Antihypertensive therapy is only a means and a process whose ultimate goal is to protect target organs to reduce complications and minimize the overall risk of cardiovascular morbidity and mortality. The basic principle of chronotherapeutics is to increase the efficacy and reduce or avoid the occurrence of adverse effects by adjusting the drug concentration in blood or tissues during the corresponding time periods by adjusting the time of drug delivery and/or dose, or by applying special agents according to the circadian rhythm characteristics of disease occurrence or exacerbation. In other words, the drug dose or activity is increased during high-risk periods of the disease, and moderately reduced during other periods. A chronotherapeutic approach helps to obtain optimal therapeutic results at minimal cost in terms of medical economics and toxic side effects. 3. 1 Lowering overall circadian blood pressure levels to achieve blood pressure compliance Lowering blood pressure is a cornerstone of the treatment of hypertension. In the last 20 years or so, many large clinical trials have demonstrated the benefits of lowering blood pressure. The WHO/ISH guidelines for the treatment of hypertension suggest that a 10 mmHg (1 mmHg = 0.133 kPa) reduction in systolic blood pressure and a 5 mmHg reduction in diastolic blood pressure can reduce the absolute risk of cardiovascular events by 10% over 10 years in very high-risk hypertensive patients. Blood pressure compliance is the control of blood pressure at a target value or lower to ensure that the harmful effects of blood pressure on the body are minimized. According to the current guidelines for the prevention and treatment of hypertension, the target for lowering treatment in general hypertensive patients is 140mmHg/90mmHg or less; for hypertensive patients with severe target organ damage (such as diabetes, kidney disease, myocardial infarction, etc.), the target is 130/80mmHg; and for elderly people over 60 years old, the systolic blood pressure should be controlled at least below 150mmHg. Anti-hypertensive drug therapy is the main measure to lower blood pressure and achieve the target. In fact, single drug therapy can only make a small percentage of patients achieve the blood pressure standard, and about 60% to 70% of hypertensive patients may need a combination of drugs, that is, the use of two or more antihypertensive drugs. When determining the combination treatment plan, the pharmacological mechanism and clinical action characteristics of each drug should be fully considered to ensure that the antihypertensive effects between drugs are synergistic or at least additive, while adverse effects can cancel each other out or at least do not overlap or add up. 3. 2 Control of the morning blood pressure peak The rapid rise in blood pressure in the early morning from a lower level during nighttime sleep is known as the morning blood pressure peak, and is also referred to as early morning hypertension. High morning peak blood pressure is an important factor that contributes to the highest frequency of cardiovascular and cerebrovascular events in the early morning. Choosing the appropriate medication and time of administration can effectively control the morning peak and thus reduce the occurrence of early morning cardiovascular events. According to the rhythmical nature of blood pressure fluctuations, choose long-acting preparations that can control blood pressure for 24h, and if short- or medium-acting preparations are used, they must be given on time; medication can be taken immediately after waking up in the early morning to control blood pressure as soon as possible to reduce their high risk; elderly patients should wake up slowly and with a small amount of activity, and gradually transition to appropriate daily life and work, especially for hypertensive patients who like to exercise in the morning, it is recommended that they should not take large Advocate family self-monitoring and management of early morning blood pressure, and provide additional antihypertensive treatment if necessary. 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 considered beneficial to restore a normal blood pressure circadian rhythm by bringing the nighttime blood pressure down to a desirable level (i.e., 10% to 20%), a goal that is easily achieved but varies from person to person. Commonly used antihypertensive drugs may have some effect on the circadian rhythm of human blood pressure. Thiazide diuretics have been found to be an effective antihypertensive agent in patients with non-arytenoid and salt-sensitive hypertension, and these drugs are effective in lowering nocturnal blood pressure and changing the circadian profile of blood pressure from non-arytenoid to arytenoid, especially in salt-sensitive hypertension. Similarly, in obese hypertensive patients (who are more likely to be salt-sensitive), diuretics are more effective in non-arrythmics than in arythmics. In a subgroup of the HOPE study [6 ], patients underwent ambulatory blood pressure monitoring at study entry and after randomization to placebo or ramipril (10 mg). The results revealed a more significant decrease in systolic blood pressure at night than during the day in patients treated with ramipril. This result suggests that angiotensin-converting enzyme inhibitors and other therapeutic agents that block the renin-angiotensin system may help restore the arytenoid state. In addition, different types of antihypertensive drugs may have different effects on the circadian rhythm of blood pressure. For example, β-blockers have a stronger antihypertensive effect during the daytime but a weaker one at night, so it is possible that the patient’s blood pressure changes from arytenoid to non-arytenoid. ACEI and angiotensin receptor antagonists, on the other hand, have a better antihypertensive effect at night than during the day, contributing to the shift from non-arytenoid to arytenoid blood pressure. It is a noninvasive index for quantitative evaluation of cardiovascular autonomic activity, mainly reflecting the dynamic regulation of cardiovascular processes by sympathetic and