In 1987, based on his prospective observational study of antihypertensive therapy in patients with coronary artery disease, Cruickshank first raised the issue of the so-called J-shaped curve between blood pressure and the risk of complications, that is, the risk of myocardial infarction is lowest when diastolic blood pressure is lowered between 85 and 90 mmHg, and further reductions, rather than being beneficial, are harmful and increase the risk of myocardial infarction. In 1989, three scholars, Held, Yusuf & Furberg, first raised the issue that calcium antagonists may increase the risk of myocardial infarction in patients with coronary artery disease. Excessive reduction of diastolic blood pressure may increase the risk of myocardial infarction. Since the 1990s, several large-sample clinical trials investigating so-called new drugs such as calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin receptor antagonists, using diuretics and beta-blockers as control drugs, have been conducted. However, these trials failed to confirm that the new antihypertensive drugs were more effective in preventing myocardial infarction. A meta-analysis of 14 clinical trials of antihypertensive therapy published by Rory Collins in the Lancet in 1990 provided more conclusive evidence for the prevention of myocardial infarction with antihypertensive therapy. The results of the meta-analysis showed that the stroke benefit was similar to the level expected in epidemiological studies, whereas the myocardial infarction benefit was only half the level expected in epidemiological studies, and that the 14 clinical trials were more consistent in demonstrating the effectiveness of antihypertensive therapy in preventing stroke, but the results regarding myocardial infarction differed substantially. Compared with controls, the risk of stroke was reduced by 42% (P<0.0001) and the risk of myocardial infarction by 14% (P<0.01) in the group treated with aggressive antihypertensive therapy with a mean reduction in diastolic blood pressure of 5 mmHg. In 1995, Furberg and Psaty et al. published an article in Circulation stating that short-acting nifedipine dose-dependently increased the risk of myocardial infarction in patients with coronary artery disease. Much of the controversy regarding the safety of dihydropyridine calcium antagonists has been related to the fact that these drugs cause reflex sympathetic activation and rapid heartbeat. However, this controversy has subsided with the publication of a series of clinical trials with large samples of long-acting calcium antagonists. In particular, the very large samples of trials conducted with the long-acting calcium antagonist amlodipine, such as ALLHAT, ASCOT, and VALUE, clearly confirmed that long-acting calcium antagonists can be very effective in reducing the risk of myocardial infarction. However, three clinical trials of antihypertensive therapy for systolic hypertension in the elderly published since then have clearly confirmed that in those elderly patients over 60 years of age with systolic blood pressure above 160 mmHg and diastolic blood pressure below 90 or 95 mmHg, antihypertensive therapy significantly reduced the risk of myocardial infarction by 23% despite their mean diastolic blood pressure level below 80 mmHg, which is already very close to the level of benefit expected in epidemiological studies In a further analysis, the risk of myocardial infarction was significantly reduced by 23%. In further analyses conducted since then, it was found that in these patients, the underlying benefit of antihypertensive therapy was due to a decrease in systolic blood pressure, but diastolic blood pressure remained safe down to 70 mmHg. The antihypertensive drugs used in the early trials of antihypertensive therapy conducted were mainly diuretics and β-blockers, both of which have relatively significant adverse effects on glucolipid metabolism, and both diabetes and dyslipidemia are major risk factors for atherosclerotic diseases such as myocardial infarction. The adverse effects of these drugs may be the reason why antihypertensive therapy is not effective in preventing myocardial infarction. Post hoc analyses of several recently published clinical trials have again raised the issue of a J-shaped curve between excessive decreases in diastolic blood pressure and the incidence of myocardial infarction. In the IDNT trial, irbesartan was more effective in reducing the risk of renal insufficiency in hypertensive patients with combined diabetic nephropathy compared with amlodipine, but the risk of myocardial infarction was significantly higher. The investigators conducted a post hoc analysis of the relationship between blood pressure and complications during follow-up and found a significantly increased risk of myocardial infarction with blood pressure below 120/85 mmHg. In the INVEST trial, which was conducted in hypertensive patients with comorbid coronary artery disease, atenolol and extended-release verapamil-based antihypertensive regimens had similar effects in preventing stroke versus myocardial infarction. However, in a subsequent post hoc analysis, it was found that the lower the diastolic blood pressure level during follow-up the lower the risk of stroke and that there was no J-shaped curve relationship; but the risk of myocardial infarction was significantly higher when the diastolic blood pressure was below 70 mm Hg and exponentially higher when the diastolic blood pressure was below 60 mm Hg. Based on these findings, in May 2007, a group of senior hypertension clinicians in the United States specified in the recommendations for antihypertensive treatment of hypertensive patients with combined coronary artery disease that diastolic blood pressure should not be lowered below 60 mmHg. A recent post hoc analysis of the ONTARGET