Myocardial Revascularization in Women

Myocardial Revasdarkation in Women Denis H. Tyras, M.D., Hendrick B. Barner, M.D., George C. Kaiser, M.D., John E. Codd, M.D., Hillel Laks, M.D., and Vallee L. Willman, M.D.

ABSTRACT During the period January, 1970, through June, 1977, 1,541 patients underwent coronary artery bypass grafting; 241 of them were women (15.6%). Operative mortality rates for the entire study were 2.4% in men and 3.7% in women, but they showed a marked decline in women during 1975 to mid-1977, with only 2 deaths in 140 patients (1.4%). Women comprised a larger percentage of patients (16.7%) in these later years. Women were slightly older, received fewer grafts, had better preservation of ventricular function on preoperative studies, and had more severe anginal symptoms than men. Patency rates were significantly lower in women at 1 month, 1 year, and 3 years. Five-year survival was not significantly different between women (88.3%) and men (93.5%). Many of these findings may be explained on the basis of women having smaller coronary arteries than men. These favorable results differ from earlier reports of higher mortality rates in women and indicate that myocardial revascularization should not be withheld from female patients.

Despite increasing utilization of myocardial revascularization in the treatment of symptomatic coronary artery disease, the impression in many centers remains that women attain far less favorable results from this operative intervention than men. Reports [l,3,8] indicate that women have higher operative mortality rates, increased incidence of perioperative infarction, strikingly lower graft patency rates, and less favorable long-term symptomatic relief of angina. This study reviews our 7%-year experience with coronary artery bypass grafting in women.

From the Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO. Presented at the Twenty-fourth Annual Meeting of the Southern Thoracic Surgical Association, Nov 3-5, 1977, Marco Island, FL. Address reprint requests to Dr. Tyras, Department of Surgery, Saint Louis University School of Medicine, 1325 S Grand Blvd, St. Louis, MO 63104. 449 0003-4975/78/0025-0511$1.25@ 1978 by Denis H. Tyras

Materials and Methods From January, 1970, to June 30, 1977, 1,541 patients had direct coronary artery bypass grafting for the treatment of coronary artery disease; 1,300 were men, and 241 were women. The records of these patients were reviewed, and follow-up data were compiled from chart review, patient interview or examination, and physician contact. Follow-up ranged between 5 and 94 months postoperatively (average, 33.6 months). Patients undergoing concomitant valve replacement, septa1defect repair, ventricular aneurysmectomy or plication were excluded from the study. Preoperative ventricular function, as determined by contrast ventriculography, was graded as normal, mildly impaired, moderately impaired, or severely impaired based on the overall ejection fraction and on the contractility of six ventricular segments viewed in the right anterior oblique projection. Coronary artery size was determined at the time of operation with calibrated intraluminal probes. Perioperative infarction rates were determined by analysis of electrocardiograms and cardiac isoenzymes [51. Women were significantly older than men (53.9 vs 52.1 years) (Table 1).There were significantly higher percentages of female patients with Class 3 or 4 angina* (89.7 vs 79.8%); women had better preservation of ventricular function on preoperative studies, with normal or only mildly impaired ventricular function (77.7 vs 68.7%). Women had significantly lower incidences of previous myocardial infarction (40.4 vs 49.7%), history of cigarette smoking (62.7 vs 8O.6%), and abnormalities on lipoprotein electrophoresis (33.3 vs 40.3%). There was no significant difference between women and *Canadian Heart Association angina classification: Class &no angina pectoris, rest, 0; Class l - o n l y with strenuous or prolonged activity, rest, 0; Class 2-with rapid stairs, uphill, cold, or emotion, rest, 0; Class &with walking one to two blocks or a flight of stairs, rest, 0; Class P w i t h any physical activity, rest

+.

