BLOOD PRESSURE VARIABILITY AND RISK OF CARDIOVASCULAR EVENTS AND MORTALITY IN ADULTS WITH HYPERTENSION: A FOCUSED SYSTEMATIC REVIEW AND EVIDENCE UPDATE
Keywords:
hypertension; blood pressure variability; cardiovascular risk; mortality; systolic blood pressure; systematic reviewAbstract
DOI: https://doi.org/10.46296/yc.v10i19.0949
Abstract
Background: Mean blood pressure (BP) remains the main therapeutic target in hypertension, but intra-individual BP fluctuations may capture residual risk not reflected by average BP. Objective: To synthesize evidence on the association of blood pressure variability (BPV) with cardiovascular events and mortality in adults with hypertension. Methods: Focused systematic review and evidence update of cohort studies and post hoc trial analyses in established hypertension. Visit-to-visit variability—standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV)—was prioritized, with 24-hour variability considered secondarily. Outcomes included major adverse cardiovascular events (MACE), stroke, coronary events, heart failure, cardiovascular mortality, and all-cause mortality. Because exposure metrics, scales, and contrasts were highly heterogeneous, a qualitative synthesis was performed. Results: Thirteen key studies were integrated. Most showed an independent graded association between higher systolic BPV and adverse outcomes. In ASCOT-BPLA, the highest decile of systolic SD was associated with stroke (HR 3.25; 95% CI 2.32–4.54). In VALUE (n=13,803), the highest quintile of systolic SD doubled cardiovascular event risk (HR 2.10; 95% CI 1.70–2.40), while each 5-mmHg increase in SD increased mortality by 10% (HR 1.10; 95% CI 1.04–1.17). In 225,759 Chinese adults with hypertension, each 10-mmHg increase in systolic SD was associated with cardiovascular disease (HR 1.35; 95% CI 1.30–1.39) and mortality (HR 1.40; 95% CI 1.34–1.45). Conversely, SPRINT did not show a consistent independent association for systolic office BPV under intensive control, and STEP suggested attenuation of prognostic value with intensive treatment. Conclusions: Elevated systolic BPV is a reproducible prognostic marker in hypertension, particularly when average BP control is not intensive or stable. BPV may complement—but should not replace—mean BP control. Standardized thresholds and measurement protocols are needed before routine use as a therapeutic target.
Keywords: hypertension; blood pressure variability; cardiovascular risk; mortality; systolic blood pressure; systematic review.
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References
Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management of blood-pressure variability. Nat Rev Cardiol. 2013;10:143–155.
Parati G, Stergiou GS, Dolan E, Bilo G. Blood pressure variability: clinical relevance and application. J Clin Hypertens. 2018;20:1133–1137.
Messerli FH, Hofstetter L, Rimoldi SF, Rexhaj E, Bangalore S. Risk factor variability and cardiovascular outcome: JACC review topic of the week. J Am Coll Cardiol. 2019;73:2596–2603.
de la Sierra A. Blood pressure variability as a risk factor for cardiovascular disease: which antihypertensive agents are more effective? J Clin Med. 2023;12:6167.
Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet. 2010;375:895–905. doi:10.1016/S0140-6736(10)60308-X.
Eguchi K, Hoshide S, Schwartz JE, Shimada K, Kario K. Visit-to-visit and ambulatory blood pressure variability as predictors of incident cardiovascular events in patients with hypertension. Am J Hypertens. 2012;25:962–968. doi:10.1038/ajh.2012.75.
Hastie CE, Jeemon P, Coleman H, et al. Long-term and ultra long-term blood pressure variability during follow-up and mortality in 14,522 patients with hypertension. Hypertension. 2013;62:698–705. doi:10.1161/HYPERTENSIONAHA.113.01343.
Chowdhury EK, Owen A, Krum H, Wing LMH, Nelson MR, Reid CM. Systolic blood pressure variability is an important predictor of cardiovascular outcomes in elderly hypertensive patients. J Hypertens. 2014;32:525–533. doi:10.1097/HJH.0000000000000028.
Kostis JB, Sedjro JE, Cabrera J, et al. Visit-to-visit blood pressure variability and cardiovascular death in the Systolic Hypertension in the Elderly Program. J Clin Hypertens (Greenwich). 2014;16:34–40. doi:10.1111/jch.12230.
