2Department of Cardiology, LIV Hospital Vadi İstanbul, İstanbul, Türkiye
Abstract
Background: Twenty-four-hour mean arterial pressure (MAP) is underutilized for the diagnosis and risk assessment of hypertension in clinical settings. The objective of this study is to assess the relation of MAP with systolic and diastolic blood pressure (BP) in diagnosing hypertension on 24-hour ambulatory blood pressure monitoring (ABPM), while also examining its diagnostic effectiveness.
Methods: This retrospective study analyzed 24-hour ABPM of 532 adults. Hypertension diagnosis was made based on 2 criteria: the standard 24-hour systolic/diastolic BP measurement criteria and the 24-hour MAP measurement criteria. The relation of the 24-hour MAP with systolic and diastolic measurements and the predictors affecting its accuracy were evaluated.
Results: A total of 532 patients were included, and 409 (76.9%) were diagnosed with hypertension based on 24-hour ambulatory systolic/diastolic BP criteria. Among hypertensive patients, 191 (46.7%) were overlooked by 24-hour MAP criteria. Multiple logistic regression analysis identified age ≥52.4 (OR = 3.23, 95% CI:2.02-5.16, P < .001), female gender (OR = 2.54, 95%CI:1.61-4.02, P < .001), and less variation in daytime/nighttime systolic/diastolic BP as significant independent predictors of overlooked hypertension by 24-hour MAP criteria.
Conclusion: Our study highlights a relation between 24-hour MAP and systolic/diastolic BP measurements in diagnosing hypertension via 24-hour ABPM, especially in older adults and women. Systolic/diastolic criteria offer greater sensitivity for hypertension detection compared to MAP alone. This underscores the need for refined diagnostic criteria and suggests that reliance on MAP alone may lead to underdiagnosis in these vulnerable populations, necessitating further investigation.
Highlights
- Underutilized MAP: Despite its potential, 24-hour MAP is underused in hypertension diagnosis.
- Diagnostic comparison: Study shows weak concordance between 24-hour MAP and systolic and diastolic BP in the diagnosis of hypertension using 24-hour ABPM
- High number of overlooked cases: Nearly half of hypertensive patients (46.7%) were missed by the MAP criteria.
- Predictors of missed cases: Age ≥52.4, female gender, and less BP variation predict missed cases.
- Clinical implications: Diagnosis using systolic/diastolic criteria may be more sensitive than using MAP criteria, warranting further research for optimal thresholds.
Introduction
Hypertension is a widespread chronic disease that affects 40% of adults worldwide.1 It is the most significant modifiable risk factor for cardiovascular disease and all-cause mortality.2,
Based on available evidence, 24-hour ambulatory blood pressure monitoring (ABPM) is superior to office blood pressure (BP) measurements in predicting total and cardiovascular mortality as well as overall and cause-specific cardiovascular complications in patients with hypertension and in population cohorts since it provides a more precise picture of BP status.4-
In addition to systolic and diastolic BP measurements, 24-hour ABPM monitoring allows the evaluation of other parameters such as mean arterial pressure, dipping and non-dipping status, early morning surge pattern, pressure loads, and pulse pressure variability. Among them, mean arterial pressure (MAP) is a crucial indicator of the circulating pressure load during a cardiac cycle. MAP is related to both systolic and diastolic BP and records risk-related data associated with each.11 In younger patients, MAP has been shown to be more important than pulse pressure in the prediction of stroke. However, in older patients, MAP has been found to be a weaker predictor of stroke and a better predictor of cardiovascular diseases.12 Office MAP emerged as a greater predictor of vascular death than systolic or diastolic BP or pulse pressure in a meta-analysis of data from 1 million individuals.13 Even though MAP has been shown to be an important parameter for sepsis, major trauma, intracranial bleeding, and stroke in intensive care units,14 guidelines for managing hypertension neither define an optimal MAP as a target nor specify how risk stratification should be done using MAP.
