Effect of moderate physical training on left ventricular mass in mild hypertensive persons.

Exercise might reduce blood pressure in mild essential hypertensive individuals, but it could raise left ventricular mass, counteracting the beneficial effects induced by a decrease in blood pressure. Seventeen (group 1) of 25 mild hypertensive patients, nonresponders to a 3-month low sodium diet (2 g/day), were admitted into a physical training program consisting of three weekly sessions of aerobics (20 minutes), bicycling at prefixed loads (20 minutes), and induced muscular relaxation (10 minutes). They were compared with 15 mild hypertensive patients (group 2), nonresponders to the low sodium diet who remained untrained. The follow-up lasted 15.7 +/- 5.8 months. There were significant blood pressure decreases in group 1 at rest (155 +/- 9.8/101 +/- 3.3 vs. 136 +/- 8.1/86 +/- 6.6 mm Hg, p less than 0.001) and at maximal effort (219 +/- 27.4/119 +/- 14.4 vs. 196 +/- 21.8/101 +/- 10.5 mm Hg, p less than 0.001). Maximal work capacity increased from 758.8 +/- 256.7 to 944.1 +/- 203.8 kpm (p less than 0.001). Echocardiographic left ventricular mass index tended to decrease (137.8 +/- 36.3 vs. 125.4 +/- 29.9 g/m2, p = NS), without any significant modification of either left ventricular volume index or left ventricular shortening fraction. No significant changes occurred in group 2. There was no correlation between blood pressure and left ventricular mass changes and left ventricular shortening fraction and left ventricular mass index changes. According to these results, it seems prudent to prescribe physical training to mild hypertensive patients because it does not induce left ventricular mass increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of atenolol in the treatment of hypertension during pregnancy.

This study assessed the effectiveness of atenolol in the treatment of moderate and severe hypertension during pregnancy. Seventy patients (mean age, 30.3 +/- 6.0 years), 35.7% primiparous, were included. Three groups were formed according to Davey and MacGillivray's classification: 1) chronic hypertension without proteinuria (12 patients), 2) gestational hypertension without proteinuria (52 patients), and 3) preeclampsia (six patients). Treatment with atenolol was started when blood pressure was 150/100 mm Hg or higher after 48 hours' rest. The treatment lasted at least 1 week; follow-up was every 2 weeks up to week 36, and from then on, weekly up to delivery. If blood pressure exceeded 160/110 mm Hg and the fetus was not yet mature, a second drug was added. A significant decrease in blood pressure was observed in the three groups (group 1: 155.8 +/- 15.0/100.8 +/- 7.6 versus 135.0 +/- 12.9/85.0 +/- 6.7 mm Hg; group 2: 154.2 +/- 13.6/104.9 +/- 9.3 versus 129.6 +/- 10.2/83.7 +/- 9.1 mm Hg; group 3: 158.3 +/- 27.1/104.1 +/- 8.0 versus 129.1 +/- 6.6/87.5 +/- 6.1 mm Hg). The doses of atenolol were 62.5 +/- 23.0 mg/day in group 1, 70.0 +/- 30.0 mg/day in group 2, and 100.0 +/- 41.0 mg/day in group 3. There was no fetal mortality. No significant difference occurred in newborn body weights. Four babies from group 2 mothers had an Apgar score of less than 7 at 1 minute, but only one remained abnormal after 5 minutes. In the same group, three cases of respiratory distress were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid wall viscosity increase is related to intima-media thickening in hypertensive patients.

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.

Non-modulating hypertension: evidence for the involvement of kallikrein/kinin activity associated with overactivity of the renin-angiotensin system. Successful blood pressure control during long-term Na+ restriction.

