Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype

OBJECTIVES The objective of this study was to assess whether the angiotensi n-converting enzyme (ACE) gene insertion/deletion (L/D) polymorphism influe nces the adequacy of the neurohormonal response to ACE inhibitors in patien ts with chronic heart failure (CHF). BACKGROUND The renin-angiotensin-aldosterone system (RAAS) plays an importa nt role in the pathophysiology of CHF, and aldosterone levels closely relat e to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevat ed serum levels of aldosterone despite long-term administration of apparent ly adequate doses of these agents. METHODS We prospectively studied 132 patients with CHF (ejection fraction < 45%) receiving long-term therapy with ACE inhibitors for over six months. P atients taking aldosterone antagonists were excluded from the study. "Aldos terone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were t hen divided into two subgroups according to the presence (group 1) or absen ce (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polym orphism was performed by polymerase chain reaction. RESULTS The prevalence of aldosterone escape in our patients was 10% (13/13 2). The two groups of patients did not differ regarding the dose of ACE inh ibitor, diuretics and their renal function. There was a statistically signi ficant different distribution of genotypes between the two groups, with a h igher proportion of DD genotype in group 1 compared with group 2 (62% vs. 2 4%, p = 0.005). CONCLUSIONS Patients with CHF with aldosterone escape have a higher prevale nce of DD genotype compared with patients with aldosterone within the norma l limits. Angiotensin-converting enzyme gene polymorphism contributes to th e modulation and adequacy of the neurohormonal response to long-term ACE-in hibitor administration in CHF. (J Am Coll Cardiol 2001;37:1808-12) (C) 2001 by the American College of Cardiology.