Abstract
Disagreements in office brachial and central blood pressure (BP) have resulted in the identification of novel hypertension phenotypes, namely isolated central hypertension (ICH) and isolated brachial hypertension (IBH). This study investigated the relationship of ICH and IBH with ambulatory BP phenotypes among 753 individuals (mean age = 47.6 ± 15.2 years, 48% males) who underwent office and 24‐hours brachial and central BP measures using a Mobil‐O‐Graph PWA monitor. Thresholds for elevated office central and brachial BP were 130/90 and 140/90 mm Hg. Results of multivariable analysis adjusted for potential confounders showed that ICH (n = 25) had 3.71‐fold (95% CI 1.48‐9.32; P = .005) greater risk of masked hypertension than normal brachial/central BP (n = 362), while IBH (n = 20) had 4.65‐fold (95% CI 1.76‐12.25; P = .002) greater risk of white coat hypertension compared with combined brachial/central hypertension (n = 346). These findings suggest that the diagnosis of ICH and IBH might be useful in identifying individuals at higher risk of presenting discordant office and ambulatory BP phenotypes.
Keywords: ambulatory blood pressure monitoring, brachial blood pressure, central blood pressure
1. INTRODUCTION
Hypertension is defined based on brachial blood pressure (BP) levels. 1 However, BP measured at the central aorta (central BP) is reported to be superior to brachial BP in predicting cardiovascular events, and central BP values of 130/90 mm Hg have been proposed as thresholds to define hypertension. 2 , 3 Disagreements in brachial and central BP measured at the office have resulted in the identification of novel hypertension phenotypes, namely isolated central hypertension (ICH) and isolated brachial hypertension (IBH), 3 but the clinical significance of these phenotypes is not established. 4 , 5 Although conflicting data have been reported, 6 previous studies have suggested that young individuals with elevated brachial systolic BP might have high rates of normal central BP and high prevalence of white coat hypertension, 7 , 8 raising the assumption that divergences in office brachial and central BP may be coupled with office and out‐of‐office brachial BP discrepancies. Therefore, the present study aimed at investigating the relationship of isolated elevations of brachial or central BP with ambulatory BP phenotypes.
2. METHODS
2.1. Study population and BP measurements
We evaluated 753 consecutive individuals with age ≥18 years enrolled from the Clinical Research Center of the Cesmac University Center from 2014 to 2016, who underwent office brachial and central BP measures and ambulatory brachial BP measures using a Mobil‐O‐Graph PWA monitor (IEM Healthcare). 9 , 10 Briefly, three office brachial and central BP readings were taken in the arm of each participant in the sitting position after 5 minutes of rest using an appropriate cuff size and their means were used in the analysis. Central BP was estimated using the C1 (brachial systolic BP [SBP] and diastolic BP [DBP]) calibration method of the Mobil‐O‐Graph PWA device. Ambulatory brachial BP monitoring comprised 24‐hours readings obtained at 30‐minute intervals and was performed in the same day of office BP measures. For the present analysis, only participants with at least 16 and 8 valid daytime and nighttime readings, respectively, were included.
Participants using lipid‐lowering and antidiabetic medications were considered to have dyslipidemia and diabetes, respectively. Body mass index was calculated as weight (kg) divided by height (m) squared. The study protocol was approved by the Pedro Ernesto University Hospital Ethics Committee and conforms to the principles of the Declaration of Helsinki. All participants provided written informed consent.
2.2. BP definitions
Phenotypes derived from office brachial and central BP were defined as normal brachial/central BP [office brachial SBP <140 mm Hg and DBP <90 mm Hg, and office central SBP <130 mm Hg and DBP <90 mm Hg]; IBH (office brachial SBP ≥140 mm Hg or DBP ≥90 mm Hg, and office central SBP <130 mm Hg and DBP <90 mm Hg); 3) ICH (office brachial SBP <140 mm Hg and DBP <90 mm Hg, and office central SBP ≥130 mm Hg or DBP ≥90 mm Hg); and combined brachial/central hypertension (office brachial SBP ≥140 mm Hg or DBP ≥90 mm Hg, and office central SBP ≥130 mm Hg or DBP ≥90 mm Hg). 1 , 3
Ambulatory BP phenotypes were defined as normotension (office brachial SBP <140 mm Hg and DBP <90 mm Hg, and 24‐hours brachial SBP <130 mm Hg and DBP <80 mm Hg), white coat hypertension (office brachial SBP ≥140 mm Hg or DBP ≥90 mm Hg, and 24‐hours brachial SBP <130 mm Hg and DBP <80 mm Hg), masked hypertension (office brachial SBP <140 mm Hg and DBP <90 mm Hg, and 24‐hours brachial SBP ≥130 mm Hg or DBP ≥80 mm Hg), and sustained hypertension (office brachial SBP ≥140 mm Hg or DBP ≥90 mm Hg, and 24‐hours brachial SBP ≥130 mm Hg or DBP ≥80 mm Hg). 1
2.3. Statistical analysis
Continuous and categorical variables are presented as mean ± standard deviation and proportions, respectively. One‐way ANOVA followed by Bonferroni's test was used to compare continuous variables, while Bonferroni‐corrected chi‐square test was used to compare categorical variables. Multivariable logistic regression analysis assessed the relationship of phenotypes derived from office brachial and central BP measures with ambulatory BP phenotypes. Multivariable models included age, sex, and variables that were statistically different among the studied groups. In addition, the sensitivity and specificity of ICH and IBH in detecting masked and white coat hypertension were estimated. P‐values <.05 were considered significant. Statistical analysis was performed using Stata software version 14.1 (StataCorp LP).
