Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that individuals with the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene are at greater risk for myocardial infarction (MI), especially among subjects normally considered to be at low risk. However, little is known about the mechanism by which the ACE polymorphism affects the risk of MI. Coronary artery spasm (CAS) is considered to be one possible mechanism for developing MI. We therefore examined the ACE polymorphism relation to CAS to determine if this was the mechanism by which the DD genotype influences MI. We studied 150 angiographically assessed Japanese males, all more than 60 yr old. CASs were detected using intracoronary injection of ergonovine maleate. Subjects were divided into three groups: those with CAS (group 1), those without CAS, but with fixed organic stenosis (group 2); and those without CAS and no organic stenosis (group 3). DD subjects were significantly represented in group 1 when compared with groups 2 (P = 0.002) and 3 (P = 0.026). These results suggest that the DD genotype relates to the greater risk for MI in the patients with CAS.
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PMID:Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction. 867 69

In the setting of chronic heart failure (CHF), therapy with angiotensin converting enzyme (ACE) inhibitors generally reduces serum aldosterone levels acutely. However, long-term ACE inhibition is associated with aldosterone suppression that is weak, variable, and unsustained, i.e. aldosterone 'escape'. Magnesium loss caused by aldosterone and by diuretics can contribute to coronary artery spasm and arrhythmias. Aldosterone can block noradrenaline uptake by the myocardium; extracellular catecholamines may lead to arrhythmias and ischaemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a potential detrimental effect on baroreflex function, a marker of prognosis in CHF. Both angiotensin II and aldosterone may stimulate myocardial fibrosis, which is associated with a higher incidence of malignant ventricular arrhythmias. ACE inhibition initiated early in the progression of CHF may prevent development of patchy myocardial fibrosis and its inherent arrhythmias and thus reduce the incidence of sudden death. Spironolactone therapy added to the regimen of an ACE inhibitor and diuretic can induce natriuresis and magnesium retention, increase myocardial noradrenaline uptake, and reduce the incidence of arrhythmias.
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PMID:Aldosterone escape during ACE inhibitor therapy in chronic heart failure. 868 54

NSAIDs, including aspirin (acetylsalicylic acid), are frequently used and effective in a broad variety of inflammatory diseases, i.e. rheumatic carditis and pericarditis. Myocarditis may constitute another suitable indication for NSAIDs in order to relieve the symptoms of the presumed viral infection or because pericardial effusion is often associated with this condition. However, concerns have been raised about their indiscriminate use in myocarditis. To clarify this issue, we conducted a systematic review of the literature concerning myocarditis, aspirin and NSAIDs. We examined five animal studies of NSAIDs (indomethacin and ibuprofen) and aspirin in coxsackievirus B3- and B4-induced myocarditis. These studies indicated a deleterious effect of NSAIDs and aspirin in this setting, demonstrating a 2- to 3-fold increase in inflammation, myocytes necrosis and even mortality when compared with placebo. This possible deleterious effect was more predominant when NSAIDs or aspirin were administered during the acute and subacute phases of myocarditis; however, it was still noted when NSAIDs were administered during the late phase of the disease (the effect of aspirin was not evaluated in late phase studies). According to these animal studies, such effect might be attributed to decreased viral clearance (possibly via interferon inhibition) and/or exaggerated cytotoxic response (via interleukin-2 or inhibition of suppressor cells factors) and/or coronary artery spasm. We found one animal study looking at autoimmune myocarditis and it did not demonstrate any beneficial or detrimental effect of aspirin. Moreover, recent data suggest that aspirin and NSAIDs may counteract part of the efficacy of ACE inhibitors and be deleterious in chronic heart failure. Taken together, these studies point to a possible deleterious effect of aspirin and NSAIDs in human myocarditis. In view of these animal studies and in the absence of controlled studies of aspirin or NSAIDs in human myocarditis, we do not recommend indiscriminate treatment with NSAIDs or high-dose aspirin in patients with myocarditis where there is no or minimal associated pericarditis.
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PMID:Risks versus benefits of NSAIDs including aspirin in myocarditis: a review of the evidence from animal studies. 1458 71

