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)

Diabetes mellitus is a potent risk factor for the development of a wide spectrum of cardiovascular (CV) complications. The complex metabolic milieu accompanying diabetes alters blood rheology, the structure of arteries and disrupts the homeostatic functions of the endothelium. These changes act as the substrate for end-organ damage and the occurrence of CV events. In those who develop acute coronary syndromes, patients with diabetes are more likely to die, both in the acute phase and during follow-up. Patients with diabetes are also more likely to suffer from chronic cardiac failure, independently of the presence of large vessel disease, and also more likely to develop stroke, renal failure and peripheral vascular disease. Preventing vascular events is the primary goal of therapy. Optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional CV risk factors to optimize blood glucose, lipid and blood pressure control. Targeting medical therapy to improve plaque stability and diminish platelet hyper-responsiveness reduces the frequency of events associated with atherosclerotic plaque burden. In patients with critical lesions, revascularization strategies, either percutaneous or surgical, will often be necessary to improve symptoms and prevent vascular events. Improved understanding of the vascular biology will be crucial for the development of new therapeutic agents to prevent CV events and improve outcomes in patients with diabetes.
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PMID:A cardiologist view of vascular disease in diabetes. 1794 77

Cardiovascular disease remains the leading cause of death worldwide. The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure, through the actions of angiotensin (Ang) II. Excessive RAAS activity may lead to hypertension and associated target organ damage. Indeed, RAAS blockade with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT (1) blockers (ARBs) has proved to be successful treatment for arterial hypertension, heart failure and diabetes. Accumulating evidence suggests that arterial stiffness is an important and independent predictor of cardiovascular risk. More recently, a role for advanced glycation end-products (AGEs) in the development of arterial stiffening has been suggested. Advanced glycation end-products form by a nonenzymatic reaction between reducing sugars and biological proteins. Mechanisms underlying these alterations include AGE cross-linking of collagen and AGE interactions with circulating proteins and AGE receptors. New pharmacologic agents that prevent AGE formation, break cross-links, or block AGE receptors reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation, and improve endothelial function. These agents promise to reduce the risk of isolated systolic hypertension, diastolic dysfunction, diabetes and thus, heart failure.
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PMID:Inhibition of renin-angiotensin system and advanced glycation end products formation: a promising therapeutic approach targeting on cardiovascular diseases. 1797 87

Appropriate evaluation of short- and medium-term cardiovascular risk in acute coronary syndromes (ACS) patients should allow to individualize and improve treatment in the future. Natriuretic peptides can be measured in plasma using reliable and fast methods. B-type natriuretic peptide (BNP) is released into the circulation by the cardiac ventricle in response to increases in wall stress. Both BNP and NT-proBNP have been shown to aid in the diagnosis of heart failure. In addition, these peptides correlate with left ventricular dilatation, remodelling and dysfunction, and have the capacity of improving significantly the early risk stratification in patients with ST- or non-ST-elevation ACS. BNP determinations can be associated to cardiac troponins (for example, cTnT) and C-reactive protein (CRP). Plasma concentrations of these biomarkers are related to different physiopathological mechanisms: tissue necrosis (cTnT), neuro-hormonal activation (BNP, NT-proBNP) or inflammatory process and plaque instability (CRP). Combining two or three of these biomarkers for better risk stratification has the potential to improve substantially the outcomes in patients with ACS.
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PMID:[Multiparametric evaluation of cardiac risk in acute coronary syndromes: value of biological blood markers]. 1807 51

Recent reports show that nifedipine not only causes vasodilation but also exerts beneficial effects on the endothelium of blood vessels. Some clinical trials evaluated nifedipine GITS (gastrointestinal therapeutic system) in patients with coronary artery disease. The investigators found that the treatment with nifedipine improved acetylcholine reactivity in coronary arteries and inhibited increases in coronary plaque volume. Furthermore, the large randomised, double-blind, placebo-controlled ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) study in patients with stable angina pectoris revealed that the treatment with nifedipine GITS led to significant reductions in the onset of overt heart failure and in the need for coronary angiography or coronary artery bypass graft surgery. These data indicate that a direct action on blood vessels, rather than coronary vasodilating or antihypertensive effects, might be responsible for improved prognosis with nifedipine.
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PMID:[ACTION study: efficacy of nifedipine in preventing cardiovascular disease in patients with coronary artery disease]. 1820 Jul 71

