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Coronary Heart Disease in Residents of Rochester, Minnesota. V. Prognosis of Patients With Coronary Heart Disease Based on Initial Manifestation
Coronary Heart Disease in Residents of Rochester, Minnesota. V. Prognosis of Patients With Coronary Heart Disease Based on Initial Manifestation LILA R. ELVEBACK, Ph.D., Department of Medical Statistics and Epidemiology; DANIEL C. CONNOLLY, M.D., Ph.D., Division of Cardiovascular Diseases and Internal Medicine
During the period 1960 through 1979,1,014 residents of Rochester, Minnesota, had a diagnosis of classic angina pectoris as the first manifestation of coronary heart disease, and 1,013 had a myocardial infarction as the initial manifestation. In the angina cohort, about 50% were men, and of them, 20% were 70 years old or older. The female patients were an average of 6 years older than the men, and 43% were 70 years old or older. In this cohort, the 5-year survival rate increased from 77% in the 1960s to 87% in the 1970s (P<0.01). The 5-year net survivorship free of a myocardial infarction increased from 76% to 85% during that same time (P<0.01). In the myocardial infarction cohort, the 5-year death rate among the 30-day survivors of myocardial infarction was the same during both decades of the study. The age-adjusted reinfarction rate per 100 person-years at risk during the first 5 years of follow-up decreased very slightly among men and increased among women; thus, it remained essentially unchanged overall. Although the case fatality rate in the myocardial infarction cohort declined sharply from the 1960s to the 1970s, the long-term prognosis of the 30-day survivors of a myocardial infarction did not improve.
The incidence of classic angina pectoris and of myocardial infarction as the initial manifestation of coronary heart disease in residents of Rochester, Minnesota, has been established for the years 1950 through 1979.1>2 The 1,014 patients in whom angina pectoris was diagnosed during the period 1960 through 1979 and the 1,013 survivors of a first myocardial infarction during that same period have been followed up and analyzed for survivorship and for the occurrence of a first (or subsequent) myocardial infarction. METHODS Details of the methods of the coronary heart disease study in residents of Rochester, Minnesota, have been described previously.' The follow-up on these Rochester patients is exceptionally good; 5-year follow-up is complete for 100% of the 1960 through 1969 group and for 99% of the 1970 through 1974 group. Not all of the patients in the 1975 through 1979 group are eligible for This investigation was supported in part by grants HL-24236 and CM-14231 from the National Institutes of Health, Public Health Service. Mayo Clin Proc 60:305-311, 1985
5-year follow-up, but 3-year follow-up is complete for 93% of them. All death certificates in this incidence cohort were coded in accordance with the eighth revision of the International Classification of Diseases. DIAGNOSTIC CRITERIA Angina Pectoris.—During the study period, the diagnosis of angina pectoris was primarily subjective and was based on the history obtained from the patient. This symptom can exist without objective evidence of cardiac disease, and abnormalities in an electrocardiogram obtained during rest or exercise were not necessary for diagnosis. After review of the patient's records, the study clinicians made the diagnosis of angina pectoris on the basis of standard patient-reported symptoms, which usually included substernal pressure, pain, tightness, or burning distress, precipitated by exercise or excitement (or both) and usually relieved promptly by rest or nitroglycerin. The diagnosis of angina pectoris was occasionally difficult to make and in a few patients was rather arbitrary. Patients who had a diagnosis of angina at the time of the first examination were classified in the angina cohort 305
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Silent myocardial infarctions were not included in our data base because electrocardiograms were not done as part of the protocol. The opportunity for the diagnosis of a silent myocardial infarction varied from patient to patient. The prognosis was summarized in terms of survivorship, survivorship free of a myocardial infarction, and rate of infarction per 100 age- and sex-specific personyears at risk. The univariate Cox regression models were used to assess the importance of individual prognostic factors as determined at the time of initial diagnosis of coronary heart disease. Factors tested were age; sex; hypertension; level of serum cholesterol; past or present cigarette smoking; family history of coronary heart disease; year of initial diagnosis; presence of a diagnosis of diabetes, cardiomegaly, or congestive heart failure; and in the angina cohort, abnormal electrocardiographic findings. We did not present multivariate stepwise results because of greatly reduced sample sizes (not all factors were known in all patients). For example, a blood pressure measurement was not available in 22% of the patients, and the cholesterol concentration at the time of initial diagnosis was unknown in 23%. In only 60% of the patients were both of these variables known.
years old or older. The mean age of the female patients exceeded that of the male patients by 6 years. At the time of initial diagnosis, hypertension was more common in the women (75%) than in the men (60%). In contrast, smoking (past or present) was less common in the women (35%) than in the men (65%). Survival.—From the first to the second decade of this study, the 5-year survival rates increased from 72 to 84% among men (P<0.01) and from 85 to 92% among women (P<0.02) (Fig. 1 left panel). Among women, the relative survival* was 98% during the first decade and 100% during the second. Among men, the relative survival was 85% during the first decade but increased to 100% during the 1975 through 1979 period. Net Survivorship Free of Myocardial Infarction.— Figure 1 shows both survivorship and net survivorship free of a myocardial infarction subsequent to the first diagnosis of angina. Net survivorship free of myocardial infarction increased from 76% during the 1960s to 85% during the 1970s (P<0.01). The highest rate of occurrence of myocardial infarction was during the first year after the diagnosis of angina. Among those patients in whom angina was diagnosed during the 1960 through 1969 period, the incidence rates of myocardial infarction for the first 5 years were 1 1 % , 8%, 6%, 5%, and 3%. These rates declined to 5%, 2%, 4 % , 2%, and 2% in the 1970 through 1979 cohort. The pattern of improvement in survivorship free of a myocardial infarction resembles closely the improvement in survival from the first to the second decade of the study (Fig. 1). Obviously, the decline in the rate of occurrence of myocardial infarction contributed substantially to the improvement in survivorship after the diagnosis of angina pectoris. Rates of Myocardial Infarction per 100 Age- and Sex-Specific Person-Years at Risk.—Table 1 shows the rates of infarction for the first year and for the first 5 years by age- and sex-specific person-years at risk for the angina cohort. As expected, the rates were higher among men than among women in all age groups and during both decades. The age-adjusted rates declined in both sexes during the second decade of the study.
