Stress response pattern in obesity and systemic hypertension.

Under resting conditions obese hypertensive patients have been described as having a greater cardiac output and lower total peripheral resistance than lean hypertensive patients. To evaluate the hemodynamic patterns under stress conditions, we determined the hemodynamic response to mental stress (first study) and during isometric exercise (second study) in hypertensive patients with a body mass index > 27 kg/m2 (obese) and < 27 kg/m2 (lean). The cohort exposed to mental stress comprised 54 white male patients (30 were lean, 24 were obese) with untreated stage I or II essential hypertension according to the World Health Organization. Obese subjects responded with a higher increase in total peripheral resistance (p < 0.02) and lower increases in heart rate (p < 0.01), cardiac output (p < 0.01) and stroke volume (p < 0.02) when compared with their lean counterparts. This was independent of any differences in chemical or baseline hemodynamic characteristics at rest. The cohort exposed to isometric stress consisted of 57 patients (30 were lean, 27 were obese) with World Health Organization stage I or II essential hypertension. Obese subjects responded with exaggerated increases in systolic (p < 0.04) and diastolic (p < 0.01) pressures, and heart rate (p < 0.04) when compared with lean patients. Body mass index emerged as an independent determinant of the increase in systolic (r = 0.03) and diastolic (r = 0.01) pressure as well as of heart rate (r = 0.03). These results indicate that obese hypertensive patients respond to (1) mental stress with vasoconstriction instead of the expected vasodilation, and to (2) isometric stress with an exaggerated increase in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials

Based on the Medical Research Council study, Brown and Brown hypothesized in 1986 that angiotensin II could protect against strokes by causing vasoconstriction of the proximal cerebral arteries, thereby preventing Charcot-Bouchard aneurysms from rupturing. In light of this hypothesis, we evaluated the cerebroprotective effects of various drug classes in recent double-blinded, prospective, randomized trials, such as SHEP, PATS, CAPPP, HOPE, PROGRESS, INSIGHT, NORDIL, LIFE, SCOPE, ANBP2, and ALLHAT. Drugs that activate the AT2 receptors, such as diuretics, calcium antagonists, and angiotensin receptor blockers (ARBs), were consistently more beneficial for stroke reduction than drugs devoid of such activation, such as beta-blockers and angiotensin-converting enzyme (ACE) inhibitors, despite an equal fall in arterial pressure (at least in patients with a low incidence of cardiac complications). These clinical and epidemiologic observations are supported by experimental data documenting greater cerebroprotection with ARBs (which increase angiotensin II levels and stimulate the AT2 receptors) than with ACE inhibitors. Stroke is the most devastating consequence of hypertensive cardiovascular disease, and our hypothesis of cerebroprotection by AT2 receptor activation should be tested by a head-to-head comparison of an ARB with an ACE inhibitor.     

Introduction: Antihypertensive therapy: Past, present, and future

Adapted from Messerli FH, Laragh JH: Antihypertensive therapy: Past, present and future. In Messerli FH (ed): The ABC's of Antihypertensive Therapy(English language ed.) New York: Raven Press. (Used with permission.)     

Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors

Angioedema is a rare, potentially life-threatening adverse event of renin-angiotensin system inhibitors. The objective of the present study was to determine the risk of angioedema from randomized clinical trials. A PubMed/CENTRAL/EMBASE search was made for randomized clinical trials from 1980 to October 2011 in patients on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or direct renin inhibitor (DRI). Trials with a total number of patients ≥100 and a duration of ≥8 weeks were included for analysis. Incidence of angioedema was pooled by weighing the incident rate of each trial by the inverse of the variance. Twenty-six trials with 74,857 patients in the ACE inhibitor arm with 232,523 person-years of follow-up, 19 trials with 35,479 patients on ARB with 122,293 person-years of follow-up, and 2 trials with 5,141 patients on DRI with 1,735 person-years of follow-up met the inclusion criteria and were included in the analysis. In head-to-head comparison in 7 trials, risk of angioedema with ACE inhibitors was 2.2 times higher than with ARBs (95% confidence interval [CI] 1.5 to 3.3). With ACE inhibitors and ARBs, incidence of angioedema was higher in heart failure trials compared to hypertension or coronary artery disease trials without heart failure (p <0.0001). Weighted incidence of angioedema with ACE inhibitors was 0.30% (95% CI 0.28 to 0.32) compared to 0.11% (95% CI 0.09 to 0.13) with ARBs, 0.13% (95% CI 0.08 to 0.19) with DRIs, and 0.07% with placebo (95% CI 0.05 to 0.09). In conclusion, incidence of angioedema with ARBs and DRI was <1/2 than that with ACE inhibitors and not significantly different from placebo. Incidence of angioedema was higher in patients with heart failure compared to those without heart failure with ACE inhibitors and ARBs.     

Salt and Hypertension: Is Salt Dietary Reduction Worth the Effort?

In numerous epidemiologic, clinical, and experimental studies, dietary sodium intake has been linked to blood pressure, and a reduction in dietary salt intake has been documented to lower blood pressure. In young subjects, salt intake has a programming effect in that blood pressure remains elevated even after a high salt intake has been reduced. Elderly subjects, African Americans, and obese patients are more sensitive to the blood pressure-lowering effects of a decreased salt intake. Depending on the baseline blood pressure and degree of salt intake reduction, systolic blood pressure can be lowered by 4 to 8 mm Hg. A greater decrease in blood pressure is achieved when a reduced salt intake is combined with other lifestyle interventions, such as adherence to Dietary Approaches to Stop Hypertension. A high salt intake has been shown to increase not only blood pressure but also the risk of stroke, left ventricular hypertrophy, and proteinuria. Adverse effects associated with salt intake reduction, unless excessive, seem to be minimal. However, data linking a decreased salt intake to a decrease in morbidity and mortality in hypertensive patients are not unanimous. Dietary salt intake reduction can delay or prevent the incidence of antihypertensive therapy, can facilitate blood pressure reduction in hypertensive patients receiving medical therapy, and may represent a simple cost-saving mediator to reduce cardiovascular morbidity and mortality.     

Drug-induced hypertension: an unappreciated cause of secondary hypertension

A myriad variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure, or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, or an increase in pressure may be encountered after their discontinuation. In general, drug-induced pressure increases are small and transient: however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. The deleterious effect of therapeutic agents is more pronounced in patients with preexisting hypertension, in those with renal failure, and in the elderly. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and facilitate antihypertensive therapy. Once chemical-induced hypertension has been identified, discontinuation of the causative agent is recommended, although hypertension can often be managed by specific therapy and dose adjustment if continued use of the offending agent is mandatory. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action.     

Diurnal variations of cardiac rhythm,arterial pressure,and urinary catecholamines in borderline and established essential hypertension

Ambulatory continuous ECG and arterial pressure (BP) were recorded simultaneously (Delmar Avionics Pressurometer II) for 24 hours in 13 age-matched normotensive subjects, 11 patients with borderline hypertension (HBP), and in 10 patients with uncomplicated established essential HBP. Urinary concentrations of epinephrine, norepinephrine, and dopamine were simultaneously collected over four successive 4-hour periods and one 8-hour period. Prevalence and total number of ventricular and supraventricular ectopic beats was low and not affected by arterial BP. Twenty-four-hour heart rate (HR) and 4-hourly excretion of epinephrine, norepinephrine, and dopamine were comparable between normotensive and HBP persons and no correlation between urinary catecholamines and arterial BP (systolic, diastolic, or mean), HR, or prevalence of ectopic beats was found in any of the three groups or in the total study population. We conclude that HBP patients without ECG evidence of left ventricular hypertrophy do not have a higher prevalence of supraventricular or ventricular ectopic beats. Urinary catecholamines are not related to circadian fluctuations or variability in arterial BP, HR, or prevalence of ectopic beats.