Risk factors in patients undergoing a second aorta-coronary bypass procedure

Risk factors in patients undergoing a second aorta-coronary bypass procedure A group of 38 patients with a second revascularization procedure was studied for factors which may have contributed to the reappearance of angina after the first operation. Our data indicate that these patients usually have the first operation at an earlier age and had fewer bypasses at that time. In addition, they had inadequate control of the plasma triglyceride and cholesterol levels.

Joseph J. Barboriak, Sc.D., Daniel P. Barboriak, Alfred J. Anderson, M.S., Alfred A. Rimm, Ph.D., Felix E. Tristani, M.D., and Robert J. Flemma, M.D., Milwaukee and Wood, Wis.

/xorta-coronary bypass has become an accepted treatment for obstructive coronary artery disease. The procedure offers long-term relief from angina pectoris in most patients.1' 2 A small group of patients, however, have experienced recurrence of angina at various times after the operation, and some patients have subsequently had secondary revascularization. These patients have had occlusion of the vein grafts or progression of atherosclerosis in their coronary arteries as verified by angiography.3~7 This study compares 38 patients having two operations with 1,769 patients having only one operation. The findings indicate that there were differences between these two patient populations. Methods A group of 38 male patients, who had a second revascularization procedure owing to reappearance of angina after the first operation, were included in the study. Five of these patients had the second procedure within the first year after operation, 15 patients were From the Departments of Pharmacology, Preventive Medicine, Medicine, and Surgery, The Medical College of Wisconsin, Milwaukee, Wis., and the Research, Medicine, and Surgical Services, Veterans Administration Center, Wood (Milwaukee), Wis. Supported in part by the National Institute of Health, Grant HL 14378. Also supported by the Medical Research Service of the Veterans Administration. Received for publication Dec. 14, 1977. Accepted for publication March 13, 1978. Address for reprints: Joseph J. Barboriak, Sc.D., Research Service/ 151, Veterans Administration Center, Wood, Wis. 53193.

reoperated upon between 1 and 3 years after the first operation, and the remaining 18 had reoperation more than 3 years after their first bypass. For comparison, we have included data on 1,769 men who had one aortacoronary bypass operation. All patients were operated upon between 1970 and 1975. The study was confined to men, since women comprised less than 20 percent of the total patient population, and their number was not sufficient for statistical analysis. To be considered candidates for the operation, the patients had to have angina pectoris and at least 75 percent occlusion of the left main or left anterior descending coronary artery or else they had to have involvement of several coronary artery branches. Coronary arteriography was performed by the techniques of Judkins8 or Sones and Shirey,9 and the findings were reviewed by experienced cardiologists. The degree of coronary occlusion was expressed as suggested by Rowe and associates,10 except that the scale was inverted; that is, a score of 0 indicated no coronary obstruction and a score of 300 indicated complete obstruction of the three coronary arteries. The left ventricular function (L VF) was graded on a scale of 1 to 6, with 1 denoting normal function and 6 denoting aneurysms or severe dyskinesia of at least two segments of one or both walls. Information on the reappearance of angina, height and weight changes, blood pressure, and smoking was obtained by direct questioning or by measuring the patients. Fasting levels of plasma cholesterol and triglycerides were determined by routine procedures11, 12 which, in our laboratory, have passed the requirements of the Lipid Standarization Program of the Center for Disease I1 1

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1 1 2 Barboriak et al.

Table I. Probable cause of reappearance of angina in 24 patients with a second aorta-coronary bypass operation Patients Probable cause

No.

Percent

Graft failure alone Progression of disease alone Insufficient revascularization alone Graft failure and progression of disease Progression of disease and insufficient revascularization Graft failure, progression of disease, and insufficient revascularization

7 4 2 5 3

29 17 8 21 13

3

13

Control, Atlanta, Georgia. These determinations were carried out before the first operation, at approximately 1 year intervals following the operation, and at the time of each repeat coronary arteriography. Lipoprotein analysis was based on the pattern of electrophoretic separation of fresh plasma on agarose.13 Lipoprotein pattern HI was confirmed by the absence of the beta lipoprotein band on disc electrophoresis.14

Table II. Information on the age, occlusion score, average number of grafts, and other hemodynamic variables of patients who eventually had a second revascularization operation One operation (N = 1,769) Age (yr.) Occlusion score LVEDP (mm. Hg) Left ventricular function No. of grafts Proportion of patients with— One graft (%) Two grafts (%) Three grafts (%) Four grafts (%) Graft flow <40ml./min. (%) Graft flow 3=40ml./min. (%) Myocardial infarction

(%)

Diabetes (%)

53 192 11.5 2.6

± 7* ± 55 ± 5.6 ± 1.6 2.4

Two operations (N = 38) 49 187 10.2 1.9

P Value

± 1 ± 53 ± 5.2 ± 1.1 1.9

<0.01 NS NS <0.05 <0.01

18 40 30 12 25

41 351 22 3) 44

<0.01

<0.05

75

56

<0.05

65

62

NS

11

17

NS

<0.05

Results

Legend: LVEDP, left ventricular end-diastolic blood pressure. NS, not significant. •Mean ± standard deviation.

