Objective: To explore the possible mechanisms underlying cough induced by angiotensin-converting enzyme inhibitors (ACEI) in patients with hypertension.
Methods: 127 patients with hypertension were enrolled to receive ACEI (97 cases prescribed cilazapril and 30 cases prescribed benazepril hydrochloride) for 8 weeks. Patients who had coughed in the period were assigned to the cough group (48 cases) and patients who hadn't coughed were assigned to the non-cough group (79 cases). The serum ACE activity before and after administration of the drugs and the polymorphism of ACE gene (including homozygous-alleles II, DD, and heterozygous ID) were analyzed. Binary logistic regression was used as a statistical method to determine the factors associated with cough.
Results: The frequencies of the I alleles and II genotype of ACE gene in the cough group (0.70% and 56.3%) were significantly higher than those in the non-cough group (0.42% and 23.3%, P < 0.05). The mean serum ACE activity before and after administration of the ACEI in the cough group [(26 +/- 6) U/L, (4 +/- 4) U/L] was significantly lower than that in the non-cough group [(33 +/- 8) U/L, (8 +/- 8) U/L, all P < 0.01]. The difference in the range of decrease of serum ACE activity after ACEI between the cough group [(22 +/- 7) U/L] and the non-cough group [(25 +/- 9) U/L] was not significant (P = 0.077). Serum ACE activity before ACEI was highest in the homozygous-alleles DD group [(36 +/- 8) U/L], secondly in the heterozygous ID group [(29 +/- 6) U/L] and the lowest in homozygous-alleles II group [(26 +/- 7) U/L], differences being significant among three groups (P < 0.01). ACEI-related cough showed no relationship with sex, smoking habit and the ACEI used.
Conclusions: The serum ACE activity was associated with polymorphism of ACE gene. Cough induced by ACEI was related to I allele and II genotype. There was a relationship between the serum ACE activity before administration of ACEI and cough induced by ACEI.