The Use of Surrogate Vascular Markers in Youth at Risk for Premature Cardiovascular Disease

Abstract

Premature cardiovascular disease (CVD) begins in youth--a crucial period when modification of the disease may have the greatest impact. Failure to diagnose preclinical CVD at this stage misses a major opportunity to prevent the long-term consequences of this disease. An array of surrogate vascular markers (SVMs) are now available that can determine the extent of preclinical vascular injury in the pediatric population. These SVMs include flow-mediated vasodilatation, carotid intima media thickness, arterial stiffness, and biomarkers including high sensitivity C-reactive protein, cell adhesion molecules and methylarginines. We believe that the use of these SVMs will help to develop a better understanding of early pathological vascular changes in youth, facilitate earlier diagnosis of preclinical atherosclerosis and provide an objective measure of the vascular effects of any therapeutic intervention aimed at risk factor modification. Ultimately, our future health will depend on carefully balancing the benefits of early diagnosis and treatment in high-risk youth with the long-term risk of CVD. The application of SVMs in the pediatric population will help us achieve this balance.

Carotid intima-media thickness and arterial stiffness as early markers of atherosclerosis in pediatric celiac disease

“…Early diagnosis of preclinical atherosclerosis can be made by measurement of carotid artery intima-media thickness (cIMT), flow-mediated vasodilatation and arterial stiffness 4 . Carotid artery intima-media thickness is a reliable surrogate marker of atherosclerosis 5,6 .…”

Effects of early-life environment and epigenetics on cardiovascular disease risk in children: highlighting the role of twin studies

“…Pediatric studies on environmental factors that may influence risk of CVD have investigated a range of CVD biomarkers (10). A range of CVD risk factors and vascular health biomarkers that have been measured in childhood are summarized in the Table 1.…”

“…Various measures of vascular health, including carotid intimamedia thickness, pulse wave velocity, flow-mediated vasodilatation, high-sensitivity C-reactive protein, and cell adhesion molecules, have been suggested as valuable biomarkers of vascular health in pediatric epidemiological studies (10,24). Current data have demonstrated that in pediatric populations, adverse changes in these biomarkers are associated with a range of CVD risk factors, including elevated blood pressure, type 1 and 2 diabetes, obesity, and hypercholesterolemia.…”

Hypercholesterolemia in Youth: Opportunities and Obstacles to Prevent Premature Atherosclerotic Cardiovascular Disease

“…These methods include flow-mediated dilatation (FMD) and measures of arterial stiffness (such as pulsed wave velocity), which can measure the earliest vascular injury associated with endothelial dysfunction; intima-media thickness (IMT), which can measure the first anatomic changes associated with arterial injury; and biomarkers of vascular health, such as high-sensitivity Creactive protein (hs-CRP), cell adhesion molecules (CAM), and the methylarginines (ie, asymmetric dimethylarginine) [31][32][33]. FMD and IMT have been the most widely used tools in the pediatric population to evaluate preclinical arterial injury attributable to hypercholesterolemia and the effect of other risk factors and changes following therapeutic interventions in the pediatric population [32]. Of these tools, IMT may be the optimal method to estimate the atherosclerotic burden and track longitudinal changes due to risk factor modulation [33].…”

“…However, therapy is largely guided by laboratory end points, including normalization of serum LDL-C, HDL-C, and triglyceride levels to gauge the success of treatment rather than longterm CHD outcomes. As noted above, the relatively recent application of surrogate vascular markers provides objective information regarding objective vascular changes with treatment [32], although such approaches are still primarily the focus of clinical trials and not day-to-day practice. Multiple issues also complicate treatment of pediatric lipid disorders.…”