Effect of Combination Therapy of Benidipine Hydrochloride and Candesartan Cilexetil on Serum Lipid Metabolism and Blood Pressure in Elderly Hypertensive Patients with Type 2 Diabetes Mellitus

Abstract

The effects of combination therapy of angiotensin receptor blockers (ARBs) and a calcium antagonist, benidipine hydrochloride, on glucose and lipid metabolism and pulse pressure were studied in elderly hypertensive patients with type 2 diabetes mellitus. Twenty-five hypertensive diabetic patients aged 65 years or older, who had been receiving candesartan cilexetil, were administered benidipine hydrochloride (4 mg/day) and followed for 4 months. After 4 months, systolic and diastolic blood pressure decreased significantly from 154/91 mmHg to 139/78 mmHg (p 0.01 versus before benidipine hydrochloride administration). Body mass index (BMI) and glycosylated hemoglobin (HbA1c) were apparently reduced but the changes were not statistically significant. The serum lipid profile showed no significant changes in serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Serum lipoprotein lipase mass levels (preheparin LPL mass) increased significantly from 51 to 59 ng/dL (p 0.01 versus before benidipine hydrochloride administration), and the LDL/HDL motility ratio calculated from PAG disc electrophoresis decreased significantly (p 0.05 versus before benidipine hydrochloride administration). When patients were divided into a systolic hypertension group (systolic blood pressure ≥ 140 mmHg and diastolic blood pressure 90 mmHg) and non-systolic hypertension group (others), preheparin LPL mass was significantly lower in the systolic hypertension group, and the decrease in pulse pressure and increase in preheparin LPL mass were significantly greater in the systolic hypertension group. Stepwise regression analysis showed that low preheparin LPL mass at baseline was associated with a decrease in pulse pressure. Add-on benidipine hydrochloride therapy in elderly hypertensive patients with type 2 diabetes mellitus significantly decreases the LDL/HDL motility ratio and pulse pressure, and significantly increases preheparin LPL mass, in addition to improving blood pressure control. These findings suggest that combination therapy with benidipine hydrochloride and candesartan cilexetil may contribute to the suppression of arteriosclerosis and may be useful for elderly hypertensive patients with diabetes mellitus.

Telmisartan Enhances Cholesterol Efflux from THP-1 Macrophages by Activating PPARγ

“…On the other hand, angiotensin inhibits the meta-bolic actions of insulin via the phosphatidylinositol 3-kinase pathway 2) , resulting in insulin resistance. Angiotensin type 1 receptor (AT1R) blockers (ARBs) and angiotensin-converting enzyme inhibitors, which function as antihypertensive agents, have been reported to prevent atherosclerosis in a study using monkeys 3) , improve insulin resistance 4) , and induce a favorable lipid profile 5,6) . Besides their metabolic effect on insulin signaling, telmisartan 7,8) and irbesartan 7) , two ARBs, have been found to activate peroxisome proliferator-activated receptor (PPAR ) in cells derived from rodents and this is independent of their AT1R blocking actions.…”

Update on the role of candesartan in the optimal management of hypertension and cardiovascular risk reduction

“…Therefore, candesartan–HCTZ combination was concluded as effective for the treatment of hypertension in patients with hypertension not optimally controlled with candesartan monotherapy. Also, in a smaller study of 25 elderly Japanese hypertensive patients with diabetes who received candesartan and add-on calcium chanel blocker (CCB) treatment benidipine hydrochloride and who were followed up for 4 months, Sasaki et al24 showed significant reduction in SBP and DBP after the addition of benidipine hydrochloride (from 154/91 to 139/78 mmHg; P < 0.01).…”

Platelet Aggregability in Patients with Hypertension Treated with Angiotensin II Type 1 Receptor Blockers

“…In patients with coronary artery disease, the formation of platelet microaggregates correlates with adverse clinical outcomes 4) . The effects of hypertension treatment agents on serum lipids have been characterized 5,6) ; however, their antithrombotic properties remain to be investigated. In vitro study has shown that losartan, an angiotensin type 1 receptor blocker (ARB), can react with thromboxane A2 receptor in human platelets 7) and may possess antithrombotic properties; however, the effects on platelet aggregation among various ARBs have not been fully investigated.…”