ACE-inhibition and Physical Function: Results from the Trial of Angiotensin-Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) Study

Overview

Journal J Am Med Dir Assoc

Publisher Elsevier

Specialty General Medicine

Date 2010 Feb 5

PMID 20129212

Citations 35

Authors

Matteo Cesari

Claudio Pedone

Raffaele Antonelli Incalzi

Marco Pahor

Affiliations

Soon will be listed here.

Abstract

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.

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References

Yusuf S, Pitt B, Davis C, Hood Jr W, Cohn J . Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992; 327(10):685-91. DOI: 10.1056/NEJM199209033271003. View

Bahi L, Koulmann N, Sanchez H, Momken I, Veksler V, Bigard A . Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?. J Appl Physiol (1985). 2003; 96(1):59-64. DOI: 10.1152/japplphysiol.00323.2003. View

Konstam M, Rousseau M, Kronenberg M, Udelson J, Melin J, Stewart D . Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators. Circulation. 1992; 86(2):431-8. DOI: 10.1161/01.cir.86.2.431. View

Yeh S, Lovitt S, Schuster M . Pharmacological treatment of geriatric cachexia: evidence and safety in perspective. J Am Med Dir Assoc. 2007; 8(6):363-77. DOI: 10.1016/j.jamda.2007.05.001. View

Sumukadas D, Struthers A, McMurdo M . Sarcopenia--a potential target for Angiotensin-converting enzyme inhibition?. Gerontology. 2006; 52(4):237-42. DOI: 10.1159/000093656. View

Carter C, Onder G, Kritchevsky S, Pahor M . Angiotensin-converting enzyme inhibition intervention in elderly persons: effects on body composition and physical performance. J Gerontol A Biol Sci Med Sci. 2005; 60(11):1437-46. DOI: 10.1093/gerona/60.11.1437. View

Estacio R, Jeffers B, Hiatt W, Biggerstaff S, Gifford N, Schrier R . The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998; 338(10):645-52. DOI: 10.1056/NEJM199803053381003. View

Tatti P, Pahor M, Byington R, di Mauro P, Guarisco R, Strollo G . Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998; 21(4):597-603. DOI: 10.2337/diacare.21.4.597. View

Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G . Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000; 342(3):145-53. DOI: 10.1056/NEJM200001203420301. View

10.

Hansson L, Forslund T, Hoglund C, Istad H, Lederballe-Pedersen O, Kristinsson A . Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients. J Cardiovasc Pharmacol. 1996; 28(1):1-5. DOI: 10.1097/00005344-199607000-00001. View

11.

Guralnik J, Fried L, Salive M . Disability as a public health outcome in the aging population. Annu Rev Public Health. 1996; 17:25-46. DOI: 10.1146/annurev.pu.17.050196.000325. View

12.

Guralnik J, Ferrucci L, Simonsick E, Salive M, Wallace R . Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med. 1995; 332(9):556-61. PMC: 9828188. DOI: 10.1056/NEJM199503023320902. View

13.

Coirault C, Hagege A, Chemla D, Fratacci M, Guerot C, Lecarpentier Y . Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure. Chest. 2001; 119(6):1755-60. DOI: 10.1378/chest.119.6.1755. View

14.

Guralnik J, Ferrucci L, Pieper C, Leveille S, Markides K, Ostir G . Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000; 55(4):M221-31. DOI: 10.1093/gerona/55.4.m221. View

15.

Sumukadas D, Witham M, Struthers A, McMurdo M . Effect of perindopril on physical function in elderly people with functional impairment: a randomized controlled trial. CMAJ. 2007; 177(8):867-74. PMC: 1995143. DOI: 10.1503/cmaj.061339. View

16.

Onder G, Penninx B, Balkrishnan R, Fried L, Chaves P, Williamson J . Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet. 2002; 359(9310):926-30. DOI: 10.1016/s0140-6736(02)08024-8. View

17.

Cesari M, Kritchevsky S, Baumgartner R, Atkinson H, Penninx B, Lenchik L . Sarcopenia, obesity, and inflammation--results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors study. Am J Clin Nutr. 2005; 82(2):428-34. DOI: 10.1093/ajcn.82.2.428. View

18.

Cesari M, Penninx B, Pahor M, Lauretani F, Corsi A, Williams G . Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004; 59(3):242-8. DOI: 10.1093/gerona/59.3.m242. View

19.

Pahor M, Franse L, Deitcher S, Cushman W, Johnson K, Shorr R . Fosinopril versus amlodipine comparative treatments study: a randomized trial to assess effects on plasminogen activator inhibitor-1. Circulation. 2002; 105(4):457-61. DOI: 10.1161/hc0402.102929. View

20.

Coirault C, Langeron O, Lambert F, Blanc F, Lerebours G, Claude N . Impaired skeletal muscle performance in the early stage of cardiac pressure overload in rabbits: beneficial effects of angiotensin-converting enzyme inhibition. J Pharmacol Exp Ther. 1999; 291(1):70-5. View