Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group.

OBJECTIVE: Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. DESIGN: The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. SETTING: Three university hospitals and one private primary care facility. PATIENTS: A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. INTERVENTION: The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. MAIN OUTCOME MEASURE: The use of arteriographic changes as a predictor of subsequent clinical coronary events. RESULTS: Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). CONCLUSIONS: Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality.

Evaluation of human panelists in assessing coronary atherosclerosis.

The Cholesterol Lowering Atherosclerosis Study, a randomized, angiographic clinical trial, has demonstrated the beneficial effect of niacin/colestipol therapy on coronary and femoral atherosclerosis. The primary outcome was a panel-determined consensus score evaluating global coronary changes determined angiographically at 2 years. This article presents an evaluation of interreader agreement in independently assessing the status of native coronary arteries and overall coronary condition. Parameters include 1) identification of the presence of lesions and lesion changes; 2) estimation of lesion severity (percent stenosis) and amount of change in lesion severity; and 3) global assessment of change in coronary status. Readers independently agreed on 1) presence of lesions (82%) and change in lesions (51%); 2) percent stenosis +/- 10% (76%) and change in stenosis +/- 10% (81%); and 3) global assessment of change in coronary status within one step (96%). Results of these analyses may be useful in effectively designing angiographic trials that use a panel of human evaluators as well as computerized methods for angiographic interpretation.

Effects of colestipol-niacin therapy on human femoral atherosclerosis.

The 2-year therapy effect on femoral atherosclerosis was evaluated in the Cholesterol Lowering Atherosclerosis Study (CLAS), a randomized, placebo-plus-diet-controlled angiographic trial of colestipol-niacin therapy plus diet in men with previous coronary bypass surgery. Different diet compositions were prescribed to enhance the differential in blood cholesterol responses between the two groups. The annual rate of change in computer-estimated atherosclerosis (CEA), a measure of lumen abnormality, was evaluated between treatment groups. A significant per-segment therapy effect was found in segments with moderately severe atherosclerosis (p less than 0.04) and in proximal segments (p less than 0.02). When segmental CEA measures were combined into a per-patient score using an adaptation of the National Heart, Lung, and Blood Institute scoring procedure, a significant therapy effect was observed (p less than 0.02). Total variance of the annual change rate in CEA was as predicted from pilot studies, but measurement variation was larger. The therapy effect observed in femoral arteries, although significant, was less marked than the strong and consistent benefit previously reported for both native coronary arteries and aortocoronary bypass grafts.

Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up.

The Cholesterol Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol-niacin therapy in 162 subjects. Two-year results (CLAS-I) showed decreased atherosclerosis progression and increased regression. We now describe a subgroup of 103 subjects treated for 4 years (CLAS-II). Changes in blood lipid, lipoprotein-cholesterol, and apolipoprotein levels were maintained, and at 4 years significantly more drug-treated subjects demonstrated nonprogression (52% drug- vs 15% placebo-treated) and regression (18% drug- vs 6% placebo-treated) in native coronary artery lesions. Significantly fewer drug-treated subjects developed new lesions in native coronary arteries (14% drug- vs 40% placebo-treated) and bypass grafts (16% drug- vs 38% placebo-treated). These results confirm CLAS-I findings and indicate that regression can continue for 4 years. They reaffirm the need for early initiation of vigorous long-term lipid lowering therapy in coronary bypass subjects.

Gender differences in coronary angiographic findings from 1972 through 1981 in Los Angeles, California.

The angiographic findings of 930 men and 257 women who were referred to a Los Angeles County hospital from 1972 through 1981 are compared. Chi square test results indicated triple-vessel disease was more common in men (37.1%) compared with women (18.7%). The prevalence of normal angiographic findings was higher in women (23.3%) than in men (8.1%). However, for men and women with evidence of coronary artery disease, virtually identical percentages of subjects had left main, single-, double-, and triple-vessel disease. Although the incidence of coronary artery disease decreased during this time for the Los Angeles population as a whole, no differences in patterns of coronary vessel lesions were evidenced.

The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results.

The Cholesterol Lowering Atherosclerosis Study (CLAS) is a prospective, placebo-controlled, angiographic trial designed to test the hypothesis that aggressive lowering of LDL cholesterol with concomitant increase in HDL cholesterol will reverse or retard the atherosclerotic process. Specifically, CLAS was designed to determine whether combined therapy with colestipol plus niacin will produce clinically significant change in coronary, carotid, and femoral artery atherosclerosis and coronary bypass graft lesions. To this purpose, 188 subjects were randomized to diet plus drug or diet plus placebo. We report on methodological aspects of planning and evaluating this study, including the choice of the study population, procedures for recruitment, the experimental design including sample size considerations, methods for evaluating outcome, and methods for evaluating compliance to treatment. Comparison of baseline data indicated no significant differences between groups at the time of randomization. Subjects were predominantly male, Caucasian, 54 years of age, 20% above ideal weight, with normal blood pressure. The average age at bypass was 50 years. The average lipids were cholesterol (243 mg/dL), HDL (45 mg/dL), and LDL (168 mg/dL). Finally, the distribution of baseline coronary stenosis was equivalent between the two groups (average number of lesions per subject = 10.6).

Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts.

The Cholesterol-Lowering Atherosclerosis Study (CLAS) was a randomized, placebo-controlled, angiographic trial testing combined colestipol hydrochloride and niacin therapy in 162 nonsmoking men aged 40 to 59 years with previous coronary bypass surgery. During two years of treatment there was a 26% reduction in total plasma cholesterol, a 43% reduction in low-density lipoprotein cholesterol, plus a simultaneous 37% elevation of high-density lipoprotein cholesterol. This resulted in a significant reduction in the average number of lesions per subject that progressed (P less than .03) and the percentage of subjects with new atheroma formation (P less than .03) in native coronary arteries. Also, the percentage of subjects with new lesions (P less than .04) or any adverse change in bypass grafts (P less than .03) was significantly reduced. Deterioration in overall coronary status was significantly less in drug-treated subjects than placebo-treated subjects (P less than .001). Atherosclerosis regression, as indicated by perceptible improvement in overall coronary status, occurred in 16.2% of colestipol-niacin treated vs 2.4% placebo treated (P = .002).

Electrocardiographic and vectorcardiographic diagnosis of posterior wall myocardial infarction. Significance of the T wave.

The electrocardiographic diagnosis of posterior wall myocardial infarction remains elusive. To determine discriminating criteria a group of 27 patients with posterior infarction proven by biplane angiocardiography were compared to 97 controls. All patients had single-vessel obstruction of the circumflex artery or one of its major branches (greater than or equal to 75 percent area stenosis) without occlusive disease in the other coronary arteries. High-frequency, high-gain electrocardiograms and Cube and McFee vectorcardiograms were analyzed. Pathologic Q waves in the inferior leads were present in only 22 percent (six) of the patients; increased R-wave amplitude or duration in the right precordial leads was found in 17 to 26 percent, and an R/S ratio greater than or equal to I in lead V1 or greater than or equal to 1.5 in lead V2 was present in 22 percent (six) of patients. Vectorcardiographic criteria which improved the diagnostic yield were: (1) the presence of a QRS loop mostly anterior to the E point, and (2) the presence of an abnormally anterior T wave. This abnormal T-wave shift was present in over 70 percent of the patients with posterior infarctions and was clearly discernible from the 12-lead ECG, as manifested by tall T waves in lead V2 and flat T waves in lead V6. To approximate the T-wave angle in the 12-lead scalar ECG, an index was calculated by subtracting the amplitude of the T wave in lead V6 from its amplitude in lead V2 (T2-T6 index). An index of 0.38 mV or more yielded a sensitivity of 81 percent and a specificity of 75 percent; however, this was not as discriminating as the vectorcardiogram where a T angle of 60 degrees or more in the horizontal plane yielded a sensitivity of 70 percent and a specificity of 97 percent.

Accelerated progression of atherosclerosis in coronary vessels with minimal lesions that are bypassed.

Accelerated progression of atherosclerosis is known to occur in surgically bypassed coronary arteries in which the preoperative stenosis was greater than 50 per cent. To assess the effect of coronary bypass on vessels with lesser degrees of stenosis, we studied 85 men who had undergone coronary bypass surgery. In this group we identified bypass grafts placed in 37 arteries with minimal atherosclerosis, which was defined as less than 50 per cent stenosis of the vessel diameter. In the same 85 men there were 93 coronary vessels with minimal atherosclerosis for which a bypass graft had not been placed. Progression of atherosclerosis, defined as further loss of at least 25 per cent of the lumen, during an average follow-up period of 37 months was more than 10 times as frequent (38 per cent vs. 3 per cent) in bypassed arteries with minimal atherosclerosis as in comparable arteries that were not bypassed. These findings support the view that minimally diseased coronary arteries should not be bypassed.

Computerized edge tracking and lesion measurement in coronary angiograms. A pilot study comparing smokers with non-smokers.

Comparison of coronary atherosclerosis change in a pilot angiographic study of retrospectively matched smokers and controls indicates more rapid progression in smokers. The findings indicate the feasibility of small-scale angiographic trials of treatment designed to ameliorate arterial damage in atherosclerotic smokers who cannot quit.

