Cardiovascular disease does not occur in a single day; its onset is discontinuous and sudden. In addition, an individual’s risk of experiencing a cardiovascular event is not constant and varies over time. To help explain the timing of what to-date have been unexpected sudden-onset cardiovascular events, we have proposed the ‘surge blood pressure resonance hypothesis’ [1,2,3]. This is based on the fact that blood pressure (BP) variability occurs across a variety of different time-phases: beat-by-beat (short-term), situational, diurnal, day-by-day, seasonal, and annually (long-term) [3,4,5,6]. All these different types of BP variability are associated with cardiovascular risk [3, 4, 6, 7].

Another important BP parameter is BP surge—an acute increase in BP that represents the pressor component of BP variability. BP surge is defined as the difference between the peak BP induced by a pressor trigger and baseline BP levels, while surge BP is defined as the peak BP with an acute BP increase. Based on its definition as the difference between peak and baseline BP values, the reproducibility of BP surge is poor due to variability in the two contributing factors. However, poor reproducibility does not necessarily diminish the clinical significance of BP surge as a potential trigger for cardiovascular events [1, 2, 6].

Surge blood pressure resonance hypothesis

The resonance hypothesis proposes that a dynamic surge in BP is the result of resonance between different types of BP with different time-phases, and that when the peaks of these different types of BP variability coincide to create a pathologically large surge in BP, an acute cardiovascular disease event is triggered (Fig. 1A) [1, 8]. Unstable (less reproducible) BP surge levels, which can be unexpectedly generated by the resonance of several BP surges triggered by various pressors under different conditions, are associated with the highest risk of a cardiovascular event [1, 2, 6].

Fig. 1
figure 1

Surge blood pressure resonance hypothesis: description [1] (A) and association with stroke risk [15] (B). A Surge blood pressure resonance hypothesis: different types of blood pressure (BP) surge and the pressor component of BP variability, with different time phases, become synchronized to generate a large dynamic surge BP, which triggers a cardiovascular (CV) disease event, especially high-risk individuals with arterial stiffness. The shortest BP surge component is beat-by-beat, occurring due to triggers such as exercise, mental stress, strain, smoking, pollution, high salt and alcohol intake, cold temperature, poor sleep, sleep apnea. B Association between surge BP detected by home BP monitoring and stroke events in the Japan Morning Surge-Home Blood Pressure (J-HOP) study. J-HOP enrolled 4231 individuals (mean 65 years) who were followed for 6.2 years; there were 94 strokes and 124 coronary artery disease events during follow-up. The incidence of stroke events (per 1000 person-year) are shown, stratified by quintiles of the average peak (Q1, <142.7 mmHg; Q2, 142.7 to <152.0 mmHg; Q3, 152.0 to <160.7 mmHg; Q4, 160.7 to <173.0 mmHg; Q5, ≥173.0 mmHg) and morning-evening average (Q1, <122.4 mmHg; Q2, 122.4 to <129.4 mmHg; Q3, 129.4 to <136.0 mmHg; Q4, 136.0 to <145.3 mmHg; Q5, ≥145.3 mmHg) home systolic BP values

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Detecting surge blood pressure in clinical practice

Theoretically, surge BP should be defined as the peak beat-by-beat systolic BP (SBP). Continuous BP monitoring would be required to determine this, but there is not currently any all-in-one BP monitoring device that can accurately and repeatedly detect true surge BP under real-world conditions. Nevertheless, the probability of detecting BP variability increases as the number of BP measurements increases.

In this paper, surge BP is defined as the peak BP levels detected by office, home, ambulatory, and wearable BP monitoring. However, because these intermittent measurements using oscillometric devices do not accurately detect surge BP, its overall impact may be underestimated [9]. In clinical practice, home BP monitoring (HBPM) is the most sensitive modality for detecting the risk of BP variability and surge because of the comparatively high number of accurate BP measurements with a validated device compared with other BP assessment methods. In fact, short-term diurnal, day-by-day, seasonal, and annual BP variability can be detected with HBPM, without artifacts. To provide as much relevant information as possible, an information and computer technology (ICT)-based HBPM-centered approach is emerging as an optimal hypertension management in the digital era [10,11,12].

Currently available evidence supports an association between surge BP (defined as the maximum/peak of BP values detected using office, home, or ambulatory measurements), is associated with a higher risk of cardiovascular events, especially stroke (Table 1). In the UK-TIA trial, the maximum office SBP measured for 2 years (i.e., the first seven study visits) was a strong risk factor for stroke [13]. After adjustment for mean office SBP, individuals with surge office SBP in the highest decile had a 15-fold higher risk of stroke compared with those who had surge office SBP in the lowest quartile (p < 0.001). Peak home SBP has also been significantly associated with stroke risk [14]. The Japan Morning Surge-Home Blood Pressure (J-HOP) study extended defined average peak home SBP as the average of the highest three BP values for each individual over the 13-day home BP assessment period [15]. In individuals with an average peak home SBP in the highest versus lowest quintile the adjusted hazard ratio (HR) for the risk of stroke was 4.39 (95% confidence interval [CI] 1.85–10.43) and for the risk of atherosclerotic cardiovascular disease was 2.04 (95% CI: 1.24–3.36). The risk of stroke in the high versus low average peak home SBP quartile was greatest in the first 5 years of follow-up (HR 22.66, 95% CI: 2.98–172.1). The pathological threshold value for average peak home SBP with respect to 5-year stroke risk was 173 mmHg (Quintile 5), and there was a linear association between the number of times peak home SBP was ≥176 mmHg and stroke risk. Furthermore, stroke risk was more closely associated with peak home SBP than mean home SBP (Fig. 1B) [15]. The risk associated with peak home SBP persisted even after adjustment for average real variability (ARV), a measure of home BP variability that is independent of mean BP [16, 17]. Thus, exaggerated peak home SBP > 175 mmHg appears to be an early and strong novel risk factor for stroke.