450 The Annals of Thoracic Surgery Vol 25 No 5 May 1978

Table 1. Preoperative Criteria Factor

Women

Men

p Value

Age (yr) k SE Angina (Class 3 or 4)a Ventricle (normal or mild impairment) Previous myocardial infarction Smoking history Lipid abnormality Hypertension Diabetes Cholesterol > 275 mg1100 ml Positive family history of coronary artery disease, diabetes, or hypertension

53.9 -L 0.51 89.7% 77.7% 40.4% 62.7% 33.3'/o 36.5% 19.3% 24.7 '/o 82.2%

52.1 2 0.22 79.8% 68.7% 49.7% 80.6% 40.3% 33.3% 15.7% 29.3% 78.3%

< 0.0005 < 0.005 < 0.005 < 0.05 < 0.005 < 0.05 NS NS NS NS

"Canadian Heart Association angina classification.

Table 2 . Menstrual and Hormone History of Female Patients Category

Percent

~~~

Premenopausal Surgical menopause Natural menopause Not stated Birth control pills Hormone therapy

14.6 17.6 47.7 20.1 1.7 11.3

men in the incidence of hypertension, diabetes, elevated serum cholesterol levels, or a family history of coronary artery disease, diabetes, or hypertension. The menstrual status of the female patients is given in Table 2 and appeared to bear no relation to the severity of coronary artery disease or to late or early results.

Results The overall operative mortality in the 1,541 patients was 2.6%, with an operative mortality rate of 3.7% (9 patients) in the 241 women and 2.4% (31 patients) in the 1,300 men. However, between January, 1975, and July, 1977, mortality rates dropped to 1.4% (2 deaths) in 140 women and 2.0% (14 deaths) in 697 men. Cumulative survival rates (actuarial) at 5 years were not significantly different, being 88*3y0in and 93.5% in men (Figure).

Actuarial survival Curves of men (circles)and women (triangles)following myocardial revascularization. 1

I

88.3

8s.3

8s.3

88.3

I

J

5

6

7

8

t 1

2

3

4

Years After Operation

451 Tyras et al: Myocardial Revascularization in Women

Table 3 . Coronary Artery Size (mm) and Number of Grafts Used ~~~

Men

Women

p Value

Right coronary artery Left anterior descending coronary artery Circumflex coronary artery

2.28 f 0.02 1.95 _+ 0.01

2.11 f 0.01 1.77 f 0.02

< 0.0005 < 0.0005

1.96 f 0.01

1.81 f 0.03

Grafts per patient, 1970-1977 Grafts per patient, 1976-1977

2.40 2.64

2.11 2.43

< 0.0005 < 0.0005 < 0.005

Artery and Grafts ~~

Table 4 . Postoperative Complications Complication

Men

Women

p Value

11.3% 8.9% 5.0% 0.8% 8.0% 6.1% 3.0%

11.2% 9.3% 4.6% 0.8% 8.2% 5.8% 3.7%

NS NS NS NS NS NS NS

Perioperative myocardial infarction 1970-1977 1976-1977

Postoperative hemorrhage Sternal infection Major arrhythmias Pulmonary Leg wound infection

Operative Findings The grafted coronary arteries in the women, measured at operation, were significantly smaller than those of the men (Table 3). Women received significantly fewer grafts than men (2.11 f 0.05 vs 2.40 f 0.02). Although the average number of grafts per patient has increased over the last several years, the difference between female and male patients persists (e.g., 1976 through 1977, 2.43 grafts per patient in women vs 2.64 grafts per patient in men). Whereas 23.5% of the women received single grafts, only 13.7% of the men did. Perioperative Myocardial lnfarction Perioperative infarction rates as determined by electrocardiogram and cardiac isoenzyme analysis were not significantly different between women and men (11.2 vs 11.3%) (Table 4). Decreases in the incidence of this complication during the period 1976 through 1977were comparable in women (9.3%) and men (8.9%).

quiring treatment, and pulmonary complications was not appreciably different in the two groups (see Table 4).

Late Results Cumulative survival rates were not significantly different over the first 6 years of follow-up (Figure). Cumulative patency rates, lower in women at 1month, 1year, and 3 years (Table 5), did not influence either the survival or the late myocardial infarction rate (3.9% in women vs 3.5% in men). Of women still potentially available for follow-up evaluation, 96% could be contacted Table 5 . Cumulative Patency Rates (Actuarial) and Late Myocardial lnfarction Factor

Men

Women

p Value ____

~

