Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

Abstract

T he understanding of the pathophysiology of atherosclerosis and its vascular complications has increased dramatically over the past decade. Numerous measurable biomarkers play a role in the atherosclerosis process, and are associated with clinically important vascular events. Not only has their evaluation advanced our knowledge of the atherosclerotic process but it has also accelerated a search for new diagnostic tools to aid in risk stratification. Putative factors include soluble biomarkers and imaging assessments of vascular structure and function. The endothelium plays a key role in vascular homeostasis through the release of a variety of paracrine factors that interact with platelets, inflammatory cells and the vessel wall. The endothelium's central location allows it to sense and respond to a variety of perturbations. Endothelial dysfunction is an early marker of disease. Risk factors can also affect mechanical properties such as arterial stiffness, which is now recognized as a major contributor to systolic hypertension in elderly people. Methods of assessing endothelial function and arterial stiffness are available for clinical research and recent evidence suggests that these measures may provide important prognostic information. ATTRIBUTES OF A SURROGATE BIOMARKEREpidemiological studies, such as Framingham, have allowed longitudinal assessment of cardiovascular events and the development of simple scoring tables for risk calculation (1,2). These factors involved include blood pressure, lipid profile, smoking status and age. More recently, many factors thought to be associated with the atherosclerotic process have been studied. Some of these have been shown to correlate with clinical outcomes and have been deemed biomarkers (3,4). However, association does not necessarily imply causation and, due to a variety of limitations, most of these markers will not be useful for the clinical evaluation of risk or drug therapy (5). To become clinically important, a biomarker must fulfill the criteria for a surrogate marker. A surrogate substitutes for clinically important end points with respect to how an individual feels, functions or survives. Classic examples include blood pressure and low density lipoprotein cholesterol. These are targets of treatment. A surrogate should meet the following criteria:• Adds independent information above currently used criteria;• Is reliably and reproducibly measured;• Accounts for a significant proportion of disease risk;• Provides good predictive value;• Is reasonably associated with the underlying pathophysiology;• If it is to be used in risk prevention, is present before the clinical appearance of the outcome; and• Is available and practical for widespread application (5-8). ADVANCES IN VASCULAR BIOLOGY

Coffee, nutritional status, and renal artery resistive index

“…18,19 Cardiovascular effects of coffee consumption and notably the development of AS can be mediated also through insulin-resistance mechanisms. 20 AI, a hallmark of vascular aging, is assessed also by the renal resistive index (RRI), and a relationship between the ultrasound RRI, BP, and renal function response is recognized as a most powerful predictor of death during follow-up of patients with atherosclerotic renovascular disease. 21 However, increased RRI may imply the presence of some type of underlying renal damage, including ischemic nephropathy, 22 and is useful for predicting long-term renal functions in renal transplant patients.…”

Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia

“…A large body of evidence has shown that HC leads to AS by causing ED, which is a marker of cardiovascular (Anderson, 2006) and atherosclerotic (Bonetti et al, 2003) risk and responsible for the triggering of the first step of AS (Ross, 1993). Consistent with the idea that the TC and LDL are the major harmful factors for endothelial function, and the higher levels of TC/LDL, the greater the arterial stiffness (Diehm et al, 2004), we found that FMD, β, and IMT were still correlated significantly with TC after adjustment for the other risk factors.…”

Review of Cardiovascular Disease in HIV-Infected Women

“…Pulse wave velocity is a surrogate marker of arterial stiffness that has been associated with CVD and [21]. There is limited data on PWV in HIV-infected women, and only two studies reported on gender in their results.…”