Relation of angiotensin-converting enzyme inhibitor treatment to insulin-like growth factor-1 serum levels in subjects >65 years of age (the InCHIANTI study)

Abstract

Observational studies have shown that the use of angiotensin-converting enzyme (ACE) inhibitors is associated with the maintenance of greater muscle strength and physical performance in older subjects. However, the mechanism that underlies these beneficial effects remains poorly understood. Because ACE inhibitors block the production of angiotensin II, which is a potent inhibitor of insulin-like growth factor-1 (IGF-1) production, it was hypothesized that treatment with ACE inhibitors is associated with higher levels of IGF-1. This hypothesis was tested in 745 subjects (417 women, 328 men) enrolled in the Invecchiare in Chianti study. Of these, 160 were receiving ACE inhibitors. The association between ACE inhibitor use and serum IGF-1 was tested by linear regression models. After adjusting for multiple potential confounders, serum levels of total IGF-1 were significantly higher in participants receiving ACE inhibitors (mean +/- SD 129.0 +/- 56.1 ng/ml) compared with the rest of the study population (mean +/- SD 116.5 +/- 54.8 ng/ml) (p <0.001). Participants with short (<3 years) and long (3 to 9 years) treatment durations had higher serum IGF-1 levels than participants who were not receiving ACE inhibitor treatment, but the difference was statistically significant only for the short-duration group (p <0.05). In conclusion, in older subjects, treatment with ACE inhibitors for <3 years is associated with significantly higher levels of IGF-1. This may be 1 of the mechanisms by which ACE inhibitors might slow the decreases in muscle strength and physical function that are often observed in older subjects.

Figure 1

Box plots depicting total IGF-1 distributions in participants receiving treatment with ACE inhibitors by relative potency. The center line within the box indicates the median value of the distribution, and the top and bottom box limits are, respectively, the 25th and 75th percentiles. The whiskers extend to the most extreme points located with 1.5 times the interquartile distance below and above the box. The test for a trend was not statistically significant.

Figure 2

Total IGF-1 levels according to duration of treatment with ACE inhibitors (years). Total IGF-1 values are reported as means ± SEs. Tests of comparison were adjusted for age, gender, hypertension, cardiac heart failure, coronary heart disease, diabetes, and the number of medications, with nonusers as the reference group.