BACKGROUND: Non-modulating hypertensives are a subset of sodium-sensitive hypertensives characterized by a failure to modulate renal, vascular and adrenal glomerulosa responsivenesses to angiotensin II appropriately. OBJECTIVE: To investigate the plasma renin activity (PRA) and urinary kallikrein-like activity (Ku) under different sodium conditions in essential hypertensive patients and in the modulating and non-modulating subsets of hypertensives. Additionally, in these groups of patients, the effects on blood pressure of a sustained Na+ restriction were evaluated. METHODS: Fifteen normotensives (10 men, aged 29 +/- 5 years) and 54 untreated hypertensives (30 men, aged 34 +/- 7 years) were each administered subsequently three different diets containing 240, 140 and 50 mmol/day Na+, each diet for 10 days. At the end of each period, the PRA, Ku, 24 h urinary volume and urinary Na+ excretion were measured. Afterwards, the essential hypertensives were classified as 29 modulating essential hypertensives (MHT, 20 men, aged 32 +/- 7 years) and 25 non-modulating essential hypertensives (NMHT, 10 men, aged 36 +/- 8 years). Non-modulating ones were identified as individuals who failed to increase their effective renal plasma flow and to decrease their filtration fraction by at least 30% from baseline values, 10 days after changing from a low (10 mmol/day) to a high (260 mmol/day) Na+ intake. Blood pressure was measured with a Dinamap 8100 Critikon device. Both PRA and Ku were measured during normal Na+ intake by standard methods. Patients were administered a low-Na+ diet (10-50 mmol/day) for 12 months. RESULTS: In essential hypertensives, Ku was lower under the three Na+ diets than it was in normotensives (P < 0.01) whereas the PRA was higher in hypertensives only during the low Na+ intake (P < 0.01). The non-modulating patients showed significantly higher PRA levels (4.0 +/- 0.8 ng ml h, P < 0.05) than did modulating ones (2.6 +/- 1.0 ng ml h) or normotensives (2.3 +/- 1.0 ng ml h). Conversely, non-modulating hypertensives had lower Ku (4.1 +/- 1.0 IU/24 h, P < 0.025) than did modulating ones (6.2 +/- 1.0 IU/24 h) or normotensives (7.8 +/- 2.0 IU/24 h). Blood pressure was significantly reduced during low Na+ intake only in normotensives (month 6: 143 +/- 4/94 +/- 2 mmHg; month 12: 139 +/- 5/89 +/- 3 mmHg) compared with baseline values (169 +/- 4/102 +/- 6 mmHg, P < 0.025). CONCLUSIONS: It was shown that, in non-modulating hypertensives, in addition to an increased PRA, a reduced kallikrein-like activity coexists and seems to be associated with the impaired Na+ handling. Moreover, in these untreated patients the Na+ restriction was able to exert an antihypertensive effect even for long periods.

Carotid wall inertial index increase is related to intima-media thickening in hypertensive patients.

OBJECTIVE: The aim of this study is to evaluate the relationship between carotid intima-media thickness (IMT) and arterial wall inertial behaviour. METHODS: The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. The common carotid artery of eleven normotensive subjects (NTA) and eleven mild-to-moderate essential hypertensive patients (HTA) were measured noninvasively using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure (P) and diameter (D) loops. A linear discrete time model was used to estimate the inertial index (K(M)) using a system modelling-identification approach. RESULTS: In NTA K(M) was 0.333+/-0.256 (mmHg x s2/mm) and IMT 0.643+/-0.061 (mm), whereas in HTA K(M) was 0.798+/-0.590 (P < 0.05) and IMT 0.760+/-0.034 (P < 0.025). When all data of K(M) versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r = 0.61 (P < 0.05) was obtained. CONCLUSION: Wall inertia increase was associated with a higher IMT, suggesting that the intima-media thickening might be partially related to vascular hypertrophy manifested as increase of inertial behaviour.

Higher urinary albumin excretion is associated with abnormal erythrocyte Na(+)/Li(+) countertransport (SLC) in non-modulating essential hypertensives and offspring of hypertensive parents.

Non-modulating is a highly reproducible type of sodium-sensitive hypertension. The aim of this study was to evaluate in non-modulating individuals the erythrocyte sodium-lithium countertransport (SLC) abnormalities, which have been mentioned as a marker of non-modulation, and the association with increased microalbuminuria, as a marker of an early kidney impairment. We measured erythrocyte SLC in 10 normotensives (NT, 28 +/- 4 years), 20 offspring of hypertensive parents being 10 modulating (MHO, 25 +/- 6 years) and 10 non-modulating (NMHO, 26 +/- 5 years), and 23 essential hypertensives being 12 modulating (MHT, 34 +/- 5 years) and 11 non-modulating (NMHT, 32 +/- 4 years). In all the subjects studied, microalbuminuria was determined by duplicate 24-h urine collection by radioimmunoassay. In non-modulating offspring of hypertensive parents and essential hypertensives. SLC was significantly elevated when compared either with normotensives without family history of hypertension, modulating offspring of hypertensive parents or essential hypertensives (P < 0.025). Likewise, 24-h urinary albumin excretion was found higher in non-modulating individuals (essential hypertensives and offspring of hypertensive parents) than in modulating individuals (P < 0.01). In conclusion, non-modulators with higher SLC countertransport sodium transport abnormalities showed higher elimination of microalbuminuria suggesting that non-modulators may have an increased risk for developing cardiovascular morbidity and kidney impairment even in normotensive subjects with familiarity history of hypertension.

