The Potential of Nocturnal Heart Rate as a Predictor of Target Organ Damage in Individuals Diagnosed with Hypertension

: Background: Elevated nocturnal heart rate (NHR) has been linked to an increased risk of cardiovascular events and mortality in hypertensive patients. However, the ability of NHR to predict the occurrence and progression of target organ damage (TOD) in these patients requires further investigation. This study aims to evaluate the predictive value of NHR in forecasting the presence and severity of TOD in hypertensive patients, using a combination of clinical and laboratory parameters. Methods: A total of 145 hypertensive patients were monitored for blood pressure and nocturnal heart rate. Patients were categorized into two groups based on the presence or absence of TOD and their NHR. The left ventricular mass index (LVMI), glomerular filtration rate (GFR), carotid intima media index (CTIM), and left ventricular ejection fraction (LVEF) were measured, and multiple linear regression was used to determine the predictive value of NHR on these indices. Results: The group with TOD had significantly higher NHR than the group without TOD. LVMI, GFR, CTIM, and LVEF varied significantly among the three subgroups, with the NHR3 group showing marked differences compared to the NHR2 and NHR1 groups ( p < 0.01 or p < 0.05). Excessively rapid NHR had diverse impacts on all categories of target organs, particularly on LVMI and CTIM. Conclusion: Augmentation of nocturnal heart rate causes heightened harm to the target organs, with the most significant impact observed in LVMI and CTIM. No significant difference in the severity of TOD was observed between patients with an NHR of less than 70 bpm and those with an NHR between 70 and 80 bpm. However, an NHR above 80 bpm resulted in more severe TOD. These findings suggest that monitoring NHR in hypertensive patients may help prevent and manage TOD.


Introduction
Hypertension is a common medical condition characterized by persistently elevated blood pressure levels [1], which can lead to damage of various organs in the body. Target organ damage (TOD) refers to the structural or functional abnormalities that occur in organs such as the heart, brain, kidneys, as a result of long-standing hypertension [2][3][4].
TOD is a major risk factor for cardiovascular morbidity and mortality, and early detection of TOD can help in the prevention and management of hypertension-related complications [5,6]. Several clinical and laboratory parameters have been used to assess the presence and severity of TOD in hypertensive patients, including blood pressure levels, electrocardiogram (ECG) findings, and imaging studies [3,5,7].
Heart rate is an important physiological parameter that is closely related to blood pressure regulation and cardiovascular function [8,9]. Previous studies have suggested that elevated nocturnal heart rate (NHR) is associated with an increased risk of cardiovascular events and mortality in hypertensive patients [10][11][12][13][14][15]. However, the predictive value of NHR on the development and progression of TOD in hypertensive patients is not well established.
Therefore, the aim of this study is to evaluate the predictive value of NHR on the presence and severity of TOD in hypertensive patients, using a comprehensive set of clinical and laboratory parameters.

Inclusion criteria
A total of 145 newly diagnosed hypertensive patients who had not received medication treatment and visited our hospital's cardiology department from January 2021 to October 2022 were selected. All patients underwent the following examinations: (1) Height and weight; (2) Blood pressure parameters; (3) Questionnaire survey to assess their medical history and lifestyle habits; (4) Cardiac and carotid ultrasound examination.

The definition of hypertension
Hypertension Criteria According to the blood pressure classification criteria of the "Chinese Guidelines for the Prevention and Treatment of Hypertension" in 2005, hypertension is defined as: SBP>140mmHg and (or) DBP>90mmHg

The definition of Target organ damage
Target organ damage is defined as the presence of microalbuminuria and alterations in the heart and blood vessels that can be observed clinically. Ultrasound examination can detect changes in blood vessels, including the presence of at least one plaque in the carotid intima, which is characterized by a local plaque thickness greater than 1.3mm or scattered presence. Scattered intimal thickening is defined as a total intimal diameter exceeding 0.9mm.

Calculation of Nighttime Heart Rate
In a serene environment, during the night time, all patients underwent an electrocardiogram test while resting in a supine position for 5-10 minutes. The test was conducted using a 12-lead electrocardiograph, wherein the 11th lead was chosen and 30 cardiac cycles were recorded. The average R-R interval was used to determine the NHR.

Measurement of blood pressure and other clinical indicators
All of the individuals who were chosen for the study underwent blood extraction from their left elbow vein and provided urine samples on three separate occasions during the morning of the second day. Various biochemical markers, including blood uric acid, urine microalbumin, and urine creatinine, were analyzed using a fully automated biochemical analyzer.

Blood pressure measurement
The patient's blood pressure was measured twice on different days, while they were in a state of rest and lying down. An appropriately sized cuff was placed 2cm above the patient's elbow joint, and a mercury sphygmomanometer was used to obtain the readings. The right upper arm blood pressure was measured three times by a trained medical staff member, with a 5-minute interval between each reading. The final systolic and diastolic blood pressure values were calculated by averaging the results of the two-day measurements.

