Francis A.L. Mathewson

Relation of Body Weight to Development of, Ischemic Heart Disease in a Cohort of Young North American Men After a 26 Year Observation Period: The Manitoba Study

The role of overweight as a risk factor for ischemic heart disease remains controversial. Therefore, in the Manitoba Study of a cohort of 3,983 men with a mean age at entry of 30.8 years, initial measurements of body weight, represented by body mass index (weight/height2), were compared with the 26 year incidence of ischemic heart disease. After adjustment for the effects of age and blood pressure in univariate and multivariate analysis, body mass index was a significant predictor of the 390 cases of ischemic heart disease. To elucidate this relation further, the cohort was further analyzed after categorization by age at entry, time of occurrence of disease after entry and manifestation of ischemic heart disease. The association with weight was most apparent in men less than 40 years of age and was not evident until 16 years of follow-up. A high body mass index was significantly associated with development of myocardial infarction, sudden death and coronary insufficiency or suspected myocardial infarction; the relation was strongest with sudden death. Among men who had a myocardial infarction, body mass index was more strongly associated with sudden death and was the best predictor of myocardial infarction occurring after 20 years of observation. Thus, after adjustment for the effect of age and blood pressure, overweight is a definite risk factor but primarily in younger men, after long periods of observation and for certain manifestations of ischemic heart disease.

The Natural History of Primary First-Degree Atrioventricular Heart Block

The long-term prognosis of first-degree heart block in the absence of organic heart disease has not been clearly defined. We addressed this question in a 30-year longitudinal study of 3983 healthy men. We identified 52 cases that were present on entry into the study and 124 incident cases during follow-up. The incidence rose steadily after age 40 and was 1.13 per 1000 person-years over the entire period. Two thirds of the cases had only moderate prolongation of the PR interval (0.22 to 0.23 second). We compared four age-matched controls with each case for histories of scarlet fever, rheumatic fever, diphtheria, smoking, blood pressure, and body-mass index. No significant differences (P greater than 0.05) were found. Likewise, mortality from all causes did not differ between cases and controls. Although somewhat higher rates of morbidity and mortality from ischemic heart disease were observed in the cases than in the controls, the differences were not significant. Progression to higher grades of heart block occurred in only two cases. In view of the prognostic findings and the rare occurrence of advanced degrees of heart block, we conclude that primary first-degree heart block with moderate PR prolongation is a benign condition. This conclusion may not apply, however, to persons with more marked prolongation of the PR interval, a very rare condition.

Predicting Risk of Ischemic Heart Disease and Cerebrovascular Disease from Systolic and Diastolic Blood Pressures

The relative importance of systolic versus diastolic blood pressure in predicting risk of ischemic heart disease or cerebrovascular disease is controversial. Since 1948 we have observed in the Manitoba Study 3983 men (most between 25 to 34 years old at entry), in whom risk of both diseases was determined using the multiple logistic model. Systolic and diastolic blood pressures after adjustment for age and body weight were compared at entry and at four other examinations during the follow-up period. When both blood pressures were considered together, a stronger association with cerebrovascular disease was found for systolic compared to diastolic blood pressure at entry and at most of the other examinations. For ischemic heart disease, diastolic pressure showed a stronger association at the earlier examinations, whereas systolic pressure was more important when the majority of the cohort was between 40 to 50 years of age. In middle-aged men the general concept that diastolic is more important than systolic is not justified for cerebrovascular disease or for ischemic heart disease.

The Natural History of Electrocardiographic Preexcitation in Men: The Manitoba Follow-up Study

OBJECTIVE To examine the natural history of preexcitation occurring on the routine electrocardiogram (ECG). DESIGN A longitudinal cohort study of 3983 originally healthy men followed prospectively for 40 years. SETTING Free-living (community-dwelling) study members residing predominantly in Canada. PARTICIPANTS Nineteen male study members with preexcitation occurring during routine examination in the 40-year follow-up of the Manitoba Follow-up Study. MEASUREMENTS Routinely requested clinical examinations and ECGs, supplemented by information supplied by the study member or his physician. MAIN RESULTS Ten study members were found to have preexcitation at enrollment, for a prevalence of 2.5 per 1000 (95% CI, 1.2 to 4.6). A delta wave was first detected during follow-up in an additional nine study members. Seventeen of 19 study members did not have the delta wave at some later time, and preexcitation was intermittently present in most of these members. Over time there was a loss of preexcitation, with 15 of 19 study members no longer exhibiting a delta wave by the end of follow-up. Five of 11 study members with symptoms had physician confirmation of an arrhythmia. Fourteen study members remain alive, and none of the five deaths was attributed to preexcitation. CONCLUSIONS Preexcitation found on routine ECG in our originally healthy male study group did not confer excess morbidity or mortality, even in those study members who developed symptomatic arrhythmias. Most preexcitation was intermittent and disappeared over time.

