Statins: another class of antihypertensive agents?

The assessment of global cardiovascular risk is an essential step in the management of atherosclerotic disease prevention. Among the risk factors to be addressed are hypertension and hyperlipidaemia; these commonly coexist. A neutral or lipid-friendly antihypertensive agent is probably useful in the presence of lipid abnormalities. Similarly, statins have been shown to decrease cardiovascular risk in hypertensive patients. There is also experimental and clinical evidence that statins have blood pressure (BP)-lowering effects. In this review, we discuss the beneficial effects of statins on BP, and provide an overview of the underlying pathophysiology. We also consider the evidence justifying the use of statins in the management of hypertensive patients.

Adipose tissue cellularity and hemodynamic indexes in obese patients with hypertension.

Fat-cell weight, fat-cell number, and hemodynamic indexes were determined in 25 obese men with sustained elevation of BP. Fat-cell weight (and not fat-cell number) was positively correlated with overweight (r = .51) and mean arterial pressure (MAP) (r = .57) in basal conditions. After body weight reduction, BP decreased significantly through a decrease in cardiac index due to a predominant decrease in heart rate. Simultaneously, fat-cell weight decreased significantly. The ratio between the change in BP and the change in body weight, ie, the ability to decrease pressure per unit weight loss, was positively related to the level of initial BP (r = .80) and reached a plateau above 120 mm Hg of the initial MAP. We suggest that, in patients with obesity and hypertension, high BP is associated with hypertrophic obesity, and after body weight reduction, the simultaneous decrease in BP, heart rate, and fat-cell weight could be mediated by neurogenic mechanisms.

Association of left ventricular diastolic dysfunction with 24-h aortic ambulatory blood pressure: the SAFAR study.

Aortic blood pressure (BP) and 24-h ambulatory BP are both better associated with target organ damage than office brachial BP. However, it remains unclear whether a combination of these two techniques would be the optimal methodology to evaluate patients' BP in terms of left ventricular diastolic dysfunction (LVDD) prevention. In 230 participants, office brachial and aortic BPs were measured by a validated BP monitor and a tonometry-based device, respectively. 24-h ambulatory brachial and aortic BPs were measured by a validated ambulatory BP monitor (Mobil-O-Graph, Germany). Systematic assessment of patients' LVDD was performed. After adjustment for age, gender, hypertension and antihypertensive treatment, septum and lateral E/Ea were significantly associated with office aortic systolic BP (SBP) and pulse pressure (PP) and 24-h brachial and aortic SBP and PP (P ⩽ 0.04), but not with office brachial BP (P ⩾ 0.09). Similarly, 1 standard deviation in SBP was significantly associated with 97.8 ± 20.9, 86.4 ± 22.9, 74.1 ± 23.3 and 51.3 ± 22.6 in septum E/Ea and 68.6 ± 2 0.1, 54.2 ± 21.9, 37.9 ± 22.4 and 23.1 ± 21.4 in lateral E/Ea, for office and 24-h aortic and brachial SBP, respectively. In qualitative analysis, except for office brachial BP, office aortic and 24-h brachial and aortic BPs were all significantly associated with LVDD (P ⩽ 0.03), with the highest odds ratio in 24-h aortic SBP. Furthermore, aortic BP, no matter in the office or 24-h ambulatory setting, showed the largest area under receiver operating characteristic curves (P ⩽ 0.02). In conclusion, 24-h aortic BP is superior to other BPs in the association with LVDD.

Intravascular volume, extracellular fluid volume, and total body water in obese and nonobese hypertensive patients.

Intraarterial blood pressure, plasma volume, extracellular and interstitial (IFV) fluid volumes, and total and intracellular (IBV) body water were evaluated in 50 men: 16 obese hypertensive patients, 16 nonobese hypertensive patients, and 18 normal subjects of similar age. In obese hypertensive subjects, the IBW/IFV ratio was significantly increased (p less than 0.01) in comparison with both control subjects and nonobese hypertensive patients. After body weight reduction, blood pressure (p less than 0.01), heart rate (p less than 0.05), and the IBW/IFV ratio (p less than 0.01) significantly decreased. The decrease in the ratio was due to an absolute increase in the interstitial fluid volume, related to a shift of fluid volume from the intracellular to the interstitial space. Thus, obese hypertensive patients have an increased water cell content, causing an altered partition between the intracellular and the interstitial spaces.