3. RESULTS
Considering the total sample (mean age = 47.6 ± 15.2 years, 48% males), there were 316 (42%), 114 (15%), 71 (9%), and 252 (34%) participants with normotension, white coat hypertension, masked hypertension, and sustained hypertension, respectively. Clinical characteristics and BP values of the participants according to office brachial/central BP phenotypes (normal brachial/central BP [n = 362]; ICH [n = 25]; IBH [n = 20]; combined brachial/central hypertension [n = 346]) are shown in Table 1. Notably, individuals with combined brachial/central hypertension were more likely to be older than those with ICH and to use antihypertensive medications that those with normal brachial/central BP. In addition, the average central SBP and DBP values in ICH were 122.1 ± 7.6 and 89.1 ± 4.7 mm Hg, respectively, which were lower than the thresholds used to define ICH (central SBP ≥130 mm Hg or DBP ≥90 mm Hg). The explanation for these values was that patients with ICH comprised a mix of patients with isolated elevations of central DBP (n = 18; central SBP = 118.3 ± 5.0 and DBP = 90.8 ± 1.9 mm Hg), isolated elevations of central SBP (n = 5; central SBP = 132.4 ± 1.1 and DBP = 82.2 ± 6.7 mm Hg), and elevations of both central SBP and DBP (n = 2; central SBP = 131.0 ± 0.0 and DBP = 90.5 ± 0.7 mm Hg).
TABLE 1.
Clinical characteristics according to office brachial/central phenotypes
| Variables | Normal brachial/central BP (n = 362) | Isolated central hypertension (n = 25) |
Isolated brachial hypertension (n = 20) |
Brachial/central hypertension (n = 346) |
|---|---|---|---|---|
| Male sex, % | 44 | 52 | 55 | 52 |
| Age, years | 47.2 ± 15.3 | 40.1 ± 12.6 | 46.0 ± 17.8 | 48.7 ± 14.9† |
| Body mass index, kg/m2 | 27.1 ± 4.2 | 28.3 ± 4.4 | 28.2 ± 4.5 | 27.8 ± 4.4 |
| Antihypertensive med, % | 25 | 28 | 30 | 39* |
| Dyslipidemia, % | 11 | 0 | 5 | 13 |
| Diabetes mellitus, % | 5 | 0 | 10 | 8 |
| Smoking, % | 1 | 0 | 0 | 4 |
| Office brachial SBP, mm Hg | 119.8 ± 10.2 | 130.6 ± 7.5* | 141.3 ± 11.6 * , † | 144.7 ± 16.1 * , † |
| Office brachial DBP, mm Hg | 76.7 ± 8.1 | 86.6 ± 4.8* | 79.3 ± 8.1* | 97.4 ± 11.1*, † , ‡ |
| Office central SBP, mm Hg | 110.2 ± 9.5 | 122.1 ± 7.6* | 123.6 ± 7.3* | 135.2 ± 14.1*, † , ‡ |
| Office central DBP, mm Hg | 78.1 ± 8.0 | 89.1 ± 4.7* | 80.3 ± 6.6† | 98.8 ± 12.4*, † , ‡ |
| 24‐h brachial SBP, mm Hg | 115.2 ± 8.8 | 121.8 ± 6.6* | 125.8 ± 10.0* | 127.2 ± 11.2* |
| 24‐h brachial DBP, mm Hg | 71.8 ± 7.6 | 77.6 ± 6.1* | 73.7 ± 5.6 | 83.0 ± 9.0*, † , ‡ |
| Ambulatory phenotypes, % | ||||
| Normotension | 83 | 56* | 0 * , † | 0 * , † |
| White coat hypertension | 0 | 0 | 65 * , † | 29*, † , ‡ |
| Masked hypertension | 17 | 44* | 0† | 0 * , † |
| Sustained hypertension | 0 | 0 | 35 * , † | 71*, † , ‡ |
Abbreviations: DBP, diastolic blood pressure; med, medications; SBP, systolic blood pressure.
P < .05 compared with normal central/brachial BP.
