Juan Eugenio Ochoa

Prognostic Value of Blood Pressure Variability and Average Blood Pressure Levels in Patients With Hypertension and Diabetes

Elevated blood pressure (BP) is a major risk factor for cardiovascular (CV) events and mortality (1) and a leading contributor to the global disease burden (2). Overwhelming evidence is now available showing that BP measured in the office shows a linear relationship with a number of CV and renal outcomes as well as with overall mortality and that lowering of office BP (OBP) with treatment is effective in reducing morbidity and mortality (3,4). However, application over the last 40 years of techniques for out-of-office BP monitoring including home BP monitoring (HBPM) and 24-h ambulatory BP monitoring (ABPM) has led to further important findings. In particular, 1 ) average BP measured in everyday life conditions may be an even better predictor of CV outcomes than isolated OBP readings and 2 ) the extent of fluctuations of BP over time may provide additional, independent prognostic information compared with both isolated office readings and average ambulatory BP (ABP) levels, respectively. These findings are of upmost relevance in the case of diabetic patients who are characterized by a significantly higher risk of CV events compared with nondiabetic individuals, with diabetes itself currently considered a CV disease equivalent (5,6). The aim of the present article is to review the available evidence on the prognostic importance of BP mean levels and of BP variability (BPV) estimates and to critically evaluate whether antihypertensive treatment strategies should be targeted at reducing not only average BP levels but also the degree of BPV in order to optimize CV protection in diabetic patients. ### Prognostic value of OBP values Consistent evidence from observational studies has indicated that the risk of CV morbidity and mortality has a strong and continuous relationship with OBP levels (3), without any evidence of a threshold down to at least 115/75 mmHg (4). Furthermore, large meta-analyses of major interventional trials …

Renal Sympathetic Denervation and Daily Life Blood Pressure in Resistant Hypertension Simplicity or Complexity

Drug-resistant hypertension is a clinically relevant problem that has attracted increasing attention over the past few years. This is certainly attributable to a growing awareness of the importance of blood pressure (BP) control in reducing hypertension-related cardiovascular risk. It is also due, however, to a recent major breakthrough in the management of resistant hypertension, because of the introduction of 2 novel invasive therapeutic approaches: carotid baroreceptor stimulation and catheter-based renal sympathetic denervation (RDN).1,2 For a number of reasons, the latter method seems to be taking the upper hand and is used with growing enthusiasm all over the world, even if the strength of the evidence in its support is not currently overwhelming. The concept of RDN derives from a known pressor effect of sympathetic stimuli, arriving to the kidney via efferent fibers located in the adventitia of renal arteries, in the frame of a complex regulation of sympathetic activity also including reflex modulation by renal afferent neural influences.3–5 Hence, the hypothesis was made that destruction of these fibers, by bilaterally applying radiofrequency electric current through an ablation catheter positioned inside renal artery, might reduce sympathetic activity in general. It was also hypothesized that, in particular, renal sympathetic fiber ablation might interfere with sympathetic renal modulation, leading to increased sodium and water excretion and to vasodilation, thereby effectively lowering elevated BP levels. This hypothesis was first tested in animal studies3,4 and subsequently explored in 2 major studies in humans: Renal sympathetic denervation in patients with Refractory Hypertension (The Symplicity HTN-1 Trial) and Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial),7 followed by a growing number of reports from registries. Although the results of Symplicity studies clearly supported the efficacy of RDN in lowering office BP, their design …

Assessment and interpretation of blood pressure variability in a clinical setting

Abstract Blood pressure (BP) is characterized by marked fluctuations occurring within the 24 h as a result of complex interactions between behavioral, environmental, humoral, and neural central or reflex influences. Significant BP variations also occur over more prolonged periods of time (i.e. between days, weeks, months, seasons and even years), not as a random phenomenon but as a result of several interacting factors yet not completely identified. Depending on the method and time interval considered for measurement, the clinical significance and prognostic implications of different types of BP variability (BPV) may substantially differ. Either in the short or in the long term, BPV has been associated with development, progression and severity of cardiac, vascular and renal organ damage and with an increased risk of cardiovascular events and mortality, independently adding to cardiovascular risk, over and above the contribution of elevated mean BP levels. The present paper provides a review on the main methods currently employed for assessment of BPV as well as on the mechanisms, clinical interpretation and prognostic significance of different types of BPV, addressing the question on whether BPV should be a target for antihypertensive treatment for the current prevention of cardiovascular disease.

False Versus True Resistant Hypertension

Current guidelines for the management of resistant hypertension define resistance to antihypertensive treatment based on office blood pressure measurements. However, given the acknowledged limitations of office blood pressure in assessing blood pressure control, a first step in the diagnostic approach of the patient with resistant hypertension consists in defining whether resistance to antihypertensive treatment is true or whether the persisting blood pressure elevation is just the result of an emotional reaction to the doctor’s visit, known as the “white-coat effect,” still evident during treatment, thus corresponding to a “false resistance” phenomenon when coupling office readings with out-of-office BP measuring techniques. Indeed, when combining office BP readings either with ambulatory or with home blood pressure monitoring, a treated patient initially identified as having resistant hypertension based on office blood pressure values may fall into one of four categories: (1) true BP control (normal in-office and out-of-office blood pressure levels); (2) true resistant hypertension (elevated in-office and out-of-office blood pressure levels); (3) false or “white-coat” resistant/uncontrolled hypertension (elevated in-office but normal out-of-office blood pressure levels); and (4) false BP control or masked resistant/uncontrolled hypertension (normal in-office but elevated out-of-office blood pressure levels). A proper assessment of blood pressure control and classification of treated hypertensive patients with the combined use of office, ambulatory, and ideally home blood pressure measurements are of upmost relevance for defining the need for performing additional diagnostic procedures (i.e., screening tests for secondary causes of resistant hypertension) and/or implementing more aggressive pharmacological or interventional strategies for the management of resistant hypertension.