Muntner P, Whittle J, Lynch AI, et al. Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality: a cohort study. Ann Intern Med. 2015;163:329–338. doi:10.7326/M14-2803.
Chang TI, Reboussin DM, Chertow GM, et al. Visit-to-visit office blood pressure variability and cardiovascular outcomes in SPRINT. Hypertension. 2017;70:751–758. doi:10.1161/HYPERTENSIONAHA.117.09788.
Mehlum MH, Liestøl K, Kjeldsen SE, et al. Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks. Eur Heart J. 2018;39:2243–2251. doi:10.1093/eurheartj/ehx760.
Coccina F, Pierdomenico AM, Cuccurullo C, Pierdomenico SD. Prognostic value of average real variability of systolic blood pressure in elderly treated hypertensive patients. Blood Press Monit. 2019;24:179–184. doi:10.1097/MBP.0000000000000381.
Wan EYF, Yu EYT, Chin WY, Fong DYT, Choi EPH, Lam CLK. Association of visit-to-visit variability of systolic blood pressure with cardiovascular disease, chronic kidney disease and mortality in patients with hypertension. J Hypertens. 2020;38:943–953. doi:10.1097/HJH.0000000000002347.
Mancusi C, Trimarco V, Losi MA, et al. Impact of visit-to-visit blood pressure variability on hypertensive-mediated target organ damage and future cardiovascular events: the Campania Salute Network. J Hypertens. 2021;39:1852–1858. doi:10.1097/HJH.0000000000002847.
Yu J, Song Q, Bai J, et al. Visit-to-visit blood pressure variability and cardiovascular outcomes in patients receiving intensive versus standard blood pressure control: insights from the STEP trial. Hypertension. 2023;80:1507–1516. doi:10.1161/HYPERTENSIONAHA.122.20376.
Lukitasari M, Jonnagaddala J, Liaw ST, Jalaludin B, et al. Visit-to-visit blood pressure variability and cardiovascular outcomes: a systematic review and dose-response meta-analysis. Eur J Prev Cardiol. 2026;33(7):1127–1137. doi:10.1093/eurjpc/zwaf546.
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71.
Fabsitz RR, Reese JA, Leidner J, et al. Visit-to-visit blood pressure variability as a risk factor for all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events among American Indians: the Strong Heart Study. Prev Chronic Dis. 2025;22:240512. doi:10.5888/pcd22.240512.
Li HL, et al. Blood pressure variability and risk of cardiovascular events and mortality. J Am Heart Assoc. 2025;14:e037658. doi:10.1161/JAHA.124.037658.
Zhao W, et al. Blood pressure variability and cardiovascular events in high-risk individuals: individual patient data analysis of SPRINT and ACCORD trials. Eur Heart J. 2026. doi:10.1093/eurheartj/ehag330.
Peng X, Song Q, Bai J, et al. Blood pressure trajectories and cardiovascular outcomes in older patients: insights from the STEP trial. J Am Coll Cardiol. 2026. doi:10.1016/j.jacc.2026.01.090.
Joanna Briggs Institute. Critical Appraisal Checklist for Cohort Studies. JBI Manual for Evidence Synthesis. Adelaide: JBI; current online version.
Feng Z, et al. Combined effect of time in target range and variability of systolic blood pressure on cardiovascular outcomes and mortality in patients with hypertension: a prospective cohort study. J Clin Hypertens (Greenwich). 2024;26:714–723. doi:10.1111/jch.14816.
Diaz KM, Tanner RM, Falzon L, et al. Visit-to-visit variability of blood pressure and cardiovascular disease and all-cause mortality: a systematic review and meta-analysis. Hypertension. 2014;64:965–982. doi:10.1161/HYPERTENSIONAHA.114.03903.
Stevens SL, Wood S, Koshiaris C, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ. 2016;354:i4098. doi:10.1136/bmj.i4098.
Wang J, Shi X, Ma C, et al. Visit-to-visit blood pressure variability is a risk factor for all-cause mortality and cardiovascular disease: a systematic review and meta-analysis. J Hypertens. 2017;35:10–17. doi:10.1097/HJH.0000000000001159.
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