Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiolipin (CL) is recognized to be an essential phospholipid in eukaryotic energy metabolism so that physiological and pathological perturbations in its synthetic and catabolic pathways play key roles in maintaining mitochondrial structure and function, and ultimately cell survival. This review describes potential regulatory mechanisms in CL synthesis and the effects of de-acylation pathways on steady state levels of CL and its interaction with cytochrome c. The latter interaction is significant in the initiation of programmed cell death. Physiological factors that modify CL acylation include ageing, dietary influences and ischemia/reperfusion where the terminal events may be either necrosis or apoptosis. In various pathologies, phospholipase activity increases in response to production of peroxidized CL. The cell may use lysosomal or mitochondrial pathways for CL degradation. However, the manner by which CL and cytochrome c leave the mitochondria is not well understood. The lipid (CL)-bound form of cytochrome c is thought to initiate apoptosis via a lipid transfer step involving mitochondrially targeted Bid. A direct relationship between CL loss and cytochrome c release from the mitochondria has been identified as an initial step in the pathway to apoptosis. An absolute requirement for CL in the function of crucial mitochondrial proteins, e.g., cytochrome oxidase and the adenine nucleotide translocase, are likely additional factors impacting apoptosis and cellular energy homeostasis. This is reflected in the occurrence of both oncotic and apoptotic events in ischemia and reperfusion injury. Other potential clinical manifestations of perturbations of CL synthesis are discussed with particular emphasis on Barth Syndrome where a primary defect can be attributed to CL metabolism and is associated with dilated cardiomyopathy. Finally, the model of fatty acid induced apoptosis is used as a paradigm to our understanding of the temporal relationship between decreased mitochondrial CL, release of cytochrome c, and initiation of apoptosis.
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PMID:Cardiolipin and apoptosis. 1253 42

Genetic variation in the apolipoprotein E (APOE) gene is a significant determinant of variation in plasma cholesterol levels and it also affects the risk of coronary artery disease (CAD). We examined the association of the APOE polymorphism with CAD severity in women from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Quantitative coronary angiography was used to classify subjects as having normal/minimal CAD (<20% stenosis), mild CAD (20-49% stenosis) and significant CAD (>or=50% stenosis). The women with or=50% stenosis were further stratified according to the number of vessel disease they have (one, two, or three). In white subjects, the frequency of APOE*4 carriers (3/4 and 4/4 genotypes) was significantly higher in the combined mild/significant CAD group (>or=20% stenosis) compared with the normal/minimal CAD group (<20% stenosis) (31.3 vs. 19.2%; P=0.025) with an adjusted OR of 2.40 (95% CI: 1.47-3.93; P=0.0005). Furthermore, the APOE*4 allele was found to be significantly associated with the increased vessel disease number (chi(2)=8.04; P=0.0046). This association of the APOE*4 allele with CAD severity was present only in women with family history of CAD. APOE polymorphism also showed significant associations with increasing plasma total cholesterol (P=0.01) and low-density lipoprotein (LDL)-cholesterol (P<0.001) in whites. These data support the hypothesis that the APOE*4 allele is an independent risk factor not only for the presence of CAD and hyperlipidemia, but also for the angiographic severity of CAD in white women with a family history of disease.
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PMID:APOE polymorphism and angiographic coronary artery disease severity in the Women's Ischemia Syndrome Evaluation (WISE) study. 1286 Feb 63

Myocardial flow reserve (MFR) is not routinely assessed in myocardial perfusion imaging (MPI) studies but has been hypothesized to affect test accuracy when assessing disease severity by coronary vessel lumenography. Magnetic resonance imaging (MRI) is an emerging diagnostic technique that can both perform MPI and assess MFR. We studied women (n = 184) enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study with symptoms suggesting ischemic heart disease. Tests performed were coronary angiography and MPI by both MR and gated radionuclide single photon emission computed tomography (gated-SPECT). The MFR index was calculated using the MR data acquired at baseline and under vasodilation (dipyridamole) conditions. The study was structured with a pilot and an implementation phase. During the pilot phase (n = 46) data were unmasked and an MFR threshold was defined to divide patients into those with an adequate (AMFRI) or inadequate (IMFRI) MFR index. During the implementation phase, the MFR index threshold was prospectively applied to patients (n = 138). In the implementation phase, MPI ischemia detection accuracy compared to severe (> or = 70%) coronary artery diameter narrowing by angiography was higher in the AMFRI vs. the IMFRI group for MRI (86% vs. 70%, p < 0.05) and gated-SPECT (89% vs. 67%, p < 0.01). The IMFRI group (n = 55, 30% of study population) had a higher resting rate-pressure product compared with the AMFRI group (10,599 +/- 2871 vs. 9378 +/- 2447 bpm mm Hg, p < 0.01), consistent with higher resting myocardial flow. When compared with each other, MRI and gated-SPECT MPI showed no difference in accuracy among MFR groups. Myocardial perfusion patterns in the IMFRI group may have resulted in atypical perfusion patterns, which either masked or mimicked epicardial coronary artery disease.
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PMID:The impact of myocardial flow reserve on the detection of coronary artery disease by perfusion imaging methods: an NHLBI WISE study. 1288 78