[Reduction of the left ventricular mass in essential hypertension patients chronically treated with monotherapy]. / Reducción de la masa ventricular izquierda en hipertensos esenciales tratados crónicamente con monoterapia.

Changes in left ventricular mass (LVM) were measured by echocardiography in 104 mild and moderate essential hypertensives treated with only one drug for at least 12 months. They were classified into 4 groups. G1: 40 patients (p) treated with atenolol (73.6 +/- 31.8 mg daily), G2: 32 p treated with enalapril maleate (17.7 +/- 8.7 mg daily), G3: 22 p treated with nifedipine (44.0 +/- 10.8 mg daily), G4: control group, 10 mild hypertensives without medication. At the end of the treatment blood pressure (BP) fell significantly in the first 3 groups (G1: 155 +/- 19/.98 +/- 11 vs. 136 +/- 11/86 +/- 15 mm Hg, G2: 163 +/- 19/104 +/- 10 vs. 139 +/- 12/90 +/- 8 mm Hg, G3: 166 +/- 17/103 +/- 7 vs. 142 +/- 7/85 +/- 7 mm Hg, p less than 0.001), but remained unchanged in G4. Heart rate was reduced significantly only in G1. Body weight did not change (71 +/- 7 vs. 67 +/- 7, p greater than .05). Patients were subclassified according to wether they had normal (N, LVM less than 120 g/m2 in females, LVm less than 135 g/m2 in males) or increased (H) LVM. There was a significant reduction in LVM in all H subgroups (G1 163 +/- 37 vs. 131 +/- 27 g/m2, G2: 155 +/- 19 vs. 126 +/- 21 g/m2, G3: 158 +/- 2 vs. 138 +/- 38 g/m2, p less than .005). The LVM/left ventricular end-diastolic volume ratio (M/V) fell in all H subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vascular dysfunction in hypertension evaluated by nonivasive assessment of arterial impedance]. / Evaluacion de las alteraciones circulatorias de la hipertension arterial mediante la determinacion no invasiva de la impedancia arterial.

The effects of high blood pressure on arterial vessels has become an important topic of research. These effects can be evaluated by analyzing three major components: systemic vascular resistance, arterial compliance and wave reflection. The increase in systemic vascular resistance and arterial stiffness produces modifications of left ventricular afterload and morphologic changes of pressure and flow waves. These effects can eventually cause structural changes of the left ventricle, an increase in oxygen consumption and a decrease in coronary perfusion. Until recently, invasive methods were the only means to evaluate arterial function. The aim of this review is to assess the usefulness of non invasive methods to determine the components of arterial impedance in order to evaluate the hemodynamic changes due to high blood pressure.

Mechanical vs intrinsic components in the improvement of brachial arterial compliance. Comparison of the effects of atenolol versus ramipril in hypertensive patients.

The aim of this study was to compare the mechanical and intrinsic effects of an angiotensin converting enzyme inhibitor, vs a beta-blocker, on brachial arterial compliance. In a double blind study, 34 essential hypertensive patients were treated for 3 months with either ramipril 2.5-5.0 mg daily (n = 17, age 57 +/- 7 y, 11 males) or atenolol 50-100 mg daily (n = 17, age 53 +/- 8 y, 11 males). Blood pressure (BP), brachial artery diameter (D), brachial-radial pulse wave velocity (PWV) and effective compliance (Ceff), were measured before and at the end of the study. Isobaric evaluation (Ciso) was performed in the entire population studied at an average mean BP of 110 mmHg. Ramipril significantly reduced BP from 155 +/- 16/94 +/- 6 mmHg to 140 +/- 15/85 +/- 7 mmHg (p < 0.001) without affecting heart rate (HR; 74 +/- 10 vs. 75 +/- 12 bpm). In addition, it significantly improved both PWV (18%; p < 0.001) and arterial compliance (45%; p < 0.001), from which 35% was related to a pressure independent effect (p < 0.01). Atenolol also induced a reduction in both BP (159 +/- 17/96 +/- 10 to 133 +/- 13/81 +/- 8 mmHg; p < 0.001) and HR (76 +/- 10 to 57 +/- 7 bpm; p < 0.001). In a similar way, PWV (11%; p < 0.05) and Ceff (30%; p < 0.05) were significantly improved without significant change in Ciso. This suggests that blood pressure reduction was responsible for compliance improvement. In conclusion, it is suggested that atenolol induces only hemodynamic changes, mediated mainly by BP reduction. In contrast, the improved brachial buffering function observed after ramipril involves not only hemodynamic changes, but also changes mediated by other mechanisms, such as modification of wall structures.

