Blood pressure circadian rhythm

　　In recent decades, with the widespread use of Ambulatory Blood Pressure Monitoring (ABPM) in clinical and scientific research, people’s understanding of blood pressure and its fluctuation pattern has been raised to a new level, and the blood pressure circadian rhythm (BPCV) and its clinical significance are briefly described as follows: 1 Blood pressure circadian rhythm in ABPM In a large sample of normal subjects and most patients with mild to moderate hypertension, the blood pressure fluctuations in ABPM showed a certain repeatable pattern, i.e., the blood pressure level was higher during the daytime, lower at night when sleeping, and started to rise at 4:00-5:00 am, with a peak at 6:00-8:00 am (also reported to be 8:00-9:00 am), then gradually stabilized, and again at 16:00-18:00 am. The peak occurs again at 16:00-18:00, then slowly decreases and reaches a trough at 0:00-2:00 am (also reported at 2:00-3:00 am) and is maintained until 4:00-5:00 am, with a long-handled spoon curve with two peaks and a trough throughout the day. This rhythmical variation in blood pressure plays an important role in adapting to the body’s activities and protecting cardiovascular structure and function. Currently, most scholars use the nighttime blood pressure decrease percentage (PER), which is the difference between the daytime mean and the nighttime mean divided by the daytime mean, as a quantitative indicator to determine the circadian rhythm of blood pressure in ABPM, generally with ≥10% indicating a normal circadian rhythm and <10% indicating a weakened or absent circadian rhythm. According to the 24-hour ambulatory blood pressure trend graph over time, i.e., the day is divided into 24 time intervals on an hourly basis, and the average systolic blood pressure or average diastolic blood pressure of each time and interval is connected to the graph, and the analysis shows an "arytenoid" change, i.e., a decrease in blood pressure at night. The opposite is true for the "non-ryptoid" type of change. Recently, a third type (deep arytenoid) has been reported, in which blood pressure drops by more than 20% at night. Patients with hypertension are classified into four types according to the circadian pattern of blood pressure fluctuations: (1) normal circadian rhythm; (2) reduced or absent circadian rhythm; (3) elevated blood pressure at night; and (4) pheochromocytoma type, which is often characterized by episodes of markedly elevated blood pressure and upright hypotension [1]. Tang Guangjun, Department of Cardiovascular Medicine, Shandong Coal Taishan Sanatorium, Shandong Province, China 2 Clinical significance of blood pressure circadian rhythm and possible mechanisms of its generation Most studies have confirmed that blood pressure rhythm is controlled by cerebral and physical activities, and is influenced by circadian rhythmic changes in sympathetic and vagal balance and regulation of humoral hormone secretion rhythm in human body. During the day, blood pressure is mainly controlled by changes in force and cerebral activity. In normal people, sympathetic activity predominates during the day, and parasympathetic activity predominates at night. At night, sympathetic activity decreases, cardiac output decreases, general muscle relaxation occurs, and peripheral vascular resistance decreases, so blood pressure decreases at night, which is important for adapting to body activities and protecting important organs such as the heart, liver and kidneys. During nighttime sleep, the human body is excluded to the maximum extent from the interference of external factors and the influence of various neurohumoral factors. Abate's study showed that non-spooning is associated with a weakened parasympathetic impulse and an increased sympathetic impulse, and that non-spooners are more likely to experience target organ damage than spooners. The reduced nocturnal blood pressure drop in hypertensive patients may be due to the increased stress sensitivity of sympathetic nervous system activity in patients with essential hypertension, and this sensitivity is further increased with the added weight of target organ involvement. This disturbance in the neurohumoral regulatory mechanism of blood pressure that does not change in response to changes in physiological activity leads to an increase in peripheral vascular resistance and a decrease in blood pressure drop at night, thus causing a disturbance in the circadian rhythm of blood pressure [2]. In hypertensive patients, the ability to regulate blood pressure is reduced, and the blood pressure level is