| Objective To explore the influential factors of antihypertensive efficacy response to Benazepril treatment in essential hypertension patients. The major influential factors of the current study included heart-rate corrected QT interval (QTc), body weight, baseline blood pressure, age and alcohol consumption. Methods In order to elucidate genetic and environmental influence on individualized response to antihypertensive, from August 2000 to December 2001, a study on pharmacogenomics in essential hypertension was conducted in County A and County B, Anhui, China. The current study was part of it. In total, 1,493 subjects (707 men, 786 women) recruited to the prospective study cohort and 1,354 of them (642 men, 712 women) completed 15 days Benazepril treatment. A standard 12-lead ECG examination was performed at baseline and the collection of clinical and epidemiological information was completed during treatment. Falls in systolic blood pressure (ASBP) and diastolic blood pressure (ADBP) were calculated as the difference before and after the treatment period. We analyzed the databy methods of residual-residual, multiple linear regression and Logistic regression. Results (1) We found a inverse association of QTc with blood pressure decrease response to Benazepril treatment, and the pattern of linearity between them was more evidence and more significant among men than among women. In male patients, 0.1 second1/2 increase of QTc was found associated with 4.29 mmHg (95%CI: 1.18 - 7.41 mm Hg) and 4.07mm Hg (95%CI: 1.45 - 6.69mm Hg) decreases in ASBP and ADBP, respectively. In female patients, 0.1 second1'2 increase of QTc was associated with 1.71 mm Hg (95%CI: -1.74 - 5.17 mm Hg) and 0.33 mm Hg (95%CI: -2.00 - 2.66 mm Hg) decreases in ASBP and ADBP, respectively. (2) Blood pressure decrease was influenced by body weight, especially in males. 1 kg increase in body weight was found to be associated with a lesser ASBP (men: 0.146 mm Hg, p<0.01; women: 0.123 mm Hg, p=0.05) and a lesser ADBP (men: 0.093 mm Hg, p=0.02; women: 0.067 mm Hg, p=0.09). (3) An increment of 1 mm Hg in baseline blood pressure was significantly associated with a greater ASBP (men: 0.399 mm Hg, p<0.01; women: 0.359 mm Hg, p<0.01l) as well as a greater ADBP (men: 0.438 mm Hg, p<0.01; women: 0.350 mm Hg, p<0.01). (4) Increment of 1 year in age was found to be significantly inversely associated with a lesser blood pressure decrease in ASBP (male, 0.184mmHg P=0.02; female, 0.189mmHg, P=0.04), but not significantly in ADBP (male, 0.052mmHg P=0.37; female, 0.102mmHg, P=0.09). (5) During 15 days treatment among males, the decrease in ASBP and ADBP in alcohol drinking groups was smaller than that of non-drinking group. An inverse dose-response relation between alcohol drinking and ASBP and ADBP was observed either. Comparing to the non-drinking group, subjects with alcohol drinking not less than 50ml per day showed 5.12mm Hg (P=0.0116) and 3.00mm Hg (P=0.0349) smaller in ASBP and ADBP respectively. Multiple Logistic regression analysis demonstrated that the effect rate of antihypertensive in alcohol drinking group with not less than 50ml per day was 45% lower (P=0.0493) in ASBP and 76% lower (P=0.4750) in ADBP than that of the non-drinking group respectively.Conclusion In the present study, we found a negative association of QTc, body weight, age and alcohol consumption and a positive association of baseline blood pressure with individual responses to Benazepril short-term treatment in essential hypertension patients. Although the linear pattern and the degree of the association showed some differences by gender, the findings suggested that the indexes might have important prognostic values in predicting short-term antihypertensive drug responses to Benazepril treatment and in guiding individualized antihypertensive and non-drug treatment. |
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