Salt sensitivity in patients with arterial hypertension

We present literature review on the role of excessive sodium consumption with food in pathogenesis of salt sensitive arterial hypertension (AH) as well as scientific data allowing to consider sensitivity to salt as independent factor of development and unfavorable course of AH associated with insulin resistance, high activity of sympathetic nervous system, and risk of cardiovascular complications. We present data on differential antihypertensive activity of drugs used for therapy of AH depending on sensitivity of patients to salt.     

Salt sensitivity as a predictor of hypertension.

Salt sensitivity of blood pressure can be identified in half of the hypertensive population and one-fourth of normotensive subjects. Salt sensitivity of blood pressure is especially frequent in normotensives from subpopulations known to have a higher frequency of hypertension, such as blacks, older subjects, and first-degree relatives of hypertensives, suggesting a link between salt and the subsequent development of hypertension. A variety of associated markers of salt sensitivity has been described. Recent studies also link calcium and salt sensitivity of blood pressure.     

Salt sensitivity and central dopaminergic activity in patients with essential hypertension

The pathophysiological role of the central dopaminergic mechanism in human essential hypertension (EH) is still unknown. We studied on the relationship between the dopaminergic activity and the salt-sensitivity. Twenty three hospitalized patients with EH were divided into the salt-sensitive group (SS, n = 12) or non salt-sensitive group (NSS, n = 11) by their responses whether they caused more than 8% increase in mean blood pressure (MBP) when the dietary salt was increased from 2g/day to 20g/day for 7 days of each. The change of central dopaminergic activity by the salt load was evaluated by the decrement of plasma prolactin (PRL) response to small dosage (25 micrograms) of thyrotropin releasing hormone. The mean percent change of PRL response by the salt load in the SS group was -6.5 +/- 8.3% (mean +/- SEM), which was significantly lower than 26.8 +/- 5.5% in the NSS group (p less than 0.01). There was a significant negative correlation between the percent changes of PRL response and the percent changes of MBP by the salt load (r = -0.448, p less than 0.05). These results suggested that the rise in blood pressure by salt load in SS patients with EH might be due to a reduced activity of the central dopaminergic mechanism.     

Salt sensitivity and central dopaminergic activity in patients with essential hypertension.

The pathophysiological role of the central dopaminergic mechanism in human essential hypertension (EHT) is still unknown, so we investigated a possible relationship between the central dopaminergic activity and salt sensitivity to blood pressure in patients with EHT. We divided 22 inpatients with EHT into salt-sensitive (SS, n = 11) and non-salt-sensitive (NSS, n = 11) groups according to an 8% increase of mean blood pressure (MBP) when dietary salt intake was increased from 2 g/day to 20 g/day for two periods of 7 days each. The change of central dopaminergic activity by salt load was evaluated as the percentage change of plasma prolactin (PRL) response to a small dose (25 micrograms) of thyrotropin-releasing hormone (TRH) administered intravenously. The mean percentage change of PRL response by salt load in the SS group was -9.4 +/- 8.5% (mean +/- SEM), which was remarkably lower than the 26.8 +/- 5.5% in the NSS group (P less than .01). There was a significant negative correlation between the percentage change of PRL response and that of MBP by salt load (r = -0.456, P less than .05). These results suggest that a lack of activation of the central dopaminergic system by salt load may contribute in part to a rise in blood pressure in SS patients with EHT.     

Salt sensitivity and hypertension in African Americans: implications for cardiovascular nurses

Hypertension is a major public health problem in the U.S. Salt sensitivity is an important factor associated with hypertension and its complications, yet it has not been addressed in the nursing literature. Salt sensitivity is a directionally appropriate rise or fall in blood pressure when salt is added or removed, respectively. The change in blood pressure in salt-sensitive subjects occurs to a degree exceeding random blood pressure fluctuations. Salt sensitivity is present in 30% of normotensive and over 50% of hypertensive persons. It is more prevalent among African Americans, older persons, and individuals with renal insufficiency or diabetes. This paper provides nurses with an overview of salt sensitivity and its significance in hypertension. It presents conceptual and operational definitions of salt sensitivity, identifies factors contributing to its development, and describes implications for nursing practice.     

Angiotensin-converting enzyme inhibitors for systemic hypertension in young and elderly patients.

Whereas many physicians have been reluctant to treat hypertension in the elderly because of perceived limited benefits and the risk of side effects associated with traditional antihypertensive agents such as diuretics and beta blockers, studies and clinical experience have shown that elderly as well as younger patients can benefit from treatment. In recent years, angiotensin-converting enzyme (ACE) inhibitors have been found to be safe and effective in both young and elderly hypertensive patients without many of the adverse effects associated with traditional agents. ACE inhibitors possess characteristics that meet many of the special needs of elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no central nervous system effects, no risk of induction of cardiac failure, and low risk of orthostatic hypotension.     

