In order to minimize cardiovascular events and deaths in the treatment of hypertension, clinical research is constantly being conducted and its treatment concepts are constantly updated and treatment strategies are changing, so it is of great practical value to grasp the key points and use them in clinical treatment. To summarize the latest treatment strategies, there are 6 main points, which can be summarized by SELECT, but it should be noted that SELECT is the prefix of each point (Smooth reduction; Early reduction; Long term reduction; Effective reduction; Combination therapy; Total risk reduction), not a trial of treatment for severe systolic hypertension (Clinical SELECT trial).
Hypertension is a highly prevalent chronic disease that endangers people’s health. The number of hypertensive patients in China is increasing year by year, and currently there are about 160 million adult hypertensive patients in the country. In this paper, hypertension (also called primary hypertension), excluding secondary hypertension, is a risk factor for many diseases, especially stroke and coronary heart disease, and a common cause of exacerbating kidney damage, heart failure and death.
The concept of total risk of cardiovascular disease was first proposed in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of Hypertension (JNC7) and the European Society of Cardiology (ESC) Guidelines for the Treatment of Hypertension in the United States in 2003, and was adopted in the Chinese guidelines for the treatment of hypertension. 2003 and 2004 Hirsh and Folsom proposed Vascular disease, hypertension and prevention, from endothelial to clinical events. 2005 ACC meeting proposed VHP (Vascular disease on Hypertension Prevention), which links vascular biology, pathophysiology, clinical research and epidemiology of cardiovascular disease. At the 2005 meeting of the American Society of Hypertension, the AS Collaborative Group clearly proposed a new definition of hypertension as a multi-causal and progressive cardiovascular syndrome that leads to changes in cardiac and vascular function and structure. The new definition clearly extends hypertension from mere blood pressure readings to total cardiovascular risk factors and suggests that systemic vascular disease be studied as a whole. That is, hypertension is not only a matter of blood pressure levels, but it forms a cardiovascular risk syndrome with abnormal arterial endothelial function, atherosclerosis, left ventricular hypertrophy, obesity, insulin resistance, abnormal glucose metabolism, sympathetic and renin-angiotensin aldosterone system (RAAS) overactivation, altered renal function, and abnormal coagulation. In recent years, increased heart rate with insulin resistance and hyperuricemia have also been included as important components of this syndrome.
Recently, in 2007, the European Society of Hypertension (ESH) and ESC revised the guidelines for the treatment of hypertension, re-emphasizing the concept of total cardiovascular risk in the diagnosis and treatment of hypertension, increasing the detection of subclinical damage to target organs (heart, blood vessels, kidney, optic papilla (fundus), brain), expanding the high-risk and very high-risk groups, proposing target values for blood pressure control in high-risk and very high-risk patients and controlling the total cardiovascular risk. The study also provides information on the target values for blood pressure control and control of total risk factors for cardiovascular disease, subclinical damage to target organs, diabetes mellitus, and diagnosed cardiovascular or renal disease. The study has raised the light for the latest strategy of hypertension treatment and has received international and domestic attention in cardiovascular and related fields.
1. Assessment of the total risk of hypertension
The assessment of the total risk of cardiovascular disease in hypertension depends on the value of blood pressure or the level of elevated hypertension and the coexistence of other cardiovascular disease risk factors.
1.1, the risk of elevated blood pressure
It is recognized from epidemiological (MRFIT) studies that elevated systolic or diastolic blood pressure increases the risk of cardiovascular events such as coronary heart disease, stroke, and renal failure, and the higher the blood pressure, the greater the risk. In our CMCS study, after adjusting for risk factors such as age, sex, total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), smoking, diabetes, and body mass index (BMI), the relative risk of total cardiovascular events was 1 for BP <110/75 mm Hg (1 mm Hg = 0.133 kPa), 2.09 for BP <120/80 mm Hg, and 2.09 for BP ＜The relative risk of total cardiovascular events is 1 for BP <120/80 mm Hg, 2.09 for BP <140/90 mm Hg, 3.23 for BP ≥180/110 mm Hg, and 11.81 for BP ≥180/110 mm Hg. The relative risk of total cardiovascular events increases with increasing BP, but the risk of increasing systolic BP is greater than that of increasing diastolic BP, especially the incidence of stroke increases with increasing systolic BP, which is of great significance in China, where the incidence of stroke is high.
