Sheng-Shou HU,the Writing Committee of the Report on Cardiovascular Health and Diseases in China

Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China

ABSTRACT The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China.This section dissects cardiovascular risk factors in China which including hypertension,dyslipidemia,diabetes mellitus,chronic kidney disease,metabolic syndrome and air pollution.Hypertension prevalence has steadily increased in China,with efforts to control it facing challenges in achieving optimal rates,especially in rural areas.Interventions like salt substitutes and intensive blood pressure control show promise but need improvement.Abnormal lipid levels,indicative of dyslipidemia,have risen significantly,posing a risk for cardiovascular diseases.Despite efforts,many patients struggle to achieve target lipid levels,necessitating improved treatment strategies.Both type 1 and type 2 diabetes mellitus affect millions of adults in China,with long-term complications adding to the disease burden.Early intervention and effective management are crucial to mitigate its impact.Prevalent among older adults,chronic kidney disease is associated with diabetes mellitus,hypertension,and cardiovascular diseases,necessitating comprehensive management approaches.The prevalence of metabolic syndrome,characterized by a cluster of risk factors,has increased in both adults and adolescents,calling for lifestyle modifications and public health interventions.Ambient and household air pollution remain significant environmental risk factors,despite some improvements in air quality.Continued efforts to reduce emissions are essential for mitigating associated health risks.Addressing these risk factors requires a multifaceted approach,including public health initiatives,policy interventions,and individual-level strategies to promote healthy lifestyles and reduce environmental exposures.Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in China.

HYPERTENSION

Tobacco control is one of the important public health priorities.Since the World Health Organization (WHO)“Framework Convention on Tobacco Control (FCTC)”entered into force in 2005,encouraging progress has been made to reduce tobacco use.Smoking prevalence among people aged over 15 years has fallen from 22.7% to 17.5% globally.[1]In 2018,the current smoking prevalence of people aged ≥ 15 years was 26.6% in China,and the number of smokers was estimated to be more than 300 million.[2]

Prevalence

Prevalence of hypertension in China

Nationwide sampling surveys from 1958 to 2018 showed that the prevalence of hypertension in China was increasing (Table 1).

Table 1 Nationwide surveys on the prevalence of hypertension in China.

Results from China Hypertension Survey indicated that the prevalence of hypertension among Chinese residents aged ≥ 18 years was higher in men than in women (crude prevalence: 28.6%vs.27.2%;weighted prevalence: 24.5%vs.21.9%) and increased with age (Figure 1).[1]The weighted prevalence of hypertension by sex,region,and ethnicity is shown in Table 2.

Figure 1 Crude prevalence of hypertension among residents by age in China Hypertension Survey.

Table 2 Weighted prevalence of hypertension among residents aged ≥ 18 years by demographic characteristics in China Hypertension Survey.

China chronic disease and risk factor surveillance

China Chronic Disease and Risk Factor Surveillance(CCDRFS) was conducted in 298 counties/districts of 31 provincial administrative units across China in 2018.A total of 179,873 participants aged ≥ 18 years were included in the final analysis by a multi-stage stratified cluster random sampling method.The prevalence of hy-pertension was 27.5% (95% CI: 26.6%–28.4%).It was higher in men than in women (30.8%vs.24.2%).[2]The prevalence of hypertension by characteristics is shown in Table 3.

Table 3 Weighted prevalence of hypertension among Chinese adults by characteristics in 2018.

China health and nutrition survey

Data of 72,452 adults aged 20–79 years from the China Health and Nutrition Survey indicated that the prevalence of hypertension increased markedly during 1991–2015 among Chinese adults (AllP<0.001),[3]especially for the rural residents and the young adults aged 20–39 years (Table 4).

Table 4 Trends in crude and aged-standardized prevalence of hypertension among adults in the China Health and Nutrition Survey 1991–2015.

Prevalence of hypertension in the older adults

A survey on 3454 patients with an average of 72 years indicated that the prevalence in the elderly (aged ≥ 65 years) was 53.10% for men and 55.69% for women,[4]which was significantly higher than that in the middleaged and young adults.The prevalence of hypertension was increasing with age.It was up to 70% in the older adults aged ≥ 95 years (Table 5).

