Julian Rosenthal

Lovastatin alters blood rheology in primary hyperlipoproteinemia : dependence on lipoprotein(a) ?

As part of a randomized, single‐blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemor‐heologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and de for mobility, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (≤ 25 mg/dL) high‐density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp (a) levels (>25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low‐density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.

PREVENTION BY SOMATOSTATIN OF RISE IN BLOOD PRESSURE AND PLASMA RENIN MEDIATED BY BETA‐RECEPTOR STIMULATION

The interrelationships of increased plasma renin and elevated blood pressure following acute β‐stimulation by orciprenaline and its prevention by somatostatin was studied in normal man. During somatostatin infusion basal values of renin and blood pressure were unchanged. Following orciprenaline both variables increased significantly. Combination of somatostatin and orciprenaline reduced the rise in plasma renin activity by 49%, mean arterial blood pressure by 21% and heart rate by 19%, compared with β‐stimulation alone.

Effects on Blood Pressure of the α-Glucosidase Inhibitor Acarbose Compared with the Insulin Enhancer Glibenclamide in Patients with Hypertension and Type 2 Diabetes Mellitus

AimTo investigate the relationship between hypertension and hyperinsulinaemia, the effects on blood pressure and insulin levels of two oral antidiabetic agents with different mechanisms of action, acarbose (an α-glucosidase inhibitor) and glibenclamide (an insulin promoter), were compared in patients with hypertension and type 2 diabetes mellitus.PatientsObese men and women (mean age 57.5 years) with mild hypertension (WHO grade I or II) and type 2 diabetes mellitus. Study design: Patients (n = 76) were randomised to receive either acarbose 300 mg/day or glibenclamide 5 mg/day for up to 6 months. Twenty-four-hour blood pressure (BP) profiles were recorded at baseline, and after 3 months and 6 months of treatment. Lifestyle modification was allowed, but no concomitant antihypertensive drugs were permitted.ResultsAt baseline, mean 24-hour systolic/diastolic BP was 134.9 ± 11.6/84.2 ± 6.2mm Hg in the acarbose-treated group versus 138.5 ± 14.1/85.9 + 6.2mm Hg in glibenclamide-treated patients. At 6 months, mean 24-hour systolic BP was reduced by a mean 5.2mm Hg with acarbose versus only 1.6mm Hg with glibenclamide (p = 0.0001). Mean 24-hour diastolic BP fell by 2.4mm Hg and 5.5mm Hg with acarbose and glibenclamide treatment, respectively (p = 0.003). Fasting serum insulin levels were significantly (p < 0.05) lower following 6 months’ treatment with acarbose versus glibenclamide (7.9 ± 2.3 mU/L vs 22.3 ± 19.1 mU/L, respectively), as were post-prandial insulin levels (51.6 ± 43.1 mU/L vs 59.0 ± 51.4 mU/L, respectively). Acarbose therapy was also associated with improvement (reduction) in bodyweight and glycosylated haemoglobin (HbA1c) values.ConclusionOral antidiabetic agents with different mechanisms of action appear to have significant effects on BP in patients with hypertension and diabetes mellitus, albeit in different ways. Acarbose may be useful in lowering BP in certain patients with type 2 diabetes mellitus, particularly those with isolated systolic hypertension.

Is Increased Plasma Viscosity A Risk Factor for High Blood Pressure

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two- stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cho lesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and dem onstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be an swered from cross-sectional data. However, even if plasma hyperviscosity rep resents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.

Predictive value of radionuclide methods in the diagnosis of unilateral renovascular hypertension

The validity of noninvasive (iodine-131 iodohippurate renogram, iodine-131 ortho-iodohippurate clearance, indium-113m EDTA-technetium-99m DTPA sequential renal scan) and invasive (xenon-133 washout) radionuclide screening tests was evaluated in the diagnosis of 105 patients with unilateral renovascular hypertension (RVH) and in 45 patients with essential hypertension (EH). In RVH positive findings on the stenosed side were noted in 73% of renograms, 73% of o-iodohippurate-clearance tests (n=22), 81% of sequential renal scans, and 90% of xenon-washout studies (n=67). In a subgroup of 55 retrospectively selected patients with normal or improved blood pressure following renovascular surgery, the preoperative findings had been positive on the stenosed side in 78% of renograms, 75% of o-iodohippurate-clearance tests (n=20), 85% of sequential renal scans, and 93% of xenon-washout studies (n=23). The sequential renal scan appears to be a sufficiently reliable method in noninvasive screening for unilateral RVH, although invasive xenon-washout studies show a higher percentage of hemodynamic alterations in the stenosed kidney. O-iodohippurate clearance tests, and in particular xenon-washout studies, can reveal arteriosclerotic lesions in the contralateral, non-stenosed kidney, which may be of importance when the decision for renovascular surgery is pending.

A multicenter trial of doxazosin in West Germany

The antihypertensive efficacy and safety of the new long-acting selective alpha 1 inhibitor doxazosin were assessed in patients seen in clinical practice. A total of 232 mild to moderate hypertensive patients were treated by 35 physicians. After an initial 2-week period (phase 1) during which eligibility to enter the study was determined (diastolic blood pressure [BP] of 95 to 114 mm Hg), all patients received doxazosin 1 to 8 mg once daily for 8 weeks (phase 2). Patients were then maintained for another 4 weeks on the dosage necessary to control diastolic BP to less than or equal to 90 mm Hg (phase 3). Efficacy and toleration of doxazosin therapy during the study period were good; 81% of evaluable patients (n = 180) achieved BP control with a once-daily mean dosage of 3.3 mg. At the end of phase 2 BPs were reduced by (systolic/diastolic) 23.8/17.3 (sitting) and 23.7/17.1 mm Hg (standing). Side effects were generally mild to moderate and either were tolerated or disappeared with continued therapy; 7 patients withdrew from the study because of intolerable side effects. Overall results demonstrated that doxazosin is suitable for treatment of mild to moderate hypertension and can be administered on a once-daily basis, which enhances compliance.

