Moderate versus intensive treatment of hypertension using amlodipine/valsartan and with the addition of hydrochlorothiazide for patients uncontrolled on angiotensin receptor blocker monotherapy: results in racial/ethnic subgroups.

Combination therapy may reduce racial/ethnic differences in response to antihypertensives. In this post-hoc analysis, we evaluated treatment response by race/ethnicity among hypertensive adults enrolled in a 12-week, double-blind study in which patients previously uncontrolled (mean sitting systolic blood pressure [MSSBP] ≥150 and <200 mm Hg) on angiotensin receptor blocker (ARB) monotherapy (other than valsartan) for 28 days or more (n = 728) were randomized to amlodipine/valsartan 10/320 mg (intensive) or 5/160 mg (moderate). Treatment-naïve patients (in previous 28 days) or those who failed on a non-ARB first underwent a 28-day run-in period with olmesartan 20 mg or 40 mg, respectively. Hydrochlorothiazide (HCTZ) 12.5 mg was added to both arms at week 4; optional up-titration to 25 mg at week 8 (if MSSBP >140 mm Hg). Intensive treatment provided greater BP lowering versus moderate treatment throughout the study, regardless of race/ethnicity (474 white, 198 African American, 165 Hispanic individuals). Least-square mean reductions from baseline to week 4 in MSSBP (primary outcome) ranged from 20.4 to 23.5 mm Hg (intensive) versus 17.5 to 19.0 mm Hg (moderate), across racial/ethnic subgroups. Both regimens were well tolerated. Amlodipine/valsartan/HCTZ combination therapy was efficacious across racial/ethnic subgroups. Maximal efficacy was obtained with intensive treatment.

Combined renin-angiotensin-aldosterone system inhibition in patients with chronic heart failure secondary to left ventricular systolic dysfunction.

The prevalence of heart failure (HF) is high and still on the rise. In 2004, an estimated 5.2 million adults in the United States carried the diagnosis of HF with a mortality rate of >19%. The incidence of HF is higher in individuals 65 years or older. As the US population grows older, the personal and economic costs of this disease are expected to grow. More than 75% of patients with HF have a history of hypertension, and blood pressure control can reduce the risk of serious cardiovascular events and death in this population. In addition to lowering blood pressure, blockade of the renin-angiotensin-aldosterone system can reduce the negative effects of chronic renin-angiotensin-aldosterone system activation on the progression of HF. This review discusses the clinical data supporting the use of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers, alone or in combination, for improving outcomes in patients with HF.

Complementary effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in slowing the progression of chronic kidney disease.

Chronic kidney disease (CKD) and end-stage renal disease continue to pose major healthcare challenges. Early initiation of therapy aimed at slowing the progression of CKD is essential. Increased renin-angiotensin-aldosterone-system activity and, in particular, elevated levels of angiotensin II (AII) play important roles in the development and progression of CKD. Therefore, pharmacologic therapies that block the effects of AII and reduce its pathogenic effects are cornerstones of clinical management. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to have renoprotective effects in addition to their ability to control blood pressure. There is accumulating clinical evidence that the combination of an ACEI and an ARB provides greater renal protection, particularly in decreasing proteinuria, than does either agent alone.

Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients.

INTRODUCTION: Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients. PATIENTS: Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with >25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr. RESULTS: 100 Caucasians, M:F=52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9+/-9 (7-47) to 39.2+/-15.4 (17-89) ml/min/1.73 m(2) BSA, 26.5 (3-46) months after stopping AB (P=0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibitor use/abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine -2.1+/-0.6 versus 1.5+/-0.4 mg/dL, P=0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44-83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB. CONCLUSIONS: Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study.

