Chinese Guideline on the Primary Prevention of Cardiovascular Diseases: Time to Start Better Cardiovascular Primary Prevention

The “Chinese guideline on the primary prevention of cardiovascular diseases” (referred to as the Chinese guideline below) has been developed recently by the Chinese Society of Cardiology of Chinese Medical Association and other major associations of cardiology by consolidating existing recommendations and scientific statements, expert consensus documents, and clinical practice guidelines into a single guidance document focused on the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in Chinese population.^[1] Cardiovascular diseases (CVDs), including stroke and ischaemic heart disease, were the leading causes of death and disability-adjusted life-years in China.^[2] Evidence-based decision making for CVDs primary prevention in a country with a fifth of the global population is therefore of the utmost importance.

Assessment of CVDs risk is the basis of primary prevention. CVDs risk assessment is determined not only by risk-factor profile and relative risk, but also by the average prevalence of risk factors as well as the average CVDs risk in the population. Well-known risk estimation tools such as the Framingham Risk Score,^[3] the Systematic Coronary Risk Evaluation model,^[4] and the Pooled Cohort Equations,^[5] were developed from western populations, therefore their applicability in Chinese population is limited. Overestimations were reported when these models were used to predict ASCVD risk in Chinese population.^[6,7] The Chinese guideline recommends a risk chart for the assessment of an individual's CVDs risk. This risk chart was based on the 10-year risk prediction model of ASCVD developed from cohorts in Chinese population, which had C statistics of 0.760 for women and 0.769 for men, demonstrating a good calibration in Chinese population.^[8] It is essential for clinicians to be able to assess risk rapidly with sufficient accuracy and the risk chart is convenient for the overall risk assessment of ASCVD in the clinical setting.

The Chinese guideline uses 5% and 10% as cut-off points to classify individuals’ 10-year ASCVD risk as low, medium, and high. A high-risk threshold should be determined not only by its capability of detecting a high-risk population for ASCVD, but also by its cost-effectiveness and availability of medical resources in the identified high-risk population for subsequent treatment procedures. The 2018 ACC/AHA/Multi-Society guideline used 7.5% as the cut-off point to start statin treatment for the primary prevention of CVDs,^[9] which has an acceptable cost-effectiveness in US adults.^[10] However, there is no cost-effectiveness report for different risk thresholds for ASCVD preventive treatment in Chinese population and the Chinese guideline continued to use 10% as previous Chinese guidelines. This threshold might be appropriate for a developing country such as China, and the cost-effectiveness should be evaluated in the future.

Lifestyle management is the cornerstone of primary prevention of CVDs, which has been recognized by guidelines of almost all major academic societies in and out of China. Appropriate lifestyle recommended by the Chinese guideline includes a balanced diet with emphasis on fruits and vegetables, foods rich in unsaturated fatty acids instead of saturated fats, and less than 5 g per day of diet salt, a sufficient amount of physical activities (at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activities), weight reduction in individuals who are overweight or obese, abstinence from smoking, avoidance of alcohol drinking, as well as healthy sleeping and stress management.

Age is the most important risk factor to predict the 10-year risk of CVDs. The predicted 10-year risk of CVDs in young and middle-aged people may not reach a high risk even if they had 3 cardiovascular risk factors. Based on the previous guidelines and studies on lifetime risk,^[11] the Chinese guideline provides a lifetime risk estimation for those with a medium 10-year ASCVD risk and an age ≤55 years. Calculation of lifetime risk provides a communication strategy for the risk management of the young and middle-aged population, which is of great significance for reinforcing adherence to lifestyle and treatment recommendations.

Similar to the European and American guidelines,^[4,5] traditional risk factors were predictors for the ASCVD risk assessment in the Chinese guideline. Inclusion of non-traditional biological and physiological risk factors, such as the ankle-brachial index, high-sensitivity C-reactive protein level, carotid intima-media thickness, and coronary artery calcium score might improve the performance of risk assessment tools. However, there are insufficient data on the roles of these non-traditional risk factors in risk assessment and their impacts on subsequent preventive treatment.^[12] The recent American guideline recommends to start risk assessment using the traditional risk factors, and meanwhile to take into account non-traditional risk factors as risk-enhancing factors in individuals with intermediate risk.^[5] The Chinese guideline also recommends risk-enhancing factors in decision making of primary prevention of CVDs.

Apart from risk assessment and prediction, the Chinese guideline emphasizes the importance of the prevention and treatment of cardiovascular risk factors such as hypertension, diabetes, and dyslipidemia.