In a recent population-based cohort of 11 596 adults, outcome-driven thresholds for 24-hour MAP and its associations with fatal and nonfatal cardiovascular endpoints were evaluated.15 Using a composite cardiovascular endpoint as the primary outcome and the 10-year risks associated with 2017 American College of Cardiology/American Heart Association thresholds for office blood pressure as the reference, 24-hour MAP of <90, ≥90 to <92, ≥92 to <96, and ≥96 mmHg delineated normotension, elevated 24-hour MAP, stage 1 hypertension, and stage 2 combined with severe hypertension, respectively.15
Given the prognostic accuracy but underutilization of 24-hour MAP for the diagnosis of and risk assessment of hypertension in clinical practice, we designed a retrospective study to assess the relation of MAP with systolic and diastolic BP in diagnosing hypertension on 24-hour ABPM, while also examining its diagnostic effectiveness in conjunction with the 2017 ACC/AHA-driven thresholds for 24-hour ABPM and recently established thresholds for 24-hour MAP.
Methods
Patients
This retrospective study analyzed 24-hour ABPM of 532 adult patients (≥18 years of age) who visited our outpatient clinic of the cardiology department with a history of high BP between the years 2015 and 2022. Demographic and clinical data were retrieved from patient records. The study protocol was approved by the Local Institutional Review Board, and the study was conducted in accordance with the Declaration of Helsinki. Artificial intelligence (AI)-assisted technologies (such as Large Language Models [LLM], chatbots, or image creators) were not used in the production of this study.
24-Hour Ambulatory Blood Pressure Measurements
ABPM was performed for 24 hours by means of an oscillometric device (Tracker 2 NIBP, Del Mar Reynolds Medical) using CardioNavigator V:2.414 (PDX) software. The device was set to measure BP every 30 minutes during the day (from 07:00 a.m. to 10:00 p.m.) and every 60 minutes during the night (from 10:00 p.m. to 07:00 a.m.). Devices were periodically calibrated with a mercury sphygmomanometer. The arm cuff was positioned on the non-dominant upper limb. In addition to 24-hour ambulatory systolic, diastolic, and MAP measurements, SDs of measurements during day and night, pulse pressure, and dipper/non-dipper pattern were evaluated.
Based on 24-hour systolic/diastolic BP measurements, stages of hypertension were defined with the following threshold values: elevated BP, 115/75 mm Hg; stage I hypertension, 125/75 mm Hg; stage II hypertension, 130/80 mm Hg; severe hypertension, 145/90 mm Hg.8,
Statistical Analysis
For the analysis of data, IBM SPSS Statistics version 21.0 software was used. Descriptive data are presented in number (percentage) or mean ± SD. Normality of continuous variables was tested using Kolmogorov–Smirnov and Shapiro–Wilk tests. The chi-square test was used for between-group comparisons of categorical variables. For the between-group comparison of continuous variables, the Student's
Results
Patients
A total of 532 patients were included in this study. The median number of ambulatory readings recorded over 24 hours was 24 ± 2. Among all patients, 409 (76.9%) were diagnosed with hypertension based on 24-hour ambulatory systolic/diastolic BP criteria. None of the patients were diagnosed with hypertension based solely on hypertension criteria for 24-hour MAP. Thus, all patients diagnosed based on 24-hour MAP were also hypertensive based on 24-hour systolic/diastolic BP criteria. Demographical and clinical data of the patients are shown in
Diagnosis with Different Criteria
Among patients diagnosed with hypertension based on 24-hour systolic/diastolic BP (n = 409), only 218 (53.3%) could meet diagnostic criteria based on 24-hour MAP; thus, 191 (46.7%) were overlooked by 24-hour MAP criteria.