higher throughout the day and 24 hours, but does not fall at night, so that the heart, brain, kidneys and other organs are under pressure load for a longer period of time, resulting in damage to target organs and susceptibility to complications; therefore, disorders of vascular circadian rhythm suggest damage to target organs, and those with loss of rhythm are severely damaged. Cardiovascular events occur more frequently [3]. Hypertensive patients with diminished or absent nocturnal blood pressure reduction are associated with a higher incidence of cardiovascular accidents, and circadian rhythm of systolic blood pressure and nocturnal systolic blood pressure level are independent risk factors for cardiovascular and cerebrovascular events in patients with essential hypertension, i.e., spoon curve has a better prognosis and non-spoon has a worse prognosis. It has also been suggested that once the target organ is damaged, its parasympathetic activity decreases, autonomic function is dysregulated, and blood pressure circadian rhythm causes alterations [4]. In addition, with increasing age and the development of atherosclerosis, arterial expandability decreases, important organs and endocrine glands are inadequate, and the sensitivity of vascular pressure receptors to regulate blood pressure decreases, hindering (especially during sleep) arterial vasodilation, so that blood pressure does not fall or even rises at night.　　3 Several factors that should be considered when analyzing the circadian rhythm of blood pressure Witte [12] and others found that the light-dark cycle itself has a greater effect on the murine supraoptic nucleus than endogenous neurohormonal effects. Therefore, the division between day and night is particularly important. A domestic scholar, Li Fang [13], and others showed that different intertemporal divisions are important for analyzing the circadian rhythm of blood pressure in humans, and different temporal divisions yield different conclusions. He used the short time method [full name short fixed sleep interval method, i.e. 10:00-23:00 points for wakefulness and 01:00-7:00 points for sleep (6 hours)], the long time method [full name long fixed sleep interval method, i.e. 07:00-22:00 points for wakefulness and 22:00-07:00 points for sleep (9 hours)], and the diary method (divided by the actual time of falling asleep and waking up in the early morning). The three methods were divided and analyzed in 100 patients, and it was concluded that the short-time method is more accurate to reflect the circadian rhythm of human blood pressure. EEG recordings are the gold standard for determining the true sleep period, but they are difficult to promote because they are expensive, affect sleep, etc. May [14] divided day and night according to the following three methods in his study of blood pressure circadian rhythms: according to the individual patient's bedtime and wake-up time (with reference to the patient's condition diary) (method IND); according to the average bedtime and wake-up time (method MEAN); according to the scientific Committee recommended method: daytime 7:00-22:00 and nighttime 22:00-7:00 (method 722). The incidence of nonspooning is low when analyzing blood pressure circadian rhythms with the IND. In conclusion, when analyzing blood pressure rhythms, the influence of human factors on blood pressure rhythms should be controlled as much as possible, and daytime and nighttime should be calculated according to the actual resting time of each individual, and the correct criteria for determining blood pressure circadian rhythms should be mastered. In addition affect sympathetic and parasympathetic nerve activities such as emotional excitement, anxiety, insomnia, exercise, night shift workers; patients' dietary habits, especially salt intake, age gender, body mass index, etc., gender factors such as paying attention to postmenopausal women, whether estrogen therapy is used, etc., all these factors will have different degrees of influence on blood pressure rhythm. Only after unifying the criteria, considering various factors affecting the circadian rhythm of blood pressure, and controlling the errors caused by human factors, can we reach a conclusion that is in line with the objective rule.　　4 The effect of abnormal blood pressure circadian rhythm on target organs A large number of studies have shown that the circadian characteristics of blood pressure in hypertensive patients are closely related to the occurrence and prognosis of their complications. It is generally accepted that an arytenoidal distribution of blood pressure is a