Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is a well known risk factor for the development of congestive heart failure. Epidemiological evidence in the community underscores the prevalence of left ventricular systolic dysfunction in diabetic patients as 2-fold with respect to non-diabetic ones, with half of them completely asymptomatic. Diastolic dysfunction in diabetic hearts, in comparison with non-diabetic, is even more frequent. The high prevalence has been explained by the frequent coexistence of an underlying diabetic cardiomyopathy, hypertension and ischemic heart disease. In these patients, the diabetic metabolic derangement, together with the early activation of sympathetic nervous system, induce a decrease of myocardial function. The activation of renin-angiotensin system results in an unfavorable cardiac remodeling. The progression from myocardial damage to overt dysfunction and heart failure is often asymptomatic for a long time and frequently undiagnosed and untreated. Currently, the widespread availability of echocardiography and possibly the use of cardiac natriuretic peptides, may allow for an earlier recognition of most of such patients. In heart failure, diabetic patients have a worse prognosis than non-diabetics. The available pharmacological treatments, such as ACE-inhibitors, beta-blockers and possibly angiotensin receptor blockers, togheter with a tight glycemic control, may be effective to reverse the remodeling process and prevent cardiovascular events. In order to identify most of the diabetic patients at risk of development of left ventricular dysfunction and to prevent its progression to overt heart failure, it seems important to elaborate a screening strategy in order to diagnose and treat most of diabetic patients with myocardial damage.
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PMID:[Diabetes mellitus, left ventricular dysfunction and congestive heart failure]. 1555 15

The sarcoplasmic reticulum (SR) is a major player in maintaining cardiac function, as it is intimately involved in the regulation of Ca2+-movements on a beat-to-beat basis. SR dysfunction due to abnormalities in SR protein content has been reported in different cardiac diseases such as ischaemic heart disease, myocardial infarction, congestive heart failure and various cardiomyopathies; thus the genes expressing the SR Ca2+-pump, Ca2+-channels, calsequestrin, phospholamban and other regulatory proteins are considered important targets for drug development. In our experience, ischaemic preconditioning (IP) and pharmacological therapies, such as anti-oxidants, beta-adrenergic receptor blockers, angiotensin receptor (AT-1) blockers, angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers are effective therapies that improve cardiac performance in the failing heart by improving SR function. Accordingly, this paper is intended to shed light on the knowledge in the field of cardiac therapy targeted to improve and protect SR function.
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PMID:Sarcoplasmic reticulum and cardiac oxidative stress: an emerging target for heart disease. 1599 77

Angiotensin II (Ang II) plays important roles in the development of cardiovascular diseases including hypertension, renal diseases, cardiac hypertrophy, congestive heart failure, and ischemic heart disease. Angiotensin II exerts classic hemodynamic and renal effects, but it is also a local biologically active mediator with direct effects on endothelial and smooth muscle cells. Two subtypes of Ang II receptors, type 1 (AT(1)) and type 2 (AT(2)), have been identified. Their roles have been investigated in depth in vivo and in vitro, although few data are available concerning the role of the AT(2) receptors in the adult circulation in humans. The two receptors, both of which belong to the superfamily of G-protein-coupled receptors, have different signaling pathways and different functions. The AT(1) receptor subtype is expressed ubiquitously and is involved in most of the well-known biological functions of Ang II. The AT(1) receptor transactivates growth pathways and mediates major Ang II effects such as vasoconstriction, increased cardiac contractility, renal tubular sodium reabsorption, cell proliferation, vascular and cardiac hypertrophy, inflammatory responses, and oxidative stress. In contrast to AT(1), the physiologic role of AT(2) receptors has long remained an enigma. The AT(2) receptors are highly expressed in fetal tissues, although their expression dramatically decreases after birth, being restricted to a few organs, including the cardiovascular system. The AT(2) receptor is re-expressed in the adult animal after cardiac and vascular injury and during wound healing, suggesting a role for this receptor in tissue remodeling, growth, or development. Recent and concordant data suggested that overstimulation of AT(2) receptors might be implied in cardiac and vascular hypertrophic processes. Both Ang II receptors are involved in hypoxia-induced neovascularization. A large set of experimental evidence suggests that activation of the AT(1) receptor results in proangiogenic effects, whereas AT(2) receptors mediate apoptosis and thus antiangiogenic effects. Furthermore, bradykinin through its B(1) or B(2) receptors is a potent activator of experimental hypoxia-induced neovascularization. Thus, pharmacologic blockade of the AT(1) receptor and resulting overactivation of AT(2) receptors could impair or delay neovascularization in ischemic tissues in patients receiving chronic treatment with angiotensin receptor blockers. In contrast, increased tissue bradykinin resulting from inhibition of converting enzyme could help to restore functional vascularization in ischemic tissues. These basic concepts deserve a second reading and reevaluation to discuss differences in vascular protection in large clinical trials with different classes of drugs acting on the renin-angiotensin system.
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PMID:How to explain the differences between renin angiotensin system modulators. 1612 50

