Abstract
Evaluation of: Miyashita H, Aizawa A, Hashimoto J et al. Cross-sectional characterization of all classes of antihypertensives in terms of central blood pressure in Japanese hypertensive patients. Am. J. Hypertens. 23(3), 260–268 (2010).
Central blood pressure (CBP) more directly imposes mechanical stress on the left ventricle, large arteries and the vital organ vasculature than peripheral blood pressure. Although CBP is most accurately measured using invasive devices, several methods have been developed recently to derive CBP by noninvasive techniques. Several studies have demonstrated that CBP is superior to peripheral blood pressure as a cardiovascular predictor in hypertensive patients, but the clinical significance of CBP measurement has not been fully examined. The paper under evaluation offers cross-sectional observational results assessing all classes of antihypertensive drugs in relation to CBP measured by a noninvasive technique. This study demonstrates that vasodilatory antihypertensives lower CBP independently of peripheral blood pressure levels without evident class-specific differences, whereas nonvasodilators may raise CBP. Thus, this study establishes the clinical significance of CBP measurement by demonstrating differences in the effects of various antihypertensive drugs on CBP and peripheral blood pressure, the more common clinical measure.
It is well known that blood pressure (BP) management is important for the prevention of cardiovascular events. Peripheral BP (brachial BP), which is usually measured in clinical settings, is an essential parameter for the evaluation and management of BP. On the other hand, central BP (CBP) Citation[1], reflecting ascending aortic BP, has also been shown to be important because it may be more predictive of outcome in specific populations Citation[2,3]. CBP is thought to indicate the pressure exerted on the heart and brain. Therefore, the 2003 European Society of Hypertension/European Society of Cardiology guidelines for the management of arterial hypertension acknowledged that CBP may be different from BP measured at the arm. However, although these guidelines acknowledged that CBP may be important as a measure of subclinical organ damage, they also stressed the need for prospective trials to establish the predictive value of CBP. After publication of these guidelines, the large-scale Anglo–Scandinavian Cardiac Outcomes Trial (ASCOT)–Conduit Artery Function Evaluation (CAFE) study reported that CBP may be a determinant of clinical outcomes and that brachial BP is not always a good indicator of the effect of BP-lowering drugs on arterial hemodynamics Citation[3]. The trial highlighted that BP-lowering drugs can have substantially different effects on CBP, despite a similar impact on brachial BP, and that central rather than brachial BP should be a treatment target. However, there is clearly a need for additional studies of CBP in other populations or in other disease states in order to establish the superiority of CBP to brachial BP in assessing clinical outcomes in antihypertensive treatment.
Recently, CBP has been evaluated noninvasively by mathematically transforming the radial artery pulse waveform to the aortic pulse waveform Citation[4–6], and it has been measured widely in clinical settings in Japan with an automated tonometric system, HEM-9000AI (Omron Healthcare, Kyoto, Japan). However, the clinical significance of CBP, which can be measured easily by automated applanation tonometry, has not been fully elucidated. Based on the background mentioned previously, further studies are needed to assess the effects of antihypertensive drugs on CBP evaluated from the radial artery pulse waveform using automated applanation tonometry. Here, we evaluate a paper in which a cross-sectional characterization of the effects of various classes of antihypertensive drugs on CBP was performed on Japanese hypertensive patients.
Methods & results
The study was a cross-sectional observation, designed as an exploratory (or data-mining) study to generate rather than to test a hypothesis. The authors sought to tentatively characterize all classes of antihypertensive agents commonly used in Japan in terms of effects on CBP. They enrolled 1727 patients with essential hypertension from seven major Japanese medical centers and their related facilities who had been on stable antihypertensive medication for at least 3 months. Patients’ medical data, including radial artery tonometry-derived parameters relating to CBP, were made available. This study also enrolled 848 nonhypertensive subjects (systolic BP [SBP] <140 mmHg and diastolic BP [DBP] <90 mmHg). Radial artery pressure pulse waveform was recorded by the automated tonometric system HEM-9000AI with patients in a sitting position after at least 5 min of rest. The HEM-9000AI algorithm automatically performed an online detection of the second peak (late systolic inflection) based on the second maxima of the fourth derivative of the radial pressure waveform to determine the radial augmentation index, as well as the late or second SBP (SBP2). In order to assess CBP-lowering effects selectively, the authors focused on central SBP levels relative to brachial SBP because absolute CBP levels largely depend on the mean BP level, which is nearly identical for both central and peripheral sites. The height of the second peak corresponds to SBP2, which is reportedly an alternative to or is closely related to directly measured central aortic SBP Citation[4]. The authors created an index, ΔSBP2, defined as SBP2 – SBP, to assess peak SBP reduction between peripheral and central sites. ΔSBP2 was assessed with a linear regression model-based adjustment. Separate regression models for ΔSBP2 were constructed for both participant groups as well as specified subpopulations. In patients treated with any single vasodilating (VD) antihypertensive agent, ΔSBP2 was 3.3 mmHg lower than that in patients treated with non-VD agents, and was 2.0 mmHg lower than that estimated in nonhypertensive subjects. There was no significant interclass difference among the results for VD antihypertensive agents. The combination of two vasodilators resulted in ΔSBP2 values 6.6 and 2.9 mmHg lower than those of non-VD combinations and nonhypertensive subjects, respectively (p < 0.001 for all comparisons). Non-VD agents and their combination resulted in ΔSBP2 values 1.1 and 3.7 mmHg higher, respectively, than those in nonhypertensive subjects (p < 0.001 for both).
