R. Iannuzzi

Long-Term Magnesium Supplementation in Essential Hypertension

The main objective of this clinical trial was to evaluate the effects of magnesium pidolate (15 mmol/day) on blood pressure at rest and during sympathetic stimulation induced by cold, isometric and tilt test; peripheral blood flow has been evaluated by strain-gauge plethysmography. Fourteen mild to moderate hypertensives (8 males, 6 females, age range 40-60 years) were randomly given magnesium or placebo in a double-blind parallel clinical trial for 6 months. In the actively treated group magnesium urinary excretion increased from 5.3 +/- 2 to 7.7 +/- 2 mmol/24 h, and serum magnesium changed from 0.9 +/- 0.1 to 1.0 +/- 0.2 mmol/l. On magnesium, BP changed at rest from 156/97 +/- 12/4 to 149/90 +/- 8/3 mm Hg, during cold pressor test from 169/105 +/- 9/6 to 174/105 +/- 15/4, during isometric exercise from 170/107 +/- 13/9 to 170/105 +/- 20/6, and during tilt test from 149/96 +/- 11/6 to 153/96 +/- 17/7 mm Hg. Similar changes were observed in the placebo group. Peripheral resistances were 14.7 +/- 4 and 9.8 +/- 2 PRU before and after magnesium, respectively. These data indicate that long-term magnesium pidolate supplementation does not affect blood pressure at rest and during sympathetic stimulation, despite a slight, nonsignificant reduction in forearm peripheral resistance.

Early changes of the arterial carotid wall in uncomplicated primary hypertensive patients. Study by ultrasound high-resolution B-mode imaging.

Arterial hypertension is frequently responsible for arteriosclerotic damage in the carotid region. Nevertheless, there is as yet no general agreement that hypertension is correlated with lesions detected by noninvasive means in the carotid arteries. We studied, by noninvasive echotomographic technique, 70 uncomplicated primary hypertensive individuals without clinically evident end-organ complications and 30 normotensive matched control subjects to detect early lesions of carotid arteries. The presence of other cardiovascular risk factors was assessed, and heart structure and function were studied by echocardiography. Although hypertensive individuals were comparable to control subjects for other risk factors, they showed a marked increase in the thickness of the intimal-medial complex of the carotid wall (0.71 +/- 0.4 versus 0.56 +/- 0.2 mm, P < .001 in the right carotid and 0.83 +/- 0.3 versus 0.58 +/- 0.2, P < .003 in the left), in left ventricular mass (203 +/- 52 versus 176 +/- 37 g, P < .05), and in the prevalence of definite plaques of the carotid wall, both monolaterally and bilaterally (P < .003 by chi 2 test). Among the different factors contributing to the increase in thickness of the carotid artery wall, standing blood pressure, serum triglycerides, and age were found to be the best predictors (they accounted for about 16% of the variability, P < .005). These results indicate that carotid arteries of hypertensive individuals undergo degenerative changes, just as shown for hypercholesterolemic and diabetic patients in other studies. This supports the use of B-mode ultrasound imaging to detect early involvement of the carotid region before the appearance of any end-organ damage of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Diameter and Blood Flow Velocities in Cerebral Circulation in Hypertensive Patients

BACKGROUND AND PURPOSE The recent development of noninvasive techniques for the evaluation of the carotid arteries has focused attention on the study of arterial wall thickness to identify early lesions of vessels in patients at high risk for atherosclerosis, such as those with hypercholesterolemia, diabetes mellitus, and hypertension. METHODS In a sample of 70 hypertensive patients without clinical evidence of target organ damage, we showed a thickening of the intimal plus medial layers compared with age- and sex-matched normotensive control subjects. In this sample we also studied the diameter of the carotid arteries by ultrasound imaging, and we studied flow velocities in common carotid, internal carotid, and middle cerebral arteries by Doppler technique. Pulsatility and resistance indexes were calculated. RESULTS Absolute values of the carotid diameter were similar in the two groups (6.3 +/- 0.7 versus 6.0 +/- 0.8 mm); however, the ratio of diameter to blood pressure was significantly reduced in hypertensive compared with normotensive subjects (5.3 +/- 0.7 versus 6.5 +/- 0.8; P < .001 for mean blood pressure). Parietal stress was increased in the hypertensive subgroup and significantly correlated with arterial diameter in the normotensive group but not in the hypertensive group. No significant differences between the two groups were observed in blood flow velocities, with the exception of a slight significant increase of mean velocity in the internal carotid artery in hypertensive patients (37.5 +/- 9.1 versus 32.7 +/- 3.0 cm/s; P < .02). CONCLUSIONS These results indicate that in addition to the degenerative changes of the common carotid wall, the diameter of the carotid artery and the relation to parietal stress show an early impairment in patients with uncomplicated hypertension.

