Peter R. Mahrer

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

Coronary heart disease is the leading cause of death in women, and mortality rates from this disease substantially and steadily increase after menopause (13). Population studies indicate that estrogen reduces the incidence of coronary heart disease in women. Bilateral oophorectomy before natural menopause increases the risk for coronary heart disease (4). This pattern of risk for coronary heart disease suggests that endogenous estrogens, including 17-estradiol, play a cardioprotective role before menopause. More than 40 observational studies have suggested that hormone replacement therapy (HRT) reduces cardiovascular morbidity and mortality in postmenopausal women (5, 6). Most of these studies were conducted in healthy postmenopausal women who used unopposed estrogen replacement therapy (ERT). Although observational studies are important, selection bias is a potential problem, especially when studying HRT, since healthier women tend to use hormones (7). Only randomized, controlled trials can ensure that patients are assigned to treatment in an unbiased manner and can establish the efficacy of HRT for reducing the progression of atherosclerosis and its clinical sequelae. The effect of unopposed ERT on progression of atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease remains untested in randomized, controlled trials. We report the results of the Estrogen in the Prevention of Atherosclerosis Trial (EPAT), a randomized, double-blind, placebo-controlled trial designed to test whether unopposed micronized 17-estradiol reduces progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. Our primary hypothesis was that unopposed ERT significantly reduces the progression of subclinical atherosclerosis. Methods Study Design Potential participants were prescreened by telephone and seen at three screening visits 2 to 4 weeks apart to collect baseline data and to determine final study eligibility. Women were eligible if they were postmenopausal (serum estradiol level < 73.4 pmol/L [<20 pg/mL]), 45 years of age or older, and had a low-density lipoprotein (LDL) cholesterol level of 3.37 mmol/L or greater ( 130 mg/dL). Women were excluded if breast or gynecologic cancer had been diagnosed in the past 5 years or if these cancers were identified during screening; if they had previously used HRT for more than 10 years or had used HRT within 1 month of the first screening visit; if they had five or more hot flushes daily that interfered with daily activity and precluded randomization, diastolic blood pressure greater than 110 mm Hg, untreated thyroid disease, life-threatening disease with a survival prognosis of less than 5 years, total triglyceride level of 4.52 mmol/L or greater ( 400 mg/dL), high-density lipoprotein (HDL) cholesterol level less than 0.78 mmol/L (<30 mg/dL), or serum creatinine concentration greater than 221 mol/L (>2.5 mg/dL); or if they were current smokers. All women, including those with diabetes mellitus, were included provided that their fasting blood glucose level was less than 11.1 mmol/L (<200 mg/dL). All participants gave written informed consent, and the study protocol was approved by the University of Southern California Institutional Review Board. Packets of study medications were prepared in a blinded manner (to both the clinical staff and participants) before the start of the study. Computer-generated random numbers were used to assign participants to unopposed estradiol or placebo in one of eight strata, defined by LDL cholesterol level (<4.15 mmol/L [<160 mg/dL] or 4.15 mmol/L), previous duration of HRT use (<5 years or 5 years), and diabetes mellitus (yes or no). As a new participant was determined to be eligible for randomization, the next packet in sequence in the appropriate stratum was obtained and recorded. The Data Coordinating Center monitored adherence to sequential assignment of medication packets. The participants, gynecologists, clinical staff, and image analysts were blinded to treatment assignment. The data monitor and data analyst were blinded to treatment assignment until analyses were completed. Participants were followed every month for the first 6 months and every other month thereafter for a total of 2 years. All participants received dietary counseling according to step II American Heart Association dietary recommendations: 200 mg of cholesterol or less per day, 25% of energy as total-fat calories, and 7% of energy as saturated-fat calories. Dietary intake was monitored at each clinic visit by using 3-day dietary booklets (Nutrition Scientific, South Pasadena, California). Participants received lipid-lowering medication (primarily hydroxymethylglutaryl coenzyme A reductase inhibitors) if their LDL cholesterol level exceeded 4.15 mmol/L (160 mg/dL). Vital signs; clinical events; adherence; and use of nonstudy medications, dietary supplements, and nutriceuticals were ascertained at each visit. Carotid artery ultrasonography was performed at baseline (two visits 1 to 3 weeks apart) and every 6 months thereafter. The baseline intimamedia thickness was the average of the two measurements. Pelvic examination (and uterine ultrasonography in participants with a uterus), Papanicolou smear, and mammography were done yearly in all participants. Uterine biopsy was performed if endometrial thickness was 5 mm or more. Adverse clinical symptoms and bleeding were assessed by the study gynecologist, who was blinded to treatment assignment. The primary trial end point was the rate of change in intimamedia thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms (815). Power calculations indicated that a sample size of 200 (100 participants per treatment group) was needed to detect a treatment effect size (the standardized difference in progression rates between the two treatment groups) of 0.40 or greater with 80% power. Two hundred twenty-two participants (111 per treatment group) were recruited to accommodate the anticipated dropout rate. Assessment of the Progression of Subclinical Atherosclerosis High-resolution B-mode ultrasonograms of the right common carotid artery were obtained by using a 7.5-MHz linear-array transducer attached to a Toshiba SSH 140A ultrasonography system (Toshiba Corp., Tokyo, Japan). The ultrasonographers were blinded to treatment assignment. Participants were placed in a supine position with the head rotated to the left by using a 45-degree head block. The jugular vein and carotid artery were located in the transverse view, with the jugular vein stacked above the carotid artery according to modification of a procedure described by Beach and colleagues (16). The transducer was then rotated 90 degrees around the central line of the transverse image of the stacked jugular vein and carotid artery to obtain a longitudinal image while the stacked position of the vessels was maintained. All images contained anatomic landmarks for reproducing probe angulation, and a hard copy of each participants baseline image was used as a guide for follow-up examinations. For each participant, the depth of field, gain, monitor intensity setting, and other instrumentation settings used at baseline examination were used at all follow-up examinations. These techniques significantly reduce measurement variability (14, 15). All images were recorded with the electrocardiogram tracing on super-VHS video tape. An image analyst who was blinded to treatment assignment measured the intimamedia thickness of the distal common carotid artery far wall with automated computerized edge detection using an in-house software package (Prosound, University of Southern California, Los Angeles, California), as described elsewhere (14, 15). Carotid intimamedia thickness was the average of approximately 70 to 100 individual measurements between the intimalumen and mediaadventitia interfaces along a 1-cm length just distal to the carotid artery bulb. This method standardized the location and the distance over which intimamedia thickness was measured and ensured that the same portion of the arterial wall was measured in each image and compared within and across all participants. Laboratory Measurements Participants fasted for 8 hours before sample collection. Total plasma cholesterol and triglyceride levels were measured by using an enzymatic method of the Standardization Program of the National Centers for Disease Control and Prevention. High-density lipoprotein cholesterol levels were measured after lipoproteins containing apolipoprotein B were precipitated in whole plasma by using heparin manganese chloride. Low-density lipoprotein cholesterol levels were estimated by using the Friedewald equation (17). Serum estradiol and fasting insulin levels were measured by using radioimmunoassay. Fasting serum glucose levels were measured by using the glucose oxidase technique on a Beckman Glucose II analyzer (Beckman Instruments, Brea, California). Hemoglobin A1c levels were measured by using high-performance liquid chromatography (Bio-Rad Diamat, Bio-Rad Corp., Hercules, California). Statistical Analysis We compared demographic and baseline clinical and laboratory values between the estradiol and placebo groups by using a t-test for independent samples for means or a chi-square test for proportions. At each study visit, adherence to study treatment was determined by calculating the percentage pill adherence (number of pills consumed divided by the number that should have been consumed) and by measuring estradiol levels. The average percentage pill adherence (over the entire study and by 6-month study period) and average serum estradiol levels (over the entire study) were compared between treatment groups by using a t-test for independent samples. The preplanned intention-to-treat analysis of the primary study end point, progression of subclinical atherosclerosis (def

