Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study

Jack R W Brownrigg; Cian O Hughes; David Burleigh; Alan Karthikesalingam; Benjamin O Patterson; Peter J Holt; Matthew M Thompson; Simon de Lusignan; Kausik K Ray; Robert J Hinchliffe

doi:10.1016/S2213-8587(16)30057-2

Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study

Jack R W Brownrigg, Cian O Hughes, David Burleigh, Alan Karthikesalingam, Benjamin O Patterson, Peter J Holt, Matthew M Thompson, Simon de Lusignan, Kausik K Ray, Robert J Hinchliffe

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

113 Citations (Scopus)

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Abstract

BACKGROUND: Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown.

METHODS: A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.

FINDINGS: During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.

INTERPRETATION: The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.

FUNDING: Circulation Foundation.

Original language	English
Pages (from-to)	588-597
Number of pages	10
Journal	Lancet Diabetes and Endocrinology
Volume	4
Issue number	7
Early online date	20 May 2016
DOIs	https://doi.org/10.1016/S2213-8587(16)30057-2
Publication status	Published - 1 Jul 2016

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Centre for Surgical Research

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10.1016/S2213-8587(16)30057-2

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ConDuCT-II
Blazeby, J.
1/04/14 → 31/03/19
Project: Research

Professor Robert J Hinchliffe
- robert.hinchliffe@bristol.ac.uk
- Bristol Medical School (THS) - Clinical Professor of Vascular Surgery
- Bristol Population Health Science Institute
Person: Academic , Member

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Brownrigg, J. R. W., Hughes, C. O., Burleigh, D., Karthikesalingam, A., Patterson, B. O., Holt, P. J., Thompson, M. M., de Lusignan, S., Ray, K. K., & Hinchliffe, R. J. (2016). Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study. Lancet Diabetes and Endocrinology, 4(7), 588-597. https://doi.org/10.1016/S2213-8587(16)30057-2

Brownrigg, Jack R W ; Hughes, Cian O ; Burleigh, David ; Karthikesalingam, Alan ; Patterson, Benjamin O ; Holt, Peter J ; Thompson, Matthew M ; de Lusignan, Simon ; Ray, Kausik K ; Hinchliffe, Robert J. / Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes : a population-level cohort study. In: Lancet Diabetes and Endocrinology. 2016 ; Vol. 4, No. 7. pp. 588-597.

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title = "Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study",

abstract = "BACKGROUND: Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown.METHODS: A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.FINDINGS: During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.INTERPRETATION: The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.FUNDING: Circulation Foundation.",

author = "Brownrigg, {Jack R W} and Hughes, {Cian O} and David Burleigh and Alan Karthikesalingam and Patterson, {Benjamin O} and Holt, {Peter J} and Thompson, {Matthew M} and {de Lusignan}, Simon and Ray, {Kausik K} and Hinchliffe, {Robert J}",

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Brownrigg, JRW, Hughes, CO, Burleigh, D, Karthikesalingam, A, Patterson, BO, Holt, PJ, Thompson, MM, de Lusignan, S, Ray, KK & Hinchliffe, RJ 2016, 'Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study', Lancet Diabetes and Endocrinology, vol. 4, no. 7, pp. 588-597. https://doi.org/10.1016/S2213-8587(16)30057-2

Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes : a population-level cohort study. / Brownrigg, Jack R W; Hughes, Cian O; Burleigh, David; Karthikesalingam, Alan; Patterson, Benjamin O; Holt, Peter J; Thompson, Matthew M; de Lusignan, Simon; Ray, Kausik K; Hinchliffe, Robert J.

In: Lancet Diabetes and Endocrinology, Vol. 4, No. 7, 01.07.2016, p. 588-597.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes

T2 - a population-level cohort study

AU - Brownrigg, Jack R W

AU - Hughes, Cian O

AU - Burleigh, David

AU - Karthikesalingam, Alan

AU - Patterson, Benjamin O

AU - Holt, Peter J

AU - Thompson, Matthew M

AU - de Lusignan, Simon

AU - Ray, Kausik K

AU - Hinchliffe, Robert J

PY - 2016/7/1

Y1 - 2016/7/1

N2 - BACKGROUND: Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown.METHODS: A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.FINDINGS: During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.INTERPRETATION: The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.FUNDING: Circulation Foundation.

AB - BACKGROUND: Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk among individuals with diabetes is unknown.METHODS: A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.FINDINGS: During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.INTERPRETATION: The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.FUNDING: Circulation Foundation.

U2 - 10.1016/S2213-8587(16)30057-2

DO - 10.1016/S2213-8587(16)30057-2

M3 - Article (Academic Journal)

C2 - 27216886

VL - 4

SP - 588

EP - 597

JO - Lancet Diabetes and Endocrinology

JF - Lancet Diabetes and Endocrinology

SN - 2213-8587

IS - 7

ER -

Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study

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