Hiltunen Timo P, Suonsyrjä Timo, Hannila-Handelberg Tuula, Paavonen Kristian J, Miettinen Helena E, Strandberg Timo, Tikkanen Ilkka, Tilvis Reijo, Pentikäinen Pertti J, Virolainen Juha, Kontula Kimmo
Department of Medicine, University of Helsinki, and Biomedicum Helsinki, Helsinki, Finland.
Am J Hypertens. 2007 Mar;20(3):311-8. doi: 10.1016/j.amjhyper.2006.09.006.
Only a minority of hypertensive individuals is adequately controlled for their hypertension, partially because reliable predictors for efficient antihypertensive drug therapy are lacking.
In a prospective, randomized, double-blind, cross-over, placebo-controlled study (The GENRES Study), 208 moderately hypertensive Finnish men (aged 35 to 60 years) were treated for 4 weeks with antihypertensive drugs from four different classes: amlodipine (5 mg), bisoprolol (5 mg), hydrochlorothiazide (25 mg), or losartan (50 mg) daily. Each individual received each of the four monotherapies in a randomized order. Four-week placebo periods were included before and between drug treatment periods. Antihypertensive responses were assessed with 24-h ambulatory and office measurements and analyzed according to age, body mass index, triceps skin fold thickness, waist-to-hip ratio, duration of hypertension, number of previous antihypertensive drugs, number of affected parents, and blood pressure (BP) levels, and profiles during placebo periods.
The median BP responses in 24-h ambulatory recordings (systolic/diastolic) were 11/8 mm Hg for bisoprolol, 9/6 mm Hg for losartan, 7/5 mm Hg for amlodipine, and 5/2 mm Hg for hydrochlorothiazide. The highest pairwise within-subject correlations in BP responses were seen for the combinations of bisoprolol-losartan and amlodipine-hydrochlorothiazide. The BP responses to bisoprolol and losartan did not vary according to the variables. Amlodipine and hydrochlorothiazide responses were positively correlated with age, placebo BP level, and lower night-time dipping on placebo.
Baseline clinical and BP parameters may be used to predict the efficacy of antihypertensive therapies. The GENRES Study material should provide an excellent platform for future pharmacogenetic analyses of antihypertensive drug responsiveness.
只有少数高血压患者的血压得到了充分控制，部分原因是缺乏有效的抗高血压药物治疗的可靠预测指标。
在一项前瞻性、随机、双盲、交叉、安慰剂对照研究（GENRES研究）中，208名中度高血压芬兰男性（年龄35至60岁）接受了为期4周的抗高血压药物治疗，药物分为四类：氨氯地平（5毫克）、比索洛尔（5毫克）、氢氯噻嗪（25毫克）或氯沙坦（50毫克），每日服用。每个个体按随机顺序接受四种单一疗法中的每一种。在药物治疗期之前和期间均设有为期4周的安慰剂期。通过24小时动态血压监测和诊室测量评估抗高血压反应，并根据年龄、体重指数、肱三头肌皮褶厚度、腰臀比、高血压病程、既往抗高血压药物数量、患病父母数量以及血压水平和安慰剂期的血压变化情况进行分析。
在24小时动态血压记录中（收缩压/舒张压），比索洛尔的血压反应中位数为11/8毫米汞柱，氯沙坦为9/6毫米汞柱，氨氯地平为7/5毫米汞柱，氢氯噻嗪为5/2毫米汞柱。比索洛尔 - 氯沙坦和氨氯地平 - 氢氯噻嗪组合的血压反应在受试者内的两两相关性最高。比索洛尔和氯沙坦的血压反应不随变量变化。氨氯地平和氢氯噻嗪的反应与年龄、安慰剂期血压水平以及安慰剂期较低的夜间血压下降呈正相关。
基线临床和血压参数可用于预测抗高血压治疗的疗效。GENRES研究资料应为未来抗高血压药物反应性的药物遗传学分析提供一个良好的平台。