Measurement of Left Ventricular Dimensions and Mass Using Ultrasonic Cardiogram in Left Lateral Position
The patient was in a left lateral position with calm breathing and using an HP2000 color ultrasonic cardiogram (probe frequency 3.

Statistical analysis
All measurement data were expressed as x±SD. Non-normally distributed data were expressed as logarithmic transformation or median. Rate comparison used the chi-square test. Linear regression or multiple linear stepwise regression analysis was used to evaluate the relationship between different continuous variables or non-continuous parameters. All data were processed using statistical software, with p<0.05 indicating statistical significance.

Nocturnal Heart Rate and Disease Duration as Markers of Target Organ Damage in Comparison to Other Factors
Compared to the group without target organ damage, the nocturnal heart rate in the target organ damage group was significantly increased, and the duration of the disease was longer. There were no statistically significant differences in other factors such as gender and BMI index (see Table 1).

Comparison of general conditions in patients with hypertension and target organ damage (TOD)
After comparing the mean values between the three NHR subgroups, there was no statistical significance in age and course of disease among the three groups (p>0.05). The NHR groups exhibited noteworthy differences in SBP, DBP, and BMI, with a statistical significance of p<0.01. The relevant data can be found in Table 2.  Significant differences were observed in LVMI, eGFR, CIMT, and LVEF between the NHR3 group and the NHR2 group and NHR1 group (p<0.01 or p<0.05). However, no significant differences were noted in the aforementioned parameters between the NHR1 group and the NHR2 group (p>0.05). Table 3 for further details.

Assessing the Impact of NHR on Target Organs: Insights from Logistic Regression Analysis
The impact of NHR on the harm inflicted on target organs by NHR was assessed through the application of Logistic regression analysis, as outlined in Table 4. The findings revealed that NHR had varying effects on all categories of target organs, with a particular emphasis on LVMI and CIMT. (Please refer to Table 4 for further details.)

Discussion
According to the results of this investigation, NHR has the potential to serve as an effective means of forecasting the likelihood of cardiovascular disease in individuals afflicted with hypertension.
This study highlights the potential use of NHR in predicting target organ damage (TOD) in people with hypertension. Hypertension increases the risk of cardiovascular diseases and TOD, including left ventricular hypertrophy, albuminuria, and carotid atherosclerosis. Early identification of highrisk individuals for TOD is crucial in preventing potential risks to cardiovascular health. [16][17][18].
The results of this investigation indicate that there is a positive correlation between elevated NHR and increased incidence of TOD among individuals [19]. Melillo Paolo et al. found that decreased heart rate variability correlated with target organ damage (TOD) in vascular and renal systems, as determined by LVMI, CIMT, eGFR, and LVEF. These results imply that an autonomic nervous system imbalance may be a contributing factor in TOD development. [20]。In the work of Angel et al., the focus was on the dynamic heart rate and its variability, rather than the clinical heart rate. This was found to be linked with a reduction in the intima-media thickness of the carotid artery and an increase in the glomerular filtration rate. However, this association disappeared after age adjustment was made [21]. There are various possible explanations for the association between a higher resting heart rate and an increased incidence of target organ damage. One possibility is that an elevated heart rate may impose a greater workload on the heart and blood vessels, resulting in structural and functional changes in these organs. This, in turn, may lead to an increase in left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), and a decrease in estimated glomerular filtration rate (EGFR) and left ventricular ejection fraction (LVEF). Additionally, an increased heart rate may be linked to other risk factors for cardiovascular disease, such as hypertension, hypercholesterolemia, smoking, physical inactivity, and obesity, which can contribute to target organ damage. These findings are consistent with the results of our research.
It is noteworthy that there was no substantial variance in age and hypertension onset time across the three groups, indicating that non-hyperemic resting heart rate (NHR) might act as an autonomous predictor of target organ damage (TOD). Although no significant difference in TOD was observed between the NHR < 70 times/min group and the 70 times/min < 80 times/min group, the extent of damage was more pronounced when NHR exceeded 80 times/min. This observation could aid in identifying individuals with a heightened risk of TOD and guiding hypertension treatment. Zhang Dongfeng and colleagues [22] found that a higher resting heart rate was independently associated with an increased risk of all-cause and cardiovascular death. Resting heart rate is a predictive factor for all-cause and cardiovascular mortality. Our study's results show similarity to the topic being discussed. Through logistic regression analysis, we observed that NHR has different impacts on various organs, with LVMI and CIMT being the most significantly affected. This discovery is noteworthy, indicating NHR as a potential indicator of the body's response to stress and physiological changes during sleep, which may cause changes in the heart and blood vessels' structure and function, ultimately leading to changes in LVMI and CIMT.