3.1 reducing arterial stiffness independently of bp: proof of concept? cavi, pwv and cardiac data in the 6-month vasera trial

Purpose/ background/ objectives: People with or at risk of Type II diabetes (T2DM) are at increased risk of vascular disease and arterial stiffness (AS). We hypothesized that spironolactone and dietary nitrate (beetroot juice) separately and together would reduce AS, measured as cardiac-ankle vascular index (CAVI Fukuda Denshi, Japan mainly BP-independent) or aortic pulse wave velocity (PWV). Methods: 126 (60% T2DM) were randomized, double-blind to spironolactone (≤50mg) or doxazosin (control ≤16mg) and active/ placebo juice (≤9/0mmol) daily. AS and echocardiographic measures (on a subgroup) were performed. Intention-to-treat analysis adjusted for between-group blood pressure (BP) change over time was performed using SAS. Results: Change in (Δ)BP was not different between spironolactone and doxazosin (mean -6.7mmHg), nor between the juices. ΔCAVI was marginally reduced on doxazosin compared to spironolactone (−0.11[−0.30,0.08] vs. 0.14[−0.06,0.34] units, p=0.080) but more for aortic PWV (−0.44 [−0.69,−0.20] vs. −0.07 [−0.32,0.18]ms−2, p=0.04). Dietary nitrate had no impact, but did rise in plasma. Spironolactone improved Δrelative wall thickness vs. doxazosin (0.01[−0.02,−0.0], p<0.01). Dietary nitrate decreased left ventricular (LV) end diastolic and systolic volume (−6.3[−11.1,−1.6]mL and −3.2[−5.9,−0.5]mL, p<0.05) and increased end diastolic mass/volume (EDMV) ratio (0.04 [0,0.7] g/mL, p<0.05) vs. placebo. There were no drug–juice interactions. Conclusions: Contrary to our hypothesis, spironolactone did not reduce AS, rather central PWV declined on doxazosin. Spironolactone enhanced LV remodelling, while dietary nitrate improved LV volumes and the EDMV ratio, perhaps indicating improved LV strain.