vagal nerves, and its study depends on the clinical application of ambulatory blood pressure monitoring technology. In view of the danger of excessive morning peak and night drop of blood pressure, temporal pharmacology requires drugs with continuous and stable antihypertensive efficacy over 24h. In this regard, the trough-to-peak ratio (T/P) can be used as a measure, together with the average blood pressure reduction (including 24h, daytime and nighttime) and ambulatory blood pressure monitoring. It is generally believed that short-acting antihypertensive drugs increase blood pressure variability, while long-acting antihypertensive drugs can achieve smooth blood pressure reduction and reduce blood pressure variability within 24h. Therefore, there is a trend toward the use of long-acting agents, i.e., agents with a high trough-to-peak ratio, to reduce blood pressure variability by lowering the blood pressure level at 24 h. A high trough-to-peak ratio (≥50 %) can avoid an excessive drop in blood pressure at the peak effect, while maintaining a good hypotensive effect at the trough concentration, so that blood pressure can be maintained at a stable level during 24 h. Therefore, in recent years, the use of antihypertensive drugs with a hypotensive T/P >60 % has been advocated. At the same time, attention should be paid to the time of administration to prevent excessive elevation of blood pressure in the morning and low blood pressure at night to reduce complications and mortality of hypertension. Combined with the chronobiological characteristics of blood pressure, for antihypertensive drugs with T/ P > 60%, their administration time is mostly advocated to be taken in the early morning, so that the peak effect of antihypertensive drugs corresponds to the peak of blood pressure in the early morning, which is conducive to the control of morning peak blood pressure, and the valley effect of antihypertensive drugs happens to be at night, thus avoiding the blood pressure falling too low at night. 3. 5 Reduce pulse pressure Increased pulse pressure is closely related to changes in the elasticity and compliance of large arteries, and increased pulse pressure is an indicator of large artery sclerosis. A large number of studies have suggested that pulse pressure is a risk factor for cardiovascular disease, especially coronary heart disease and heart failure, and is particularly predictive of the occurrence of coronary heart disease and death in the middle-aged and elderly. Simple systolic hypertension and increased pulse pressure account for a large proportion of elderly patients with hypertension. Aging and hypertension are common causes of increased vascular stiffness. In clinical work, early intervention should be performed on systolic and pulse pressure levels in elderly hypertensive patients, which can be achieved by many non-pharmacological therapies to improve arterial compliance, such as aerobic exercise, diet control, and reducing salt intake, which are important to reduce large artery stiffness, delay the onset and development of atherosclerosis, and reduce cardiovascular complications. 3. 6 Lowering Central Arterial Pressure ASCOT – BPLA ( Anglo – Scandinavian Cardiac Outcomes Trial – Blood Pressure Lowering Arm , Anglo Scandinavian Cardiac Endpoint Events Trial – Blood Pressure Lowering Component) branch of the study ASCOT – CAFE (Conduit The Artery Functional Endpoint (CAFE) study has generated a lot of interest and has given a new perspective on BP-lowering therapy, namely the reduction of central arterial pressure [7]. Central artery pressure has unlocked the mystery of how relatively small clinic blood pressure differences can yield relatively large therapeutic benefits. The so-called “beyond blood pressure” effect may be the “beyond cuff” effect. The central arterial pressure is the aortic blood pressure, which generally refers to the systolic pressure at the root of the ascending aorta. As the reverse pressure wave reaches the brachial artery slightly earlier than the aorta, overlapping in the brachial artery in late systole and in the aorta in early diastole, the systolic and pulse pressure in the brachial artery is greater than that in the central artery under normal physiological conditions, usually rising 10 mmHg to 15 mmHg. The two only gradually approach each other after almost the same time. In recent years, some prospective clinical follow-up studies have confirmed that elevated central arterial pressure is very closely related to organ damage and complications in the heart, brain, and kidney, and that it is a better predictor of cardiovascular events than peripheral arterial (brachial) pressure. The results of the ASCOT-BPLA suggest that amlodipine based regimens are superior to atenolol based regimens. In a randomized crossover study comparing the effects of thiazide diuretics, beta-blockers, dihydropyridine calcium antagonists and angiotensin-converting enzyme inhibitors on brachial and central artery systolic pressures, thiazide diuretics and dihydropyridine calcium antagonists were found to reduce brachial and central artery systolic pressures by the same amount; beta-blockers reduced central artery systolic pressures less than brachial; angiotensin conversion enzyme inhibitors lowered central artery systolic pressure more than brachial artery [8 ]. In conclusion, studies on the chronobiology and chronotherapeutics of hypertension have elucidated the relationship between the biological rhythm of blood pressure and target organ damage in hypertensive patients, and have guided the clinical selection of appropriate drugs and the timing of their administration in order to maintain or restore a relatively “healthy” blood pressure rhythm pattern while effectively reducing the circadian mean blood pressure level. This will help reduce the occurrence of cardiovascular diseases such as coronary heart disease, acute myocardial infarction, and stroke by reducing their variability. It is believed that as research progresses, chronotherapy will play a greater role in the selection of hypertension treatment plans and the development of antihypertensive drugs.