The use of ß-blockers could not be evaluated in this observational study. Approximately 30% of the patients received such drugs at some time (from the time of the initial diagnosis to 20 years later). Selection of patients for the use of ß-blockers, for alleviation of hypertension, angina, or dysrhythmia, masks any improvement in prognosis.
Case Fatality Rates Associated With Myocardial Infarction.—Table 2 shows the age-adjusted case fatality rates associated with myocardial infarction. In men, the case fatality rate was slightly higher among those with a prior diagnosis of angina than among those in whom a myocardial infarction was the first manifestation of coronary heart disease. In women, both the 24-hour and the
RESULTS IN THE ANGINA PECTORIS COHORT Initial Cohort.—Approximately half of the angina cohort were male patients, and of them, about a fifth were 70
'Relative survival is the ratio of the observed survivorship to that expected. In this study, expected survivorship was based on age- and sex-specific cohort life tables.
whether or not a myocardial infarction occurred subsequently. If, however, the patient had no prior diagnosis of angina but a history of previous angina pectoris was elicited in retrospect at the time of hospitalization for the first acute myocardial infarction, the myocardial infarction was considered the initial manifestation of coronary heart disease. Myocardial Infarction.—The clinical diagnosis of myocardial infarction was based on the following factors: (1) a clinical history indicative of acute myocardial ischemia, (2) the presence of serial electrocardiographic changes indicative of myocardial damage, and (3) the diagnostic elevation of serum enzymes—serum glutamic-oxalacetic transaminase (introduced in 1955), lactate dehydrogenase (introduced in 1963), creatine kinase (introduced in 1964), and MB fraction of creatine kinase (introduced in 1971).
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307
-1970-79 1960-69
Years After Diagnosis Fig. 1. /.eft Pane/, Survivorship of patients with angina diagnosed in the 1960s (N = 431) and angina diagnosed in the 1970s (N = 583). Right Panel, Net survivorship free of myocardial infarction in this cohort of patients who had angina as the initial manifestation of coronary heart disease. In this analysis, the history of a patient who died without having had a myocardial infarction was censored at the time of death.
30-day case fatality rates were si ightly lower among those with a prior diagnosis of angina than among those with myocardial infarction as the initial manifestation of coronary heart disease. The mean age of patients at the time of first myocardial infarction after angina had been diagnosed was 69 years, and 50% of these patients were 70 years old or older. The age- and sex-adjusted 5-year survivorship subsequent to the myocardial infarction was 55% compared with 72% for those without prior angina. The myocardial infarctions that were the first manifestation of coronary heart disease (no prior diagnosis of angina) occurred in a younger group of patients (mean age, 64 years; 36% age 70 years or older). Prognostic Factors at the Time of Initial Diagnosis of Angina Pectoris.—The well-known risk factors for the development of coronary heart disease (age, sex, hypertension, cigarette smoking, elevated cholesterol level, diabetes, electrocardiographic abnormalities, and family history of coronary heart disease at the time of initial diagnosis of angina) also serve as prognostic factors for long-term survivorship after a diagnosis of angina as the
first manifestation of coronary heart disease. Prior diagnoses of cardiomegaly or congestive heart failure at the time of diagnosis of angina are important variables in prognosis. Table 1.—Rates of Myocardial Infarction per 100 Person-Years at Risk Among 1,014 Patients in Whom the Initial Manifestation of Coronary Heart Disease Was Angina Pectoris Infarction rate/1 OC person-years First yeart Age (yr)*
Men
<60 60-69 ä= 70 Age-adjusted
11.6 12.7 6.7 9.9
<60 60-69 S70 Age-adjusted
9.2 3.6 7.7 7.0
Women 1960-1969 2.2 2.6 4.6 3.3 1970-1979 4.7 3.1 1.4 2.9
'Based on age-specific person-years at risk. tAfter diagnosis of angina pectoris.
First 5 yearst Men cohort 6.7 8.6 7.5 7.6 cohort 4.0 2.9 5.9 4.4
Women 2.2 3.7 3.6 3.2 3.2 1.9 1.8 2.2
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Table 2.—Age-Adjusted* Case Fatality Rates Among Patients Who Experienced Myocardial Infarction diagnosis
1
1960-1969 1970-1979
30 22
1960-1969 1970-1979
38 27
2
3
1
2
Death rates «24 hours (%) 36 43 32 25 25 26 21 20 Death rates within 30 days (%) 46 50 42 31 31 43 29 26
3 35 22 50 30
'Adjusted to the age distribution of all patients with first myocardial infarctions, including those with prior angina. tThe numbered column headings denote groups of patients with the following characteristics: 1. Myocardial infarction as first manifestation of coronary heart disease. (Sudden unexpected deaths in patients in whom an infarction had been diagnosed electrocardiographically and deaths in which the certificate had been coded for coronary heart disease were included.) 2. First myocardial infarction after an initial manifestation of angina pectoris. 3. Second myocardial infarction after an infarction had been diagnosed as first manifestation of coronary heart disease.