Extracellular and interstitial fluid volume in obesity with and without associated systemic hypertension.

Fluid volumes and cardiac and renal hemodynamics were investigated in 44 obese men, 22 with normal blood pressure and 22 with sustained essential hypertension. For the same degree of obesity hypertensive patients had a higher value in extracellular (p less than 0.05) and interstitial fluid (p less than 0.01) volumes than normotensive subjects, while plasma volume, total body water, body cellular water, cardiac output, renal blood flow and glomerular filtration rate were similar. For the same level of blood pressure, the expansion of extracellular and interstitial fluid volume paralleled the degree of obesity. Thus, obese patients with hypertension have an absolute increase in extracellular and interstitial fluid volumes. The increase was related both to the degree of overweight and to the mechanisms of hypertension.

Comparison of oral MK 421 and propranolol in mild to moderate essential hypertension and their effects on arterial and venous vessels of the forearm.

The efficacy of MK 421 and propranolol was compared in 48 patients with mild to moderate hypertension. Each patient was randomly assigned to receive 1 of the drugs for 12 weeks. Additionally, a subgroup of 28 patients underwent studies of forearm arterial and venous circulation by means of pulsed Doppler and mercury-in-silastic plethysmography. Both drugs reduced supine and standing blood pressure (BP) (p less than 0.001). Propranolol reduced heart rate (p less than 0.001), while MK 421 did not change it. Brachial artery diameter, blood velocity and flow increased after MK 421 (p less than 0.001), but were not changed after propranolol therapy. Forearm vascular resistance decreased after MK 421 (p less than 0.001) and after propranolol (p less than 0.05). Forearm venous tone was unaffected on MK 421, but increased after propranolol (p less than 0.01). Thus, in moderate hypertension, 3 months of treatment with MK 421 or propranolol similarly decrease BP, but affect the forearm circulation differently: MK 421 dilates both the brachial artery and the arterioles of the forearm, but does not affect the venous vessels, and propranolol causes little arterial change but increases the forearm venous tone.

Home self-monitoring of blood pressure: is fully automated oscillometric technique as good as conventional stethoscopic technique?

Home blood pressure (HBP) measurement is becoming increasingly popular as an additional source of information for the practicing physician. Whether HBP measured with a fully automated oscillometric device (oHBP) is more reliable than HBP measured with an aneroid sphygmomanometer and a stethoscope (sHBP) remains unclear. We compared sHBP with oHBP using as a reference method daytime ambulatory blood pressure (ABP), as this is believed to be a better index of an individual's overall level of pressure. Forty-six hypertensive patients measuring HBP with aneroid devices were retrained by a standard 30 min protocol that included training in the technique of measurement, checking patients' devices, and testing patients' performance in stethoscopic measurement. Patients were randomized to measure for 2 weeks either sHBP using their own calibrated aneroid devices or oHBP using a validated fully automated oscillometric device (Omron HEM-705CP). Then 24 h ABP monitoring was performed (SpaceLabs 90207) and patients crossed over for a second 2 week period by using the alternative HBP measurement technique. Mean sHBP was not different from mean oHBP, and there was a close correlation between them (r = 0.82/0.76 for systolic/diastolic BP, P < .001). Daytime ABP was not different from oHBP or sHBP and was closely related to both of them (oHBP, r = 0.59/0.72 systolic/diastolic BP, P < .001; sHBP, 0.50/0.65, P < .001). Age was significantly related with diastolic ABP-sHBP difference (r = 0.33, P < .05). These results suggest that HBP measured with validated fully automated oscillometric devices is equally reliable in predicting average ABP as that measured with calibrated aneroid sphygmomanometers used by very carefully trained patients. In clinical practice, HBP monitoring by using reliable automated devices is probably more feasible than to achieve a high standard of stethoscopic HBP measuring technique.

Blood pressure during siesta: effect on 24-h ambulatory blood pressure profiles analysis.