Predictive Factors for White-Coat Hypertension

The alerting reaction associated with the doctor’s visit or more in general with the situation of being in a medical environment causes important interference with blood pressure (BP) measurement in the clinical setting, possibly leading to misclassification of BP levels [1]. Indeed, more than 30 % of subjects who present an acute elevation of BP levels in the doctor’s office (white-coat effect, WCE) may be diagnosed as having white-coat hypertension (WCH, or isolated office hypertension, i.e., the condition characterized by persistently elevated office BP levels and normal ambulatory and/or home BP levels). In recognition of this, current hypertension guidelines have included the suspicion of WCH among the clinical indications for performing out-of-office BP monitoring [2, 3]. However, since performing ambulatory BP monitoring in all subjects who present with elevation in BP levels in the medical office is not always feasible, several studies have been conducted in the attempt to identify clinical and demographic factors that could help the practicing physician to suspect WCH and thus to reasonably proceed with performance ambulatory BP monitoring. However, no clear evidence has been so far provided regarding the clinical features that should be considered in order to raise this suspicion. The first pioneering studies implementing continuous intra-arterial BP recordings indicated that the magnitude of the WCE during a physician visit is largely variable among different subjects, which makes it hardly predictable in the individual patient [1]. Moreover, this interindividual variability in the magnitude of the WCE was not entirely explained by differences in clinical or demographic patients’characteristics (i.e., age, sex, 24-h BP levels) nor by the degree of spontaneous 24-h BP variability [1]. Inconclusive have also been the results of studies exploring the role of other potential predictors for WCE and WCH, such as the pressor response to physical and mental laboratory stress, psychobehavioral factors, or physical activity.

White Coat Hypertension: Definition, Terminology and Prevalence

The medical visit, or more in general the situation of being in a clinical environment, often leads the patient to experience an alerting reaction and a transient increase in blood pressure (BP) levels [1–3], known as the “white coat effect” [4]. This represents a major problem associated with BP measurement in clinical practice, as it prevents BP measures obtained in the clinic from accurately reflecting the “true” subject’s blood pressure values. Although the first description of this phenomenon was performed by the end of the nineteenth century [5], it was thanks to the observations made by studies implementing sophisticated systems for continuous BP monitoring in ambulatory conditions that the nature and mechanisms responsible for the pressor response to the medical visit could be better understood [1, 3]. These pioneering studies not only provided direct and precise quantitative assessment of the BP rise associated with the doctor’s visit but also indicated that it is the alerting reaction and not the cuff inflation at the moment of BP measurement that causes this pressor response [1, 6].

Diagnostic Approach to White Coat Effect and White Coat Hypertension

An accurate measurement of blood pressure (BP) levels has important implications for clinical decision making, as it is the basis for a reliable diagnosis of hypertension and for assessment of BP control in treated subjects. The BP rise associated with the alerting reaction during the medical visit, the so-called white coat effect (WCE), represents a major problem associated with conventional BP measurement as it may lead to overestimation of initial BP levels in the absence of treatment and/or to underestimation of the effect of antihypertensive drugs in treated subjects. As a consequence of this, there will be a significant number of subjects with elevated BP levels in the office but with persistently normal out-of-office BP levels (a condition defined as “white coat” hypertension, WCH, or “isolated office” hypertension). Likewise, a considerable number of treated subjects will have apparent resistant hypertension in the office, despite achieving adequate out-of-office BP control with antihypertensive drugs (a condition defined as white coat resistant hypertension, WCRH). From a practical standpoint, the quantification of the magnitude of the WCE would allow estimating subjects’ actual BP levels, thus reducing misclassification of hypertension and providing a better assessment of BP control. However, an accurate and direct estimation of the WCE requires implementation of complex and sophisticated BP measurement techniques (i.e., beat-to-beat BP recordings) before, during, and after the medical visit [1, 2] which prevents it to be obtained routinely either in a clinical setting or in population studies. To overcome these difficulties, alternative, indirect approaches for estimation of the alarm reaction to the medical visit, based on discontinuous ambulatory BP recordings, have been proposed. The most popular of these indirect methods for the assessment of the WCE consists in the straightforward estimation of the difference between clinic BP and average daytime ambulatory BP levels (measured either with ambulatory or home BP monitoring) [3, 4]. By using this methodology, it is also possible to identify WCH (elevated in-office but normal out-of-office blood pressure levels) as well as WCRH (apparent resistant hypertension based on the finding of persisting elevated OBP measures accompanied by adequate control of out-of-office BP levels) in treated subjects. Since both of these conditions occur with a relatively high frequency in clinical practice, current hypertension guidelines [5, 6] have included suspicion of WCH in untreated patients among the clinical indications for out-of-office BP monitoring. Along the same line, guidelines for the management of resistant hypertension request as a mandatory step the exclusion of WCRH by means of a 24-h ambulatory BP monitoring, before proceeding with any interventional therapy of this condition [7].