Invited commentary

Article Outline

• Copyright

This study by Dr Thatipelli and colleagues from the Mayo Clinic is a complex analysis that rewards careful reading and analysis. A brief summary of their findings is important. By life table analysis, abnormal ankle brachial index (ABI) was associated with higher rates of both cardiovascular morbidity (CVM) (P =.02) and all-cause mortality (ACM) (P < .001). Positive dobutamine stress echocardiography (DSE) (inducible wall motion abnormality) was not associated with increased rates of either CVM or ACM, while abnormal DSE (either inducible or fixed wall motion abnormality) was associated with a trend toward a higher CVM (P = .052), and with higher ACM (P = .02). Furthermore, when tested by multivariate regression analysis, abnormal ABI held the strongest association with ACM, while neither positive nor abnormal DSE studies were associated with significantly increased ACM. Also coronary intervention (percutaneous transluminal coronary angioplasty and stenting or coronary artery bypass grafting in 69 trial patients) did not influence the incidence of CVM or ACM. Finally, there was no correlation between ABI and severity of induced wall motion abnormalities.

So, what does all this mean? The authors argue plausibly that abnormal ABI is a measure of increased total atherosclerotic burden, positive DSE is a measure of the acute pathophysiologic effects of coronary atherosclerosis, and abnormal DSE is an indicator of the presence of coronary atherosclerosis. Based on these interpretations, the authors conclude that total atherosclerotic burden and not acute pathophysiologic effects of coronary disease best predicts prognosis. This conclusion is further supported by their observations that abnormal but not positive DSE influenced ACM and that coronary interventions had no influence on CVM or ACM. They speculate that the effect of total atherosclerotic burden on CVM and ACM is mediated by clotting system activation associated with plaque burden.

This conclusion, if proven valid, helps to explain the benefits of antiplatelet agents and statins as modifiers of coagulation system activation and plaque burden accumulation respectively, and may guide the future development of novel secondary prevention strategies.

While the limitations of this study (retrospective design, highly selected cohort, exclusions, and use of “all-cause” mortality as an endpoint) are obvious and acknowledged by the authors, their finding that abnormal ABI is the more accurate predictor of CVM and ACM is important and provocative. The implications of this finding may be far-reaching but await validation by the authors’ planned prospective study correlating CT measured total body plaque burden, clotting system activation, and prognosis.