Blood pressure (BP) during siesta declines to levels similar to those of night time sleep. The objective of the study was to assess the effect of siesta on 24-h ambulatory BP (ABP) data. Two different approaches were employed for the definition of day and night periods: (1) actual patient reported day and night intervals (ACT) with siesta period analysed as a third time period; and (2) arbitrary day and night time intervals (ARB) with the presence of siesta being ignored. A total of 203 24-h ABP recordings were analysed, with a siesta during ABP monitoring reported in 154 of them. Mean siesta BP was very close to ACT night time BP. Among recordings with a siesta, ACT daytime BP was higher and night time BP lower than the corresponding ARB BPs (P < 0.001). The magnitude of night time BP drop was greater with ACT intervals, resulting in a lower percentage of non-dippers (P < 0.001). Among 49 recordings without a siesta, differences between ACT and ARB BPs were less pronounced for daytime but not for night time. Differences in the magnitude of nocturnal BP drop between ACT and ARB periods, although statistically significant, did not affect the prevalence of non-dippers. In conclusion, analysis of 24-h BP profiles by using ARB instead of ACT day and night intervals results in underestimation of the nocturnal BP drop and overestimation of the proportion of non-dippers. This bias is more pronounced in patients who take a siesta during ABP monitoring.

Home monitoring of blood pressure: limited value in general practice.

To investigate the reliability of home blood pressure (HBP) measurement as it is generally used in practice, we studied 50 consecutive newly referred hypertensive patients that were measuring HBP for at least 6 months before referral. No specific instructions on the technique of HBP measurement were given to the patients. HBP was compared to clinic BP (CBP) by using daytime ambulatory BP (ABP) as a reference method. The technique of HBP measurement used by the patients was assessed on the basis of a detailed questionnaire and the accuracy of the devices was tested against a mercury column. There was no difference between the degree of similarity of ABP with HBP or CBP (mean value of discrepancies and correlation coefficients) for systolic BP (SBP) and little difference for diastolic BP (DBP). However, the variability of discrepancies between HBP and ABP was equal to the corresponding variability between CBP and ABP, indicating that HBP was not better predictor of ABP than CBP. Although patients measured HBP more frequently than generally recommended, poor standardisation of measurement and wrong technique were particularly common. In conclusion, in the present study HBP measurement offered no advantage over CBP in predicting ABP. The theoretical advantages of HBP may be partially offset by incorrect technique and less standardised conditions of measurement. Without patients education and regular maintenance of devices HBP offers no advantage over CBP and should not be used. (This article is based on data presented at the 7th European Hypertension Society Meeting in Milan, June 1995).

Plasma insulin, plasminogen activator inhibitor, and ankle-brachial systolic blood pressure ratio in overweight hypertensive subjects.

BACKGROUND: In hypertensive subjects, the ratio between ankle and brachial systolic blood pressure (ABI) has been shown to be an independent risk factor for cardiovascular diseases, particularly in the elderly. Plasma insulin may be an important interconnecting factor explaining this observation. PURPOSE: In a population of middle-aged subjects with essential hypertension and moderate overweight, we identified whether the decrease in the ABI ratio was associated with the clinical and biochemical factors involved in resistance to insulin. Patients with diabetes and/or arteriosclerosis obliterans of the lower limbs were excluded from the population. Subjects were or were not on antihypertensive therapy. RESULT: On the basis of univariate correlations, the ABI ratio was found to be significantly and negatively associated not only with the degree of abdominal fat distribution, but also with the usual biological features of resistance to insulin: plasma triglycerides and cholesterol; plasma glucose and insulin; and plasminogen activator inhibitor (PAI) antigen. In a multivariate analysis in subjects with untreated hypertension, the ABI ratio was significantly and negatively associated with only three variables: age, plasma insulin and PAI antigen. In treated hypertensive subjects, only the role of age and insulin remained significant. CONCLUSION: Since the alterations of the ABI ratio may be considered as a marker of the changes in the structure and function of arteries of the lower limbs, the study provides evidence that plasma insulin and PAI antigen, independently of the presence of significant atherosclerotic occlusive lesions, are susceptible to alter the pressure wave transmission in conduit arteries of the lower limbs.

[Comparative hemodynamic effects of 2 vasodilators: dihydralazine and diltiazem in permanent essential arterial hypertension]. / Effets hémodynamiques comparés de deux vasodilatateurs: la dihydralazine et le diltiazem dans l'hypertension artérielle permanente essentielle.

