Early abnormalities in left ventricular diastolic function of sodium-sensitive hypertensive patients.

The aim of this study was to evaluate whether salt-sensitivity in essential hypertension produces a significant comparative difference in diastolic function and ventricular mass when compared with sodium-resistance. Recent epidemiological data have demonstrated a positive correlation between sodium intake and arterial pressure. Furthermore, a positive correlation has been detected between sodium intake and left ventricular hypertrophy (LVH) independently of arterial pressure. Thirty-one patients who had never been treated before for uncomplicated hypertension were studied. Each subject received a 30 mmol/per day sodium diet for 14 days, supplemented with a further 190 mmol of sodium in the first study week (220 mmol for the first 7 days and 30 mmol for the second 7 days). Throughout the study compliance was assessed by measuring daily urinary sodium excretion. Sodium sensitivity of blood pressure was defined as the difference (5% or more) between blood pressure at the end of the low and high sodium intake periods. On this basis 16 patients were defined as salt-sensitive (SS) and 15 patients as salt-resistant (SR). The two groups were homogeneous for age, sex and race. Baseline mean arterial pressure (MAP) was comparable between SS (108 +/- 1.8 mm Hg) and SR (107 +/- 2.1 mm Hg, P = NS). Each patient was submitted to M-MODE and two-dimensional echocardiogram studies in order to estimate left ventricular mass using the Penn conventional formula and parameters of left ventricular diastolic function. The left ventricular mass measurement showed higher values in the SS group although this did not reach statistical significance (118.4 +/- 4.4 vs 112.0 +/- 4.2 gr/mq, P = NS). Both interventricular septal and posterior wall thickness did not demonstrate significant differences between the two groups. The salt-sensitive group showed impaired left ventricular diastolic function; in particular, the first diastolic peak representing the early maximum of diastolic filling velocity (E) was lower in SS subjects than in SR subjects (71.6 +/- 2.9 vs83.1 +/- 3.3 cm/sec, P < 0.02). No significant difference was detected in the second peak representing the atrial maximum of filling velocity (A) (69.0 +/- 2.3 vs 66.0 +/- 2.0 cm/sec, P = NS). As a consequence the E/A ratio was significantly different (0.73 +/- 0.2 in the SR vs 1.2 +/- 0.04 in the SS group, P < 0.05). Moreover, the peak E integral was lower in SS than in SR subjects (8. 7 +/- 0.6 vs11.2 +/- 0.5 cm, P < 0.005; no difference for the peak A integral (6.0 +/- 0.3 vs 5.7 +/- 0.4 cm, P = NS). The E peak deceleration time was significantly reduced in the SS group (400.3 +/- 13.5 vs 500.9 +/- 12.8 cm/sec, P < 0.001). No significant difference was found for the isovolumetric relaxation time (IVRT) (95.7 +/- 4.3 vs 92.2 +/- 4.0, P = NS). Our data show an impaired diastolic function expressed by a reduced early diastolic filling velocity (peak E) and a significantly abnormal E/A ratio in SS in comparison with SR subjects. Therefore abnormalities in diastolic function are detectable earlier in SS hypertensive subjects than in SR irrespective of actual MAP.

Dipyridamole-induced ischemia as a prognostic marker of future adverse cardiac events in adult patients with hypertrophic cardiomyopathy. Echo Persantine Italian Cooperative (EPIC) Study Group, Subproject Hypertrophic Cardiomyopathy.

BACKGROUND: Myocardial ischemia may play a role in the natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and the prognostic value of dipyridamole-induced ischemia, 79 patients with HCM and without concomitant coronary artery disease (53 men; mean age, 46+/-15 years) underwent a high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole test with 12-lead ECG and two-dimensional echo monitoring and were followed up for a mean of 6 years. METHODS AND RESULTS: Twenty-nine patients (37%) showed ECG (ie, ST depression > or = 2 mV) signs of myocardial ischemia during dipyridamole test (group 1), whereas 50 (63%) had a negative test (group 2). No patient had transient wall motion abnormalities during the dipyridamole test. During the follow-up, 16 events (ie, left ventricular or atrial enlargement, unstable angina, syncope, atrial fibrillation, and bundle-branch block) occurred in 29 patients in group 1 and 5 in 50 patients in group 2 (55% versus 10%, P<.001). Patients with a positive dipyridamole test showed worse 72-month event-free survival rates compared with patients with a negative test (36.2% versus 84.2%, P<.001). A forward stepwise event-free survival analysis identified dipyridamole test positivity by ECG criteria (chi2=19.7, P=.0001), rest gradient (chi2=11.3, P=.0008), and age (chi2=4.1; P=.0413) as independent and additive predictors of subsequent events. CONCLUSIONS: ECG signs of myocardial ischemia elicited by dipyridamole are frequent in patients with HCM and identify patients at higher risk of cardiac events, suggesting a potentially important pathogenetic role of inducible myocardial ischemia in determining adverse cardiac events in these patients.

