The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: a randomized factorial design trial.
Level 2 - randomized trial
Individual randomized controlled trial with a 2x2 factorial design.
PubMed 24400341 · doi:10.1016/j.exger.2013.10.009
What was done
Forty-eight sedentary, healthy older adults (mean age 70 ± 4 years) without manifest disease or medication use were randomized in a 1-year 2x2 factorial trial into four groups: exercise training plus alagebrium (200 mg/day), exercise training plus placebo, no exercise plus alagebrium (200 mg/day), or no exercise plus placebo. Investigators measured maximal aerobic capacity (VO2max), endothelial function via venous occlusion plethysmography with intra-arterial infusions of acetylcholine, sodium nitroprusside, and L-NMMA, arterial stiffness via pulse wave velocity, and calculated cardiovascular risk using the Lifetime Risk Score (LRS).
What was found
In the exercise groups, VO2max improved significantly from 23.9 ± 4.5 to 27.2 ± 4.6 mL O2/min/kg (p < 0.001), and LRS improved significantly. However, endothelial responses to vasoactive infusions did not change, and arterial stiffness did not change in any of the four groups. Alagebrium demonstrated no independent effect on vascular function and did not potentiate the effects of exercise training.
Why it matters
Preclinical animal models suggested that breaking advanced glycation end-product crosslinks with alagebrium combined with exercise could reverse cardiovascular aging. This trial shows that in older humans, a 1-year regimen of exercise and alagebrium improves fitness and risk scores but fails to reverse established arterial stiffness or endothelial dysfunction.
Limits
The total sample size was small (48 participants across 4 arms, roughly 12 per group), limiting statistical power to detect subtle vascular changes. The cohort was restricted to unmedicated, healthy older individuals, which limits generalizability to older adults with clinical cardiovascular disease or diabetes. Numerical results for endothelial responsiveness and pulse wave velocity are not reported in the abstract.
Cited by
- contradicts In sedentary 70-year-olds, combining 1 year of exercise training with an advanced glycation end-product (AGE) cross-link breaker resulted in the equivalent of approximately a 15-year reduction in vascular age, whereas either intervention alone produced no benefit.