Graft patency 1m o 1Y' 3 Y'

5 Y' Postoperative Complications Late myocardial The incidence of postoperative hemorrhage, infarction sternal wound infection, major arrhythmia re-

92.6% 87.4% 85.4% 82.5% 3.5%

89.4% 82.0% 80.7% 80.7% 3.9%

< 0.05 < 0.005 < 0.05 NS NS

452 The Annals of Thoracic Surgery Vol 25 No 5 M a y 1978

and 69.8% of them were free from angina (Class 0) at that time while 22% were markedly improved, having Class 1 (9.4%) or Class 2 (12.7%) angina (Canadian Heart Association angina classification). Of the remaining female patients, 2.8% had Class 3 and 5.2% Class 4 angina.

Comment In recent years, discouraging reports have cast doubt upon the effectiveness of coronary artery bypass grafting in women. Bolooki and associates [31 reported an operative mortality of 8% in women (2% in men), a perioperative infarction rate three times higher in women than in men, and less improvement in ventricular performance, less effective relief of angina, and markedly lower early patency rates in their female patients. Al-Bassam and co-workers [13 in a much larger series reported an operative mortality of 9.2% in women and 4.8% in men; this was reduced to 7.1% in women and 2.9% in men during the most recent year of their study. Late attrition over a 4-year follow-up interval did not appear to be different for the two groups. On the other hand, in a report of the experience of the Cleveland Clinic [7] there were low operative mortality rates (1.7% in women vs 1.2% in men) and a low incidence of perioperative myocardial infarction (6.5% in women vs 5.0% in men), but significantly lower graft patency rates at 1 year in a small group of patients restudied (74.4% in women vs 84.1% in men). Women comprised 15.6% of our series, a somewhat higher percentage than that reported by other groups. There was no significant difference in operative mortality for women (3.7%) compared with men (2.4%); in fact, during the most recent 2% years of the study, operative mortality was slightly lower in women (1.4%) than in men (2.0%).Long-term survival was encouragingly high at 5 years for both men (93.5%) and women (88.3%). This experience is similar to that reported by Golding and Groves [71. Analysis of preoperative risk factors revealed some similarities to and a few differences from other reports [l, 21. There was no significant difference between men and women in the incidence of hypertension, diabetes (as determined by Wilkerson grading of glucose tolerance tests

[91), family history, or serum cholesterol level. Women did have significantly less frequent lipoprotein abnormalities, a less intense smoking history, and fewer previous myocardial infarctions. Spray and Roberts [12] concluded from a postmortem study that women have smaller coronary arteries than men and that therefore less atheroscleroti'c plaque is necessary to produce a flow-restrictive obstruction to coronary blood flow in women than in men. Accepting this, it could be expected that women with coronary artery disease would have anginal symptoms earlier in the course of the disease. Thus, there should be better preservation of ventricular function and a lower incidence of previous myocardial infarction. Bolooki and co-workers [3] noted that preoperative ventricular function was better in women in their study. At least two other series [l,21 showed a lower incidence of prior myocardial infarction in women undergoing myocardial revascularization. In our series, women had greater preservation of preoperative ventricular function and a lower incidence of prior myocardial infarction (see Table 1). If ventricular function is an important determinant of operative and late survival, women could be expected to fare reasonably well in these two categories, as they have in our experience. In fact, a cumulative 5-year survival of 88.3% in women exceeds reported longevity statistics in several other series [lo, 11, 131. Attempts at analysis of menstrual and hormonal history have yielded no clues to the cause of coronary atherosclerosis [6]. More women were seen with Class 3 or 4 angina, which may be due to earlier high-grade stenosis in a smaller coronary artery or to the less frequent application of screening exercise electrocardiograms to women. Intraoperative calibration of coronary arteries demonstrated significantly smaller size in women. Women required fewer grafts than men, which may be either because of less advanced disease or such severe disease that fewer arteries were accessible for grafting. The latter seems less likely in that only 6% of women and 4% of men received single grafts despite multivessel coronary artery disease.