1.2. Hazards of hypertension with other cardiovascular disease risk factors
The risk of hypertension depends not only on the blood pressure level but also on the presence of other cardiovascular risk factors (e.g., dyslipidemia, smoking, diabetes mellitus, obesity, etc.) as well as on the combination of other disease conditions. The majority of hypertensive patients have other risk factors, and the higher the blood pressure, the more risk factors are present [risk factors refer to smoking, diabetes, hypertension, obesity (BMI ≥24), low HDLC (<1.04 mmol/L, 40 mg/dl), high TC (≥6.24 mmo1/L, 240 mg/dl)]. Patients with different risk factors in the CMCS study in China amounted to 63.6%, and those with high values of normotension (120-139/80-89 mm Hg) with one to two or more risk factors accounted for 56.6%, grade 1 hypertension 61.7%, grade 2 hypertension 67.1%, and grade 3 hypertension 67.7%. According to epidemiological studies in China, if hypertension alone without risk factors is taken as 1, the relative risks of cardiovascular events, coronary events and stroke increase by 1.9, 3.6 and 6.7 times respectively when comparing hypertension with 1, 2 and 3 risk factors; coronary events increase by 3.1, 5.8 and 11.6 times; and stroke increases by 1.7, 3.3 and 7.3 times respectively. The increase in stroke was 1.7, 3.3 and 7.3 times, respectively. It can be seen that the more risk factors, the greater the risk of these events, and 1 + 1 ≠ 2.
The 2007 European hypertension guidelines are similar to our hypertension guidelines in general, but the newly added risk trade-offs are metabolic syndrome, renal disease and subclinical damage to target organs or diabetes mellitus, and the initiation of antihypertensive medication for diagnosed cardiovascular or renal disease.
The risk stratification and prognosis of our hypertension treatment guidelines: Grade 1 hypertension: SBP 140-159 mm Hg; Grade 2 hypertension: SBP 160-179 mm Hg; Grade 3 hypertension: SBP ≥ 180 mm Hg or DBP ≥ 110 mm Hg. The risk stratification and definitions of the 1999 guidelines were followed, but the quantitative estimation of prognosis was based on the 10-year cardiovascular morbidity in our cohort population. The absolute risk was based on <15% for low-risk patients, 15% to 20% for intermediate-risk patients, 20% to 30% for high-risk patients, and >30% for very high-risk patients as the criteria for the Chinese population. European hypertension guidelines for total cardiovascular risk stratification (ESH2007): normotension: SBP 120-129 mm Hg or DBP 80-84 mm Hg; normal high value: SBP 130-139 mm Hg or DBP 85-89 mm Hg; grade 1 hypertension: SBP 140-159 mm Hg or DBP 90-99 mm Hg; grade 2 hypertension The increased risk in each risk stratum means higher than the average risk in the stratum.
2.Treatment strategy for total cardiovascular risk of hypertension
The main treatment goal: to minimize the total cardiovascular risk. Treatment strategies: (1) reduce the elevated blood pressure itself; (2) reverse all associated risk factors. Treatment strategy focus: reduce the elevated blood pressure itself, the benefit of hypertension treatment mainly from blood pressure reduction, China’s adult dyslipidemia treatment guidelines state that people who have hypertension or are receiving antihypertensive treatment are equivalent to having three other cardiovascular disease risk factors.
Benefits of antihypertensive therapy in hypertensive patients with cardiovascular disease risk syndrome: Hypertensive patients who can lower their blood pressure to reach the target level can substantially reduce stroke, coronary heart disease and other cardiovascular events. The rate of cardiovascular disease death varies significantly with whether hypertension treatment achieves the target goal or not. Benetos et al. reported treated hypertensive patients, 8893 cases of both sexes, with 25,880 cases of matched untreated patients, followed for 8 to 12 years. The results showed that cardiovascular mortality was significantly higher in those with high BP levels than in those with lower BP levels (4% vs. 12%, P < 0.001), and survival was even lower in those with untreated BP (BP ≥ 140/90 mm Hg) than in those with untreated BP ≥ 140/90 mm Hg.