Aging and the cardiovascular system.

As a result of aging, a variety of structural and biochemical changes occur in arterial walls that result in hemodynamic adaptations. With age, there is a thickening of intima and media, together with an increase in the number of smooth muscle cells, synthesis of collagen and elastin, and deposition of calcium, glycosaminoglycans, free and esterified cholesterol, and sphingolipids. These changes are similar to those observed in atherosclerosis, which is accompanied by marked increases of intimal smooth muscle cells and connective tissue constituents. The net effects of both aging and atherosclerosis are a loss of elasticity and distensibility. This results in a decrease in arterial compliance or capacitance, which in turn means that with increasing age systolic blood pressure (SBP) tends to be higher, and diastolic blood pressure (DBP) lower. As a consequence of structural changes both in myocardium and vessels, cardiac output and renal and hepatic blood flow undergo adaptive alterations in order to meet the requirements of central hemodynamics and peripheral circulation. The implications of these processes of aging demand appropriate treatment of cardiovascular disorders, in particular hypertension, which occurs in 30-50% of patients above the age of 60 years. Appropriate treatment may demand dose adjustment and careful selection of antihypertensive drugs with a minimum of side effects, which additionally are capable of diminishing preload and afterload.

Effects of felodipine ER and hydrochlorothiazide on blood rheology in essential hypertension—a randomized, double‐blind, crossover study

Abstract. The haemorheological effects of felodipine extended release (ER), a new dihydropyridine calcium antagonist, were compared with hydrochlorothiazide (HCTZ) in 28 mild to moderate hypertensives (18 men and 10 women, aged 30–70 years) in a randomized, double‐blind, crossover trial. Antihypertensive drugs were gradually discontinued. Felodipine ER, 10 mg, was given once daily for 2 weeks, and after another wash‐out period of 1 week, patients were switched to 25 mg HCTZ, once daily, and vice versa. Whole blood viscosity (BV) at three different shear stresses, haematocrit (Hct), plasma viscosity (PV), red blood cell (RBC) aggregation, RBC deformability, and fibrinogen were measured under standardized conditions 2.5 h after medication, and after 2 weeks of treatment (24 h post‐dosing). Felodipine ER improved BV acutely, but not during treatment over a 2‐week period. By contrast, HCTZ did not affect BV, but decreased RBC deformability 2.5 h after medication intake. After 2 weeks of treatment, the negative effect on RBC deformability had increased slightly. Furthermore, fibrinogen and PV were significantly elevated at this stage. In summary, felodipine ER did not improve blood rheology over a 2‐week treatment period in this study. HCTZ exhibited marginal but significant negative effects on fibrinogen, PV and indices of RBC deformability, but not on RBC aggregation.

Hemodynamic and renin responses to somatostatin in essential hypertension.

Abstract Recent studies indicate that somatostatin inhibits furosemide-induced hyperreninemia; 1,2 in addition, somatostatin has been reported to block increases of blood pressure induced by administration of β-adrenergic agents. 3 These findings in normal subjects prompted further investigations in patients with essential hypertension.

Pranidipine, a novel calcium antagonist, once daily, for the treatment of hypertension: A multicenter, double-blind, placebo-controlled dose-finding study

SummaryThe antihypertensive effects and tolerance of once-daily (od), pranidipine, a novel dihydopyridine derivative with a long duration of action, were evaluated in a double-blind, placebo-controlled, parallel-group dose-finding study. A total of 199 patients, with a diastolic blood pressure (BP) of 95–115 mmHg, were included in the trial. After 4 weeks on placebo, patients were randomly assigned to either placebo or pranidipine at 1, 2, 4, or 8 mg od for a further 4 weeks. A dose response was seen in the reduction (Δ) of diastolic BP: placebo, Δ1.7 mm Hg; 1 mg, Δ6.4 mmHg; 2 mg, Δ7.5 mmHg, p<0.01; 4 mg, Δ11.5 mmHg, p<0.01; and 8 mg, Δ10.6 mmHg, p<0.01. There were no meaningful changes in heart rate. The number of responders (decrease of diastolic blood pressure to <90 mmHg and by 10 mmHg or more from baseline value) in each group also revealed a dose-response relationship: placebo=9%; 1 mg=25%, n.s.; 2 mg=27%, n.s.; 4 mg=41.5%, p<0.01; and 8 mg=41%, p<0.01 (compared with placebo). Plasma concentrations of pranidipine also demonstrated linear dose-response relationships. An increase in adverse events was observed within the 8 mg group. The degree of reduction in BP and the number of responders were not greater in the 8 mg group compared with the 4 mg group, although the plasma concentration (mean values, ng/dl) of pranidine in the 8 mg group was higher (2.2 on day 42; 2.3 on day 56) compared with the 4 mg group (1.4 on day 42; 1.6 on day 56). In conclusion, pranidipine is a well-tolerated and 24-hour effective novel calcium antagonist that reduces BP in a dose-related manner up to 4 mg od.