PREVENTIVE
MEDICINE
Occlusive
8, 419-428
(1979)
Coronary Artery Disease and Parental of Myocardial Infarction’
History
ALFRED J. ANDERSON,* RICHARDF.LOEFFLER,* JOSEPH J. BARBORIAK,~ AND ALFRED A. RIMM*,* *Department of Preventive Medicine, The Medical College of Wisconsin. Post Office Box 26509, Milwaukee, Wisconsin 53226, and tResearch Service, Wood Veterans Administration Center and The Departments of Pharmacology and Medicine, The Medical College of Wisconsin, Milwaukee, Wisconsin 53193
The extent of coronary occlusive disease as determined by arteriography was correlated with parental history of MI in this study of 1671 male and 520 female heart patients. In both male and female patients having no or minimal occlusive disease, a significantly lower proportion was found to have parental history of MI than did those with more extensive disease. Parental history of MI was included in a multiple linear regression model along with age, plasma cholesterol, plasma triglycerides, obesity, hypertension, hyperglycemia, cigarette smoking, and alcohol intake as independent variables and the extent of occlusive disease was used as the dependent variable. This analysis indicated that parental MI history had a significant association with occlusive disease that cannot be accounted for by elevations of the other risk factors. Certain risk factors (i.e., cholesterol, triglycerides, smoking, and diabetes) were found to be highly correlated to the severity of coronary occlusion. For patients with lower levels of cholesterol, triglycerides, smoking, and diabetes, significantly greater occlusion was observed in patients with a parental MI history compared with those who did not. For patients with higher levels of these risk factors, the association between parental history of MI and degree of occlusion was minimal. The results suggest that parental history of MI may play a direct causal role in the pathogenesis of coronary occlusive disease.
A number of studies ( 10, 20, 21, 23, 25) have suggested that coronary heart disease tends to aggregate in families. Hedstrand and Aberg (16) observed that patients with a high-risk profile for cardiovascular disease have parents with increased cardiovascular morbidity and mortality. Studies of twins (7-9, 15) have provided further evidence for a genetic influence on coronary heart disease (CHD). Others have suggested that the family aggregation of CHD may be mediated by familial resemblances with respect to other accepted risk factors, both genetic and environmental. However, some studies have indicated that the clustering of CHD cannot be totally accounted for by familial resemblances of certain risk factors, such as hypertension, plasma lipid levels, or smoking history (3, 8, 13, 14, 23). 1 Supported in part by United States Public Health Service NIH HL- 14378 and Veteran’s tration Research Funds. * To whom requests for reprints should be addressed.
Adminis-
419 0091.7435/79/030419-10$02.00/O Copyright @ 1979 by Academic Press. Inc. All rights of reproduction in any form reserved.
420
ANDERSON
ET AL.