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

The role of lipid-lowering therapy in primary and secondary prevention of ischemic heart disease continues to be debated [1]. Concerns include whether lowering lipid levels consistently inhibits or reverses the development of coronary artery lesions, influences cardiac and all-cause morbidity and mortality, and offers a prudent use of medical resources. Because ischemic heart disease remains the leading cause of death in developed countries, these are important questions. Early trials that assessed various lipid-lowering therapies reported little or no angiographic evidence of efficacy, in large part because of modest changes in serum lipids and lipoprotein levels, small sample sizes, and other methodologic problems [2-4]. However, beginning with the Cholesterol Lowering Atherosclerosis Study (CLAS), seven lipid-lowering studies with interventions ranging from multifactorial lifestyle modification, to diet and exercise or diet and either monotherapy or combination drug therapy, to ileal bypass surgery, have shown clear reductions in the progression of atherosclerotic disease or actual lesion regression [5-12], or both. In three trials, clinical coronary events were significantly reduced [7, 8, 10]. The Program on the Surgical Control of the Hyperlipidemias (POSCH), which showed that cholesterol lowering (through partial iliac bypass surgery) had a beneficial effect on coronary artery lesions [8], recently found that the 3-year global change score, an overall consensus judgment of angiographic changes in coronary lesions determined by blinded panels of experts, was predictive of subsequent coronary events (P < 0.0001), fatal coronary events (P = 0.003), and all-cause mortality (P = 0.01) over 3 to 10 years [13]. Although not in the context of a lipid-lowering trial, Waters and colleagues [14] found that patients with angiographic progression of disease at 2 years (by quantitative coronary angiography) also had a significantly increased risk for clinical coronary events during a 44-month follow-up period. In CLAS, we showed that diet in conjunction with colestipol and niacin therapy had a beneficial effect on coronary artery lesions at 2 and 4 years based on the global change score [5, 15] and at 2 years based on quantitative coronary angiography [16]; CLAS was the only angiographic trial to have used both the findings of quantitative coronary angiography and the global change score as end points. We present the results of a second angiographic trial using these two end points. The Monitored Atherosclerosis Regression Study (MARS) was a double-blind, placebo-controlled, randomized trial that tested the reduction of low-density lipoprotein (LDL) cholesterol levels using lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. We compare our results regarding the effect of reducing lipid levels on coronary artery status with those of the CLAS and POSCH trials. Methods Patients were enrolled in the study if they were younger than 70 years and had coronary artery disease in at least two segments, with at least one segment showing diameter stenosis of 50% or more (but not total occlusion) and unaltered by percutaneous transluminal coronary angioplasty. Total cholesterol levels ranged from 4.92 to 7.64 mmol/L (190 to 295 mg/dL). Major exclusion criteria included hypertension (diastolic blood pressure >115 mm Hg or, if the patient was receiving treatment, >100 mm Hg), diabetes mellitus, and the use of lipid-lowering drugs within 2 months of randomization. Women were excluded if they were premenopausal, unless they had undergone surgical sterilization. Candidates for coronary artery bypass graft surgery were excluded, but candidates for percutaneous transluminal coronary angioplasty were not. Between 1985 and 1989, 270 patients were randomly assigned within one of eight blocks, defined by sex, smoking status (current smoker or nonsmoker), and plasma total cholesterol ( 6.22 mmol/L [240 mg/dL] or >6.22 mmol/L) to receive either lovastatin, 40 mg twice a day, or placebo. Treatment groups had identical targets for cholesterol and fat intake (daily cholesterol intake 250 mg; 27% of calories as fat, with saturated fat constituting 7% of total fat calories and monounsaturated and polyunsaturated fats each accounting for 10% of fat calories). In 58% of cases, patients were recruited through cardiac catheterization laboratories and had undergone baseline coronary arteriography for clinical indications. The percutaneous femoral technique was used, and sufficient right and left anterior oblique views were obtained to show all lesions clearly [11]. During the trial, back-titration of the lovastatin dosage, which was necessary if two consecutive total cholesterol levels were less than 3.11 mmol/L (120 mg/dL) or if one total cholesterol level was less than 2.85 mmol/L (110 mg/dL), was done once for 15 patients and twice for 3 patients. To maintain the blind, the dosage for a matched placebo