Atherosclerosis at your fingertips?

Intracoronary endothelial function assessment, while yielding important information, is not feasible for large-scale application because it is expensive and requires catheterisation. Looking for non-invasive alternatives, measurement of flow-mediated dilation (FMD) of the brachial artery was an important step forward. Measuring in a peripheral arterial bed instead of in the coronary circulation is defendable from the viewpoint that atherosclerosis can be regarded as a systemic condition. FMD is non-invasive: increased flow through the artery is induced by reactive hyperaemia after a 5-minute occlusion of the arm, arterial diameter changes are measured by ultrasound. Peripheral arterial tonometry (PAT) was a next step; this non-invasive method also relies on reactive hyperaemia after a 5-minute occlusion of the arm but compares baseline and reactive hyperaemia plethysmograms measured at a fingertip; hence, PAT is done in a microvascular bed instead of in a conduit artery. Because PAT is low risk, easy to perform and highly operator-independent, it is suitable for large-scale measurement. Consequently, there is much interest to validate this technique in all stages of atherosclerotic disease. In the current issue of this Journal, Van den Heuvel and colleagues [1] publish a study that assesses the value of PAT to identify subjects at low risk among patients with new onset stable chest pain. Low risk was defined as no revascularisation—PCI or CABG—within one year. In addition to PAT, patients underwent exercise testing, CT angiography The endothelium separates blood and the vascular wall. Endothelial stimulation by agonists or by shear stress has effects on the smooth musculature in the vessel wall by paracrine communication. After the finding that intact endothelium is essential for acetylcholine to produce arterial vasodilation, various agents were discovered that stimulated the endothelium to produce endothelium-derived relaxing or contracting factors (EDRF/EDCF), the major EDRF being nitric oxide (NO). Additionally to vasodilation, NO inhibits platelet and monocyte adhesion and smooth muscle cell proliferation and migration, all key factors in the genesis and progression of atherosclerosis. Thus, dysfunctional endothelium, characterised by limited NO production, has lost part of its vasodilatory function and promotes atherosclerosis. In 1986, Ludmer and colleagues infused acetylcholine and the NO donor nitro-glycerine in the left anterior descending artery (LAD). Nitro-glycerine invariably caused LAD vasodilation but acetylcholine caused only vasodilation in the normal arteries, while arteries with stenosis showed vasoconstriction or even temporal occlusion. This study paved the road for invasive assessment of coronary endothelial integrity and its association with atherosclerosis in the coronary circulation. In 1989, Cox and colleagues measured flow-mediated LAD diameter changes by quantitative angiography, using adenosine infusions to increase blood flow. Dilation was markedly impaired in atherosclerotic vessels. However, all vessels dilated with nitro-glycerine. Hence, absence of flow-mediated dilation in atherosclerosis reflects impaired endothelial vasodilator