relatively healthy type, whereas patients with a non-arytenoidal or super-arytenoidal distribution have a significantly higher risk of stroke, renal dysfunction, and left ventricular hypertrophy [1 ,6 ]. Hua Qi et al [7 ] used 24-hour ambulatory blood pressure monitoring and echocardiography to compare the ambulatory blood pressure rhythm and the characteristics of cardiac structure and function in 338 patients with primary hypertension. It was found that the 24-hour systolic blood pressure, 24-hour diastolic blood pressure, nocturnal systolic blood pressure, and nocturnal diastolic blood pressure were significantly higher in the non-aspirate group than in the arytenoid group, and the left ventricular myocardial mass and left ventricular myocardial mass index increased significantly in the non-aspirate group compared with the arytenoid group, and the peak flow rate in early diastole slowed down, and the peak flow rate, flow rate integral, and A/E ratio in atrial systolic blood flow increased. Hoshide et al [8 ] also found a significantly increased risk of LV hypertrophy and cardiac remodeling in a group of normotensive subjects. Recently, Kario [9] showed that the risk of asymptomatic cerebrovascular disease or stroke was significantly higher in non-ascending and super-ascending subjects with different circadian blood pressure rhythms than in those with ascending blood pressure rhythms. Wang Zhaoyu et al [10 ] studied the effect of circadian variation in blood pressure on cardiac and aortic remodeling in patients with hypertension. The authors performed 24-hour ambulatory blood pressure monitoring in 64 patients with grade 1 to 2 hypertension, and ultrasound was used to detect structural parameters of the heart and arterial structural parameters such as lumen diameter and intima-media thickness of the aorta, femoral artery, and N artery, as well as functional parameters reflecting compliance or dilatation, and 36 normotensive patients were used as controls. The results showed that the left atrial internal diameter, left ventricular wall thickness, and left ventricular muscle mass were significantly increased in the non-arrythmic group with abnormal circadian rhythm of blood pressure compared with the normotensive control group, and the intima-media thickness and area of the aorta, femoral artery and N artery were increased. The aortic lumen diameter and area increased, and the pulse wave velocity increased significantly. In the arytenoid hypertension group with normal circadian rhythm, the differences in cardiac and vascular remodeling indexes were not statistically significant when compared with the normotensive control group. This suggests that the abnormal circadian rhythm of blood pressure in mild to moderate hypertension may have an adverse effect on cardiac and aortic remodeling. Meng Qiuyun et al [11 ] investigated the relationship between abnormal blood pressure circadian rhythm and renal damage in hypertensive patients. Blood and urine β2-microglobulin (β2-MG), urine microalbumin (mAIB), blood urea nitrogen (BUN), and blood creatinine (Cr) were measured in the two groups. Blood and urine β2-MG, urine mAIB, blood BUN, and Cr were found to be increased in those with abnormal blood pressure circadian rhythm compared with those with normal circadian rhythm. This suggests that renal damage is more severe in those with a non-ascending blood pressure circadian rhythm than in those with an ascending one. On the contrary, there are also data suggesting that abnormal blood pressure rhythm is not associated with target organ damage in hypertension. This may be due to the differences in the criteria used by scholars to determine the non-ascending blood pressure. The cut-off values for the magnitude of the nocturnal blood pressure drop and the sampling period for nocturnal blood pressure may be different in some studies. In order to minimize the influence of different sleep habits on the study results, it has also been suggested that the analysis of diurnal blood pressure should be based on individual sleep and wakefulness, i.e., "actual sleep blood pressure" instead of "nocturnal blood pressure"[12] . In the Study on Ambulatory Monitoring of Pressure and Lisinopril Administ ration, it was also shown that in patients with untreated hypertension and in those who achieved stable blood pressure reduction with medication, regardless of whether their blood pressure curves were arytenoid or non-arytenoid, their blood pressure curves were not as high as those in the study. In both untreated hypertensive patients and those with stable BP with medication, their diurnal BP fluctuated by about 40%, regardless of whether their BP curves were arytenoid or non-arytenoid. After 12 months of antihypertensive treatment, the recovery of left ventricular hypertrophy did not differ between arytenoid and non-arytenoid blood pressure, but was only related to the treatment of 24-hour mean blood pressure, daytime blood pressure, or nighttime blood pressure. Therefore, more convincing criteria are needed to study target organ damage in hypertensive patients with circadian rhythms of blood pressure.　　