Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although observational studies suggest that estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality in postmenopausal women, use of unopposed ERT for prevention of coronary heart disease in healthy postmenopausal women remains untested. OBJECTIVE: To determine the effects of unopposed ERT on the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University-based clinic. PATIENTS: 222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL). INTERVENTION: Unopposed micronized 17beta-estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medication if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/L (160 mg/dL). MEASUREMENTS: The rate of change in intima-media thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms obtained at baseline and every 6 months during the 2-year trial. RESULTS: In a multivariable mixed-effects model, among women who had at least one follow-up measurement of carotid intima-media thickness (n = 199), the average rate of progression of subclinical atherosclerosis was lower in those taking unopposed estradiol than in those taking placebo (-0.0017 mm/y vs. 0.0036 mm/y); the placebo-estradiol difference between average progression rates was 0.0053 mm/y (95% CI, 0.0001 to 0.0105 mm/y) (P = 0.046). Among women who did not receive lipid-lowering medication (n = 77), the placebo-estradiol difference between average rates of progression was 0.0147 mm/y (CI, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not differ between estradiol and placebo recipients who took lipid-lowering medication (n = 122) (P > 0.2). CONCLUSIONS: Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking unopposed ERT with 17beta-estradiol than in women taking placebo. Reduction in the progression of subclinical atherosclerosis was seen in women who did not take lipid-lowering medication but not in those who took these medications.

Intensity of antianginal therapy in patients referred for coronary angiography: a comparison of fee-for-service and health maintenance organization therapeutic strategies.

BACKGROUND: No formal criteria have been developed to guide medical therapy for angina prior to revascularization, and no comparisons have been made between health maintenance organization (HMO) and fee-for-service (FFS) hospitals with respect to angina treatment. HYPOTHESIS: Using a literature-based measure of medical intensity, we tested the hypothesis that there is no difference in anginal medical therapeutic intensity between HMO and FFS systems. METHODS: For each antianginal drug, we developed a model from which an intensity score between 0 and 100 could be calculated. Average and maximal daily doses of drug were fit to a sigmoid curve such that they represented scores of 50 and 99, respectively. Overall intensity scores were obtained by weighted and unweighted averaging of three scores from nitrates, calcium-channel blockers, and beta blockers. This model was applied to 199 patients undergoing angiography at an FFS and an HMO hospital. RESULTS: HMO patients were taking more classes of antianginal drug (1.9 vs. 1.0, p < 0.001). Overall unweighted (17.7 vs. 11.7, p = 0.02) and weighted (27.3 vs. 16.9, p = 0.003) intensity scores for both HMO and FFS patients were low. HMO intensity scores for the use of beta blockers were greater than FFS scores (19.2 vs. 9.6, p = 0.002). The intensity scores for the use of nitrates and calcium blockers were similar. CONCLUSIONS: Models for the measurement of anginal medical therapy intensity can provide important information regarding medical therapy prior to revascularization. The overall intensity of medical therapy was low in both health care systems. These findings have important implications for patient management, guideline development, and national healthcare policy.

Time related quality of life after elective cardiac operation.

BACKGROUND: Due to improved operative techniques, myocardial preservation, and perioperative care, open heart procedures are now being performed in older and sicker patients. As a result, the quality of life has become an important issue in the decision making process. METHODS: Between January 1993 and October 1994, 604 patients above 65 years of age who underwent non-emergent open heart operations were followed prospectively over a 2-year period. The Health Status Questionnaire forms were distributed to all patients preoperatively and to hospital survivors at 3, 12, and 24 months. The questionnaire contains 36 questions and is divided into eight categories. Follow-up was 100% complete with 99.6% of questionnaires returned. RESULTS: Significant quality of life improvements were noted in all categories after surgery. After reaching a peak at 12 months, there were small, but significant declines in scores relating to physical health and health perception at 24 months. In contrast, measurements for mental attributes continued to increase with time. By multivariate analysis, diabetes, older age, and female gender had a relatively adverse influence on quality of life despite improvement after operation. Similarly, patients with chronic obstructive pulmonary disease or having redo operations had lower health perception with some physical limitations. While procedure type (coronary artery bypass grafting) was associated with preoperative bodily pain, congestive heart failure symptoms were not an independent factor affecting quality of life. CONCLUSIONS: Quality of life improves with cardiac surgical interventions in this studied age group and should not be denied even in the elderly population.

Underuse and overuse of diagnostic testing for coronary artery disease in patients presenting with new-onset chest pain.

