title: ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.
abstract: OBJECTIVE
  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.
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Mauro
authors: M
authors: Contini
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Elisa
authors: E
authors: Compagnino
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Gaia
authors: G
authors: Cattadori
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.|Department of Clinical and Molecular Medicine, University "La Sapienza", Rome, Italy.
authors: Damiano
authors: D
authors: Magrì
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Marina
authors: M
authors: Camera
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Anna
authors: A
authors: Apostolo
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Stefania
authors: S
authors: Farina
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Pietro
authors: P
authors: Palermo
authors: Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
authors: Karl
authors: K
authors: Gertow
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors: Elena
authors: E
authors: Tremoli
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy.|Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy.
authors: Cesare
authors: C
authors: Fiorentini
authors: Centro Cardiologico Monzino, IRCCS, Milano, Italy. piergiuseppe.agostoni@unimi.it.|Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Milan, Italy. piergiuseppe.agostoni@unimi.it.|Centro Cardiologico Monzino, Department of Clinical Sciences and Community Health, Cardiovascular Section, University of Milan, Via Parea 4, 20138, Milano, Italy. piergiuseppe.agostoni@unimi.it.
authors: Piergiuseppe
authors: P
authors: Agostoni
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005080:Exercise Test / Q000379:methods; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*; D012129:Respiratory Function Tests / Q000379:methods
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D001241:Aspirin
keywords: Angiotensin; Exercise; Genetics; Heart failure; Lung