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

Abstract

Structured Abstract Objective Aortic stiffness is an important predictor of future morbidity and mortality. Diabetes is associated with increased aortic stiffness, but the importance of non-diabetic glucometabolic status for accelerated aortic stiffening is unclear. We tested the hypothesis that adverse glucometabolic status is associated with accelerated aortic stiffening in non-diabetic individuals, 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 4386 non-diabetic participants 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 over 4 years of follow-up. At baseline, cfPWV was associated with fasting and 2-hour postload glucose, HbA1c, and HOMA-insulin resistance (HOMA-IR). HbA1c and HOMA-IR were associated with progression of cfPWV after adjusting for physiological confounders and cardiovascular risk factors. A 1SD higher HbA1c and HOMA-IR were associated with greater increases in cfPWV (0.11m/s per 5 years, 95%CI 0.04, 0.18, P=0.003 and 0.09m/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 HbA1c. Conclusions HbA1c is independently associated with accelerated progression of aortic stiffness in non-diabetic individuals. These findings suggest that long-term glucometabolic status, even in non-diabetic individuals, could be an important target for preventative strategies against vascular ageing.

Association of insulin resistance, from mid-life to late-life, with aortic stiffness in late-life: the Atherosclerosis Risk in Communities Study

“…Change in insulin resistance may be minimal in the absence of weight change [35]; or obscured by the lack of standardization of insulin assays that hinder the comparison of assays over time [15]. However, a recent study has reported an association between an increase in long-term glucometabolic impairment and an increase in aortic stiffness associated with hemoglobin A1c and HOMA-IR [36]. Recent reports identified associations of aortic stiffness with dysregulation in various metabolic pathways in the setting of type 2 diabetes.…”

Non-invasive measurements of arterial function: What? When? Why should we use them?

“…High aortic PWV has been shown, in two meta-analyses, to be associated with increased risk of CV events,14 15 independent of conventional risk factors of the FRS,15 with the caveat of study heterogeneity 16. In longitudinal studies, aortic PWV predicted CV mortality in the general population and in subjects with hypertension, diabetes mellitus (DM), glucose intolerance and chronic kidney disease 17–24. Nonpharmacological interventions, such as moderate-to-high exercise levels reduced progression of PWV compared with a sedentary lifestyle 25.…”

Association of aortic stiffness with cognitive decline: Whitehall II longitudinal cohort study

“…Aortic stiffness, due to loss of elasticity of the artery wall, increases with age and risk factor exposure [4][5][6][7] is associated with higher systolic, pulse pressure and atherosclerosis [8], which are in turn important predictors of cardio-and cerebrovascular morbidity and mortality as well as predictors of cognitive decline [9]. The links between cardiovascular disorders and cognitive decline and dementia remain unclear.…”