PURPOSE: To determine the extent of overuse and underuse of diagnostic testing for coronary artery disease and whether the socioeconomic status, health insurance, gender, and race/ethnicity of a patient influences the use of diagnostic tests. SUBJECTS AND METHODS: We identified patients who presented with new-onset chest pain not due to myocardial infarction at one of five Los Angeles-area hospital emergency departments between October 1994 and April 1996. Explicit criteria for diagnostic testing were developed using the RAND/University of California, Los Angeles, expert panel method. They were applied to data collected by medical record review and patient questionnaire. RESULTS: Of the 356 patients, 181 met necessity criteria for diagnostic cardiac testing. Of these, 40 (22%) failed to receive necessary tests. Only 7 (3%) of the 215 patients who received some form of cardiac testing had tests that were judged to be inappropriate. Underuse was significantly more common in patients with only a high school education (30% vs 15% for those with some college, P = 0.02) and those without health insurance (34% vs 15% of insured patients, P = 0.01). In a multivariate logistic regression model, only the lack of a post-high school education was a significant predictor of underuse (odds ratio 2.2, 95% confidence interval 1.0 to 4.4). CONCLUSION: Among patients with new-onset chest pain, underuse of diagnostic testing for coronary artery disease was much more common than overuse. Underuse was primarily associated with lower levels of patient education.

Community practice of primary angioplasty for myocardial infarction.

Results obtained with primary angioplasty at the community level do not duplicate the results of the published trials. Major changes in current community practice patterns are needed to achieve the success rates of the published trials.

Nonselective angiography of the internal mammary artery: a fast, reliable, and safe technique.

Selective cannulation of the mammary artery can be time consuming and carries a risk of arterial injury. The nonselective technique described here is faster, safer, and as reliable as the standard selective technique. A consecutive series of patients with previous coronary artery bypass graft surgery (CABG) were randomized to undergo either selective or nonselective mammary artery angiography. Selective angiography was performed using the standard selective technique. Nonselective angiography was performed by placing a standard catheter in the subclavian artery and hand injecting 10 ml of contrast while inflating a blood pressure cuff 10 mm above the systolic pressure in the ipsilateral arm. Fifty-six patients were studied, 30 patients selectively, and 26 patients nonselectively. The time to visualize adequately both native and grafted mammary arteries in the selective group was 4.83 + 5.00 min and in the nonselective group 1.76 + 1.16 minutes (P = 0.006). A nonselective technique for visualizing the mammary artery is significantly faster and as reliable as the standard selective technique.

Spontaneous regression of restenosis: an angiographic study.

OBJECTIVES: This study was designed to examine the possibility that spontaneous regression in stenosis severity occurs over time in patients with restenosis after percutaneous transluminal coronary angioplasty. BACKGROUND: The underlying mechanisms of restenosis are intimal hyperplasia and smooth muscle cell proliferation in response to vascular injury. We hypothesized that the initial hyperplastic response is followed by dynamic remodeling and eventual spontaneous regression, leading to stabilization or a reduction in stenosis severity. METHODS: A total of 136 patients participated in a trial to evaluate the efficacy of fish oil versus placebo in preventing restenosis after angioplasty. One hundred thirteen patients completed this study with angiographic follow-up, of whom 56 had restenosis. Of these, 19 were asymptomatic and did not undergo repeat revascularization; 15 consented in a separate study to undergo repeat angiography, which was performed 6 to 25 months later to assess the possibility of regression. RESULTS: There was a significant mean (+/- SD) decrease in lesion severity from 66.9 +/- 8.7% to 47.5 +/- 9.0% (p < 0.0001) and a significant mean increase in minimal lumen diameter from 0.91 +/- 0.31 mm to 1.44 +/- 0.35 mm (p < 0.0001). No patient showed progression of stenosis, but regression of restenosis, defined as a decrease in minimal lumen diameter > or = 0.2 mm, was noted in 12 of the patients. CONCLUSIONS: Although all 15 study patients were asymptomatic, similar changes may occur in symptomatic patients. A trial of medical therapy may be appropriate in asymptomatic or mildly symptomatic patients before further interventions. This strategy would avoid unnecessary invasive procedures, prevent a "restenosis cycle" and result in significant cost savings.

Spontaneous coronary dissection: a cluster of cases with this rare finding.