trial also clearly showed that in patients with low baseline blood pressure levels, further reductions in blood pressure increased the risk of myocardial infarction (Journal of Hypertension 2009 ; 27 : 1360-1369 ). In order to maximize the effect of antihypertensive therapy for the prevention of myocardial infarction, careful selection of antihypertensive drugs is needed while differentiating patients. In relatively healthy hypertensive patients who do not yet have complications, comorbidities, or target organ damage, especially those who are relatively young and have lower blood pressure, there may be significant hypotensive symptoms such as dizziness and fatigue, but the risk of serious complications due to hypotension is relatively low. However, those patients who have already had serious complications, those with comorbidities such as diabetes and kidney disease, those with clear evidence of target organ damage, and especially those with advanced hypertension, should have their blood pressure lowered less and more slowly, and large fluctuations in blood pressure should be avoided. This could explain why no J-shaped curve relationship was found in prospective observational studies conducted in the population, which could also explain why antihypertensive treatment significantly reduces myocardial infarction in older systolic hypertensive patients over 60 years of age, which could also explain why J-shaped curves are often seen in hypertensive patients with comorbid diabetic nephropathy and comorbid coronary artery disease. Treatment is also simpler in patients with simple hypertension; while treatment is more complex in patients with complex hypertension, and the most appropriate drug should be carefully selected for high-quality, smooth blood pressure control. Recently, studies have shown that variability or fluctuating elevation of blood pressure is a cardiovascular risk factor independent of blood pressure level in patients with severe hypertension, which also suggests the importance of smooth blood pressure control. Smooth control of blood pressure requires long-acting antihypertensive drugs, drugs that are less affected by environmental and lifestyle factors, and molecularly long-acting calcium antagonists. Among the five major classes of antihypertensive drugs, calcium antagonists have strong antihypertensive effects, are easy to use, and are less affected by lifestyle factors such as sodium intake, which may be an important reason for the widespread use of these drugs in China. However, calcium antagonists with short duration of action or fast-acting calcium antagonists can lead to severe reflex sympathetic activation, increased heart rate, increased myocardial oxygen consumption, and increased risk of myocardial infarction in coronary heart disease when they rapidly lower blood pressure in a short period of time (Figure l ). Therefore, the history of the development of calcium antagonists in the past half century is actually the history of the continuous search for long-acting drugs and long-acting formulations. Nifedipine, felodipine, nisoldipine, diltiazem, verapamil, etc. are short-acting formulations themselves, but all have achieved different degrees of long-acting through the modification of formulation technologies such as slow release or controlled release, while amlodipine, lacidipine, lercanidipine, etc. have achieved different degrees of long half-life due to the long molecular longevity. Amlodipine is the only calcium antagonist that has been shown to be effective in reducing the risk of myocardial infarction. In the ALLHAT trial, amlodipine had a similar effect on preventing myocardial infarction as the angiotensin-converting enzyme inhibitor lenopril, both in hypertensive patients with existing coronary artery disease at baseline and in hypertensive patients without coronary artery disease at baseline. In the ASCOT trial with the addition of the angiotensin-converting enzyme inhibitor perdopril and in the ACCOMPLISH trial with the combination of benazepril, amlodipine was significantly better than β-blockers and diuretics in preventing myocardial infarction (Figures 1 and 2 ). These findings may be closely related to the slow onset of action and smooth control of blood pressure with amlodipine, a molecularly long-acting agent. Some studies have shown that amlodipine is more potent in controlling blood pressure while having a lower incidence of hypotensive symptoms. Hypotensive symptoms may be the most valuable basis for assessing the smoothness of the antihypertensive effect in clinical work with patients. Ambulatory blood pressure monitoring indicators such as the trough/peak ratio or smoothing index can help to some extent to determine whether a drug is long-acting, but their use in a given patient is of very limited value. Symptomatic hypotension is the result of inappropriate treatment or overtreatment and should be avoided whenever possible when the emphasis is on lowering blood pressure to achieve the target. Antihypertensive therapy is a very effective cardiovascular drug treatment. In patients with all types of hypertension, lowering blood pressure significantly reduces the risk of cardiovascular complications and can prolong the patient's life span, the greater the absolute benefit when the patient is at higher risk of disease due to complications, comorbidities and target organ damage. However, it is necessary to choose long-acting antihypertensive drugs with slow onset of action and smooth control of blood pressure as much as possible to fully utilize the effects of antihypertensive therapy. This is especially important for patients with various types of hypertension at high cardiovascular risk, such as patients with coronary heart disease, diabetes mellitus, chronic kidney disease, and elderly hypertensive patients.