P < .05 compared with isolated central hypertension.
P < .05 compared with isolated brachial hypertension.
The prevalence of masked hypertension was 17% in normal brachial/central BP and 44% in ICH (P = .001), while the prevalence of white coat hypertension was 65% in IBH and 29% in combined brachial/central hypertension (P = .001) (Table 1 and Figure 1). In analysis adjusted for age, sex, use of antihypertensive medications, and office brachial SBP, ICH had 3.71 (95% confidence interval 1.48‐9.32; P = .005) greater odds of presenting masked hypertension than normal central/brachial BP, while IBH had 4.65 (95% confidence interval 1.76‐12.25; P = .002) greater odds of presenting white coat hypertension than combined central/brachial hypertension. Among individuals with normal office brachial BP (<140/90 mm Hg), the sensitivity and specificity of ICH in detecting masked hypertension were 44% (95% CI = 24‐65) and 83% (95% CI = 79‐87), while among individuals with high office brachial BP (≥140/90 mm Hg), the sensitivity and specificity of IBH in detecting white coat hypertension were 65% (95% CI = 41‐85) and 71% (95% CI = 66‐76).
FIGURE 1.
Unadjusted prevalence of ambulatory hypertension phenotypes among office brachial/central phenotypes. *P < .05 compared with normal central/brachial BP; ‡P < .05 compared with isolated brachial hypertension
4. DISCUSSION
The major finding of the present study was that IBH and ICH were associated with greater risk of white coat and masked hypertension, respectively. Importantly, these associations persisted after adjusting for relevant confounding factors, including baseline office brachial BP levels. 11 , 12 The marked association between IBH and white coat hypertension shown herein agrees with previous data suggesting a high prevalence of both normal central BP levels and white coat hypertension among young hypertensive individuals, 7 , 8 and further demonstrates that this relationship is not restricted to younger individuals. Conversely, the association of IBH with white coat BP effect indicates that increases in sympathetic drive could also play a role on isolated elevation of brachial BP at the office. 8
The relation between ICH and out‐of‐office hypertension phenotypes has been barely explored. A former study found no association between masked hypertension and isolated elevation of central BP among 201 treated hypertensive patients. 13 However, the small sample size and the different criteria used to define elevated brachial BP (solely brachial SBP ≥140 mm Hg) and central BP (solely central SBP ≥116 mm Hg) in that study may have contributed to explain the discrepancies with our current findings.
Regardless of the underlying mechanisms, the association of ICH and IBH with ambulatory BP phenotypes has clinical implications. Current guidelines recommend out‐of‐office BP measures for the diagnosis and management of hypertension, 1 but this approach may be hindered by limited availability of devices and patients’ adherence issues, 14 raising the need for identification of preferential targets for out‐of‐office BP measures. Given the increasing availability of techniques that allow feasible and simultaneous brachial and central BP measures, 3 , 9 the diagnosis of discordant elevations of central or brachial BP at the office could be used to identify preferential targets for out‐of‐office BP measures. Conversely, in services that routinely perform ambulatory BP monitoring, the presence of masked hypertension could be used to recognize individuals at higher risk of having elevation of central BP among those with normal brachial BP at the office.
Some limitations of this report must be acknowledged. First, our findings were derived from one single center and, therefore, might not be generalizable to all ICH and IBH individuals. Second, our data regarding central BP measures are specific to the Mobil‐O‐Graph PWA device operating at the C1 (brachial SBP and DBP) calibration method and may not apply to other central BP devices with different generalized transfer functions or calibration methods to derive central BP. 15 Third, out‐of‐office measures were derived from ambulatory BP monitoring. Therefore, further studies are needed to confirm whether the current results are reproducible with home BP monitoring.
In conclusion, the present study showed that IBH and ICH were associated with greater risk of white coat and masked hypertension, respectively, suggesting that dissociations in brachial and central BP might be useful in identifying individuals at higher risk of presenting ambulatory BP phenotypes.
CONFLICT OF INTEREST
None.
AUTHOR CONTRIBUTIONS
WNJ and ADMF contributed to the design of the work, the analysis and interpretation of data, and drafted the manuscript. AMGP, MAMG, AAB, and ACS contributed to the acquisition, analysis and/or interpretation of data, and revised the manuscript critically for important intellectual content. All gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy.
Feitosa ADM, Paiva AMG, Mota‐Gomes MA, Brandão AA, Sposito AC, Nadruz W Jr.. Ambulatory blood pressure phenotypes and isolated elevation of office central or brachial blood pressure. J Clin Hypertens. 2020;22:1936–1940. 10.1111/jch.14012
Feitosa and Paiva both authors contributed equally to this study
Funding information
The study was supported by the Brazilian National Council for Scientific and Technological Development (CNPq; grant 306154/2017‐0) for Dr Nadruz.
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