QT prolongation and torsade de pointes ventricular tachycardia produced by Ketanserin.

A 65-year-old man with arterial hypertension received oral treatment with Ketanserin, a new drug, during a period of five months. He developed marked QT interval prolongation and have several Stokes-Adams attacks. A Holter recording obtained during one of these episodes showed torsade de pointes ventricular tachycardia. The arrhythmias occurred during maximum QT interval prolongation. The correlation between Ketanserin and QT interval prolongation was evaluated by using several Holter studies during administration and withdrawal of the drug. The effect of Ketanserin on the QTc interval was analyzed retrospectively in six patients who had been taking the drug orally. Following a period of four to eight months, the QTc interval was prolonged by the drug (5 to 31%, mean 17%) in five patients. We conclude that torsade de pointes is a potential hazard of long-term treatment with Ketanserin.

Left ventricular mass regression and diastolic function improvement in mild and moderate hypertensive patients treated with lisinopril.

Thirty patients (18 male), mean age 49.5 +/- 6.3 years, were treated with lisinopril 10-40 mg once daily for 16 weeks. The effect of treatment on left ventricular mass and improvement in left ventricular diastolic function (measured by echo-Doppler) was assessed. Blood pressure changes were measured conventionally in the clinic and by ambulatory blood pressure monitoring. Clinic blood pressure decreased from 168.3 +/- 13.8/105.5 +/- 5.4 mm Hg to 137.5 +/- 4.1/88.8 +/- 4.1 mm Hg (p < 0.005 for both systolic and diastolic blood pressures), and the heart rate from 75.2 +/- 3.7 to 74.4 +/- 7.6 beats per minute (NS). The frequency of ambulatory systolic blood pressure values > 140 mm Hg decreased in percentage from 63.3 +/- 12.8 to 29.9 +/- 9.1% (p < 0.005) and the frequency of ambulatory diastolic blood pressure values > 90 mm Hg decreased in percentage from 61.1 +/- 12.8 to 28.6 +/- 7.5% (p < 0.005). Septal and left ventricular posterior wall thickness decreased from 11.2 +/- 0.9 to 10.3 +/- 0.6 mm and from 10.9 +/- 0.9 to 10.1 +/- 0.6 mm, respectively (both p < 0.005). Left ventricular diastolic diameter and the shortening fraction did not change significantly. Left ventricular mass, calculated from left ventricular wall thickness and diastolic diameter, decreased from 132.6 +/- 11.5 to 119.9 +/- 6.3 g/m2 (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolic syndrome and related cardiovascular risk.

The metabolic syndrome is a complex association of several risk factors including insulin resistance, dyslipidemia, and essential hypertension. Insulin resistance has been associated with sympathetic activation and endothelial dysfunction, which are the main mechanisms involved in the pathophysiology of hypertension and its related cardiovascular risk. According to the Sixth Report of the Joint National Committee, and guidelines of the World Health Organization/International Society of Hypertension, the presence of multiple risk markers suggests that both hypertension and risk factors should be aggressively managed in order to obtain a better outcome. Primary prevention of obesity at different levels--individual, familial, and social-- starting early in childhood has proven to be cost effective, and will be mandatory to reduce the world epidemic of obesity and its severe consequences.

Long-term effectiveness of BAY e 5009-nitrendipine in the treatment of mild and moderate arterial hypertension.

Thirty-seven white patients of both sexes were studied to determine the efficacy and tolerance of nitrendipine for long ambulatory treatment in patients suffering from mild to moderate essential arterial hypertension whose response to the drug had been effective in a previous study. They all suffered from mild essential arterial hypertension, with diastolic arterial blood pressure (DBP) of 95-104 mm Hg, and moderate arterial hypertension with DBP of 105-114 mm Hg, in WHO Stage I or II, according to the clinical, radiological, electrocardiographic, and ophthalmoscopic examinations. In a previous study, all of them had been subjected to tensional controls, performed hourly during an 8-h period to assess their hypertension. Later, they were treated with increasing doses of nitrendipine, administered once or twice daily, until DBP figures under 90 mm Hg were obtained in at least five of the eight controls of each daily profile. All of them agreed to take part in the present research and underwent heart rate and arterial blood pressure controls in supine and standing position every 14 days during 24 periods. Simultaneous clinical and weight controls were performed. Moreover, an electrocardiogram was made every 28 days, and blood and urine tests were performed every 3 months. Of the 37 patients, 31 completed the 24 periods of 2 weeks each. Therefore, of 888 possible controls only 837 controls were made and submitted for assessment. Eighteen patients (48.6%) went on with the initial dose throughout the study or were able to reduce it. Eleven (29.7%) had to increase it, and in eight cases (21.6%) it was either increased or reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose finding study in chronic congestive heart failure patients. Results of a short- and long-term study.

