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      Nondiabetic Glucometabolic Status and Progression of Aortic Stiffness: The Whitehall II Study

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          Abstract

          OBJECTIVE

          Aortic stiffness is an important predictor of future morbidity and mortality. Diabetes is associated with increased aortic stiffness, but the importance of nondiabetic glucometabolic status for accelerated aortic stiffening is unclear. We tested the hypothesis that adverse glucometabolic status is associated with accelerated aortic stiffening in individuals without diabetes, independently of known risk factors for arterial stiffening.

          RESEARCH DESIGN AND METHODS

          Glucometabolic status and other cardiovascular risk factors were assessed at baseline in 2008–09, and carotid femoral pulse wave velocity (cfPWV) at baseline and follow-up in 2012–13, in 4,386 participants without diabetes of the Whitehall II Study.

          RESULTS

          The mean age of the cohort at cfPWV baseline was 60 years, and 74% were male. cfPWV increased from (mean ± SE) 8.30 ± 0.03 to 8.98 ± 0.04 m/s during 4 years of follow-up. At baseline, cfPWV was associated with fasting and 2-h postload glucose, HbA 1c, and HOMA-insulin resistance (HOMA-IR). HbA 1c and HOMA-IR were associated with progression of cfPWV after adjusting for physiological confounders and cardiovascular risk factors. A 1 SD higher HbA 1c and HOMA-IR were associated with greater increases in cfPWV (0.11 m/s per 5 years [95% CI 0.04, 0.18], P = 0.003 and 0.09 m/s per 5 years [0.01, 0.17], P = 0.03, respectively). Additional adjustment for BMI weakened the association with HOMA-IR but not with HbA 1c.

          CONCLUSIONS

          HbA 1c is independently associated with accelerated progression of aortic stiffness in individuals without diabetes. These findings suggest that long-term glucometabolic status, even in individuals without diabetes, could be an important target for preventative strategies against vascular aging.

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          Most cited references54

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          Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man

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            Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects.

            The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors. Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups. We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p  70 years, respectively; pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor of coronary heart disease (HR: 1.23 [95% CI: 1.11 to 1.35]; p < 0.001), stroke (HR: 1.28 [95% CI: 1.16 to 1.42]; p < 0.001), and CVD events (HR: 1.30 [95% CI: 1.18 to 1.43]; p < 0.001). Reclassification indices showed that the addition of aPWV improved risk prediction (13% for 10-year CVD risk for intermediate risk) for some subgroups. Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association.

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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                April 2017
                25 January 2017
                : 40
                : 4
                : 599-606
                Affiliations
                [1] 1Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, U.K.
                [2] 2Steno Diabetes Center A/S, Gentofte, Denmark
                [3] 3Danish Diabetes Academy, Odense, Denmark
                [4] 4Department of Public Health, Aarhus University, Aarhus, Denmark
                [5] 5Research Department of Epidemiology and Public Health, University College London, London, U.K.
                [6] 61st Department of Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary
                Author notes
                Corresponding author: Carmel M. McEniery, cmm41@ 123456cam.ac.uk .
                Author information
                http://orcid.org/0000-0003-3636-0705
                Article
                1773
                10.2337/dc16-1773
                5360278
                28122839
                a8960e02-0add-43de-b63b-d3692af4f74a
                © 2017 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

                History
                : 16 August 2016
                : 6 January 2017
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 51, Pages: 8
                Funding
                Funded by: British Heart Foundation, DOI http://dx.doi.org/10.13039/501100000274;
                Award ID: RG/13/2/30098
                Funded by: British Medical Research Council, DOI http://dx.doi.org/xxx;
                Award ID: K013351
                Funded by: British Stroke Association, DOI http://dx.doi.org/xxx;
                Award ID: TSA 2008/05
                Funded by: National Heart, Lung, and Blood Institute, DOI http://dx.doi.org/10.13039/100000050;
                Award ID: R01-HL-036310
                Funded by: National Institute on Aging, DOI http://dx.doi.org/10.13039/100000049;
                Award ID: R01-AG-013196
                Award ID: R01-AG-034454
                Categories
                Cardiovascular and Metabolic Risk

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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