Expert commentary
This cross-sectional study demonstrated that VD antihypertensives lower CBP independently of peripheral BP levels without evident class-specific differences, whereas non-VD agents may raise CBP. The authors conclude that, among all classes of antihypertensive drugs, any single VD antihypertensive agent (whether a calcium channel blocker, ARB, ACE inhibitor or α-blocker) would be likely to lower CBP, whereas a non-VD agent (a diuretic or β-blocker) would likely raise the CBP above the physiological level when peripheral BP is adjusted to the same level.
This evaluated paper is one of several studies demonstrating the efficacy of CBP measurement in assessing the effects of antihypertensive drugs. However, there are limitations that must be recognized. Owing to the cross-sectional and observational design in which the selection of antihypertensive drugs was left to the clinicians, some indication bias was inevitable. In addition, the dose and duration of specified antihypertensive medications were not taken into consideration. However, the findings obtained from this study are sufficiently promising to encourage the exploration of CBP measurement in large, randomized clinical trials.
Furthermore, the results of this study are consistent with those of reported studies Citation[3,7], including the CAFE study, in which CBP was measured with another machine, the SphygmoCor® device (AtCor Medical, Sydney, Australia). Therefore, this study also confirmed the feasibility of HEM-9000AI, which is the most widely used system in Japanese clinical studies for measuring CBP from the radial artery pressure pulse waveform. Finally, the feature of each antihypertensive class in terms of CBP and its prognostic predictive value should be assessed by large-scale randomized intervention trials.
Five-year view
Many lines of evidence have shown that CBP is a better predictor of future cardiovascular events, including death, than peripheral BP. Several noninvasive, validated and easy-to-use techniques exist to estimate CBP, including the radial artery tonometry (HEM-9000AI) system used in the evaluated paper, and its cost is acceptable in clinical settings. Over the next 5 years, we will continue to see further accumulation of evidence regarding the clinical usefulness of this method in the field of CBP. Nevertheless, we should not forget that CBP is one of the surrogate markers for future cardiovascular events. The question of whether CBP provides value over and above peripheral BP is pivotal. Evidence is growing that this may indeed be the case. For example, the superiority of CBP relative to peripheral BP in terms of its association with left ventricular hypertrophy has been reported in several studies Citation[8,9]. However, more data are needed to establish that CBP should be used as a surrogate marker in clinical practice. In particular, the most desirable data will elucidate whether the improvement of radial artery tonometry-derived CBP by antihypertensive drugs actually improves hypertension-induced target organ damage such as left ventricular hypertrophy, and provides improved clinical outcomes, including overall survival.
Key issues
• Central blood pressure (CBP) more directly imposes mechanical stress on the left ventricle, large arteries and vital organ vasculature than peripheral blood pressure such as brachial pressure.
• Although CBP is most accurately measured by invasive devices, several methods have been devised to derive CBP from analyses of applanated radial pulses.
• Although the Conduit Artery Function Evaluation (CAFE) study demonstrated that CBP is superior to brachial blood pressure as a cardiovascular predictor in hypertensive patients, the effects of antihypertensive drugs on CBP have not been fully examined.
• In the evaluated cross-sectional observational study, CBP measurement suggests that vasodilatory antihypertensives lower CBP independently of peripheral blood pressure levels without evident class-specific differences, whereas nonvasodilators may raise CBP.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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