The renin-aldosterone system and renal function in kidney transplantation.

Six renal transplant recipients, six uninephrectomized patients and six normal subjects were subjected to the physiological manoeuvre of head-out water immersion (WI), in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. The denervated, transplanted kidneys of the six patients were able to maintain a sodium excretory response to WI identical to that obtained in the controls (from 121 +/- 18 to 236 +/- 29 mumol/min, p < 0.005 vs 113 +/- 17 to 213 +/- 18 mumol/min, p < 0.005, respectively). Kidney transplant patients were also characterized by a preserved suppression of renin-aldosterone system (from 1.2 +/- 0.2 to 0.5 +/- 0.1 ng/ml/h, p < 0.03 and 12 +/- 1.0 to 7.0 +/- 1.0 ng/dl, p < 0.005, respectively) and stimulation of atrial natriuretic peptide (from 84 +/- 15 to 153 +/- 25 pg/ml, p < 0.05) to central hypervolemia by water immersion. The present study, while confirming the ability of the denervated kidney to handle sodium normally, also suggests that atrial natriuretic peptide could assume a crucial role in regulating renin secretion.

Water immersion and salt-sensitivity in essential hypertension.

It has been demonstrated that an exaggerated natriuretic response to central hypervolaemia is not necessarily associated with hypertension; many hypertensive subjects manifest either an appropriate or a blunted natriuresis in response to ECFV expansion attained by head-out water immersion. In this study, we tested the hypothesis that an underlying condition of salt-sensitivity may explain the heterogeneity of the natriuretic response of essential hypertension. Both salt-sensitivity tests and 2h water-immersion studies were randomly performed in 18 untreated essential hypertensives under a selected and controlled diet. Salt-sensitivity was defined as a significant drop in mean arterial pressure of 10% or greater, calculated as the difference between the average of the 25 readings under the high and the low salt period. Water immersion did result in a significant natriuretic and calciuretic response in the whole hypertensive group (n = 18, p < 0.001 and p < 0.05, respectively), while the examination of the individual excretion disclosed either exaggerated and appropriate or blunted urinary response. When the hypertensive group was classified in relation to salt-sensitivity, the greater fall in mean arterial pressure during low salt diet (salt-sensitivity) was associated with the more pronounced natriuretic response during water immersion (r = -0.66, p < 0.003). An identical correlation (r = -0.58, p < 0.01) was also found between changes in mean arterial pressure (low salt diet) and urinary calcium excretion (water immersion) in the same hypertensives. The water immersion-induced suppression of plasma aldosterone and the increase in plasma atrial natriuretic peptide did result from comparable magnitude in the salt-sensitive and in salt-resistant subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium and sodium handling during volume expansion in essential hypertension.

To evaluate the actual role of extracellular fluid volume (ECFV) expansion per se in modulating the rate of urinary calcium excretion, a thermoneutral water immersion (WI) study was conducted in 10 normal subjects and 30 patients with essential hypertension. Central hypervolemia by 2 hours of WI caused a significant diuretic and natriuretic response (P < .005) in normal subjects; no significant changes were detected in urinary calcium and magnesium excretion. WI provoked either an appropriate or exaggerated natriuresis (P < .001) in 21 hypertensive patients; these subjects also exhibited a highly positive correlation between urinary sodium and calcium excretion during WI (P < .001). In the remaining nine hypertensive patients, WI produced a significant diuretic response, but a barely discernible (P = NS) natriuresis (inappropriate response). These subjects also exhibited a significant reduction of urinary calcium (P < .001) and magnesium (P < .01) excretion. The data indicate that (1) volume expansion per se may have a role in regulating calcium excretion in hypertensive subjects; (2) a calcium leak may be attributable to a close relationship between urinary sodium and calcium metabolism, and causally related to a disturbance of sodium and volume homeostasis in hypertension.