[Left ventricular function in hypertension without left ventricular hypertrophy: echographic study with modelisation of left ventricular-aortic coupling]. / Performance et rendement du ventricule gauche chez l'hypertendu sans hypertrophie ventriculaire gauche : étude échographique par modélisation du couplage ventriculo-aortique.

Because the functional interaction between the LV and arterial systems, termed ventricular-arterial coupling, is recognized as a key determinant of LV performance, the objective of the present study was to assess the impact of uncomplicated HT without LVH on LV performance using simultaneously echocardiography and carotid tonometry. LV maximal power (PmaxVG), cardiac power output (CPO), LV efficiency (CPO/PmaxVG), input aortic and output LV elastance (Ea and Ees) were assessed in 20 normotensive control subjects (NT) and 10 patients with untreated HT. PmaxVG was calculated according to the integral of the product of LV wall stress with strain rate (as an index of gradient velocity). Cyclic variation of wall thickness and SR were measured by speckel-tracking. Ea and Ees were derived and modelized from the pressure-volume curve. No difference in age, BMI and sex ratio was observed between NT and HT. Systolic BP (160±18 vs. 119±10mmHg), LV mass (99±15 vs. 76±12g/m(2)), PWV (9.7±2 vs. 6.9±1m/s) were significantly higher (P<0.01) in HT when compared to NT. In HT increased of CPO and Ea was compensated by an increase of LV (15±4 vs. 12±3%, P<0.02) and Ees (5.5±2 vs. 4.5±1.5mmHg/mL), which are significantly elevated in HT (P<0.05). No difference was observed in Ea/Ees between NT and HT. In conclusion at the early phase of HT, in patients without LVH, LV performance and ventricular-arterial coupling were adapted to post-load elevation. This adaptation may be the result of an increased of LV contractility.

Age-related increase of pulse pressure and plasminogen activator inhibitor-1 I/D gene polymorphism in essential hypertension.

BACKGROUND: Pulse pressure (PP), a marker of cyclic strain on the arterial wall, is a significant predictor of cardiovascular (CV) risk, particularly regarding the incidence of coronary arterial stenosis. Genes related to haemostatic and/or fibrinolytic factors are consistently influenced in vitro by mechanical strain. OBJECTIVE: The goal of the present study was to determine, in the three genotypes of the plasminogen activator inhibitor (PAI)-1 gene polymorphism, the gender-adjusted difference in the relationships between age and PP in subjects with never treated essential hypertension. RESULTS: In the studied population, the genotype deletion (D)/D at position -675 of the PAI-1 insertion (I)/D gene polymorphism was associated with a significant increase in the adjusted slope of the curve relating age to PP by comparison with the two other genotypes. No comparable difference in age-related changes in systolic, diastolic or mean blood pressure was found. CONCLUSION: In subjects with essential hypertension, the PAI-1 I/D gene polymorphism modulates the age-mediated increase of PP, suggesting new insights on the complex interactions between genes, mechanical factors and CV risk.

[Cardiac consequences of primary hyperaldosteronism]. / Conséquences cardiaques de l'hyperaldostéronisme primaire.

The activation of the renin-angiotensin system is associated with vascular and cardiac hypertrophy. But there are few data on the renal and cardiac consequences of the hypersecretion of aldosterone. In the experimental setting, hyperaldosteronism leads to an excess of fibrous interstitial tissue and cardiac hypertrophy. In man, these consequences are those of hyperaldosteronism. The aim of this study was to assess the cardiac consequences of hyperaldosteronism in a series of 31 patients with a documented Conn adenoma, in comparison with a matched population of 31 patients with primary hypertension. For the same level of blood pressure, cardiac hypertrophy is more prominent in hyperaldosteronism and there is a positive correlation between the level of plasma aldosterone and left ventricular wall thickness. Left ventricular hypertrophy is of the concentric type. In addition, an increase in myocardial fibrosis (that can now be quantified by echocardiography) is observed, with a positive correlation between plasma aldosterone and reflected ultrasound which might correspond to increased myocardial collagen. These anatomic modifications of myocardial structure result in diastolic dysfunction. Overall, Conn adenoma is associated in accelerated disease, which is partly independent of the level of blood pressure.

