Blood pressure variability: from lie detector to clinical medicine

In all living organisms, blood pressure (BP) changes naturally, and SBP and DBP vary even from beat to beat. For research and clinical purposes, blood pressure variability (BPV) is classified by timescale and measurement method. Very short-term (beat-to-beat or second-to-second) BPV reflects rapid fluctuations driven mainly by autonomic regulation and is measured using intra-arterial or photoplethysmographic techniques. Short-term BPV refers to changes over 24 h, typically captured by ambulatory blood pressure monitoring (ABPM), revealing patterns such as circadian rhythms, dipping, or morning surges. Long-term BPV includes visit-to-visit variability over weeks, months, or years and is usually assessed using office or home BP measurements, reflecting broader environmental and behavioral influences. BPV indices differ in their sensitivity to mean BP and the time sequence of readings; for example, standard deviation (SD) and coefficient of variation are closely tied to average BP, while average real variability (ARV) is unaffected by the mean and reflects temporal BP changes. Variation independent of the mean (VIM) removes the confounding effect of mean BP and is derived through nonlinear regression, making it suitable for comparing BPV across cohorts with different mean values. Weighted SD and ARV are better for capturing short-term BPV from ambulatory monitoring, whereas SD and VIM are used in long-term BPV assessments from office or home measurements 1,2. William Moulton Marston (1893–1947), an American psychologist, lawyer, and the creator of the fictional comic character Wonder Woman, was the first to propose and systematically study the use of SBP changes for practical purposes, beginning his research around 1915 as a graduate student at Harvard. Inspired by his wife Elizabeth Holloway Marston's observation that her BP rose during emotional excitement, Marston developed the systolic BP test, which used a standard sphygmomanometer to measure intermittent BP responses during questioning. His method relied on comparing an individual's baseline BP responses to “control” versus relevant (potentially incriminating) questions, and his findings were published as early as 1917, later forming the scientific foundation for the modern polygraph, “lie detector” 3. Further foundational work on BPV as a physiological phenomenon occurred throughout the 20th century, with advances in beat-to-beat BP measurement and the recognition of short-term, mid-term, and long-term variability as clinically relevant from the 1970 s onward. Early BPV research established that fluctuations in BP across various time scales are influenced by behavioral, humoral, and mechanical factors, and this concept formed the basis for subsequent studies linking BPV to cardiovascular risk 2. BPV – across short-term, mid-term, and long-term time scales – is now recognized as an independent risk factor for adverse cardiovascular outcomes and target organ damage in hypertensive patients, beyond the impact of mean BP. Higher BPV has been strongly associated with increased risk of events such as stroke, dementia, coronary artery disease, heart failure, progression of chronic kidney disease, and mortality after admission to the emergency department. BPV is a clinically meaningful risk marker for target-organ damage independent of mean BP. Multiple studies reported an association between high BPV and subclinical complications, including brain (white matter lesions), heart (left ventricular hypertrophy), vessels (increased arterial stiffness, microvascular rarefaction, endothelial dysfunction), and activation of inflammatory and neurohormonal pathways. Recent reviews have provided extensive, detailed summaries of current knowledge on BPV, integrating methodological, pathophysiological, and epidemiological insights 2,4. A substantial body of evidence shows antihypertensive drug classes differ in their effects on BPV, with long-acting dihydropyridine calcium channel blockers (such as amlodipine) and thiazide diuretics most consistently reducing both short-term and long-term BPV in clinical trials and meta-analyses. This reduction in BPV is believed to contribute to better cardiovascular outcomes beyond lowering mean BP, as seen in the ASCOT-BPLA trial. The ASCOT-BPLA trial found that an amlodipine/perindopril-based antihypertensive regimen, despite small differences in achieved BP, was superior to atenolol/bendroflumethiazide in reducing major cardiovascular events, all-cause mortality, and new-onset diabetes in high-risk hypertensive patients 5. However, in the ASCOT-BPLA trial, both amlodipine and the beta-blocker atenolol were dosed once daily. Amlodipine achieves a higher trough-to-peak ratio than atenolol when administered once daily, indicating more sustained BP control throughout the dosing interval. This was confirmed in a substudy in which BP was estimated using ABPM, which showed better nocturnal BP control in the amlodipine arm 6. Lifestyle modification is an essential, evidence-based component of hypertension management, recommended as the first-line strategy