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; Silvia Pinnola; Elena Venturi; Michaela Kozakova; Li-Ming Gan; Volker Schnecke; Jan Nilsson; SUMMIT Consortium

doi:10.1186/s12872-016-0346-8

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 BelchSilvia Pinnola, Elena Venturi, Michaela Kozakova, Li-Ming Gan, Volker Schnecke, Jan Nilsson (Lead / Corresponding author), SUMMIT Consortium

Molecular and Clinical Medicine

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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 language	English
Article number	171
Pages (from-to)	1-10
Number of pages	10
Journal	BMC Cardiovascular Disorders
Volume	16
DOIs	https://doi.org/10.1186/s12872-016-0346-8
Publication status	Published - 5 Sept 2016

Keywords

Renin
Type 2 diabetes
Atherosclerosis
Arterial stiffness
Endothelial dysfunction

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© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Gonçalves, I., Edsfeldt, A., Colhoun, H. M., Shore, A. C., Palombo, C., Natali, A., Fredrikson, G. N., Björkbacka, H., Wigren, M., Bengtsson, E., Östling, G., Aizawa, K., Casanova, F., Persson, M., Gooding, K., Gates, P., Khan, F., Looker, H. C., Adams, F., ... SUMMIT Consortium (2016). Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes. BMC Cardiovascular Disorders, 16, 1-10. Article 171. https://doi.org/10.1186/s12872-016-0346-8

@article{5f93786272774c44850ce15b4021eaa3,

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{\c c}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)",

year = "2016",

month = sep,

day = "5",

doi = "10.1186/s12872-016-0346-8",

language = "English",

volume = "16",

pages = "1--10",

journal = "BMC Cardiovascular Disorders",

issn = "1471-2261",

publisher = "Springer Verlag",

}

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

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

C2 - 27596252

SN - 1471-2261

VL - 16

SP - 1

EP - 10

JO - BMC Cardiovascular Disorders

JF - BMC Cardiovascular Disorders

M1 - 171

ER -

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

Abstract

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