[I/D gene polymorphism of the angiotensin-converting enzyme and left ventricular hypertrophy. Response to converting enzyme inhibitors]. / Polymorphisme I/D du gène de l'enzyme de conversion de l'angiotensine et hypertrophie ventriculaire gauche. Réponse aux inhibiteurs de l'enzyme de conversion.

BACKGROUND: The present study was designed to assess whether the angiotensin-converting enzyme (ACE) gene I/D polymorphism influence the ACE inhibitors effect on the regression of left ventricular hypertrophy. METHODS: Sixty hypertensive subjects never treated by antihypertensive drugs, aged 46 +/- 11 years, were included in the study. Follow-up with ACE inhibitor treatment was 60 +/- 26 months. Genotypes for ACE I/D polymorphism (DD, ID or II) were determined by PCR. The left ventricular mass index (LVMI) was assessed by two-dimensional directed M-mode echocardiography. RESULTS: ACE genotype distribution was in agreement with the Hardy-Weinberg equilibrium: 21 patients had the DD genotype, 29 were ID, and 10 were II. At baseline, age, systolic arterial pressure and LVMI didn't differ on the basis of genotype. Body mass index was significantly higher in II than in ID and DD groups. Regression of LVMI with ACE inhibitor treatment was similar in the 3 genotypes (-8.9%, -0.6%, -12.1% in DD, ID and II groups respectively). In addition, decrease of systolic arterial pressure was identical in 3 groups. CONCLUSION: ACE gene I/D polymorphism seems not to influence regression of left ventricular hypertrophy by ACE inhibitors in essential hypertension.

Glucose tolerance and age-associated decline in renal function of hypertensive patients.

BACKGROUND: Renal function is thought to decrease with age in the general population, but the determinants of this age-associated evolution are poorly understood. Hypertension and diabetes mellitus, two leading causes of chronic renal failure in the elderly, may accelerate this decline. PATIENTS AND METHODS: Urinary clearances of [99mTc]diethylene triaminopentaacetic acid (DTPA) (glomerular filtration rate) and [131I]hippuran (effective renal plasma flow) were assessed in 227 never-treated essential hypertensives aged 20-69 years. Based on the oral glucose tolerance test, the study population consisted of 4% patients with previously unknown diabetes mellitus, 24% with impaired glucose tolerance and 72% with normal glucose tolerance. RESULTS: When the population of 218 non-diabetic subjects was considered, glomerular filtration rate was inversely correlated with age and arterial blood pressure, and positively correlated with effective renal plasma flow, filtration fraction and fasting plasma glucose. In multivariate analysis, age and blood pressure were independent determinants of renal plasma flow, whereas renal plasma flow, age and fasting plasma glucose were independent determinants of glomerular filtration rate. The slope of the regression line relating glomerular filtration rate to age was steeper in patients with impaired glucose tolerance than in those with normal glucose tolerance (-1.52 +/- 0.28 versus -0.65 +/- 0.12, P < 0.01). CONCLUSIONS: These results suggest that impaired glucose tolerance, which is seldom searched for in patients with essential hypertension, may be an important determinant of the age-associated decline in renal function.

Left ventricular adaptation to hypertension and plasma renin activity.

