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Review
. 2015 Oct;38(10):1921-9.
doi: 10.2337/dc14-2732. Epub 2015 Jul 15.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration

Matthias W Lorenz  1 , Jackie F Price  2 , Christine Robertson  2 , Michiel L Bots  3 , Joseph F Polak  4 , Holger Poppert  5 , Maryam Kavousi  6 , Marcus Dörr  7 , Eva Stensland  8 , Pierre Ducimetiere  9 , Kimmo Ronkainen  10 , Stefan Kiechl  11 , Matthias Sitzer  12 , Tatjana Rundek  13 , Lars Lind  14 , Jing Liu  15 , Göran Bergström  16 , Liliana Grigore  17 , Lena Bokemark  16 , Alfonsa Friera  18 , David Yanez  19 , Horst Bickel  20 , M Arfan Ikram  6 , Henry Völzke  21 , Stein Harald Johnsen  22 , Jean Philippe Empana  23 , Tomi-Pekka Tuomainen  10 , Peter Willeit  24 , Helmuth Steinmetz  25 , Moise Desvarieux  26 , Wuxiang Xie  15 , Caroline Schmidt  16 , Giuseppe D Norata  27 , Carmen Suarez  28 , Dirk Sander  29 , Albert Hofman  30 , Ulf Schminke  31 , Ellisiv Mathiesen  22 , Matthieu Plichart  32 , Jussi Kauhanen  10 , Johann Willeit  11 , Ralph L Sacco  13 , Stela McLachlan  2 , Dong Zhao  15 , Björn Fagerberg  16 , Alberico L Catapano  33 , Rafael Gabriel  34 , Oscar H Franco  6 , Alpaslan Bülbül  25 , Frank Scheckenbach  25 , Anja Pflug  25 , Lu Gao  35 , Simon G Thompson  36
Affiliations
Review

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration

Matthias W Lorenz et al. Diabetes Care. 2015 Oct.

Abstract

Objective: Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.

Research design and methods: In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.

Results: Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).

Conclusions: Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

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Figures

Figure 1
Figure 1
Forest plot of HR of the combined end point (MI, stroke, or vascular death) per SD of average mean CCA-IMT in subjects with diabetes. Note that pooled small studies included Atherosclerosis and Insulin Resistance study (AIR); CAPS; Chinese Multi-provincial Cohort Study (CMCS); Diabetes, Impaired glucose tolerance in Women and Atherosclerosis (DIWA); Edinburgh Artery Study (EAS); Estudio epidemiológico sobre enfermedades y factores de riesgo cardiovasculares en ancianos españoles (EPICARDIAN); Kuopio Ischaemic Heart Disease study (KIHD); NOMAS/INVEST; Progression of Lesions in the Intima of the Carotid (PLIC); and Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR).
Figure 2
Figure 2
Forest plot of HR of the combined end point (MI, stroke, or vascular death) per SD of annual mean CCA-IMT progression in subjects with diabetes. Note that pooled small studies included Atherosclerosis and Insulin Resistance study (AIR); CAPS; Chinese Multi-provincial Cohort Study (CMCS); Diabetes, Impaired glucose tolerance in Women and Atherosclerosis (DIWA); Edinburgh Artery Study (EAS); Estudio epidemiológico sobre enfermedades y factores de riesgo cardiovasculares en ancianos españoles (EPICARDIAN); NOMAS/INVEST; Progression of Lesions in the Intima of the Carotid (PLIC); and Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR).
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