Predictors of Overlooked Hypertension by 24-Hour Mean Arterial Pressure
Discussion
This study has demonstrated that using the American College of Cardiology/American Heart Association thresholds for systolic/diastolic BP (<125/<75 mm Hg vs. ≥125/≥75 mm Hg), the diagnosis of HT with 24-hour ABPM is more sensitive when made in accordance with systolic/diastolic criteria than with 24-hour MAP criteria alone. To the best of our knowledge, this is the first study to evaluate the relation of MAP with systolic and diastolic BP in a 24-hour ambulatory setting in the diagnosis of adult hypertension, other than the study by Sulakova et al
The physiological relevance of MAP can be explained by several factors. Blood flow to the tissues seems to be more closely related to MAP rather than diastolic/systolic BP. For instance, the bloodstream only spends a brief period of time at the peak systolic pressure, making it an inadequate determinant of blood flow.18 MAP is the pressure regulated by the constriction and dilation of arterioles. By the time blood reaches the distal arterioles where important vascular regulation occurs, it is no longer significantly pulsatile. Consequently, the systolic and diastolic pressures hold little meaning at the level of the arteriolar vascular bed.18 Since MAP is consistent across the arterial tree and less affected by distal pulse amplification,19 the question of whether central versus brachial BP increases cardiovascular risk is not a concern.20 MAP’s significance resides in the fact that it allows the blood in circulation to supply key organs with oxygen and crucial nutrients.21 While lower MAP may be deleterious in unstable hemodynamics, higher levels of MAP are linked to target organ damage, cardiovascular, and cerebrovascular diseases.22-
The maximal oscillation of the cuff typically corresponds reasonably well to the invasively measured mean; therefore, the oscillating automated BP cuff monitor actually reports an accurate MAP.24 A common technique for estimating MAP is the maximum amplitude algorithm, which considers the cuff pressure at the oscillometric waveform envelope’s maximum amplitude, which corresponds to the arterial wall being unloaded and where the transmural pressure is zero. Using proprietary algorithms, the systolic and diastolic BPs are computed from the estimated MAP.25 Maximum amplitude algorithm was used by the software implemented in automated ambulatory devices to compute MAP in our study.
Among patients diagnosed with hypertension based on 24-hour systolic/diastolic BP according to 2017 American College of Cardiology/American Heart Association thresholds, only 53.3% could meet the diagnostic criteria based on recently defined 24-hour MAP15 in our study; thus, 46.7% were overlooked by 24-hour MAP criteria. In the study by Melgarejo et al15 where the association of fatal and nonfatal cardiovascular outcomes with 24-hour MAP was evaluated, when systolic BP and MAP were considered, 54.2% of the patients were normotensive for both BP indexes, 7.0% had high systolic BP but normal MAP, 5.0% had normal systolic BP but elevated MAP, and 33.8% had both elevated systolic BP and MAP. For cross-classification with diastolic BP, these numbers were 55.4%, 5.7%, 4.5%, and 34.4%, respectively. The higher percentage of patients overlooked by 24-hour MAP thresholds compared with systolic/diastolic thresholds in our study might be related to ethnic differences and a higher percentage of patients under antihypertensive treatment (19.6% vs. 41.0%) in our study. On the other hand, Sulakova et al17 showed that the inclusion of MAP in the definition of ambulatory hypertension significantly increased the number of hypertensive patients by 19%. None of the patients were diagnosed with hypertension based solely on hypertension criteria for 24-hour MAP in our study. Although the results of this study contradict our study, the patient groups in both studies are completely different. BP levels and BP normal upper limits change with growth and body size, making interpretation of 24-hour ABPM in children more difficult than in adults.7 The normative pediatric ABPM results include systolic BP, diastolic BP, MAP, percentiles, and Z scores that are related to age and height;26 however, these values do not precisely define ambulatory hypertension.