A multi-center open trial was carried out with 103 patients with chronic congestive heart failure (CHF) of diverse etiologies with oedemas, 25 with hepatomegalia, placed in classes II or III of NYHA functional capacity, with increasing doses of 30, 60 and 90 mg of muzolimine qd to ascertain (1) the effective dose for the elimination of oedemas and hepatomegalia and (2) whether such a dose keeps its efficacy throughout a long administration period. After a wash-out period of 3-7 days, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) in supine and standing positions, body weight (BW) and 24 hour diuresis were controlled and laboratory tests were performed. Muzolimine was administered and an assessment of the therapeutic effect was carried out every week. When the clinical results were ineffective, the dose was increased weekly up to 90 mg. When the results were partial, the same dose was given for another week and when it was effective the search for the dose was concluded. Out of the 103 patients, 67 needed only 30 mg of muzolimine for an effective elimination of oedemas and hepatomegalia, 32 needed 60 mg and only 4 had to have the dose increased to 90 mg to obtain efficacy. The SBP and DBP diminished by 6.3% and 7.2% respectively, and HR was reduced, though not significantly. BW diminished an average of 2.4 Kg and the diuresis increased significantly from a mean value of 1.043 ml/24 h to 1.714 ml/24 h. Sixty-two patients with effective results agreed to undergo chronic treatment for 24 weeks and be controlled every 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative trial of lisinopril and nifedipine in mild to severe essential hypertension.

A total of 136 patients with mild to severe uncomplicated essential hypertension were evaluated in a multicenter, randomized, double-blind, double-placebo, parallel study to compare the effect of lisinopril, a new angiotensin-converting enzyme inhibitor, with that of nifedipine. Following a 2-week placebo control period the patients were treated with either 20-80 mg/day of lisinopril (n = 89) or with 40-80 mg/day of nifedipine (n = 47). Blood pressure was significantly reduced in both groups after 4, 8, and 12 weeks of treatment. There was no difference in the effect of lisinopril compared to nifedipine. No serious clinical or laboratory adverse experiences were observed during the study. The incidence of clinical side effects was significantly lower in the lisinopril group than in the nifedipine group (21.3 vs. 48.9%, p less than or equal to 0.01). There were no significant changes in laboratory data in either group. The results indicate that lisinopril is as effective as nifedipine in the treatment of uncomplicated essential hypertension and that lisinopril is well tolerated and has an acceptable safety profile.

Non-invasive assessment of systemic elastic behaviour in hypertensive patients: analysis of possible determinants.

Knowledge about the viscoelastic behaviour of the arterial wall has been proved to have physiological importance and clinical usage. Our purpose was to study the changes of the systemic arterial wall's elastic properties non-invasively, in patients with established essential and with borderline hypertension, and to evaluate its possible determinants. Three groups of normotensive, borderline and established essential hypertensive patients were evaluated. Arterial pulse wave velocity (PWV) was measured and arterial compliance (Cm) was derived in all patients. Pulse wave velocity was obtained from the pressure values of digitized carotid and radial arteries. Arterial compliance (Cm = dD/dP with P pressure and D diameter) was calculated using a formula derived from the Bramwell and Hill equation: Cm = (1,334 x D)/(2 rho x PWV2), where for D humeral diameter was used as measured by high resolution echograph, and rho is the blood density (rho = 1.06). Pulse wave velocity was significantly higher in established essential hypertensive patients with respect to normotensive patients (p < 0.05). Arterial compliance was significantly diminished in established and in borderline hypertensive patients with respect to normotensive patients (p < 0.05), which implies early alterations in hypertensive cardiovascular disease. Multiple regression analysis of the cofactors showed that age and diastolic pressure are independent determinants of Cm. Impairment of the arterial wall's intrinsic elastic properties was demonstrated in established essential hypertension, independent of age and diastolic pressure.