Hypertension-related target organ damage

Many biological variables are continuously distributed 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 cardiovascular 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% confidence 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 damage 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–angiotensin–aldosterone axis. From the diagnostic standpoint, beyond presenting different reference values [4], office, home, and 24-h ambulatory 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]. Assuming that target organ damage is consequent to the prevailing blood pressure ‘burden’, it may be argued that this classification may identify patients at a different risk (or extent) of target organ damage. In other words, assuming that hypertensive patients have a higher blood pressure burden than patients whose blood pressure values are repeatedly elevated during the office visits, but not when self-measured at home, one may think that target organ damage is more prevalent in the former group than in patients with isolated office hypertension. Similar differences might be hypothesized for masked hypertension, a clinical situation in which a patient has elevated out-of-office blood pressure despite normal office blood pressure values [4]. An interesting contribution to a better understanding of the complex interrelationship between blood pressure values and target organ damage is offered by Hänninen et al.[16] in a paper that is published in the present issue of the Journal of Hypertension. Taking advantage of the data collected in the Finn-Home Study, the authors compared the prevalence of target organ damage in an unselected Finnish adult population cohort of 1989 participants, who were classified as masked hypertensive (n = 181; 9.1%), white-coat hypertensive (n = 311; 15.6%), sustained hypertensive (n = 654; 32.9%), or normotensive (n = 843; 42.4%) patients, according to office (duplicate measurements on one visit by a nurse) and home (duplicate measurements on 7 days) blood pressure measurements. Twelve-lead electrocardiogram, carotid intima–media thickness, and pulse wave velocity were evaluated to assess cardiovascular target organ damage. Cornell voltages, electrocardiographically derived left ventricular hypertrophy prevalence, and pulse wave velocity progressively increased from normotension to white-coat, masked and sustained hypertension, respectively. Age and sex-adjusted cardiac target organ damage was significantly less prevalent in normotensive individuals, whereas carotid intima–media thickness and pulse wave velocity were significantly higher in masked and sustained hypertensive patients. Cardiovascular target organ damage was less prevalent in white-coat than in sustained hypertensive patients. Interestingly, classification of patients into normotension and white-coat, masked and sustained hypertension lost statistical significance when home blood pressure was included as explanatory variable in the multivariate models. These data suggest a ‘continuum’ of target organ damage ranging from normotension to white-coat, masked, and sustained hypertension, which is very likely to be dependent on the different prevailing blood pressure burden on the cardiovascular system. They also confirm that masked hypertension is not at all a benign condition, with a 13.9% age, sex, and BMI-adjusted prevalence of electrocardiographically derived left-ventricular hypertrophy. For comparison, prevalence was 17.1% in sustained hypertensive patients and 4.4% in normotensive individuals belonging to the same population cohort. The presence of target organ damage has a profound adverse effect on prognosis. It has been shown that at any given blood pressure level, the presence of left ventricular hypertrophy is associated with an increased cardiovascular risk [17], beyond being associated with a number of adverse consequences for the heart, including a reduction in systolic and diastolic function [18,19], reduced coronary reserve [20], and increased incidence of arrhythmias [21]. Also carotid intima–media thickness [22] and pulse wave velocity [23] have been identified as predictors of cardiovascular events. In the present study, the prevalence of target organ damage was assessed by evaluating these three markers, that is left ventricular hypertrophy, increased carotid intima–media thickness, and pulse wave velocity. According to the observed results, both the prevalence and the extent of target organ damage in patients with masked hypertension are closer to those observed in sustained hypertensive than in normotensive or white-coat hypertensive patients. Although in the Finn-home population masked, white-coat, and sustained hypertensive patients had metabolic and lifestyle risk factors that may modify the associations between blood pressure categories and target organ damage [24], these data further underscore the close relationship between the prevailing blood pressure burden and the development of target organ damage. Elevated home blood pressure, which is present in masked and in sustained hypertension, carries a higher risk for target organ damage, whereas white-coat hypertension appears to have a lesser impact on the cardiovascular system. Once more, every effort should be made towards a proper control of blood pressure values in order to reduce the extent of hypertension-induced cardiovascular damage. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.