Epstein (12), for example, indicated that familial aggregation of CHD in men could not be explained in terms of the familial resemblance of the risk factors serum cholesterol and blood pressure and must, therefore, be due to other still undetermined influences. When attempting to evaluate the risk associated with a positive familial history of CHD, most studies used non-invasive endpoints such as angina pectoris and nonfatal and fatal MI. These endpoints can indicate only indirectly the relationship between a positive parental history and coronary occlusive disease. A more direct method of evaluating this relationship is to determine the actual extent of occlusion by coronary arteriography. In this study we have examined the association between parental history of MI and the degree of coronary occlusion, and how this relationship is influenced by certain previously studied factors associated with coronary occlusion: age, plasma cholesterol and triglyceride levels, obesity, hypertension, hyperglycemia, cigarette smoking, and alcohol intake. METHODS
A group of 1671 male and 520 female patients referred to St. Luke’s or Wood Veteran’s Hospital in Milwaukee, Wisconsin between 1972 and 1977 for diagnostic angiographic examinations and who volunteered to complete a comprehensive medical and social inventory were studied. The criteria for having arteriography was stable or progressing angina pectoris, previous MI, positive stress test, or chest pain of unknown origin if the patient was in a critical employment area (i.e., airplane pilot). Only patients for whom all data were complete were included in the study. The coronary angiography was carried out using the technique described by Sones and Shirey (26) or by Judkins (17) and the films were reviewed by cardiologists experienced in the interpretation of angiograms. The total extent of the occlusion was calculated as suggested by Rowe et al. (22) with the exception that inverted values were used, a score of 0 indicating the absence of any flow interference and 300 denoting a total occlusion of the three main coronary arteries. Analysis for plasma total cholesterol and triglycerides was performed on fasting blood samples, which were collected before angiography , prior to heparin administration (5, 18). Data concerning such factors as previous MI, angina pectoris, diabetes, obesity, hypertension, smoking, and alcohol intake, were obtained by direct questioning of the patient and checked against the appropriate medical records. The agreement between the two sources was at least 85% for all factors. Parental history of MI was obtained by direct questioning of the patient. Questioning a patient concerning his or her parents’ cause of death has been found to be reliable for sources related to CHD (27). In addition, since all of these patients have symptoms of CHD, they are probably more aware of relatives with CHD. The degree of smoking was classified for each patient according to length of time, quantity, and type of smoking habit, using the 5-point scale proposed by Anderson et al. (2). This scale ranged from a score of 1, indicating nonsmokers, to 5, designating heavy cigarette smokers with a 30-year or more history. The intake of various alcoholic beverages was converted to milliliters of absolute alcohol per week as previously described by Barboriak er al. (4). Because age is significantly
PARENTAL
MI
HISTORY
AND
CORONARY
OCCLUSION
421
correlated to occlusion score and the other risk factors, the relation of parental history of MI to these other factors was studied for patients less than 50 years of age and those 50 or older. Statistical techniques used to examine the relationship of each risk factor to occlusion were x2, I test, and multiple regression. RESULTS
The proportion of patients, in each of the occlusion score groups, with at least one parent having suffered an MI are given in Table 1. Patients in the occlusion score group less than 50 were compared with each of the two higher occlusion score groups. The proportion of male patients with parental MI history was significantly higher in the two groups with the higher occlusion scores than in the patients with occlusion scores less than 50. This was observed for patients less than 50 years of age (34, 50, and 48%) as well as for patients over 50 years of age (24, 40, and 39%). In both age groups, there was no appreciable difference in the proportion of patients with parental MI history between the two higher occlusion score groups. The younger female patients had an increase in the proportion with parental MI history from the low to the two higher occlusion score groups (37, 58, and 56%). Due to the small number of patients, these increases were not significant. A significant difference