ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism

Mauro Contini, Elisa Compagnino, Gaia Cattadori, Damiano Magrì, Marina Camera, Anna Apostolo, Stefania Farina, Pietro Palermo, Karl Gertow, Elena Tremoli, Cesare Fiorentini, Piergiuseppe Agostoni

Research output: Contribution to journalArticlepeer-review


Purpose: The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor’s protection of the lungs in HF during acute fluid overload. Methods: 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. Results: ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco −2.3 ± 1.3 vs. -0.8 ± 1.9 and −0.6 ± 1 mL/mmHg/min, p <0.0001 and p <0.01; Dm −7 ± 5 vs. -3.2 ± 7.4 and −1.3 ± 5 mL/mmHg/min, p <0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 ± 1.9 vs. -0.8 ± 2.3, p = 0.01). Conclusions: ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalCardiovascular Drugs and Therapy
Publication statusAccepted/In press - Feb 4 2016


  • Angiotensin
  • Exercise
  • Genetics
  • Heart failure
  • Lung

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine
  • Pharmacology


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