Wei-Zhong ZHANG

Shanghai Institute of Hypertension, Shanghai, China

Keywords: Blood Pressure; Cardiovascular risk; Guideline; Hypertension

The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiated and organized by the Chinese Hypertension League. Based on the“2010 Chinese Guidelines for the Management of Hypertension” and recent evidence from domestic and international research in the field of hypertension, considering national conditions and the current situation of hypertension management in China, and reference to the latest European and American hypertension guidelines, the 2018 Guidelines make comprehensive and in-depth elaborations and recommendations of the diagnosis and assessment of hypertension,strategies and goals of prevention and treatment of hypertension and pathway of intervention, etc. The 2018 Guidelines not only provide Chinese medical personnel with guidance and reference for the clinical practice and population management of hypertension, but also serve as the latest textbook on updating concepts and knowledge in the field of hypertension.

The background situation of the 2018 Guidelines is that although the blood pressure control rate of the overall hypertensive population in China is higher than before, it is still relatively low (15.3%), even in the treated patients(about 30%). An important purpose of updating guidelines is to strengthen, optimize and standardize the management of hypertension, and strive to significantly increase the blood pressure control rate in a relatively short period of time in the overall hypertensive population in China (to 50%),especially in the treated hypertensive patients (to 70%). The core concept of the 2018 guidelines is a management strategy that combining blood pressure levels with cardiovascular risk assessment, to initiate antihypertensive treatment and establish blood pressure target with an intensified, optimized and standardized way in patients with blood pressure ≥ 140/90 mmHg and high cardiovascular risks, as well as the recommendation of initial combination therapy pathway. The characteristics of the 2018 Guidelines are as follows: in making the specific recommendations, it not only focuses on the leading role of evidence, but also the collective wisdom of Chinese experts. It allows treatments based on consideration of the specific conditions of patients and clinical experience of physicians. These characteristics make the new guidelines rooted in the soil of Chinese situation while advancing with the times.

When looking through the 2018 Guidelines, the following important contents are worthy of attention, interpretation and comments, compared with the latest European and American guidelines of hypertension.

(1) In regard to the definition, classification and diagnosis of hypertension. Since a continuous, independent and direct positive correlation was founded between blood pressure levels and cardiovascular risk (heart, brain, kidney and vascular disease events), which means the higher the blood pressure level, the greater the risk, the definition of so-called high blood pressure and hypertension are just man-made. A reasonable cut point should be the blood pressure value above which the related events were relatively high (positive predictive rate) and under which the related events were relatively lower (false positive predictive rate). The big data on the relationship between office blood pressure and cardiovascular risks showed that the blood pressure cut point of the positive predictive rate and the false positive predictive rate was 140/90 mmHg. Results of clinical intervention studies for more than 50 years have shown that antihypertensive therapy could reduce cardiovascular risk events only if the baseline blood pressure levels were above 140/90 mmHg.

Although more people could be included to the suitable population range of blood pressure management by if lowering the blood pressure definition of hypertension (to(130/80 mmHg), especially the old people, medical re-sources might be increasing significantly, especially in areas which population have lower blood control rate. Moreover,in people with a relatively low blood pressure level of ＜140/90 mmHg and relatively low cardiovascular risk, treatment management would not increase the benefits significantly. Therefore, it is appropriate and necessary at this stage for the 2018 Chinese Guidelines to keep the definition and classification of hypertension in 2010 Chinese Guidelines.

Since the diagnosis, assessment and evaluation of therapeutic effect of hypertension mainly depend on the results of blood pressure measurement and its changes, the 2018 guidelines emphasize the trinity blood pressure measurement (office blood pressure measurement, home blood pressure monitoring and ambulatory blood pressure monitoring) to accurately obtain blood pressure values. The methods of blood pressure measurement and application status recommended by the 2018 Guidelines are crucial, not only for screening and diagnosis of hypertension, including mask hypertension, but also for increasing awareness of hypertension. In addition, home blood pressure monitoring is conducive to the development of remote blood pressure monitoring and follow-up (in Internet +). Certainly, it is necessary to strengthen guidance on how to interpret the blood pressure readings of the trinity blood pressure measurement in practical applications.

(2) In regard to the cardiovascular risk stratification in patients with hypertension. The fundamental goal of management of hypertension is to reduce the incidence of cardiovascular, cerebrovascular, kidney and vascular diseases events that have not occurred yet but will occur in the future.High blood pressure (meeting the definition by hypertension)and elevated degree of blood pressure (grading) are the main risk factors for cardiovascular risk, but not the only determining factor. Cardiovascular risk also depends on the stage of the disease (target organ damage and comorbidities)and other strong and independent cardiovascular risk factors.Therefore, it becomes inevitable and consensus to initiate antihypertensive drug therapy and recommend the blood pressure target and initiating combination therapy pathway based on the strategies that combine blood pressure levels with cardiovascular risk, and assessment of patient's condition according to the stratification of cardiovascular risk.