During the first year after diagnosis of angina, the most important factors for predicting the occurrence of a myocardial infarction were smoking, electrocardiographic abnormalities, sex, and hypertension. If the first 5 years after diagnosis of angina are considered, calendar year of diagnosis can be added to this list. During the first 5 years of follow-up, 320 first myocardial infarctions occurred. We were unable to identify any variables that were useful for predicting 30-day survival after the first myocardial infarction. Among the 30-day survivors of the first myocardial infarction in the angina cohort, however, we found that a history of congestive heart failure, smoking, electrocardiographic abnormalities at the time of diagnosis of angina, and hypertension were prognostic factors for subsequent survivorship. Discussion.—The reports in the literature about the prognosis of patients who have experienced angina pectoris often include those whose angina developed after a myocardial infarction. The Framingham study3 yielded information on the prognosis of male patients with angina as the initial manifestation of coronary heart disease. These patients were denoted as those with uncomplicated angina. In men older than 45 years of age, the probability of having a coronary attack within 8 years was about 50%. In our angina cohort, including all patients 30 years old or older, the probability among male patients of surviving free of myocardial infarction was 58% for those in whom angina had been diagnosed during the 1960s and 7 1 % for those in whom it had been diagnosed during the
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1970s. Only about 10% of our angina cohort were 45 years old or younger at the time of diagnosis of angina. In the Framingham study, the prognosis for female patients was better than that for male patients, a finding that prevailed in our study as well (among female patients, the probability of surviving free of myocardial infarction for 8 years was 76% and 80%, respectively, during the 2 decades of our study). In the Rochester study, only clinically recognized myocardial infarctions were included. Weinblatt and associates4 reported on the prognosis of 275 men, 25 to 64 years of age at the time of entry into a group health insurance plan, who had a diagnosis of angina pectoris in the absence of a prior myocardial infarction or valvular heart disease. At 21/2 years after diagnosis, 10.5% had died and 12.5% had suffered a myocardial infarction. In our series, including all patients 30 years old or older, at 2V2 years after diagnosis of angina, 11.5% had died and 14% had suffered a first myocardial infarction. In 1946, Parker and associates5 reported on 3,440 Mayo Clinic patients in whom angina had been diagnosed during the years 1927 through 1936. This was not a population-based study, and patients with prior myocardial infarctions were included. In this early report, however, the authors make the following interesting statement: "...there is now reason to believe that the average patient who has angina pectoris may anticipate a longer survival than was thought reasonable to predict a few years ago." In 1952, Block and associates6 extended the study by Parker and colleagues to include 6,882 Mayo Clinic patients who had received a diagnosis of angina during the years 1927 through 1944; they noted an increased 5-year survival rate (from 52% to 58%). Pryor and associates7 reported an improvement in prognosis and in event-free survivorship in a series of 1,911 consecutive medically treated patients with chest pain who had been referred to the Duke University Medical Center for cardiac catheterization during the period 1961 through 1981. An unknown proportion of the patients had had a prior myocardial infarction. In our study, survivorship for patients with angina pectoris as the first manifestation of coronary heart disease improved from the 1960s to the 1970s. During this study period, the declining rate of occurrence of myocardial infarctions after the diagnosis of angina was clearly the major contributor to the improvement in survivorship. RESULTS I N THE M Y O C A R D I A L I N F A R C T I O N COHORT Initial Cohort—During the period 1960 through 1979, 1,013 residents of Rochester, Minnesota, survived for 30
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309
100-
90-
80-
3
4
5
1
Years After I n i t i a l MI Fig. 2. Left Panel, Long-term survival of 30-day survivors of a myocardial infarction as the initial manifestation of coronary heart disease during the periods 1960 through 1969 (N = 431) and 1970 through 1979 (N = 582). Right Panel, Net survivorship free of reinfarction for this cohort during the 2 decades of our study.
days after a myocardial infarction had occurred as the first manifestation of coronary heart disease. Approximately two thirds of these patients were men, and of these men, 22% were 70 years old or older. In this cohort, the women were an average of 9 years older than the men (53% were 70 years old or older). Hypertension was more common in the women (89%) than in the men (56%), as was pulmonary edema or congestive heart failure at the time of the initial myocardial infarction (35% versus 25%). In contrast, only 46% of the women were past or present cigarette smokers compared with 73% of the men. Survival.—Although the case fatality rate (death within 30 days) decreased considerably from the 1960s to the 1970s, the long-term survivorship of the 30-day survivors of a myocardial infarction remained essentially unchanged (Fig. 2). The 5-year survival rate was 72% for those patients who had a myocardial infarction during the 1960s as well as for those who had a myocardial infarction during the 1970s. The advantage noted in survivorship for women in comparison with men in the angina cohort was not evident in the myocardial in-
farction cohort. The 5-year survivorship was 74% for the men and 68% for the women in this cohort. Sudden deaths (within 24 hours after myocardial infarction) constituted 40% of the late deaths among men and 24% of the late deaths among women. Survival Free of Reinfarction Among the 30-Day Survivors of the Initial Myocardial Infarction.—The 5-year survival free of a myocardial infarction was 69% for men and 73% for women. For those patients younger than age 70 years at the time of the initial myocardial infarction, reinfarction rates were less for the women than for the men. Forthose 70 years old or older (22% of the men and 53% of the women), little difference was noted in the reinfarction rates. The survivorship free of reinfarction in this cohort did not decline from the 1960s to the 1970s. Reinfarction Rates per 100 Person-Years at Risk.—Table 3 shows reinfarction rates by age and sex, based on age- and sex-specific person-years at risk, among the 1,013 survivors of the initial myocardial infarction. As with first infarctions, the rates of reinfarction generally were higher among men than among women. The age-adjusted rate of reinfarction for the first 5 years of
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Table 3.—Reinfarction Rates per 100 Person-Years at Risk Among 1,013 Survivors of a Myocardial Infarction That Was the Initial Manifestation of Coronary Heart Disease Reinfarction rate/100 person-years First yeart Age (yr)*
Men
Women
First 5 yearst Men
Women
1960-1969 cohort 10.3 12.0 16.3 13.3 8.7 19.0 14.0 13.8
12.0 6.6 8.2 6.9 15.5 8.5 12.0 7.8 1970-1979 cohort 13.2 5.4 7.0 11.1 13.7 6.0 11.6 7.3
2.9 3.2 7.1 4.7 6.6 4.2 6.6 5.9
'Based on age-specific person-years at risk. tAfter diagnosis of initial myocardial infarction.