Cardiac hemodynamic and diameter, blood flow velocity, volumic flow of the brachial artery measured by pulsed Doppler, were studied before and after diltiazem administration in comparison with dihydralazine in hypertensive patients. After diltiazem administration, blood pressure and total peripheral resistance significantly decreased (P less than 0.001) while cardiac index and heart rate increased (P less than 0.01). After 25 minutes perfusion cardiac output and heart rate returned toward control values, while blood pressure and total peripheral resistance remained decreased. The result contrasted with those observed after dihydralazine, which induced an increase in cardiac index and heart rate. The caliber of the brachial artery decreased significantly (P less than 0.001) after dihydralazine and increased after diltiazem (P less than 0.01). This study shows that 1). The antihypertensive effect of diltiazem was due to a fall in total peripheral resistance associated with a transient baroreflex mediated tachycardia, and 2) diltiazem dilated also large arteries.

[Systolic arterial hypertension in patients amputated for injury]. / L'hypertension artérielle systolique des amputés traumatiques.

The blood pressure of 106 men who had undergone amputation of one limb on account of war injury was compared with that of 184 male controls of the same ages. All subjects with a diastolic pressure above 90 mmHg were excluded from the study. The diastolic pressure was statistically equivalent in both groups, but the amputees had a significantly higher systolic pressure. Changes in the visco-elastic properties of the arterial system related to amputation might be responsible for this rise in systolic pressure.

Assessment of differences between repeated pulse wave velocity measurements in terms of 'bias' in the extrapolated cardiovascular risk and the classification of aortic stiffness: is a single PWV measurement enough?

Currently, there is no recommendation regarding the minimum number of pulse wave velocity (PWV) measurements to optimize individual's cardiovascular risk (CVR) stratification. The aim of this study was to examine differences between three single consecutive and averaged PWV measurements in terms of the extrapolated CVR and the classification of aortic stiffness as normal. In 60 subjects who referred for CVR assessment, three repeated measurements of blood pressure (BP), heart rate and PWV were performed. The reproducibility was evaluated by the intraclass correlation coefficient (ICC) and mean±s.d. of differences. The absolute differences between single and averaged PWV measurements were classified as: ≤0.25, 0.26-0.49, 0.50-0.99 and ≥1 m s(-1). A difference ≥0.5 m s(-1) (corresponding to 7.5% change in CVR, meta-analysis data from >12 000 subjects) was considered as clinically meaningful; PWV values (single or averaged) were classified as normal according to respective age-corrected normal values (European Network data). Kappa statistic was used to evaluate the agreement between classifications. PWV for the first, second and third measurement was 7.0±1.9, 6.9±1.9, 6.9±2.0 m s(-1), respectively (P=0.319); BP and heart rate did not vary significantly. A good reproducibility between single measurements was observed (ICC>0.94, s.d. ranged between 0.43 and 0.64 m s(-1)). A high percent with difference ≥0.5 m s(-1) was observed between: any pair of the three single PWV measurements (26.6-38.3%); the first or second single measurement and the average of the first and second (18.3%); any single measurement and the average of three measurements (10-20%). In only up to 5% a difference ≥0.5 m s(-1) was observed between the average of three and the average of any two PWV measurements. There was no significant agreement regarding PWV classification as normal between: the first or second measurement and the averaged PWV values. There was significant agreement in classification made by the average of the first two and the average of three PWV measurements (κ=0.85, P<0.001). Even when high reproducibility in PWV measurement is succeeded single measurements provide quite variable results in terms of the extrapolated CVR and the classification of aortic stiffness as normal. The average of two PWV measurements provides similar results with the average of three.

Diagnostic value of rapid urease test and urea breath test for Helicobacter pylori detection in patients with Billroth II gastrectomy: a prospective controlled trial.