The earlier the target level was reached and the longer the duration, the greater the reduction in all cardiovascular events. According to the new concept of hypertension and total risk of cardiovascular disease and new strategies of treatment mentioned above, how to treat elevated BP and reverse all associated risk factors to achieve maximum reduction of death and cardiovascular events? The main points are the following 6 points, namely.
2.1. Smooth blood pressure reduction (Smooth reduction)
Smooth blood pressure reduction is an important element of high quality blood pressure reduction in lowering blood pressure to target target values. Smooth blood pressure reduction mainly refers to (1) 24 h control of blood pressure to fall smoothly and reduce blood pressure fluctuations, i.e., variability; (2) suppression of the morning peak phenomenon of blood pressure to reduce cardiovascular events. Ambulatory blood pressure studies have shown that steady blood pressure lowering is different from fluctuating blood pressure lowering in terms of target organ protection. 24-h steady blood pressure lowering can better reverse left ventricular hypertrophy, i.e., protect target organs.
Blood pressure variability refers to the degree of fluctuation of blood pressure within a certain period of time, which is independent of the average blood pressure and can aggravate target organ damage and significantly increase the incidence of cardiovascular and cerebrovascular disease and death rate. The higher the SI, the smoother the BP reduction. The morning peak phenomenon of blood pressure refers to the rapid rise in the early morning hours, with systolic blood pressure rising by an average of 14 mm Hg compared with that at night, or even rising sharply by 70-80 mm Hg. The risk of hypertension in the early morning hours is sympathetic excitation, elevated catecholamine levels, accelerated heart rate, increased blood flow shear, easy rupture of atheromatous plaque and arterial thrombosis. It has been reported that the early morning hours are the high incidence of myocardial infarction, sudden cardiac death and stroke.
To reduce blood pressure smoothly and control the morning peak phenomenon, antihypertensive drugs with a blood concentration trough-to-peak ratio greater than 50% and a high smoothing index should be selected to control blood pressure levels 18 to 24 h after drug administration. The existing long-acting calcium antagonists (amlodipine), controlled-release nifedipine, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) other than captopril, the long-acting beta-blocker bisoprolol, and controlled-release metoprolol can all be used. Changing the time of dosing from morning to bedtime is also a practical approach. In order to smoothly lower blood pressure and control the morning peak of hypertension, short-acting drugs, such as short-acting nifedipine tablets, should not be used.
2.2.Early reduction of blood pressure (Early reduction)
Early reduction of blood pressure should consider the intervention of normal high value (pre-hypertension), research shows that adult hypertension is defined as 140/90 mm Hg is artificial, the ideal blood pressure is 120/80 mm Hg. normal high value of 120-139/80-89 mm Hg that increases the risk of cardiovascular disease, the existing guidelines advocate lifestyle intervention, but recently ESH2007 hypertension guidelines have been proposed in combination However, the ESH 2007 hypertension guidelines have recently suggested that even patients with a combined risk factor of 120-139/80-89 mm Hg should have pharmacological interventions. The prevalence of normal high (prehypertension) in the United States is 31%, with an age-adjusted prevalence of 39.0% for men and 23.1% for women. A study in Heilongjiang, China, showed a prevalence of 47.0%, 51.2% for men and 42.6% for women.
Risk of prehypertension: The Framingham study found that prehypertension progressed to clinical hypertension with many predisposing factors, including abnormal endothelial function, small artery wall thickening, enhanced vasoconstriction, sympathetic and RAAS activation, etc. The rate of progression to hypertension after 4 years was 49.5% (95% CI 42.6%-56.4%) significantly higher than the ideal hypertensive population of 25.5% (95% CI 20.4%-31.4%). CI 20.4% to 31.4%).