High blood pressure (BP) is a major risk factor for CVDs globally. However, there are differences in recommendations by BP management guidelines, such as the definition and classification of BP categories, BP thresholds for initiation of pharmacological therapy, and BP treatment goals.^[13] Findings from large multicenter randomized controlled trials differ from one another. The Chinese guideline represents an evidence-based consensus on BP management. It's noteworthy that the Chinese guideline tailored essential and optimal BP treatment targets in a practical format, which is easy-to-use particularly in low, but also in high resource settings. Considering that awareness, treatment, and control of hypertension were low in China,^[14] treating BP to <140/90 mmHg was recommended essentially in the Chinese guideline. There are only a few clinical trials comparing different BP goals on clinical outcomes. Hence any recommendation on target levels largely derives from observational studies and post hoc analyses of randomized trials. Findings from the Systolic Blood Pressure Intervention Trial (SPRINT),^[15] which showed a significantly lower rate of the primary composite cardiovascular outcome with intensive treatment to systolic BP <120 mmHg than standard treatment to systolic BP < 140 mmHg (HR = 0.75, 95% CI: 0.64–0.89), challenged the above goal recommendations in patients with elevated cardiovascular risk but without diabetes. In addition, a BP level of at least 130/80 mmHg was associated with a significantly increased risk of CVDs compared with normal BP in young and middle-aged Chinese adults.^[16] Considering that BP measurements in the community are not likely to be performed using the SPRINT protocol, together with current evidence, an optimal BP target of less than 130/80 mmHg was recommended in most patients with hypertension in the Chinese guideline. Because SPRINT excluded hypertensive patients with a history of diabetes or stroke, it should be noted that there is still uncertainty in BP control targets in these groups of patients. More high-quality studies are needed to provide rigorous evidence to guide BP management.

Unlike type 1 diabetes, the development and progression of type 2 diabetes are heavily affected by lifestyle factors, such as dietary habit, physical activity, and body weight. The Chinese guideline advocates lifestyle management as the first measure for the prevention and management of type 2 diabetes. Given the close relationship between diabetes and CVDs, glucose-lowering agents must show cardiovascular safety. Metformin has remained the first-line therapy due to its efficacy, safety, affordability, and limited side-effect. Recently, sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide-1 receptor (GLP-1R) agonists have been demonstrated to reduce the risk of CVDs events.^[5] Therefore, on the basis of lifestyle modification and metformin, it may be reasonable to use additionally a SGLT-2 inhibitor or a GLP-1R agonist to improve glycemic control and reduce CVDs risk.

The crucial role of dyslipidaemia in the development of CVDs is documented by extensive research. It has been reported that people in East Asia may have better statin responsiveness and lower baseline low-density lipoprotein cholesterol compared to people from North America and Europe.^[17] Moreover, safety issue is a major concern when using high-intensity statin in Chinese population.^[17] Taken together, from the view of efficacy, safety, and cost effectiveness, moderate-intensity statin therapy was indicated for most patients in the Chinese guideline.

As stated in the Chinese guideline, a high proportion of the chronic disease burden can be attributed to a relatively small number of modifiable risk factors. In the China Cardiometabolic Disease and Cancer Cohort (4C) study, we found that 62.8% of CVDs cases were attributable to a small number of modifiable risk factors, with metabolic risk factors accounting for the largest proportion of population-attributable fraction for CVDs, followed by physical inactivity, unhealthy diet, and current smoking.^[18] Generally, individuals without traditional CVDs risk factors using current definitions are typically considered to have an ideal risk profile. However, previous studies revealed that individuals without traditional cardiovascular risk factors, even with optimal risk levels and ostensibly healthy status, had subclinical atherosclerosis, and coronary artery calcium.^[19,20] This indicates that there are still residual risks caused by other factors, including genetic predisposition, socioeconomic and psychosocial factors, environmental pollution, and other non-traditional risk factors.^[12] With more risk factors proved to be associated with CVDs occurrence, comprehensive CVDs management and prevention measures must be implemented to achieve the lowest CVDs risk.

The increased burden of CVDs imposes a great pressure on the Chinese medical system. Great efforts are needed to strengthen the primary prevention and management of risk factors. The Chinese guideline provides detailed primary prevention recommendations on both a population and an individual level, providing first guidance on CVDs primary prevention in Chinese adults. A strong primary care system with a sufficient number of well-qualified health professionals is essential to deliver the care. Government policies and investments are needed to promote the primary prevention in community individuals and health professionals. With the increasingly educated people and community on CVDs prevention and better-equipped environment for clinical treatment, this well-developed and comprehensive Chinese guideline will be an important step forward towards a better primary prevention of CVDs in China.

Funding

This work was supported by the grants from the National Key R&D Program of China (2017YFC1310700, 2016YFC1305600).

Conflicts of interest

None.