follow-up decreased slightly from the 1960s to the 1970s among men but showed a nonsignificant increase among women. Prognosis of the 30-Day Survivors of a Myocardial Infarction.—The variables that are important in the development of coronary heart disease are also prognostic factors in long-term survivorship in this group: cardiomegaly, age, sex, hypertension, elevated cholesterol level, diabetes, and family history of coronary heart disease at the time of initial myocardial infarction. Identifying those patients at high risk for reinfarction, however, was extremely difficult. Even though age remained a factor, the difference between the sexes was no longer significant. Although 116 reinfarctions occurred during the first year of follow-up, we were unable to identify any predictive factors. During the first 5 years of follow-up (during which time 280 reinfarctions occurred), only age and diabetes were significant predictors. Case Fatality Rates (24 Hours and 30 Days).—Table 2 shows the case fatality rates for three groups of patients who had myocardial infarctions. During both decades of the study, the 24-hour and 30-day case fatality rates for men increased steadily from group 1 (patients with a myocardial infarction as the initial manifestation of coronary heart disease) to group 3 (patients with a second myocardial infarction after surviving 30 days subsequent to the initial infarction). In women, the distinctions were not so clear, but, as expected, the highest rates were in those with second myocardial infarctions. Both 24-hour and 30-day case fatality rates decreased substantially during the second decade of the study in all groups and in both sexes. Discussion.—Many of the reported series of patients with coronary heart disease are based on hospitalized
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patients or those in a coronary care unit. Few studies have focused on initial myocardial infarctions, and most published series have included patients who have had prior angina. In 1960, Juergens and associates8 reported on 279 Rochester residents who had a first clinically recognized myocardial infarction during the period 1935 to 1951. The 5-year survival for those who had had no prior angina was 63%. This figure had increased to 72% during the 2 decades of our study (1960 through 1979). The most common cause of death in the study by Juergens and colleagues was recurrence of myocardial infarction, as it was for the myocardial infarction cohort in our study. Kannel and associates9 discussed the prognosis of patients (193 men and 53 women) after an initial myocardial infarction. In these patients, however, the infarction was not necessarily the first manifestation of coronary heart disease; first myocardial infarctions after the diagnosis of angina pectoris were also included. During the first 5 years, reinfarction occurred in 13% of the men and 39% of the women. Weinblatt and associates'0 reported on the prognosis of 881 men with myocardial infarction who were 25 to 64 years of age at the time of entry into a health insurance plan. This series included patients with a prior diagnosis of angina. The reinfarction rate during the first 4V2 years for 1-month survivors without prior angina was 23%. In our series, for men 30 years old or older, the corresponding rate was 30%. The results in the Rochester study did not confirm the report by others that female patients have a disadvantage in case fatality or early mortality after myocardial infarction. Despite the fact that the women were considerably older, they did as well as or better than the men.
CONCLUSIONS Among those patients whose first manifestation of coronary heart disease was angina pectoris, the occurrence of myocardial infarction declined significantly and survivorship improved significantly from the 1960s to the 1970s. Among those whose first manifestation of coronary heart disease was a myocardial infarction, the 30-day case fatality declined considerably from the 1960s to the 1970s, but no improvement occurred in reinfarction rates or subsequent survivorship among the 30-day survivors. ACKNOWLEDGMENT We thank Virginia A. Gosselin, Marie L. Notermann, Anastasia M. Ryan, and Chu-Pin Chu for their major contributions to this study.
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OF PATIENTS W I T H CORONARY HEART DISEASE
REFERENCES 1.
2.
3.
4.
5.
Connolly DC, Oxman HA, Nobrega FT, Kurland LT, Kennedy MA, Elveback LR: Coronary heart disease in residents of Rochester, Minnesota, 1950-1975. I. Background and study design. Mayo Clin Proc 56:661-664, 1981 Elveback LR, Connolly DC, Kurland LT: Coronary heart disease in residents of Rochester, Minnesota. II. Mortality, incidence, and survivorship, 1950-1975. Mayo Clin Proc 56:665-672, 1981 Kännel WB, Feinleib M: Natural history of angina pectoris in the Framingham Study: prognosis and survival. Am J Cardiol 29:154-163, 1972 Weinblatt E, Frank CW, Shapiro S, Sager RV: Prognostic factors in angina pectoris: a prospective study. I Chronic Dis 21:231-245, 1968 Parker RL, DryT], Willius FA, Gage RP: Life expectancy in angina pectoris. JAMA 131:95-100, 1946
10.
