Discussion
muscle mass, sarcopenic
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, RECRUITMENT
Our data show that, in the LACE cohort of sarcopenic individuals, the number of men carrying the I allele (II and ID combined) was lower than predicted from the general UK population. The I allele frequency in men in our study is 0.353 compared to the expected 0.474. Furthermore, we found that II/ID men had greater muscle strength than those with the DD genotype. This observation is opposite to the effects of the I/D polymorphism seen in the non-sarcopenic population where the D allele is found enriched in power athletes and is associated with greater muscle mass and strength in a number of diverse cohorts including those representing elite athletes, normal healthy individuals and patients with chronic obstructive pulmonary disease [We did not observe either of these effects in women. Previous studies have shown that women have a higher proportion of type I fibres in the quadriceps compared to men [The LACE trial, from which these samples were taken, did not report any effect of perindopril on muscle mass or strength and a meta-analysis performed following the trial also concluded that ACE inhibition did not increase muscle mass or strength. In this analysis we show that there is no positive effect of ACE inhibition either in individuals with the II/ID genotypes or the DD genotypes although we did see an increase in muscle strength in DD individuals enrolled in the trial, whether or not they were on perindopril or leucine. The presence of this increase in strength may have been a consequence of a combination of the two agents that would have been identifiable had the trial been allowed to recruit its full cohort, a consequence of altered activity as a response to being recruited to a trial or potentially a type II error given the size of the trial. The reason that it is only observed in the DD group could suggest either that this group is most likely to respond to both activity and potentially to drug therapies due to a higher proportion of type II fibres or that as these individuals started with a lower QMVC there was a greater response to any increase in activity. Physical activity was not measured in this study. Whether trial recruitment acted as a trigger to increase activity would not have been detectable as it would not be possible to quantify pre-recruitment activity.Consistent with a change in behaviour, individuals carrying the I allele showed an increase in SPPB by 1 point over the 12 months. Both changes (increased strength in DD individuals and increased SPPB in II/ID individuals) only occurred in the absence of perindopril. It is not clear why this change was restricted to those not on perindopril but given the drop-out rate was higher for those on perindopril than those not taking perindopril, it is possible that adverse responses to perindopril treatment reduced the effect of being recruited to a trial.The LACE trial and a meta-analysis of available randomised controlled trials did not identify any effect of ACEi on muscle mass or strength (33), one possible reason for this is that the trial did not combine pharmacological treatment with exercise. In support of this possibility some studies have suggested that exercise responses are larger in patients taking ACEi than in those not taking ACEi [