高血压患者服用血管紧张素转换酶抑制剂后咳嗽机制的前瞻性研究

目的　观察原发性高血压患者的性别、服药种类、吸烟习惯、血管紧张素转换酶 (ACE)基因多态性及其服药前、后血清ACE水平变化与咳嗽的关系及研究服用ACE抑制剂 (ACEI)类药物后发生咳嗽的机制。方法　入选高血压患者 12 7例 ,依据服用ACEI(97例口服西拉普利、30例口服盐酸贝那普利 ) 8周后是否出现咳嗽分为咳嗽组 (4 8例 )和不咳嗽组 (79例 )。比较两组ACE基因多态性 (II型、ID型、DD型 )及服药前、后血清ACE水平的差异 ,并将相关因素进行Logistic回归分析 ,预测出是否咳嗽的方程式。结果　 12 7例患者中有 4 8例 (37 8% )出现咳嗽。咳嗽组ACE的I等位基因及II基因型频率分布分别为 0 70 %和 5 6 3% ,不咳嗽组分别为 0 4 2 %和 2 3 3% ,两组比较差异有显著性(P <0 0 5 )。咳嗽组服药前、后血清ACE水平分别为 (2 6± 6 )U/L、(4± 4 )U/L ,不咳嗽组分别为 (33±8)U/L、(8± 8)U/L ,两组服药前、后血清ACE水平比较差异有显著性 P均 <0 0 1)。咳嗽组和不咳嗽组服药前、后血清ACE水平变化幅度分别为 (2 2± 7)U/L、(2 5± 9)U/L ,两组血清ACE水平变化幅度比较差异无显著性 P =0 0 77)。服药前血清ACE水平DD型最高 [(36± 8)U/L],ID型次之 [(2 9± 6 )U/L],II型最低 [(2 6± 7)U/L],服药前 3个基因型间

A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension

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.