Prognosis after acute myocardial infarction: Relation to blood pressure values before infarction in a prospective cardiovascular study

Abstract The relation of preexisting hypertension to survival after myocardial infarction is uncertain, but it has been examined primarily in studies with limited data on previous blood pressure values. Therefore in the Manitoba Study cohort, 3,983 men under observation since 1948, the last recorded blood pressure before the first myocardial infarction as well as the change in blood pressure from a measurement made 5 years previously was related to survival after the infarction. With use of the life table method, progressively increasing values for systolic or diastolic blood pressure were found to be associated with worsening prognosis. Subjects with a systolic pressure of 140 mm Hg or greater or a diastolic pressure of 90 mm Hg or greater had a significantly ( P P To standardize the follow-up period, short-term mortality rates were based on data from patients under study for up to 1 month after myocardial infarction and long-term mortality rates on those from subjects under observation 1 month to 3 years after infarction. In multivariate analysis—after adjusting for the effect of age at infarction, previous evidence of angina pectoris or coronary insufficiency, previous episodes of left ventricular failure, transmural or nontransmural infarction and site (anterior or inferior) of transmural infarct—blood pressure was a significant ( P P P

Natural history of left bundle-branch block.

The purpose of this study was to examine factors associated with the development of complete left bundle-branch block and the prognosis in a group of people not in hospital, who had no clinical evidence of ischaemic or valvular heart disease. Twenty-nine cases of left bundle-branch block without clinical evidence of ischaemic heart disease were noted in the Manitoba cohort of 3983 men under observation since 1948. The most frequent electrocardiographic finding before development of left bundle-branch block was a normal electrocardiogram; left ventricular hypertrophy though infrequent, was the only abnormality significantly more common than in the rest of the group. The development of left bundle-branch block was associated with distinct leftward shift of the frontal plane mean QRS axis. The most frequent clinical cardiovascular event observed after development of the block was sudden death without previous clinical evidence of ischaemic heart disease. The five-year incidence of sudden death as the first manifestation of heart disease was 10 times greater in men with left bundle-branch block than in those without it.

Blood pressure and body mass index patterns—A longitudinal study

Abstract The patterns of longitudinal changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index ( BMI = weight height 2 ) are explored on 3054 male subjects who remained alive and free of ischemie heart disease and/or stroke after 27 yr of follow-up in the Manitoba Follow-up Study. BMI tends to increase during adulthood, maintains in middle ages, and drops in old ages. With moderate acceleration, SBP continues to rise with age. DBP tends to rise with age until mid-fifties and then levels off. The correlations of age with BMI changes over time from significant positive at entry to significant negative by the end of the study period. The correlation of age with SBP changes from non-significant to highly significant positive; and with DBP, the correlation is significant but increases only in the first 10 yr, after which it fluctuates and decreases. These findings have implications on the relative importance of BMI, SBP andd DBP as coronary risk factors in younger and older men. Despite the high variability of blood pressure and the regression toward the mean phenomenon, BMI, SBP and DBP tend to retain their relative positions in their own distributions even after 25 yr. The correlation between the initial and later readings decreases with time but remains highly significant. The correlation between two readings five years apart is stronger in older men than in younger men. The future levels of blood pressure are predictable not only by its own attained levels, but also by age and BMI. Inclusion of all three of these factors improves the prediction. The overall distribution of the linear rate of change in BMI is bimodal, whereas that of SBP and DBP is unimodal. The differences in age does not account for these distributions, because similar unimodalities are also observed in men of the same single age. The variations in the rate of rise for men of the same single age indicate that factors other than age are responsible. Strong positive association between age and the mean linear rate of rise also indicate that the responsible factors are acting more effectively in older men. On the rate of rise, analytical results support the importance of age, not the attained level of blood pressure. The attained level of BMI, though strongly associated with the levels of blood pressure, is not related to the rate of change in blood pressure. The change of BMI, however, is strongly associated with those of blood pressure. In young men, the change of BMI is similarly associated with those of SBP and DBP; in older men, it is more related to that of DBP. As a mean of controlling high blood pressure, early prevention of weight gain is suggested. Although SBP and DBP are highly correlated and their correlation improves with time, evidence shows that they do not have the same pattern of change: SBP follows a fluctuating upward trend while DBP follows a quadratic trend. These observations confirm the findings from cross-sectional studies. By using orthogonal transformation, the parameters of an orthogonal polynomial fitted exactly to each individual are analyzed. This method of analysis gives similar results as obtained by using other methods and is shown to be simple, informative and effective in describing individual patterns of change over time, suggesting evidence of etiological interest and establishing relationships between trends of change.