Protection of ischemic myocardium has been attempted by a variety of pharmaceutical and non-pharmaceutical methods. When the coronary intervention is not indicated by some reasons in patients with ischemic heart failure, medical treatments are expected to offer cardioprotection against the persistence of stenotic/occlusive lesions of the epicardial coronary artery. The pharmaceuticals such as the angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta blocker, Ca antagonist, ATP-sensitive K channel opener and statin, or non-pharmaceutical approaches such as physical exercise, cardiac resynchronization, ventricular assist devices, and preconditioning upon ischemic insults appear to improve myocardial endothelial nitric oxide (NO) synthase (eNOS) function. Such eNOS activation contributes to amelioration of the cardiac dysfunction and remodeling induced by myocardial ischemia. Therefore, based on clinical evidence and basic research on clinical demand, we postulate a concept of 'myocardial endothelial NO activator' from the standpoint of mechanistic insights beyond the class-effects of each pharmaceutical category and each non-pharmaceutical intervention. In addition to such continuous eNOS activation for treating chronic ischemic heart failure, rapid eNOS activation in the setting of acute ischemic events upon chronic myocardial ischemia by new strategies such as postconditioning seems to be also essential for developing further effective anti-heart-failure therapies.
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PMID:Noninvasive myocardial endothelial intervention in the persistence of coronary stenosis: a concept of myocardial endothelial nitric oxide activator through heart failure research on clinical demand. 1655 26

The decision to offer patients with myocardial ischemia a coronary artery bypass graft (CABG) surgery has been largely determined by extent of coronary artery disease (CAD) and left ventricular function, since the early 1970's. Based upon subset analyses, and long-term follow-up, of three moderate-sized trials of stable patients and two small trials of unstable angina (excluding recent myocardial infarction, MI) patients, the notion has persisted that patients with left main narrowing >50% or three-vessel stenoses >70%, or even two-vessel stenoses >70%, where one of the vessels is the proximal left anterior descending, derive a "survival benefit" relative to medical therapy (MED), from CABG (anatomic paradigm). The MED of the original CABG versus MED trials consisted of little more than anti-anginal medications, used on an as-needed basis. In the ensuing 3 decades, multiple large, well done, randomized clinical trials have established a survival benefit for 4 different forms of MED among a broad spectrum of CAD patients. Aspirin; lipid lowering, especially with statins; b-blockers; and angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blocking agents; have all been shown to enhance survival, as well as reduce other objective adverse outcomes of CAD. The advances in MED, coupled with the small but significant mortality and morbidities of both CABG and percutaneous coronary intervention (PCI), are among the reasons to skeptically consider potential "survival benefit" of revascularization. A more common and far more easily justified reason to consider revascularization is to relieve "medically refractory" myocardial ischemia, particularly when the ischemia is accompanied by symptoms. Accordingly, documentation of medically refractory myocardial ischemia provides the answer to the first question of myocardial revascularization, "Is this patient likely to derive clinical benefit from revascularization, at this time?" It is only after this question has been answered that one needs to consider the relative advantages and disadvantages of PCI versus CABG (physiologic paradigm). Two of the relative advantages of PCI, namely speed of reperfusion, and relatively low morbidity, are among the reasons that most randomized trial data, and most clinical application of revascularization to patients with MI (ST-elevation MI [STEMI], and non-STEMI) have been by PCI. In contrast, for stable patients with medically refractory ischemia, anatomic considerations continue to be relevant to the choice between CABG and PCI. Specific advantages of CABG include: its potential to revascularize chronically occluded vessels with collaterals supplying viable myocardium; the fact that conduits protect territories rather than simply treating lesions; and the greater durability of conduits compared to bare-metal stents (drug-eluting stents may change the picture). Based on these principles, physiologic, rather than anatomic, considerations are most useful in determining whether to revascularize, and how urgently to revascularize (STEMI is an emergent indication and high-risk non-STEMI an urgent indication). Coronary anatomy, including both number of vessels and lesion characteristics, continues to help decide between CABG and PCI, and in formulating patient specific strategies.
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PMID:PCI versus CABG versus medical therapy in 2006. 1701