Chronic pressure and volume overload result in morphologically and functionally distinct forms of myocardial hypertrophy. In essential hypertension, the respective effect of these factors on the morphology of the left ventricle remains unknown. In the present study, we hypothesised that activity of the renin angiotensin system (assessed by plasma renin activity) may be associated to the variability of the left ventricular adaptation to essential hypertension. To assess this relation, we categorised by echocardiography 333 never-treated hypertensive patients, according to values of left ventricular mass and relative wall thickness. Higher systolic and pulse arterial pressure was strongly associated with concentric left ventricular hypertrophy (27% of hypertensives). When compared to the normal left ventricle group, patients with eccentric left ventricular hypertrophy (15% of hypertensives) had a high cardiac index (5 +/- 1 vs 4 +/- 0.8 L/min/m2; P = 0.0001), a lower basal plasma renin activity (0.81 +/- 0.63 vs 1.45 +/- 1.3 ng/ml/h; P = 0.02) and similar mean values of left ventricular performance and glomerular filtration rate. A tendency for depressed myocardial contractility assessed by the midwall shortening/end-systolic stress was associated with concentric left ventricular remodelling and hypertrophy when compared to hypertensive with a normal left ventricle. In conclusion, at the early phase of essential hypertension, in patients without renal dysfunction, each anatomic pattern of cardiac adaptation to hypertension was associated with a distinct profile of haemodynamics, myocardial function and activity of the renin-angiotensin system. Journal of Human Hypertension (2000) 14, 181-188.

Nephrotic-range proteinuria in patients with renovascular disease.

PURPOSE: Proteinuria is usually considered a manifestation of glomerular disease. We sought to describe the characteristics of patients with nephrotic-range proteinuria resulting from renovascular disease and to compare them with those of patients who had glomerulonephritis. SUBJECTS AND METHODS: We identified 14 patients with nephrotic-range proteinuria and renovascular disease and compared them with 14 patients who had nephrotic-range proteinuria and biopsy-proven glomerulonephritis, matched for sex, age, and glomerular filtration rate. RESULTS: Patients with renovascular disease were more likely to have known atherosclerotic vascular disease [13 of 14 (93%) vs 3 of 14 (21%), P < 0.0001) and were usually smokers [12 of 14 (85%) vs 3 of 14 (21%), P < 0.0001]. They also had a greater mean (+/- SD) difference between the lengths of their kidneys (29 +/- 10 vs 5 +/- 5 mm, P < 0.001); greater systolic blood pressure (203 +/- 22 vs 174 +/- 25 mm Hg, P < 0.005), plasma renin activity (17 +/- 19 vs 2 +/- 2 ng/mL/h, P = 0.005), and plasma aldosterone concentration (40 +/- 23 vs 11 +/- 10 ng/dL, P = 0.0001); and lower serum potassium levels (3.3 +/- 0.5 vs 3.8 +/- 0.5, P <0.05). Effective renal plasma flow was lower (139 +/- 68 vs 307 +/- 185 mL/min/1.73 m3) and filtration fraction was markedly greater (0.28 +/- 0.04 vs 0.15 +/- 0.07, P = 0.0001) in the patients with renovascular disease. After the oral administration of captopril, blood pressure, effective renal plasma flow, and glomerular filtration rate decreased only among patients with renovascular disease. Of the 14 patients with renovascular disease, 13 had evidence of renal artery thrombosis seen at angiography; 2 patients required dialysis, and 3 others died during follow-up. CONCLUSION: Our findings suggest that the patients with nephrotic-range proteinuria resulting from renovascular disease have distinct characteristics and a poor prognosis.

[Determinant of left ventricular hypertrophy in the hypertensive woman. Influence of hormone replacement therapy for menopause]. / Déterminants de l'hypertrophie ventriculaire gauche chez la femme hypertendue. Influence du traitement hormonal substitutif de la ménopause.

BACKGROUND: This study investigated the influence of hormone replacement therapy on the variability of the cardiac hypertrophic response to hypertension in postmenopausal women. METHODS: 25 menopausal essential hypertensive women (mean age 54 +/- 0.8 years, range 45 to 70) treated with estrogen (without progestin) for at least 1 year were studied and compared with 25 menopausal age-matched women (55 +/- 1 years old, range 46 to 70) not taking such therapy. No women had ever received antihypertensive therapy. Left ventricular mass corrected by height2.7 and relative wall thickness were assessed by M mode echocardiography. RESULTS: Age, blood pressure, body mass index, 24 h urinary sodium excretion and plasma renin activity were in the 2 groups with and without hormone replacement therapy. Left ventricular mass corrected by height2.7 was significantly higher in the group with without estrogen replacement therapy when compared to menopausal women with estrogen replacement (55 +/- 3 vs 45 +/- 4 g/m2.7 p < 0.02). In addition the slope of the regression line between LV mass and systolic BP was significantly higher (p < 0.01) in the group of women without hormonal therapy r = 0.50 p < 0.001. CONCLUSION: These results suggest that estrogen therapy of menopause attenuate the cardiac hypertrophic response to hypertension.

