Coronary collaterals

Cardiovascular diseases, in particular coronary artery disease, are the leading cause of death and disease in industrialized countries. Atherosclerotic changes of the arterial vessel wall constitute one of the major causes for the occurrence of cardiovascular disease. Important risk factors for cardiovascular disease have been identified, but they fail to explain why some patients with atherosclerosis become symptomatic and have recurrent symptomatic disease, and others do not. Apart from the extent of coronary atherosclerosis (among other factors), the susceptibility of organs to episodes of ischemia is probably of importance. Well-developed collateral vessels, or "natural bypasses", may offer an important alternative source of blood supply, and thereby protect an organ from episodes of ischemia. Unfortunately, not every organ or even individual has well-developed collateral vessels, if developed at all. Current knowledge on coronary collaterals and its most important determinants involved, are reviewed in Chapter 2. The mechanism of the development of coronary collaterals is subject to increasing preclinical and clinical research. Many factors and patient characteristics have already been proposed to play a role in collateral development. For instance, myocardial ischemia, physical exercise, hypertension, and the use of various cardiovascular drugs. So far, however, for many of these factors, results are inconsistent and, therefore, their pathophysiologic role and importance is still unclear. In addition, the potential clinical relevance of coronary collaterals has attracted much attention. Coronary collaterals may in fact play an important prognostic role in patients with coronary artery disease during episodes of myocardial ischemia. Well-developed coronary collaterals may determine the prognosis of a patient not only in the event of an acute myocardial infarction, but also in stable coronary artery disease. Yet, different findings have been reported so far, as well. Therefore, we first investigated several determinants of the presence and extent of coronary collaterals collectively in a single group of patients, notably cardiac ischemic burden, high blood pressure, smoking and alcohol, and the metabolic syndrome. Second, we investigated the presence and extent of coronary collaterals as a prognostic determinant of cardiovascular outcome in two different studies with different study populations. Several determinants (Chapter 3), already identified as well-established risk factors for cardiovascular morbidity and mortality, turned out to play an important role in the presence of coronary collaterals, as well. These included cardiac ischemic burden (positive association), high blood pressure (inverse association), and smoking (positive association) and alcohol (J-curve). However, the metabolic syndrome, that encompasses a cluster of impaired glucose metabolism, hypertension, dyslipidemia and central obesity, was not associated. In addition, coronary collaterals turned out to mark an unfavourable prognosis in relatively high-risk patients, but a protective effect in relatively low-risk patients (Chapter 4). We believe that this different effect of coronary collaterals in the various risk groups may explain the conflicting evidence on the protective role of collaterals, reported in the literature, so far. Finally, in Chapter 5 we discuss these different findings by several cardiovascular endpoint-studies in greater detail. The prognostic significance of the presence of coronary collaterals appears to be considerably modified by the patient's risk-level of coronary heart disease. Furthermore, we discuss the different methods, that are currently used to assess coronary collateral circulation, and in particular their relationship and limitations. We propose that the presence of coronary collaterals may provide an additional marker of myocardial vulnerability, and therefore, an additional marker to identify the "vulnerable patient". In addition, in particular for those patients with myocardial ischemia and at low cardiac risk, who are unsuitable for conventional coronary interventions, therapeutic induction of coronary collateral growth may provide an attractive treatment option