Abstract Body (Do not enter title and authors here): Background: Total pulse wave velocity (PWV) can be subdivided into two mechanisms: load-dependent PWV due to the distending effect of blood pressure and structural PWV due to arterial wall remodeling. Hyperglycemia and diabetes are associated with greater total arterial stiffness, however, their impact on the mechanistic components of arterial stiffness is not known.
Hypothesis: Elevated hemoglobin A1c (HbA1c), a marker of poor long-term glucose control, will be associated with increasing structural PWV over time.
Methods: 2728 participants in the Multi-Ethnic Study of Atherosclerosis cohort had initial HbA1c measured a median of 1.6 (25^th,75^th percentile [1.4, 1.8]) years post-baseline (exam 2). B-mode carotid ultrasound was used to calculate total carotid PWV at baseline (exam 1) and again after 9.5 [9.2, 9.8] years (exam 5). Structural PWV was determined by adjusting the PWV to a blood pressure of 120/80 mmHg using a non-linear pressure-diameter relationship, while load-dependent PWV was obtained by subtracting structural PWV from total PWV. Multivariable linear regression models related HbA1c to PWV adjusted for baseline demographics and cardiovascular risk factors. Continuous variables were modeled as restricted cubic splines to allow for non-linear associations.
Results: At baseline, participants were 59 [52, 67] years old, and 240 (8.9%) had diabetes. HbA1c measured at exam 2 was 5.4 [5.2, 5.8] percent. Higher HbA1c was associated with higher total PWV, structural PWV and load-dependent PWV (p<0.001) at exam 5. The associations of HbA1c with total and structural PWV were notably non-linear, with stiffness beginning to increase at an HbA1c at ~5% and plateauing at an HbA1c of approximately 6.5% (Figure). Between individuals with high-versus-low HbA1c (7 vs 5 %), the difference in total PWV over 9.5 years (0.61 [0.37, 0.84] m/s) was primarily driven by structural PWV (0.52 [0.30, 0.74] m/s).
Conclusion: Elevated HbA1c values above 5% were associated with increasing total carotid stiffness. This difference in total PWV was driven primarily by increasing structural stiffness.