Based on data reported to the United Network for Organ Sharing through December 2001: 1. The number of heart transplant procedures performed in the United States increased slightly (< 1%) during each of the last 2 complete years from 2,187 transplants during 1999 to 2,197 transplants during 2000, followed by an additional increase in 2001 to 2,202 transplants. A more substantial increase was seen in the number of lung transplants performed: from 890 transplants in 1999 to 956 in 2000 (+7%) and an additional increase to 1,053 transplants in 2001 (+10%). Fewer than 30 heart-lung transplants were performed in 2001. Living-donor lung transplants comprised 2-3% of lung transplants performed between 1995-2001. 2. Pediatric recipients were more frequently on life support in the ICU; more likely to have an ischemia time of at least 4 hours; more often gender mismatched; and more often ABO-compatible rather than ABO-identical with the donor than adult recipients for all thoracic organ types. 3. The most common indication for transplant since 1996 in adult heart recipients was coronary artery disease (50%), followed closely by cardiomyopathy (42%). Among pediatric heart recipients, the 2 most common indications: cardiomyopathy (46%) and congenital heart disease (43%) accounted for approximately 90% of the transplants. The indications for lung transplants were more disparate. In adult lung recipients, the 4 most common diagnoses (COPD - 42%, IPF - 17%, CF - 15% and A1A - 9%) encompassed more than 80% of the transplants. More than half of the pediatric lung transplants were performed in recipients with CF. The 3 most frequently cited indications for adult heart-lung transplant recipients (Eisenmenger's Syndrome, other congenital heart diagnoses and PPH) accounted for greater than 75% of the transplants. 4. Approximately 30-35% of adult heart transplants since 1999 have been performed in patients who were Status 1A. For pediatric transplant recipients, Status 1A comprised 60-70% of the transplants. 5. The one-year survival rate for transplants performed during the first three-quarters of 2001 was 85% for both adult and pediatric heart transplant recipients and 77% for both adult and pediatric recipients of lung transplants. For adult heart-lung transplants performed during 2000, the one-year survival rate was 69%. 6. The long-term patient survival rates were: 39% for adult heart recipients and 50% for pediatric heart recipients at 12 years; 18% at 11 years for adult lung recipients and 31% at 9 years for pediatric lung recipients; and 24% at 11 years for adult heart-lung recipients and 21% at 8 years for pediatric heart-lung recipients. 7. Drug-treated rejection and drug-treated infection were reported to occur before discharge in approximately 20-40% of transplant recipients, with the exception of pediatric lung and heart-lung recipients, with rates varying by organ and age group. Drug-treated infections were reported before discharge in more than 60% of pediatric lung recipients and approximately half of pediatric heart-lung recipients. 8. Approximately 60% of adult heart recipients and 70% of pediatric heart recipients were hospitalized at least once during the first 3 years following their transplant.
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PMID:Thoracic organ transplantation in the US. 1297 35

The role of glycoprotein IIb/IIIa platelet receptor antagonist therapy for patients with an acute coronary syndrome (ACS) and a history of coronary artery bypass grafting (CABG) remains incompletely defined. We examined the outcomes of patients with an ACS and prior CABG who were treated with tirofiban versus placebo among subjects with prior CABG in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Of 1,570 patients treated with tirofiban plus heparin (n = 773) or heparin alone (n = 797), 231 had prior CABG. Compared with patients without prior CABG, those with prior CABG were more likely to have risk factors for a complicated ACS course, including severe coronary artery disease and heart failure (all p <0.0001), typically had clinical predictors of benefit from tirofiban, such as ST-segment depression (p = 0.01) or a TIMI risk score >or=4 (p <0.001), and were more likely to die or have a myocardial infarction or refractory ischemia at all time points examined (p <0.0001). Among patients with prior CABG, decreases in the incidence of death, myocardial infarction, or refractory ischemia with tirofiban and heparin versus heparin alone were noted at 7 and 30 days (7 days: 16.9% vs 29.0%, p = 0.035; 30 days: 25.0% vs 40.2%, p = 0.015). Trends toward a decrease in death, myocardial infarction, and refractory ischemia with tirofiban and heparin versus heparin alone in the prior CABG subgroup were noted at 48 hours and 180 days (48 hours: 6.5% vs 14.0%, p = 0.09; 180 days: 37.1% vs 48.6%, p = 0.057). Bleeding rates were similar in patients with and without prior CABG. Tirofiban was well tolerated and tended to decrease the considerable risk for ischemic ACS complications in patients with prior CABG.
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PMID:Tirofiban therapy for patients with acute coronary syndromes and prior coronary artery bypass grafting in the PRISM-PLUS trial. 1505 Apr 86