Patients who meet systolic/diastolic BP criteria for hypertension but not MAP criteria (i.e., missed cases) in our study were significantly older and had lower SDs of BP during day and night; additionally, missed cases were more common among female patients. According to a U.S. National Health and Nutrition Examination Survey, both men’s and women’s systolic BP rises with age, but it is higher in males than in females starting in early adulthood.27 In addition, recent studies using 24-hour ABPM have shown that BP is higher in men than in women at similar ages. Among 352 Danish men and women, aged 20-79, who were considered normotensive for their age, Wiinberg et al28 discovered that BP rose with age in both sexes, but males had 610 mm Hg higher 24-hour MAP than females until the age of 70-79 years, when BP was similar for men and women. This may provide an explanation for the higher percentage of missed cases in women. Diastolic BP increases progressively in both men and women due to increased peripheral resistance by the remodeling of the arterioles in the overall population until approximately the sixth decade of life, after which it decreases progressively with the reduction of arterial compliance. With increased arterial stiffness, the normal buffering capacity of the vessels during systole is impeded, leading to increased systolic blood pressure.29 Physiologic changes associated with aging lead to an increase in systolic BP, MAP, and pulse pressure but a decrease in diastolic BP.30 In our study, older patients (≥52.4 years) who were more likely to be missed by MAP had significantly lower 24-hour diastolic BP compared to younger patients (74.9 vs. 81.1 mm Hg), although they did not differ in terms of 24-hour systolic BP. However, as being older than 52 years of age can hardly be classified as ‘elderly’, according to any given standard, this does not necessarily bring about isolated systolic hypertension, which is generally encountered in much older patient populations. Among different potential causes, BP variability plays a crucial role in the diagnostic discrepancy between MAP and SBP/DBP findings on 24-hour ABPM. In older adults, BPV increases due to factors such as autonomic dysfunction, decreased baroreflex sensitivity, and medication effects.31-
Findings of this study need to be evaluated within the context of several limitations. A key and foremost limitation of this study is the inclusion of a substantial proportion of patients already diagnosed with hypertension under antihypertensive treatment. This status could have influenced the study outcomes, particularly the MAP-based hypertension diagnoses. As a result, the findings may not fully represent the characteristics of untreated hypertension. Future research should prioritize studying treatment-naive, newly diagnosed patients to provide a clearer understanding of the relation between MAP and SBP/DBP in hypertension diagnosis. Secondly, as this is a retrospective study, prospective studies could offer more robust data, overcoming the inherent constraints of retrospective designs. Finally, the lack of long-term follow-up prevents the evaluation of cardiovascular outcomes in the long term.
Conclusion
Our findings reveal a weak concordance between 24-hour MAP and systolic/diastolic BP measurements in diagnosing hypertension via 24-hour ABPM, particularly among older and female patients. The enhanced sensitivity of systolic/diastolic criteria over MAP highlights the potential for underdiagnosis when relying solely on MAP. This underscores the necessity of revising diagnostic criteria and prompts further prospective studies to elucidate the clinical utility and establish precise thresholds for 24-hour MAP, particularly in these vulnerable populations.
Footnotes
References
- Hermida RC, Smolensky MH, Ayala DE, Portaluppi F. Ambulatory Blood Pressure Monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults. Chronobiol Int. 2015;32(10):1329-1342. https://doi.org/10.3109/07420528.2015.1113804
- Stanaway JD, Afshin A, Gakidou E. Collaborators GBDRF. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1923-1994. https://doi.org/10.1016/S0140-6736(18)32225-6
- . Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736-1788. https://doi.org/10.1016/S0140-6736(18)32203-7
- Hansen TW, Kikuya M, Thijs L. Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7,030 individuals. J Hypertens. 2007;25(8):1554-1564. https://doi.org/10.1097/HJH.0b013e3281c49da5
- Boggia J, Li Y, Thijs L. Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study. Lancet. 2007;370(9594):1219-1229. https://doi.org/10.1016/S0140-6736(07)61538-4
- Yang WY, Melgarejo JD, Thijs L. Association of office and ambulatory blood pressure with mortality and cardiovascular outcomes. JAMA. 2019;322(5):409-420. https://doi.org/10.1001/jama.2019.9811
- Mancia G, Fagard R, Narkiewicz K. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-2219. https://doi.org/10.1093/eurheartj/eht151
- Whelton PK, Carey RM, Aronow WS. 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice guidelines. J Am Coll Cardiol. 2017;71():e127-e248.
