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Biomedical subjects

J H O'Keefe

Publications and source records attributed to J H O'Keefe.

At least 19 recordsLinked to original sources

Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease?

Angiotensin-converting enzyme (ACE) inhibitors appear to possess unique cardioprotective benefits, even when used in patients without high blood pressure or left ventricular dysfunction (the traditional indications for ACE inhibitor therapy). The ACE inhibitors improve endothelial function and regress both left ventricular hypertrophy and arterial mass better than other antihypertensive agents that lower blood pressure equally as well. These agents promote collateral vessel development and improve prognosis in patients who have had a coronary revascularization procedure (i.e., percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery). Insulin resistance, present not only in type 2 diabetes but also commonly in patients with hypertension or coronary artery disease, or both, sensitizes the vasculature to the trophic effects of angiotensin II and aldosterone. This may partly explain the improvement in prognosis noted when patients who have atherosclerosis or diabetes are treated with an ACE inhibitor. Therapy with ACE inhibitors has also been shown, in two large, randomized trials, to reduce the incidence of new-onset type 2 diabetes through largely unknown mechanisms. The ACE inhibitors are safe, well tolerated and affordable medications. The data suggest that most people with atherosclerosis should be considered candidates for ACE inhibitor therapy, unless they are intolerant to the medication, or have systolic blood pressures consistently <100 mm Hg. Patients who show evidence of insulin resistance (with or without overt type 2 diabetes) should also be considered as candidates for prophylactic ACE inhibitor therapy. Although angiotensin receptor blockers should not be considered equivalent to ACE inhibitors for this indication, they may be a reasonable alternative for patients intolerant of ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Lipid risk factor correlates of ischemic heart disease as diagnosed by myocardial perfusion scintigraphy.

Patients with known coronary artery disease frequently change their lifestyles (e.g., diet, exercise, and smoking habit) after the diagnosis is made. Such changes can alter lipid risk factor levels and obscure etiologic risk factor associations with the presence of coronary artery disease. It is therefore preferable to determine the contribution of potential risk factors before the diagnosis of coronary artery disease has been established. In this trial, we used stress nuclear myocardial perfusion imaging to diagnose coronary artery disease in patients presenting for evaluation of chest pain. Two groups of age- and sex-matched patients were identified: a normal group (patients with no evidence of coronary artery disease), and an abnormal group (patients whose scans indicated the presence of significant coronary artery disease due to either fixed or reversible perfusion defects). Blood samples were drawn before scanning and analyzed for lipid risk factors. Compared to the normal group, the abnormal group had higher levels of triglycerides (189±91 vs. 135±51 mg/dL, p=0.003), lower levels of high-density lipoprotein cholesterol (39±9 vs. 45±14 mg/dL, p=0.037), and higher levels of small, dense low-density lipoprotein (LDL(3)) (42±18 vs. 32±13 mg/dL, p=0.007). Total cholesterol, low-density lipoprotein, and lipoprotein(a) levels were similar between groups. These findings suggest that ischemic heart disease, as assessed by myocardial perfusion scintigraphy, is more closely associated with the low high-density lipoprotein/high triglyceride syndrome than with increased low-density lipoprotein or total cholesterol levels. (c) 2000 by CHF, Inc.

Journal Article↗

From Inuit to implementation: omega-3 fatty acids come of age.

During the past 25 years, the cardiovascular effects of marine omega-3 (omega-3) fatty acids have been the subject of increasing investigation. In the late 1970s, epidemiological studies revealed that Greenland Inuits had substantially reduced rates of acute myocardial infarction compared with Western control subjects. These observations generated more than 4,500 studies to explore this and other effects of omega-3 fatty acids on human metabolism and health. From epidemiology to cell culture and animal studies to randomized controlled trials, the cardioprotective effects of omega-3 fatty acids are becoming recognized. These fatty acids, when incorporated into the diet at levels of about 1 g/d, seem to be able to stabilize myocardial membranes electrically, resulting in reduced susceptibility to ventricular dysrhythmias, thereby reducing the risk of sudden death. The recent GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevention study of 11,324 patients showed a 45% decrease in risk of sudden cardiac death and a 20% reduction in all-cause mortality in the group taking 850 mg/d of omega-3 fatty acids. These fatty acids have potent anti-inflammatory effects and may also be antiatherogenic. Higher doses of omega-3 fatty acids can lower elevated serum triglyceride levels; 3 to 5 g/ d can reduce triglyceride levels by 30% to 50%, minimizing the risk of both coronary heart disease and acute pancreatitis. This review summarizes the emerging evidence of the use of omega-3 fatty acids in the prevention of coronary heart disease.