The American Heart Association scientific statement on the treatment of hypertension in the prevention and management of ischemic heart disease was published recently. The main recommendations were as follows: (1) For most adults with hypertension, the blood pressure (BP) goal is <140/90 mm Hg but should be <130/80 [corrected] mm Hg in patients with diabetes mellitus, chronic kidney disease, known coronary artery disease (CAD), CAD equivalents (carotid artery disease, abdominal aortic aneurism, and peripheral vascular disease), or 10-year Framingham risk score of >/=10%. For those with left ventricular dysfunction, the recommended BP target is <120/80 mm Hg. (2) For primary CAD prevention, any effective antihypertensive drug or combination is indicated, but preference is given to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide diuretics. (3) For the management of hypertension in patients with established CAD (stable or unstable angina, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction), beta-blockers and ACE inhibitors (or ARBs) are the basis of treatment. If further BP lowering is needed, a thiazide diuretic and/or a dihydropyridine CCB (not verapamil or diltiazem) can be added. If a beta-blocker is contraindicated or not tolerated, diltiazem or verapamil can be substituted. (4) If there is left ventricular dysfunction, recommended therapy consists of an ACE inhibitor or ARB, a beta-blocker, and either a thiazide or loop diuretic. In patients with more severe heart failure, an aldosterone antagonist and hydralazine/isosorbide dinitrate (in black patients) should be considered.
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PMID:Hypertension and coronary artery disease: a summary of the American Heart Association scientific statement. 1791 7

Hypertension is one of the major risk factors for cardiovascular morbidity and mortality. Lowering blood pressure (BP) may reduce the risk of stroke by 40% and the risk of ischemic heart disease by 20%. Despite the varied drugs available to lower BP, more than 50% of the hypertensive patients are not well-controlled. The major reason for the failure to control BP is noncompliance which is related to the side effects and inconvenience of drug administration. Aliskiren, a new oral direct renin inhibitor is very effective in BP reduction. It is given once daily and has very few side effects, almost like a placebo. It is well combined with diuretics, angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers. Unlike ACE inhibitors and angiotensin receptor blockers that block the renin angiotensin axis in its last part and thereby raise the rein-levels, the direct renin inhibitor block the renin-angiotensin axis in its beginning and keep the renin levels suppressed. Aliskiren is a promising agent but further prospective studies with morbidity and mortality data as endpoints are required, before the drug can be recommended as a first choice agent.
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PMID:[Is there a need for direct renin inhibitors?]. 1848 62