According to the 10-year incidence of cardiovascular events in middle-aged population, cardiovascular risk is stratified into four categories: very high, high, moderate and low risk. The cardiovascular risk of patients with hypertension has differential. Elderly patients are mostly at high risk or very high risk. However, middle-aged patients with grade 1 or 2 hypertension, who are the majority of hypertensive population, may be classified as low risk, moderate risk,high risk or very high risk, even if their blood pressure are at the same level.

The primary goal of cardiovascular risk stratification is to identify patients at high cardiovascular risk. The cardiovascular risk of hypertension in the 2018 Guidelines refers to composite risks of all the heart, brain, kidney and vascular events associated with hypertension, rather than just atherosclerotic cardiovascular disease (ASCVD) events. ASCVD does not include events directly related to hypertension such as cerebral hemorrhage, cerebral small vessel disease, heart failure, atrial fibrillation and renal failure.

The 2018 Guidelines still recommend assessment of the cardiovascular risk using tabulating method which is based on European Guidelines and has been promoted and implemented in Chinese hypertensive population for more than a decade, including blood pressure level grading, number of significant risk factors, target organ damage, comorbidities of diabetes, chronic kidney disease and clinical cardiovascular and cerebrovascular diseases. Patients with diabetes or chronic kidney disease are classified as at very high risk or high risk depending on whether there is a complication. This qualitative assessment method was confirmed by the results of prospective multicenter cohort follow-up observational study in Chinese hypertensive patients. The composite endpoint events had statistically significant differences in patients with different cardiovascular risk level. This result is consistent with the clinical and population cardiovascular risk profiles in the real-world situation.

The concept of risk stratification in hypertensive patients is very important, however, it is necessary to acknowledge that the current methods and the basis of risk stratification is still imperfect, not simple and convenient enough as well. It is not accurate enough for risk stratification since the evaluation of several risk factors need not only be qualitative, but also be quantitative, such as blood lipids, blood glucose, obesity, homocysteine and other factors. These factors should be continuously updated. Long-term observation of the actual cardiovascular risk status of patients at different risk levels in large populations of hypertension is an important way to correct and improve risk stratification method.

(3) In regard to the target of blood pressure control. In the aspect of overall antihypertensive treatment strategies,the 2018 Guidelines adjust blood pressure control target values from the previous 140/90 mmHg (single target) to 140/90 mmHg or 130/80 mmHg (dual target), which is an important part of the guideline revision. Evidence from clinical studies of antihypertensive therapy for 50 years shows that long-term control of blood pressure levels in hypertensive patients below 140/90 mmHg can achieve therapeutic benefits and significantly reduction of cardiovascular risk. However, after deep analysis of the factors affecting the size of the benefit, the cardiovascular risk level at baseline and the blood pressure reduction under antihypertensive therapy become the main determinants of the size of the benefit. The higher the cardiovascular risk or the greater the blood pressure reduction, the greater the benefit to quite a certain extent. Systematic review and meta-analysis have demonstrated that patients with high cardiovascular risk or above could achieve more therapeutic benefits when blood pressure below 130/80 mmHg than below 140/90 mmHg, which is the evidence of the intensive blood pressure control of less than 130/80 mmHg.

However, from another perspective, the negative effects of intensive antihypertensive therapy and blood pressure target must be considered, that means the benefit/harm ratio.In patients at low or moderate cardiovascular risk, although the intensive antihypertensive therapy can reduce the relative risk (rate of incidents), the reduction of absolute risk(number of incidents) is very small. On the other hand,some patients at high risk or above may not be able to tolerate the intensive therapy and achieve long-term adherence to treatment. To emphasis on the intensive blood pressure control targets of below 130/80 mmHg in all hypertensive patients will inevitably increase the number and proportion of so-called refractory hypertension. From the perspective of weighing benefits and harm of treatment, it is obviously unreasonable to set a same target value of blood pressure control for all hypertensive patients across the board. Therefore, the 2018 Guidelines establish a dual-target value for blood pressure control in hypertensive patients, with a basic and primary goal of below 140/90mmHg and a supplement and intensive goal of below 130/80 mmHg. The blood pressure target for the elderly patients with hypertension is based on the same consideration, except that the target value of systolic blood pressure is raised by 10 mmHg.

