Amlodipine: effective for treatment of mild to moderate essential hypertension and left ventricular hypertrophy.

This was a 20-week, open-label, uncontrolled clinical investigation of the long-acting calcium antagonist amlodipine in 33 male or female patients with essential hypertension and left ventricular hypertrophy (LVH). A once-daily dose (5-10 mg/day) of amlodipine provided a consistent antihypertensive effect, reducing the sitting diastolic (-13.8% change) and systolic (-13.0% change) blood pressures by clinically meaningful and statistically significant (p = 0.0001, n = 33) amounts. Amlodipine had no effect on heart rate. A significant regression in LVH was seen (left ventricular mass index reduced from 169.0 [SD 30.7] g/m(2) to 140.6 [SD 19.6] g/m(2), p < 0.01, n = 12). There was also a significant reduction in total peripheral resistance and improvement in left ventricular diastolic filling (E/A ratio increased from 0.86 pre-treatment to 1.03 post-treatment, p = 0.038, n = 12). These results are consistent with other studies in showing that a relatively short treatment regimen with amlodipine is associated with a significant reduction in left ventricular mass index.

A single (investigator)-blind randomised control trial comparing the effects of quinapril and nifedipine on platelet function in patients with mild to moderate hypertension.

The effect of quinapril and nifedipine on platelet aggregation, vascular endothelial function and coagulation system activity, was compared in a parallel-group, investigator-blind study carried out on patients with mild to moderate hypertension but no other diseases or receiving medication which might affect platelet function, vascular endothelium or coagulation. Forty patients (two groups of 20 patients each) and 20 control subjects were recruited. Patients were randomised to receive either quinapril or nifedipine retard and the dose escalated to control hypertension. Platelet aggregation studies were assessed serially and beta-thromboglobulin, angiotensin-converting enzyme (ACE), von Willebrand factor (vWF) coagulation factors VIIIc, XII and fibrinogen were measured at the beginning and end of the 12-week period. Blood pressure was adequately controlled in all patients in both groups. Platelet function was impaired in certain parameters (slope of the reaction with ADP and collagen and maximum aggregation with collagen) in the patient group compared to controls before treatment and this improved in patients on quinapril but not on nifedipine; likewise beta-thromboglobulin was higher in the patient group and fell significantly in the quinapril group but not those on nifedipine. Measurements of endothelial function and coagulation were normal before treatment and showed no alteration during the study, except in the expected fall in plasma ACE in the quinapril group. The results indicate that the ACE inhibitor, quinapril, has a beneficial effect on platelet function unlike the calcium channel blocker, nifedipine.

Evidence of platelet activation in hypertension.

To test the hypothesis that platelet activation is present in hypertension, we measured plasma markers beta thromboglobulin and soluble P-selectin in hypertensive patients and normotensive controls. Both markers were raised in the patients (P < 0.05), and in a subgroup of patients, beta thromboglobulin was reduced with successful treatment of hypertension with the ACE inhibitor quinapril. We suggest that reversible platelet activation is present in hypertension. This may be a contributing factor to the link between this risk factor and the development of thrombotic disease such as stroke.

Left ventricular diastolic function in hypertensive patients with unstable angina and single coronary artery disease.

The present study was performed to investigate left ventricular diastolic (LVD) function in hypertensive patients with unstable angina. Three groups of 17 patients each were studied. Group 1 consisted of hypertensives with unstable angina (HTU); group 2, normotensives with unstable angina (NTU); and group 3, untreated, uncomplicated hypertensives (HT). The LVD function was assessed echocardiographically by transmitral valve Doppler flow to measure the ratio between the early diastolic filling (E) and the atrial contraction phase (A). An E/A ratio of < 1 was suggestive of LVD dysfunction. Left ventricular mass (LVM), from an M-mode echocardiogram using the Penn-Cube formula, was corrected to body surface area (LVM/S) using a standard nomogram. Data are represented as median values and analyzed by Mann-Whitney test. P was significant at < .05. The HTU group had an E/A ratio of 0.8, and the NTU and HT groups had ratios of 1.17 and 1.1, respectively. There was significant diastolic dysfunction in the HTU group compared with the NTU and HT groups (P = .037 and .049, respectively). Although the LVM/S was significantly higher in the HTU group when compared with the HT group (110.6 and 96.9, respectively, P = .017), there was no significant difference between the HTU and NTU groups (123.1), P = .67. Hypertensive patients with unstable angina have significant LVD dysfunction that seems to be independent of LVM and ischemia. This may be attributable to increased stiffness of the left ventricle or structural left ventricular abnormalities.

The role of platelets in essential hypertension.

Recent research is helping us understand the complex interactions that occur between platelets and their environment. The several intracellular events that occur during platelet activation are being identified as ar their effects on other platelets, the endothelium and coagulation factors. Heightened platelet activation is seen early in essential hypertension and probably plays an important role in the initiation and progression of atherosclerosis and the disorders associated with it. This review identifies some of the changes in platelet structure and function in essential hypertension and their role in the pathogenesis of hypertensive vascular disease.

The effect of antihypertensive drugs on in vivo platelet activity in essential hypertension.

OBJECTIVE: To investigate whether antihypertensive drugs have a beneficial effect upon the abnormal in vivo platelet function found in patients with essential hypertension. DESIGN: A cross-sectional study in which plasma beta-thromboglobulin, a marker of in vivo platelet activation, was measured in patients with essential hypertension on various antihypertensive drugs. All were free from any other diseases which might affect platelet function. METHODS: Plasma beta-thromboglobulin was measured in 24 patients with untreated essential hypertension, 21 normotensive control patients, 16 patients receiving angiotensin converting enzyme (ACE) inhibitors, 16 patients receiving a beta-adrenoceptor blocker, 12 patients receiving calcium antagonists and 12 patients receiving a diuretic alone. RESULTS: Untreated hypertensives had significantly elevated plasma beta-thromboglobulin levels compared with controls. Plasma beta-thromboglobulin levels in patients receiving beta-blockers and diuretics were not significantly different from untreated hypertensives. Treatment with calcium antagonists was associated with lower plasma beta-thromboglobulin levels, but this difference was not statistically significant. In contrast, treatment with ACE inhibitors was associated with significantly lower plasma beta-thromboglobulin levels compared with untreated hypertensives. CONCLUSION: These results suggest that antihypertensive drugs have different effects upon abnormal in vivo platelet function in patients with essential hypertension. The apparent beneficial effect of ACE inhibitors may mean that they have more impact than other drug groups in the prevention of coronary heart disease.