Downloaded from http://journals.lww.com/jhypertension by BhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eJPG+b4DlKuAX44qu/vwzmc= on 07/29/2018 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Hypertension-related target organ damage: is it a continuum? Stefano Perlini a and Guido Grassi b,c See original paper on page 1136 M any biological variables are continuously distrib- uted in the population, showing a normal or near- normal statistical distribution encompassing ‘low’, ‘intermediate’, and ‘high’ values that can be subdivided only by arbitrary cut-off values. Blood pressure values do not represent an exception, showing an unimodal distribution in the population [1], as well as a relatively continuous relationship with cardiovascular risk down to systolic and diastolic levels of 115–110 and 75–70 mmHg, respectively [2,3]. Therefore, labeling an individual as ‘hypertensive’ or ‘normotensive’ is dependent on the cut-off values, and as suggested by the 2007 European Society of Hypertension/ European Society of Cardiology guidelines ‘the threshold for hypertension (and the need for drug treatment) should be considered as flexible based on the level and profile of total cardiovascular risk’ [4]. Indeed, it has been shown that even in the normotensive range, the incidence of cardio- vascular disease progressively increases from optimal to normal to high-normal blood pressure values [5]. In detail, as compared with optimal blood pressure, high-normal blood pressure is associated with a risk factor-adjusted hazard ratio for cardiovascular disease of 2.5 (95% confi- dence interval 1.6 – 4.1) in women and 1.6 (1.1 – 2.2) in men [5]. Also pulse pressure may play a role, and it has been recently shown that in hypertensive outpatients the increased cardiovascular risk attributed to the presence of metabolic syndrome may in part be associated with increased heart rate and pulse pressure [6]. Among many other factors, chronic exposure to increased blood pressure levels induces several changes in the structure and function of tissues and organ systems that clinicians collectively recognize as target organ damage and that are responsible for hypertension-related morbidity and mortality. It is obviously of paramount importance to recognize target organ damage before it becomes clinically evident as a cardiovascular event or as irreversible damage. Given its profound impact on prognosis, the presence of target organ damage should be actively searched in order to choose and modulate the consequent therapeutic approach. As a general guideline, in order to properly decide patient-tailored treatment blood pressure values should be matched with total cardiovascular risk profile and evidence of target organ damage [4]. Moreover, in the past decade, regression of target organ damage has been addressed by several clinical trials as a surrogate end point in the evaluation of treatment impact on hypertension- related sequelae. Within this framework, it has to be noted that blood pressure values (and related thresholds that can be used for diagnosis and treatment) are dependent on the setting in which blood pressure is measured, that is office, home, or 24-h ambulatory recordings. After the pioneering study by Mancia et al. [7], we have become more and more aware of the clinical relevance of blood pressure variability and of the variations that can be induced in a given patient by the very same act of having her/his blood pressure measured. These aspects may have several consequences on the possible target organ damage induced by the prevailing ‘average’ blood pressure burden as well as by the sudden increases and decreases of blood pressure values that can be either spontaneous or induced by different stimuli. To add a further level of complexity, the processes underlying the development and the progression of target organ dam- age may be amplified by arterial stiffness [8,9], by the amplitude of concomitant heart rate changes [10], by the effects of sympathetic overactivity [11], by the modulation of extracellular matrix remodeling [12,13], as well as by the effect of several humoral systems such as the renin–angio- tensin–aldosterone axis. From the diagnostic standpoint, beyond presenting different reference values [4], office, home, and 24-h ambu- latory blood pressure measurements allow the further classification of patients as hypertensive, isolated office (white-coat) or masked (isolated ambulatory) hypertensive [4]. It has been shown that each blood pressure elevation (office, home, or ambulatory) carries an increase in risk [14] and in target organ damage [15], which adds to that of the other blood pressure elevations [14]. Journal of Hypertension 2013, 31:1083–1085 a Clinica Medica II, Department of Internal Medicine, Fondazione Policlinico IRCCS San Matteo, University of Pavia, b Clinica Medica, University of Milano Bicocca and c Istituto di Ricerca a Carattere Scientifico IRCCS Multimedica, Sesto San Giovanni, Milan, Italy Correspondence to Stefano Perlini, Clinica Medica II, Dipartimento di Medicina Interna, Universita ` di Pavia, P. le Golgi 19, 27100 Pavia, Italy. Tel: +39 0382 502 285; fax: +39 0382 526 897; e-mail: stefano.perlini@unipv.it J Hypertens 31:1083–1085 ß 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0b013e32836157da Journal of Hypertension www.jhypertension.com 1083 Editorial Comment