311
Block WJJr, Crumpacker EL, DryTJ, GageRP: Prognosis of angina pectoris: observations in 6,882 cases. JAMA 150:259-264, 1952 Pryor DB, Harrell FEJr, Lee KL, Califf RM, Rosati RA: An improving prognosis over time in medically treated patients with coronary artery disease. A m J Cardiol 52:444-448, 1983 Juergens JL, Edwards JE, Achor RWP, Burchell HB: Prognosis of patients surviving first clinically diagnosed myocardial infarction. Arch Intern Med 105:444-450, 1960 Kannel W B , Sorlie P, McNamara PM: Prognosis after initial myocardial infarction: the Framingham Study. Am J Cardiol 44:53-59, 1979 Weinblatt E, Shapiro S, Frank CW, Sager RV: Prognosis of men after first myocardial infarction: mortality and first recurrence in r e l a t i o n to s e l e c t e d p a r a m e t e r s . A m J P u b l i c H e a l t h 58:1329-1347, 1968
During the period 1960 through 1979,1,014 residents of Rochester, Minnesota, had a diagnosis of classic angina pectoris as the first manifestation of coronary heart disease, and 1,013 had a myocardial infarction as the initial manifestation. In the angina cohort, about 50% were men, and of them, 20% were 70 years old or older. The female patients were an average of 6 years older than the men, and 43% were 70 years old or older. In this cohort, the 5-year survival rate increased from 77% in the 1960s to 87% in the 1970s (P<0.01). The 5-year net survivorship free of a myocardial infarction increased from 76% to 85% during that same time (P<0.01). In the myocardial infarction cohort, the 5-year death rate among the 30-day survivors of myocardial infarction was the same during both decades of the study. The age-adjusted reinfarction rate per 100 person-years at risk during the first 5 years of follow-up decreased very slightly among men and increased among women; thus, it remained essentially unchanged overall. Although the case fatality rate in the myocardial infarction cohort declined sharply from the 1960s to the 1970s, the long-term prognosis of the 30-day survivors of a myocardial infarction did not improve.
The incidence of classic angina pectoris and of myocardial infarction as the initial manifestation of coronary heart disease in residents of Rochester, Minnesota, has been established for the years 1950 through 1979.1>2 The 1,014 patients in whom angina pectoris was diagnosed during the period 1960 through 1979 and the 1,013 survivors of a first myocardial infarction during that same period have been followed up and analyzed for survivorship and for the occurrence of a first (or subsequent) myocardial infarction. METHODS Details of the methods of the coronary heart disease study in residents of Rochester, Minnesota, have been described previously.' The follow-up on these Rochester patients is exceptionally good; 5-year follow-up is complete for 100% of the 1960 through 1969 group and for 99% of the 1970 through 1974 group. Not all of the patients in the 1975 through 1979 group are eligible for This investigation was supported in part by grants HL-24236 and CM-14231 from the National Institutes of Health, Public Health Service. Mayo Clin Proc 60:305-311, 1985
5-year follow-up, but 3-year follow-up is complete for 93% of them. All death certificates in this incidence cohort were coded in accordance with the eighth revision of the International Classification of Diseases. DIAGNOSTIC CRITERIA Angina Pectoris.—During the study period, the diagnosis of angina pectoris was primarily subjective and was based on the history obtained from the patient. This symptom can exist without objective evidence of cardiac disease, and abnormalities in an electrocardiogram obtained during rest or exercise were not necessary for diagnosis. After review of the patient's records, the study clinicians made the diagnosis of angina pectoris on the basis of standard patient-reported symptoms, which usually included substernal pressure, pain, tightness, or burning distress, precipitated by exercise or excitement (or both) and usually relieved promptly by rest or nitroglycerin. The diagnosis of angina pectoris was occasionally difficult to make and in a few patients was rather arbitrary. Patients who had a diagnosis of angina at the time of the first examination were classified in the angina cohort 305
306
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Silent myocardial infarctions were not included in our data base because electrocardiograms were not done as part of the protocol. The opportunity for the diagnosis of a silent myocardial infarction varied from patient to patient. The prognosis was summarized in terms of survivorship, survivorship free of a myocardial infarction, and rate of infarction per 100 age- and sex-specific personyears at risk. The univariate Cox regression models were used to assess the importance of individual prognostic factors as determined at the time of initial diagnosis of coronary heart disease. Factors tested were age; sex; hypertension; level of serum cholesterol; past or present cigarette smoking; family history of coronary heart disease; year of initial diagnosis; presence of a diagnosis of diabetes, cardiomegaly, or congestive heart failure; and in the angina cohort, abnormal electrocardiographic findings. We did not present multivariate stepwise results because of greatly reduced sample sizes (not all factors were known in all patients). For example, a blood pressure measurement was not available in 22% of the patients, and the cholesterol concentration at the time of initial diagnosis was unknown in 23%. In only 60% of the patients were both of these variables known.
years old or older. The mean age of the female patients exceeded that of the male patients by 6 years. At the time of initial diagnosis, hypertension was more common in the women (75%) than in the men (60%). In contrast, smoking (past or present) was less common in the women (35%) than in the men (65%). Survival.—From the first to the second decade of this study, the 5-year survival rates increased from 72 to 84% among men (P<0.01) and from 85 to 92% among women (P<0.02) (Fig. 1 left panel). Among women, the relative survival* was 98% during the first decade and 100% during the second. Among men, the relative survival was 85% during the first decade but increased to 100% during the 1975 through 1979 period. Net Survivorship Free of Myocardial Infarction.— Figure 1 shows both survivorship and net survivorship free of a myocardial infarction subsequent to the first diagnosis of angina. Net survivorship free of myocardial infarction increased from 76% during the 1960s to 85% during the 1970s (P<0.01). The highest rate of occurrence of myocardial infarction was during the first year after the diagnosis of angina. Among those patients in whom angina was diagnosed during the 1960 through 1969 period, the incidence rates of myocardial infarction for the first 5 years were 1 1 % , 8%, 6%, 5%, and 3%. These rates declined to 5%, 2%, 4 % , 2%, and 2% in the 1970 through 1979 cohort. The pattern of improvement in survivorship free of a myocardial infarction resembles closely the improvement in survival from the first to the second decade of the study (Fig. 1). Obviously, the decline in the rate of occurrence of myocardial infarction contributed substantially to the improvement in survivorship after the diagnosis of angina pectoris. Rates of Myocardial Infarction per 100 Age- and Sex-Specific Person-Years at Risk.—Table 1 shows the rates of infarction for the first year and for the first 5 years by age- and sex-specific person-years at risk for the angina cohort. As expected, the rates were higher among men than among women in all age groups and during both decades. The age-adjusted rates declined in both sexes during the second decade of the study.