Salt sensitivity of hypertension and responses to angiotensin converting enzyme inhibition with benazepril

Salt intake, and the sensitivity of blood pressure (BP) to excessive salt intake is thought to contribute to the pathogenesis of essential hypertension in some patients. This study was designed to ascertain whether salt sensitivity of BP is a determinant of BP and renal vascular responsiveness to angiotensin converting enzyme (ACE) inhibition. In 24 patients with essential hypertension, ranging in age from 30 to 68 years, renin status, renal hemodynamics, and sensitivity of BP to steady state changes in salt intake were assessed. Twenty-four hour ambulatory BP monitoring (ABPM) was employed to measure baseline BP and BP response to 4 weeks' treatment with benazepril at 20 or 40 mg/day. Benazepril induced a highly-significant reduction in BP (P < .001) and increase in renal plasma flow (530 ± 17 to 580 ± 19 mL/min/1.73 m²; P < .001). Systolic BP fell from 143 ± 2 to 129 ± 2 mm Hg (P < .001), and diastolic BP fell from 91 ± 1.6 to 80 ± 2 mm Hg (P < .001). The magnitude of the BP and renal vascular response to ACE inhibition was not influenced by the sensitivity of BP to salt intake. In a multivariate analysis neither body mass index nor age influenced the BP response to ACE inhibition or the relationships between salt intake and a BP response to ACE inhibition. We conclude that the factors that influence sensitivity of BP to salt intake do not influence the systemic or renal hemodynamic response to ACE inhibition.     

An overview of the pharmacokinetics and pharmacodynamics of amlodipine in elderly persons with systemic hypertension

Pharmacokinetic and pharmacodynamic data were compared between elderly and young patients with hypertension who received single intravenous doses of amlodipine, a dihydropyridine calcium antagonist, followed by oral administration of amlodipine up to 10 mg once daily for 12 weeks. After intravenous administration, elderly patients had prolonged elimination half-life values (58 ± 11 vs 42 ± 8 hr; p < 0.05) caused by decreased clearance (19 ± 5 vs 7 liters/hr; p < 0.05). Systolic and diastolic blood pressures were significantly decreased from baseline throughout the 3-month treatment period in both groups. After long-term oral administration, elderly and young patients had comparable decreases in mean blood pressure at a given drug plasma concentration. The antihypertensive effect of amlodipine is well correlated with plasma concentration and, at a given concentration, is similar in both elderly and young patients.     

Responses to intravenous and oral diltiazem in elderly and younger patients with systemic hypertension

Diltiazem concentrations and blood pressure, heart rate, PR interval and forearm vascular resistance responses to intravenous (25 and 50 mg) and oral (120 mg) diltiazem were compared in 13 elderly persons (mean age 68 +/- 4 years) and 10 young persons (mean 30 +/- 5 years) with essential hypertension. Diltiazem elimination was slower in the elderly. After a dose of 25 mg, clearance was 13 +/- 4 ml/min/kg in the elderly and 23 +/- 7 in the young (p less than 0.05); after 50 mg, 16 +/- 6 and 21 +/- 12 ml/min/kg (p less than 0.05); and after oral administration, 22 +/- 9 and 35 +/- 14 ml/kg/min (p less than 0.02). No age-related differences in volume of distribution (by model or area methods) were seen. Elimination half-lives were 4.5 +/- 2.2 hours in the elderly and 3.8 +/- 0.7 hour in the young persons (p less than 0.01); 4.5 +/- 1.6 and 3.3 +/- 0.7 hours (p = 0.10); and 4.7 +/- 1.5 and 3.3 +/- 1.8 hours (p = 0.08) after 50, 25 and 120 mg. Maximal decreases in mean blood pressure were from 113 +/- 14 to 91 +/- 12 mm Hg (19%) in the elderly patients and from 108 +/- 8 to 99 +/- 9 mm Hg in the younger patients (8%) after 50 mg; from 106 +/- 13 to 93 +/- 14 mm Hg and from 109 +/- 11 to 99 +/- 13 mm Hg, respectively, after 25 mg; and from 113 +/- 10 to 97 +/- 10 mm Hg and from 109 +/- 11 to 97 +/- 8 after 120 mg orally.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effect of sustained-release isosorbide dinitrate for isolated systolic systemic hypertension in the elderly

A double-blind, randomized trial was performed in 40 patients, mean age (+/- standard deviation) 80 +/- 4 years, with isolated systolic systemic hypertension to evaluate the antihypertensive effect of oral sustained-release isosorbide dinitrate (ISDN), 20 to 40 mg twice daily, vs placebo. After 12 weeks of treatment, supine systolic blood pressure (BP) decreased from 192 +/- 10 to 162 +/- 12 mm Hg with ISDN (p less than 0.001) and from 189 +/- 10 to 175 +/- 15 mm Hg with placebo (p less than 0.001). On the basis of variance analysis, the decrease in systolic BP was significantly lower with ISDN (27 mm Hg) than with placebo (13 mm Hg). Similar results were observed for supine and erect systolic BP measured at 8 AM and 4 PM, 8 and 12 hours after drug intake. No significant differences in diastolic BP, heart rate or side effects occurred. After the ISDN tapering off-period (2 weeks), systolic BP increased significantly but did not change with placebo. The study provided evidence that in elderly patients with systolic hypertension, sustained-release ISDN induced a selective and sustained decrease in systolic BP, antihypertensive effect was observed 8 and 12 hours after drug administration, and no tolerance phenomenon was noted.     

