Arterial stiffness as a noninvasive tissue biomarker of cardiac target organ damage

Current Biomarker Findings Dovepress open access to scientific and medical research Review Open Access Full Text Article Current Biomarker Findings downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Arterial stiffness as a noninvasive tissue biomarker of cardiac target organ damage This article was published in the following Dove Press journal: Current Biomarker Findings 28 January 2014 Number of times this article has been viewed Nicole L Spartano 1 Jacqueline A Augustine 1 Wesley K Lefferts 1 William E Hughes 1 Jessica Garay Redmond 1 Eileen D Martin 1 Jeffrey T Kuvin 2 Brooks B Gump 3 Kevin S Heffernan 1 Department of Exercise Science, Syracuse University, Syracuse, NY, USA; 2Division of Cardiology, Tufts Medical Center, Boston, MA, USA; 3 Department of Public Health, Syracuse University, Syracuse, NY, USA 1 Biomarkers of cardiac target organ damage (cTOD) Correspondence: Kevin S Heffernan The Human Performance Laboratory, Department of Exercise Science, Syracuse University, Syracuse, NY, 13244, USA Email Prevention of cardiovascular (CV) disease (CVD) remains a major public health priority.1 Hypertension and its associated complications serve as a primary substrate for the pathogenesis of CVD. Increasingly, new recommendations in the management of hypertension and hypertensive CVD risk prediction call for the assessment of subclinical target organ damage.2,3 Subclinical (asymptomatic) target organ damage is an intermediate step between chronic risk factor exposure and future clinical events (eg, stroke, myocardial infarction, heart failure).4,5 The National Institutes of Health define a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”6 A biomarker can be a circulating biomarker, in which sampling occurs in the blood, urine, or tissue, or can be an imaging or tissue biomarker recorded from an ultrasound (eg, left ventricular [LV] hypertrophy [LVH] or carotid intima media thickness) or other “imaging” modality (eg, applanation tonometry, pulse wave analysis).7–9 23 submit your manuscript | www.dovepress.com Current Biomarker Findings 2014:4 23–34 Dovepress © 2014 Spartano et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/CBF.S38738 Powered by TCPDF (www.tcpdf.org) Abstract: The primary prevention of cardiovascular (CV) disease is hindered by the inadequacy of traditional risk factors to stratify CV risk. The presence of cardiac target organ damage (cTOD), as detected by measures of left ventricular (LV) hypertrophy and dysfunction, is associated with future CV outcomes, but is not currently assessed in asymptomatic individuals. Arterial stiffness contributes to cTOD and may represent a biomarker that can detect vascular dysfunction before the clinical manifestations of cTOD. Measurement of arterial stiffness may provide insight into premature risk for cTOD and afford opportunity for early intervention to prevent further damage. The purpose of this review is to examine the utility of arterial stiffness as a noninvasive biomarker of subclinical cTOD. To this end, we will examine the evidence supporting the association between arterial stiffness and measures of cTOD. We will then explore the developmental origins of arterial stiffness and cTOD and outline the progression of CV damage that occurs with age. We discuss the mechanistic role of pressure from wave reflections as a crucial link between arterial stiffness and cTOD. Finally, we examine these associations in context by exploring sex and racial differences in arterial stiffness as related to cTOD. Our comprehensive examination of the literature suggests that early identification of arterial stiffness would be a useful biomarker of future cTOD risk. Keywords: arterial stiffness, left ventricular hypertrophy, wave reflections, blood pressure Current Biomarker Findings downloaded from https://www.dovepress.com/ by 213.32.59.121 on 12-Jul-2018 For personal use only. Spartano et al Desirable features of a biomarker for cTOD are as follows: the biomarker should be reproducible, stable, cost-effective, acceptable to the patients, capture known physiology, provide novel insight into pathophysiology, and be responsive to therapy; it should explain a significant proportion of the outcome independent of other risk factors and aid in incremental risk prediction; it should have established normal/reference limits and standardized methodology; and, finally, change in the biomarker should alter outcome and help guide disease management.9 This biomarker should be applicable to men and women as well as different ages and different races/ethnicities.9 In order to truly understand the structural and/or functional changes of target organs, use of novel tissue biomarkers have been proposed. Measurement of arterial stiffness may be such a tissue biomarker. Arterial stiffness integrates the cumulative impact of genetic factors, epigenetic factors, lifestyle factors, CV risk factors, and environmental factors on the arterial wall over time. This is important, as individual risk factors can fluctuate over time and their measurement, recorded at the time of risk assessment, may therefore be unreliable and not reflect their true impact on the arterial wall. The purpose of this review will be to explore the potential utility of measuring arterial stiffness and its associated hemodynamic sequelae (ie, increased pressure from wave reflections and pulse pressure [PP] amplification) as novel biomarkers of subclinical cTOD. Earlier detection and/or prediction of cTOD with measures of arterial stiffness may afford opportunity for prevention before overt damage occurs. Arterial stiffness as a biomarker for cTOD Arterial compliance reflects the ability of large central elastic arteries such as the aorta and carotid to expand and recoil during systole and diastole. This buffering capacity functions to dampen the amplitude of fluctuations in pressure and flow in the systemic circulation, thereby preventing transmission of excess pulsatile energy into target organs.10 Loss of arterial compliance or an increase in the stiffness of the vessel alters ventricular–vascular coupling such that arterial load is increased, contributing to the pathogenesis of cTOD and ultimately heart fa (...truncated)