Hypertension and arterial stiffness

In this issue of The Journal of Clinical Hypertension, Dr Antza and colleagues explored whether white coat hypertension (WCHT) and masked hypertension (MHT) were related to increased arterial stiffness in an untreated population.1 In a cohort of 542 consecutive subjects never been on antihypertensive medications, a significant association between MHT and raised carotid-femoral pulse wave velocity (c-f PWV) emerged.1 Additionally, patients presenting with WCHT showed higher values of systolic blood pressure variability (BPV) in comparison with true normotensive.1 MHT resembled to true hypertension according to day and night systolic variability in BP.1 These findings expand the current body of knowledge about blood pressure (BP) phenotypes and provide useful insights upon the pathophysiological mechanisms linking hypertension to target organ damage. Blood pressure monitoring has been established in clinical and research settings as a reliable technique to assess BP, heart rate, and their circadian variations, and it has been shown to correlate with target organ damage and mortality better than office BP measurements.1, 2 Blood pressure monitoring can result into the detection of two distinct hypertension phenotypes, namely WCHT and MHT. WCHT refers to the untreated condition in which BP is high in the office, whereas it is normal when measured by ambulatory and/or home BP monitoring.3 The prevalence of WCHT ranges from 30% to 40% of the subjects presenting with an increased office BP and raises with the increasing age, reaching more than 50% in the very old population.3 WCHT has been also shown to be more common in women and non-smokers.3 Notably, although out-of-office BP values are within normality as by definition, they tend to be higher than those recorded in true normotensive subjects.3 Conversely, MHT refers to untreated patients whose BP is normal in the office and elevated when measured by ambulatory or home BP monitoring.3 This condition, which has been occasionally described as “reversed WCHT,” can account for about 15% of the patients with an office BP within normal range.4 Its prevalence is higher among men, younger people, and smokers; the use of alcohol, tobacco and caffeine, anxiety and job stress represent further risk factors.3 Subjects presenting with WCHT and MHT have increased adrenergic activity, a higher prevalence of dysmetabolic risk factors, and a greater risk to develop diabetes mellitus and sustained hypertension.3 Far from being clinically innocent conditions, WCHT and MHT have been related to asymptomatic cardiac and vascular damage as well as an overall raised long-term risk of cardiovascular events, after adjustment for demographic and metabolic risk factors.5-8 Interestingly, patients with WCHT and MHT have higher BPV than normotensive people,1, 9 and this may, at least partially, explain the relationship linking these hypertension phenotypes to adverse cardiovascular outcome. Indeed, there is accruing evidence that BPV does not merely represent a random effect phenomenon or a background noise that dilutes the prognostic value of BP assessment, but it is reproducible within individuals over time.10-13 Short- and long-term fluctuations of BP levels actively contribute to the development of target organ damage regardless of mean BP values. Raised BPV can promote arterial remodeling and microvascular injury,14 and it has been associated with increased risk of cardiovascular events, poor vascular outcome, and anatomical and functional alterations in the brain.15-23 The class-specific and dose-dependent effects of antihypertensive drugs in controlling BP fluctuations further make BPV an attractive therapeutic target.24-29 Arterial stiffness demonstrated by reduced arterial compliance and distensibility is a distinctive feature and valuable independent predictor of cardiovascular hazard, with an accuracy that is even higher than the traditional vascular risk factors.30 Elevated c-f PWV is the current reference standard for assessing aortic wall stiffness, and it has been associated with increased risk of incident hypertension and higher cumulative probability of major cardiovascular events.31 Under physiological conditions, arterial stiffness increases progressively from heart to periphery and the proximal aorta is more distensible than the distal tract.32 Together with the proximo-distal tapering of the arterial diameter, the stiffness gradient determines an impedance mismatch that induces reflection of the pressure wave.32 Partial wave reflections reduce the transmission of pulsatile energy to the periphery and, hence, protect microcirculation. When proximal aortic stiffness increases and physiological gradient is reduced or reverted, the pulse propagation cannot be adequately dampened, is transmitted to smaller arteries, and impinges on the microcirculation.32 In addition, less reflected waves return to the central aorta and increase systolic BP and pulse pressure by superimposing on the incident pressure waves.32 Hypertension and arterial stiffness are closely related, and there is still debate whether the former represents a cause or a consequence of the latter.33 Sustained high BP levels induce the synthesis and cross-linking of vascular collagens, fragmentation of elastin in arterial walls, and spatial distribution of vascular smooth muscular cells and extracellular matrix.31, 32 In this regard, hypertension can be considered an accelerated form of vascular aging, which increases vascular thickness and structural stiffening.31 On the other hand, longitudinal studies exploring the relationship between carotid and aortic stiffness and development of hypertension suggested that arterial stiffening precedes and contributes to future changes in systolic hemodynamic load.34, 35 Furthermore, the association between abnormal indices of arterial stiffness and incidence of hypertension persists after the adjustment for BP values at baseline and known risk factors for hypertension.31 Similarly, there is ambiguity about the kind of arteries that are damaged first. The most recent perspective proposes the existence of a cross talk rather than a sequential involvement, whereby alterations in large arteries, as increased arterial stiffness and wall hypertrophy, and remodeling of small resistance vessels, like reduced diameter and vascular rarefaction, occur in parallel and interact each other in a vicious circle that increases mean and central systolic BP and, ultimately, leads to target organ damage.32, 36 Although the pathophysiology linking hypertension to arterial stiffness remains still not completely unraveled, there is converging evidence that optimal BP control is difficult to achieve in patients presenting with hypertension and arterial stiffness.31, 37 In this regard, it is worth to notice that antihypertensive drugs that predominantly or exclusively affect diastolic or mean arterial pressure may not represent the best choice in patients with markedly raised systolic and pulse pressure and increased arterial stiffness, and some classes of BP-lowering agents, including angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, can improve aortic stiffness.31 Nonpharmacological strategies, like physical activity, weight loss, and smoking cessation, have been also proposed as potentially effective “de-stiffening” interventions.38 The assessment of office and ambulatory BP may allow the early identification of hypertension phenotypes associated with increased vascular risk and, hence, have prognostic relevance. Further studies are warranted to evaluate whether other hemodynamic variables in addition to arterial stiffening, as total peripheral resistance, carotid intima-media thickness, amplitudes of the decomposed carotid pressure waves, and cerebrovascular reactivity,39, 40 may allow a better characterization of the individual cardiovascular risk and whether tailoring treatment according to the hemodynamic profile may actually improve vascular outcome.31 None.