recipient was also back-titrated. Lipid, lipoprotein, and apolipoprotein levels were measured using standardized laboratory procedures [11]; safety laboratory tests were done; concomitant medications, drug and diet compliance [11], lenticular opacification [17], and symptoms and adverse events were assessed during the trial. A follow-up angiogram (n = 247), done 2 years after randomization, duplicated the protocol followed for the baseline angiogram, including nitroglycerin use, except in the 25 patients (8 receiving lovastatin and 17 receiving placebo) for whom nitroglycerin was required only at follow-up because of angina. Lesions in patients with a nitroglycerin mismatch were excluded from the quantitative coronary analyses. Baseline films and procedure reports, reviewed before follow-up angiography was done, ensured matching of all variables including the sequence of arteriographic projections, roentgenographic field, and catheter size. An optional double-blind 2-year extension of the original randomized therapy (MARS-II) was accepted by 70% of the patients (98 receiving lovastatin and 75 receiving placebo). Results of MARS-II have not yet been reported. Evaluation of Coronary Angiograms All evaluable film pairs (n = 246) showing identical coronary artery views, with treatment allocation and temporal order masked, were evaluated by an expert panel of two angiographers and a moderator [11, 18]. (One placebo recipient did not have an evaluable angiogram by panel procedures.) Using the first film, the panel reached a consensus on lesion identification and percent diameter stenosis, and these data were recorded by the moderator. Using the second film, the panel reached a consensus on the degree of change in each lesion and obtained a global change score (0 [no demonstrable change] to 3 [extreme change]) that integrated panel-based visual changes. A direction for change (- for regression, + for progression) was subsequently assigned by the study statistician when the temporal blind was broken. Quantitative coronary angiography analyses were done by a single technician blinded to treatment but not to temporal ordering [11, 19]. Film pairs (n = 220) were processed in tandem using dual projectors to match frames for orientation and degree of contrast filling, and arterial segments were defined from branch to branch. Three sequential frames exposed during end-diastole were digitized when possible; if such a sequence was unavailable, three sequential frames from other phases of the cardiac cycle were digitized. The right anterior oblique view was preferred for the quantitative coronary angiography analysis, but other views were substituted if they were superior. Percent diameter stenosis and minimum lumen diameter were measured in each lesion identified by the panel and in lesions identified by the quantitative coronary angiography analyst but not by the panel; these latter lesions tended to be in smaller segments and were less severe. Edge coordinates were corrected for pin-cushion distortion (artifactual coronary artery edge distortion seen in angiographic films) measured from the image of a 1-cm anteroposterior grid filmed at the beginning of each angiogram. Each end point was averaged over three sequential frames. The primary end point was the average (per-patient) change from baseline in percent diameter stenosis in all lesions that showed 20% stenosis at baseline or at follow-up as evaluated by quantitative coronary angiography. Power calculations based on this end point (and standard deviations estimated to be in the range of 6% to 8%) indicated that an effective sample size of 250 patients had at least an 80% power to detect a treatment difference of 2% to 3% in diameter stenosis at the 0.05 significance level (two-sided) [11]. Three equally weighted secondary end points were average (per-patient) change in minimum lumen diameter (assessed by quantitative coronary angiography), the global change score (assessed by the panel), and the proportion of patients with progression or regression of disease (assessed by quantitative coronary angiography). A patient defined as having progression or regression had lesion change of one type only, either progressing or regressing, but not both types; a patient with a mixed lesion response (that is, with both progressing and regressing lesions) was considered unchanged. A progressing or regressing lesion was defined by a change in percent diameter stenosis of 12% or greater. This cutoff is equal to twice the standard deviation (5.7%) elicited by analysis of repeated angiograms (at the beginning and end of the same angiographic session) of the same lesion in 17 patients (55 lesions) in the MARS study. New lesions and new total occlusions were not counted as progressing lesions; recanalizations were not counted as regressing lesions. Analyses of change in both percent diameter stenosis and minimum lumen diameter were specified a priori for large ( 50% at baseline) lesions [11]. Fo