AIM: The aim of this work was to assess the reliability of rapid urease test (RUT) and urea breath test (UBT) for detecting Helicobacter pylori (H. pylori) in patients with Billroth II (BII) gastrectomy, using histology as reference. METHODS: In this prospective controlled study, 31 consecutive patients with BII gastrectomy and 73 controls who had an indication for endoscopy were included. Their H. pylori status was assessed with biopsies for histology, RUT and UBT. Histology served as the gold standard. Only the biopsies from the gastric fundus were evaluated. Specificity, sensitivity, positive and negative predictive value, degree of agreement and k-statistics were used. RESULTS: RUT and UBT for detecting H. pylori in the control group had excellent agreement [97%, kappa (k)=0.94 and 99%, k=0.97 respectively] with biopsies. In BII patients, RUT from fundic biopsies had very good agreement (87%, k=0.74) compared to histology from fundic biopsies, whereas the UBT was unreliable (agreement: 71%, k=0.41) compared to histology. CONCLUSION: The RUT from fundic biopsies in BII patients is a reliable test for H. pylori detection, whereas the UBT is unreliable.

Sex-dependence of body fat distribution in patients with obesity and hypertension.

The relationship of body fat distribution with blood pressure, fat cell weight and extracellular fluid volume was studied and compared in 20 obese hypertensive men and 20 obese hypertensive women of similar age, degree of overweight and blood pressure level. Body fat distribution, as reflected by the ratio between waist and hip circumference (W/H ratio), was significantly higher in male than in female obese patients. The W/H ratio was positively and independently correlated with systolic arterial pressure both in males and females. However, for the same W/H ratio, systolic arterial pressure was higher in females. The W/H ratio was positively correlated with gluteal fat cell weight only in males and not in females. Both in males and females, the W/H ratio was positively correlated with extracellular fluid volume, independently of the level of blood pressure level and/or the degree of obesity. The study provided evidence that the relationship between body weight and blood pressure in obese hypertensives is affected by the sex-dependence of body fat distribution with possible interferences on fat cell weight and extracellular fluid volume. Several epidemiological studies have emphasized the positive correlation observed between body weight and blood pressure in many. Many investigations have documented the association of blood pressure with body weight, weight to height, overweight or other indices of fatness such as skinfold thickness. However, the correlation coefficients of these different relationships were found constantly small, indicating that the relationship between overweight and blood pressure is somewhat complex. In patients with hypertension, body weight was shown to be strongly related with the levels of both blood pressure and extracellular fluid volume. On the other hand, patients with overweight and hypertension were found to be principally affected by hypertrophic obesity, as shown by the evaluation of fat cell weight. However these findings were exclusively observed in males. No solid data were reported in females. The relationships between body weight and extracellular fluid on one hand, and between body weight and fat cell weight on the other hand, are certainly different in males and in females. First, in females, extracellular fluid volume is submitted to cyclic changes in sodium balance involving the effect of sex steroid hormones. Second, body fat distribution, a parameter which is weakly correlated to blood pressure, is different in males and females. In males, body fat predominates in the upper part of the body while, in females, adiposity is mainly observed in the lower part of the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Additive hypotensive effect of a dihydropyridine calcium antagonist to that produced by a thiazide diuretic: a double-blind placebo-controlled crossover trial with ambulatory blood pressure monitoring.

The study was designed to investigate whether a long-acting dihydropyridine calcium antagonist has additional antihypertensive effect when combined with currently used low-dose thiazide diuretic therapy. After 6 weeks with open chlorthalidone monotherapy at 25 mg daily, hypertensive patients with trough diastolic BP 90-115 mm Hg were randomly assigned to receive double-blind lacidipine, 4 mg daily or matching placebo for 4 weeks, while continuing to receive background chlorthalidone. Then patients crossed over to the alternative regimen for a second 4-week period. Clinic and 24-h ambulatory blood pressure (BP) were measured on the final day of chlorthalidone monotherapy and on the final day of each double-blind treatment. Seventeen patients completed the study [mean age, 51.0 +/- 6.9 (SD) years]. Clinic BP was lower with lacidipine versus placebo (systolic, p < 0.01; diastolic, p < 0.05). Daytime ambulatory BP was reduced with lacidipine (p < 0.05), whereas nighttime BP was unchanged. Mean 24-h ambulatory diastolic BP also was reduced on lacidipine (p < 0.05). Heart rate was increased on lacidipine during both daytime (p < 0.01) and nighttime (p < 0.05). In conclusion, when added to chlorthalidone, lacidipine produced a significant reduction in clinic and ambulatory BP during daytime but not nighttime. This was associated with increased heart rate. Modem long-acting dihydropyridines may produce small but clinically significant additive antihypertensive effects in patients uncontrolled on low-dose thiazide monotherapy.