Introduction

Blood pressure levels are intricately linked to various pathophysiological phenomena that underlie multiple diseases, predominantly of vascular origin. Investigating the circadian behavior of blood pressure holds promise in elucidating diagnostic and treatment challenges within the hypertensive population of Mexico City. Non-communicable diseases, particularly arterial hypertension, continue to dominate global mortality statistics, likely owing to their multifaceted modifiability. In Mexico, the prevalence of hypertension, as defined by the criteria established in the 2014 «Eighth Joint National Committee (JNC 8)»¹ American Hypertension Guidelines, was documented in the National Health Survey (ENSANUT) of 2022. The survey revealed a diagnosis of systemic arterial hypertension in 43.9% of adults, with a prevalence of 29.4% among individuals aged over 20, slightly higher in males at 31.3% and females at 27.7%.² However, some experts argue that these Figures underestimate the true prevalence, prompting methodological refinements in various statistical trials better to capture the incidence and prevalence of arterial hypertension. This challenge was exemplified in 2005 by the «Re-encuesta Nacional de Hipertensión Arterial (RENAHTA): Consolidación Mexicana de los Factores de Riesgo Cardiovascular. Cohorte Nacional de Seguimiento» which, unfortunately, failed to demonstrate significant deviations from the earlier findings of ENSANUT.³

The complexities of hypertension extend beyond frequency and prevalence to encompass diagnostic criteria and optimal follow-up and treatment paradigms, as evidenced by a study published by García Zamora et al. In their analysis of the «PROSPERO» registry, encompassing four studies involving 29,820 patients with intensive arterial hypertension treatment, they found that despite intensive treatment, mortality rates remained unaltered. Specifically, the relative risk (RR) was found to be 0.89 with a 95% Confidence Interval (CI 95%): 0.68-1.07; p = 0.16, with no impact on total mortality (p = 0.45) for any of the evaluated causes.⁴

Currently, the established indications for Ambulatory Blood Pressure Monitoring (ABPM) remain relatively unchanged and fundamentally address three conditions.⁵ Firstly, patients with elevated arterial hypertension readings in outpatient office settings termed the «white coat phenomenon». Secondly, individuals with blood pressure readings within the normal range during office visits but with a history of elevated pressure during daily activities are known as «masked hypertension».⁶ Finally, continuous blood pressure monitoring is recommended to evaluate the nocturnal blood pressure behavior in cases of «isolated nocturnal hypertension».⁷,⁸ However, the pathogenic aspects of the latter indication remain poorly understood,⁹ as evidenced by various conditions associated with the nocturnal behavior of arterial hypertension, such as periodic limb movement. It seems that sympathetic discharges are the etiological cause with greater support. One study aimed at demonstrating the relationship between arterial hypertension and periodic limb movement took place in Cordova, a province of Spain. In this study, 11 individuals with a previous diagnosis of periodic limb movement were compared with seven control individuals using polysomnography. The patients with periodic limb movement had an average age of 57 ± 14 years, whereas the control group had an average age of 64 ± 6 years. However, the age difference between the two groups was not statistically significant (p = 0.284).

Contrary to the expected hypothesis, the results showed intriguing findings regarding blood pressure. The average blood pressure obtained over 24 hours by ambulatory blood pressure monitoring was lower in the periodic limb movement group compared to the control group. Specifically, the systolic pressure was 114.2 ± 11 mmHg in the periodic limb movement group versus 123 ± 11 mmHg in the control group, with a p-value of 0.095. Similarly, the diastolic pressure was 65.7 ± 5 mmHg in the periodic limb movement group and 74.4 ± 11 mmHg in the control group, with a p-value of 0.027.¹⁰ These unexpected findings raise questions about the underlying mechanisms and their implications for hypertension management. This prompts further investigation into whether circadian patterns of blood pressure behavior are linked to extravascular complications.¹¹ Multiple studies have sought to address this question. In 2018, a study in Cuba attempted to establish a link between the circadian behavior of blood pressure and specific conditions like left ventricular hypertrophy and insulin resistance among 46 hypertensive patients. Surprisingly, the initial hypothesis suggesting a direct relationship between insulin resistance and blood pressure behavior was not supported by the study’s findings.

