ACE-inhibition and physical function: results from the Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study

Objectives: Aim of the present study was to evaluate whether an ACE inhibitor intervention is able to significantly improve physical performance and muscle strength in a sample of older persons.

Design: Double-blind, cross-over, randomized, placebo-controlled trial.

Setting: The Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.

Participants: Participants were 257 subjects aged 55 years and older with high cardiovascular risk profile.

Intervention: Six months of fosinopril use versus placebo.

Measurements: The Short Physical Performance Battery score (rescaled to obtain a continuous variable ranging from 0 to 3 points), and the hand grip strength were measured at the baseline visit, and after 6 and 12 months of follow-up. Paired t test analyses were performed to compare results of physical function measures after ACE inhibition and placebo interventions.

Results: Mean age of the sample population was 65.97 (standard deviation 7.41) years old. No statistically significant difference was found at the Short Physical Performance Battery (P=.23) and hand grip strength (P=.57) results after ACE inhibition (2.113, standard deviation [SD] 0.284; and 37.044 kg, SD 12.993 kg, respectively) compared to placebo (2.096, SD 0.298; and 36.898 kg, SD 13.178 kg, respectively). No significant effects from ACE inhibition were also found when the 3 subtests composing the Short Physical Performance Battery (ie, 4-meter walking speed, balance, and chair stand tests) were separately analyzed. Consistent negative results were obtained after analyses were restricted to participants showing the highest compliance to treatment and/or receiving the maximum fosinopril dosage.

Conclusion: No significant modifications in physical performance and muscle strength were reported after 6 months of fosinopril use in older persons with high cardiovascular risk profile. Given these negative findings, it is possible that the beneficial effects of ACE inhibitors on physical function might be attributable to the activation of a virtuous cycle determined by an improved cardiovascular system. Further specifically designed studies are needed to confirm our findings, and expand them to different populations and ACE inhibitors. If our findings will be confirmed, the extracardiovascular properties of ACE inhibitors in older persons might be substantially resized.