Cardiovascular Agents↗

Isolated left anterior descending coronary artery disease: percutaneous transluminal coronary angioplasty versus stenting versus left internal mammary artery bypass grafting.

BACKGROUND: Single-vessel coronary artery disease is usually treated with PTCA; however, this approach when applied to the left anterior descending coronary artery (LAD) is hampered by high restenosis rates, often approaching 50%. Coronary stenting (STENT) and left internal mammary artery bypass grafting of the LAD (LIMA-LAD) are other options that have been successfully used for single-vessel LAD disease. The optimal mode of revascularization for patients with isolated single-vessel LAD disease is unclear. The purpose of the present study was to examine PTCA versus STENT versus LIMA-LAD with respect to short- and intermediate-term outcomes. METHODS AND RESULTS: This was an observational retrospective cohort study comparing in-hospital and intermediate-term outcomes and functional class among patients with isolated single-vessel LAD disease revascularization. Consecutive eligible patients were grouped according to their initial revascularization procedure and systematically followed up. A total of 704 patients qualified for the study: 469 in the PTCA group, 137 in the STENT group, and 98 in the LIMA-LAD group. Follow-up data were complete for 97% of patients and averaged 27+/-13 months. In-hospital mortality for the PTCA, STENT, and LIMA-LAD groups was 1.1%, 0%, and 0% (P=0.51), respectively. Median hospital stays after the procedure for the respective treatment groups were 1, 1, and 5 days (P<0.001), and occurrences of in-hospital myocardial infarction were 0.9%, 1.5%, and 1.0% (P=NS). Repeat revascularization procedures were performed in 30%, 24%, and 5% of the PTCA, STENT, and LIMA-LAD groups (P=<0. 001 for LIMA-LAD versus other groups, P=0.11 for PTCA versus STENT). Actuarial 2-year mortality was 3.9%, 2.6%, and 1% in the PTCA, STENT, and LIMA-LAD groups (P=0.33). CONCLUSIONS: Revascularization for isolated LAD disease using PTCA, STENT, or LIMA-LAD results in low in-hospital adverse event rates and good long-term results. Repeat procedures are required less often after LIMA-LAD than after either PTCA or STENT. Long-term mortality was not statistically different, but the trend was for the lowest mortality with LIMA-LAD, a somewhat higher mortality with STENT, and the highest mortality with PTCA.

Aged↗

A randomized, controlled trial of the effects of remote, intercessory prayer on outcomes in patients admitted to the coronary care unit.

CONTEXT: Intercessory prayer (praying for others) has been a common response to sickness for millennia, but it has received little scientific attention. The positive findings of a previous controlled trial of intercessory prayer have yet to be replicated. OBJECTIVE: To determine whether remote, intercessory prayer for hospitalized, cardiac patients will reduce overall adverse events and length of stay. DESIGN: Randomized, controlled, double-blind, prospective, parallel-group trial. SETTING: Private, university-associated hospital. PATIENTS: Nine hundred ninety consecutive patients who were newly admitted to the coronary care unit (CCU). INTERVENTION: At the time of admission, patients were randomized to receive remote, intercessory prayer (prayer group) or not (usual care group). The first names of patients in the prayer group were given to a team of outside intercessors who prayed for them daily for 4 weeks. Patients were unaware that they were being prayed for, and the intercessors did not know and never met the patients. MAIN OUTCOME MEASURES: The medical course from CCU admission to hospital discharge was summarized in a CCU course score derived from blinded, retrospective chart review. RESULTS: Compared with the usual care group (n = 524), the prayer group (n = 466) had lower mean +/- SEM weighted (6.35 +/- 0.26 vs 7.13 +/- 0.27; P=.04) and unweighted (2.7 +/- 0.1 vs 3.0 +/- 0.1; P=.04) CCU course scores. Lengths of CCU and hospital stays were not different. CONCLUSIONS: Remote, intercessory prayer was associated with lower CCU course scores. This result suggests that prayer may be an effective adjunct to standard medical care.