Prevención de la fibrilación auricular en los pacientes con insuficiencia cardiaca / Prevention of atrial fibrillation in patients with heart failure

La insuficiencia cardiaca promueve la aparición de fibrilación auricular y ésta agrava la insuficiencia cardiaca. La fibrilación auricular puede afectar en cualquier momento a un gran porcentaje de los pacientes con insuficiencia cardiaca. La manifestación y presentación clínica cambia con el paso del tiempo y depende de cada paciente. Empeora la sintomatología de los pacientes, como una complicación más de su enfermedad, y causa frustración tanto a los pacientes como a los médicos. Se estima que hasta un 50% de los pacientes con insuficiencia cardiaca presentan fibrilación auricular en algún momento de su evolución, por lo que son necesarias medidas tanto para la prevención de la embolia como para el alivio de los síntomas. La interferencia farmacológica con señales específicas de las vías de transducción es prometedora. Hasta ahora, los agentes más efectivos son los inhibidores de la enzima de conversión de la angiotensina y los antagonistas de los receptores de la angiotensina II, que reducen el estrés oxidativo, restauran las concentraciones de óxido nítrico, inhiben la formación de tejido fibroso y pueden reducir la ectopia de las venas pulmonares. El desenmascaramiento de factores genéticos implicados aún no conocidos puede tener gran repercusión. Es necesario un mejor conocimiento de la fisiología molecular. Esto puede ayudar a desarrollar nuevos regímenes de tratamiento o terapia híbrida con combinación de fármacos «antiarrítmicos» y «no antiarrítmicos» para aumentar la eficacia del tratamiento (AU)

The presence of heart failure increases the risk of atrial fibrillation, a condition which in turn aggravates heart failure. At any point in time, a large percentage of patients with heart failure are affected by atrial fibrillation. Its clinical characteristics change over time and vary according to the individual patient. It worsens patients’ symptoms, adds a further a complication to their illness, and is problematic for both patients and physicians. It is estimated that 50% of patients with heart failure will experience atrial fibrillation, and will require treatment to prevent embolism and relieve symptoms. The ability of drugs to interfere with specific signal transduction pathways is promising. To date, the most effective agents appear to be angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists. These compounds reduce oxidative stress, restore the nitric oxide level, inhibit the formation of fibrous tissue, and can ameliorate pulmonary vein ectopy. Uncovering the, as yet unknown, genetic factors involved could have significant implications. Better understanding of the relevant molecular biology is essential. This could lead to new treatment regimes or to hybrid therapy with a combination of antiarrhythmic and non-antiarrhythmic drugs, which could improve treatment effectiveness (AU)

Changes in endothelium-derived hyperpolarizing factor in hypertension and ageing: response to chronic treatment with renin-angiotensin system inhibitors.

1. Endothelial function is impaired in hypertension and ageing and this may be associated with an increase in cardiovascular disease. Several clinical studies have shown that blocking the renin-angiotensin system (RAS) improves endothelial function not only in hypertensive patients, but also in normotensive patients with cardiovascular disease. 2. The aim of the present study was to test whether endothelium-derived hyperpolarizing factor (EDHF)-mediated smooth muscle hyperpolarization and relaxation are altered in hypertension and ageing and, if so, whether chronic treatment with RAS inhibitors (the angiotensin-converting enzyme inhibitor enalapril and the angiotensin AT1 receptor antagonist candesartan) would correct such changes. 3. Endothelium-derived hyperpolarizing factor-mediated responses were examined in mesenteric arteries from 12-month-old spontaneously hypertensive rats (SHR) and 3-, 6-, 12- and 24-month-old normotensive Wistar-Kyoto (WKY) rats. Furthermore, both strains were treated for 3 months with either RAS blockers or a conventional therapy with hydralazine and hydrochlorothiazide from 9 to 12 months of age. 4. In arteries of 12-month-old SHR, EDHF-mediated responses were impaired compared with age-matched WKY rats. In SHR, all antihypertensive treatments improved the impairment of EDHF-mediated responses; however, RAS inhibitors tended to improve these responses to a greater extent compared with conventional therapy with hydralazine and hydrochlorothiazide. 5. In arteries of WKY rats, EDHF-mediated responses were impaired at the age of 12 and 24 months compared with 3- and 6-month-old rats, with the response tending to be impaired to a greater extent in 24-month-old rats. 6. Three months of treatment of WKY rats, until 12 months of age, with RAS inhibitors, but not with conventional therapy with hydralazine and hydrochlorothiazide, improved the age-related impairment of EDHF-mediated responses, despite a similar reduction in blood pressure by both treatments. 7. These findings suggest that: (i) EDHF-mediated hyperpolarization and relaxation decline with hypertension and ageing in rat mesenteric arteries; (ii) antihypertensive treatment restores the impaired EDHF-mediated responses in hypertension; (iii) RAS inhibitors may be more efficacious in improving endothelial dysfunction associated with hypertension; and (iv) chronic treatment with RAS inhibitors improves the age-related impairment of EDHF-mediated responses, presumably through the blockade of RAS but not blood pressure lowering alone.

Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period.

BACKGROUND: Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent. METHODS: The study was a double-blind, randomized trial that compared telmisartan (40 to 80 mg once daily) versus valsartan (80 to 160 mg once daily) on early morning BP in 490 patients with hypertension. Ambulatory BP recordings were performed at baseline after a placebo period and again after 6 and 8 weeks of double-blind therapy in a randomized cross-over design. The monitoring patients received either an active dose or a placebo dose (to mimic a "missed" dose). The primary study end point was reduction in the BP in the early morning period (last 6 h of the dosing period). RESULTS: After the active dose, telmisartan reduced the BP during the last 6 h of the dosing period by -11/-7.6 +/- 0.8/0.6 mm Hg compared to -8.7/-5.8 +/- 0.8/0.6 mm Hg on valsartan (P = .02 for systolic BP and.01 for diastolic BP). On the day of the missed dose, telmisartan reduced the early morning BP by -9.0/-6.3 +/- 0.7/0.6 mm Hg versus -7.4/-5.1 +/- 0.7/0.4 mm Hg on valsartan (P = .09 for systolic BP and.06 for diastolic BP). On the day of the missed dose, reductions in 24-h average BP for the two antihypertensive agents were -10.3/-6.9 mm Hg for telmisartan versus -8.7/-5.9 mm Hg for valsartan (P = .06 for systolic BP and.056 for diastolic BP). CONCLUSIONS: On a day of active therapy, telmisartan lowered both systolic and diastolic BP to a greater extent than valsartan for the last 6 h of the dosing interval. On a day in which a dose was missed, there was a notable trend for greater BP reduction during the latter part of the dosing interval on telmisartan versus valsartan. These results demonstrate that telmisartan achieved a greater effect than valsartan on BP during the early morning period in patients with hypertension.

Acute vascular effects of the angiotensin II receptor antagonist olmesartan in normal subjects: relation to the renin-aldosterone system.

The extent to which the clinical effects of angiotensin receptor blockers (ARB) are related to ambient renin system activity remains poorly defined. Therefore, we measured blood pressure (BP), large (C1) and small (C2) arterial compliance, systemic vascular resistance (SVR), plasma renin activity (PRA), and the 24-h urinary excretion of sodium (UNaV) and aldosterone before and 1, 2, 4, and 24 h after administration of single doses of placebo, and 5, 20, and 40 mg of the ARB olmesartan medoximil to 12 unmedicated normotensive subjects. In the basal state, SVR was inversely related to UNaV (r = -0.3, P =.04); the greater the UNaV, the more vasodilated the subject. Indices of arterial compliance, both C1 (r = -0.32, P =.03) and C2 (r = -0.35, P =.02) were inversely related to the basal PRA. Renin also predicted olmesartan-induced changes in C1 (r = 0.43, P =.004) and C2 (r = 0.33, P =.04). The greater the basal PRA, the less the arterial compliance, and the more compliance improved after olmesartan. Both systolic (P =.003) and diastolic (P <.0001) BP fell significantly on olmesartan compared with placebo (MANOVA with time), and relations were observed between the basal PRA and olmesartan-induced changes in pressure (systolic BP: r = -0.414, P =.012; diastolic BP: r = -0.561 P <.0001)-the greater the initial PRA, the more olmesartan lowered BP. Furthermore, the more pressure fell, the more PRA rose reciprocally (r = -0.44, P =.007). Finally, aldosterone excretion fell (sig = 0.05) on each dose of olmesartan compared with placebo. We conclude that 1) the inverse relation of UNaV and SVR illustrates the reciprocal role of volume versus constrictor factors in maintaining normal BP; and 2) PRA is a physiologic determinant of arterial compliance in normal individuals and of the response to the ARB olmesartan. Measurement of PRA may help to predict clinical ARB responses in individual subjects.

Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide.

BACKGROUND: Most patients with hypertension require more than one agent to control blood pressure (BP). The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide (HCTZ). METHODS: This was a randomized, double-blind, factorial design study. After a placebo run-in period, eligible patients (n = 502) with a baseline mean seated diastolic blood pressure (SeDBP) of 100 to 115 mm Hg were randomized to one of 12 groups: placebo, olmesartan medoxomil monotherapy (10, 20, or 40 mg/day, HCTZ monotherapy (12.5 or 25 mg/day), or one of six groups of olmesartan medoxomil/HCTZ combination therapy. The primary endpoint was the change in mean trough SeDBP from baseline at week 8. Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses, but did not compare BP reductions with different combination doses. RESULTS: Olmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure (SeSBP) at week 8 than did monotherapy with either component. All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dose-dependent manner. Reductions from baseline in mean trough SeSBP/SeDBP were 3.3/8.2 mm Hg, 20.1/16.4 mm Hg, and 26.8/21.9 mm Hg with placebo, olmesartan medoxomil/HCTZ 20/12.5 mg, and olmesartan medoxomil/HCTZ 40/25 mg, respectively. All treatments were well tolerated. CONCLUSIONS: Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and was well tolerated.

Combination angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy: its role in clinical practice.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly prescribed for the management of hypertension. In addition, each of these drug classes has been shown to be effective in the treatment of congestive heart failure, proteinuric chronic kidney disease, and most recently the high-cardiac-risk profile patient. The individual success of each of these drug classes has fueled the theory that given together, the overall biologic effect of both would surpass that of either given alone. The foundation of this premise, although biologically plausible, has yet to be proven in a compelling enough fashion to support the everyday use of these two drug classes in combination. Additional clarifying studies are required to establish whether specific patient subsets exist that might benefit from such combination therapy.

Quality of life measured in a practice-based hypertension trial of an angiotensin receptor blocker.

Effectiveness of antihypertensive treatment depends not only on drugs that avoid or minimize symptomatic side effects but also on therapy that has a positive effect on quality of life. This study assessed the effect on quality of life of a contemporary agent (an angiotensin receptor blocker) and evaluated the validity and practicality of using a quality-of-life instrument in the practice-based setting. A total of 2716 hypertensive patients, either untreated or on single-agent therapy, were started on or switched to 40 mg telmisartan for 6 weeks; in patients whose blood pressures remained above 130/85 mm Hg after 2 weeks, the dose was increased to 80 mg for the remaining 4 weeks of treatment. Quality of life was measured by patient self-administration of the Psychological General Well-Being Index (GWBI) at baseline and at the end of the study. Sixty-eight percent (n=1858) of patients treated with telmisartan fully completed both GWBI tests; the test score increased by 5.2+/-0.3 (p<0.0001) from 77.7+/-0.4. This improvement was observed across all six emotional and health subscales of the GWBI. White and black patients, those aged <65 or >/=65 years, and men and women had similar increases, though the baseline value in women was sharply lower (p<0.001) than in men. The GWBI rose more in patients whose blood pressure was controlled by treatment (<140/90 mm Hg) than in noncontrolled patients (6.1 vs. 4.1, p<0.0001); for all patients the decreases in systolic and diastolic blood pressures produced by telmisartan correlated significantly (p<0.001 for each) with the increases in the GWBI scores. Controlling blood pressure appears to be an important element in improving subjective health perceptions of hypertensive patients.