Table 5 Prevalence of hypertension in the Chinese older adults.

Data from China Health and Nutrition Survey indicated that the prevalence of hypertension among elderly people in China during 1991–2015 was higher in urban areas than in rural areas,[5]and the urban-rural prevalence gap showed dynamic changes.The trend was decreasing from 1993 to 1997,expanding from 1997 to 2011,and decreasing again from 2011 to 2015 (Figure 2).

Figure 2 Crude and standardized prevalence of hypertension among older adults in urban and rural areas during 1991–2015.

Prevalence of stage 2 hypertension among Chinese population

China Health and Nutrition Survey conducted 9 rounds of cross-sectional surveys among adults aged ≥18 years during 1991–2015.[6]Within this time frame,the age-standardized prevalence of stage 2 hypertension(SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg) increased from 5.5% to 7.4%.The relative increasing rate was greater in men than in women,and the highest was in people aged 18–39 years (Table 6).

Table 6 Age-standardized prevalence of stage 2 hypertension in Chinese adults during 1991–2015.

AAI was computed by dividing the difference of prevalence between 1991 and 2015 by the number of years covered;ARI was calculated by dividing the average annual change by the baseline prevalence in 1991.AAI: average annual increase;ARI: average relative increase.

A total of 2,618,757 adults aged 35–75 years (mean age:55.6 ± 9.8 years) from 31 provincial administrative units were recruited in the China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) during 2014–2018.Findings indicated that 378,457 participants(14.5%) had stage 2 or above hypertension,which was defined as SBP ≥ 160 mmHg and/or DBP ≥ 100 mmHg.Among them,61.3% had isolated systolic severe hypertension (SBP ≥ 160 mmHg and DBP <100 mmHg),12.8% had isolated diastolic severe hypertension (DBP≥ 100 mmHg and SBP <160 mmHg),and 26% had combined systolic-diastolic severe hypertension (SBP ≥ 160 mmHg and DBP ≥ 100 mmHg).Of the entire cohort,2.9% had an SBP ≥ 180 mmHg.[7]

Incidence of Hypertension among Chinese Population

A dynamic prospective cohort study included 12,952 Chinese adults aged ≥ 18 years from China Health and Nutrition Survey.Age-standardized incidence of hypertension increased from 40.8 per 1000 person-years (95%CI: 38.3–43.4) during 1993–1997 to 48.6 (95% CI: 46.1–51.0) during 2011–2015 (Table 7).Individuals in Eastern,Central and Northeastern China had greater risks of hypertension occurrence in comparison with their counterparts in Western China.[8]

Table 7 Crude and age-standardized incidence (per 1000 person-years) of hypertension in China during 1993–2015.

Prevalence of Prehypertension among Chinese Adults

Data from China Health and Nutrition Survey indicated that the age-standardized prevalence of prehypertension among Chinese adults aged ≥ 18 years increased from 30.1% in 1991 to 43.1% in 2015.[6]Prehypertension was consistently more prevalent in men (than women)and people aged 40–59 years (than those aged 18–39 years and ≥ 60 years) (Table 8).

Table 8 Age-standardized prevalence of prehypertension among Chinese adults during 1991–2015.

Results from China Hypertension Survey indicated that the crude and weighted prevalence of prehypertension were 39.1% and 41.3%,respectively,among Chinese adults aged ≥ 18 years.[1]They increased with age at first and then decreased.The difference between prevalence among various age groups was statistically significant(Figure 3).The (weighted) prevalence of prehypertension was remarkably higher in men than in women(47.8%vs.34.6%,P<0.001).No significant difference was found between rural and urban areas (41.4%vs.41.1%)and between Han and other ethnicities (41.3%vs.40.8%).

Figure 3 Crude prevalence of prehypertension among Chinese residents aged ≥ 18 years in China Hypertension Survey.