Alpha-Tocopherol Supplementation in Healthy Individuals Reduces Low-Density Lipoprotein Oxidation but Not Atherosclerosis The Vitamin E Atherosclerosis Prevention Study (VEAPS)

Background—Epidemiological studies have demonstrated an inverse relationship between vitamin E intake and cardiovascular disease (CVD) risk. In contrast, randomized controlled trials have reported conflicting results as to whether vitamin E supplementation reduces atherosclerosis progression and CVD events. Methods and Results—The study population consisted of men and women ≥40 years old with an LDL cholesterol level ≥3.37 mmol/L (130 mg/dL) and no clinical signs or symptoms of CVD. Eligible participants were randomized to DL-&agr;-tocopherol 400 IU per day or placebo and followed every 3 months for an average of 3 years. The primary trial end point was the rate of change in the common carotid artery far-wall intima-media thickness (IMT) assessed by computer image-processed B-mode ultrasonograms. A mixed effects model using all determinations of IMT was used to test the hypothesis of treatment differences in IMT change rates. Compared with placebo, &agr;-tocopherol supplementation significantly raised plasma vitamin E levels (P <0.0001), reduced circulating oxidized LDL (P =0.03), and reduced LDL oxidative susceptibility (P <0.01). However, vitamin E supplementation did not reduce the progression of IMT over a 3-year period compared with subjects randomized to placebo. Conclusions—The results are consistent with previous randomized controlled trials and extend the null results of vitamin E supplementation to the progression of IMT in healthy men and women at low risk for CVD.

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.

Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial

BACKGROUND There is serological and epidemiological evidence of an association between Chlamydia pneumoniae infection and coronary artery disease. Results of previous smaller studies have indicated a reduction of recurrent ischaemic events in patients with acute coronary syndrome when given macrolide antibiotics. We aimed to assess whether short-term treatment with the macrolide antibiotic azithromycin reduces recurrent ischaemic events in patients admitted for unstable angina or myocardial infarction. METHODS We assessed the effect of azithromycin in a multicentre, double-blind randomised trial in 1439 patients with unstable angina or acute myocardial infarction. Patients were randomly allocated to receive 500 mg azithromycin on the first day after randomisation, followed by 250 mg daily for 4 days or placebo. Patients were followed up for 6 months. The primary endpoints were death, recurrent myocardial infarction, or recurrent ischaemia necessitating revascularisation. Analysis was done by intention to treat. FINDINGS Treatment with azithromycin did not result in reduction of either individual endpoints or any of the primary endpoints. Of the 716 patients in the azithromycin group, 23 (3%) died, 17 (2%) developed myocardial infarction, 65 (9%) had recurrent ischaemia needing revascularisation, and 100 (14%) had one or more of these endpoints. In the placebo group (n=723) the corresponding numbers of patients were 24 (4%), 22 (3%), 59 (8%), and 106 (15%), respectively (p=0.664, 95% CI 0.72-1.24). 62 (9%) of patients in the azithromycin group and 59 (8%) in the placebo group reached the secondary endpoint of ischaemia or congestive heart failure necessitating admission (difference 0.5%, 95% CI 0.75-1.53; p=0.707). We recorded few side-effects. INTERPRETATION Short-term treatment with azithromycin does not reduce development of recurrent events in patients with acute coronary syndrome.

Impaired fibrinolysis in coronary artery disease

We assessed endogenous endothelial-dependent fibrinolysis in 99 subjects with coronary artery disease (CAD) documented by angiography and in 28 control subjects with normal coronary arteries on angiography. We used specific, sensitive assays for plasma tissue-type plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor (PAI) activity, plasminogen, and alpha-2 plasmin inhibitor (alpha-2 PI). Mean PAI activity was significantly higher, and mean t-PA activity after venous occlusion of the upper arm (a standard test of the capacity of vascular endothelium to release t-PA) was significantly lower in subjects with CAD than in subjects with normal coronary arteries. The mean increment in t-PA antigen after venous occlusion was significantly lower than normal in subjects with CAD with onset of symptoms before age 45 years. Subjects with CAD had a significantly increased mean plasma fibrinogen level compared with control subjects, and a significant positive correlation was observed between PAI activity and plasma fibrinogen in subjects with CAD. No significant abnormalities of plasminogen or alpha-2 PI were observed in any subset of subjects with CAD. These data support an association between impaired fibrinolysis and CAD, with contributions from both increased PAI activity and in younger subjects from reduced endothelial t-PA release.

High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis A Randomized Controlled Trial

Background and Purpose— Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression. Methods— In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 &mgr;mol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B12+50 mg vitamin B6) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome). Results— Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy ≥9.1 &mgr;mol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 &mgr;mol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups. Conclusion— High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin “replete” individuals at low risk for cardiovascular disease with a fasting tHcy ≥9.1 &mgr;mol/L.

Prevalence of subclavian artery stenosis in patients with peripheral vascular disease

Internal mammary arteries (IMA) as conduits in coronary artery bypass grafting are superior to saphenous vein grafts. If there is subclavian artery stenosis (SAS) proximal to the IMA graft, impairment of flow to the IMA may occur. If the stenosis is severe, retrograde flow from the grafted coronary artery to the brachial artery may lead to angina. Following the identification of 2 cases of angina secondary to subclavian artery stenosis at their institution, the authors prospectively performed arch angiography in a cohort of patients with manifestations of periph eral vascular disease undergoing diagnostic coronary angiography to assess the prevalence of subclavian stenosis. Fifty-two patients were enrolled in the protocol, with 48 patients having technically acceptable studies. Of these 48, 41.6% had measurable stenosis of at least one of the brachiocephalic arteries, with 35% of patients with at least a 30% stenosis of the left subclavian artery and 18.7% with more than 50% stenosis. They conclude that patients with significant peripheral vascular disease undergoing coronary angiography who are potential candidates for revascularization may benefit from arch angiography as part of their initial evaluation.

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.

SCLERODERMA: RELATION OF PULMONARY CHANGES TO ESOPHAGEAL DISEASE

Excerpt Scleroderma is a systemic disease involving the collagenous tissues. The skin, gastrointestinal tract, and the cardiovascular, musculoskeletal, genitourinary and pulmonary systems may be in...