Changes in serum lipids concentration induced by either trichlormethiazide alone or combination therapy with propranolol were observed for 2 years in 91 patients with established essential hypertension. The effects of clinofibrate on such changes was also studied in 28 patients who had already received trichlormethiazide at least for 6 months.
Patients were divided into 3 groups according to dosis of trichlormethiazide (TM) used and with or without propranolol.
Group A; 23 patients treated with 2mg of TM
Group B; 41 patients treated with 4mg of TM
Group C; 27 patients treated with TM and propranolol
Total cholesterol, HDL cholesterol, triglyceride and beta lipoprotein as well as fasting blood sugar, serum electrolytes and uric acid were meassured in 6 months interval up to 2 years. Patients whose body weight changed by ±2kg during observation were all excluded on this study.
Significant increases in total cholesterol, triglyceride and beta lipoprotein were observed at the 6th month after diuretic therapy and kept significantly high values for another 12 to 18 months. Concomitant increases in FBS and uric acid were also noted. Dose response relations were clearly demonstrated on triglyceride and beta lipoprotein between group A and B, showing earlier elevation and higher levels in Group B than in Group A. Additive use of propranolol accelerated above tendencies. Characteristic change with combination therapy (Group C) was significant and continuous decrease in HDL cholesterol which was not found by TM alone, with resultant decrease in atherogenic index. Concomitant use of clinifibrate, 600mg daily, with TM lowered total cholesterol and triglyceride significantly to their control values or below but had little effects on HDL cholesterol and beta lipoprotein.
Increase in inactive insulin secretion to stimulate triglyceride synthesis in the liver as suggested by Olefsky or hemodynamic effect to lower blood pressure with use of diuretics might be responsible for metabolic consequence after diuretic therapy. Clinofibrate effectively reversed the increased serum lipid concentration to the control level even continuing TM therapy. Above observation indicated that clinofibrate might have some protective effects against arteriosclerotic vascular disease in patients with diuretic therapy.
