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

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.

Figure 1

The association between HbA_1c and change in cfPWV. Plotted points show the cfPWV change per 5 years for each quintile of HbA_1c, plotted at the median of each quintile. The solid line shows the linear association, and the dashed lines show the 95% CI. Values shown are adjusted to white men without diabetes at age 65 with a MAP of 90 mmHg. Test for quadratic (nonlinear) effect gave a P value = 0.48.