We estimate the weight of various risk factors in heart disease, and the particular weight of age as a risk factor, individually and combined with other factors. To establish the weights we use the information theoretical measure of normalized mutual information that permits determining both individual and combined correlation of diagnostic parameters with the disease status. The present information theoretical methodology takes into account the non-linear correlations between the diagnostic parameters, as well as their non-linear changes with age. Thus it may be better suited to analyze complex biological aging systems than statistical measures that only estimate linear relations. We show that individual parameters, including age, often show little correlation with heart disease. Yet in combination, the correlation improves dramatically. For diagnostic parameters specific for heart disease the increase in the correlative capacity thanks to the combination of diagnostic parameters, is less pronounced than for the less specific parameters. Age shows the highest influence on the presence of disease among the non-specific parameters and the combination of age with other diagnostic parameters substantially improves the correlation with the disease status. Hence age is considered as a primary "metamarker" of aging-related heart disease, whose addition can improve diagnostic capabilities. In the future, this methodology may contribute to the development of a system of biomarkers for the assessment of biological/physiological age, its influence on disease status, and its modifications by therapeutic interventions.
Keywords: biomarkers of aging; biomarkers of disease; in silico assessment of anti-aging interventions; normalized mutual information; system aging.