Apoptosis, a form of programmed cell death (PCD), plays an important role in the initiation and progression of a number of cardiovascular disease, such as heart failure, myocardial infarction, and atherosclerosis. One of the most prominent characteristics of apoptosis is the externalisation of phosphatidylserine (PS), a plasma cell membrane phospholipid, which in healthy cells only is present on the inner leaflet of the plasma cell membrane. Annexin A5, a 35 kD plasma protein, has strong affinity for PS in the nano-molar range. Through the coupling of Annexin A5 to contrast agents, visualization of apoptotic cell death in vivo in animal models and in patients has become feasible. These imaging studies have provided novel insight into the extent and kinetics of apoptosis in cardiovascular disease. Furthermore, Annexin A5 imaging has proven to be a suitable imaging biomarker for the evaluation of cell death modifying compounds and plaque stabilizing strategies. Recent insight in PS biology has shown that PS externalisation not only occurs in apoptosis, but is also observed in activated macrophages and stressed cells. In addition, it has been shown that Annexin A5 not only binds to exteriorized PS, but is also internalized through an Annexin A5 specific mechanism. These latter findings indicate that Annexin A5 imaging is not exclusively valuable for apoptosis detection, but can also be used to visualize inflammation and cell stress. This will open novel opportunities for imaging and drug delivery strategies. In this review we will discuss the introduction of Annexin A5 in preclinical and clinical imaging studies and provide an outlook on novel opportunities of Annexin A5 based targeting of PS.
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PMID:Annexin A5: an imaging biomarker of cardiovascular risk. 1832 65

Clinical biomarkers of cardiac function could also be monitored postmortem. Among the natriuretic peptides, the aminoterminal portion of pro-brain natriuretic peptide (NT-proBNP) appears to be a more reliable postmortem tool than the BNP, owing to its longer half-life and greater stability. In living persons, NT-proBNP is considered to be a marker of heart failure, and its level rises after cardiac ischemia. The goal of this study was first to evaluate the postmortem stability of NT-proBNP, then to measure the NT-proBNP levels in postmortem cases of heart failure related to coronary ischemia. The goal of this study was also to evaluate the correlations between different specimens collected at autopsy (e.g. blood, serum, vitreous humor and pericardial fluid). The study included 96 cases, which were classified into 4 groups according to the autopsy and histological findings. The NT-proBNP levels were significantly higher in individuals who had suffered from chronic cardiac ischemia, with or without acute coronary events, than in either control cases or those who had suffered from acute thromboembolism or acute rupture of a plaque without chronic cardiac ischemia. The highest levels were registered in individuals who had suffered from acute coronary thromboembolism in association with chronic coronary ischemia. Good correlations in the NT-proBNP levels for the different specimens were observed between samples of femoral blood, serum, and pericardial fluid. Our data indicated that postmortem measurements of NT-proBNP are reliable and compatible with clinical findings.
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PMID:Evaluation of postmortem measurement of NT-proBNP as a marker for cardiac function. 1855 94

The mortality rate after myocardial infarction fell sharply with the advent of reperfusion methods and the use of efficient antithrombotic and antiischemic drugs. However, new infarcts, heart failure, arrythmias and sudden death remain frequent, especially in the first two years after the initial event. Large clinical studies have defined and validated therapies for secondary prevention, but the recommended measures are not always properly implemented. Patients with and without ST elevation after myocardial infarction share the same pathophysiologic mechanism, namely atherosclerotic plaque rupture or erosion, with different degrees of superimposed thrombosis and distal embolization. Secondary prevention is the same for these two patient categories. Acute coronary syndromes are associated with an increased risk of adverse cardiovascular outcomes (new myocardial ischemia, left ventricular dysfunction or sudden death) and require aggressive secondary prevention. However, risks factors such as smoking, hypertension, obesity, hypercholesterolemia and diabetes frequently persist. In addition, medical practice does not always respect consensus guidelines. Early risk stratification is necessary to detect residual myocardial ischemia in viable myocardium. After the acute phase, the prognosis depends on the degree of left ventricular dysfunction and the extent and severity of residual ischemia. Exercise and ambulatory electrocardiography, stress echocardiography, perfusion scintigraphy using vasodilator stress, magnetic resonance imaging and coronary angiography are all useful for identifying high-risk patients. Secondary prevention should include risk factor management with lifestyle modifications such as weight reduction, a reduction in saturated fats and an increase in monounsaturated fatty acids. Smoking cessation is crucial, and regular physical activity (30 min per day at least 5 days a week) is beneficial. Cardiac rehabilitation has been shown to improve exercise tolerance and cardiovascular outcome.
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PMID:[Secondary prevention after myocardial infarction]. 1866 72

