UMLS:C0018801 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This editorial considers the use of the first selective oral renin inhibitor, aliskiren, in reducing angiotensin (Ang) II reactivation or aldosterone (ALDO) escape during renin-angiotensin-aldosterone system (RAAS) inhibition. RAAS blockade with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT(1) blockers (ARBs) is very useful for the treatment of arterial hypertension, chronic heart failure (CHF), atherosclerosis and diabetes. 'Ang II reactivation' and 'ALDO escape' or 'breakthrough' have been observed during either ACEI or ARB treatment, and may attenuate the clinical benefit of RAAS blockade. Renin and Ang I accumulate during ACE inhibition, and might overcome the ability of an ACEI to effectively suppress ACE activity. There is also data suggesting that 30 - 40% of Ang II formation in the healthy human during RAAS activation is formed via renin-dependent, but ACE-independent, pathways. Moreover, ACE gene polymorphisms contribute to the modulation and adequacy of the neurohormonal response to long-term ACE inhibition, at least in patients with CHF (up to 45% of CHF patients have elevated Ang II levels despite the long-term use of an ACEI) or diabetes. The reactivated Ang II promotes ALDO secretion and sodium reabsorption. ALDO breakthrough also occurs during long-term ARB therapy, mainly by an AT(2)-dependent mechanism. This was related to target-organ damage in animal models. Oral renin inhibition with aliskiren has showed excellent efficacy and safety in the treatment of hypertension. Aliskiren can be co-administered with ACEIs, ARBs or hydrochlorothiazide. Furthermore, there is evidence suggesting that aliskiren reduces Ang II reactivation in ACE inhibition and ALDO escape during treatment with an ACEI or an ARB, at least to the degree that this is associated with the RAAS. For RAAS-independent ALDO production, the combination of aliskiren with eplerenone might prove useful.
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PMID:Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? 1737 10

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p<0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p<0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p=0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p<0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p<0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.
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PMID:Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). 1739 2

The TROPHY study was designed to show the feasibility of pharmacological prevention of hypertension with respect to the group of patients with "prehypertension" as defined by the JNC VII recommendations. This clinical trial compared candesartan 16 mg/day with placebo and the result at 4 years was a reduction in the relative risk of developing hypertension of 15.6%. The antihypertensive drug delayed the onset of hypertension in a mainly overweight masculine population. Staessen, Zhu and O'Brien's groups suggest measuring an index of arterial rigidity obtained from ambulatory blood pressure monitoring: the ambulatory arterial stiffness index (AASI). This is calculated as [1- slope of systolic/diastolic pressure]. The reference values for AASI vary with age from 0.50 to 0.70. The CAFE study, a spin-off of the ASCOT trial, showed that the central blood pressure decreased more than the peripheral blood pressure with the association amlodipine-perindopril as compared with atenolol and a thiazide diuretic. The capacity of an antihypertensive drug or an association of antihypertensives to decrease the central blood pressure could be a pertinent factor of evaluation to be taken into account in the interpretation of clinical trials. The study of the Italian cohort PAMELA showed a progressive increase in cardiovascular and global mortality with respect to the findings of increased blood pressure by one, two or three methods of measurement (at the office, at home, ambulatory) compared with patients declared normotensive by the same methods. This registry confirmed the implication of masked hypertension on cardiovascular prognosis and also showed that "white coat" hypertension was not completely benign. The "3 cities" study is a French epidemiological study of persons over 65 years of age. The control of the blood pressure of the treated elderly hypertensives was 57% in men and 70% in women when the cut-off was 160/95 mmHg and 31% for all patients in a cut-off level of 140/90 mmHg. Lafontan et al. are studying the mobilisation of fat induced by exercise, resistant to betablockers therapy and attributed to natriuretic peptides. This metabolic pathway could be of relevance in the metabolic syndrome and in cardiac failure. Renin inhibitors, such as aliskiren, are being developed. The outlook is the possible use of these drugs with ACE inhibitors or angiotensin II inhibitors, taking into account the risk/benefit ratio.
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PMID:[The best of hypertension in 2006]. 1740 64

Cardiovascular disease represents a continuum that starts with risk factors, such as hypertension, and progresses to atherosclerosis, target organ damage, and ultimately leads to heart failure or stroke. Renin-angiotensin-aldosterone system (RAAS) blockade with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) has been shown to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby potentially reducing the risk of cardiovascular events. Such a reduction has been shown with ACE inhibitors in patients with coronary artery disease, but no such data are currently available for ARBs. Both ACE inhibitors and ARBs have been shown to reduce damage in target organs, such as the heart and kidney, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Trials, such as the Ongoing Telmisartan Alone in Combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomised Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND), that compare telmisartan, ramipril, and their combination in high-risk patients with vascular end-organ damage, should provide important new insights into the benefits of intervention with RAS blockade along the cardiorenovascular continuum.
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PMID:Angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors: where do we stand now? 1830 33

