ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.
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.
['Contini|Mauro|M|', 'Compagnino|Elisa|E|', 'Cattadori|Gaia|G|', 'Magrì|Damiano|D|', 'Camera|Marina|M|', 'Apostolo|Anna|A|', 'Farina|Stefania|S|', 'Palermo|Pietro|P|', 'Gertow|Karl|K|', 'Tremoli|Elena|E|', 'Fiorentini|Cesare|C|', 'Agostoni|Piergiuseppe|P|']
D000806:Angiotensin-Converting Enzyme Inhibitors D001241:Aspirin D004656:Enalapril D005080:Exercise Test D005260:Female D005838:Genotype D006333:Heart Failure D006801:Humans D008168:Lung D008297:Male D008875:Middle Aged D007703:Peptidyl-Dipeptidase A D011110:Polymorphism, Genetic D012129:Respiratory Function Tests
Lung Heart failure Angiotensin Exercise Genetics