The use of ß-blockers could not be evaluated in this observational study. Approximately 30% of the patients received such drugs at some time (from the time of the initial diagnosis to 20 years later). Selection of patients for the use of ß-blockers, for alleviation of hypertension, angina, or dysrhythmia, masks any improvement in prognosis.
Case Fatality Rates Associated With Myocardial Infarction.—Table 2 shows the age-adjusted case fatality rates associated with myocardial infarction. In men, the case fatality rate was slightly higher among those with a prior diagnosis of angina than among those in whom a myocardial infarction was the first manifestation of coronary heart disease. In women, both the 24-hour and the
RESULTS IN THE ANGINA PECTORIS COHORT Initial Cohort.—Approximately half of the angina cohort were male patients, and of them, about a fifth were 70
'Relative survival is the ratio of the observed survivorship to that expected. In this study, expected survivorship was based on age- and sex-specific cohort life tables.
whether or not a myocardial infarction occurred subsequently. If, however, the patient had no prior diagnosis of angina but a history of previous angina pectoris was elicited in retrospect at the time of hospitalization for the first acute myocardial infarction, the myocardial infarction was considered the initial manifestation of coronary heart disease. Myocardial Infarction.—The clinical diagnosis of myocardial infarction was based on the following factors: (1) a clinical history indicative of acute myocardial ischemia, (2) the presence of serial electrocardiographic changes indicative of myocardial damage, and (3) the diagnostic elevation of serum enzymes—serum glutamic-oxalacetic transaminase (introduced in 1955), lactate dehydrogenase (introduced in 1963), creatine kinase (introduced in 1964), and MB fraction of creatine kinase (introduced in 1971).
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-1970-79 1960-69
Years After Diagnosis Fig. 1. /.eft Pane/, Survivorship of patients with angina diagnosed in the 1960s (N = 431) and angina diagnosed in the 1970s (N = 583). Right Panel, Net survivorship free of myocardial infarction in this cohort of patients who had angina as the initial manifestation of coronary heart disease. In this analysis, the history of a patient who died without having had a myocardial infarction was censored at the time of death.
30-day case fatality rates were si ightly lower among those with a prior diagnosis of angina than among those with myocardial infarction as the initial manifestation of coronary heart disease. The mean age of patients at the time of first myocardial infarction after angina had been diagnosed was 69 years, and 50% of these patients were 70 years old or older. The age- and sex-adjusted 5-year survivorship subsequent to the myocardial infarction was 55% compared with 72% for those without prior angina. The myocardial infarctions that were the first manifestation of coronary heart disease (no prior diagnosis of angina) occurred in a younger group of patients (mean age, 64 years; 36% age 70 years or older). Prognostic Factors at the Time of Initial Diagnosis of Angina Pectoris.—The well-known risk factors for the development of coronary heart disease (age, sex, hypertension, cigarette smoking, elevated cholesterol level, diabetes, electrocardiographic abnormalities, and family history of coronary heart disease at the time of initial diagnosis of angina) also serve as prognostic factors for long-term survivorship after a diagnosis of angina as the
first manifestation of coronary heart disease. Prior diagnoses of cardiomegaly or congestive heart failure at the time of diagnosis of angina are important variables in prognosis. Table 1.—Rates of Myocardial Infarction per 100 Person-Years at Risk Among 1,014 Patients in Whom the Initial Manifestation of Coronary Heart Disease Was Angina Pectoris Infarction rate/1 OC person-years First yeart Age (yr)*
Men
<60 60-69 ä= 70 Age-adjusted
11.6 12.7 6.7 9.9
<60 60-69 S70 Age-adjusted
9.2 3.6 7.7 7.0
Women 1960-1969 2.2 2.6 4.6 3.3 1970-1979 4.7 3.1 1.4 2.9
'Based on age-specific person-years at risk. tAfter diagnosis of angina pectoris.
First 5 yearst Men cohort 6.7 8.6 7.5 7.6 cohort 4.0 2.9 5.9 4.4
Women 2.2 3.7 3.6 3.2 3.2 1.9 1.8 2.2
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PROGNOSIS OF PATIENTS WITH CORONARY HEART DISEASE
Table 2.—Age-Adjusted* Case Fatality Rates Among Patients Who Experienced Myocardial Infarction diagnosis
1
1960-1969 1970-1979
30 22
1960-1969 1970-1979
38 27
2
3
1
2
Death rates «24 hours (%) 36 43 32 25 25 26 21 20 Death rates within 30 days (%) 46 50 42 31 31 43 29 26
3 35 22 50 30
'Adjusted to the age distribution of all patients with first myocardial infarctions, including those with prior angina. tThe numbered column headings denote groups of patients with the following characteristics: 1. Myocardial infarction as first manifestation of coronary heart disease. (Sudden unexpected deaths in patients in whom an infarction had been diagnosed electrocardiographically and deaths in which the certificate had been coded for coronary heart disease were included.) 2. First myocardial infarction after an initial manifestation of angina pectoris. 3. Second myocardial infarction after an infarction had been diagnosed as first manifestation of coronary heart disease.
