LETTERS TO THE EDITOR
Mechanism of protection against vascular smoking-induced changes by hormone replacement therapy
H. Richard Hellstrom, MDa
a Department of Pathology, College of Medicine, State University of New York, 750 East Adams Street, Syracuse, New York 13210, USA
hellstro{at}twcny.rr.com
I read with interest Teede et al.’s (1) report that hormone replacement therapy (HRT) protects against smoking-induced changes that favor ischemic heart disease (IHD). The ability of one agent to prevent IHD (HRT) to protect against another risk factor (smoking) raises basic issues about the prevention of IHD. The standard prevention of IHD is based on correcting each operative risk factor, and the reduction of the risk of smoking by HRT cannot be explained by such a position.
The recently proposed altered homeostatic theory (2) provides a mechanism by which HRT can prevent smoking-induced changes. This hypothesis asserts that the major risk factors favor disease by the single mechanism of shifting homeostasis inappropriately toward defensive action (fight/flight), and that the major factors that prevent IHD reverse this inappropriate shift. Thus, any preventative measure (such as HRT) can offset any risk factor (such as smoking). Most individuals have multiple risk factors, and the ability of single preventative measures, such as HRT, vitamin E, exercise and low dose aspirin, to reduce the incidence of IHD in the general population (3) suggests neutralization of diverse risk factors by single agents.
The altered homeostatic theory was prompted by a study (3) that showed that major risk factors for IHD, such as stress, smoking, abnormal lipids, cocaine, diabetes, obesity and homocysteine, each express the combination of spasm of resistance vessels (S-RV) and a thrombotic tendency (S-RV/clotting), and major preventative factors, such as HRT, the exercised state, vitamin E and low dose aspirin, each express the combination of vasodilation of resistance vessels (V-RV) and an antithrombotic tendency (V-RV/anticlotting).
That major risk and preventative factors express S-RV/clotting and V-RV/anticlotting, respectively, seems highly consistent with risk factors operating by one mechanism that is opposed by preventative factors. Relating these opposing mechanisms to shifts of homeostasis was based on multiple factors. In brief, the idea of altered homeostasis was derived from the S-RV concept of ischemic diseases (3,4), which attributes symptoms to S-RV and S-RV to altered vascular homeostasis. For the altered homeostatic theory, alterations of homeostasis were extended to involve other components of homeostasis, such as the autonomic nervous system and metabolic processes. In Teede et al.’s study, HRT improved cholesterol, intimal carotid thickening and systemic arterial compliance, which is consistent with improvement of multiple body functions.
The idea of an altered homeostatic balance was derived from the opposition of the autonomic nervous system (sympathetic nervous system defensive fight/flight vs. parasympathetic nervous system conservation/withdrawal). The association of sympathetic hyperactivity with multiple risk factors (2) and the expression of S-RV/clotting by the alpha-sympathetic nervous system (2) led to relating the homeostatic shift with inappropriate fight/flight. Also helpful was Selye’s idea (5) that stress favors disease by prompting an imbalance of homeostasis with overactivity of the defensive sympathetic fight/flight response (2). Further, the significant involvement of inflammation—a basic homeostatic defense mechanism—in IHD (2,6,7) strengthened the idea that risk factors shift homeostasis toward defensive action.
The possibility that any preventative measure operates against any risk factor has enormous implications for the prevention of IHD. For example, risk factors that are impossible or difficult to correct, such as age, smoking, diabetes and obesity, could be treated by preventative agents, such as HRT (in postmenapausal women), exercise, vitamin E and low dose aspirin.
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References
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1. Teede HJ, Liang Y-L, Shiel LM, McNeil JJ, McGrath BP. Hormone replacement therapy in postmenopausal women protects against smoking-induced changes in vascular structure and function. J Am Coll Cardiol. 1999;34:131–137[Abstract/Free Full Text]
2. Hellstrom HR. The altered homeostatic theory: a holistic approach to multiple diseases, including atherosclerosis, ischemic diseases, and hypertension. Med Hypotheses 1999;53:194–9.
3. Hellstrom HR. New evidence for the spasm of resistance vessel concept of ischemic diseases. Med Hypotheses 1999;53:200–9.
4. Hellstrom HR. The spasm of resistance vessel concept of ischemic heart disease and other ischemic diseases. Med Hypotheses. 1990;33:31–41[CrossRef][Medline]
5. Chrousos GP, Gold PW. The concepts and stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA. 1992;267:1244[Abstract/Free Full Text]
6. Grayston JT. Antibiotic treatment trials for secondary prevention of coronary artery disease events. Circulation. 1999;99:1538–1539[Free Full Text]
7. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979[Abstract/Free Full Text]
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