BACKGROUND: We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI). METHODS: A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI. RESULTS: In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥ 55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]). CONCLUSIONS: These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.

Cardiology Department Faculty Hospital Brno Jihlavska 20 Brno 625 00 Czech Republic

Zobrazit více v PubMed

Yao S. Myocardial repair/remodeling following infarction: roles of local factors. Cardiovasc Res. 2009;81:482–490. PubMed PMC

Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. Journal of Clinical Investigation. 1990;86:1343–1346. doi: 10.1172/JCI114844. PubMed DOI PMC

Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F. et al.Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. American Journal of Human Genetics. 1992;51:197–205. PubMed PMC

Danser AHJ, Schalekamp MADH, Bax WA, Van den Brink AM, Saxena PR, Riegger GAJ. et al.Angiotensin-converting enzyme in the human heart: Effect of the deletion/insertion polymorphism. Circulation. 1995;92:1387–1388. PubMed

ISIS-4: A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. The Lancet. 1995;345:669–682. doi: 10.1016/S0140-6736(95)90865-X. PubMed DOI

Gruppo Italiano per lo Studio della Soprawivenza nell'Infarto Miocardico. GISSI-3: effects of lisiriopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. The Lancet. 1994;343:1115–1122. PubMed

The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Lancet. 1993;342:821–828. PubMed

Borghi C, Cicero AFG, Ambrosioni E. Effects of early treatment with zofenopril in patients with myocardial infarction and metabolic syndrome: The SMILE Study. Vascular Health and Risk Management. 2008;4:665–671. PubMed PMC

Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown J, Cuddy TE. et al.Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction - Results of the survival and ventricular enlargement trial. New England Journal of Medicine. 1992;327:669–677. doi: 10.1056/NEJM199209033271001. PubMed DOI

Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K. et al.A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. New England Journal of Medicine. 1995;333:1670–1676. PubMed

Ertl G, Kloner RA, Alexander RW, Braunwald E. Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor. Circulation. 1982;65:40–48. PubMed

Palmer BR, Pilbrow AP, Yandle TG, Frampton CM, Richards AM, Nicholls MG. et al.Angiotensin-converting enzyme gene polymorphism interacts with left ventricular ejection fraction and brain natriuretic peptide levels to predict mortality after myocardial infarction. Journal of the American College of Cardiology. 2003;41:729–736. doi: 10.1016/S0735-1097(02)02927-3. PubMed DOI

Ulgen MS, Ozturk O, Alan S, Kayrak M, Turan Y, Tekes S. et al.The relationship between angiotensin-converting enzyme (insertion/deletion) gene polymorphism and left ventricular remodeling in acute myocardial infarction. Coronary Artery Disease. 2007;18 doi: 10.1097/MCA.0b013e328010a4c4. PubMed DOI

Nagashima J, Musha H, So T, Kunishima T, Nobuoka S, Murayama M. Effect of angiotensin-converting enzyme gene polymorphism on left ventricular remodeling after anteroseptal infarction. Clinical Cardiology. 1999;22:587–590. doi: 10.1002/clc.4960220909. PubMed DOI PMC

Ohmichi N, Iwai N, Maeda K, Shimoike H, Nakamura Y, Izumi M. et al.Genetic basis of left ventricular remodeling after myocardial infarction. International Journal of Cardiology. 1996;53:265–272. doi: 10.1016/0167-5273(96)02562-4. PubMed DOI

Pinto YM, Van Gilst WH, Herre Kingma J, Schunkert H. Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. Journal of the American College of Cardiology. 1995;25:1622–1626. doi: 10.1016/0735-1097(95)00090-Q. PubMed DOI

Zee RYL, Solomon SD, Ajani UA, Pfeffer MA, Lindpaintner K. A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the 'Healing and Early Afterload Reducing Therapy' Study. Clinical Genetics. 2002;61:21–25. doi: 10.1034/j.1399-0004.2002.610104.x. PubMed DOI

Johnson A, Gong Y, Wang D, Langaee T, Shin J, Cooper-DeHof R. et al.Promoter polymorphism in ACE (Angiotensin I-converting enzyme) associated with clinical outcomes in hypertension. Clin Pharmacol Ther. 2009;85:36–44. doi: 10.1038/clpt.2008.194. PubMed DOI PMC

Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1) Nucleic Acids Research. 1992;20:1433. doi: 10.1093/nar/20.6.1433-a. PubMed DOI PMC

Samani NJ, Thompson JR, O'Toole L, Channer K, Woods KL. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation. 1996;94:708–712. PubMed

Yoshida M, Iwai N, Ohmichi N, Izumi M, Nakamura Y, Kinoshita M. D allele of the angiotensin-converting enzyme gene is a risk factor for secondary cardiac events after myocardial infarction. International Journal of Cardiology. 1999;70:119–125. doi: 10.1016/S0167-5273(99)00064-9. PubMed DOI

Cambien F, Costerousse O, Tiret L, Poirier O, Lecerf L, Gonzales MF. et al.Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction. Circulation. 1994;90:669–676. PubMed

Gardemann A, Weiss T, Schwartz O, Eberbach A, Katz N, Hehrlein FW. et al.Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients. Circulation. 1995;92:2796–2799. PubMed

Nakai K, Itoh C, Miura Y, Hotta K, Musha T, Itoh T. et al.Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation. 1994;90:2199–2202. PubMed

Cohn J, Tognoni G. Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. New England Journal of Medicine. 2001;345:1667–1675. doi: 10.1056/NEJMoa010713. PubMed DOI

Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: Experimental observations and clinical implications. Circulation. 1990;81:1161–1172. PubMed

Rott D, Behar S, Leor J, Hod H, Boyko V, Mandelzweig L. et al.Effect on survival of acute myocardial infarction in Killip classes II or III patients undergoing invasive coronary procedures. American Journal of Cardiology. 2001;88:618–623. doi: 10.1016/S0002-9149(01)01802-1. PubMed DOI

Flaherty JD, Bax JJ, De Luca L, Rossi JS, Davidson CJ, Filippatos G. et al.Acute Heart Failure Syndromes in Patients With Coronary Artery Disease. Early Assessment and Treatment. Journal of the American College of Cardiology. 2009;53:254–263. doi: 10.1016/j.jacc.2008.08.072. PubMed DOI