The relation of blood pressure to stroke prognosis.

The relation between blood pressure before stroke and survival after the event, was examined in the Manitoba study cohort of 3983 men. The last recorded blood pressure before the first stroke and the change in blood pressure from a measurement 5 years earlier were used. Increasing magnitude of systolic blood pressure and its 5-year changes were associated with worsening prognosis. The same association was less apparent for diastolic blood pressure and was not found for 5-year change in diastolic pressure. After adjusting for the effect of age at stroke and previous evidence of ischemic heart disease in multivariate analysis, systolic blood pressure and its 5-year change were each significant predictors of short-term (30 days) mortality. Considering all these factors as well as diastolic blood pressure, systolic blood pressure was the best predictor of short-term mortality. Thus, high blood pressure and large positive 5-year change in systolic blood pressure before stroke occurrence are significant predictors of a poor prognosis.

Evidence that height is an independent risk factor for coronary artery disease (the Manitoba follow-up study)

Abstract In conclusion, height is a risk factor for CAD. A similar trend was noted for cardiovascular and total mortality. The mechanism underlying this association may involve both genetic and environmental factors.

Natural history of marked left axis deviation (left anterior hemiblock)

Abstract The purpose of this study was to examine several electrocardiographic variables that may be associated with the development of marked left axis deviation (ÂQRS −45 ° to −90 °) in men free of ischemic heart disease and to determine whether left axis deviation is associated with an increased probability of developing other conduction disturbances. During the 28 year observation period in the Manitoba Study cohort of 3,983 men, 222 new cases of marked left axis deviation were noted in the absence of heart disease. The majority, 81.5 percent (181 men), had the same Q waves or absence of Q waves in leads I or aVL, or both, before and on detection of left axis deviation, 10.4 percent (23 men) had new Q waves or increased width of previous Q waves, and 8.1 percent (18 men) had Q waves that disappeared or became smaller. Not all cases of left axis deviation resulted from a superior and leftward movement of ÂQRS; 10.4 percent (23 men) had an indeterminate ÂQRS on entry due to an S 1 S 2 S 3 pattern. Left axis deviation developed in a significantly ( P 1 S 2 S 3 on entry (44 percent, 23 of 52 men) than of those without S 1 S 2 S 3 on entry (5.1 percent, 199 of 3,906 men). Of the 247 cases of left axis deviation, 25 were detected on and 222 after entry into the study. Complete right bundle branch block developed in 2.4 percent of these men (6 of 247), a larger proportion than those without left axis deviation. In the absence of development of intercurrent ischemic heart disease, complete left bundle branch block developed in 0.8 percent (two men), and none had complete atrioventricular block. Men with an S 1 S 2 S 3 pattern on entry or with left axis deviation before age 40 years comprised a subgroup that did not develop other conduction disturbances. The presence or absence of Q waves in lead I or aVL, or both, did not influence the association between left axis deviation and right bundle branch block. Therefore (1) the development of left axis deviation was not associated with a significant change in Q waves in leads I or aVL, or both; (2) an indeterminate ÂQRS from an S 1 S 2 S 3 pattern is significantly associated with the subsequent development of left axis deviation; and (3) in the absence of clinically apparent heart disease, the likelihood of the development of complete right bundle branch block is increased slightly in men with marked left axis deviation.