- Williams B, Mancia G, Spiering W. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. https://doi.org/10.1093/eurheartj/ehy339
- Jones NR, McCormack T, Constanti M, McManus RJ. Diagnosis and management of hypertension in adults: NICE guideline update 2019. Br J Gen Pract. 2020;70(691):90-91. https://doi.org/10.3399/bjgp20X708053
- Flint AC, Conell C, Ren X. Effect of systolic and diastolic blood pressure on cardiovascular outcomes. N Engl J Med. 2019;381(3):243-251. https://doi.org/10.1056/NEJMoa1803180
- Verdecchia P, Schillaci G, Reboldi G, Franklin SS, Porcellati C. Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension. Circulation. 2001;103(21):2579-2584. https://doi.org/10.1161/01.CIR.103.21.2579
- Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. 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. 2002;360(9349):1903-1913. https://doi.org/10.1016/s0140-6736(02)11911-8
- Magder SA. The highs and lows of blood pressure: toward meaningful clinical targets in patients with shock. Crit Care Med. 2014;42(5):1241-1251. https://doi.org/10.1097/CCM.0000000000000324
- Melgarejo JD, Yang WY, Thijs L. Association of fatal and nonfatal cardiovascular outcomes with 24-hour mean arterial pressure. Hypertension. 2021;77(1):39-48. https://doi.org/10.1161/HYPERTENSIONAHA.120.14929
- Huang QF, Yang WY, Asayama K. Ambulatory blood pressure monitoring to diagnose and manage hypertension. Hypertension. 2021;77(2):254-264. https://doi.org/10.1161/HYPERTENSIONAHA.120.14591
- Suláková T, Feber J. Should mean arterial pressure be included in the definition of ambulatory hypertension in children?. Pediatr Nephrol. 2013;28(7):1105-1112. https://doi.org/10.1007/s00467-012-2382-7
- Yartsev A. Cardiovascular system, systolic, diastolic and mean arterial pressure. Deranged Physiology. 2015;():1-26. https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20035/systolic-diastolic-and-mean-arterial-blood-pressure
- Boggia J, Luzardo L, Lujambio I. The diurnal profile of central hemodynamics in a general Uruguayan population. Am J Hypertens. 2016;29(6):737-746. https://doi.org/10.1093/ajh/hpv169
- McEniery CM, Cockcroft JR, Roman MJ, Franklin SS, Wilkinson IB. Central blood pressure: current evidence and clinical importance. Eur Heart J. 2014;35(26):1719-1725. https://doi.org/10.1093/eurheartj/eht565
- Papaioannou TG, Protogerou AD, Vrachatis D. Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals. Hypertens Res. 2016;39(9):640-647. https://doi.org/10.1038/hr.2016.41
- Sesso HD, Stampfer MJ, Rosner B. Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in Men. Hypertension. 2000;36(5):801-807. https://doi.org/10.1161/01.hyp.36.5.801
- Domanski MJ, Davis BR, Pfeffer MA, Kastantin M, Mitchell GF. Isolated systolic hypertension : prognostic information provided by pulse pressure. Hypertension. 1999;34(3):375-380. https://doi.org/10.1161/01.hyp.34.3.375
- Beloncle F, Radermacher P, Guerin C, Asfar P. Mean arterial pressure target in patients with septic shock. Minerva Anestesiol. 2016;82():777-784.
- Chandrasekhar A, Yavarimanesh M, Hahn JO. Formulas to explain popular oscillometric blood pressure estimation algorithms. Front Physiol. 2019;10():1415-. https://doi.org/10.3389/fphys.2019.01415
- Wuhl E, Witte K, Soergel M, Mehls O, Schaefer F. Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens. 2002;20(10):1995-2007. https://doi.org/10.1097/00004872-200210000-00019
- Roger VL, Go AS, Lloyd-Jones DM. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18-e209. https://doi.org/10.1161/CIR.0b013e3182009701
- Wiinberg N, Høegholm A, Christensen HR. 24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens. 1995;8(10 ):978-986. https://doi.org/10.1016/0895-7061(95)00216-2
- Franklin SS. Arterial stiffness and diastolic blood pressure: what is the connection?. Artery Res. 2006;1(suppl):S1-S6. https://doi.org/10.1016/S1872-9312(07)70001-7
- Li Y, Thijs L, Zhang ZY. Opposing age-related trends in absolute and relative risk of adverse health outcomes associated with out-of-office blood pressure. Hypertension. 2019;74(6):1333-1342. https://doi.org/10.1161/HYPERTENSIONAHA.119.12958
- Franklin SS, Gustin W, Wong ND. Hemodynamic patterns of age-related changes in blood pressure. The Framingham heart study. Circulation. 1997;96(1):308-315. https://doi.org/10.1161/01.cir.96.1.308
- Benetos A, Adamopoulos C, Bureau JM. Determinants of accelerated progression of arterial stiffness in normotensive subjects and in treated hypertensive subjects over a 6-year period. Circulation. 2002;105(10):1202-1207. https://doi.org/10.1161/hc1002.105135
- Zhang Y, Agnoletti D, Blacher J, Safar ME. Blood pressure variability in relation to autonomic nervous system dysregulation: the X-CELLENT study. Hypertens Res. 2012;35(4):399-403. https://doi.org/10.1038/hr.2011.203