Data for patients with multiple operations were reviewed in an attempt to categorize the cause of recurrent angina (Table I). Vein graft failure, defined as more than 90 percent occlusion of any graft, was seen in 15 of 24 patients for whom these data were available. Progression of the original coronary artery disease, defined as 75 percent occlusion of one artery which was not obstructed at the time of initial arteriography and ungrafted at surgery, or 50 percent occlusion of two such arteries, was seen in 15 of 24 patients. Insufficient revascularization, defined as the absence of graft to a coronary artery and more than 75 percent occlusion of the lumen, was recorded for eight patients. The data on average age and some hemodynamic variables of the patients are illustrated in Table II. At the time of the initial operation, the patients who eventually had a second revascularization were, on the average, 4 years younger than the group with only one operation (49 versus 53 years, p < 0.01). Although the initial average coronary artery occlusion scores did not show a significant difference, patients who had a second operation originally had fewer multiple bypasses, as reflected in the average number of grafts (1.9 versus 2.4 percent, p < 0.001), and a higher percentage of procedures involving only one bypass graft (41 versus

18 percent, p < 0.01). The group with two operations also had a higher prevalence of grafts with low blood flow rate (44 versus 25 percent with flow rates less than 40 ml. per minute, p < 0.05). There was no marked difference between the groups in the prevalence of previous myocardial infarction (65 versus 62 percent). The initial left ventricular function (LVF) of patients who subsequently had a second revascularization procedure was less impaired than the LVF of patients with only one operation. It is probable that this finding reflects the more vigorous selection process applied to the candidates for a second operation. Information on the prevalence of risk factors such as hypertension, hyperlipidemia, or a history of smoking, as determined at follow-up visits after bypass (average interval 16 months) is shown in Table III. The main difference in risk factors was confined to plasma lipid levels. Both plasma cholesterol and triglyceride levels in the group with two operations were higher than in patients with only one operation. This difference is also reflected in the prevalence of abnormal lipoprotein distribution: Three times as many patients with two operations had lipoprotein type IV as compared to patients with one operation (60 versus 21 percent, p < 0.01). The patients with two operations

Volume 76 Number 1 July, 1978

also had a somewhat higher diastolic blood pressure (82 versus 76 mm. Hg, p < 0.05) when measured after the first operation.

Table ID. Information on the prevalence of some risk factors in patients with one or two aortacoronary bypass operations*

Discussion The findings of the present study suggest that the patients who eventually had a second revascularization procedure exhibited certain common features which tended to be different in kind or degree from similar features in patients with only one bypass operation. 1. The patients having two operations had the first bypass operation at a younger age than the other group, a fact which indicates a predilection for earlier development of coronary artery disease. A similar tendency to have the first operation at a younger age has been reported previously for other series of patients with a second revascularization procedure. 4,6 A tendency toward more frequent vein graft occlusion also has been observed in young patients having femoropopliteal vein bypass surgery.15 One may assume that these patients are probably a priori at a higher risk of progression of the vascular disease. 2. Our data indicate that a higher proportion of the patients requiring repeat revascularization had an inadequate initial revascularization, as reflected in the average number of bypasses. It has been our experience16 and that of other investigators17 than an inadequate number of grafts is usually associated with a higher prevalence of postoperative complications and graft closures. 3. The group who eventually had a second operation experienced lower blood flow in the vein grafts, with 44 percent of the grafts having a flow rate of less than 40 ml. per minute. Reports from this18 and other institutions19 have indicated that a low blood flow rate may be one of the most significant predictors of vein graft failure. 4. The patients requiring reoperation had markedly elevated plasma lipid levels. Reports in the literature have suggested that consistently elevated plasma lipid levels may be associated with the development of atherosclerotic lesions in the vein graft itself.20 In the over-all evaluation, it would appear that the main factors predisposing the patients to the need of a second revascularization are, to a large extent, correctable or are being corrected as more data and experience on the outcome of aorta-conary bypass are accumulated. As single bypass procedures are becoming exceptions, the proportion of patients with inadequate revascularization is being reduced. However, the data

11 3

Repeat revascularization

Blood pressure (mm. Hg) Systolic Diastolic Plasma cholesterol (mg./dl.) Plasma triglycerides (mg./dl.) Lipoprotein type (%) II IV Normal Smoking, ever (%) Smoking, now (%)