Aged↗

Combination drug therapy for dyslipidemia.

Effective treatment of dyslipidemia improves prognosis. Statin therapy has been documented to decrease the cardiovascular event rate in the setting of elevated low-density lipoprotein (LDL) cholesterol levels and coronary heart disease, but most patients are not treated to the target (LDL <or=100 mg/dL) set by the National Cholesterol Education Program. The triglyceride level is also being increasingly recognized as an important mediator in the process of progressive atherosclerosis and cardiovascular events. Studies suggest the target level for triglycerides should be the same as for LDL cholesterol levels-- no more than 100 mg/dL. In order to achieve these LDL and triglyceride levels, combination therapy is required frequently. Probably the most effective combination for mixed dyslipidemia is a statin with niacin. The use of adjunctive omega-3 supplementation also should be considered especially for patients with elevated triglyceride levels. Other adjunctive agents including sitostanol ester (in the form of a margarine) and a well-tolerated second generation bile acid sequestrant that will lower LDL cholesterol an additional 10% to 18% and will be available soon.

Anion Exchange Resins↗

Improving the adverse cardiovascular prognosis of type 2 diabetes.

Approximately 80% of all patients with diabetes die of cardiovascular disease. The traditional management of type 2 diabetes has been ineffective in altering this dismal prognosis. Insulin resistance is the fundamental defect of type 2 diabetes. Insulin resistance often leads to hyperinsulinemia, which is associated with hypertension, atherogenic dyslipidemia, left ventricular hypertrophy, impaired fibrinolysis, visceral obesity, and sedentary lifestyle. Although all these conditions are associated with atherosclerosis and adverse cardiovascular events, the therapeutic efforts in patients with diabetes have focused predominantly on normalizing glucose levels. Improved insulin sensitivity through lifestyle modifications or pharmacologic therapy (troglitazone and metformin) will lower both insulin and glucose levels as well as diminish dyslipidemia and hypertension. In contrast, sulfonylurea agents lower glucose by increasing insulin levels and may increase the risk of cardiovascular events. Therapy including aspirin, lipid agents (for example, statins), angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, postmenopausal estrogen replacement, and vitamin E should be considered for patients with type 2 diabetes. In most patients with diabetes who have multivessel coronary artery disease, coronary artery bypass grafting is superior to coronary angioplasty for improving long-term cardiovascular prognosis. This superiority is mediated in part by the use of a left internal mammary graft to the left anterior descending coronary artery. Urgent coronary angioplasty or thrombolytic therapy should be considered for all patients with diabetes who have acute myocardial infarction.

Antihypertensive Agents↗

Usefulness of technetium-99m sestamibi infarct size in predicting posthospital mortality following acute myocardial infarction.

In this multicenter study, 249 patients who underwent tomographic technetium-99m sestamibi infarct size measurement at hospital discharge were followed up for a median duration of 7 months. Infarct size was significantly associated with mortality (chi-square = 5.8, p = 0.02) and could stratify patients into lower and higher risk subsets: 1-year mortality 2% for infarct size < 14% versus 8% for infarct size > or = 14% of the left ventricle.

Aged↗

Intercenter variability in outcome for patients treated with direct coronary angioplasty during acute myocardial infarction.

