Middeke M, Richter W O, Schwandt P, Holzgreve H
Reha-Zentrum Spreewald, II, Medizinische Klinik and Poliklinik, University of Munich, Germany.
Int J Clin Pharmacol Ther. 1997 Jun;35(6):231-4.
Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.
尽管降压药物能有效降低血压，但它们的代谢副作用可能会增加冠心病风险。由于常常需要且经常使用不同降压药物的联合治疗，我们开展了一项随机研究，比较氢氯噻嗪与索他洛尔固定组合（A组）或氢氯噻嗪与卡托普利组合（B组）对40例原发性高血压男性患者血压以及脂质和葡萄糖代谢的影响，研究为期1年。两个治疗组的血压均显著降低（p<0.001）：12个月后，A组（平均剂量：氢氯噻嗪33mg、索他洛尔197mg）血压从160/105mmHg降至128/88mmHg，B组（氢氯噻嗪33mg、卡托普利64mg）血压从162/106mmHg降至135/89mmHg。两个治疗组的体重均未观察到显著变化。两个治疗组的甘油三酯均升高（p<0.05）（A组从183mg/dl升至262mg/dl，B组从160mg/dl升至196mg/dl），高密度脂蛋白胆固醇均降低（A组p<0.001，B组p<0.05）（A组从45.1mg/dl降至35.7mg/dl，B组从49.3mg/dl降至46.3mg/dl），而低密度脂蛋白胆固醇仅在A组显著升高（p<0.05），从153mg/dl升至164mg/dl。两个治疗组的总胆固醇和脂蛋白(a)浓度均未观察到显著变化。治疗1年后，仅A组的空腹血糖和糖化血红蛋白A1显著升高（p<0.05）（分别从91.6mg/dl升至98.0mg/dl，从6.3%升至6.9%）。两种联合用药方案下，血清肌酐和钾水平均降低，尿酸显著升高。我们的数据表明，利尿剂/β受体阻滞剂联合用药长期治疗后对脂质和葡萄糖代谢有不良影响。利尿剂/血管紧张素转换酶抑制剂联合用药对脂质代谢的影响较小，对葡萄糖代谢无不良影响。然而，血管紧张素转换酶抑制剂成分不能完全抵消利尿剂的代谢作用。两种联合用药方案对脂蛋白(a)均无影响。我们得出结论，对于原发性高血压的治疗，氢氯噻嗪与血管紧张素转换酶抑制剂联合用药的代谢情况优于与β受体阻滞剂联合用药。
