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Diuretics are recommended as first-line antihypertensive treatment in elderly patients. Although attention is usually paid to prevent hypokalaemia with diuretic therapy, risk of hyponatraemia is often ignored. We performed this study to characterise hypertensive patients at increased risk to develop hyponatraemia. We reviewed charts of hypertensive patients hospitalised in Chaim Sheba Medical Center for hyponatraemia from 1990 to 1997. Patients with other causes of hyponatraemia were excluded. The General Practice Maccabi database was used to estimate age and sex distribution of patients prescribed diuretics for hypertension. We identified 180 hypertensive patients (149 F, 31 M; mean age 76.4 +/- 9.2 years) hospitalised because of hyponatraemia. Across all age groups, odds ratio (OR) to develop hyponatraemia was three times higher for women vs men (OR 3.10, 95% confidence interval (CI): 2.07-4.67). One hundred and sixty-two patients (90%) were older than 65 years. Patients of both sexes older than 65 years were 10 times (and if they were older than 75 years 16 times) more likely to develop hyponatraemia than those younger than 65 years (OR 9.87, 95%, CI: 5.93-16.64). Most patients (74.5%) used a thiazide-based diuretic; only 10% used a low dose (<25 mg/day). In 37% of patients diuretics were used for more than 1 year before hyponatraemia developed. Diuretic-induced hyponatraemia may be insidious and appear even after prolonged diuretics use. Elderly women seem to be at particularly high risk. In this population diuretic use should be associated with close monitoring of sodium and potassium levels.

Two-dimensional guided M-mode echocardiography was used to estimate left ventricular mass and left ventricular performance in 140 untreated hypertensive patients, 38 (27%) of whom had left ventricular hypertrophy. Left ventricular contractility as reflected by ratio of end-systolic wall stress to end-systolic volume index and normalised early left ventricular peak filling rate were decreased in the patients with left ventricular hypertrophy compared with those without hypertrophy and correlated inversely with the left ventricular mass (r = -0.44; P < 0.0001 and r = -0.31; P = 0.0004, respectively). Positive correlations were found between the peak filling rate and either the ejection fraction or the contractility index (r = 0.44; P < 0.0001 and r = 0.24; P = 0.004, respectively). Left ventricular mass also correlated with mean arterial pressure in the whole study population (r = 0.43; P < 0.0001). The data suggest that with the development of left ventricular hypertrophy both contractility and filling of the left ventricle become progressively impaired in hypertensive patients. The decline in cardiac function with progressive left ventricular hypertrophy may represent a pathophysiological correlate of the epidemiological observation identifying left ventricular hypertrophy as one of the most powerful risk factors for future cardiovascular morbidity and mortality. The present study shows that with development of left ventricular hypertrophy in essential hypertension both contractility and filling of the left ventricle become progressively impaired.

Arterial hypertension is a complication of cyclosporine therapy in heart transplant recipients. We studied cardiovascular adaptation to cyclosporine-induced hypertension by determining haemodynamic and echocardiographic indexes in 25 cardiac transplant recipients matched by mean arterial pressure, age, sex, height and weight to 25 patients with established essential hypertension. Twenty-five normotensive subjects matched by age, sex and body habitus were used as controls. Systemic vascular resistance was 15% higher (P = 0.07) and cardiac and stroke volume indices were 20% and 25% lower (P < 0.01), respectively, in the hypertensive cardiac transplant recipients compared with patients with essential hypertension. Patients with essential hypertension and hypertensive cardiac transplant recipients had greater posterior wall thickness and left ventricular mass index than normotensive subjects (P < 0.01); however, hypertensive cardiac transplant recipients had a greater left ventricular mass (245 +/- 7 vs. 223 +/- 8 g, P < 0.05) than patients with markedly established essential hypertension. Left ventricular ejection fraction was significantly lower in hypertensive cardiac transplant recipients when compared with either normotensives or patients with established essential hypertension. These results indicate that established essential and cardiac transplant hypertension are associated with markedly increased systemic vascular resistance. However, after heart transplantation, hypertension is associated with higher systemic vascular resistance, lower cardiac output, stroke volume and stroke work compared with patients with established essential hypertension at the same level of mean arterial pressure. The cardiac adaptation to cyclosporine-induced hypertension has more severe concentric left ventricular hypertrophy and impaired left ventricular systolic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients in whom monotherapy does not control blood pressure a second agent is required. Common combinations in clinical practice are a beta-blocker plus a diuretic, an angiotensin converting enzyme (ACE) inhibitor plus a diuretic, a beta-blocker plus a dihydropyridine calcium antagonist, and an ACE inhibitor plus a calcium antagonist. Since both ACE inhibitors and calcium antagonists are metabolically inert and exert favorable effects on target organ disease, their combination is of particular interest. When combined, these two drug classes have additive effects on antihypertensive efficacy, reduction of left ventricular hypertrophy, and protection of the renal circulation. However, whether or not these favorable pathophysiologic changes induced with combination therapy of ACE inhibitors and calcium antagonists will translate into a reduction of morbidity and mortality remains to be documented.