BACKGROUND: Direct coronary angioplasty is an effective therapy for acute myocardial infarction, but its success may be dependent on both ready availability and operator skill. The purpose of this study was to investigate the impact of the center performing direct coronary angioplasty for acute myocardial infarction while controlling for parameters known to affect outcome. METHODS AND RESULTS: The study group consisted of 99 patients with ST elevation who were treated with direct angioplasty in four high-volume centers. Patients were injected with technetium-99m sestamibi intravenously and then taken to the cardiac catheterization laboratory. Antegrade flow was graded before and after direct coronary angioplasty. Single photon emission computed tomography was performed 1 to 6 hours after injection to measure myocardium at risk and residual blood flow to the jeopardized zone using previously published quantitative methods. A repeat sestamibi injection and tomographic acquisition were performed at hospital discharge to measure actual infarct size. There were no significant differences by center for baseline clinical characteristics, mean myocardium at risk (29% to 37% left ventricle [LV]), time to reperfusion (3.1 to 4.1 hours), residual blood flow, infarct location, or antegrade flow. Despite these similarities, there were differences in outcome measures by center. Mean infarct size was as follows: center 1, 15%; center 2, 12%; center 3, 10%, center 4, 23% (all LV; p = 0.11 ). Mean left ventricular ejection fraction at discharge also demonstrated significant differences: center 1, 0.57; center 2, 0.47; center 3, 0.53; center 4, 0.47 (p = 0.002). The prevalence of Thrombolysis in Myocardial Infarction grade 3 flow after angioplasty significantly differed by center: center 1, 92%; center 2, 94%; center 3, 87%; center 4, 71 %; (p = 0.01). There was a low mortality rate for all four centers ranging from 0% to 6%. After adjustment for myocardium at risk, residual blood flow, and time to reperfusion, the primary outcome of the center where the angioplasty was performed was an independent determinant of both infarct size and left ventricular ejection fraction. CONCLUSION: The success of direct coronary angioplasty in reducing infarct size and preserving left ventricular function depends on the center performing the procedure. Direct measurement of the effectiveness of this reperfusion modality in community practice is required to assess the impact of this effect.

Aged↗

The optimal mode of coronary revascularization for diabetics. A risk-adjusted long-term study comparing coronary angioplasty and coronary bypass surgery.

AIMS: Some recent studies have reported-superior outcomes for diabetic patients following coronary bypass surgery compared with coronary angioplasty. However, the available data are conflicting, are based on relatively small numbers of diabetic patients, and have limited duration of follow-up. The aims of this study were to compare risk adjusted long-term survival in diabetic patients following first-time revascularization via either coronary bypass surgery or coronary angioplasty; and, to identify variables independently associated with mortality. METHODS AND RESULTS: This was a two centre database project involving 15809 patients undergoing either coronary angioplasty or coronary bypass surgery as their initial revascularization procedure. Diabetes was present in 1938 (12%). Mean follow-up was 4.6+/-2.7 years for angioplasty and 6.6+/-4.3 years surgery diabetic patients. Multivariable time-related analyses in the hazard function domain for death were performed. Overall ten-year survival for pharmacologically treated diabetics was better after coronary bypass surgery (60%) than angioplasty (46%, <0.0001). However, the risk-adjusted survival advantage conferred by bypass surgery over angioplasty was strongest for patients receiving oral agents for diabetic control (75% vs 62%) and less impressive for diet (84% vs 81%) and insulin-treated diabetics (63% vs 64%). The major factors independently associated with worse outcome after angioplasty were incomplete revascularization, and the use of a sulfonylurea agent. The use of the left internal mammary graft improved survival in surgical patients. CONCLUSIONS: In general, diabetic patients had better long-term survival after bypass surgery than angioplasty. Incomplete revascularization and sulfonylurea therapy worsened outcome after angioplasty, and use of the left internal mammary improved outcome after bypass surgery.

Angioplasty, Balloon, Coronary↗

Bypass surgery versus coronary angioplasty for revascularization of treated diabetic patients.

BACKGROUND: The purpose of this study was to evaluate outcomes after coronary bypass surgery versus coronary angioplasty in 525 patients with pharmacologically treated diabetes. Diabetic patients constitute a significant portion of patients considered for coronary revascularization. Some studies have shown no difference in long-term outcome when comparing revascularization mode. Recently, the Bypass Angioplasty Revascularization Investigation reported better survival with bypass surgery over angioplasty in treated diabetic patients. However, the above studies have been limited by small cohorts of diabetic patients. METHODS AND RESULTS: By using a single-institution comprehensive database, a retrospective cohort design was used to study 525 consecutive pharmacologically treated diabetic patients who underwent coronary revascularization. Patients treated with surgery (n=246) were statistically similar when comparing age, gender, angina class, and ejection fraction to patients (n=279) treated with angioplasty. Follow-up was complete in 95% of bypass patients and 99% of angioplasty patients. Mean follow-up was 55.5 months. Complete revascularization was accomplished more often in the surgery group (79%) than in the angioplasty group (42%; P<.001). During a 6-year follow-up, repeat revascularization (8% versus 64%; P=.001), cardiac events (32% versus 41%; P=.04), and death (30% versus 37%; P=.08) occurred less in the bypass patients than the angioplasty patients. Multivariable analysis identified age >70 years, ejection fraction <40%, class IV angina, and incomplete revascularization, but not mode of revascularization, as correlates of late mortality. CONCLUSIONS: For most pharmacologically treated diabetic patients, freedom from death, myocardial infarction, and subsequent revascularization during long-term follow-up is superior with bypass surgery compared with angioplasty. This worse outcome was mediated in part by the frequent occurrence of incomplete revascularization with angioplasty.