The relationship between abnormal blood pressure circadian rhythms and target organ damage in hypertension is controversial, and the causal relationship between abnormal blood pressure circadian rhythms and target organ damage is still not well understood, but they are certainly closely related. It is generally believed that restoring the normal circadian rhythm of blood pressure is beneficial. In recent years, scholars at home and abroad have conducted several studies on the effects of commonly used antihypertensive drugs on the circadian rhythm of blood pressure. Zhang Weizhong et al [14 ] were the first to observe the effects of short-term treatment with amlodipine on abnormal blood pressure rhythm and left ventricular diastolic function. 28 hypertensive patients with abnormal blood pressure circadian rhythm were treated with amlodipine 5-10 mg/d for 6 weeks, and ambulatory blood pressure monitoring and echocardiography were performed before and at the 6th week of treatment. The results showed that among the 25 patients who completed the follow-up treatment, 15 patients with abnormal blood pressure circadian rhythm reversed and 10 patients with no reversal. The left ventricular diastolic function was significantly improved in the patients with reversal. This suggests that the abnormal circadian rhythm of blood pressure can be reversed in about 60% of patients with essential hypertension after amlodipine treatment, thus improving their left ventricular diastolic function. However, Fang Ningyuan et al[15 ] concluded the opposite, that amlodipine had no significant effect on the circadian rhythm of blood pressure. Recently, Qiu Yuangang et al [16 ] found that long-acting calcium antagonists, diuretics, angiotensin-converting enzyme inhibitors, or angiotensin receptor antagonists may be beneficial in maintaining a normal blood pressure circadian rhythm in 79 patients with arytenoid and 129 patients with non-arytenoid essential hypertension. Some studies have also suggested that different types of antihypertensive drugs may have different effects on the circadian rhythm of blood pressure, and some antihypertensive drugs may even change patients' blood pressure from arytenoid to non-arytenoid [17 ]. Thus, the significance of reversing abnormal blood pressure circadian rhythms and the measures to effectively reverse them are not known. Blood pressure circadian rhythms are influenced by multiple factors such as age, gender, race, season, geography, and even dietary structure [1 ]. Several factors are involved in the regulation of blood pressure circadian rhythm, such as sympathetic and parasympathetic nerves, renin-angiotensin, hypothalamic-pituitary-adrenal axis, etc.　　In today's era of evidence-based medicine, multicenter, large-scale, large-sample clinical trials should be conducted to study the circadian rhythm of blood pressure, i.e., to investigate whether there is a difference in long-term prognosis between patients with and without improvement in the circadian rhythm of abnormal blood pressure with the same reduction in blood pressure. In conclusion, human blood pressure has typical circadian rhythm characteristics, and blood pressure circadian rhythm is influenced by various factors, and blood pressure circadian rhythm may have clinical significance independent of blood pressure level. With the popularization and promotion of ambulatory blood pressure monitoring technology, the study of circadian rhythm of human blood pressure will be more in-depth. In addition to the antihypertensive effect of antihypertensive drugs, the effect of drugs on blood pressure rhythm should also be observed by ambulatory blood pressure monitoring in the treatment of hypertensive patients.　　Contributions to the literature: 1 Li Qiaoying, Li Zhijun, Wang Shaojun. Clinical significance of blood pressure circadian rhythm. 2004 National Time Biomedical Conference (Haikou, December 3-8, 2004) 2 Peng Wanzhong, Gao Zhisheng, Guo Yifang. Overview of research on circadian rhythm of human blood pressure. Clinical Journal, Vol. 20, No. 21, Nov. 5, 2005