During the first year after diagnosis of angina, the most important factors for predicting the occurrence of a myocardial infarction were smoking, electrocardiographic abnormalities, sex, and hypertension. If the first 5 years after diagnosis of angina are considered, calendar year of diagnosis can be added to this list. During the first 5 years of follow-up, 320 first myocardial infarctions occurred. We were unable to identify any variables that were useful for predicting 30-day survival after the first myocardial infarction. Among the 30-day survivors of the first myocardial infarction in the angina cohort, however, we found that a history of congestive heart failure, smoking, electrocardiographic abnormalities at the time of diagnosis of angina, and hypertension were prognostic factors for subsequent survivorship. Discussion.—The reports in the literature about the prognosis of patients who have experienced angina pectoris often include those whose angina developed after a myocardial infarction. The Framingham study3 yielded information on the prognosis of male patients with angina as the initial manifestation of coronary heart disease. These patients were denoted as those with uncomplicated angina. In men older than 45 years of age, the probability of having a coronary attack within 8 years was about 50%. In our angina cohort, including all patients 30 years old or older, the probability among male patients of surviving free of myocardial infarction was 58% for those in whom angina had been diagnosed during the 1960s and 7 1 % for those in whom it had been diagnosed during the
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1970s. Only about 10% of our angina cohort were 45 years old or younger at the time of diagnosis of angina. In the Framingham study, the prognosis for female patients was better than that for male patients, a finding that prevailed in our study as well (among female patients, the probability of surviving free of myocardial infarction for 8 years was 76% and 80%, respectively, during the 2 decades of our study). In the Rochester study, only clinically recognized myocardial infarctions were included. Weinblatt and associates4 reported on the prognosis of 275 men, 25 to 64 years of age at the time of entry into a group health insurance plan, who had a diagnosis of angina pectoris in the absence of a prior myocardial infarction or valvular heart disease. At 21/2 years after diagnosis, 10.5% had died and 12.5% had suffered a myocardial infarction. In our series, including all patients 30 years old or older, at 2V2 years after diagnosis of angina, 11.5% had died and 14% had suffered a first myocardial infarction. In 1946, Parker and associates5 reported on 3,440 Mayo Clinic patients in whom angina had been diagnosed during the years 1927 through 1936. This was not a population-based study, and patients with prior myocardial infarctions were included. In this early report, however, the authors make the following interesting statement: "...there is now reason to believe that the average patient who has angina pectoris may anticipate a longer survival than was thought reasonable to predict a few years ago." In 1952, Block and associates6 extended the study by Parker and colleagues to include 6,882 Mayo Clinic patients who had received a diagnosis of angina during the years 1927 through 1944; they noted an increased 5-year survival rate (from 52% to 58%). Pryor and associates7 reported an improvement in prognosis and in event-free survivorship in a series of 1,911 consecutive medically treated patients with chest pain who had been referred to the Duke University Medical Center for cardiac catheterization during the period 1961 through 1981. An unknown proportion of the patients had had a prior myocardial infarction. In our study, survivorship for patients with angina pectoris as the first manifestation of coronary heart disease improved from the 1960s to the 1970s. During this study period, the declining rate of occurrence of myocardial infarctions after the diagnosis of angina was clearly the major contributor to the improvement in survivorship. RESULTS I N THE M Y O C A R D I A L I N F A R C T I O N COHORT Initial Cohort—During the period 1960 through 1979, 1,013 residents of Rochester, Minnesota, survived for 30
PROGNOSIS OF PATIENTS W I T H CORONARY HEART DISEASE
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309
100-
90-
80-
3
4
5
1
Years After I n i t i a l MI Fig. 2. Left Panel, Long-term survival of 30-day survivors of a myocardial infarction as the initial manifestation of coronary heart disease during the periods 1960 through 1969 (N = 431) and 1970 through 1979 (N = 582). Right Panel, Net survivorship free of reinfarction for this cohort during the 2 decades of our study.
days after a myocardial infarction had occurred as the first manifestation of coronary heart disease. Approximately two thirds of these patients were men, and of these men, 22% were 70 years old or older. In this cohort, the women were an average of 9 years older than the men (53% were 70 years old or older). Hypertension was more common in the women (89%) than in the men (56%), as was pulmonary edema or congestive heart failure at the time of the initial myocardial infarction (35% versus 25%). In contrast, only 46% of the women were past or present cigarette smokers compared with 73% of the men. Survival.—Although the case fatality rate (death within 30 days) decreased considerably from the 1960s to the 1970s, the long-term survivorship of the 30-day survivors of a myocardial infarction remained essentially unchanged (Fig. 2). The 5-year survival rate was 72% for those patients who had a myocardial infarction during the 1960s as well as for those who had a myocardial infarction during the 1970s. The advantage noted in survivorship for women in comparison with men in the angina cohort was not evident in the myocardial in-
farction cohort. The 5-year survivorship was 74% for the men and 68% for the women in this cohort. Sudden deaths (within 24 hours after myocardial infarction) constituted 40% of the late deaths among men and 24% of the late deaths among women. Survival Free of Reinfarction Among the 30-Day Survivors of the Initial Myocardial Infarction.—The 5-year survival free of a myocardial infarction was 69% for men and 73% for women. For those patients younger than age 70 years at the time of the initial myocardial infarction, reinfarction rates were less for the women than for the men. Forthose 70 years old or older (22% of the men and 53% of the women), little difference was noted in the reinfarction rates. The survivorship free of reinfarction in this cohort did not decline from the 1960s to the 1970s. Reinfarction Rates per 100 Person-Years at Risk.—Table 3 shows reinfarction rates by age and sex, based on age- and sex-specific person-years at risk, among the 1,013 survivors of the initial myocardial infarction. As with first infarctions, the rates of reinfarction generally were higher among men than among women. The age-adjusted rate of reinfarction for the first 5 years of
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PROGNOSIS OF PATIENTS WITH CORONARY HEART DISEASE
Table 3.—Reinfarction Rates per 100 Person-Years at Risk Among 1,013 Survivors of a Myocardial Infarction That Was the Initial Manifestation of Coronary Heart Disease Reinfarction rate/100 person-years First yeart Age (yr)*
Men
Women
First 5 yearst Men
Women
1960-1969 cohort 10.3 12.0 16.3 13.3 8.7 19.0 14.0 13.8
12.0 6.6 8.2 6.9 15.5 8.5 12.0 7.8 1970-1979 cohort 13.2 5.4 7.0 11.1 13.7 6.0 11.6 7.3
2.9 3.2 7.1 4.7 6.6 4.2 6.6 5.9
'Based on age-specific person-years at risk. tAfter diagnosis of initial myocardial infarction.