Microalbuminuria in essential hypertension.

Urinary excretion of albumin exceeds normal values in 10 to 25% of patients with essential hypertension. The level of albuminuria is highly correlated with arterial pressure, and more closely with ambulatory arterial pressure. The interaction between albuminuria and arterial pressure is enhanced by overweight, smoking, protein intake, insulin resistance, lipid abnormalities, and possibly genotypes of the components of the renin-angiotensin system. The renal mechanisms of microalbuminuria are not well elucidated. Notably, an increase in filtration fraction suggestive of intraglomerular hypertension was observed in patients with hyperfiltration. Microalbuminuria may be a marker of diffuse vascular abnormalities predisposing to cardiovascular disease and/or hypertensive renal disease heralding future renal failure, but its predictive value needs to be tested in more long-term follow-up studies. Antihypertensive treatment has a varied influence on albuminuria; angiotensin-converting enzyme inhibitors may correct this abnormality (at least partially) better than other agents.

[Primary dysautonomia in the elderly: the diagnostic value of the inversion of the circadian rhythm of arterial blood pressure]. / Dysautonomie primitive du sujet âgé: intérêt diagnostique de l'inversion du cycle nycthéméral de la pression artérielle.

PURPOSE: Ambulatory blood pressure monitoring allows characterization of the circadian variations in blood pressure. METHODS: In order to investigate the diagnostic value of circadian variations in blood pressure in the elderly, 11 patients with autonomic failure and 11 control subjects paired on age, blood pressure level and daily life activity range were studied. RESULTS: Periodic postural disorders, positive response to passive tilt-test and alpha denervation supersensitivity to noradrenaline were found in all patients with autonomic failure. In control subjects, blood pressure levels assessed by ambulatory monitoring were lower at night. Conversely, circadian variations in blood pressure were higher at night and lower in the morning in patients with autonomic failure. The nadir of blood pressure measurement was related with the reported time of peak incidence of orthostatic symptoms. CONCLUSION: Ambulatory 24-hour blood pressure monitoring may therefore be of value in the diagnosis and management of patients with autonomic failure.

Renal characteristics and effect of angiotensin suppression in oral contraceptive users.

-The determinants of the increase in arterial blood pressure associated with the use of estrogen-progestogen oral contraceptives (OC) remain poorly known. The purpose of this study was to assess the renal characteristics and the role of the renin-angiotensin system in women with OC-associated hypertension. Urinary clearances of technetium-labeled diethylene triaminopentaacetic acid (glomerular filtration rate) and 131I-ortho iodohippurate (effective renal plasma flow) were estimated before and after acute administration of captopril in 38 women who became hypertensive while taking OC, 38 non-OC users with essential hypertension matched for age, body mass index, and level of blood pressure, and 38 normotensive women (19 with and 19 without OC). Plasma renin activity was higher in OC hypertensives when compared with those with essential hypertension, but captopril-induced changes in blood pressure and renal hemodynamics and function were similar in both groups. In addition, 24-hours urinary albumin excretion was increased in OC users when compared with nonusers with similar arterial blood pressure. In 13 hypertensive women followed up for 6 months after OC withdrawal, a decrease in plasma renin activity, blood pressure, and glomerular filtration rate but no significant change in urinary albumin excretion and captopril-induced changes in blood pressure and renal hemodynamics were observed. These results indicate that the use of OC is associated with an increased albuminuria and no evidence of a prominent role for the renin-angiotensin system in the maintenance of high blood pressure and renal hemodynamics when compared with non-OC users with essential hypertension.

