FIXED ANTIHYPERTENSIVE DRUG-COMBINATION I N PATIENTS AT HIGH CARDIOVASCULAR RISK

Background: Antihypertensive drug combinations have two major advantag es: First, dosage of the single components can be reduced, and second, putative side effects can be minimized. Therefore, we analysed in a c ohort of patients with multiple cardiovascular risk factors the metabo lic effects of two fixed antihypertensive drug combinations. Patients and Methods: 225 patients with essential hypertension (dBP greater tha n or equal to 95 less than or equal to 115 mm Hg) and adipositas (BMI 30.6 +/- 2.5) were randomly treated during 6 months with either quinap ril and hydrochlorothiazide (HCTZ) or with metoprolol and hydrochlorot hiazide. Compared with healthy controls, patients exhibited significan t elevated concentrations of trigylcerides (226 +/- 86 vs. 146 +/- 73 mg/dl) and fasting insulin (22.2 +/- 1.8 vs. 9.8 +/- 4.6 mu U/ml). Res ults: The antihypertensive effects and the tolerance of both substance s were good and comparable after 3 and 6 months. Serum triglycerides i ncreased Juring metoprolol/hydrochlorothiazide treatment (230 +/- 81 v s. 244 +/- 185 mg/dl; median 174 vs. 204 + 17%), as well as during tre atment with quinapril/hydrochlorothiazide (222 +/- 155 vs. 235 +/- 162 mg/dl; median 166 vs. 174; + 5%). Fasting blood glucose levels, insul in, fructosamine, HBA 1 c and free fatty acids remained unchanged. In a subgroup of 88 postmenopausal women with upper body obesity (WHR > 0 .85) treatment with quinapril/hydrochlorothiazide normalized the VLDL- triglyceride/VLDL-cholesterol ratio (3.8 vs. 5.9, p < 0.05), whereas t he ratio only increased from 3.6 to 4.2 in the metoprolol/hydrochlorot hiazide group. These changes in the ACE-inhibitor group were due to a decrease in VLDL-cholesterol (41.1 +/- 4.2 vs. 33.9 +/- 9.6). Conclusi ons: These data demonstrate that quinapril or metoprolol in combinatio n with hydrochlorothiazide do not differ significantly with regard to their effects on blood-pressure lowering, lipoprotein profil;, and glu cose metabolism Only in the subgroup of adipose postmenopausal women, the modulated VLDL-composition might suggest the elimination of athero genic VLDL-remnants/IDL during quinapril/hydrochlorothiazide treatment .