How well are Risk Factors established?

To establish the relevance of an imputed risk factor, evidence is sought from epidemiology studies. The frequency of the condition is measured in two or more groups of patients that have different frequencies of the factor being evaluated. The groups can be made up of cohorts of patients who are followed for a period of time, or the afflicted group together with a selected "case-control" group, consisting of one or more otherwise normal subjects for each diseased patient who are matched closely for age, sex, etc.

Statistical analyses allow calculation of the risk, which is usually expressed as a "Risk Ratio", a "Relative Risk", an "Odds Ratio", or a "Hazard Ratio", with the 95% confidence interval. It is generally accepted that confidence intervals give more useful information than the more usual P values. Multivariate (regression) analyses are used to neutralize the effects of one possible risk factor on another. Survival analyses (using Kaplan-Meier curves with confidence limits) can display the percentage of subjects with the condition in the comparison groups over a period of time.¹ It has recently become popular to express the benefits of an intervention as the number of subjects that need to be influenced (treated) in order to prevent one event - the so-called "potential for benefit".

Levels of Proof

In establishing the actual relevance of a risk factor, one can envisage three levels of evidence. The scientific basis for recommendation for risk intervention is based upon a 3- step process, which can be illustrated by consideration of a blood chemistry risk factor:

1. Demonstration by epidemiological methods that a given value of a given measurement confers a risk;
2. Demonstration that it is possible to reduce this value;
3. Demonstration that reducing the value reduces the risk for disease.

Risk factors can be at a different stage of proof with regard to steps 1-3 above. For instance, raised LDL-cholesterol has satisfied steps 1-3 with respect to coronary artery disease (CAD), while for others, such as polyunsaturated fatty acid intake or vitamins C and E supplements, only step 1 has been satisfied. We shall try in these pages to specify the step or degree of evidence fulfilled for each risk factor we consider.

Tackling Risk Factors

For some, indeed many, conditions, multiple risk factors combine to give an overall increased level of risk. This was done some years ago for the Framingham Heart Study.² We are currently developing updated combined risk tools for cardiovascular conditions such as acute MI and stroke, which will be posted to these pages.

For practical purposes, there are two ways to tackle changeable Risk Factors:

• Lifestyle Changes
• Medical Intervention

Lifestyle changes include diet, physical activity (endurance/aerobic and strength/resistance exercises), and overcoming an addiction (eating, smoking, excess alcohol, gambling, etc). The major impetus for change must come from the patients themselves. However, assistance is often required to overcome laziness, boredom and even dislike of the positive steps that must be taken. Support groups and medication may also be needed. Unfortunately, studies have shown that the family practitioner, who should be in the forefront in promulgating lifestyle changes, is largely ineffective in these efforts.

Medical intervention often involves lifetime treatment even when the patient is feeling quite well. Family members and physicians must offer every encouragement for the patient to stick to the prescribed medication, and to attend for regular check-ups.

These pages contain advice for health professionals on how to promote a high level of implementation of preventive measures. Among the arguments used is the concept of the world epidemic of CAD presently facing the developed countries, and which will soon confront the less well-developed countries - it is here that preventive steps will have their greatest benefits.

Unfortunately, young persons are convinced of their immortality. When presented with alarming data on risk factors they shrug it off with "that will never happen to me". This blinkered viewpoint often persists into middle age. The best approach, therefore, is to personalize the risks. Health professionals should be able to identify and even quantify specific risk factors for individual patients, and give an idea of the predictive accuracy of a risk factor profile for a given person. We intend to provide tools for such an approach - initially for the cardiovascular area, and later for other well-studied disease areas.

Summary

The existence of risk factors for a large number of diseases has led to a surge of interest in improving lifestyle in order to prevent or postpone ill health. It is envisioned that the future practice of medicine will largely be dedicated to preventing, in addition to treating, diseases. Knowledge of which risk factors are relevant for a particular disease allows the most appropriate steps to be taken. If health professionals do not provide this information, people will get it elsewhere - possibly with less-than-optimal results. Regular physical check-ups, including lab exams, will detect any "silent" risk factors, such as high blood pressure or a high cholesterol level that can be taken care of before they lead to disabling illness. They also provide the physician with an ideal opportunity to emphasize the benefits of a healthy lifestyle, and correct any obvious deviations. By these means, the onset of many diseases may be postponed until late in life. You can explain to your patients that they should live better today, so that they age better tomorrow.