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney.

Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT(1)-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT(1)-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.

Long-term combined therapy with an angiotensin type I receptor blocker and an angiotensin converting enzyme inhibitor prolongs survival in dilated cardiomyopathy.

The efficacy of ACE inhibitors (ACEIs) in the treatment of chronic heart failures is well documented. However, ACEIs may provide incomplete blockade of the renin-angiotensin system (RAS) because of the alternative pathways for angiotensin II (All) production. We hypothesized that more complete blockade of RAS by adding an AT1 receptor blocker (ARB) may have greater potential to decrease mortality associated with heart failure and improve cardiac function than monotherapy with ACEIs. The objective of this study was to evaluate the effect of combined therapy on cardiac functions and survival in cardiomyopathic hamsters. Male cardiomyopathic hamsters (BIO TO2) were administered either placebo (group C), enalapril (30 mg/kg/day) (group E), or enalapril (30 mg/kg/day) + valsartan (500 mg/ kg/day) (group EV), starting at the age of 6 weeks. Kaplan-Meier analysis was performed to assess the differences in survival. Cardiac functions were evaluated by echocardiogram and cardiac catheterization. Group EV showed significant increases in fractional shortening, LV dP/dTmax, and deceleration time, and showed significant decreases in left ventricular diastolic dimension, LV dP/dTmin, and early diastolic mitral velocity/atrial systolic velocity. Treatment with enalapril resulted in longer survival compared with placebo. Moreover, life expectancy (median probability of survival: 433 days) increased significantly in group EV compared with group E (P<0.05) as well as group C (P<0.001). It is concluded that combined therapy improved cardiac function and survival compared to placebo or enalapril monotherapy.

A chronotherapeutic approach to effective blood pressure management.

The major randomized trials in hypertension have unequivocally demonstrated the benefits of treatment. None of these trials have sought to address the issue of the potential superiority of 24-hour blood pressure control. However, there is a volume of epidemiologic evidence to suggest that prevention of target organ damage requires the sustained reduction of blood pressure throughout the full 24-hour period between doses. Historically, some antihypertensive drugs have been approved for use at high doses to achieve apparent blood pressure control at the end of the once-daily dosing interval. This approach is flawed; attention is focused on this single time point at the end of the dosing interval, without due regard to the antihypertensive response during the rest of the dosing interval. Subsequently, guidelines formulated by the US Food and Drug Administration suggest that all antihypertensive drugs should consistently achieve a trough:peak ratio decline in blood pressure of at least 50%. Evidence suggests that antihypertensive drugs, such as calcium antagonists and angiotensin II receptor blockers, differ in their ability to provide 24-hour blood pressure control. For example, unlike some other angiotensin II receptor blockers, telmisartan provides consistent reduction of blood pressure during the 24-hour period.

Angiotensin II subtype 1 (AT1) receptors contribute to ischemic contracture and regulate chemomechanical energy transduction in isolated transgenic rat (alphaMHC-hAT1)594-17 hearts.

BACKGROUND: The role of AT1 receptors in myocardial ischemia/reperfusion injury is unclear. We, therefore, investigated the effects of the AT1 receptor antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT1 overexpressing transgenic [transgenic(alphaMHC-hAT1)594-17] and Sprague-Dawley rats (SD) subjected to ischemia/reperfusion injury. METHODS AND RESULTS: Hearts of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs-Henseleit buffer with or without 10 microM Irb in Langendorff mode. After 15 min of stabilization, pressure-volume curves were obtained and the hearts subjected to 20 min ischemia followed by 30 min reperfusion. A second set of pressure-volume curves was obtained thereafter. Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), total coronary flow (CF) and oxygen consumption (MVO2) were recorded continuously. Myocardial efficiency was derived from the slope of relations of MVO2 to pressure/volume area. After 20 min ischemia, LVEDP was significantly higher in transgenic than in SD (35.7+/-1.8 vs. 29.2+/-1.0 mmHg, P<0.05) or Irb treated transgenic hearts (24.3+/-1.6 mmHg, P<0.05). Myocardial efficiency was increased by Irb before ischemia. Ischemia increased efficiency in SD but not in transgenic rats, Irb increased efficiency in transgenic hearts post-ischemia. CONCLUSION: Transgenic hearts developed ischemic contracture more rapidly than SD hearts as indicated by higher LVEDP during ischemia. This response was antagonized by Irb, indicating a role of AT1 receptors in ischemic contracture, AT1-receptors also appear to be involved in the control of myocardial efficiency.

