Discussion
The prospective studies that have included measures of impaired lung function such as PFR, FEV or FEV1 and that have shown an association with the incidence of fatal CHD have come from many settings, often the USA,4 ,5 ,7 ,10 but also from the UK and other European countries,2 ,6 ,8 ,12 ,14 China,11 ,15 Australia and New Zealand,9 and India.13 Some have collected data from more than one country.1 ,3 Many studies have typically reported relative risks (RRs) of 2 or less for the association between measures of impaired lung function and CHD, though in two North American studies,7 risks up to 4 were recorded. A systematic review of the relationship between FEV1 and cardiovascular mortality reported a pooled RR of 1.75 comparing those in the lowest quintile to the highest quintile of FEV1.16 In NPHS-1, the apparent effect of PFR on CHD, showing a HR difference of 53% between the lowest and highest quartiles, was modest using baseline characteristics (ie, analysis based on all participants) and had largely disappeared based on those who had follow-up examinations.
There do not appear to be large or consistent differences between FEV, FEV1 and PFR that would affect the findings of epidemiological studies. A study of older participants in east Boston5 also used only PFR, and gave much the same results as ours and as those for other studies (differences may be important in assessing lung function in clinical settings, such as acute asthma attacks in children.)
Data for men who had previously had major CHD events were not included in the analyses. However, abnormal ECGs often reflecting early pathological changes of CHD were, not surprisingly, significantly associated with CHD mortality. Omission of ECG data from other studies may thus well account for the generally stronger associations of PFR and other measures of impaired lung function with CHD than in NPHS–1, since these other studies have not been in a position to allow for the early pathology of CHD and the correlation of PFR with ECG findings. Smoking, cholesterol and systolic blood pressure were other independent risk factors associated with CHD death. We are aware of only one other study that has included measurement of plasma fibrinogen, which increases with the level of smoking but remains a strong independent risk factor for CHD. However, this study,30 CARDIA, dealt mainly with the association of fibrinogen with risk factors including COPD that contribute to CHD, rather than prospective associations with CHD itself.
In the present study, the association of plasma fibrinogen with fatal CHD was highly statistically significant in the multivariable analysis (table 2), which takes account of correlations between different risk factors. An explanation might be the contribution of fibrinogen to thrombosis in CHD, or as a marker of the degree of an inflammatory process in COPD and CHD. The trend was similar but reduced in the time-updated model (table 3), although there was little evidence for an association. There was a suggestion that factor VII may be associated with CHD in the multivariable model using baseline data, and may thus have contributed to the thrombotic element in CHD, though the finding was at a marginal level and there was no association in the time-updated model. There was no evidence that factors V and VIII and platelet count (as other components of the haemostatic system) were associated with fatal CHD. The Whitehall Cohort II study concluded that socioeconomic differences were not important in explaining the association between lung function and mortality.12
Virtually all prospective studies are missing data for some variables. Long-term follow-up periods almost inevitably mean that their data will be subject to competing risks of non-cardiac mortality. However, few allow for these points. We have used well-tested and accepted methods of imputation to allow for missing values in our data, and the results were similar compared with the analyses not using these methods. Allowance for competing risks of non-CHD mortality also made little difference.
Treatment of COPD appears to reduce the onset of cardiovascular disease.31 However, Lange et al6 concluded that “although impaired ventilatory function is a significant predictor of death from myocardial infarction and other cardiovascular diseases, it should not be regarded as a genuine risk factor for ischaemic heart disease.” We would agree with this view, in that the inclusion of a wide range of characteristics associated with CHD, including fibrinogen and abnormal ECG findings, suggests that measures such as PFR are not strongly and independently associated with fatal CHD, and that the view that they usefully predict CHD should be modified accordingly.