Although the efficacy of glycoprotein IIb/IIIa inhibition in non-ST-elevation acute coronary syndromes is greatest in patients who undergo percutaneous coronary intervention (PCI), it was hypothesized that high-risk patients managed without PCI also benefit. The TIMI risk score was calculated for 1,570 patients randomized to tirofiban plus heparin versus heparin in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. In high-risk patients (score > or =4) treated without PCI, tirofiban reduced the risk for death, myocardial infarction, and refractory ischemia at 30 days (28.8% vs 21.9%; odds ratio [OR] 0.69, p = 0.04). This benefit was similar in magnitude as that for patients who underwent PCI (32.4% vs 22.2%; OR 0.60, p = 0.06). No benefit was evident in low-risk patients.
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PMID:Usefulness of tirofiban among patients treated without percutaneous coronary intervention (TIMI high risk patients in PRISM-PLUS). 1537 86

Lessons from monkey models contribute significantly to a better understanding of the controversies in reconciling the differences in postmenopausal hormone treatment outcomes between observational and randomized trial data. Monkey studies brought attention to premenopausal estrogen deficiency with resulting premature coronary artery atherosclerosis. Recently, those monkey studies were confirmed for premenopausal women in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) Study. Monkey studies have provided convincing evidence for the primary prevention of coronary artery atherosclerosis when estrogens are administered soon after the development of estrogen deficiency. Equally convincing are the data from monkey studies indicating the total loss of these estrogens beneficial effects if treatment is delayed for a period equal to six postmenopausal years for women. An attempt has been made using the monkey model to identify the hormone treatment regimen most effective in preventing the progression of coronary artery atherosclerosis. By a substantial margin, the most effective approach is that of using estrogen containing oral contraceptive during the perimenopausal transition, followed directly by hormone replacement therapy postmenopausally. Because of similarities between human and nonhuman breast, monkeys have had a major role in clarifying controversies surrounding the breast cancer risk of estrogen only versus estrogen plus progestin therapies. The results of monkey studies suggest little or no effects of estrogen only treatment; whereas, estrogen+progestin clearly increases breast cancer risk.
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PMID:Controversies about HRT--lessons from monkey models. 1588 11

Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.
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PMID:Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. 1645 67

Considerable experimental and clinical data indicate that sex has an important influence on cardiovascular physiology and pathology. This report integrates selected literature with new data from the Women's Ischemia Syndrome Evaluation (WISE) on vascular findings in women with ischemic heart disease (IHD) and how these findings differ from those in men. A number of common vascular disease-related conditions are either unique to (e.g., hypertensive disorders of pregnancy, gestational diabetes, peripartum dissection, polycystic ovarian syndrome, etc.) or more frequent (e.g., migraine, coronary spasm, lupus, vasculitis, Raynaud's phenomenon, etc.) in women than men. Post-menopausal women more frequently have many traditional vascular disease risk conditions (e.g., hypertension, diabetes, obesity, inactivity, and so on), and these conditions cluster more frequently in them than men. Considerable evidence supports the notion that, with these requisite conditions, women develop a more severe or somewhat different form of vascular disease than men. Structurally, women's coronary vessels are smaller in size and appear to contain more diffuse atherosclerosis, their aortas are stiffer (fibrosis, remodeling, and so on), and their microvessels appear to be more frequently dysfunctional compared with men. Functionally, women's vessels frequently show impaired vasodilator responses. Limitations of existing data and higher risks in women with acute myocardial infarction, need for revascularization, or heart failure create uncertainty about management. A better understanding of these findings should provide direction for new algorithms to improve management of the vasculopathy underlying IHD in women.
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PMID:Some thoughts on the vasculopathy of women with ischemic heart disease. 1645 68

Despite a dramatic decline in mortality over the past three decades, coronary heart disease is the leading cause of death and disability in the U.S. Importantly, recent advances in the field of cardiovascular medicine have not led to significant declines in case fatality rates for women when compared to the dramatic declines realized for men. The current review highlights gender-specific issues in ischemic heart disease presentation, evaluation, and outcomes with a special focus on the results published from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. We will present recent evidence on traditional and novel risk markers (e.g., high sensitivity C-reactive protein) as well as gender-specific differences in symptoms and diagnostic approaches. An overview of currently available diagnostic test evidence (including exercise electrocardiography and stress echocardiography and single-photon emission computed tomographic imaging) in symptomatic women will be presented as well as data using innovative imaging techniques such as magnetic resonance subendocardial perfusion, and spectroscopic imaging will also be discussed.
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PMID:Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. 1645 70


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