Spontaneous coronary dissection is a rare entity. It has been reported to be usually fatal, with greater than an 80% mortality rate. From April 1990 through March 1993, 10 patients had spontaneous coronary dissection. This is a significant increase in the incidence of this diagnosis, with only one prior case at this institution in 1983 (p < 0.001). All of the patients survived. Of the 10 patients, eight were women, and seven of those were premenopausal. Only one was post partum. Acute myocardial infarction was the presenting condition in nine patients. Three patients had spontaneous dissections involving two arteries. Only one patient had associated atherosclerotic coronary artery disease. Surgery was required for continued symptoms in three patients, with difficulty grafting the dissected artery in two. Nine patients have no symptoms, and one has class II angina. With aggressive medical therapy the prognosis of patients with spontaneous coronary dissection may not be as dismal as previously reported.

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

A new technique for right heart catheterization with a Swan-Ganz balloon catheter via femoral vein in the patient with dilated right heart chambers, utilizing a modified transseptal-type sheath.

Right heart catheterization with a Swan-Ganz balloon catheter via femoral vein in the patient with dilated right atrium and ventricle is frequently difficult due to excessive catheter coiling in the dilated atrium. A new technique is described in this situation. By using a modified transseptal-type sheath positioned counterclockwise in right atrium as an introducing sheath, a balloon catheter can be easily advanced to the distal pulmonary artery by smooth counterclockwise direction and secure support from this sheath.

Transfer of acutely ill cardiac patients for definitive care. Demonstrated safety in 755 cases.

The safety of transporting acutely ill cardiac patients for cardiac catheterization has not been established. We describe 755 consecutive patients sent by ambulance from community hospitals to a tertiary center during an 18-month period. Eighty-seven percent of the patients were class III or IV New York Heart Association classification for angina. At catheterization, left ventricular dysfunction (ejection fraction less than 55%) was present in 40%. Forty-three percent of patients required urgent intervention (coronary artery bypass surgery or percutaneous transluminal coronary angioplasty). The patients were transported by paramedic ambulance up to 99 km (less than or equal to 62 miles) without a physician in attendance. No complications occurred in patients transferred within our guidelines. We believe that seriously ill cardiac patients can be transferred safely for definitive care. A single tertiary center providing immediate access to catheterization and surgical facilities can service a large population and many community hospitals.

Efficacy and safety of outpatient cardiac catheterization.

Outpatient cardiac catheterization has become the standard in our laboratory. The only exclusion for outpatient study is current hospitalization for cardiac symptoms. Thus, any patient well enough to be at home is studied on an outpatient basis. We reviewed our experience on 4,094 diagnostic studies of which 3,537 (86%) were done on a same-day basis. The complication rates were generally lower than in published series with a mortality of 0.05%. There were no admissions for late bleeding. Ninety-seven percent of the procedures were done by the percutaneous technique utilizing 7-French catheters. Patients were heparinized, and protamine was not used. The low complication rate is to a large extent due to meticulous postoperative care by critical care nurses in an outpatient observation unit contiguous to the laboratory. Outpatient cardiac catheterization is a safe, cost-saving approach applicable to a large majority of cardiac patients.

Idiopathic coronary artery dissection: a rare in vivo diagnosis.

A 42-year-old white female, who had an acute myocardial infarction, developed postinfarction angina and underwent coronary angiography seven weeks after the event. Coronary angiogram demonstrated a primary dissection of the left anterior descending artery. To our knowledge this is the sixth such report of a patient with primary dissection of a coronary artery demonstrated by angiography and the fourth such patient reported to achieve and maintain asymptomatic status without operative intervention.

Outpatient cardiac catheterization and coronary angiography.

The cost of hospitalization required for cardiac catheterization led us to evaluate this procedure in 308 adult outpatients. Patients wee scheduled on the basis of stability of symptoms. Two hundred eighty-eight underwent left heart catheterizations and coronary arteriography. Ninety-five percent of the procedures were performed by the percutaneous technique. Fifty patients had normal studies and 30 patients had congenital or valvular disease. Two hundred twenty-eight patients had significant coronary artery disease, 85 patients had triple vessel disease, and 45 patients had left main coronary artery disease. There were six significant complications: one death; two myocardial infarctions; one air embolism, and two patients with hematomas. Three of the complications were in patients with left main disease. Only two of the complications can be ascribed to the outpatient nature of the procedure. The complication rate is comparable to that reported in the literature. Fifteen hundred subsequent cases were studied as outpatients, with a very low mortality and morbidity. It is concluded that cardiac catheterization can be performed on an outpatient basis with safety comparable to inpatient studies, and at a great economic savings.