for both prevention and treatment across all guidelines. Core interventions include dietary changes (reducing sodium intake to less than 2.3 g/day, increasing fruits, vegetables, and potassium-rich foods), regular aerobic exercise, weight reduction if overweight, moderation of alcohol intake, and smoking cessation 7. The DASH diet (Dietary Approaches to Stop Hypertension) lowers BP significantly – by approximately 5–11 mmHg systolic – within weeks of implementation, with even greater effects when combined with sodium reduction. Beyond BP control, the DASH diet offers additional metabolic benefits, making it a first-line, evidence-based recommendation in hypertension guidelines worldwide. Long-term adherence to the DASH diet is associated with significant reductions in cardiovascular risk, including lower incidence of heart failure, coronary heart disease, stroke, and overall cardiovascular disease (CVD). Meta-analyses and cohort studies consistently show that the highest adherence to the DASH diet is associated with approximately a 20% reduction in CVD events and CVD mortality compared with the lowest adherence group. The cardioprotective effects are largely mediated by sustained reductions in BP, improved lipid profiles, better glucose control, weight management, and anti-inflammatory properties 8. In the study titled “Effects of Dietary Patterns and Sodium Intake on Blood Pressure Variability: Results from the DASH and DASH-Sodium Trials,” Zhou et al.9 analyzed the effect of the DASH diet or sodium reduction on BPV, using multiple validated variability metrics, including VIM (variation independent of mean). The findings show that while both the DASH diet and sodium restriction effectively lower absolute BP levels, neither intervention significantly changes BPV – whether assessed in the office or with 24-h ambulatory monitoring – when using robust, mean-independent measures. No significant differences in BPV were observed between dietary groups, across sodium intake strata, or in most subgroup analyses, and any isolated findings lacked a consistent pattern. The study's results suggest that the cardiovascular benefits of DASH and sodium reduction are attributable to reductions in mean BP rather than to effects on BPV itself 9. In other studies in both normotensive and hypertensive individuals, sodium consumption had no noticeable effect on BPV estimated with different measures (coefficient of variation, ARV) 10–12. In another analysis of the DASH-Sodium trial, Chang et al.13 found that a combined DASH diet and low-sodium intake significantly reduced both systolic and diastolic ARV compared with a control diet with high sodium intake, and this effect was partly independent of mean BP for diastolic ARV. However, the reduction of systolic ARV was largely explained by the reduction in mean SBP, while the reduction in diastolic ARV persisted after adjustment and was strongly associated with the urinary sodium-to-potassium ratio. The apparent differences between these two studies regarding the effect of low sodium on BPV are largely attributable to methodological choices, BPV metric selection, population heterogeneity, and statistical adjustment for mean BP. In contrast, Zhou et al.9 used data from the DASH and DASH-Sodium trials and, most importantly, employed VIM as the primary BPV metric, thereby eliminating the confounding influence of changes in mean BP and allowing direct assessment of variability effects independent of average BP. There is strong evidence that nonadherence to antihypertensives, such as missed doses, irregular timing, or sudden discontinuation, causes fluctuating drug levels, leading to unstable BP control and greater visit-to-visit or day-to-day BPV. Overall, BPV may serve as both an indicator and a consequence of nonadherence, highlighting the importance of consistent medication use for stable BP control and risk reduction. Targeted behavioral interventions that improve adherence (such as remote coaching and adherence support) have been shown to reduce BPV independent of effects on mean BP 14. Although BPV is now recognized as an independent predictor of hypertension-related complications, a causal relationship has not been firmly established. It remains uncertain whether BPV itself causes organ damage or merely reflects the influence of underlying pathophysiological processes, such as vascular stiffness, sympathetic overactivity, autonomic dysfunction, drug nonadherence, or inadequate BP control. There is currently no consensus on the optimal BPV indices, no universally accepted clinical cutoff for “high” BPV, and limited practical guidance for primary care, making individualized risk prediction and intervention planning challenging. Long-acting antihypertensive agents are now preferred, as they provide more consistent BP lowering throughout 24 h and better control for patients with elevated BPV. The study by Zhou et al.9 questions the clinical significance of BPV but reinforces the importance of effective lifestyle modification and BP reduction as the cornerstone of hypertension management. ACKNOWLEDGEMENTS None. Conflicts of interest There are no conflicts of interest.