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Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131 I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and ␤2 microglobulin were higher in PA than EH (88 ؎ 26 versus 39 ؎ 12 and 0.91 ؎ 0.23 versus 0.26 ؎ 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 ؎ 3/13 ؎ 2 mmHg), urinary excretion of albumin and ␤2 microglobulin (by 48 ؎ 19 and 0.53 ؎ 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 ؎ 3 and 54 ؎ 15 ml/min per 1.73 m 2 , respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.J P rimary aldosteronism (PA) is a possibly common form of endocrine hypertension in which aldosterone production is inappropriate and at least partially autonomous with regard to physiologic control by angiotensin. In recent years, the widespread use of the plasma aldosterone/ renin ratio as a screening test for PA has led to a marked increase in the proportion of hypertensive patients identified as such (1). Whether the diagnostic workup of aldosterone-producing adenomas is cost-effective regarding the potential for curability or effective protection of target organs by specific treatment remains controversial (2). Several experimental and, to a lesser extent, clinical studies suggest that long-term exposure to increased aldosterone levels may result in renal as well as cardiac and vascular toxicity that is in part independent of the BP level (3,4). Target organ damage, as assessed by the measurement of left ventricular mass or urinary excretion of albumin, may be inappropriately high with respect to the BP level in patients with PA (5,6). However, the relationship between albuminuria and renal function parameters is not clear. Specifically, it is not known whether PA-associated albuminuria may relate to a state of hyperfiltration suggested in a study in which GFR was assessed by the measurement of creatinine clearance (7). For investigating the effect of aldosterone excess...

The existence of a direct relationship between body mass and arterial pressure is well recognized; however, the effect of obesity on known target organs of hypertension is not clearly understood. We undertook the present studies to assess the influence of obesity on renal function and urinary albumin excretion in 40 normotensive subjects and 80 nevertreated hypertensive patients matched for age, sex, arterial pressure level, and known duration of hypertension in whom an oral glucose tolerance test was within normal limits. Glomerular filtration rate and effective renal plasma flow (expressed as absolute values or values normalized for height) were increased in overweight compared with lean subjects whether normotensive or hypertensive. Glomerular filtration rate was positively correlated with protein intake (as assessed from urinary excretion of urea) and fasting serum insulin level. Urinary excretion of albumin but not IgG and beta 2 microglobulin was higher in hypertensive patients compared with normotensive subjects. The overweight condition clearly enhanced the influence of arterial pressure on albuminuria; in fact, a steeper regression line between albumin excretion rate and arterial pressure was found in overweight compared with lean subjects. These results indicate that the overweight condition is associated with renal hyperfiltration and hyperperfusion, irrespective of the presence of hypertension, and that obesity magnifies the effect of hypertension on albuminuria, thus raising the possibility of an increased susceptibility of obese hypertensive patients to the development of renal damage.

In addition to its widely contested influence on arterial pressure, dietary sodium may exert some nonpressure-related effects on left ventricular mass in humans. In the present study, we hypothesized that sodium intake (estimated by two consecutive measurements of 24-h urinary sodium excretion) may amplify the effect of arterial pressure on target organ damage (ie, left ventricular mass and microalbuminuria) in a large group of normotensive subjects and patients with never-treated uncomplicated essential hypertension. Left ventricular mass (M-mode echocardiography) and urinary albumin excretion were assessed in 839 subjects (471 men and 368 women) aged 15 to 70 years, with elevated (60%) or normal arterial pressure. In the entire population, multivariate analysis indicated that the relationship between urinary sodium excretion and left ventricular mass index (beta = 0.02, P < .01) as well as urinary albumin excretion (beta = 0.001, P < .0001) was independent from sex, age, body mass index, and systolic arterial pressure. When subjects were divided into quintiles according to urinary sodium excretion, left ventricular mass index and urinary albumin excretion increased significantly from the lowest to the highest quintile in both genders, despite similar values of systolic arterial pressure. The slope of the regression line linking systolic arterial pressure to left ventricular mass index (in men) and urinary albumin excretion (in the entire population) obtained within each quintile of urinary sodium excretion, progressively and linearly increased from the lowest to the highest quintile. These results suggest that sodium intake may amplify the effect of arterial pressure on both the left ventricle and the kidney, and thus suggest that dietary sodium may be an independent factor of cardiovascular risk.