follow-up decreased slightly from the 1960s to the 1970s among men but showed a nonsignificant increase among women. Prognosis of the 30-Day Survivors of a Myocardial Infarction.—The variables that are important in the development of coronary heart disease are also prognostic factors in long-term survivorship in this group: cardiomegaly, age, sex, hypertension, elevated cholesterol level, diabetes, and family history of coronary heart disease at the time of initial myocardial infarction. Identifying those patients at high risk for reinfarction, however, was extremely difficult. Even though age remained a factor, the difference between the sexes was no longer significant. Although 116 reinfarctions occurred during the first year of follow-up, we were unable to identify any predictive factors. During the first 5 years of follow-up (during which time 280 reinfarctions occurred), only age and diabetes were significant predictors. Case Fatality Rates (24 Hours and 30 Days).—Table 2 shows the case fatality rates for three groups of patients who had myocardial infarctions. During both decades of the study, the 24-hour and 30-day case fatality rates for men increased steadily from group 1 (patients with a myocardial infarction as the initial manifestation of coronary heart disease) to group 3 (patients with a second myocardial infarction after surviving 30 days subsequent to the initial infarction). In women, the distinctions were not so clear, but, as expected, the highest rates were in those with second myocardial infarctions. Both 24-hour and 30-day case fatality rates decreased substantially during the second decade of the study in all groups and in both sexes. Discussion.—Many of the reported series of patients with coronary heart disease are based on hospitalized
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patients or those in a coronary care unit. Few studies have focused on initial myocardial infarctions, and most published series have included patients who have had prior angina. In 1960, Juergens and associates8 reported on 279 Rochester residents who had a first clinically recognized myocardial infarction during the period 1935 to 1951. The 5-year survival for those who had had no prior angina was 63%. This figure had increased to 72% during the 2 decades of our study (1960 through 1979). The most common cause of death in the study by Juergens and colleagues was recurrence of myocardial infarction, as it was for the myocardial infarction cohort in our study. Kannel and associates9 discussed the prognosis of patients (193 men and 53 women) after an initial myocardial infarction. In these patients, however, the infarction was not necessarily the first manifestation of coronary heart disease; first myocardial infarctions after the diagnosis of angina pectoris were also included. During the first 5 years, reinfarction occurred in 13% of the men and 39% of the women. Weinblatt and associates'0 reported on the prognosis of 881 men with myocardial infarction who were 25 to 64 years of age at the time of entry into a health insurance plan. This series included patients with a prior diagnosis of angina. The reinfarction rate during the first 4V2 years for 1-month survivors without prior angina was 23%. In our series, for men 30 years old or older, the corresponding rate was 30%. The results in the Rochester study did not confirm the report by others that female patients have a disadvantage in case fatality or early mortality after myocardial infarction. Despite the fact that the women were considerably older, they did as well as or better than the men.
CONCLUSIONS Among those patients whose first manifestation of coronary heart disease was angina pectoris, the occurrence of myocardial infarction declined significantly and survivorship improved significantly from the 1960s to the 1970s. Among those whose first manifestation of coronary heart disease was a myocardial infarction, the 30-day case fatality declined considerably from the 1960s to the 1970s, but no improvement occurred in reinfarction rates or subsequent survivorship among the 30-day survivors. ACKNOWLEDGMENT We thank Virginia A. Gosselin, Marie L. Notermann, Anastasia M. Ryan, and Chu-Pin Chu for their major contributions to this study.
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OF PATIENTS W I T H CORONARY HEART DISEASE
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Connolly DC, Oxman HA, Nobrega FT, Kurland LT, Kennedy MA, Elveback LR: Coronary heart disease in residents of Rochester, Minnesota, 1950-1975. I. Background and study design. Mayo Clin Proc 56:661-664, 1981 Elveback LR, Connolly DC, Kurland LT: Coronary heart disease in residents of Rochester, Minnesota. II. Mortality, incidence, and survivorship, 1950-1975. Mayo Clin Proc 56:665-672, 1981 Kännel WB, Feinleib M: Natural history of angina pectoris in the Framingham Study: prognosis and survival. Am J Cardiol 29:154-163, 1972 Weinblatt E, Frank CW, Shapiro S, Sager RV: Prognostic factors in angina pectoris: a prospective study. I Chronic Dis 21:231-245, 1968 Parker RL, DryT], Willius FA, Gage RP: Life expectancy in angina pectoris. JAMA 131:95-100, 1946
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Block WJJr, Crumpacker EL, DryTJ, GageRP: Prognosis of angina pectoris: observations in 6,882 cases. JAMA 150:259-264, 1952 Pryor DB, Harrell FEJr, Lee KL, Califf RM, Rosati RA: An improving prognosis over time in medically treated patients with coronary artery disease. A m J Cardiol 52:444-448, 1983 Juergens JL, Edwards JE, Achor RWP, Burchell HB: Prognosis of patients surviving first clinically diagnosed myocardial infarction. Arch Intern Med 105:444-450, 1960 Kannel W B , Sorlie P, McNamara PM: Prognosis after initial myocardial infarction: the Framingham Study. Am J Cardiol 44:53-59, 1979 Weinblatt E, Shapiro S, Frank CW, Sager RV: Prognosis of men after first myocardial infarction: mortality and first recurrence in r e l a t i o n to s e l e c t e d p a r a m e t e r s . A m J P u b l i c H e a l t h 58:1329-1347, 1968