[Left ventricular consequences of hypertension in the elderly]. / Les conséquences de l'hypertension artérielle sur le ventricule gauche du sujet âgé.

Modifications of left ventricular morphology observed during ageing are very similar to those encountered during hypertension, as if hypertensive patients present premature ageing of their cardiovascular system. Hypertension in the elderly amplifies the concentric remodelling and alteration of diastolic function observed in normotensive subjects during ageing. The main determinant of these modifications of morphology and cardiac function is the increased rigidity of large arterial trunks with age. Treatment of hypertension therefore represents one of the essential ways to control this pathological ageing.

[Effect of chronic bradykinin infusion on angiotensin II hypertension in rats]. / Effet de l'administration chronique de bradykinine dans l'hypertension induite par l'angiotensine II chez le rat.

In previous studies, we demonstrated that in ANG II-treated rats, prevention of cardiac hypertrophy (CH) by enalapril was blunted by bradykinin (BK) blockade by Hoe140. The putative role of BK was assessed by chronic exogenous BK infusion and in 46 male Sprague-Dawley rats infused with ANG II. ANG II (200 ng/kg/min) alone and associated with BK at low (BKlow, 15 ng/kg/day), mid (BKmid, 100 ng/kg/day) and high doses (BKhigh, 100 ng/kg/min) were delivered by Alzet osmotic pumps for 10 days and compared to control animals (Veh). Values of systolic arterial pressure (SAP, mmHg) in conscious rats and heart weight (HW, mg/g bw) at the end of the study are reported below. Results were submitted to ANOVA and are expressed as mean +/- SEM.

[Aging and regression of cardiac hypertrophy in the hypertensive patient]. / Vieillissement et régression de l'hypertrophie cardiaque chez l'hypertendu.

OBJECTIVE: This study was aimed at determining factors acting on the regression of left ventricular hypertrophy due to essential hypertension. METHODS: It was a non-randomized, echocardiographic study of 60 previously untreated hypertensive subjects (20 to 75 years of age). RESULTS: Following a 5-year therapy, the decrease in the left ventricular mass was 14%. Normalization of blood pressure and reversal of left ventricular hypertrophy were obtained in 50% and 58% of patients, respectively. Patients of the non-responder group (non-response being defined as a less than 10% decrease in the left ventricular mass) were older and had a longer history of high blood pressure. A positive correlation was observed between age and decrease in the left ventricular mass, the latter being less marked in older patients. Antihypertensive drugs classes had no influence on reversal of left ventricular hypertrophy. CONCLUSION: Ageing may be a factor of resistance to the decrease in left ventricular mass with therapy. These results suggest that early screening and management of hypertension are essential.

[Determinants of the left ventricular mass in obese patients. Influence of lean body mass]. / Déterminants de la masse ventriculaire gauche chez le sujet obèse. Influence de la masse maigre.

Systolic blood pressure and body mass index (BMI) are the main determinants of the left ventricular mass (LVM). The mechanism of this cardiac hypertrophy in the obese individual is multifactorial and involves hemodynamic as well as metabolic factors. The association of LVM with the morphologic features of the individual are well known. The aim of this study was to assess the influence of the morphologic and metabolic features of obese women on LVM. 2D echocardiography evaluation of LVM was done in 24 normotensive, normoglycemic obese women (BMI [27.5-52.2 Kg/m2). Lean and fat body mass were determined by bio-impedancemetry, insulin sensitivity (Si) by the minimal model (Bergman), and basal metabolism by using indirect calorimetry. There was a positive correlation between LVM and BMI (r = 0.61; p = 0.001), waist to hip ratio (r = 0.45; p = 0.03), basal metabolism (r = 0.61, p = 0.001), lean (r = 0.74, p = 0.0002) and fat (r = 0.49; p = 0.01) body mass. Fasting glycemia was positively correlated with LVM (r = 0.62; p = 0.001), but not Si. LVM was also positively correlated to the triglyceride level. No relations were found with systolic or diastolic blood pressure. Multivariate regression analysis was performed to determine the relative contribution of lean body mass (the morphologic variable with the best association to LVM in univariate analysis), blood glucose, waist to hip ratio, age and triglycerides. The multiple r for the model was 0.87 (p < 0.001). Lean body mass and blood glucose were found to be the only significant and independent predictors of LVM (p = 0.001 and p = 0.03 respectively). We conclude that: 1) lean body mass is an important determinant of LVM in obese normotensive individuals. Hence, in obese women, correcting LVM for lean body mass might be more accurate than correcting it for body surface area or height. 2) There is no relationship between LVM and insulin sensitivity. The link between blood glucose and LVM needs to be studied further.