Sexual dysfunction is currently considered a serious quality-of-life-related health problem, exerting a major impact on patients' and their sexual partners' life. Available data indicate that essential hypertension is a risk factor for sexual dysfunction, as male and female sexual dysfunction is more prevalent in hypertensive patients than normotensive individuals. Several mechanisms have been implicated in the pathogenesis of sexual dysfunction in hypertensive patients, and major determinants include severity and duration of hypertension, age, and antihypertensive therapy. Female sexual dysfunction, although more frequent than its male counterpart, remains largely under-recognized. Older antihypertensive drugs (diuretics, beta-blockers, centrally acting) exert negative results, whereas newer drugs have either neutral (calcium antagonists, angiotensin-converting enzyme inhibitors) or beneficial effects (angiotensin receptor blockers). Erectile dysfunction is related to ischemic heart disease and might be an 'early therapeutic window' of asymptomatic coronary artery disease. It seems of utmost importance for every physician treating hypertensive patients to become familiar with sexual dysfunction (through better education and specific seminars) for the proper management of these patients.
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PMID:Sexual dysfunction: the 'prima ballerina' of hypertension-related quality-of-life complications. 1885 43

Of the more than 5 million Americans who have heart failure (HF), 30% to 50% have HF with preserved ejection fraction (HF-PEF). HF-PEF commonly occurs in elderly patients, especially women, with comorbidities of hypertension, left ventricular hypertrophy, diabetes, myocardial ischemia, and obesity. HF-PEF is associated with high morbidity and mortality. Although two large multicenter randomized, placebo-controlled trials evaluating an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) in patients with HF-PEF did not demonstrate any statistically significant benefit in their primary end points, they did suggest that these agents may have a modest role in reducing HF hospitalizations. Although calcium channel blockers and beta-blockers may be of benefit in patients with HF-PEF, large clinical trial data are not available to support their routine use in all patients with HF-PEF. Subgroup analysis does not support the use of digoxin in patients with HF-PEF in sinus rhythm. Current therapeutic recommendations for HF-PEF are aimed at 1) management of HF symptoms with sodium and fluid restriction along with diuretics for volume overload and 2) treatment of concomitant comorbidities, especially hypertension, rate and possibly rhythm control of atrial fibrillation, and evaluation and treatment of myocardial ischemia and anemia. ACEIs, ARBs, calcium channel blockers, and beta-blockers are recommended for HF-PEF patients who have other established indications for their use. Results are awaited from ongoing clinical trials with another ARB, irbesartan, and an aldosterone blocker, spironolactone.
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PMID:Treatment of patients with heart failure and preserved ejection fraction. 1902 82

To evaluate cardiovascular disease (CVD) after renal transplantation we established a CVD database (no-intervention) including all patients transplanted among 2000-2002 in 14 hospitals from Spain (Renal Forum Group) (n=2600). They were prospective followed annually thereafter and we present herein the most important results concerning survival figures and CVD at four years. Mean recipient age was 49.7+/-13.7 years: 16% retransplanted and 12.5% hyperimmunized. Tacrolimus, mycophenolate mofetil, and steroids was used in 63%. Acute rejection (AR) rate at 1 year was 14.8%. Graft and patient survival at 48 months were 85.6% (death censored) and 91.7% respectively. The first cause of graft loss was vascular in the first year, death with function during the 2-3 years, and chronic allograft nephropathy at the 4th year. Donor age, time on dialysis, acute tubular necrosis (ATN), AR, SCr at 6 months, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in the first year, and systolic blood pressure at 24 months were independent risk factors for graft loss at 4th year. The first cause of death was CVD (predominantly ischemic heart disease (IHD) in the first year). Recipient age, ATN, and SCr at 6 months were independent predictors of mortality. Despite worsening of donor age, comorbidity, and advanced age of recipients, survival figures at four years are considered good in our Spanish non-selected population. Cardiovascular mortality is the most important cause of death and graft loss particularly, IHD in the first year. Therefore, to decrease post-transplant mortality a careful cardiovascular evaluation and treatment in the waiting list and a close follow-up of patients after transplantation is mandatory.
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PMID:Renal transplantation in the modern immunosuppressive era in Spain: four-year results from a multicenter database focus on post-transplant cardiovascular disease. 1903 36


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