Blood Pressure Levels among Population

Results from China Hypertension Survey indicated that the mean weighted SBP and DBP were 126.1 mm-Hg and 76.0 mmHg,respectively.[1]SBP increased with age,while DBP increased at first with age and then decreased (Figure 4).The weighted blood pressure levels were 128.0/77.8 mmHg for men and 124.2/74.2 mmHg for women.They increased with BMI and were significantly higher in the population with family history of hypertension than in those without.No statistical difference was found between Han and other ethnicities(126.2/76.0 mmHgvs.125.9/75.8 mmHg) and between rural and urban areas (126.4/76.0 mmHgvs.125.6/76.0 mmHg).

Figure 4 Blood pressure levels among Chinese residents aged≥ 18 years by age.

Data from China Health and Nutrition Survey indicated that from 1991 to 2015,SBP increased from 115.9 mmHg to 123.6 mmHg and DBP from 74.9 mmHg to 79.6 mmHg (bothP<0.001 for age-adjusted trend).[6]Over the same period,the mean SBP and DBP both increased significantly across age-and sex-groups (Table 9).

Table 9 Age-standardized mean SBP and DBP among Chinese adults during 1991–2015.

Awareness,Treatment,and Control of Hypertension

Studies on the awareness,treatment and control rates of hypertension in China over the years are shown in Table 10.

Table 10 Awareness,treatment and control of hypertension from various nationwide surveys in China.

China hypertension survey

China Hypertension Survey study found that the(crude) awareness,treatment and control rates of hypertension in Chinese adults aged ≥ 18 years were higher in women than in men with statistically significant difference (Figure 5).[1]The (crude) awareness,treatment and control rates of hypertension,as well as control rate among treated patients,were higher in urban residents than in rural residents (Figure 6).The (weighted) awareness,treatment and control rates of hypertension increased with age,while the control rate among treated patients increased at first and then decreased (Figure 7).

Figure 5 Awareness,treatment and control rates of hypertension by sex in China Hypertension Survey.

Figure 6 Awareness,treatment and control rates of hypertension by region in China Hypertension Survey.

Figure 7 Awareness,treatment and control rates of hypertension by age in China Hypertension Survey.

Compared with previous surveys,the awareness,treatment and control rates of hypertension were all significantly improved (Figure 8).

Figure 8 Awareness,treatment and control rates of hypertension during 1991–2015.

China chronic disease and risk factor surveillance

China Chronic Disease and Risk Factor Surveillance indicated that the awareness,treatment and control rates of hypertension in 2018 among Chinese adults aged ≥ 18 years were 41.0% (95% CI: 39.7%–42.4%),34.9% (95% CI:33.6%–36.1%) and 11.0% (95% CI: 10.2%–11.8%),respectively.[2]These rates by characteristics are shown in Table 11.

Table 11 Awareness,treatment and control of hypertension among Chinese adults by characteristics in 2018.

China health and nutrition survey

Data of 72,452 adults aged 20–79 years from China Health and Nutrition Survey study indicated that from 1991 to 2015,the crude/age-standardized rate of hypertension awareness increased from 29.4%/24.2% to 43.8%/27.2%,and that of treatment from 19.2%/15.1% to 39.2%/23.6% (allP<0.001 for trend).[3]The prevalence of awareness and treatment increased in all subgroups except for those aged 20–39 years (Table 12).The overall crude/age-standardized prevalence of control increased from 3.5%/3.6% in 1991 to 13.8%/8.4% in 2015 among hypertensive patients,and from 18.4%/28.4% to 35.1%/37.7% among treated patients (P<0.001 for trend)(Table 13).

Table 12 Trends in prevalence of awareness and treatment among Chinese adults during 1991–2015.

Table 13 Trends in prevalence of control and control under treatment among Chinese adults during 1991–2015.