Takotsubo cardiomyopathy (TTS) is a peculiar clinical condition often affecting postmenopausal women after a stressful trigger. The underlying mechanisms have not been completely elucidated but several hypotheses have been advanced, with catecholamine cardiotoxicity, microvascular dysfunction and coronary artery spasm each suggested to play a role. The incidence of stroke after TTS appears to range from 0% to 7.7%, and interestingly TTS has been described as both a cause and a complication of stroke. We sought to assess the incidence and predictors of stroke during the index event (peri-index event stroke) in a heterogeneous TTS population. We conducted a retrospective descriptive study reviewing patients who were discharged with a diagnosis of TTS from the Einstein Medical Center, Philadelphia, PA and Danbury Hospital, Danbury, CT in the period between 2003 and 2014. A total of Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population 206 patients met the modified Mayo Clinic criteria and were included in the study. The patients' overall mean age was 67.8 years; 87% (n=179) were females and 25% (n=53) were African Americans. The following incidence rates were found: stroke 7%, in-hospital heart failure 26.7%, and in-hospital death 7%. On multivariate analysis independent predictors (expressed as odds ratios with 95% confidence intervals) of periindex event stroke were: i) African American race (OR 3.2, 95% CI 1.2-10.2, p=0.048); ii) hypertension (OR 10.5, 95% CI 1.3-88, p=0.03). ACE inhibitor use was a protective factor for developing peri-index event stroke (OR 0.15, 95% CI 0.04-0.5, p=0.001). There was a trend towards dual antiplatelet therapy (DAPT) being protective for stroke (OR 0.3, 95% CI 0.05-1.1, p=0.08). The incidence of peri-index event stroke was 7%. African American race and hypertension were found to be independent predictors of peri-index event stroke. Prospective clinical trials are needed to confirm these findings and to better determine the impact of hypertension as a risk factor for stroke and to assess the role of DAPT in preventing it.
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PMID:Incidence and predictors of stroke during the index event in an ethnically diverse Takotsubo cardiomyopathy population. 2767 9

Anaphylaxis is life-threatening and should be addressed urgently. Its treatment is not without side effects and an accurate diagnosis must be made to prevent potential harm by the wrongful use of medication. A 46-year-old woman with hypertension treated with angiotensin converting enzyme inhibitor (ACEI) presented to the emergency department with non-pitting oedema of the face and limbs. A hasty diagnosis of anaphylaxis was made and intravenous adrenaline administered. The patient developed a myocardial infarction caused by coronary artery spasm that required invasive intervention. The initial clinical picture was resolved when the ACEI was discontinued unmasking a case of ACEI-induced angioedema. The correct differentiation of these two apparently similar clinical entities is of utmost importance in the management of emergency department patients.
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PMID:A rash decision. The hazards of the wrongful use of adrenaline. 2909 Feb 69

Coronary artery spasm (CAS) defined by a severe reversible diffuse or focal vasoconstriction is the most common diagnosis among INOCA (ischemia with no obstructive coronary artery disease) patients irrespective to racial, genetic, and geographic variations. However, the prevalence of CAS tends to decrease in correlation with the increasing use of medicines such as calcium channel blockers, angiotensin converting enzyme inhibitor, and statins, the controlling management of atherosclerotic risk factors, and the decreased habitude to perform a functional reactivity test in highly active cardiac catheterization centers. A wide spectrum of clinical manifestations from silent disease to sudden cardiac death was attributed to this complex entity with unclear pathophysiology. Multiple mechanisms such as the autonomic nervous system, endothelial dysfunction, chronic inflammation, oxidative stress, and smooth muscle hypercontractility are involved. Regardless of the limited benefits proffered by the newly emerged cardiac imaging modalities, the provocative test remains the cornerstone diagnostic tool for CAS. It allows to reproduce CAS and to evaluate reactivity to nitrates. Different invasive and noninvasive therapeutic approaches are approved for the management of CAS. Long-acting nondihydropyridine calcium channel blockers are recommended for first line therapy. Invasive strategies such as PCI (percutaneous coronary intervention) and CABG (coronary artery bypass graft) have shown benefits in CAS with significant atherosclerotic lesions. Combination therapies are proposed for refractory cases.
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PMID:Coronary Artery Spasm: New Insights. 3250 42