One study showed that 90.0% of patients over 75 years of age with prehypertension progressed to hypertension. 1.8-fold increased risk of cardiovascular events: The U.S. TROPH study enrolled 772 patients, aged 30 to 65 years, with blood pressure 130 to 139/≤89 mm Hg patients, treated with the drug candesartan 16 mg/d (391 patients) versus a placebo group (381 patients) for 2 years and observed for 2 years after discontinuation of the drug. The results showed a 2-year increase in blood pressure of 2.0/1.1 mm Hg. The incidence of hypertension at 2 years was 13.6% in the drug group and 40.4% in the placebo group, with a relative risk reduction of 66% (RR 0.34, P=0.001), and the incidence of hypertension at 4 years was 53.2% versus 63.0%, (RR 0.84, P=0.007); serious adverse events were 3.5% in the drug group and 5.9% in the placebo group. 5.9%, indicating that approximately 2/3 of patients with normal high blood pressure (or prehypertension) develop hypertension within 4 years, and that the significance of treating only 4 cases of prehypertension over 2 years to prevent 1 case from developing hypertension is clear. 2007 ESH guidelines consider that patients with normal high (or prehypertension) who have a combination of 3 or more risk factors, metabolic syndrome, 1 subclinical lesion, diabetes or related clinical conditions, antihypertensive drug therapy should be initiated based on lifestyle interventions.
For patients with diagnosed hypertension, it is important to lower the blood pressure to reach the target goal as early as possible. From the results of the VALUE study, whether the valsartan-based drug regimen or the amlodipine-based drug regimen was used in the high-risk patients in this study, most of whom were older and had atherosclerotic vascular disease, the subgroup that lowered the target goal within 6 months of dosing with both regimens compared with the subgroup that did not reach the target goal, fatal and nonfatal cardiac events, the The differences in fatal and nonfatal stroke, all-cause death, myocardial infarction, and hospitalization for heart failure were statistically significant. This suggests the importance of early BP lowering (within weeks, rather than months) to achieve target goals in hypertensive patients to improve prognosis.
2.3. Long term Reduction
Hypertension is a decades-long chronic disease, the long-term nature of treatment should pay sufficient attention to the target target value of long-term treatment to significantly reduce stroke, myocardial infarction and other related cardiovascular events, the longer the duration, the lower the cardiovascular events, the lower the cardiovascular risk. Published large-scale clinical trials of antihypertensive drugs, regardless of meta-analysis (BPLTCC), antihypertensive drugs compared with placebo, or new drugs (ACEI or ARB), CCB compared with older drugs (diuretics, β-blockers) are seen to experience several years before a significant reduction in cardiovascular events and death.
2.4. Effective reduction in blood pressure (Effective reduction)
According to Lewington et al. 61 prospective observational studies, a decrease in mean systolic blood pressure by 2 mm Hg was associated with a 7% reduction in the risk of death from coronary heart disease and a 10% reduction in the risk of death from stroke in more than a million adult cases.
Many previous large clinical trials have shown that the benefit of hypertension treatment comes primarily from the blood pressure reduction itself. The current definition of hypertension is artificial, and the interrelationship between cardiovascular risk and blood pressure is continuous, with no lower threshold. The goal of effective antihypertensive therapy should be to achieve the maximum reduction in blood pressure that the patient can tolerate and to obtain the greatest reduction in cardiovascular risk. Growing evidence suggests that the primary determinant of risk reduction is the level of blood pressure achieved, i.e., the target goal value. Hypertensive patients are classified as low, intermediate, and high very high risk due to their blood pressure level combined with the number of risk factors, the presence of target organ damage, concomitant cardiovascular disease, and renal damage to assess total risk.
The ESH/ESC 2007 guidelines for the treatment of hypertension state that.
(1) Target blood pressure levels for hypertensive patients: all hypertensive patients should be reduced to at least 140/90 mm Hg or less, and lower if tolerated, and to at least 130/80 mm Hg or even <120/80 mm Hg in patients with diabetes, smoking, and high or very high risk.
(2) The additional difficulty of antihypertensive therapy should also be considered in elderly patients, diabetic patients, and patients with cardiovascular disease.
