Electrocardiographic indicators of autonomic balance and mortality : a case-cohort approach.

The aim of the study reported in this thesis is. to investigate in a population of apparently healthy middle-aged civil servants, the predictive value for cardiovascular mortality of presumed electrocardiographic indicators of autonomic imbalance. For the sympathetic/parasympathetic balance RR- and PQ-interval lengths were considered as indicators. QT-interval length was taken as a manifestation of the balance between left and right sympathetic innervation. Minor abnormalities in ST-segment level and T-wave amplitude may reflect both kinds of imbalance. however. may also be a consequence of myocardial or epicardial disease. The following questions were studied in relation to these electrocardiographic parameters: Are these parameters separately. at rest or after exercise. associated with the risk of allcause. cardiovascular and coronary heart disease mortality? Are the observed associations between these parameters and mortality risk independent of established cardiovascular risk factors? To what extent do these electrocardiographic parameters combined predict coronary heart disease mortality risk? In addition to the electrocardiographic subject matter. this thesis also contains a methodological digression. Its purpose is to evaluate the performance of the case-cohort sampling design relative to other cost-efficient designs and to extend methods of data analysis for this design

Agreement between oral contraceptive users and prescribers: implications for case-control studies

Case-control studies examining the effects of oral contraceptives (OC) are prone to misclassification bias due to errors in assessment of OC use. Concern about inaccurate exposure histories has increased since current studies require women to recall OC use over prolonged periods of time. In preparation for a case-control study of breast cancer and OC use, an investigation was carried out to assess agreement between women's lifetime histories of OC use (covering a period of up to 20 years) and prescribers' records. OC histories were obtained during personal interview with 218 women who had used OC at some point in their lives (127 breast cancer patients, 91 controls). Recall was aided by an album with color photographs of all OC marketed in the Netherlands from 1962 onwards (n = 65), and a calendar that covered the women's life span from date of birth to menopause. The participants were asked for the names of all physicians who prescribed OC for them. The rate of response from the prescribers was high (94%), but only half of the forms provided useful information. Patient-prescriber agreement on brand names (including dosage) was 70%. About half of the women agreed with their prescribers on starting dates to within less than a year's difference. Approximately the same percentage of agreement was found for stopping dates. Multiple linear regression indicated that agreement on brand names and dates of usage was lower for women of low socioeconomic status, for healthy women (as compared to breast cancer patients) and for periods of pill use that had to be recalled from the more distant past. Agreement on total duration of use was high enough to permit testing of a moderately strong duration-response relationship in a case-control study

Well shaped ST segment and risk of cardiovascular mortality

OBJECTIVE--To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN--Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING--General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS--Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES--Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS--In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION--These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment