Blood Pressure Variability: Mechanisms, Measurement, Subtypes, and Clinical Implications

Main Article Content

Joseph L. Izzo


The complex topic of short- and long-term blood pressure (BP) variability confounds the diagnosis, classification, and management of hypertension. True pathophysiologic BP variation (systematic and non-systematic deviations between- and within-individuals) is related to heart rate, respiration, complex responses of the sympathetic nervous system, vascular reactivity, and arterial stiffness. Measurement errors (systematic biases and random error) further compound the analysis. Most studies use serial clinic BP values, 24-hour ambulatory BP recordings, or home BP values with standard statistical indicators (standard deviation, variance, or coefficient of variation) or absolute real variability (mean difference of successive values). Clinical impact in retrospective secondary analyses includes a modest increase in cardiovascular disease (CVD) risk (equivalent to a few mmHg in mean systolic BP) yet questions remain whether adjustment for mean BP is needed. BP variability is reduced to a small degree by calcium antagonists and increased by ACE inhibitors, beta-blockers, and alpha-blockers but no interventional trial has addressed the question of whether reducing BP variability confers CVD risk protection. BP variability is not specifically discussed in practice guidelines but it is tacitly acknowledged by recommendations to repeat BP measurements, standardize technique, and confirm the hypertension diagnosis by home or ambulatory BP measurements to account for the “white coat effect.” There is no formal consensus on how to quantitate or manage BP variability despite a real-world need for better diagnostic and therapeutic guidance. Practitioners should thus focus on control of (mean) BP using combinations of agents that improve CVD outcomes. Future consensus guidance should directly address BP variability and should include educational materials for physicians, patient-contact staff, and patients.

Keywords: blood pressure, blood pressure variability, hypertension

Article Details

How to Cite
IZZO, Joseph L.. Blood Pressure Variability: Mechanisms, Measurement, Subtypes, and Clinical Implications. Medical Research Archives, [S.l.], v. 10, n. 10, oct. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 19 june 2024. doi:
Review Articles


1. Parati G, Stergiou GS, Dolan E, Bilo G. Blood pressure variability: clinical relevance and application. The Journal of Clinical Hypertension. 2018;20(7):1133-1137. doi:
2. Rosei EA, Chiarini G, Rizzoni D. How important is blood pressure variability? European Heart Journal Supplements. 2020;22:E1-E6. doi:10.1093/eurheartj/suaa061
3. Gunstad J, Cohen RA, Tate DF, et al. Blood pressure variability and white matter hyperintensities in older adults with cardiovascular disease. Research Support, N.I.H., Extramural. Blood pressure. 2005;14(6):353-8.
4. Webb AJ, Rothwell PM. Physiological correlates of beat-to-beat, ambulatory, and day-to-day home blood pressure variability after transient ischemic attack or minor stroke. Stroke. Feb 2014;45(2):533-8. doi:10.1161/strokeaha.113.003321
5. Asayama K, Wei FF, Liu YP, et al. Does blood pressure variability contribute to risk stratification? Methodological issues and a review of outcome studies based on home blood pressure. Hypertension research : official journal of the Japanese Society of Hypertension. Feb 2015;38(2):97-101. doi:10.1038/hr.2014.153
6. Del Giorno R, Balestra L, Heiniger PS, Gabutti L. Blood pressure variability with different measurement methods: Reliability and predictors. A proof of concept cross sectional study in elderly hypertensive hospitalized patients. Medicine. 2019;98(28):e16347.
7. Parati G, Torlasco C, Pengo M, et al. Blood pressure variability: its relevance for cardiovascular homeostasis and cardiovascular diseases. Hypertension Research. 2020/07/01 2020;43(7):609-620. doi:10.1038/s41440-020-0421-5
8. Izzo J, Nagpal S, Mukhopadhyay D, et al. Variation in mean arterial pressure and its hemodynamic components during 24-hour ambulatory pulse wave analysis: impact of age, race, and gender. Journal of hypertension. 2022;40(Suppl 1):e116-e117.
9. Parati G, Izzo JL, Jr., Gavish B. Respiration and blood pressure. In: Izzo JL, Jr, Sica DA, Black HR, eds. Hypertension Primer. American Heart Association; 2008:136-8:chap A43.
10. Teboul JL, Monnet X, Chemla D, Michard F. Arterial Pulse Pressure Variation with Mechanical Ventilation. Am J Respir Crit Care Med. 2019;199(1):22-31. doi:10.1164/rccm.201801-0088CI
11. Izzo JL, Jr. The sympathetic nervous system in acute and chronic blood pressure elevation. In: Oparil S, Weber MA, eds. Hypertension: Companion to Brenner and Rector's The Kidney. Second ed. Elsevier-Saunders; 2005:60-76:chap 6.
12. Izzo JL, Jr., Sander E, Larrabee PS. Effect of postural stimulation on systemic hemodynamics and sympathetic nervous activity in systemic hypertension. Am J Cardiol. 1990 1990;65:339-342.
13. Izzo JL, Anwar MA, Elango K, et al. Decoupling of Heart Rate and Blood Pressure: Hemodynamic Counter-regulatory Mechanisms and their Implications. Artery Research. 2019/12/24 2019;25(3-4):87-94. doi:
14. Izzo JL, Jr., Smith RJ, Larrabee PS, Kallay MC. Plasma norepinephrine and age as determinants of systemic hemodynamics in men with established essential hypertension. Hypertension (Dallas, Tex : 1979). 1987 1987;9:415-419.
15. Izzo JL, Taylor AA. The sympathetic nervous system and baroreflexes in hypertension and hypotension. journal article. Curr Hypertens Rep. 1999;1(3):254-263. doi:10.1007/s11906-999-0030-9
16. Folkow B. Structural factors: the vascular wall. Consequences of treatment. Hypertension (Dallas, Tex : 1979). Sep-Oct 1983;5(5 Pt 2):Iii58-62. doi:10.1161/01.hyp.5.5_pt_2.iii58
17. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. Mar 13 2007;115(10):1285-95. doi:10.1161/circulationaha.106.652859
18. Harrison DG. Endothelial function and oxidant stress. Clin Cardiol. Nov 1997;20(11 Suppl 2):Ii-11-7.
19. Mitra S, Goyal T, Mehta JL. Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther. Oct 2011;25(5):419-29. doi:10.1007/s10557-011-6341-5
20. Sung BH, Izzo JL, Jr., Wilson MF. Effects of cholesterol reduction on BP response to mental stress in patients with high cholesterol. AmJHypertens. 1997 1997;10(6):592-599.
21. Sung BH, Izzo JL, Jr., Dandona P, Wilson MF. Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus. Hypertension (Dallas, Tex : 1979). 1999;34(1):83-8.
22. Maseli A, Aeschbacher S, Schoen T, et al. Healthy Lifestyle and Blood Pressure Variability in Young Adults. American journal of hypertension. Jul 1 2017;30(7):690-699. doi:10.1093/ajh/hpx034
23. Ishida T, Miura S, Fujimi K, et al. Visit-to-Visit Variability and Reduction in Blood Pressure After a 3-Month Cardiac Rehabilitation Program in Patients With Cardiovascular Disease. Int Heart J. Sep 28 2016;57(5):607-14. doi:10.1536/ihj.16-026
24. Pagonas N, Dimeo F, Bauer F, et al. The impact of aerobic exercise on blood pressure variability. Journal of human hypertension. Jun 2014;28(6):367-71. doi:10.1038/jhh.2013.121
25. Gavish B, Izzo JL. Arterial Stiffness: Going a Step Beyond. American journal of hypertension. November 1, 2016 2016;29(11):1223-1233. doi:10.1093/ajh/hpw061
26. Mackenzie IS, McEniery CM, Dhakam Z, et al. Comparison of the effects of antihypertensive agents on central blood pressure and arterial stiffness in isolated systolic hypertension. Hypertension (Dallas, Tex : 1979). Aug 2009;54(2):409-13. doi:10.1161/hypertensionaha.109.133801
27. Schwartz JE, Feig PU, Izzo JL, Jr. Pulse Wave Velocities Derived From Cuff Ambulatory Pulse Wave Analysis. Hypertension (Dallas, Tex : 1979). Jul 2019;74(1):111-116. doi:10.1161/hypertensionaha.119.12756
28. Mena LJ, Felix VG, Melgarejo JD, Maestre GE. 24-Hour Blood Pressure Variability Assessed by Average Real Variability: A Systematic Review and Meta-Analysis. Journal of the American Heart Association. 2017;6(10):e006895. doi:doi:10.1161/JAHA.117.006895
29. Kario K, Shimbo D, Hoshide S, et al. Emergence of Home Blood Pressure-Guided Management of Hypertension Based on Global Evidence. Hypertension (Dallas, Tex : 1979). 2019;74(2):229-236. doi:doi:10.1161/HYPERTENSIONAHA.119.12630
30. Rothwell PM, Howard SC, Dolan E, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Lancet (London, England). Mar 13 2010;375(9718):895-905.
31. Muntner P, Joyce C, Levitan EB, et al. Reproducibility of visit-to-visit variability of blood pressure measured as part of routine clinical care. Journal of hypertension. Dec 2011;29(12):2332-8. doi:10.1097/HJH.0b013e32834cf213
32. Mancia G, Facchetti R, Parati G, Zanchetti A. Visit-to-visit blood pressure variability, carotid atherosclerosis, and cardiovascular events in the European Lacidipine Study on Atherosclerosis. Circulation. 2012;126(5):569-78.
33. Asayama K, Kikuya M, Schutte R, et al. Home blood pressure variability as cardiovascular risk factor in the population of Ohasama. Research Support, Non-U.S. Gov't. Hypertension (Dallas, Tex : 1979). 2013;61(1):61-9.
34. Silagy CA, McNeil JJ, Farish S, et al. Components of blood pressure variability in the elderly and effects on sample size calculations for clinical trials. American journal of hypertension. Jul 1992;5(7):449-58. doi:10.1093/ajh/5.7.449
35. Fazio S, Palmieri EA, Izzo R, et al. An exaggerated systolic blood pressure response to exercise is associated with cardiovascular remodeling in subjects with prehypertension. Comparative Study. Italian Heart Journal: Official Journal of the Italian Federation of Cardiology. Nov 2005;6(11):886-92.
36. Wilson NV, Meyer BM. Early prediction of hypertension using exercise blood pressure. PreventativeMed. 1981 1981;10:62-68.
37. Schultz MG, La Gerche A, Sharman JE. Blood Pressure Response to Exercise and Cardiovascular Disease. Curr Hypertens Rep. Oct 18 2017;19(11):89. doi:10.1007/s11906-017-0787-1
38. Uusitalo AL, Laitinen T, Väisänen SB, et al. Physical training and heart rate and blood pressure variability: a 5-yr randomized trial. American journal of physiology Heart and circulatory physiology. May 2004;286(5):H1821-6. doi:10.1152/ajpheart.00600.2003
39. Lin GM, Tsai KZ, Lin CS, Han CL. Physical Fitness and Long-term Blood Pressure Variability in Young Male Military Personnel. Current hypertension reviews. 2020;16(2):156-160. doi:10.2174/1573402115666191023111351
40. Hamer M, Jones J, Boutcher SH. Acute exercise reduces vascular reactivity to mental challenge in offspring of hypertensive families. Journal of hypertension. 2006;24(2):315-20.
41. Postolache T, Gautier S, Laloux B, et al. Positive correlation between the blood pressure and heart rate response to the cold pressor test and the environmental temperature in older hypertensives. American Journal of Hypertension. 1993;6(5 Pt 1):376-81.
42. Maier KJ, Waldstein SR, Synowski SJ. Relation of cognitive appraisal to cardiovascular reactivity, affect, and task engagement. Ann Behav Med. Aug 2003;26(1):32-41. doi:10.1207/s15324796abm2601_05
43. Stergiou GS, Alpert B, Mieke S, et al. A Universal Standard for the Validation of Blood Pressure Measuring Devices. Hypertension (Dallas, Tex : 1979). 2018;71(3):368-374. doi:doi:10.1161/HYPERTENSIONAHA.117.10237
44. Sewell K, Halanych J H, Russell L B, et al. Blood Pressure Measurement Biases in Clinical Settings, Alabama, 2010–2011. . Prev Chronic Dis 2016;13:150348.
45. Morcos RN, Carter KJ, Castro F, et al. Sources of Error in Office Blood Pressure Measurement. The Journal of the American Board of Family Medicine. 2019;32(5):732-738. doi:10.3122/jabfm.2019.05.190085
46. Westhoff TH, Schmidt S, Meissner R, et al. The impact of pulse pressure on the accuracy of wrist blood pressure measurement. Journal of human hypertension. 2009/06/01 2009;23(6):391-395. doi:10.1038/jhh.2008.150
47. Casiglia E, Tikhonoff V, Albertini F, Palatini P. Poor Reliability of Wrist Blood Pressure Self-Measurement at Home. Hypertension (Dallas, Tex : 1979). 2016;68(4):896-903. doi:doi:10.1161/HYPERTENSIONAHA.116.07961
48. Mukkamala R, Yavarimanesh M, Natarajan K, et al. Evaluation of the Accuracy of Cuffless Blood Pressure Measurement Devices: Challenges and Proposals. Hypertension (Dallas, Tex : 1979). 2021;78(5):1161-1167. doi:doi:10.1161/HYPERTENSIONAHA.121.17747
49. Pickering TG, Gerin W, Schwartz AR. What is the white-coat effect and how should it be measured? Blood Press Monit. Dec 2002;7(6):293-300. doi:10.1097/00126097-200212000-00001
50. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. 10.1161/HYP.0000000000000065. Journal of the American College of Cardiology. 2018;71:e127-e248.
51. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. Journal of hypertension. 2018;36(10):1953-2041. doi:10.1097/hjh.0000000000001940
52. Rabi DM, McBrien KA, Sapir-Pichhadze R, et al. Hypertension Canada’s 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children. Canadian Journal of Cardiology. 2020/05/01/ 2020;36(5):596-624. doi:
53. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension (Dallas, Tex : 1979). 2020;75(6):1334-1357. doi:doi:10.1161/HYPERTENSIONAHA.120.15026
54. Roerecke M, Kaczorowski J, Myers MG. Comparing Automated Office Blood Pressure Readings With Other Methods of Blood Pressure Measurement for Identifying Patients With Possible Hypertension: A Systematic Review and Meta-analysis. JAMA Internal Medicine. 2019;179(3):351-362. doi:10.1001/jamainternmed.2018.6551
55. Tobe S, Dubrofsky L, Nasser D, et al. Randomized Controlled Trial Comparing Automated Office Blood Pressure Readings After Zero or Five Minutes of Rest. Hypertension (Dallas, Tex : 1979). 06/28 2021;78doi:10.1161/HYPERTENSIONAHA.121.17319
56. Asayama K, Thijs L, Li Y, et al. Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population. Hypertension (Dallas, Tex : 1979). 2014;64(5):935-42.
57. Schultz MG, Hare JL, Marwick TH, Stowasser M, Sharman JE. Masked hypertension is "unmasked" by low-intensity exercise blood pressure. Research Support, Non-U.S. Gov't. Blood pressure. Oct 2011;20(5):284-9.
58. Stergiou GS, Palatini P, Modesti PA, et al. Seasonal variation in blood pressure: Evidence, consensus and recommendations for clinical practice. Consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. Journal of hypertension. Jul 2020;38(7):1235-1243. doi:10.1097/hjh.0000000000002341
59. Radke KJ, Izzo JL, Jr. Seasonal variation in haemodynamics and blood pressure-regulating hormones. Research Support, Non-U.S. Gov't. Journal of human hypertension. Jun 2010;24(6):410-6.
60. Lewington S, Li L, Sherliker P, et al. Seasonal variation in blood pressure and its relationship with outdoor temperature in 10 diverse regions of China: the China Kadoorie Biobank. Journal of hypertension. Jul 2012;30(7):1383-91. doi:10.1097/HJH.0b013e32835465b5
61. Daly PA, Landsberg L. Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. Diabetes Care. 1991 1991;14(3):240-248.
62. Izzo JL, Jr. Prehypertension: demographics, pathophysiology, and treatment. Review. Curr Hypertens Rep. Aug 2007;9(4):264-8.
63. Evangelou E, Warren HR, Mosen-Ansorena D, et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nature genetics. Oct 2018;50(10):1412-1425. doi:10.1038/s41588-018-0205-x
64. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. Apr 2020;16(4):223-237. doi:10.1038/s41581-019-0244-2
65. Agarwal R. Implications of Blood Pressure Measurement Technique for Implementation of Systolic Blood Pressure Intervention Trial (SPRINT). J Am Heart Assoc. Feb 3 2017;6(2)doi:10.1161/jaha.116.004536
66. Parati G, Schumacher H. Blood pressure variability over 24 h: prognostic implications and treatment perspectives. An assessment using the smoothness index with telmisartan–amlodipine monotherapy and combination. Hypertension Research. 2014/03/01 2014;37(3):187-193. doi:10.1038/hr.2013.145
67. Parati G. Blood pressure variability: its measurement and significance in hypertension. Journal of Hypertension Supplement. 2005;23(1)
68. Smith TR, Drozda JP, Jr., Vanslette JA, Hoeffken AS, Nicholson RA. Medication class effects on visit-to-visit variability of blood pressure measurements: analysis of electronic health record data in the "real world". Journal of clinical hypertension (Greenwich, Conn). Sep 2013;15(9):655-62. doi:10.1111/jch.12165
69. Webb AJ, Fischer U, Mehta Z, Rothwell PM. Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis. Lancet (London, England). Mar 13 2010;375(9718):906-15.
70. Basson MD, Newman WE, Klug MG. Correlations Among Visit-to-Visit Blood Pressure Variability and Treatment With Antihypertensive Medication With Long-Term Adverse Outcomes in a Large Veteran Cohort. American journal of hypertension. Oct 27 2021;34(10):1092-1099. doi:10.1093/ajh/hpab087
71. Izzo JL, Jr., Yedlapati SH, Faheem SM, et al. Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril. Journal of the American Society of Hypertension : JASH. Nov-Dec 2012;6(6):399-404. doi:10.1016/j.jash.2012.08.007
72. Allen K, Shykoff BE, Izzo JL, Jr. Pet ownership, but not ACE inhibitor therapy, blunts home blood pressure responses to mental stress. Hypertension. 2001;38(4):815-20.
73. Schulte W, Neus H, Thönes M, von Eiff AW. Basal blood pressure variability and reactivity of blood pressure to emotional stress in essential hypertension. Basic Research in Cardiology. 1984/01/01 1984;79(1):9-16. doi:10.1007/BF01935802
74. Drummond PD. Cardiovascular Reactivity in Borderline Hypertensives during Behavioural and Orthostatic Stress. Psychophysiology. 1985;22(6):621-628. doi:
75. Izzo JL, Jr., Rajpal M, Karan S, et al. Hemodynamic and central blood pressure differences between carvedilol and valsartan added to lisinopril at rest and during exercise stress. Journal of the American Society of Hypertension. 2011;6(2):117-123. doi:10.1016/j.jash.2011.12.001
76. Pickering TG. Blood pressure variability and ambulatory monitoring. Current Opinion in Nephrology & Hypertension. 1993;2(3):380-5.
77. Izzo JL, Jr. Blood pressure variability and reactivity. In: Izzo JL, Jr., Sica DA, Black HR, eds. Hypertension Primer. Fourth ed. Wolters Kluwer Health/Lippincott, Williams and Wilkins; 2008:177-180:chap A56.
78. Izzo JL, Jr., Jia Y, Zappe DH. Influence of Age and Race on 24-Hour Ambulatory Blood Pressure Responses to Valsartan, Hydrochlorothiazide, and Their Combination: Implications for Clinical Practice. Journal of clinical hypertension (Greenwich, Conn). Feb 2017;19(2):143-150. doi:10.1111/jch.12891
79. Feldman RD, Zou GY, Vandervoort MK, et al. A Simplified Approach to the Treatment of Uncomplicated Hypertension: A Cluster Randomized, Controlled Trial. Hypertension (Dallas, Tex : 1979). April 1, 2009 2009;53(4):646-653. doi:10.1161/hypertensionaha.108.123455
80. Pringle E, Phillips C, Thijs L, et al. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population. Journal of hypertension. 2003;21(12):2251-7.
81. Verdecchia P, Angeli F, Gattobigio R, et al. Impact of blood pressure variability on cardiac and cerebrovascular complications in hypertension. American journal of hypertension. 2007;20(2):154-61.
82. Hansen TW, Thijs L, Li Y, et al. Prognostic value of reading-to-reading blood pressure variability over 24 hours in 8938 subjects from 11 populations.[Erratum appears in Hypertension. Hypertension (Dallas, Tex : 1979). 2010;55(4):1049-57.
83. Chowdhury EK, Owen A, Krum H, et al. Systolic blood pressure variability is an important predictor of cardiovascular outcomes in elderly hypertensive patients.
Journal of hypertension. 2014;32(3):525-33.
84. Stevens SL, Wood S, Koshiaris C, et al. Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. BMJ (Clinical research ed). 2016;354:i4098-i4098. doi:10.1136/bmj.i4098
85. Kronish IM, Lynch AI, Oparil S, et al. The Association Between Antihypertensive Medication Nonadherence and Visit-to-Visit Variability of Blood Pressure. Hypertension (Dallas, Tex : 1979). 2016;68(1):39-45. doi:doi:10.1161/HYPERTENSIONAHA.115.06960
86. 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. Journal of Clinical Hypertension. 2014;16(1):34-40.
87. Chang TI, Reboussin DM, Chertow GM, et al. Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Hypertension (Dallas, Tex : 1979). Oct 2017;70(4):751-758. doi:10.1161/hypertensionaha.117.09788
88. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet (London, England). Dec 14 2002;360(9349):1903-13.
89. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: JNC 7 Express. Jama. 2003;289(19):2560-72.