Modern medicine is overwhelmed by a plethora of both established risk factors and novel biomarkers for diseases. The majority of this information is expressed by probabilistic measures of association such as the odds ratio (OR) obtained by calculating differences in average "risk" between exposed and unexposed groups. However, recent research demonstrates that even ORs of considerable magnitude are insufficient for assessing the ability of risk factors or biomarkers to distinguish the individuals who will develop the disease from those who will not. In regards to coronary heart disease (CHD), we already know that novel biomarkers add very little to the discriminatory accuracy (DA) of traditional risk factors. However, the value added by traditional risk factors alongside simple demographic variables such as age and sex has been the subject of less discussion. Moreover, in public health, we use the OR to calculate the population attributable fraction (PAF), although this measure fails to consider the DA of the risk factor it represents. Therefore, focusing on CHD and applying measures of DA, we re-examine the role of individual demographic characteristics, risk factors, novel biomarkers and PAFs in public health and epidemiology. In so doing, we also raise a more general criticism of the traditional risk factors' epidemiology. We investigated a cohort of 6103 men and women who participated in the baseline (1991-1996) of the Malmö Diet and Cancer study and were followed for 18 years. We found that neither traditional risk factors nor biomarkers substantially improved the DA obtained by models considering only age and sex. We concluded that the PAF measure provided insufficient information for the planning of preventive strategies in the population. We need a better understanding of the individual heterogeneity around the averages and, thereby, a fundamental change in the way we interpret risk factors in public health and epidemiology.
Keywords: ACE, Average causal effect; AUC, Area under the ROC curve; CABG, Coronary artery bypass graft; CHD, Coronary heart disease; CRP, C-reactive protein; Coronary heart disease; DA, Discriminatory accuracy; Discriminatory accuracy; FPF, False positive fraction; HDL, High-density lipoprotein cholesterol; HR, Hazard ratios; ICE, Individual causal effect; Individual heterogeneity; LDL, Low-density lipoprotein cholesterol; Lp-PLA2, Lipoprotein-associated phospholipase A2; MDC study, The Malmö Diet and Cancer; Multilevel analysis; NTBNP, N-terminal pro–brain natriuretic peptide; OR, Odds ratio; Over-diagnosis; Overtreatment; PAF, Population attributable fraction; PAH, Phenylalanine hydroxylase; PCI, Percutaneous coronary intervention; PKU, Phenylketonuria; Population attributable fraction; RCT, Randomized clinical trial; ROC, Receiver operating characteristic; RR, Relative risk; Risk factors; TPF, True positive fraction.