Palombo, Carlo

AU - Khan, Faisel

AU - Östling, Gerd

AU - Aizawa, Kunihiko

AU - Kennbäck, Cecilia

AU - Casanova, Francesco

AU - Persson, Margaretha

AU - Gooding, Kim

AU - Gates, Phillip E

AU - Looker, Helen

AU - Dove, Fiona

AU - Belch, Jill

AU - Pinnola, Silvia

AU - Venturi, Elena

AU - Kozakova, Michaela

AU - Goncalves, Isabel

AU - Kravic, Jasmina

AU - Björkbacka, Harry

AU - Nilsson, Jan

N1 - © 2018 by the American Diabetes Association.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - OBJECTIVE: Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS: The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS: The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm 2 [16.1-92.2] vs. 19.5 mm 2 [9.5-40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS: Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.

AB - OBJECTIVE: Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS: The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS: The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm 2 [16.1-92.2] vs. 19.5 mm 2 [9.5-40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS: Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.

KW - Aged

KW - Ankle Brachial Index

KW - Biomarkers/blood

KW - Cardiovascular Diseases/blood

KW - Carotid Intima-Media Thickness

KW - Cohort Studies

KW - Diabetes Mellitus, Type 2/blood

KW - Endothelial Cells/physiology

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Plaque, Atherosclerotic/blood

KW - Predictive Value of Tests

KW - Prognosis

KW - Risk Assessment

KW - Risk Factors

KW - Vascular Stiffness/physiology

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U2 - 10.2337/dc18-0185

DO - 10.2337/dc18-0185

M3 - Article

VL - 41

SP - 2212

EP - 2219

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 10

ER -