Risk Factors for Hypertension

Dietary intake of excessive sodium and insufficient potassium

Excessive intake of dietary salt is associated with an increased risk of hypertension.Sodium reduction has already been endorsed by WHO as one of the three optimal measures to prevent chronic diseases.A study was performed in 130 hospitals from 23 provincial administrative units across China during 2016–2019.Results showed that for every 1 unit of Na/K ratio increase,BP increased by 0.46/0.24 mmHg.[9]Another study recruited 20,995 adults with high risk of CVD (72.6% had a history of stroke and 88.4% had hypertension) and followed them up for an average of 4.74 years.[10]A total of 4172 participants died during the trial.The incidence rate of fatal and non-fatal stroke was reduced by 14% with the salt substitute than with regular salt (RR=0.86,95%CI: 0.77–0.96,P=0.006),as were the rates of MACE by 13% (RR=0.87,95% CI: 0.80–0.94,P<0.001) and death by 12% (RR=0.88,95% CI: 0.82–0.95,P<0.001).In addition,the salt substitute was also beneficial with respect to death from vascular causes and nonfatal ACS.

Overweight and obesity

In a cohort study that enrolled 23,165 participants,the RR of hypertension was 3.71 (95% CI: 3.26–4.22) for general obesity and 3.62 (95% CI: 3.19–4.12) for central obesity.[11]Furthermore,weight change could lead to greater changes in BP among middle-aged and elderly people who were overweight or obesity at baseline.Every 10% of weight gain was associated with an increase of 4.94 mmHg for SBP and an increase of 2.50 mmHg for DBP.[12]

Excessive consumption of alcohol

Frequent excessive consumption or occasional heavy drinking of alcohol are harmful to the health.According to the longitudinal data of 12,577 adults in the CHNS 1991–2011,the prevalence of hypertension was higher in participants with a high drinking frequency than in thosewith a low drinking frequency among both genders.The risk of hypertension increased with the drinking frequency.Compared with the non-drinking group,drinking frequency ≤ 2 times/week (OR=1.51,95% CI: 1.26–1.82) and >2 times/week (OR=2.13,95% CI: 1.77–2.56)were positively correlated with hypertension in men.[13]In addition,specific types of alcoholic beverages were associated with different risk of hypertension.The ORs from low to high were 1.51 for beer (95% CI: 1.07–12.13),1.71 for wine (95% CI: 1.01–2.86),and 2.01 for spirits (95%CI: 1.21–3.32).[14]

Environmental factors

Results from a survey in 8 provincial administrative units during 2007–2010,[15]a nationwide cross-sectional study in 28 provincial administrative units of China during 2011–2012,[16]and the CHARLS study suggested that air pollution was associated with increased risk of hypertension.[17]CHS found that the ambient temperature also had an effect on BP (Table 14).[18]

Table 14 Effects of environmental factors on blood pressure in different studies.

Psychological factors

A meta-analysis of 41 studies on the association between hypertension and depression indicated that the prevalence of depression among hypertensive patients was 28.5% in China.[19]Mental stress from occupation or socioeconomic status was significantly associated with hypertension.A cluster randomized clinical trial was conducted among 4,166 employees with hypertension from 60 workplaces in China to assess the effect of a workplace-based multi-component intervention strategy on hypertension control.[20]After 24 months of intervention,BP control rate in the intervention group was significantly higher than that in the control group (66.2%vs.44.0%;OR=1.77,95% CI: 1.58–2.00).The intervention effect on SBP level was -5.8 mmHg (95% CI: -6.8 to -4.9 mmHg) and that on DBP level was -3.6 mmHg (95%CI: -4.4 to -2.9 mmHg).

Social determinants status

A sample of 299,220 Chinese adults from CHS were included for analysis in a cross-sectional survey.People living in a higher economic area or those with a lower level of education or retirement/unemployment conditions had a higher risk of hypertension,especially for male or rural residents.The awareness,treatment,andcontrol of hypertension were lower among the participants living in a worse environment of economic development and social circumstances and those with lower education level or poor employment/study conditions.These findings added to the growing evidence about the effect of social determinants on hypertension.[21]