Radial, carotid and aortic distensibility in congestive heart failure: effects of high-dose angiotensin-converting enzyme inhibitor or low-dose association with angiotensin type 1 receptor blockade.

UNLABELLED: objectives; The aim of this study was to determine whether in patients with congestive heart failure (CHF) a distensibility (Dist) reduction: 1) similarly occurs in different arteries; 2) is related to CHF severity; and 3) is reversible with treatment. background: Several studies suggest that CHF is accompanied by a reduced arterial Dist. METHODS: We measured diameter in radial artery, carotid artery (CA) and abdominal aorta (AO) by echotracking. Distensibility was obtained by relating it to blood pressure. Data were collected in 30 patients with CHF (New York Heart Association functional class I to III) under standard treatment with diuretic, digitalis and angiotensin-converting enzyme (ACE) inhibitor in whom CHF severity was assessed by maximum oxygen consumption (VO(2)max) percentage and in 30 age- and gender-matched controls. Patients with CHF were then randomized to maintain standard treatment (n = 10), double the ACE inhibitor dose (n = 10) or add an angiotensin II antagonist (n = 10) and restudied after two months. RESULTS: Distensibility was markedly reduced in the CHF group in all three vessels (p < 0.01), CA and AO Dist being related to CHF severity (p < 0.05). After two months, Dist did not change in the group maintained under standard treatment, but it increased significantly (p < 0.05) and similarly when the ACE inhibitor dose was doubled or an angiotensin II antagonist was added. CONCLUSIONS: Congestive heart failure is characterized by a reduction of Dist of large-elastic and middle-sized muscular arteries. The reduction of large-elastic artery Dist is related to the CHF severity. These alterations can be reversed by drugs, effectively interfering with the renin-angiotensin system either at the ACE or at the angiotensin receptor level.

Effects of angiotensin II receptor antagonists on [(123)I]metaiodobenzylguanidine myocardial imaging findings and neurohumoral factors in chronic heart failure.

Previous studies have not investigated the ef-ficacy of angiotensin II (AII) receptor antagonists against cardiac sympathetic overactivity in patients with chronic heart failure (CHF) using [(123)I]metaiodobenzylguanidine (MIBG) myocardial imaging. We studied 34 CHF patients with fractional shortening of the left ventricular (LV) diameter <==25% or LV ejection fraction <==45% in echocardiograms. An AII receptor antagonist (losartan or candesartan) was administered. Before and 6 months after the administration, MIBG myocardial imaging and echocardiography were performed, and neurohumoral factors were investigated. MIBG imaging revealed that the antagonist did not significantly change the heart-to-mediastinum ratio. However, the washout rate fell significantly (from 32.6% +/- 7.6% to 28.2% +/- 7.5%; P < 0.001). No significant changes occurred in LV diameter, fractional shortening, or LV ejection fraction. Circulating atrial (ANP) and brain natriuretic peptides (BNP), and aldosterone fell significantly. Changes in the MIBG washout rate correlated positively with changes in BNP ( r = 0.35, P < 0.05). In 19 patients also being treated with angiotensin-converting enzyme (ACE) inhibitors, the MIBG washout rate also fell significantly with AII antagonists, as did BNP and aldosterone. The decreased MIBG washout and BNP in patients with CHF induced by the AII receptor antagonists suggests the efficacy of these agents in modifying cardiac sympathetic function and neurohumoral factors, even with ACE inhibition. Combination therapy with AII receptor antagonists and ACE inhibitors appears effective for CHF.