Nevertheless, the study shed light on the nocturnal behavior of blood pressure, uncovering significant anomalies. Among the participants, 58% exhibited abnormal nocturnal blood pressure patterns. This included 15% with the non-dipper phenomenon, 7% with Extreme dippers, and an additional 5% with Reverse dippers.¹² These findings underscore the existence of potential independent vascular risk factors within the hypertensive population, although their precise nature remains unclear.

Material and methods

In an observational, retrospective, descriptive, and cross-sectional study, PDF files of Ambulatory Blood Pressure Monitoring (ABPM) reports obtained from the cardiology outpatient clinic were meticulously reviewed. This encompassed all individuals undergoing follow-up in a specialized first-contact clinic in Mexico City, dedicated to the control and monitoring of arterial hypertension, as well as the management of various cardiovascular pathologies, receiving referrals from health centers across the city. Evaluation of accepted indications for ABPM in the cardiology clinic was not conducted, adhering strictly to the prevailing normative criteria for specialty outpatient care in the institution.

Between June 1, 2018, and October 15, 2023, ambulatory blood pressure monitoring was conducted using a Schiller model BR 102 plus device. The device was programmed to record blood pressure at 30-minute intervals during daytime hours from 08:00 to 22:00 and during nighttime hours from 22:00 to 08:00 the following day. The decision to perform ABPM was solely based on clinical criteria and the follow-up protocol established by the responsible cardiologist.

A comprehensive database was constructed from the total ABPM records in PDF format, capturing essential variables such as age, sex, height, weight, body mass index (BMI), overall blood pressure averages, daytime, and nighttime blood pressure averages, as well as maximum blood pressure readings at various times and the corresponding hours of those peaks. An analysis of variance was conducted for multiple quantitative variables, and a Student’s t-test was employed to determine differences between groups in independent variables, with a significance level set at p < 0.05.

Results

A total of 768 ABPM reports obtained between June 1, 2018, and October 15, 2023, were scrutinized. However, 42 studies were excluded due to incomplete information for analysis. Among these, 26 lacked nighttime blood pressure recordings during ABPM, eight lacked weight and height measurements, and eight lacked age records in the ABPM report, rendering them unsuitable for analysis. Additionally, 78 ABPM studies performed to establish the diagnosis of arterial hypertension were set aside, constituting 10% of the total sample, as these patients were suspected to have the «white coat phenomenon and masked hypertension».

The groups of patients with previously diagnosed hypertension and established prior treatment totaled 648 individuals, who were further subdivided into two groups: those with information on office blood pressure measurements for comparison with ABPM averages.

Of the 648 studies conducted on hypertensive patients in follow-up, 425 corresponded to women (65.5% of the total records), while 223 corresponded to men (34.5%). Multivariate analysis revealed four variables with statistically significant differences when comparing men and women (Table 1).

The remaining variables showed no statistical significance. Notably, no significant differences were found in the subgroup of patients with office blood pressure readings compared to the average values obtained in ABPM.

The circadian rhythm of systolic blood pressure allowed patients to be categorized into four distinct groups based on their nocturnal blood pressure behavior. These groups include:

Statistical analysis revealed small but significant differences in blood pressure behavior between men and women, with a calculated p-value of 0.059. Specifically, it was observed that 71.3% of women exhibited a dipper response, compared to 73.4% of men. The next most common group consisted of patients with inverse dipper patterns, accounting for 23.7% of women and 21.8% of men. Non-dipper behavior was less prevalent, accounting for 3.1% of men and 2.8% of women. Additionally, extreme dipper patterns were found in 1.7% of men and 1.8% of women. However, none of these individual percentages demonstrated statistically significant differences between genders (Table 2).

In the gender-based analysis, notable disparities were observed in systolic and diastolic blood pressure values, primarily revolving around the timing of maximum peaks of hypertension. Additionally, a slight discrepancy in body mass index was identified between the inverse dipper and non-dipper groups, with values of 29.04 and 29.06, respectively, yielding a statistically significant p-value of 0.00018. Among men exhibiting dipper and extreme dipper responses, a marginal age difference was noted, with the first group averaging 64.05 years and the latter 64.5 years, resulting in a p-value of 0.09.