Comparison in young and elderly patients of pharmacodynamics and disposition of labetalol in systemic hypertension

Pharmacodynamics and pharmacokinetics of labetalol, a combined alpha- and beta-adrenoceptor antagonist drug, were studied in elderly and young hypertensive patients. After receiving intravenous labetalol, elderly patients had a greater maximal mean decrease in systolic blood pressure (BP) (39 +/- 8 vs 25 +/- 13 mm Hg, p less than 0.02); however, maximal decrease in diastolic BP was similar in elderly (18 +/- 10 mm Hg) and young (17 +/- 6 mm Hg) patients. After receiving oral labetalol, elderly patients had a greater maximal decrease in standing systolic BP (41 +/- 16 vs 16 +/- 14 mm Hg, p less than 0.001) and similar decreases in standing diastolic BP (21 +/- 7 vs 17 +/- 9 mm Hg). Sitting maximal BP decreases after oral labetalol treatment were similar in elderly and young patients (12 +/- 16 vs 17 +/- 7 mm Hg systolic and 24 +/- 6 vs 12 +/- 7 diastolic). The decrease in heart rate was greater in young patients after intravenous labetalol administration. To evaluate labetalol pharmacodynamics, a linear model was used. Slope of labetalol concentration vs systolic BP for elderly vs young patients was 0.928 +/- 1.05 vs 0.326 +/- 0.490 ng/ml X mm Hg-1 (difference not significant). The slope of labetalol concentration vs heart rate for elderly vs young patients was 0.176 +/- 0.063 vs 0.406 +/- 0.303 ng/ml X beats/min-1 (p less than 0.05), with 2 elderly patients showing no decrease in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Salt sensitivity in blacks. Salt intake and natriuretic substances

Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; their mean arterial pressure rose by 7 +/- 0.2 and 6 +/- 0.2%, respectively, when salt intake was increased from 40 to 180 mmol/day. The hypertensive group exhibited decreased (p less than 0.05) dopamine excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p less than 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamine may be a pathogenic factor in the development and maintenance of hypertension in blacks.     

Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension

Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.     

老年难治性高血压

老年高血压的诊断也以收缩压(SBP)≥140mmHg和／或舒张压(DBP)≥90mmHg作为标准，单纯收缩期高血压(ISH)多见。随着增龄，老年人心脏收缩力下降，心排血量降低；主动脉及其主要分支的弹性降低，顺应性下降外周血管阻力逐渐升高；主动脉壁的可膨胀性在心脏收缩时也下降，脉压增大，收缩压较舒张压增高更明显。     

Treating hypertension in the elderly

This article discusses various topics related to treating hypertension in the elderly, including pseudohypertension, systolic hypertension, characteristics of young and elderly hypertensive patients, diagnostic considerations in evaluating elderly hypertensive patients, and general therapeutic considerations.     

Atrial fibrillation and isolated systolic hypertension: the systolic hypertension in the elderly program and systolic hypertension in the elderly program-extension study

We performed a post hoc analysis of the Systolic Hypertension in the Elderly Program database to assess the incidence of atrial fibrillation in the elderly hypertensive population, its influence on cardiovascular events, and whether antihypertensive treatment can prevent its onset. The Systolic Hypertension in the Elderly Program was a double-blind placebo-controlled trial in 4736 subjects with isolated systolic hypertension aged >or=60 years. Atrial fibrillation was an exclusion criterion from the trial. Participants were randomly assigned to stepped care treatment with chlorthalidone and atenolol (n=2365) or placebo (n=2371). The occurrence of atrial fibrillation and cardiovascular events over 4.7 years as well as the determination of cause of death at 4.7 and 14.3 years were followed. Ninety-eight subjects (2.06%) developed atrial fibrillation over 4.7 years mean follow-up, without significant difference between treated and placebo groups. Atrial fibrillation increased the risk for: total cardiovascular events (RR 1.69; 95% CI 1.21 to 2.36), rapid death (RR 3.29; 95% CI 1.08 to 10.00), total (RR 5.10; 95% CI 3.12 to 8.37) and nonfatal left ventricular failure (RR 5.31; 95% CI 3.09 to 9.13). All-cause and total cardiovascular death were significantly increased in the atrial fibrillation group at 4.7 years (HR 3.44; 95% CI 2.18 to 5.42; HR 2.39; 95% CI 1.05 to 5.43) and 14.3 years follow-up (HR 2.33; 95% CI 1.83 to 2.98; HR 2.21; 95% CI 1.54 to 3.17). Atrial fibrillation increased the risk for total cardiovascular events, rapid death, and left ventricular failure. All-cause mortality and total cardiovascular mortality were significantly increased in hypertensives with atrial fibrillation at 4.7 and 14.3 years follow-up.