The altered homeostatic theory: A hypothesis proposed to be useful in understanding and preventing ischemic heart disease, hypertension, and diabetes--including reducing the risk of age and atherosclerosis

Abstract

Evidence will be presented to support the usefulness of the altered homeostatic theory in understanding basic pathogenetic mechanisms of ischemic heart disease (IHD), hypertension, and diabetes, and in improving prevention of these disorders. The theory argues that: IHD, hypertension, and diabetes share the same basic pathogenesis; risk factors favor a sympathetic homeostatic shift; preventative factors favor a parasympathetic homeostatic shift; risk and preventative factors oppose each other through a dynamic risk/prevention balance; and prevention should be based on improving the risk/prevention balance. Prevention based on improving the risk/prevention balance should be more effective, as this method is regarded as reflecting more accurately basic pathogenetic mechanisms. As example, the theory argues that the risk of supposedly nonmodifiable risk factors as age and the risk of relatively nonmodifiable atherosclerosis can be reduced significantly. The possible validity of the altered homeostatic theory was tested by a study based on multiple associations. Findings support a common pathogenesis for IHD, hypertension, and diabetes based on a sympathetic homeostatic shift, and the usefulness of prevention based on improving the risk/prevention balance by using standard pharmaceutical and lifestyle preventative measures. The same set of multiple and diverse risk factors favored IHD, hypertension, and diabetes, and the same set of multiple and diverse pharmaceutical and lifestyle preventative measures prevented these disorders. Also, the same set of preventative agents generally improved cognitive function and bone density, and reduced the incidence of Alzheimer's disease, atrial fibrillation, and cancer. Unexpectedly, evidence was developed that four major attributes of sympathetic activation represent four major risk factors; attributes of sympathetic activation are a tendency toward thrombosis and vasoconstriction, lipidemia, inflammation, and hyperglycemia, and corresponding risk factors are endothelial dysfunction (which expresses thrombosis/vasoconstriction and epitomizes this tendency), dyslipidemia, inflammation, and insulin resistance. These findings, plus other information, provide evidence that dyslipidemia acts mainly as a marker of risk of IHD, rather than being the basic mechanism of this disorder. However, prevention generally is based solely on improvement of dyslipidemia; basing prevention on dyslipidemia relatively underemphasizes the importance of other significant risk factors and, by certifying its validity, discourages alternate pathogenetic approaches. Also, development of myocardial infarction is approached differently. It seems generally accepted that dyslipidemia results rather automatically in infarction through the sequence of atherosclerosis, atherosclerotic complications, and thrombosis. In contrast, distinction is made between development of atherosclerosis and acute induction of infarction--where atherosclerosis is only one of multiple risk factors.