| Objection To observe clinical efficacy and security of amlodipine plus amiloride compound or telmisartan treatment on primary hypertension, as well as the influences of genetic factors, psychological factors and required factors.Method 180 patients with primary hypertension in Changsha were randomly grouped into combination therapy group A or combination group B. In group A, the daily dosage was 2.5mg amlodipine plus half piece of amiloride compound (amiloride 1.25mg, hydrochlorothiazide 12.5mg), qd; in group B, the daily dosage was 2.5mg amlodipine plus 40mg telmisartan, qd. After 2 weeks of treatment, for the patients with blood pressure≧140/90mmHg, the dosage of amiloride compound was increased to 1 piece/d, and the dosage of telmisartan was increased to 80mg/d. And, after 4 weeks of treatment, the dosage of amlodipine was increased to 5mg for the patients with blood pressure≧140/90mmHg. During the 24-week follow-up period, blood pressure, heart rate, biochemical indexes and side effects were observed, polymorphism of CYP3A4 and CYP3A5 were determined by PCR-RFLP and PCR, the psychological activities evaluation was investigated by Self-Rating Anxiety Scale (SAS), and other required related factors including body weight, height, pulse wave velocity were detected and analyzed. Results 1. There were 163 patients completing the whole process. Reduction value of systolic blood pressure in group A and group B was (31.7±11.4) mmHg and (31.7±12.1) mmHg (P=0.992), respectively; reduction value of diastolic blood pressure in group A and group B was (14.1±8.1) mmHg and (16.2±8.3) mmHg (P=0.112), respectively. The total efficacy of group A and group B was 90.9% (70/77) and 95.3% (82/86) (P>0.05), respectively. The significance of group A and group B was 64.9% (50/77) and 73.3% (63/86) (P>0.05), respectively. The rate of reaching the standard of group A and group B was 84.4% (65/77) and 93.0% (80/86) (P>0.05), respectively.2. Among 163 patients with primary hypertension, wild type of CYP3A4*1G was 53.4%, mutant homozygote was 11.6%, mutant heterozygote was 35.0%, and the allele mutant rate was 29.1%; wild type of CYP3A5*3 was 9.8%, mutant homozygote was 39.3%, mutant heterozygote was 50.3%, and the allele mutant rate was 65.1%. The distribution of allele and genotype was consistent with Hardy-weinberg balance.2.1 Reduction value of diastolic blood pressure for CYP3A4*1*1 in group A was much more than that of CYP3A4*1G*1G (15.9±9.8mmHg VS 9.0±2.6mmHg; P=0.014); while reduction value of systolic blood pressure had no statistical difference; reduction value of diastolic pressure with CYP3A4*1*1 and CYP3A4*1*1G in group B was much more than that of CYP3A4*1G*1G (16.8±8.3mmHg VS 9.3±6.8mmHg, 16.8±8.1mmHg VS 9.3±6.8mmHg; P=0.015, P=0.025); while reduction value of systolic blood pressure had no statistical difference. The rate of reaching the standard and efficacy for CYP3A4*1*1 in group B were much higher than those of CYP3A4*1G*1G (98.1% VS 62.5%,98.1% VS 75.0%; P=0.006; P=0.043).2.2 Reduction value of systolic blood pressure for CYP3A5*3*3 in group A was much more than that of CYP3A5*1*1 (35.3±11.3mmHg VS 25.4±9.2mmHg; P=0.016); while reduction value of diastolic blood pressure had no statistical difference; reduction value of systolic blood pressure or diastolic blood pressure for CYP3A5*1*1, CYP3A5*1*3, and CYP3A5*3*3 in group B had no statistical difference. The rate of reaching the standard and efficacy for CYP3A5*1*1, CYP3A5*1*3, and CYP3A5*3*3 in A and B groups had no statistical difference.2.3 As for haploid of CYP3A4*1/CYP3A5*3, the reduction value of systolic blood pressure or diastolic blood pressure had no statistical difference (CYP3A4*1*1/CYP3A5*3 VS CYP3A4*1G/CYP3A5*1*1 or CYP3A4*1*1/CYP3A5*3 VS CYP3A4*1G/CYP3A5*3).3. As for psychological factors, the rate of reaching the standard for patient without anxiety in group A and group B was higher than that with serious anxiety (91.8% VS 55.6%; 97.9% VS 71.4%; P=0.015; P=0.041). As for required factors, the patients with high baseline systolic pressure, normal weight index and waist-to-hip ratio had the better blood pressure reduction efficacy.4. The multiplicity results showed that influence factors in Logistic regression equation included CYP3A4*1G, weight index, psychological factor and age, and the total predicted correctness rate was 92.6%.Conclusions 1. Amlodipine plus amiloride compound or telmisartan treatment could reduce blood pressure obviously without significant difference between two groups; the combination therapy held excellent tolerance with little side effects.2. Genetic factor was one of the factors to induce the different efficacy in amlodipine-based combination therapy. CYP3A4*1G,CYP3A5*3 were gene mutant with significance.3. Psychological factors could take effect on reduction of blood pressure. The efficacy of patient without anxiety was better than that with serious anxiety. Fat and baseline systolic blood pressure were relative to efficacy of amlodipine-based combination therapy.4. The multiplicity results showed that genetic factors, Psychological factors, fat, systolic pressure and age could influence the efficacy. |
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