Isolated office hypertension and end-organ damage

Background Patients with elevated blood pressure levels in the doctors office but normal blood pressures at other times have recently been described as having ‘isolated office hypertension’ (IOH). There is debate concerning whether this condition is really benign and thus not in need of treatment. Most of the previous studies on this topic included patients who had already been administered antihypertensive treatment, which unavoidably alters their cardiovascular profile. Objective To evaluate whether recently discovered and never-treated patients with isolated office hypertension have structural or functional abnormalities in comparison with normotensive controls. Methods Patients included in the study underwent 24 h ambulatory blood pressure monitoring, M-mode echocardiography and high-resolution echography of carotid arteries. Parameters of lipid and carbohydrate metabolism were also determined. Results We investigated 76 patients (20 with IOH and 56 with sustained hypertension) who had recently been diagnosed hypertensive but never been administered antihypertensive treatment and 32 matched controls. No changes were detected in left ventricular mass (LVM h2.7, 41.5 ± 11, 44.5 ± 10 and 41.5 ± 10 g/cm2.7 in IOH, sustained hypertension and controls, respectively) and in intimal–medial thickness (IMT, 0.54 ± 0.13, 0.59 ± 0.14 and 0.55 ± 0.16 mm, respectively). However, the left ventricular diastolic function was significantly different (E/A = 1.08 ± 0.3, 1.04 ± 0.3 and 1.43 ± 0.3, respectively, P = 0.02) and the carotid diameter significantly lower than that expected from the pressure–diameter relationship for normotensives. Conclusions These results, at variance with those of others, suggest that IOH affects the cardiovascular system even during the early phases of the disease and indicate the need for prospective clinical trials to evaluate the benefit from early treatment of IOH patients.

Serum cholesterol affects blood pressure regulation

A close relationship between abnormalities of the lipid metabolism and arterial hypertension has been observed in several epidemiological studies. The aim of the present study was to investigate whether serum cholesterol might affect blood pressure (BP) levels at rest, during ambulatory monitoring or during sympathetic stimulation—independently of other variables such as body weight or serum insulin—thus influencing the outcome of hypertensive complications. Seventy-three patients with sustained newly-discovered and never-treated hypertension were divided into tertiles according to their serum cholesterol levels and their resting BP, 24-h BP and BP during isometric exercise (handgrip) were compared. Cardiac mass and carotid wall thickness were measured by echographic technique. The results were that tertiles were similar for body weight, blood glucose and serum insulin, but different for serum cholesterol and triglycerides. BP at rest and during 24-h monitoring was similar in the three groups, whilst a significant difference was detected during sympathetic stimulation by handgrip, with systolic and diastolic BP increasing by 16/12, 28/19 and 30/23 mm Hg (P < 0.01) in lower, medium and higher tertiles, respectively. Intima-media layer of the carotid arteries was also significantly thickened in the groups with higher cholesterol levels (0.54 ± 0.07, 0.67 ± 0.14, 0.68 ± 0.15, P < 0.05). These data support the conclusion that even in patients with recently discovered hypertension, cholesterol levels may influence the BP response to adrenergic stimulation as well as the outcome of target organ disease.

Clinic-daytime blood pressure difference and cardiovascular damage.

OBJECTIVE To investigate whether the clinic-daytime blood pressure difference can provide information on vascular reactivity to stress comparable to that of simple noninvasive stimuli such as a cold pressor test and isometric exercise, and whether there is any relationship between this blood pressure difference and noninvasive measurements of the left ventricular mass and carotid arterial wall. DESIGN Patients with newly discovered, never-treated, sustained hypertension were included in the study after a 1 month run-in, during which time their blood pressure was measured three times at 2 week intervals. METHODS Blood pressure was measured by a noninvasive procedure at rest and during a cold pressor test and an isometric exercise. The difference was calculated for systolic, diastolic and mean blood pressure as resting minus daytime ambulatory blood pressure. Parameters of the posterior wall and septal thickness of the left ventricle, aortic root and left atrium were studied by M-mode echocardiography. Carotid wall thickness and diameter were measured using ultrasound. RESULTS The 90 patients enrolled in the study were divided into tertiles of clinic-daytime blood pressure difference. The composition of the groups differed in sex, since the majority of women were in the highest tertile, but was comparable for age, body mass index, renin-aldosterone axis and lipid and carbohydrate metabolism. Blood pressure responses to cold and isometric exercise were more pronounced in patients in the lowest tertile of blood pressure difference. No intergroup differences were detected in echocardiographic parameters of ventricular (left ventricular mass, tertiles I-III: 46.5 +/- 10, 42.3 +/- 8, 44.8 +/- 13 g/m2.7, respectively) and carotid (intima-media thickness, tertiles I-III 0.58 +/- 0.1, 0.54 +/- 0.1, 0.62 +/- 0.1 mm, respectively) structure. CONCLUSIONS The present study indicates that the clinic-daytime blood pressure difference provides different information on cardiovascular reactivity compared with that obtained from the cold pressor test and isometric exercise. Moreover, it does not seem to have any relationship with ventricular hypertrophy and/or carotid wall thickening.

Effects of Isradipine on 24-h Blood Pressure, Left Ventricular Hypertrophy and Hemodynamics in Type II Diabetic Hypertensive Patients.