Intervention for Hypertension

Village doctor-led intervention for blood pressure control in rural China

China Rural Hypertension Control Project (CRHCP)was a large-scale cluster randomized trial and was carried out in rural China as an innovative pattern for comprehensive management of hypertension and intensive BP control.[22]In the intervention group,well-trained village doctors initiated and titrated antihypertensive medications according to a standard protocol under the supervision of primary care physicians.Village doctors also provided health instructions on home BP monitoring,lifestyle changes,and medication adherence.At 18 months,8,865 (57.0%) of 15,414 patients in the intervention group and 2,895 (19.9%) of 14,500 patients in the control group had a BP <130/80 mmHg,with a group difference of 37.0%.From baseline to 18 months,the mean BP decreased by 26.3/14.6 mmHg in the intervention group and by 11.8/7.5 mmHg in the control group.These findings suggested that village doctor-led inter-vention would result in significant improvement of BP control among rural residents in China.

Intensive blood pressure control in older patients with hypertension

For fear of the adverse outcomes,intensive BP control for older patients with hypertension had been controversial.Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) was a multi-center,randomized,controlled trial and enrolled 8,511 older patients with hypertension: 4,243 in the intensive treatment group (SBP target of 110 to less than 130 mmHg) and 4,268 in the standard treatment group (SBP target of 130 to less than 150 mmHg).[23]During a median follow-up of 3.34 years,primary outcome events occurred in 147 patients (3.5%) in the intensive treatment group,as compared with 196 patients (4.6%) in the standard treatment group (HR=0.74,95% CI: 0.60–0.92;P=0.007).The incidence of primary outcome events was significantly lower in the intensive treatment group than in the standard treatment group,with an absolute difference of 1.1 percentage points.The results for most of the individual components of the primary outcome also favored intensive treatment.The HR was 0.67 (95% CI: 0.47–0.97)for stroke,0.67 (95% CI: 0.47–0.94) for ACS,0.27 (95% CI:0.08–0.98) for acute decompensated heart failure,0.69(95% CI: 0.40–1.18) for coronary revascularization,0.96(95% CI: 0.55–1.68) for atrial fibrillation,and 0.72 (95% CI:0.39–1.32) for death from cardiovascular causes.

Traditional Chinese Medicines for Antihypertension

With great development in recent years,traditional Chinese medicines have made a considerable contribution to the treatment of hypertension.However,there is still insufficient data on their use for evidence-based medicine.A randomized,double-blind,double-dummy,multi-center trial compared Songling Xuemaikang capsule (SXC),a Chinese herbal formula,versus losartan in patients with mild essential hypertension.[24]Participants were randomly allocated to receive either SXC (n=314)or losartan (n=314).The decrease of DBP from baseline to 8 weeks was 7.9 mmHg in SXC group and 8.1 mmHg in losartan group.SXC was non-inferior to losartan in reducing DBP.Incidence and severity of adverse events were similar between groups.It was suggested that the BP-lowering efficacy,safety and adherence of SXC were comparable to those of losartan.

Another single-center randomized,single-blind,placebo-controlled trial investigated the efficacy and safety of a Chinese herbal formula,gastrodia-uncaria granules (GUG),in patients with masked hypertension.[25]After treatment for 4 weeks,daytime SBP/DBP were reduced by 5.44/3.39 mmHg in the GUG group,which was 2.52/1.79 mmHg lower than the BP reduction in placebo group.In addition,GUG was safe and well tolerated.This study confirmed the efficacy of Chinese herbal medicines,such as GUG,in the treatment of masked hypertension and promoted their use in the intervention for hypertension.