(3) Which patients are currently defined as high-risk/very high-risk patients? The 2007 ESH/ESC guidelines for the treatment of hypertension specify: (1) SBP ≥ 180 mm Hg and/or DBP ≥ 110 mm Hg; (2) SBP > 160 mm Hg with low DBP (< 70 mm Hg); (3) diabetes mellitus; (4) metabolic syndrome; (5) ≥ 3 cardiovascular risk factors; (6) ≥ 1 of the following subclinical organ damage: ECG suggestive of left ventricular hypertrophy (LVH ), especially load ECG (UCG) suggestive of left ventricular hypertrophy (LVH, especially centripetal hypertrophy); increased arterial stiffness; mildly elevated serum creatinine; decreased GFR estimates and creatinine clearance; microalbuminuria or albuminuria; and (vii) definite cardiovascular disease or renal disease.
It can be seen that the 2003 ESH/ESC hypertension treatment guideline target level of 130/80 mmHg is limited to diabetes mellitus and chronic kidney disease. With the accumulation of evidence from evidence-based clinical trials, the definition of high-risk and very high-risk patients with blood pressure down to 130/80 mmHg has been extended to multiple diseases or syndromes in 2007.
2.5.Combination therapy of antihypertensive drugs
The current antihypertensive drugs can be divided into diuretics, beta blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium antagonists (CCB) and alpha blockers. Except for α-blockers, for which there is a lack of long-term large-scale evidence-based medical evidence, the other five classes of antihypertensive drugs can be used as the starting and long-term maintenance drugs for antihypertensive therapy. However, the range of blood pressure reduction for each type of single-dose therapy is about 10 mm Hg, i.e., the “rule of 10”, which is difficult to achieve for most patients, especially for high-risk/very high-risk patients, whose blood pressure targets are also relatively low and difficult to achieve, so most of them need to be combined with two or more antihypertensive drugs. And the current combination of antihypertensive drugs is the mainstream strategy of hypertension treatment today.
The Optimal Treatment of Hypertension (HOT) and the UK Prospective Study of Diabetes (UKPDS) have demonstrated that about 70% of patients need a combination of 2 or more antihypertensive drugs for strict blood pressure control. The lower the target blood pressure, the greater the proportion and variety of drugs in combination, and the more difficult it is to control systolic blood pressure than diastolic blood pressure.
2.5.1. Which patients need combination therapy
The majority of patients with hypertension grade II (BP 160/100 mmHg) or higher, or even grade I hypertension combined with three risk factors or existing target organ damage, or concurrent diabetes mellitus, or high-risk/very high-risk patients with clinical cardiovascular disease, as well as elderly patients with hypertension, systolic hypertension, or patients with a target BP of 20/10 mm Hg or higher, require drug combination therapy.
Rational drug combinations are optimized only if they have a pharmacological basis, the duration of action of the individual drugs is consistent, and the dose of the proportional components is appropriate. The common action of antihypertensive drugs is to lower blood pressure, but the mechanism of action, intensity of action, effects on glucose, lipid and water-salt metabolism, adverse effects and level of evidence-based medical evidence differ among various types of antihypertensive drugs. Theoretically, the selection of antihypertensive drugs for patients should take into account: (1) the level or severity of hypertension; (2) the number of concomitant risk factors; (3) the presence and extent of target organ damage; (4) the clinical situation of co-morbidities; (5) the evidence and strength of the selected drugs in reducing cardiovascular morbidity and mortality; and (6) the interaction between drugs and patients with coexisting diseases. The practical use of drugs also requires consideration of local drug availability and the patient’s financial ability.
The combination of antihypertensive drugs with different mechanisms of action at low doses is used to complement each other, and their synergistic effects not only increase the antihypertensive effect, but also reduce adverse effects and make it easy to achieve the target value of blood pressure reduction.
