Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes

Isabel Gonçalves, Andreas Edsfeldt, Helen M. Colhoun, Angela C. Shore, Carlo Palombo, Andrea Natali, Gunilla Nordin Fredrikson, Harry Björkbacka, Maria Wigren, Eva Bengtsson, Gerd Östling, Kunihiko Aizawa, Francesco Casanova, Margaretha Persson, Kim Gooding, Phil Gates, Faisel Khan, Helen C. Looker, Fiona Adams, Jill Belch & 7 others Silvia Pinnola, Elena Venturi, Michaela Kozakova, Li-Ming Gan, Volker Schnecke, Jan Nilsson, SUMMIT Consortium

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Abstract

BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D.

METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI).

RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients.

CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.

Original languageEnglish
Article number171
Pages (from-to)1-10
Number of pages10
JournalBMC Cardiovascular Disorders
Volume16
DOIs
Publication statusPublished - 5 Sep 2016

Fingerprint

Renin
Type 2 Diabetes Mellitus
Blood Vessels
Renin-Angiotensin System
Carotid Intima-Media Thickness
Ankle Brachial Index
Endarterectomy
Pulse Wave Analysis
Vascular Stiffness
Carotid Endarterectomy
Hyperemia
Body Mass Index
Cardiovascular Diseases
Biomarkers
Pressure

Keywords

  • Renin
  • Type 2 diabetes
  • Atherosclerosis
  • Arterial stiffness
  • Endothelial dysfunction

Cite this

Gonçalves, I., Edsfeldt, A., Colhoun, H. M., Shore, A. C., Palombo, C., Natali, A., ... SUMMIT Consortium (2016). Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes. BMC Cardiovascular Disorders, 16, 1-10. [171]. https://doi.org/10.1186/s12872-016-0346-8
Gonçalves, Isabel ; Edsfeldt, Andreas ; Colhoun, Helen M. ; Shore, Angela C. ; Palombo, Carlo ; Natali, Andrea ; Fredrikson, Gunilla Nordin ; Björkbacka, Harry ; Wigren, Maria ; Bengtsson, Eva ; Östling, Gerd ; Aizawa, Kunihiko ; Casanova, Francesco ; Persson, Margaretha ; Gooding, Kim ; Gates, Phil ; Khan, Faisel ; Looker, Helen C. ; Adams, Fiona ; Belch, Jill ; Pinnola, Silvia ; Venturi, Elena ; Kozakova, Michaela ; Gan, Li-Ming ; Schnecke, Volker ; Nilsson, Jan ; SUMMIT Consortium. / Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes. In: BMC Cardiovascular Disorders. 2016 ; Vol. 16. pp. 1-10.
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title = "Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes",
abstract = "BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D.METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI).RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients.CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.",
keywords = "Renin, Type 2 diabetes, Atherosclerosis, Arterial stiffness, Endothelial dysfunction",
author = "Isabel Gon{\cc}alves and Andreas Edsfeldt and Colhoun, {Helen M.} and Shore, {Angela C.} and Carlo Palombo and Andrea Natali and Fredrikson, {Gunilla Nordin} and Harry Bj{\"o}rkbacka and Maria Wigren and Eva Bengtsson and Gerd {\"O}stling and Kunihiko Aizawa and Francesco Casanova and Margaretha Persson and Kim Gooding and Phil Gates and Faisel Khan and Looker, {Helen C.} and Fiona Adams and Jill Belch and Silvia Pinnola and Elena Venturi and Michaela Kozakova and Li-Ming Gan and Volker Schnecke and Jan Nilsson and {SUMMIT Consortium}",
note = "Funding - Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006, the Swedish Heart-Lung Foundation, the Swedish Research Council and Marianne and Marcus Wallenberg Foundation)",
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Gonçalves, I, Edsfeldt, A, Colhoun, HM, Shore, AC, Palombo, C, Natali, A, Fredrikson, GN, Björkbacka, H, Wigren, M, Bengtsson, E, Östling, G, Aizawa, K, Casanova, F, Persson, M, Gooding, K, Gates, P, Khan, F, Looker, HC, Adams, F, Belch, J, Pinnola, S, Venturi, E, Kozakova, M, Gan, L-M, Schnecke, V, Nilsson, J & SUMMIT Consortium 2016, 'Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes', BMC Cardiovascular Disorders, vol. 16, 171, pp. 1-10. https://doi.org/10.1186/s12872-016-0346-8

Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes. / Gonçalves, Isabel; Edsfeldt, Andreas; Colhoun, Helen M.; Shore, Angela C.; Palombo, Carlo; Natali, Andrea; Fredrikson, Gunilla Nordin; Björkbacka, Harry; Wigren, Maria; Bengtsson, Eva; Östling, Gerd; Aizawa, Kunihiko; Casanova, Francesco; Persson, Margaretha; Gooding, Kim; Gates, Phil; Khan, Faisel; Looker, Helen C.; Adams, Fiona; Belch, Jill; Pinnola, Silvia; Venturi, Elena; Kozakova, Michaela; Gan, Li-Ming; Schnecke, Volker; Nilsson, Jan (Lead / Corresponding author); SUMMIT Consortium.

In: BMC Cardiovascular Disorders, Vol. 16, 171, 05.09.2016, p. 1-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes

AU - Gonçalves, Isabel

AU - Edsfeldt, Andreas

AU - Colhoun, Helen M.

AU - Shore, Angela C.

AU - Palombo, Carlo

AU - Natali, Andrea

AU - Fredrikson, Gunilla Nordin

AU - Björkbacka, Harry

AU - Wigren, Maria

AU - Bengtsson, Eva

AU - Östling, Gerd

AU - Aizawa, Kunihiko

AU - Casanova, Francesco

AU - Persson, Margaretha

AU - Gooding, Kim

AU - Gates, Phil

AU - Khan, Faisel

AU - Looker, Helen C.

AU - Adams, Fiona

AU - Belch, Jill

AU - Pinnola, Silvia

AU - Venturi, Elena

AU - Kozakova, Michaela

AU - Gan, Li-Ming

AU - Schnecke, Volker

AU - Nilsson, Jan

AU - SUMMIT Consortium

N1 - Funding - Innovative Medicines Initiative (the SUMMIT consortium, IMI-2008/115006, the Swedish Heart-Lung Foundation, the Swedish Research Council and Marianne and Marcus Wallenberg Foundation)

PY - 2016/9/5

Y1 - 2016/9/5

N2 - BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D.METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI).RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients.CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.

AB - BACKGROUND: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D.METHODS: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI).RESULTS: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients.CONCLUSIONS: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.

KW - Renin

KW - Type 2 diabetes

KW - Atherosclerosis

KW - Arterial stiffness

KW - Endothelial dysfunction

U2 - 10.1186/s12872-016-0346-8

DO - 10.1186/s12872-016-0346-8

M3 - Article

VL - 16

SP - 1

EP - 10

JO - BMC Cardiovascular Disorders

JF - BMC Cardiovascular Disorders

SN - 1471-2261

M1 - 171

ER -