Arterial Stiffness and Emerging Biomarkers: Still a Long Journey to Go.

Abstract

Cardiovascular (CV) disease is the leading cause of death worldwide, highlighting the importance of tackling this major health problem. The Framingham Heart study identified the major CV risk factors and a wealth of evidence since then established the significance of hypertension, dyslipidemia, diabetes mellitus, and obesity for CV risk prediction. However, traditional risk factors fail to fully predict CV events in many cases, establishing the need for additional risk predictors. Emerging CV biomarkers have to fulfill 3 major requirements in order to establish a role in everyday clinical practice: (a) demonstrate an independent association with CV morbidity and mortality, (b) prove the ability for CV risk prediction beyond traditional risk factors, and (c) reduce CV events after ‘‘treatment’’ of the specific biomarker. Arterial stiffness is among the most studied and promising biomarkers for better CV risk prediction. Arterial stiffness has been reported to be an independent and strong predictor of CV morbidity and mortality. Indeed, a recent meta-analysis of 27 longitudinal studies (>20 000 individuals) revealed a positive, strong, and linear association between pulse wave velocity (an accurate measure of aortic stiffness) and not only CV morbidity and mortality but all-cause mortality as well. Furthermore, recent evidence points toward the ability of arterial stiffness to predict future events beyond the established CV risk factors. A meta-analysis of 16 longitudinal studies (>15 000 participants) unveiled an additional predictive value of arterial stiffness beyond traditional risk factors that enable patient reclassification to a greater CV risk, especially for patients at intermediate risk. The third requirement for defining an effective CV biomarker remains elusive, since there is no specific therapy currently available for arterial stiffness. The net effect of arterial destiffening after antihypertensive and statin therapy cannot be clearly differentiated from the primary actions of these drugs on blood pressure (BP) and lipid levels, respectively. In this issue of Angiology, Fu et al report a large crosssectional study evaluating the association between central arterial stiffness and hemodynamics with several novel biomarkers. The study included more than 1500 Chinese individuals participating in a health checkup program. Carotid–femoral pulse wave velocity was assessed using the Complior device (Createch Industrie, Garges les Gonesse, France), whereas the Sphygmocor device was used for the assessment of augmentation index. Several emerging biomarkers were also assessed, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), homocysteine, uric acid, and lipid indexes. Multivariate analysis revealed that arterial stiffness was independently related to age, pulse pressure, lipid indices, and homocysteine levels. In contrast, several other biomarkers such as NT-proBNP, hsCRP, uric acid, and the lipid accumulation product index were not independently associated with arterial stiffness, when adjustments for traditional risk factors were made. Accumulating evidence strongly indicates that age and BP are 2 major determinants of arterial stiffness. Fu et al confirmed this association in a large sample of low-risk Chinese individuals. The authors report an independent association of arterial stiffness with triglyceride (TG) levels and the TG to highdensity lipoprotein cholesterol (HDL-C) ratio. The non-lowdensity lipoprotein lipid indices have been long recognized as independent CV risk factors. The association of high TGs and low HDL-C with increased arterial stiffness suggests that (a) high TG and low HDL-C levels are implicated in the pathogenesis of arterial stiffening, (b) arterial stiffening may partly mediate the increased CV risk associated with low HDL-C and high TG levels, and (c) pharmacological targeting of TG and HDL-C levels might improve arterial stiffening. Treating dyslipidemia can affect arterial stiffness. Experimental and clinical evidence suggests that statins exert beneficial effects on arterial stiffness, although differences between statins and dosage have not yet been defined. The effect of fibrates and omega 3 supplements are not yet definite. Available data in animals and humans support an association