Autophagy is a catabolic pathway for bulk turnover of long-lived proteins and organelles via lysosomal degradation. Growing evidence reveals that autophagy is involved in the progression or prevention of many human diseases. Here we discuss the role of autophagy in the normal heart, in heart disease and atherosclerosis. In the heart, autophagy functions predominantly as a pro-survival pathway during cellular stress by removing protein aggregates and damaged organelles, protecting the heart against famine, excessive beta-adrenergic stimulation and ischemia. However, when severely triggered, e.g. during reperfusion, the autophagic machinery may lead to cell death. Furthermore, autophagy modulates cardiac hypertrophy and the transition from hypertrophy to heart failure. During aging, lipofuscin is formed via autophagy in the heart and impairs autophagy. Basal autophagy in atherosclerotic plaques is a survival mechanism safeguarding plaque cells against cellular distress, in particular oxidative injury, metabolic stress and inflammation, by removing harmful oxidatively modified proteins and damaged components. Hence, autophagy is anti-apoptotic and contributes to cellular recovery in an adverse environment. However, excessively stimulated autophagy causes autophagic death in plaque cells and is detrimental. Ceroid that is formed via autophagy in atherosclerotic arteries impairs autophagy and induces apoptosis. Basal autophagy can be intensified by appropriate drugs and pharmacological approaches have been developed to stabilize rupture-prone plaques through selective induction of macrophage autophagic death, without affecting the plaque stabilizing smooth muscle cells.
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PMID:Autophagy in the cardiovascular system. 1915 12

An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.
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PMID:The renin angiotensin system in the development of cardiovascular disease: role of aliskiren in risk reduction. 1918 45

ACE inhibition is now recognized as superior to placebo on outcomes in stable coronary artery disease (CAD), including total and cardiovascular mortality, fatal and nonfatal myocardial infarction, heart failure, revascularization and stroke. This review examines clinical evidence for the mode of action of ACE inhibitors in CAD, which is dominated by the results of a single trial, EUROPA, and its substudies. The generally accepted mode of action for ACE inhibitors in CAD is blood pressure reduction. However, the EUROPA data demonstrate that endothelial protection, with the effect of arresting or reducing the processes of atherosclerosis is also important. Chronic overexpression of tissue ACE in CAD disrupts the angiotensin II/bradykinin balance with a net result of endothelial dysfunction. ACE inhibitors reduce production of angiotensin II, which prevents vasoconstriction, reduces adhesion molecules and growth factors, decreases oxidative stress and prevents apoptosis. A concomitant decrease in the degradation of bradykinin as a result of ACE inhibition raises levels of this kinin, leading to vasodilation and an antiapoptotic action, as well as opposition of the negative actions of angiotensin II. We now have clinical trial evidence of these processes in CAD patients participating in the EUROPA study by measurement of markers of endothelial function, including nitric oxide synthase (eNOS), the rate of apoptosis and levels of von Willebrand factor (vWf). Serum from CAD patients was found to significantly downregulate eNOS protein expression and activity versus that of healthy controls (p < 0.01), most probably as a result of upregulation of tissue ACE. One year of treatment with perindopril upregulated eNOS protein expression and activity (19% and 27% vs placebo; p < 0.05). Similarly, vWf was elevated at baseline and significantly reduced after 1 year of treatment with perindopril (p < 0.001). Increased endothelial apoptosis by serum of CAD patients was accompanied by excess angiotensin II and tumour necrosis factor-alpha and a reduction in bradykinin; all of these parameters were reversed by treatment. We therefore have clinical results showing that perindopril normalizes the angiotensin II/bradykinin balance, reduces inflammation and prevents endothelial apoptosis. Accumulating preclinical evidence for the absence of a class effect for ACE inhibitors includes differences in terms of effect on eNOS and rate of endothelial apoptosis. These differences appear to be related to tissue affinity, penetration of atherosclerotic plaque and affinity for the target enzyme. Consideration of these features is important when administering ACE inhibition as secondary prevention in CAD patients. In this context, current European guidelines for stable angina pectoris recommend prescription of agents and doses with proven efficacy in secondary prevention.
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PMID:Insight into the mode of action of ACE inhibition in coronary artery disease: the ultimate 'EUROPA' story. 1927 71


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