Left ventricular hypertrophy (LVH) in essential hypertension has been identified as a major and pressure independent risk factor for the occurrence of sudden death and other cardiovascular morbidity and mortality. Previous studies by our group have shown that patients with LVH exhibit more frequent and more severe ventricular ectopy than patients without LVH or normotensive subjects. These ventricular dysrhythmias are independent of the morphological form of LVH and occur in patients with normal coronary arteries. Most recent data from our laboratory documents that some calcium antagonists reduce LVH and, in parallel, suppress ventricular dysrhythmias. In contrast, antihypertensive therapy with a thiazide diuretic had no effect on ventricular dysrhythmias or LVH, despite the fact that blood pressure was lowered to the same extent as with the calcium channel blockers. What remains to be determined is whether or not the ominous prognosis of patients with LVH will be improved by specific antihypertensive therapy, that over and above lowering pressure, also improves hypertensive target organ disease, such as LVH and associated ventricular dysrhythmias.

The cardiovascular reactivity to isometric stress test before and after antihypertensive therapy was evaluated by invasive haemodynamic techniques in 23 patients with mild to moderate essential hypertension. A beta-blocking agent (atenolol 50 to 100 mg daily) was given to 11 patients; 12 patients received calcium entry blockers (diltiazem 240 to 360 mg daily or verapamil 240 to 480 mg per day). The pressor response to isometric stress before therapy consisted of an increase in systolic, diastolic, and mean arterial pressure (all P less than 0.01) that was similar in both treatment groups. The rise in arterial pressure was mainly due to an increase in cardiac output (P less than 0.01), as total peripheral resistance did not change significantly. After treatment with the beta-blocker, the increase in total peripheral resistance during isometric stress was exaggerated (P less than 0.01), and, conversely, the increase in cardiac output was attenuated (P less than 0.01). In contrast, treatment with calcium entry blockers preserved the haemodynamic reactivity pattern of the untreated state: arterial pressure increased during isometric stress through an increase in cardiac output, while total peripheral resistance remained unchanged. Since the haemodynamic culprit of essential hypertension is an elevated peripheral resistance, a drug that numerically increases this culprit under conditions of resting and isometric stress becomes less attractive than one that lowers peripheral resistance and preserves the physiologic response pattern.

Established essential hypertension is characterised haemodynamically by a normal cardiac output and elevated total peripheral resistance. As hypertensive cardiovascular disease progresses, and the patient grows older, cardiac output falls and total peripheral resistance is further elevated. The activity of the renin-angiotensin-aldosterone (RAA) system declines throughout life and reaches its lowest levels in the elderly, unless there is congestive heart failure. In long-standing hypertension, target organ disease such as left ventricular hypertrophy, nephrosclerosis and cerebrovascular damage is commonly observed. Rational antihypertensive therapy should therefore aim to lower total peripheral resistance, spare cardiac output, and maintain or improve blood flow to target organs. ACE inhibitors lower arterial pressure by decreasing total peripheral resistance, they maintain or improve cardiac contractility, promote regression of left ventricular hypertrophy, and increase renal blood flow. Lisinopril is a novel ACE inhibitor that does not contain a sulphydryl group. It is not a prodrug and thus does not require bioactivation by the liver. Lisinopril has a long duration of action, allowing it to be used as a single daily dose in the treatment of hypertension. Preliminary studies from our laboratory indicate that lisinopril reduces cardiac output and preload to the left ventricle. Lisinopril also reduces left ventricular hypertrophy and lowers renal vascular resistance, thereby increasing renal blood flow. In patients with mild to moderate hypertension, lisinopril is more effective than hydrochlorothiazide in reducing both systolic and diastolic blood pressure, and is at least as effective as atenolol or metoprolol in reducing diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)