Risk factor thresholds: their existence under scrutiny

Abstract

Interventions to lower blood pressure, serum cholesterol, and other risk factors reduce the risk of cardiovascular disease regardless of initial levels. It follows, say Malcolm Law and Nicholas Wald, that the goal is not to “normalise” risk factors but to reduce them as much as possible. This means targeting everyone at high risk, as determined by age or known cardiovascular disease rather than by the level of the risk factors Physiological variables such as blood pressure, serum cholesterol, body mass index, and bone mineral density are important in the aetiology of common diseases. They are not direct environmental causes of disease, like smoking, but they may be seen as biochemical or biophysical variables, under partial genetic control, that are intermediates between environmental factors and disease itself. It is known that risk can be reduced by lowering high levels of these variables by drug treatment or lifestyle change. But there is a view that changing the average values of these physiological variables is not worth while, a view that implies the presence of thresholds in the dose-response relations between the level of the variable and the risk of disease. This view is reinforced by terminology that regards extreme values as indicating a disease state (such as hypertension, hypercholesterolaemia, osteoporosis, and obesity) and average values as being “normal” (normotensive, normocholesterolaemia). Clinical guidelines specify risk factor thresholds1–5; these have been set at successively lower levels over time and redefined as “action levels” but they still deny treatment below specified values. We examine seven important dose-response relations to determine whether it is useful to impose risk factor thresholds or whether there are better ways to identify patients who should be treated. #### Summary points Understanding the dose-response relations between “physiological variables” (blood pressure, serum cholesterol, body mass index, bone mineral density) and the …