One operation (N = 1,769)

Two operations (N = 38)

P Value

128 + 20t 76 ± 12 226 ± 48

130 ± 13 82 ± 9 254 ± 60

NS <0.05 <0.01

151 ± 109

312 ± 303

<0.01

6 21 72 83 19

12 60 28 83 17

NS <0.01 <0.01 NS NS

♦Values for both groups obtained approximately 16 months after the first bypass operation. tMean ± standard deviation.

from this and other studies20 indicate that the possible contributory role of elevated blood lipid levels to the late vein graft complications has not been sufficiently recognized or that adequate measures for control of blood lipid levels were not instituted. In view of the observation that more than 50 percent of vein graft biopsies obtained at a second revascularization procedure had extensive atherosclerotic lesions,21 a program of strict control of elevated blood lipid levels, including attention to the compliance with suggested dietary and pharmacologic measures, appears worthy of undertaking. We appreciate the interest and support of the members of the Milwaukee Cardiovascular Data Registry and the assistance of Steven Blumlein, M.D. REFERENCES 1 Manley JC, Johnson WD: Effects of surgery on angina (pre- and postinfarction) and myocardial function (failure). Circulation 46:1208-1221, 1972 2 Anderson RP, Shahbudin HR, Bonchek LI, et al: The prognosis of patients with coronary artery disease after coronary bypass operations. Circulation 50:274-282, 1974 3 Johnson WD, Hoffman JF Jr, Flemma RJ, Tector AJ: Secondary surgical procedure for myocardial revascularization. J THORAC CARDIOVASC SURG 64:523-529, 1972 4 Stiles QR, Lindesmith GG, Tucker BL, Hughes RK, Meyer BW: Experience with fifty repeat procedures for

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myocardial revascularization. J THORAC CARDIOVASC SURG 72:849-853, 1976

5 Irarrazaval MJ, Cosgrove DM, Loop FD, Ennix CL Jr, Groves LK, Taylor PC: Reoperations for myocardial revascularization. J THORAC CARDIOVASC SURG 73:181-

188, 1977 6 Winkle RA, Alderman EL, Shumway NE, et al: Results of reoperation for unsuccessful coronary artery bypass surgery. Circulation 52:61-65, 1975 7 Keon WJ, Bedard FP, Akyurekli Y, et al: Experience with reoperation following coronary artery bypass grafting. Can J Surg 20:142-146, 1977 8 Judkins MP: Selective coronary radiography. A percutaneous transfemoral technic. Radiology 89:815-824, 1967 9 Sones FJ, Shirey EK: Cine coronary arteriography. Mod Cone Cardiovasc Dis 31:735-738, 1962 10 Rowe GG, Thomsen JH, Stenlund RR, et al: A study of hemodynamics and coronary blood flow in men with coronary artery disease. Circulation 39:139-148, 1969 11 Block WD, Jarret JK, Levine JB: Ues of a single color reagent to improve the automated determination of serum total cholesterol, Automation in Analytical Chemistry, Lt Skeggs, Jr, New York, 1965, Mediad, pp 345-347 12 Kessler G, Lederer H: Fluorometric measurement of triglycerides, Automation in Analytical Chemistry, Lt Skeggs, Jr, New York, 1965, Mediad, pp 341-344

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13 Noble RP: Electrophoretic separation of plasma lipoproteins in agarose gel. J Lipid Res 9:693-700, 1968 14 Frings CS, Foster LB, Cohen PS: Electrophoretic separation of serum lipoproteins in polyacrylamide gel. Clin Chem 17:111-114, 1971 15 Bouhoutsos J, Martin P: The influence of age on prognosis after arterial surgery for atherosclerosis of the lower limb. Surgery 74:637-640, 1976 16 Rimm AA, Blumlein S, Barboriak JJ, et al: The probability of closure in aortocoronary vein bypass grafts. JAMA 236:2637-2640, 1976 17 Stiles QR, Lindesmith GG, Tucker BL, et al: Long-term follow-up of patients with coronary artery bypass grafts. Circulation 54:32-34, 1976 18 Walker JA, Friedberg HD, Flemma RJ, et al: Determinants of angiographic patency of aortocoronary vein bypass grafts. Circulation 46:86-90, 1972 19 Sheldon WC, Loop FD: Direct myocardial revascularization-1976. Clev Clin Q 43:97-108, 1976 20 Barboriak JJ, Pintar K, Koms ME: Atherosclerosis in aortocoronary vein grafts. Lancet 2:621-624, 1974 21 Pintar K, Barboriak JJ, Korns ME, et al: Progression of degenerative damages in aortocoronary vein grafts. Progr Biochem Pharmacol (in press)