(4) In regard to initial antihypertensive medicine. In the 2018 Guidelines, antihypertensive therapy initiated with currently used evidence-based agents including calcium channel blockers (CCB), angiotensin converting enzyme inhibitors (ACEI), angiotensinⅡreceptor blockers (ARB),diuretics and beta blockers, as well as combinations. The current overall treatment strategy for hypertension is as follows: lowering and sustainable control of elevated blood pressure, referred to as antihypertensive therapy, controlling strong coexisting cardiovascular risk factors, blocking pathophysiological pathway of the development of the disease and reversing target organ damage, referred to as treatment beyond blood pressure control. Among these, the main benefit of antihypertensive therapy comes from the blood pressure reduction itself, which has been demonstrated.Therefore, the major considerations should include contraindications, antihypertensive effects, side-effects and prices;include whether the patients can effectively comply with the treatment; consider the therapeutic evidence of different types of antihypertensive drugs in patients with different stages of disease.

It is impossible to always adopt a regimen in the longterm antihypertensive therapy. The different effects of different types of antihypertensive drugs on prognosis which were directly head to head compared in clinical trials, has little effect on long-term treatment in the real world, such as thiazide diuretics are more beneficial in prevention of heart failure, beta blockers are less effective in reducing stroke,and so on. Optimized selection of initial antihypertensive medicine depends on the development and replacement of more new types of antihypertensive drugs.

In Chinese hypertensive population, especially in young and middle-aged patients, clinical practice and a large-scale therapeutic observational study (HOT-China) have indicated that beta blockers along or in combination with calcium channel blockers could achieve a relatively higher blood pressure control rate and better adherence. The role of beta blockers is still irreplaceable in patients whose sympathetic nervous system is significantly hyperactive, such as patients with episodes of hypertension caused by anxiety and sleep dysfunction. Therefore, the initial antihypertensive drugs recommended in the 2018 Guidelines include beta-blockers,which is beneficial to the diversity of antihypertensive treatment regimens to adapt the needs of different patients, also,is beneficial to improving the relatively lower antihypertensive treatment rate and control rate in Chinese population.

(5) In regard to the initial combination treatment pathway.In the history of antihypertensive drug therapy, the treatment pathway has undergone the stages of single-agent sequential therapy, step-care combination therapy, free combination therapy and initial combination therapy. Since it is impossible or unlikely to achieve the goal of blood pressure control under monotherapy with using the current common antihypertensive drugs, and in order to the neutralization of adverse reactions with monotherapy, the combination therapy has long been considered the major pathway of treatment. In recent years, since the goal of blood pressure control has been intensified and the value of blood pressure target has been reduced, nevertheless, therapeutic observational studies have shown that the initial combination therapy could achieve a higher blood pressure control rate and lower incidences of cardiovascular and cerebrovascular disease end points, the initial combination therapy has got a lot of support. The initial combined therapy pathway is one of the highlights of the 2018 Guidelines, which is beneficial to improve the lower blood pressure control rate, reduce the proportion of monotherapy, and increase the proportion of combination therapy in patients under antihypertensive treatment in management of hypertension in China.

Initial combination therapy pathway needs to be gradually promoted considering the current status and the physicians' experiences of treatment in China. Therefore, the 2018 Guidelines makes several restrictive provisions while affirming the concept of initial combination therapy, which is mainly recommend in patients with hypertension grade 2 or 3, or at high or very high cardiovascular risk, at the meantime, avoid applying to patients who are frail or estimated to be intolerant to treatment.

(6) In regard to the combined intervention of multiple risk factors. Combined intervention of multiple risk factors is an important part of the overall treatment strategy for hypertension. Since multiple risk factors, especially metabolic risk factors, are primarily associated with poor lifestyles, the 2018 Guidelines emphasize active lifestyle (exercise, diet,etc.) interventions.

For the principle of intervention with non-antihypertensive drugs, relying on both evidence and practice to weigh the relationship between treatment benefit and treatment harm in different situations, the 2018 Guidelines give appropriate and discreet recommendations about lipid-lowering, antihyperglycemic and antiplatelet therapy. Low- or moderate-intensity statins can be used in patients with more than one metabolic risk factors or target organ damage.CCSPS study in China has indicated that statin therapy can significantly reduce all-cause mortality and incidence of cardiovascular events in patients with hypertension and dyslipidemia. The goal of glycemic control in patients with diabetes: HbA1c ＜ 7%, or appropriate adjustment according to the individual condition and circumstances. Low-dose aspirin (100 mg/day) and/or a P2Y12 receptor inhibitor were recommended in patients with ASCVD. Patients less than 70 years of age and at high cardiovascular risk can be administered with low-dose aspirin (100 mg/day) when the level of blood pressure is stable, while careful considering and paying close attention to adverse bleeding reactions.

The 2018 Chinese Guidelines for the Management of Hypertension has finally been published based on the previous editions. I hope that my colleagues will learn, promote and apply new guidelines, because promotion and application are more important than formulation of the guidelines. I believe that intensified, optimized and standardized management of Chinese patients with hypertension will certainly promote and facilitate new prospect of hypertension management in China. At the same time, we should discover and identify the defects and issues of the 2018 Guidelines. In addition, we also should do more research works and accumulate more evidences from China actual practice of prevention and control of hypertension.