Table 1 Studies documenting the stroke risk associated with surge blood pressure
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Daytime maximum SBP measured by ambulatory BP monitoring (ABPM) is also an independent risk factor for cardiovascular events, especially in individuals with increased arterial stiffness. In the Japan Ambulatory Blood Pressure Monitoring Prospective (JAMP) study, individuals who had an ambulatory arterial stiffness index (AASI) ≥0.5783 plus a daytime maximum ambulatory BP (the highest 1-h moving average of two consecutive ambulatory SBP readings during the daytime) in the top quartile (≥179.4 mmHg) were at increased risk of stroke events compared with individuals who had high AASI and daytime maximum ambulatory BP in the other quartiles (adjusted HR 1.89, 95% CI: 1.13–3.15) [18].

Who is at risk of surge BP?

The impact of surge BP as a trigger for cardiovascular events is much greater in individuals with stiffened arteries, especially the aorta. When the aorta is soft it can absorb the power of beat-by-beat pulses. However, a stiff aorta cannot absorb the power of surge BP generated by resonance, resulting in the transmission of unattenuated surge BP levels to the peripheral cerebral and coronary arteries. In the presence of an atherosclerosis, surge BP can trigger plaque rupture, resulting in atherothrombotic stroke and coronary artery disease events. Lacunar stroke, hemorrhagic stroke, and heart failure can also be triggered. The concept of systemic hemodynamic atherothrombotic syndrome (SHATS) has been proposed [8]. This is a vicious cycle of BP variability and vascular damage (advanced large artery stiffness and small artery remodeling) that results in organ damage and cardiovascular events. The SHATS concept partly explains how exaggerated surge BP can trigger cardiovascular events, especially in elderly individuals with hypertension or those with a history of stroke.

Pathological thresholds of surge BP

There are pathological thresholds for surge BP (peak/maximum BP) in office, home, and ambulatory situations. An exaggerated SBP response to exercise in the laboratory setting has been defined as a maximal value of ≥210 mmHg for men and ≥190 mmHg for women [19, 20]. In the 6578 asymptomatic participants in the Lipid Research Clinics Prevalence Study, a BP of >180/90 mmHg versus ≤180/90 mmHg during stage 2 of the Bruce exercise protocol was associated with increased cardiovascular mortality risk in normotensive individuals, but not in those with hypertension [21]. Although there is less evidence regarding cardiovascular risk thresholds for surge BP compared with mean BP, we propose the following pathological surge BP thresholds (defined using standard repeated BP measurements): 175 mmHg for home SBP, 180 mmHg for ambulatory SBP, and 220 mmHg for office SBP.

New technology and wearable BP monitoring

A cuffless approach to BP monitoring would be the ideal method for obtaining large numbers of BP readings during daily life, and devices that do this are already available. However, the accuracy of some of these devices for out-of-office use is not well validated [22]. Wearable oscillometric BP monitoring devices can be used for ABPM in clinical practice with good accuracy. The watch-type oscillometric BP monitoring device, HeartGuide® (Omron Healthcare, Kyoto, Japan) has been validated against international standards in the resting laboratory condition [23]. In addition, a comparative study in which individuals were asked to wear the HeartGuide® device and undergo simultaneous ABPM found that the difference between BP measurements from each device at almost the same time was acceptable both in and out of the office [24]. In a study that utilized the HeartGuide® watch-type device, we found that BP increased during psychological stress in individuals with hypertension [25]. Furthermore, the highest three values of all wearable and ambulatory wearable BP measurements in working individuals with hypertension was significantly correlated with the left ventricular mass index measured by cardiac magnetic resonance imaging [26].

A recent multisensor ABPM device equipped with an actigraph, humidity sensor and thermometer (TM-2441, A&D, Tokyo, Japan) is an “all-in-one” BP monitoring device that could be used for HBPM and office BP measurements in real-world practice and clinical studies [27]. This BP monitoring device allows identification of the peak BP values associated with increased physical activity (physical activity-related BP surge) and actisensitivity (the slope of BP surge in relation to the change in physical activity) [3, 28]. Actisensitivity was found to show seasonal variation, being greater in winter than in summer [28]. Future wearable, multisensor BP monitoring devices should facilitate the identification of personal pressors that cause BP surge. This information could then be used to anticipate pathological surge BP-based on the resonance of each BP surge.

Implication of surge BP for perfect 24-h BP control

We have proposed the concept of perfect 24-h BP control, designed to minimize the level of cardiovascular risk associated with hypertension [3]. This includes three important components, including one relating to control of exaggerated BP variability:

  • Reducing average 24-h BP

  • Achieving appropriate diurnal BP rhythm (dipper type)

  • Maintaining physiological oscillation of BP variability (i.e., the avoidance of exaggerated BP variability triggered by external factors)

Conclusion

Consideration and management of different types of BP variability plays a central role in the personalized management of hypertension. This aims to reduce the magnitude and frequency of surge BP, and is in addition to current average BP-based management strategies. Commitment to this approach should facilitate the achievement of perfect 24-h BP control and significantly reduce the rate of future cardiovascular events.