Endothelial function as a functional expression of cardiovascular risk factors

Abstract

Traditional cardiovascular risk (CV) factors based on the Framingham study have been used to estimate the risk of CV events and determine target cholesterol levels for primary prevention. Recently published systematic reviews have, however, demonstrated that the Framingham risk score is limited in certain cohorts and requires adjustment. Indeed, traditional CV risk factors fail to predict the development of coronary heart disease in 25-50% of cases. This underscores the complex interplay between traditional CV risk factors, genetic predisposition and other atheroprotective factors present in individuals of different populations in predicting CV events. Endothelial dysfunction, a functional expression of the inherent atherosclerotic risk representing an integrated index of both the overall CV risk-factor burden and the sum of all vasculoprotective factors in an individual, may serve as the missing link between CV risk factors and atherosclerotic disease. Endothelial function measurements may aid in future prediction of CV events and help identify high-risk patients for targeted therapy as well as provide a primary therapeutic end point for clinical follow-up of these patients. Recently introduced reactive hyperemia peripheral arterial tonometry is emerging as a promising tool in endothelial function measurement and CV risk stratification.

Figure 1. Reactive hyperemia peripheral arterial tonometry recordings of subjects with normal and abnormal hyperemia response

Normal response is characterized by a distinct increase in the signal amplitude after cuff release compared with baseline.

Figure 2. Using reactive hyperemia peripheral arterial tonometry, digital pulse volume changes during reactive hyperemia were assessed in 94 patients without obstructive coronary artery disease and either normal (n = 39) or abnormal (n = 55) coronary microvascular endothelial function

The receiver operated characteristic curve analysis was carried out to identify the reactive hyperemia peripheral arterial tonometry index value for optimal discrimination between the presence/absence of coronary endothelial dysfunction, reactive hyperemia peripheral arterial tonometry index of 1.35 discriminates best between presence/absence of coronary endothelial dysfunction. AUC: Area under the curve. Reproduced with permission from [30].

Figure 3. Distribution of traditional cardiovascular risk factors in patients with normal endothelial function, mild or severe endothelial dysfunction of the coronary (A) or peripheral (B) vasculature

In these studies, prevalence of hypercholesterolemia, hypertension and smoking status were similar in all groups irrespective of the status of endothelial function, indicating that the presence of known risk factors is not the only determinant of endothelial function. NS: Not significant. Reproduced with permission from [3].