[Endothelial dysfunction and cardiac performance in untreated hypertension]. / Dysfonction endothéliale et performance cardiaque chez l'hypertendu jamais traité.

Similar to endothelial modulation of vascular tone, nitric oxide (NO) released from the coronary and endocardial endothelium may modulated LV performance with an improvement of LV diastolic distensibility. The aim of the present study was to assess a potential relationship between endothelial function and LV performance in essential hypertension. Thirty-nine normotensive subjects (NT) and 46 never treated hypertensive patients (HT) were grouped according to the renal vasodilatatory response to infusion of L-arginine (30 g within 60 min). HT patients responders to L-arginine (n = 19) were defined by an increased > or = 5% of renal plasma flow (RPF) estimated by the clearance of I-Hippuran. LV mass index and afterload-corrected fractional shortening were determined by echocardiography. Mitral peak early (E) and late (A) diastolic flow velocity were assessed by Doppler. Results of ANOVA were (means +/- SD): [table: see text] In HT patients E/A was positively correlated with %RPF (r = 0.27; p < 0.01) and negatively correlated with age (r = -0.52 p < 0.01) and systolic BP (r = -0.36 p < 0.01). In multiple regression analysis the relation between E/A and %RPF was dependent of age. This results confirm that aging and hypertension are the main determinants of the alteration of LV diastolic function. The link between these factors may be the endothelium which abnormal regulatory function secondary to aging and HT may be associated to an impairment of NO dependent LV relaxation.

Albuminuria predicts renal functional outcome after intervention in atheromatous renovascular disease.

BACKGROUND: Atheromatous renovascular disease is increasingly recognized as a cause of renal failure; however, the benefit of intervention on renal function outcome cannot be clearly anticipated. OBJECTIVE: To identify reliable predictor(s) of renal functional outcome after revascularization in patients with atheromatous renovascular disease. DESIGN: The effect of percutaneous transluminal renal angioplasty (n = 5) or surgery (n = 18) on glomerular filtration rate ([99mTc]-diethylene triaminopenta-acetic acid clearance) and renal haemodynamics was prospectively assessed in 23 patients with atheromatous renovascular disease (unilateral occlusion in five, unilateral stenosis in four, stenosis of a single kidney in five, unilateral occlusion associated with contralateral stenosis in six, bilateral stenosis in three). Renal function was altered in 18 patients. RESULTS: At early follow-up study (5 +/- 1 months) after intervention, glomerular filtration rate improved (i.e. increased by more than 15%) in six patients, deteriorated in five and remained unchanged in 12 patients. The change in glomerular filtration rate associated with intervention was inversely correlated with the pre-intervention level of urinary albumin excretion and positively with the change in effective renal plasma flow after intervention. Stepwise regression analysis showed that pre-intervention urinary albumin excretion was the only predictor of the glomerular filtration rate response to intervention. At late follow-up study (32 +/- 6 months, n = 13), glomerular filtration rate was stable compared with early follow-up determination in non-proteinuric patients whereas it had deteriorated further in proteinuric patients. CONCLUSION: In patients with atheromatous renovascular disease, albuminuria may be considered as a marker of pre-existing intra-renal vascular and glomerular damage and a reliable predictor of renal functional outcome after intervention.