Angioplasty, Balloon, Coronary↗

Noninvasive prediction of residual blood flow within the risk area during acute myocardial infarction: a multicenter validation study of patients undergoing direct coronary angioplasty.

BACKGROUND: In a previous study from a single center, radionuclide measures of collateral flow with technetium 99m sestamibi have been shown to be significantly associated with angiographic residual (antegrade and collateral) flow and independent predictors of final infarct size in acute myocardial infarction. This study examined whether the previously described radionuclide measures of blood flow to the infarct zone were reproducible with different laboratories and imaging systems. METHODS AND RESULTS: Residual flow to the infarct zone was assessed by both invasive and noninvasive methods in 77 patients with first-time myocardial infarction (32 anterior, 45 nonanterior). All patients underwent acute coronary angiography before any intervention within 8 hours of the onset of chest pain (4.0 +/- 1.5 hours; range 1.2 to 7.9 hours). 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1 to 6 hours after injection. A central core laboratory processed the acquired images from three centers, each with a unique camera and computer system. Three previously published methods based on the severity of the acute perfusion defect were used to measure residual flow to the infarct zone (nadir, severity index, area). Antegrade (Thrombolysis in Myocardial Infarction flow) and collateral flow before direct angioplasty were blindly graded on a four-point scale (0 to 3) from the acute angiogram. The simple sum of the two grades was defined as the angiographic flow index, representing residual flow to the jeopardized zone. All three noninvasive measures of residual flow were highly associated with the angiographic flow index in a linear fashion: severity index (p = 0.0006), area (p = 0.003), and nadir (minimum/maximum counts; p = 0.004). This association was independent of the laboratory where the data were acquired. CONCLUSIONS: Despite different laboratories and camera systems, radionuclide measures of residual flow were highly associated with the angiographic flow index before reperfusion therapy. These results suggest that these measures are applicable on a broader scale for the noninvasive determination of collateral and antegrade flow in acute myocardial infarction.

Coronary Angiography↗

Estrogen replacement therapy after coronary angioplasty in women.

OBJECTIVES: The purpose of this study was to assess the effects of estrogen replacement therapy on long-term outcome, including restenosis, myocardial infarction, stroke and death after a first percutaneous transluminal coronary angioplasty (PTCA) procedure, in postmenopausal women. BACKGROUND: Observational and epidemiologic studies, basic laboratory research and clinical trials consistently suggest that estrogen replacement therapy is associated with beneficial cardiovascular effects in women. These cardioprotective actions may be particularly relevant to women with coronary artery disease, such as those who have undergone PTCA. METHODS: This was a retrospective study that included 337 women who underwent elective PTCA between 1982 and 1994. The treatment group consisted of 137 consecutive women receiving long-term estrogen therapy at the time of elective PTCA and during follow-up. The control group comprised 200 women who were computer-matched with the estrogen group. The mean follow-up period was 65 +/- 35 months. RESULTS: Actuarial survival was superior in the estrogen group; the 7-year survival rate was 93% for the estrogen group versus 75% for the control group (p = 0.001). The cardiovascular event rate (death, nonfatal myocardial infarction or nonfatal stroke) was significantly lower in the estrogen group at 7 years (12% vs. 35% in the control group, p = 0.001). The need for subsequent revascularization during follow-up was similar in the two groups. Multivariable analysis identified diabetes, estrogen therapy (adjusted risk ratio 0.38, 95% confidence interval 0.19 to 0.79) and left ventricular ejection fraction < 40% as independent correlates of cardiovascular death or myocardial infarction during follow-up. CONCLUSIONS: Estrogen replacement therapy was associated with an improved long-term outcome after PTCA in postmenopausal women.

Actuarial Analysis↗