The effects of 5 mg slow-release isradipine given once daily for both office-taken and monitored 24-h blood pressure, left ventricular mass and forearm hemodynamics have been evaluated by noninvasive methods for 6 months in 12 type II diabetic patients aged 40–60 years with concomitant arterial hypertension of mild to moderate degree. A significant reduction in both supine (from 164/96 to 146/85 mmHg) and standing blood pressure (from 164/100 to 143/89 mmHg) was observed at the end of the treatment period. A slight reduction was detected in waking blood pressure and a more marked reduction in sleeping blood pressure measured by an ambulatory blood pressure monitoring system, although the statistical significance was only approached because of the huge daily variability in blood pressure levels. A significant reduction in left ventricular mass index was detected by M-mode echocardiography (from 153 ± 72 to 122 ± 84 g/m2 body surface area) without any impairment of left ventricular systolic function. Brachial artery compliance was not significantly increased (from 1.86 ± 0.7 to 2.21 ± 0.9 cm4 · dyne-1 · 107) and impedance slightly but nonsignificantly reduced (from 99.6 ± 52 to 65.7 ± 13 dyne5 · cm-5 · 102) by the treatment. These results show that long-term isradipine treatment reduces blood pressure values and left ventricular hypertrophy. However, the findings of this study need to be confirmed in a larger population sample in order to establish whether isradipine really improves the overall cardiovascular risk profile.

METABOLIC EFFECTS OF ISRADIPINE IN NON-INSULIN-DEPENDENT DIABETES MELLITUS(NIDDM) HYPERTENSIVE PATIENTS

Dear Sir: Some antihypertensive drugs have been shown to induce untoward side effects on glucose and lipid metabolism that may accelerate the early development of arteriosclerotic lesions. Several calcium entry blockers have been shown to have a neutral effect on both glucose and lipid metabolism [1]. Isradipine, one of the most recently developed molecules of the dihydropiridine derivatives, has already been proven to cause a significant reduction in blood pressure [2]. The present study was intended to evaluate whether the antihypertensive effect of slow-release isradipine given at the dosage of 5 mg o.d. for 6 months is accompanied by untoward side effects on insulin secretion, glucose control, and lipid profile in hypertensive patients with concomitant type II diabetes mellitus. This open trial included 12 patients (both sexes) with a mild to moderate hypertension [diastolic blood pressure (DBP) 95110 mmHg] and non-insulin-dependent diabetes mellitus (NIDDM) in stable phase treated for diabetes with either nonpharmacological means alone (well-balanced, low-fat diet enriched in undigestible fibers) or diet plus oral hypoglycemic drugs. The protocol excluded patients with malignant or secondary hypertension, target organ damage, moderate hypercholesterolemia (serum cholesterol >250 mg/dl), frank obesity [body mass index (BMI = weight/height 2) >30 for males and >28 for females], use of other drugs interfering with blood pressure and/ or carbohydrate metabolism, pregnancy, lactation, or use of oral contraceptives. Compliance with t reatment was evaluated by questioning the patients at each visit and by counting the remaining pills in each box. After a 4 week washout placebo period, patients were prescribed isradipine at the dose of 5 mg once daily for 6 months. Duplicate measurements of blood pressure (BP) and heart rate (HR) were taken between 9 and 11 a.m. on two occasions before beginning treatment: at 2-week intervals during the first month of therapy and at monthly intervals until the end of the study using an automatic sphygmomanometer (Sentron, Bard Biomedical). The last tablet before BP measurements was taken at 9 am on the previous day. Fasting blood glucose (FBG), giycosylated hemoglobin (Hb Ale), total cholesterol (Chol), triglycerides (Tg) and HDL cholesterol (HDL-chol) were measured before treatment, at the end of the first month of treatment, and at the end of the study. At the same time, glucose and insulin responses to an intravenous glucose tolerance test (IvGTT) were also evaluated. The probability of a patient developing CHD within 10 years was calculated by using the Framingham equations for coronary heart disease (CHD) [3]. Data are given as means -+ SD. Statistical analysis was performed by analysis of variance. Since four patients were unable to complete the 6 month follow-up, the statistical analysis was performed only on the remaining 8 cases. The mean age of the patients was 53 -+ 5 years; body mass index (weightfaeight 2) was 28.1 _ 4.3. Diabetes mellitus at ent ry was well compensated, as shown by the values of HbAlc, FBG, and postprandial blood glucose. No change in these parameters was observed throughout the study (Table 1). Systolic and diastolic BP were reduced after 1 month of isradipine therapy, and the fall in BP remained unchanged during the 6 month observation period. HR was only slightly reduced during isradipine therapy (Table 1). Glucose and insulin responses during IvGTT were similar during the study period, as shown in Figure 1. Total cholesterol and Tg were unchanged, whilst HDL cholesterol increased significantly during treatment (Table 1). The calculated risk of developing CHD within 10 years was significantly reduced from 9.15% to 6.43% (p < 0.01), during treatment. Calcium entry blockers might impair insulin secretion, which is a calcium-mediated process, as shown with acute administration of nifedipine [4]. In the present study we have found that the BP reduction was not accompanied by any impairment in carbohydrate or lipid metabolism, thus extending to isradipine the metabolic neutrality of other dihydropiridine derivatives.