Reversal of exercise-induced hemodynamic and electrocardiographic abnormalities after coronary artery bypass surgery.

Forty patients (35 men and five women) who experienced hypotension during maximal symptom-limited exercise test were retested after a 12 +/- 4-month interval. Mean age was 53.5 years. All patients had multiple-vessel disease. Seventeen patients underwent coronary artery bypass surgery because of disabling angina, and 23 patients without disabling angina continued under medical management. At entry, there were no significant differences in age, left ventricular function or exercise performance between the medical and surgical groups. At follow-up, the surgical group showed an average increase in the exercise duration of 2.2 +/- 1.7 minutes (p less than 0.001), maximal heart rate of 17 +/- 15 beats/min (p less than 0.001), maximal systolic blood pressure of 26 +/- 23 mm Hg (p less than 0.001) and maximal rate-pressure product of 60 +/- 41 (p less than 0.001). These measurements did not change significantly in the medically managed group. Exercise-induced hypotension is apparently caused by ischemic left ventricular dysfunction, since in the majority of patients, it is reversible after successful revascularization. This observation is supported by the lack of improvement in a comparable group of patients managed without surgery.

Abnormal blood pressure response and marked ischemic ST-segment depression as predictors of severe coronary artery disease.

The usefulness of an abnormal blood pressure response and a marked ischemic ST-segment depression during exercise testing as predictors of severe coronary artery disease was assessed in 378 consecutive patients who had a maximal symptom-limited exercise test before coronary arteriography. An abnormal blood pressure response occurred in 90 patients. The sensitivity of this response for three-vessel or left main disease was 38.6%, the specificity 87.4% and the predictive value 70%. A marked ischemic ST-segment abnormality (MIST) appeared in 85 patients. The sensitivity of MIST for three-vessel or left main disease was 38.6%, the specificity 89.8% and the predictive value 74.1%. One hundred thirty-eight patients had either an abnormal blood pressure response or a marked ST-segment change. The sensitivity of either response for three-vessel or left main disease was 56.4%, the specificity 78.6%, and the predictive value 66.7%. Exercise duration and ejection fraction were not significantly different in patients with normal or abnormal blood pressure. We conclude that abnormal blood pressure and marked ischemic ST-segment depression during exercise testing are helpful in identifying a subset of patients with advanced coronary artery disease. The physiologic mechanism for these responses is probably exercise-induced ischemia.

Long-term effects of physical training on coronary patients with impaired ventricular function.

Eighteen patients with coronary heart disease and an ejection fraction of 0.40 or less were entered into an individualized exercise training program. Maximal symptom-limited exercise stress test and cardiac catheterization studies were performed initially and 12--42 months (average 18.5 months) after exercise training. At the time of the follow-up study, the mean functional aerobic impairment (FAI) improved from 32.1 to 23.4% (p less than or equal to 0.01); resting and submaximal heart rates were significantly lower (p less than 0.01 and 0.05, respectively). There was no significant change in the pulmonary artery or left ventricular end-diastolic pressure, cardiac index, stroke index, left ventricular end-diastolic volume or ejection fraction. Exercise training, therefore, can be beneficial even for patients with impaired ventricular function. Increase in physical work capacity was not correlated with improvement of ventricular function; on the other hand, exercise training did not cause deterioration of ventricular function.

Spatial reconstruction of human femoral atheromas showing regression.

Reports of atherosclerotic changes in human subjects previously described have been based on evaluation of arteriographic edge contours. They imply unchanged roentgenographic and physiologic conditions, including identical patient positioning and vascular tone which cannot always be obtained in sequential studies. We have previously described the development of quantitative angiographic densitometry which permits measurement of vascular cross-sectional chord length distributions and areas, independent of rotational changes in vascular position. In this paper we report on application of the method to sequential femoral angiograms in two patients in whom there were significant increases in vascular cross-sectional area after a program of exercise and risk reduction. The method excludes interpretive errors due to circumferential changes in vascular tone.

Reproducibility of a consensus panel in the interpretation of coronary angiograms.

This report describes the consistency of coronary angiogram evaluation by a four man panel of experts rendering "consensus opinion." The panel evaluated films from 38 patients at two grading sessions separated by an interval of seven months. Fourteen patients' films were selected at random for duplicate evaluation. These contained 186 lesion sites. The panel was 95% consistent in designating significant stenosis (greater than or equal to 70%). "Consensus" panel reading appears more consistent than "group opinion" panel reading. The over-all standard deviation of the difference in panel reading was 14%. The panel was most consistent in evaluating the right coronary artery, proximal LAD, and proximal circumflex. In the left main segment two of fourteen duplicate evaluations showed major discrepancy.