Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors.

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.

Hypercholesterolaemia alters arterial and blood factors related to atherosclerosis in hypertension.

To evaluate the influence of hypercholesterolaemia on arterial and blood factors related to cardiovascular disease in hypertension, 20 normocholesterolaemic and 31 hypercholesterolaemic hypertensive patients underwent determinations of whole blood filterability (WBF), plasma fibrinogen concentration (PF) and aortic pulse wave velocity (PWV). Both of the groups had similar age, body mass index, cumulative smoking dose and blood pressure. Hypercholesterolaemics had lower WBF (P less than 0.02), higher PF (P less than 0.02) and higher PWV (P less than 0.01) than normocholesterolaemics. In the whole population WBF correlated with age (P less than 0.005), mean blood pressure (P less than 0.01), total cholesterol (P less than 0.05) and plasma fibrinogen (P less than 0.01). However, in a multivariate analysis where age and pressure were controlled as variables, only the association between WBF and PF remained significant (P less than 0.001). Thus, the higher fibrinogen affects whole blood filterability in hypercholesterolaemic hypertensive patients. In the whole population PWV correlated positively with HDL cholesterol (P less than 0.01) and age (P less than 0.001) and the association with HDL cholesterol remained significant in a multivariate analysis (P less than 0.001) where age was controlled. The effect of ageing on arterial rigidity seems to be similar in both hypertensive groups as deduced from the identical regression slopes relating pulse wave velocity to age. So in hypertension with high cholesterol, arterial rigidity was increased without changes in arterial stiffening with age.

Cardiovascular effects of cigarette smoking.

The risk of cardiovascular morbidity and mortality is greatly affected by cigarette smoking. In order to study the pressor response to smoking, 10 normotensive and 10 mild or moderate essential-hypertensive smokers (> 20 cigarettes daily) were compared with 2 comparable groups of non-smokers. All subjects were asked to smoke 4 cigarettes during 1 h; blood pressure (BP) and heart rate (HR) were monitored beat-to-beat by a non-invasive device (Finapres Ohmeda) during the smoking period and during the immediately preceding non-smoking hour. Furthermore, all subjects underwent 24-hour ambulatory BP monitoring. In all groups, each cigarette induced a similar and statistically significant increase from baseline for both BP and HR. The recovery from the marked rise in BP and HR was very slow so that in the smoking hours BP and HR were persistently higher than in non-smoking hours; there were no statistically significant differences between the four groups. During 24-hour ambulatory monitoring both normo- and hypertensive smokers showed higher BP values and higher BP variability in comparison with the respective non-smokers' group. In conclusion, smoking habits were associated with a persistent increase in BP in each group we studied, possibly contributing to a smoking-related cardiovascular risk.

Risk factors and early extracoronary atherosclerotic plaques detected by three-site ultrasound imaging in hypercholesterolemic men. Prévention Cardio-vasculaire en Médecine du Travail METRA Group.

Ultrasonic detection of atherosclerotic plaque of carotid abdominal aortic and femoral arteries and evaluation of risk factors were performed in 208 hypercholesterolemic men without cardiovascular disease. Twenty-six percent of them had no plaque. Plaque at the carotid, aortic, and femoral sites was found in 37%, 48%, and 53% of subjects, respectively. Plaque was associated (1) in carotid arteries with increased total and low-density lipoprotein cholesterol; (2) in the aorta with increased age, pressure, glycemia, and smoking; and (3) in femoral arteries with increased age, systolic pressure, low-density lipoprotein cholesterol, and smoking. Multiple regression analysis showed correlations between carotid plaque and low-density lipoprotein cholesterol; aortic plaque and age, smoking, glycemia, and pressure; femoral plaque and age, smoking, and pressure. This suggests that multiple risk factors influence lesions, and risk profile differs according to atherosis site.

Relation of risk factors for cardiovascular disease to early atherosclerosis detected by ultrasonography in middle-aged normotensive hypercholesterolemic men. PCV Metra Group.

The relations between carotid arteries and/or abdominal aortic plaque and cardiovascular risk factors were investigated by ultrasonography in 161 untreated hypercholesterolemic normotensive men. Of them, 58 had no plaque (NP group), 34 had carotid but not aortic plaque (CP group), 34 had aortic but not carotid plaque (AP group) and 35 had both carotid and aortic plaques (CAP group). Groups significantly differed for age, smoking, blood pressure, and the ratio of total to HDL cholesterol. Age was higher in CAP group than in NP and CP groups and in AP and CP groups than in NP group. Life long smoking dose was higher in CAP group than in CP, AP, and NP groups. Systolic and diastolic pressures were higher in CAP group than in NP group, systolic pressure was higher in CAP group than in CP group, and diastolic pressure was higher in AP group than in CP and NP groups. The ratio of total to HDL cholesterol was higher in CAP group than in AP, CP, and NP groups. Multiple regression analysis showed that carotid plaque was only related to age, while aortic plaque and the number of sites affected by plaque were correlated to age, smoking and diastolic pressure. These findings suggest that in hypercholesterolemia risk factors other than lipids seem to influence arterial plaque and that risk profile differs according to the plaque location.

[Contrary effects of hypertension and cigarette smoking on the conditions of wall shear in large arteries]. / Effets opposés de l'hypertension artérielle et du tabagisme sur les conditions de cisaillement pariétal au niveau des grosses artères.

Systolic wall shear conditions were studied in the brachial artery of 4 groups of subjects including 11 non-smokers normotensives (NSNT), 25 non smokers hypertensives (NSHT), 21 smokers normotensives (SNT) and 10 smokers hypertensives (SHT). Brachial artery diameter (D) and systolic centerline blood velocity (VCLS) were measured with a pulsed Doppler device and blood viscosity at 96 sec-1 was measured with a coaxial cylinder viscometer. The wall shear rate (gamma S) corresponding to systolic velocity was calculated using a Womersley model of pulsatile flow according to the formula: alpha = (D/2) (omega/mu) 1/2, omega being the angular pulse frequency and mu the kinematic viscosity. The wall shear stress was then calculated as the product between wall shear rate and viscosity. The analysis of results in the 4 groups showed that both hypertension and smoking increased blood viscosity bu their effects on wall shear were opposite since hypertension decreased shear and stress while smoking did not change it. However, in hypertensive patients, smoking induced a clear elevation in wall shear rate and stress, whereas in smokers hypertension did not change shear conditions. Thus, opposite and interactive effects of hypertension and smokers exist on large artery wall shear phenomena which could induce differences in response of functional and structural endothelial cells to these two vascular risk factors.