Prevention of Hypertension

In recent years,the Chinese government has carried out a number of projects,such as “Healthy China Action”,“Medium and Long Term Plan for Prevention and Treatment of Chronic Diseases in China”,“National Essential Public Health Services Program”,“Construction of National Demonstration Area for Comprehensive Prevention and Control of Chronic Diseases”,and“China Healthy Lifestyle Action for All”;built a couple of supportive environments,such as healthy community,healthy workplace,healthy school,healthy restaurant,healthy footpath,and health theme park;developed a variety of appropriate health technologies and tools,such as oil control kettle,salt limiting spoon,body mass index scale,and graduated wine glass;implemented special actions,such as “Three Reductions and Three Health Benefits (salt reduction,oil reduction,sugar reduction,healthy bones,healthy weight,and healthy oral cavity)”,adequate physical activity,tobacco control and alcohol restriction,mental health;and figured out a series of new action modes during the process of implementation on principle of adaptation to local conditions,such as healthy kitchen,balance between diet and physical activity,maintenance of healthy weight,and other special activities.[26]On the support of “National Essential Public Health Services Program”,[27]we should measure BP for all residents aged ≥ 35 years on their first clinic visit,formulate health management standard for hypertension,and explore the pilot construction of demonstration institutions for management of chronic diseases with hypertension as the starting point.By 2019,there were about 109 million registered hypertensive patients nationwide,and the standardized management rate of hypertensive patients increased by 29.28% in comparison with that in 2009.The gap among eastern,central and western regions was gradually narrowing (Table 15).The control rate in the population who were managed for hypertension increased from 50.88% in 2009 to 67.72% in 2019 (Figure 9).[28]

Figure 9 Standardized management rate and BP control rate among hypertensive patients in China during 2009–2019.BP: blood pressure.

Table 15 Distribution of standardized management rate among hypertensive patients in China during 2009–2019.

Summary

Hypertension is a major public health problem in China.The prevalence increases by years,but the improvement on BP control is not ideal.With the advent of aging society,management of hypertension will be confronted with great challenges.Many studies,including those on the risk factors (such as dietary intake of excessive sodium and insufficient potassium,overweight and obesity,environmental factors,mental disorders,and social determinants) and those on the interventions (such as community health management in urban and rural areas,intensive BP control in hypertensive patients,and traditional Chinese medicines for treatment of hypertension),have provided substantial evidence to improve the management of hypertension.However,there are still challenges in effectively preventing new-onset hypertension,increasing the rates of awareness and treatment,especially the control rate.

Hypertension in Children

Identification of hypertension in children

Criteria

Assessment of BP in children should consider their age,sex,and height.The diagnosis of hypertension in children is based on BP measurements on 3 occasions in different days and by reference to the 95thpercentile (P95)BP values in boys and girls.It is defined as SBP and/or DBP ≥ P95.Childhood hypertension can be categorized into stage 1 hypertension(defined as SBP and/or DBP ranging from P95 to P99+5 mmHg) and stage 2 hypertension (defined as SBP and/or DBP ≥ P99+5 mmHg)based on the elevation of BP levels.[29]“Blood Pressure References by Age and Height for Chinese Children Aged 3–17 Years” (Chinese references 2017) was issued in 2017.[30]It was recommended by the “China Guidelines for Prevention and Treatment of Hypertension(2018 Revision)” as a gold standard for assessment of BP in Chinese children.

In order to facilitate rapid diagnosis of hypertension in children by clinicians,pediatricians simplified the“Chinese Standards 2017” to a Formula for BP Reference (“Formula Standard”) through back substitution verification (Table 16).Studies showed that the consistency rate for diagnosing hypertension in children between “Formula Standard ” and “Table Standard ”was close to 95%,and childhood hypertension defined by “Formula Standard ” performed well in predicting the risk of sub-clinical cardiovascular target organ damage (TOD) later in adulthood.[31]In practice,clinicians could use the “Formula Standard” at first to screen children with suspected hypertension and then make a definite diagnosis by age-and sex-specific BP reference“Table Standard ”.

Table 16 Simplified formula standard for screening hypertension in Chinese children and adolescents.