2.5.2. Which antihypertensive drug combinations are optimal
Comparing the ESH/ESC 2003 and 2007 guidelines for the treatment of hypertension, it can be seen that the hexagonal shape of the combination of six antihypertensive drugs has changed significantly. α-blockers were discontinued early due to the lack of evidence from large-scale evidence-based medical trials [in the Antihypertensive and Lipid-Lowering Treatment for Heart Attack Prevention Trial (ALLHAT) study α-blockers had significantly more heart failure than clothianidin]. The combination with alpha blockers is no longer recommended. The combination of diuretics with β-blockers has more pronounced metabolic abnormalities, so the ESH/ESC 2007 guidelines for the treatment of hypertension consider it inappropriate in patients at high risk for metabolic syndrome and diabetes mellitus. The combination of thiazide diuretics with potassium-protective diuretics (spironolactone, aminoglutethimide, etc.) may prevent thiazide-induced hypokalemia and prevent sudden death, prevent glucose intolerance and reduce diabetes-induced hypokalemia. the combination of ACEI and ARB may lower blood pressure more, reduce diabetic and nondiabetic proteinuria, and improve heart failure, but more evidence is needed on the advantages of the 2 combinations. The optimal combination recommended in the hexagonal box is a calcium antagonist combined with an ACEI, or an ARB, or a β-blocker, with the solid line representing the preferred combination for the general hypertensive population. Calcium antagonists combined with ACEI, or ARB, is the optimal regimen for diabetes and chronic kidney disease and stroke.
The optimized combination regimen has been demonstrated for the ASCOT trial, the largest European clinical study of hypertension, which included 19,257 hypertensive patients whose hypertensive fraction was ASCOT-BPLA amlodipine±perindopril compared with atenolol±bendroflumethiazide, and showed that CCB±ACEI was more effective than beta blockers±diuretics for the primary endpoint of nonfatal myocardial infarction + fatal coronary heart disease by 10% (P=0.1052), cardiovascular death by 24% (P=0.0010), all-cause death by 11% (P=0.0247), coronary events by 13%, fatal and non-fatal stroke by 23% (P=0.003), and others such as new-onset diabetes by 30% (P<0.0001), new-onset renal impairment by (P=0.0187).
In the recent ESC 2007 meeting large-scale clinical trial ADVANCE (the Action in Diabetes and Vascular disease: Preter AX and diamicro N MR Controlled Evaluation) the combination of perindopril and indapamide (trade name Bupropion ) and gliclazide extended-release tablets for the evaluation of a controlled study of intervention in diabetes and vascular disease with a low-dose perindopril/indapamide combination (Bepril) compared with placebo in 11140 patients with a mean follow-up of 4.3 years. The results were a 9% reduction in macrovascular and microvascular primary endpoints, a 14% reduction in overall mortality, and an 18% reduction in cardiovascular disease-related mortality in the Bepril group compared with the control group, all of which were statistically different. No serious drug-related adverse effects occurred, and the group with normal blood pressure also benefited. This is an optimal regimen for the current antihypertensive treatment of diabetes. More optimization protocols are in progress for different high-risk/very high-risk groups.
2.5.3 Systolic hypertension alone
Patients with systolic hypertension with SBP >160 mm Hg and low DBP (<70 mm Hg) are also at high/very high risk, mostly in the elderly. In the INVEST (International Verapamil Cluster Doppler Study) study, cardiovascular events decreased gradually with decreasing blood pressure, but a J-shaped curve was observed, i.e., cardiovascular events increased when blood pressure decreased to 115/70 mm Hg, especially when DBP was <70 mm Hg. Analysis showed a decrease in cardiac coronary supply and an increase in myocardial infarction at DBP <70 mm Hg or <60 mmHg. Existing antihypertensive drugs lower DBP at the same time as SBP, which is very difficult to treat for such high-risk patients.
2.6 Total risk treatment – treatment of all relevant reversible risk factors (Total risk reduction)
The ESH/ESC 2007 hypertension treatment guidelines again emphasize that hypertension is often associated with risk factors for metabolic abnormalities and subclinical organ damage, and that all hypertensive patients should be treated not only for the degree of hypertension but also for other coexisting risk factors, target organ damage, and total risk of concomitant disease.
The total risk is usually expressed as the absolute risk of cardiovascular events over a 10-year period, and age is an important risk factor, but young people have a low absolute risk even with high blood pressure and additional risk factors.
(1) Underlying disease: For the aforementioned high-risk/very high-risk patients with clinical cardiovascular disease, renal disease, and diabetes mellitus, in addition to treating their primary concomitant disease, the target blood pressure control target is 130/80 mm Hg, and for patients with diabetic nephropathy with urinary protein excretion >1 g/24 h, blood pressure is better at 125/75 mm Hg.