In cases where ABPM served as a diagnostic tool for arterial hypertension, no significant demographic distinctions were observed among the 79 individuals studied, comprising 58 women and 20 men. However, statistically significant differences were evident in the timing of maximum blood pressure values. For women, the hour with the highest systolic pressure was approximately 12:53 pm, while for men, it occurred around 2:09 pm, with a p-value of 0.001. Similarly, the hour of maximum nocturnal diastolic hypertension for women was recorded at 11:08 pm, whereas for men, it was at 10:10 pm, with a p-value of 0.0008. Notably, despite these temporal variations, average blood pressure values remained quite similar across genders.

The average blood pressure behavior among hypertensive patients in the study was slightly higher in men, with readings of 122/73 mmHg compared to 121/68 mmHg in women. During daytime hours, men exhibited an average blood pressure of 124/74 mmHg, whereas women recorded 123/70 mmHg. Nighttime blood pressure averaged 118/69 mmHg in men and 116/63 mmHg in women. Although men displayed a slightly greater reduction in systolic blood pressure (4.8 mmHg) and diastolic pressure (6 mmHg) during nighttime, these differences did not reach statistical significance by gender. Moreover, no notable disparities were found between office blood pressure and average ABPM readings for hypertension diagnosis, as illustrated in Table 3.

Discussion

The impact of abnormal circadian blood pressure patterns on vascular and metabolic diseases has been extensively documented in various studies, hinting at a common underlying etiology.¹⁴ A recent systematic review delved into the cardiometabolic implications of circadian rhythm disruptions in the North American population, particularly associated with occupational factors. This review explored the interplay between meal timing, work schedules, and their correlation with body mass index, diabetes prevalence, hypertension, and cerebrovascular diseases. The findings revealed alarming statistics, including a 23% prevalence of obesity and overweight, a 14% increase in diabetes mellitus, and a metabolic syndrome prevalence ranging from 11% to 35% among individuals with disrupted circadian rhythms. Notably, hypertension exhibited a 10% prevalence but with a staggering 30% elevated risk of occurrence, underscoring the profound impact of circadian rhythm changes on health.¹⁵

The daily patient record was not consulted for the preparation of this study. However, the significance of this study potentially lies in its revelation that blood pressure behavior may deviate from expected norms even among individuals without significant changes in their daily activities. Surprisingly, only 71.5% of men and 73.4% of women exhibited a normal blood pressure pattern (dipper) despite their average blood pressure values falling within the normal range. Various efforts have been made to elucidate these phenomena, such as the research published by Murray E.C. et al., which investigated vascular response phenotypes in early hypertension. Their study, involving 73 newly diagnosed hypertensive individuals without standard treatment, compared with a control group of 79 hypertensive individuals matched for demographic characteristics, found that all newly diagnosed hypertensive individuals displayed vascular stiffness but not endothelial dysfunction.¹⁶ This finding aligns with previous multicenter studies associating the duration of hypertension with vascular intima necrosis and greater endothelial dysfunction.

However, our study reveals gender-specific behavioral differences among individuals without a prior hypertension diagnosis. This aspect is particularly noteworthy as the timing of peak hypertension could unveil underlying factors yet to be fully understood between men and women. Despite similar systolic and diastolic pressure values, distinct differences in the times of peak hypertension were observed. These findings underscore the complexity of blood pressure regulation and the need for further investigation into gender-specific mechanisms influencing blood pressure patterns (Table 4).

Conclusion

The circadian behavior of blood pressure, characterized by the physiological dipper pattern, was observed in only 72.6% of hypertensive individuals, even among those with normal average blood pressure values. The inverse dipper pattern emerged as the second most prevalent group in the studied population, comprising 22.5% of individuals. Minor disparities were noted between men and women regarding the timing of peak hypertension.

The group of researchers is developing work on the behavior of obstructive sleep apnea in cardiovascular disease, which could further enrich knowledge about this disease and its growing prevalence.