Screening strategies

Domestic and international guidelines on management of hypertension in children have unanimously recommended that elevation of BP screened at one visit should be confirmed by at least 2 more consecutive visits in different days.A strategy to screen hypertension at 3 separate visits in different days was adopted in the China Child and Adolescent Cardiovascular Health (CCACH)survey during 2012–2015 (which recruited 44,396 children aged 6–17 years from Changchun,Beijing,Jinan,Shanghai,Chongqing,and Chengdu) and a school-based survey in 6 provincial administrative units across China(6-PAU survey) during 2018–2019 (which recruited 16220 children aged 12–17 years from Anhui,Hebei,Heilongjiang,Beijing,Jiangsu,and Shandong).[32,33]Both studies found that the prevalence of confirmed hypertension after 3 separate visits declined by more than 50%(78.4% in CCACH survey and 65.1% in 6-PAU survey) in comparison with that of initial hypertension at the first visit.Although the prevalence of initial hypertension varied by Chinese references 2017 and American Academy of Pediatrics (AAP) 2017 at the first visit,the prevalence of confirmed hypertension after 3 separate visits in different days came close (3.7%vs.3.3% in CCACH survey and 8.4%vs.5.9% in 6-PAU survey)(Figure 10).Therefore,a strategy to screen childhood hypertension at 3 separate visits in different days would be helpful to learn the precise prevalence of hypertension among Chinese population aged <18 years.

Figure 10 Prevalence of hypertension among Chinese children at 3 separate visits in different days. Chinese references 2017 refers to “Blood Pressure References by Age and Height for Chinese Children Aged 3–17 Years” published in 2017.[30] AAP 2017 refers to“United States Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents” updated by American Academy of Pediatrics (AAP) in 2017.[34]

Secondary hypertension

Up to now,the reports on the etiology of secondary hypertension in Chinese children all come from singlecenter retrospective analysis of inpatient medical records.Data of 1,470 pediatric inpatients who were discharged with a diagnosis of hypertension from Beijing Children’s Hospital during 2015–2020 were analyzed in a retrospective study.[35]It was found that secondary hypertension accounted for more than half (68.8%) of hospitalized children with hypertension,with renal disease being the leading cause (46.3%),followed by rheumatic autoimmune,hematologic,tumor and CVD.Other causes,including medications,toxicity and infection,accounted for 12.4% of the cases.

Prevalence and characteristics of hypertension in children

Prevalence

Data of 197,191 Han nationality participants aged 7–17 years from CNSSCH 2010 indicated that the prevalence of hypertension was 14.5% among Chinese school-aged children.[36]It was higher in boys than in girls (16.1%vs.12.9%) and increased with age (P<0.001) (Figure 11).

Figure 11 Prevalence of hypertension among Chinese children and adolescents by age in 2010.

Secular trends

According to the data from 9 waves of CHNS 1991–2015,[37]the overall age-standardized prevalence of hy-pertension among Chinese school-aged children in surveillance areas rose from 8.5% in 1991 to 19.2% in 2015(Figure 12).Isolated diastolic hypertension (IDH) accounted for the largest share (over two thirds) of hypertension phenotypes,and the prevalence increased from 6.2% to 14.1% over 25 years.

Figure 12 Trends in the prevalence of hypertension among Chinese children and adolescents aged 7-17 years during 1991-2015.

Influencing factors of hypertension in children

Overweight and obesity

Obesity is the most common risk factor for primary hypertension in children.Data of 943,128 Chinese children and adolescents aged 7–17 years (boys 49.7%) were obtained from CNSSCH 1995–2014.[38]The population attributable risk (PAR) for hypertension because of overweight and obesity steadily increased from 6.3% in 1995 to 19.2% in 2014.The PAR for systolic hypertension because of overweight and obesity was always 2-fold greater than that for diastolic hypertension (7.4%-26.2%vs.6.2%-13.4%) (Figure 13).This study implied that the management of childhood hypertension should focus on the overweight and obese children.

Figure 13 Trends in the PAR for hypertension because of overweight and obesity in Chinese children during 1995–2014.Logistic regression model was used to adjust for age,sex,height,area and economic status.PAR: population attributable risk.

Dietary nutrition and metabolic diseases

Breastfeeding duration A study recruited 57,201 participants aged 7–18 years (51.6% boys) from 7 provincial administrative units (Chongqing,Hunan,Guangdong,Liaoning,Ningxia,Shanghai,and Tianjin) across China in 2012 to investigate the associations between breastfeeding duration and hypertension in children and adolescents.[39]After full adjustment for confounders,such as sex,age,birth weight,overweight/obesity status,dietary behaviors,and physical activity,compared to the non-breastfeeding group,breastfeeding for 6–12 months was associated with a 13% lower odds of hypertension (OR=0.87,95% CI: 0.76–0.99),while prolonged breastfeeding (>12 months) with a 21% higher odds (OR=1.21,95% CI: 1.08–1.37).No significant association was found between breastfeeding for 0-5 months and the odds of hypertension (OR=0.94,95% CI:0.82–1.07).

