The mean age at coronary heart disease event among cases was 62 years (mean duration of follow up 9.5 years). There were highly significant differences between cases and controls with respect to known vascular risk factors such as smoking, obesity, blood pressure, and blood lipids concentrations (table ).
Baseline characteristics of men with coronary heart disease and of controls matched for age and town. Values are mean (SD) unless stated otherwise
Associations among different acute phase reactants
In controls without evidence of coronary heart disease at baseline, the correlation coefficients of the associations between plasma C reactive protein and serum amyloid A protein, leucocyte count, and albumin were 0.58, 0.33, and −0.19 respectively (P<0.0001 for each), and the correlation coefficients between serum amyloid A protein and leucocyte count and albumin were 0.19 and 0.14 respectively (P<0.0001 for each). These associations among the four acute phase reactants were not adjusted for values of one another to avoid overadjustment since they may reflect a common underlying process (see tables on BMJ 's website). Leucocyte count and serum albumin concentration were not strongly related (R=−0.06, P=0.08).
Acute phase reactants, classic vascular risk factors, and other characteristics
C reactive protein concentration was strongly associated with cigarette smoking, body mass index, and low forced expiratory volume in one second (P<0.0001 for each), and the associations were little changed by adjustments for age, town, smoking, and indicators of socioeconomic status. Associations of C reactive protein with high density lipoprotein cholesterol, triglyceride, urate, and insulin, however, weakened substantially after such adjustments (table A on BMJ 's website). There were strong and highly significant associations of serum amyloid A protein with body mass index and total cholesterol (P<0.0001) and with low forced expiratory volume (P<0.001) which remained significant after adjustment for possible confounders, but such adjustment substantially weakened the association with high density lipoprotein cholesterol (table B on website). Strong adjusted associations were observed between leucocyte count and cigarette smoking and packed cell volume (P<0.0001 for each, table C on website) and between low albumin and age and cigarette smoking (P<0.0001 for each, table D on website) and between albumin and blood pressure, total cholesterol, and packed cell volume (P<0.0001 for each). Possible associations existed between albumin and high density lipoprotein cholesterol, triglycerides, and serum markers of renal function. No consistent associations were observed of these acute phase proteins with H pylori seropositivity, C pneumoniae IgG titres, plasma total homocysteine concentrations, or a range of childhood or adult indicators of socioeconomic status.
Acute phase reactants and incident coronary heart disease
The odds ratio for coronary heart disease was 3.46 (95% confidence interval 2.59 to 4.62; χ2 =71, df=1) in men in the top third compared with those in the bottom third of baseline C reactive protein concentration (tertile cut offs, >2.4 v <0.9 mg/l). The odds ratio fell to 2.13 (1.38 to 3.28;χ2 =11.8, df=1) after smoking, vascular risk factors, and indicators of socioeconomic status were adjusted for (table ). Comparisons between the top and bottom thirds of the other factors gave the following adjusted odds ratios for coronary heart disease: 1.65 (1.07 to 2.55) for serum amyloid A protein (>9 v <6 mg/l); 1.12 (0.71 to 1.77) for leucocyte count (>7.8 v 6.4×109/l); and 0.67 (0.43 to 1.04) for albumin (>46 v <44 g/l). These results were not materially changed in analyses restricted to the 329 cases and 820 controls with no evidence of coronary heart disease at baseline (table ) or in analyses restricted to the 227 cases and 779 controls who had complete information on childhood socioeconomic status. The findings were also unaffected by varying the prespecified cut-off levels for analysis of each factor.
Odds of coronary heart disease in men who had values of inflammatory factors in top third of distribution of controls relative to those who had values in bottom third of this distribution