453 Tyras et al: Myocardial Revascularization in Women

With smaller coronary arteries, lower patency rates could be anticipated [3, 71. Although our cumulative patency rates were lower in women than in men, they were appreciably better than ‘those reported by Bolooki and co-workers (50%) [3] or the Cleveland Clinic (74.4%) E71. Whereas perioperative or late myocardial infarction may be partially related to graft occlusion, other factors such a s extent of coronary disease and degree of collateral blood flow may be important. Essentially equivalent perioperative and late myocardial infarction rates in men and women would tend to indicate that graft patency, coronary artery size, number of grafts, and preoperative ventricular function cannot individually explain perioperative infarction. A high incidence of relief of angina has been achieved in our female patients, with 92% being either asymptomatic or improved. This compares favorably with the result expected in men

factors and coronary artery obstruction in male and female patients with aortocoronary bypass operation. Vasc Surg 10:81, 1976 3. Bolooki H, Vargas A, Green R, et al: Results of direct coronary artery surgery in women. J Thorac Cardiovasc Surg 69:271, 1975 4. Cameron A, Kemp HG Jr, Shimomura S, et al: Coronary artery bypass surgery. Long-term follow-up. NY State J Med 77:27, 1977 5. Codd JE, Kaiser GC, Wiens RD, et al: Myocardial injury and bypass grafting. J Thorac Cardiovasc Surg 70:489, 1975 5a. Council on Cardiovascular Surgery: American Heart Association Coronary Artery Disease Reporting System. Circulation 51:22, 1975 6. Engel HJ, Page HL Jr, Campbell WB: Coronary artery disease in young women. JAMA 230:1531, 1974 7. Golding LR, Groves LK: Results of coronary artery surgery in women. Cleve Clin Q 43:113, 1976 8. Logue RB, King SB 111, Douglas JS Jr: A practical approach to coronary artery disease, with special reference to coronary bypass surgery. Curr Probl Cardiol 1:1, 1976 [I,3,41. 9. O’Sullivan JB: Oral glucose tolerance tests, in In summary, although women appear to have Diabetes Mellitus: Diagnosis and Treatment, Vol 2. Edited by GJ Hamwi and TS Danowski. New smaller coronary arteries than men and lower York, American Diabetes Association, 1967, p p patency rates after coronary artery bypass graft47-50 ing, significantly better preoperative ventricular 10. Reul GJ Jr, Cooley DA, Wukasch DC, et al: Longfunction has been associated with acceptable term survival following coronary artery bypass. operative mortality rates, good long-term surAnalysis of 4,522 consecutive patients. Arch Surg vival, and relief of angina. These results are more 110:1419, 1975 favorable than those of earlier studies which re- 11. Sheldon WC, Rincon G, Pichard AD, et al: Surgical treatment of coronary artery disease: pure graft ported higher mortality rates in women. Myooperations, with a study of 741 patients followed cardial revascularization should not be withheld 3-7 years. Prog Cardiovasc Dis 18:237, 1975 from female patients. 12. Spray TL, Roberts WC: Status of the grafts and the native coronary arteries proximal and distal to References coronary anastomotic sites of aortocoronary 1. Al-Bassam MS, Dawson JT, Garcia E, et al: Evaluabypass grafts. Circulation 55:741, 1977 tion of risk factors and follow-up in women fol- 13. Stiles QR, Lindesmith GG, Tucker BL, et al: lowing coronary artery bypass. Bull Texas Heart Long-term follow-up of patients with coronary Inst 2:391, 1975 artery bypass grafts. Circulation 54:Suppl 3:32, 2. Barboriak JJ, Rimm AA, Anderson AJ, et al: Risk 1976