Excessive aldosterone secretion is detrimental to the heart, vessels and kidneys, contributing to hypertension and the signs and progression of heart failure. Aldosterone secretion, abnormally elevated in heart failure and hypertension, can be blunted with angiotensin-converting enzyme inhibitors. Amlodipine, used to treat hypertension and heart failure, was hypothesized to activate the renin-angiotensin-aldosterone system (RAAS). A study was conducted with six normal adult male beagle dogs. Each dog received amlodipine (0.57 mg/kg b.i.d.) for 6 days, followed by amlodipine (0.57 mg/kg b.i.d.) and enalapril (0.57 mg/kg b.i.d.) for 4 days. Blood pressure, heart rate, serum chemistries and urinary aldosterone excretion, as a measure of RAAS activation, were compared with baseline values. Blood pressure fell by approximately 7% with amlodipine (P = 0.05) and a further 7% with the combination of amlodipine and enalapril (P < 0.01). Blood urea nitrogen increased with the combination (P < 0.05) but only one dog became mildly azotemic. Renin-angiotensin-aldosterone system activation, based on 24 h urinary aldosterone excretion and by aldosterone:creatinine ratio was increased by approximately threefold (P < 0.05) with amlodipine administration. This effect was blunted by enalapril, such that aldosterone excretion was no longer different from that observed under control conditions, although values for 24-h aldosterone excretion did not return to pretreament levels.
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PMID:The effect of amlodipine and the combination of amlodipine and enalapril on the renin-angiotensin-aldosterone system in the dog. 1780 30

Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, target organ damage, and ultimately to myocardial infarction, heart failure, stroke or death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby reducing the risk of cardiovascular events. Such a reduction has been shown mainly for ACE inhibitors in patients with coronary artery disease, but recent studies revealed that ARBs are not inferior in this respect. However, no such data are currently available on the combination of these drugs. Both ACE inhibitors and ARBs have been shown to reduce target organ damage in organs such as the kidney, brain and heart, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Experimental data point to an influence of ACE inhibitors and ARBs on the number and function of endothelial progenitor cells revealing additional mechanisms of action of these drugs. The VALIANT trial has shown equivalent effects of ARB valsartan and the ACE-inhibitor captopril in patients post myocardial infarction, but the dual RAS-blockade, compared to monotherapy, did not further reduce events. In secondary prevention, the most-recently published ONTARGET study provides evidence that on top of a better tolerability AT(1)-receptors antagonists are equal to ACE inhibitors in the prevention of clinical endpoints like cardiovascular mortality and morbidity, myocardial infarction and stroke. The combined RAS blockade, however, achieved no further benefits in vascular high-risk patients and was associated with more adverse events. In chronic heart failure, ValHeFT and CHARM-ADDED have shown that combined RAS inhibition with ACE inhibitor and valsartan or candesartan reduced morbidity and mortality in certain patient subgroups. Accumulating evidence also points to benefits of the combination therapy in individuals with proteinuric nephropathies. In conclusion, while combined RAS-inhibition is not generally indicated in patients along the cardio-reno-vascular continuum, it has already proven to be effective in heart failure patients with incomplete neuroendocrine blockade. In secondary prevention, monotherapy with either RAS inhibitor is equally efficacious. Furthermore, novel pharmacologic agents such as renin inhibitors may prove useful in preventing common side effects of RAS blockade such as angiotensin escape and AT(1)-receptor upregulation, giving clinicians additional therapeutic tools to optimally treat the individual patient.
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PMID:RAS blockade with ARB and ACE inhibitors: current perspective on rationale and patient selection. 1845 36

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).
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PMID:[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment]. 1901 37

Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, end-organ damage, and ultimately to chronic heart failure (CHF) and premature death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II type 1 receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Several mechanisms govern the progression of structural myocardial damage to end-stage CHF. Chronic neuroendocrine activation fosters left ventricular remodeling and dilatation and leads to clinical symptoms of CHF via forward/backward failure. RAS inhibition is a cornerstone of neuroendocrine blockade in CHF patients, and combined RAS blockade is especially effective in patients presenting with repetitive cardiac decompensations. This review focuses on the therapeutic role of inhibitors of different RAS components in chronic heart failure caused by systolic left ventricular dysfunction.
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PMID:The therapeutic role of RAS blockade in chronic heart failure. 1912 20

Renin-angiotensin-aldosterone system (RAAS) is not only generated in the circulation by renin and angiotensin-converting enzyme but also is produced locally in numerous organs. Local RAAS is the main pharmacological target to treat cardiovascular disease, such as hypertension, heart failure, myocardial infarction, and renal disease. Moreover, many novel molecules modifying RAAS are determined. This review summarizes the recent findings about the progress of the study of RAAS.
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PMID:[The progress of the study of RAAS]. 1934 24

Renin-angiotensin-aldosterone system (RAAS) overactivity is associated with increased cardiovascular risk, a finding that may be explained by the key role of the RAAS in stimulating vascular and cardiac remodeling. Inhibition of RAAS activity with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has been shown to reduce cardiovascular mortality in patients with heart failure. ACE inhibitors have also been shown to reduce the incidence of stroke, myocardial infarction (MI), and heart failure in high-risk patients without heart failure. These findings led to the evaluation of the ARB telmisartan versus the ACE inhibitor ramipril in the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), a cardioprotection trial conducted in high-risk patients without left ventricular dysfunction or heart failure. The results of this trial showed that the ACE inhibitor ramipril and the ARB telmisartan are equally effective in reducing the incidence of cardiovascular death, MI, stroke, and hospitalization for heart failure in patients without heart failure or left ventricular dysfunction but at high risk for cardiovascular disease (CVD). These results confirm that RAAS inhibition, using ACE inhibitors or ARBs, is an effective approach to reducing cardiovascular mortality and morbidity in patients without heart failure who are at high risk for CVD.
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PMID:Recent advances in cardiovascular risk reduction: implications of ONTARGET. 1940 52

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