To determine whether urinary sodium excretion (a rather rough estimate of sodium intake) can influence left ventricular mass independently of arterial pressure, 91 untreated subjects with essential hypertension and 50 normotensive subjects of similar age were studied. Left ventricular mass index (M-mode echocardiography) was positively correlated with urinary sodium excretion in hypertensive (r = 0.22, P less than 0.01) as well as normotensive subjects (r = 0.22, P less than 0.05), and systolic arterial pressure was correlated only in hypertensive subjects (r = 0.23, P less than 0.01). When hypertensive subjects were divided into groups with appropriate or inappropriate left ventricular mass by reference to a theoretical optimal left ventricular mass for each subject's level of systolic arterial pressure, left ventricular mass was appropriate in 68% and inappropriate in 32% of subjects. Urinary sodium excretion was higher in subjects with inappropriate left ventricular mass compared with those with appropriate left ventricular mass. In conclusion, sodium excretion may be an important modulator of the influence of arterial pressure on the left ventricle in normotensive subjects and subjects with essential hypertension.

Abstract-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 131 I-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. 1 OC use may also result, albeit rarely, in accelerated hypertension 2 and biopsy-proven renal damage in the absence of primary renal disease.3 When compared with earlier studies, a decreased cardiovascular morbidity was recently observed in OC users, possibly because of a tendency to refrain from OC in smoking older women and the reduction in dosages of both estrogen and progestogen components to about one fifth to one sixth.1 The absolute cardiovascular risk associated with OC use is now rather low in women with no risk factors for cardiovascular disease. 4 However, a recent worldwide survey indicated that among current OC users, a history of hypertension increased the risk of ischemic stroke by 11-fold in western Europeans and even more in subjects from developing countries. 5A small elevation in blood pressure is observed in almost all women taking OC, 6 reaching a level Ͼ140 to 90 mm Hg in 5% of those taking combined products containing Ͼ50 g estrogen. 7 In a recent large prospective cohort study conducted in American nurses, a doubling in the adjusted relative risk for hypertension was documented in current users of low-dose OC.8 Although hypertension is a fairly common side effect of OC, it is not agreed on whether the risk of OC-associated hypertension increases with the duration of OC use. 4,9 In addition, the mechanisms involved in the...

Pulse pressure (a marker of arterial stiffening) is suggested as an independent determinant of the treatment-associated decline in renal function in essential hypertension. No influence of target organ damage (albuminuria of left ventricular hypertrophy) was detected.

Abstract-In essential hypertension, the regression of left ventricular hypertrophy is an important goal of treatment. In addition to treatment-associated changes in blood pressure (BP), the roles of other determinants of left ventricular hypertrophy regression, including dietary sodium intake, deserve investigation. In the present study, the change in echographic left ventricular mass index (LVMI) was assessed in 182 patients with never-treated essential hypertension at baseline and after 3 years of treatment by angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists given at recommended doses and associated with other antihypertensive agents. Treatment was associated with satisfactory control of BP (Ͻ140/90 mm Hg) in 64% of patients, and left ventricular hypertrophy prevalence decreased from 56% to 39%. Twenty-four-hour urinary sodium was positively related to LVMI at baseline and at the end of the study, independently of age, sex, and systolic BP. Supine plasma aldosterone concentration was correlated with LVMI only at baseline but not in multivariate analysis. In response to treatment, the percentage of change in LVMI was positively correlated with the absolute changes in systolic BP, urinary sodium, and plasma aldosterone concentration, independently of baseline LVMI. The population was divided into 3 tertiles according to final values of gender-specific urinary sodium. When, within each urinary sodium tertile, patients were divided into those with plasma aldosterone concentration below and above the median (11.6 ng/dL), LVMI progressively increased across sodium tertiles only in patients with high plasma aldosterone concentration. Systolic BP was similar across all of the groups. In conclusion, aldosterone requires the presence of high dietary salt for the expression of its unfavorable effect on the heart. (Hypertension. 2010;56:865-870.)Key Words: left ventricular hypertrophy Ⅲ sodium intake Ⅲ hypertension Ⅲ aldosterone Ⅲ renin-angiotensin blockade A lthough left ventricular hypertrophy (LVH) is considered as an adaptative mechanism that preserves cardiac pump function in the presence of pressure or volume overload, it also represents a preclinical disease strongly predictive of cardiovascular morbidity and mortality in hypertension. 1 Moreover, some evidence indicates that reduction or aggravation of LVH, respectively, improves or enhances the risk of subsequent complications. [2][3][4] In the Pressioni Arteriose Monitorate e Loro Associazioni cohort of 398 treated subjects with essential hypertension, a prevalence of LVH of 19% was found when adequate control (Ͻ140/90 mm Hg) of blood pressure (BP) was achieved, whereas the prevalence of LVH was 29% in the presence of uncontrolled BP. 5 Because a number of treated patients exhibit levels of left ventricular mass (LVM) that exceed the need to sustain cardiac workload, it was suggested that nonhemodynamic factors may modulate or consistently influence the regression of LVH. 6 During the last decade, dietary sodium and aldosterone wer...