(2) Lipid-regulating drugs: Patients with confirmed cardiovascular disease or type 2 diabetes should consider statin therapy to lower plasma TC and LDL to <4.5 mmol/L (175 mg/dl) and <2.6 mmol/L (100 mg/dl), respectively, or lower if possible, with the latter being 2.01 mmol/L (80 mg/dl). Patients with hypertension without significant cardiovascular disease but at high cardiovascular risk (≥20% event risk over 10 years) should be considered for statin therapy, even if baseline TC and LDL are not elevated.
(3) Antiplatelet therapy: Hypertensive patients without cardiovascular events, without ulcer disease and other bleeding risks, applying low-dose aspirin (75-150 mg/d), age >50 years, mildly elevated serum creatinine level or one high cardiovascular risk should take aspirin, but in order to avoid the risk of cerebral hemorrhage, antiplatelet therapy should be administered after blood pressure control.
(4) Blood glucose control: Effective blood glucose control is extremely important in patients with hypertension and diabetes mellitus. Dietary control and pharmacological treatment of diabetes mellitus in such patients should reduce fasting blood glucose to ≤6.1 mmol/L (108 mg/dl) glycosylated hemoglobin (HbA1c) <6.5% (should be at least <7.0%).
(5) Combination of antihypertensive and lipid-lowering drugs: The ASCOT, a large randomized controlled study of patients with hypertension with hypercholesterolemia, is a model trial and is typical of more comprehensive control of hypertension and multiple related cardiovascular risk factors. The study enrolled 19,257 hypertensive patients with antihypertensive combined with lipid-lowering. The hypertension part was called the ASCOTBPLA subgroup, with amlodipine ± perindopril versus atenolol ± bendroflumethiazide two regimens. In the second part, 10,305 patients out of 19,257 with plasma total cholesterol TC ≤6.5 mmol/L (250 mg/dl) were treated with lipid-lowering therapy with atorvastatin 10 mg/d versus placebo control in a double-blind design set up as the ASCOTLLA subgroup. Patients had baseline blood pressure ≥160/100 mm Hg (untreated) or ≥140/90 mm Hg if they were on antihypertensive medication, aged 40-79 years, without myocardial infarction or clinical coronary artery disease, but with 3 or more cardiovascular risk factors. Follow-up was scheduled for 5 years. The results showed that at 3.3 years of treatment with amlodipine±perindopril-based antihypertensive combined with lipid-lowering, the lipid-lowering component of ASCOTLLA decreased by 36% (P=0.0005) compared with the placebo group for the primary endpoints of nonfatal infarction and fatal coronary heart disease, suggesting a greater benefit of antihypertensive plus lipid-lowering. the ASCOT trial became the first and only large cardiovascular mortality with a significant difference in both all-cause mortality active drug-controlled clinical study of hypertension. The ASCOT trial is the only large active drug-controlled clinical study of hypertension to show a significant difference in all-cause mortality. The ongoing ACCORD trial of lowering blood pressure and lipids and glucose will certainly help to recognize the benefits of controlling total risk. The benefits of control for metabolic syndrome, subclinical organ damage such as left ventricular hypertrophy, carotid plaque/intima-media thickness (IMT) thickening, and microalbuminuria have also been confirmed by clinical trials or their subgroup analyses.
Conclusion
With the continuous development and improvement of evidence-based medicine, the study of hypertension and concomitant risk factors and concomitant diseases requires a risk assessment of the risk of cardiovascular events and death in hypertension, distinguishing between low risk, intermediate risk, and high risk to very high risk. Treatment strategies that hold the light high and control the total risk, not only of hypertension itself but also of reversing all risk factors, i.e., strategies to control the total risk are the key to reducing cardiovascular events and death. However, evidence-based medicine is a group treatment and clinical practice is an individual treatment. Patients are very different and vary greatly over time, and many patients do not meet the inclusion and exclusion criteria of evidence-based clinical trials. The optimal combination of drugs and other lipid-regulating and anti-platelet drugs should be carefully considered to make it more individualized, scientific, effective and economic, to reduce cardiovascular events, reduce disability and mortality, to protect people’s health, to extend the quality of life, and to strive for the scientific development of an innovative motherland.