Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial

Helen M. Colhoun; D. John Betteridge; Paul Durrington; Graham Hitman; Andrew Neil; Shona Livingstone; Valentine Charlton-Menys; Weihang Bao; David A. DeMicco; Gregory M. Preston; Harshal Deshmukh; Kathryn Tan; John H. Fuller

doi:10.2337/db11-0291

Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial

Helen M. Colhoun (Lead / Corresponding author), D. John Betteridge, Paul Durrington, Graham Hitman, Andrew Neil, Shona Livingstone, Valentine Charlton-Menys, Weihang Bao, David A. DeMicco, Gregory M. Preston, Harshal Deshmukh, Kathryn Tan, John H. Fuller

Research output: Contribution to journal › Article › peer-review

147 Citations (Scopus)

Abstract

Objective: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).

Research Design and Methods: We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.

Results: sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.

Conclusions: Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.

Original language	English
Pages (from-to)	2379-2385
Number of pages	7
Journal	Diabetes
Volume	60
Issue number	9
Early online date	19 Jul 2011
DOIs	https://doi.org/10.2337/db11-0291
Publication status	Published - Sept 2011

Keywords

Cardiovascular disease
Endproducts rage
Association
Atherosclerosis
Complications
Failure
Level
Srage
Gene
Form

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Colhoun, H. M., Betteridge, D. J., Durrington, P., Hitman, G., Neil, A., Livingstone, S., Charlton-Menys, V., Bao, W., DeMicco, D. A., Preston, G. M., Deshmukh, H., Tan, K., & Fuller, J. H. (2011). Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial. Diabetes, 60(9), 2379-2385. https://doi.org/10.2337/db11-0291

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title = "Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial",

abstract = "Objective: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).Research Design and Methods: We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.Results: sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.Conclusions: Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.",

keywords = "Cardiovascular disease, Endproducts rage, Association, Atherosclerosis, Complications, Failure, Level, Srage, Gene, Form",

author = "Colhoun, {Helen M.} and Betteridge, {D. John} and Paul Durrington and Graham Hitman and Andrew Neil and Shona Livingstone and Valentine Charlton-Menys and Weihang Bao and DeMicco, {David A.} and Preston, {Gregory M.} and Harshal Deshmukh and Kathryn Tan and Fuller, {John H.}",

year = "2011",

month = sep,

doi = "10.2337/db11-0291",

language = "English",

volume = "60",

pages = "2379--2385",

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Colhoun, HM, Betteridge, DJ, Durrington, P, Hitman, G, Neil, A, Livingstone, S, Charlton-Menys, V, Bao, W, DeMicco, DA, Preston, GM, Deshmukh, H, Tan, K & Fuller, JH 2011, 'Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial', Diabetes, vol. 60, no. 9, pp. 2379-2385. https://doi.org/10.2337/db11-0291

Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial. / Colhoun, Helen M. (Lead / Corresponding author); Betteridge, D. John; Durrington, Paul et al.
In: Diabetes, Vol. 60, No. 9, 09.2011, p. 2379-2385.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes

T2 - an analysis from the CARDS trial

AU - Colhoun, Helen M.

AU - Betteridge, D. John

AU - Durrington, Paul

AU - Hitman, Graham

AU - Neil, Andrew

AU - Livingstone, Shona

AU - Charlton-Menys, Valentine

AU - Bao, Weihang

AU - DeMicco, David A.

AU - Preston, Gregory M.

AU - Deshmukh, Harshal

AU - Tan, Kathryn

AU - Fuller, John H.

PY - 2011/9

Y1 - 2011/9

N2 - Objective: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).Research Design and Methods: We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.Results: sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.Conclusions: Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.

AB - Objective: Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoforrn (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).Research Design and Methods: We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.Results: sRAGE and esRAGE were strongly correlated (rho = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.Conclusions: Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.

KW - Cardiovascular disease

KW - Endproducts rage

KW - Association

KW - Atherosclerosis

KW - Complications

KW - Failure

KW - Level

KW - Srage

KW - Gene

KW - Form

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U2 - 10.2337/db11-0291

DO - 10.2337/db11-0291

M3 - Article

C2 - 21771973

SN - 0012-1797

VL - 60

SP - 2379

EP - 2385

JO - Diabetes

JF - Diabetes

IS - 9

ER -

Total soluble and endogenous secretory receptor for advanced glycation end products as predictive biomarkers of coronary heart disease risk in patients with type 2 Diabetes: an analysis from the CARDS trial

Abstract

Keywords

UN SDGs

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