Generalizability of Occupational Cohort Study Findings

To the Editor: A primary concern in epidemiologic research is the application of results to the “real world”—that is, the extent to which findings are generalizable across epochs and populations. It is widely assumed that nationally representative studies provide the most population-transportable results. In the context of etiologically orientated cardiovascular disease (CVD) research, although several nationally representative cohort studies do exist, investigators also initiate cohort studies using convenience samples based on society membership, religious order, church group, morbidity, educational institution, insurance policy cover, specific geographical location, and, perhaps most frequently, occupational group.1 Although there is evidence that the prevalence of unfavorable risk factors and the incidence of disease occur at lower levels in occupational groups relative to the general population (the so-called “healthy-worker” effect),2 it is unclear what implications this has for understanding disease etiology, that is, the association between potential risk factors and disease—the objective of most cohort studies. Unaware of any empirical examination of this issue, we computed risk factor–CVD associations in an occupational cohort study (Whitehall II)3 and assessed their generalizability by comparing them with those reported in publications from a well-established UK-wide general population-based study (the British Regional Heart Study BRHS of men)4 and a US study from which risk algorithms for cardiovascular disease are widely computed (the Framingham study of men and women).5 Wherever possible in our analyses of Whitehall II study raw data, we replicated published analyses from the BRHS4 and the Framingham study.5 See the eAppendix (https://links.lww.com/EDE/A834) for an additional note on our analytic procedures. As anticipated, the rate of incident coronary heart disease (CHD) in the Whitehall II study (3.23 per 1000 man-years) was markedly lower than that in the BRHS4 (8.16). In addition, levels of CHD risk factors were more favorable in Whitehall II relative to the BRHS cohort6: mean systolic blood pressure (121.8 mmHg vs. 145.1 mmHg), cigarette smoking (12.7% vs. 41.3%), high body mass index ≥28.5 kg/m2 (13.0% vs. 16.1%), and alcohol intake of >6 drinks/day (3.9% vs. 24.9%). In the Figure, we present the relation of classic risk factors with coronary heart disease in the BRHS4 and the Whitehall II study. Comparing hazard ratios between the studies, the direction of association was the same for all risk factor–CHD relations and, in most cases, the magnitude of these relations was similar or identical. The only exceptions were the effect estimates for former smokers relative to never smokers, where the relation was weaker in the Whitehall II study, and for higher relative to lower BMI, where the relation was stronger in Whitehall II.FIGURE: Classic risk factors for coronary heart disease. Analyses are based on 7198 men (799 CHD events) in the British Regional Heart Study (BRHS) and 4456 men (229 CHD events) in the Whitehall II study. Results are hazard ratios (95% confidence intervals). Adjustments are for age, lifestyle factors, diabetes, and preexisting CHD (without diagnosis). In addition, when the blood pressure and cholesterol variables were the exposures of interest, there was mutual adjustment for each variable. For insulin, adjustment was also made for systolic blood pressure and total cholesterol. P values are for tests of between-study heterogeneity.Although the rate of CVD events in Framingham was not reported, we were able to compute the proportion of cases and, again, as expected, these were lower in the Whitehall II than Framingham study members for both men (9% vs. 18%) and women (7% vs. 10%). In eFigure 1A (men) and 1B (women), https://links.lww.com/EDE/A834, we compare risk factors for CVD in the Framingham5 and Whitehall II studies. In both sets of analyses, the direction of association was again the same for all risk factor–CVD relations and, in all cases, the magnitude of these effects was similar. The only departure from this observation was the somewhat stronger association between age and CVD in Whitehall II for men and women. In conclusion, despite marked differences in both risk factors and disease incidence that favored the Whitehall II study, in the context of standard risk factor–CVD associations, we found close agreement between the findings from this occupational cohort study, a UK-wide general population study (BRHS), and an iconic, community-based US study (Framingham). G. David Batty Martin Shipley Adam Tabák Archana Singh-Manoux Eric Brunner Annie Britton Mika Kivimäki Research Department of Epidemiology and Public Health University College London London, United Kingdom email protected