was seen between the less than 50 and the 50- 149 occlusion score group in the older females (37 and 53%). When divided into two occlusion score groups, O-49 and 50-300, the proportion of female patients with a parental history of MI was found to be significantly different for both age groups. The values presented in Table 1 indicate that there may be a distinct relationship between a positive parental history of MI and the degree of occlusion. To further define this relationship, other factors associated with CHD were examined. The mean values of these other factors studied are given in Table 2 for patients grouped by sex and parental history of MI. The mean occlusion scores, for both males and females, were significantly higher (P < 0.01) in patients with a positive parental history of MI (133 and 148 for males, and 56 and 77 for females). The mean values of cholesterol were found to be significantly different between the two groups (244 and 249 mgldl, P < 0.05 for males, and 238 and 253 mgldl, P < 0.01 for females). Males with a positive parental history of MI had a significantly lower mean age (53.1 and 52.1 years P -=c0.05). In addition to showing a relationship between parental history of MI and occlusion score, the results in Table 2 indicate the necessity for considering associations between other risk factors and parental MI history. To determine whether or not a positive parental history demonstrates an association beyond that accounted for by these other risk factors, the multiple linear regression technique was used. The results are given in Table 3. A parental history of MI significantly entered the regression equation (P < 0.05) in all cases except for females age
MEDICINE
Occlusive
8, 419-428
(1979)
Coronary Artery Disease and Parental of Myocardial Infarction’
History
ALFRED J. ANDERSON,* RICHARDF.LOEFFLER,* JOSEPH J. BARBORIAK,~ AND ALFRED A. RIMM*,* *Department of Preventive Medicine, The Medical College of Wisconsin. Post Office Box 26509, Milwaukee, Wisconsin 53226, and tResearch Service, Wood Veterans Administration Center and The Departments of Pharmacology and Medicine, The Medical College of Wisconsin, Milwaukee, Wisconsin 53193
The extent of coronary occlusive disease as determined by arteriography was correlated with parental history of MI in this study of 1671 male and 520 female heart patients. In both male and female patients having no or minimal occlusive disease, a significantly lower proportion was found to have parental history of MI than did those with more extensive disease. Parental history of MI was included in a multiple linear regression model along with age, plasma cholesterol, plasma triglycerides, obesity, hypertension, hyperglycemia, cigarette smoking, and alcohol intake as independent variables and the extent of occlusive disease was used as the dependent variable. This analysis indicated that parental MI history had a significant association with occlusive disease that cannot be accounted for by elevations of the other risk factors. Certain risk factors (i.e., cholesterol, triglycerides, smoking, and diabetes) were found to be highly correlated to the severity of coronary occlusion. For patients with lower levels of cholesterol, triglycerides, smoking, and diabetes, significantly greater occlusion was observed in patients with a parental MI history compared with those who did not. For patients with higher levels of these risk factors, the association between parental history of MI and degree of occlusion was minimal. The results suggest that parental history of MI may play a direct causal role in the pathogenesis of coronary occlusive disease.
A number of studies ( 10, 20, 21, 23, 25) have suggested that coronary heart disease tends to aggregate in families. Hedstrand and Aberg (16) observed that patients with a high-risk profile for cardiovascular disease have parents with increased cardiovascular morbidity and mortality. Studies of twins (7-9, 15) have provided further evidence for a genetic influence on coronary heart disease (CHD). Others have suggested that the family aggregation of CHD may be mediated by familial resemblances with respect to other accepted risk factors, both genetic and environmental. However, some studies have indicated that the clustering of CHD cannot be totally accounted for by familial resemblances of certain risk factors, such as hypertension, plasma lipid levels, or smoking history (3, 8, 13, 14, 23). 1 Supported in part by United States Public Health Service NIH HL- 14378 and Veteran’s tration Research Funds. * To whom requests for reprints should be addressed.
Adminis-
419 0091.7435/79/030419-10$02.00/O Copyright @ 1979 by Academic Press. Inc. All rights of reproduction in any form reserved.
420
ANDERSON
ET AL.
Epstein (12), for example, indicated that familial aggregation of CHD in men could not be explained in terms of the familial resemblance of the risk factors serum cholesterol and blood pressure and must, therefore, be due to other still undetermined influences. When attempting to evaluate the risk associated with a positive familial history of CHD, most studies used non-invasive endpoints such as angina pectoris and nonfatal and fatal MI. These endpoints can indicate only indirectly the relationship between a positive parental history and coronary occlusive disease. A more direct method of evaluating this relationship is to determine the actual extent of occlusion by coronary arteriography. In this study we have examined the association between parental history of MI and the degree of coronary occlusion, and how this relationship is influenced by certain previously studied factors associated with coronary occlusion: age, plasma cholesterol and triglyceride levels, obesity, hypertension, hyperglycemia, cigarette smoking, and alcohol intake. METHODS
A group of 1671 male and 520 female patients referred to St. Luke’s or Wood Veteran’s Hospital in Milwaukee, Wisconsin between 1972 and 1977 for diagnostic angiographic examinations and who volunteered to complete a comprehensive medical and social inventory were studied. The criteria for having arteriography was stable or progressing angina pectoris, previous MI, positive stress test, or chest pain of unknown origin if the patient was in a critical employment area (i.e., airplane pilot). Only patients for whom all data were complete were included in the study. The coronary angiography was carried out using the technique described by Sones and Shirey (26) or by Judkins (17) and the films were reviewed by cardiologists experienced in the interpretation of angiograms. The total extent of the occlusion was calculated as suggested by Rowe et al. (22) with the exception that inverted values were used, a score of 0 indicating the absence of any flow interference and 300 denoting a total occlusion of the three main coronary arteries. Analysis for plasma total cholesterol and triglycerides was performed on fasting blood samples, which were collected before angiography , prior to heparin administration (5, 18). Data concerning such factors as previous MI, angina pectoris, diabetes, obesity, hypertension, smoking, and alcohol intake, were obtained by direct questioning of the patient and checked against the appropriate medical records. The agreement between the two sources was at least 85% for all factors. Parental history of MI was obtained by direct questioning of the patient. Questioning a patient concerning his or her parents’ cause of death has been found to be reliable for sources related to CHD (27). In addition, since all of these patients have symptoms of CHD, they are probably more aware of relatives with CHD. The degree of smoking was classified for each patient according to length of time, quantity, and type of smoking habit, using the 5-point scale proposed by Anderson et al. (2). This scale ranged from a score of 1, indicating nonsmokers, to 5, designating heavy cigarette smokers with a 30-year or more history. The intake of various alcoholic beverages was converted to milliliters of absolute alcohol per week as previously described by Barboriak er al. (4). Because age is significantly
PARENTAL
MI
HISTORY
AND
CORONARY
OCCLUSION
421
correlated to occlusion score and the other risk factors, the relation of parental history of MI to these other factors was studied for patients less than 50 years of age and those 50 or older. Statistical techniques used to examine the relationship of each risk factor to occlusion were x2, I test, and multiple regression. RESULTS
The proportion of patients, in each of the occlusion score groups, with at least one parent having suffered an MI are given in Table 1. Patients in the occlusion score group less than 50 were compared with each of the two higher occlusion score groups. The proportion of male patients with parental MI history was significantly higher in the two groups with the higher occlusion scores than in the patients with occlusion scores less than 50. This was observed for patients less than 50 years of age (34, 50, and 48%) as well as for patients over 50 years of age (24, 40, and 39%). In both age groups, there was no appreciable difference in the proportion of patients with parental MI history between the two higher occlusion score groups. The younger female patients had an increase in the proportion with parental MI history from the low to the two higher occlusion score groups (37, 58, and 56%). Due to the small number of patients, these increases were not significant. A significant difference was seen between the less than 50 and the 50- 149 occlusion score group in the older females (37 and 53%). When divided into two occlusion score groups, O-49 and 50-300, the proportion of female patients with a parental history of MI was found to be significantly different for both age groups. The values presented in Table 1 indicate that there may be a distinct relationship between a positive parental history of MI and the degree of occlusion. To further define this relationship, other factors associated with CHD were examined. The mean values of these other factors studied are given in Table 2 for patients grouped by sex and parental history of MI. The mean occlusion scores, for both males and females, were significantly higher (P < 0.01) in patients with a positive parental history of MI (133 and 148 for males, and 56 and 77 for females). The mean values of cholesterol were found to be significantly different between the two groups (244 and 249 mgldl, P < 0.05 for males, and 238 and 253 mgldl, P < 0.01 for females). Males with a positive parental history of MI had a significantly lower mean age (53.1 and 52.1 years P -=c0.05). In addition to showing a relationship between parental history of MI and occlusion score, the results in Table 2 indicate the necessity for considering associations between other risk factors and parental MI history. To determine whether or not a positive parental history demonstrates an association beyond that accounted for by these other risk factors, the multiple linear regression technique was used. The results are given in Table 3. A parental history of MI significantly entered the regression equation (P < 0.05) in all cases except for females age