Dietary habitsA study was performed among 15,268 primary school children aged 6–12 years (52.0%boys) in Chongqing city to determine the efficacy of nuts intake on BP.[40]After adjustment for confounders,such as sex,age,BMI,and dietary patterns,50–100 g/d of nuts intake was associated with the lowest BP.Compared with the 50–100 g/d group,the >100 g/d or <50 g/d nuts intake groups had 2–11 mmHg higher BP levels.A total of 10,536 children and adolescents aged 7–18 years(48.6% boys) were enrolled in a cross-sectional study in Guangzhou City to explore the associations between soy food intake and hypertension in 2018.[41]The adjusted OR of hypertension among the participants with a high frequency of all soy food intake (>3 times/week) was decreased by 17% (OR=0.83,95% CI: 0.70–0.97) compared to those with low intake (0–1 times/week).

HyperuricemiaData of 8,807 children aged 6–16 years in Beijing were obtained from a 2-year follow-up cohort study,School-based Cardiovascular and Bone Health Promotion Program (SCVBH),to investigate the relationship of uric acid (UA) with the incidence risk of hypertension.[42]The UA increased by 1-SD,the risk of hypertension increased by 17% (OR=1.17,95% CI:1.09–1.27).In comparison with the normal group (UA was normal at both baseline and follow-up),the risk of hypertension increased by 32% (OR=1.32,95% CI:1.09–1.60) for newly diagnosed hyperuricemia group(UA was normal at baseline,but elevated at follow-up)and by 50% (OR=1.50,95% CI: 1.05–2.16) for the persistent hyperuricemia group (UA was elevated at both baseline and follow-up),while that in the reversal group(UA was elevated at baseline,but normal at followup) was not increased (OR=0.99,95% CI: 0.51–1.90).

Physical fitness

Good physical fitness can protect the cardiovascular system.Data on physical fitness and BP of 214,301 school students aged 7–18 years (50.0% boys) were extracted from CNSSCH 2014.[43]Six components of physical fitness (forced vital capacity,standing long jump,sit-andreach,body muscle strength,50 m dash and endurance running) were measured,standardized,and aggregated as a summary physical fitness indicator (PFI).The odds of hypertension were inversely associated with physical fitness.They decreased by 13%–32% in the PFI groups of P20 to ≥ P90 compared to the group of PFI

Figure 14 Odds of hypertension in children and adolescents based on PFI percentile categories.Odds of hypertension were calculated after adjustment for the age,sex,region,socioeconomic status,and nutrition status.

Environmental factors

Air pollutantsA cross-sectional investigation was conducted in 2013 among 37,610 participants aged 7–18 years from 7 provincial administrative units in China and analyzed the association of childhood hypertension with long-term exposure to PM2.5and its major components [black carbon (BC),organic matter (OM),inorganic nitrate (NO3-),sulfate (SO42-),and soil particles(SOIL)].[44]After adjustment for a variety of covariates,per interquartile range (IQR) increment in PM2.5mass and BC levels were significantly associated with a higher prevalence of hypertension.The OR was 1.56 (95% CI:1.08–2.25) for PM2.5and 1.19 (95% CI: 1.04–1.35) for BC.No significant association was observed between hypertension and other 4 major components of PM2.5.

Synthetic compoundsA total of 1,044 children aged 6–8 years from Shenzhen were enrolled in the Environment and Health in Children in the Pearl River Delta study during 2016–2017 to investigate the association between BP and urinary monomethyl phthalate (MMP).[45]After adjustment for a variety of confounders,such as age,sex,BMI,family history of CVD,family income,education level of parents,and dietary habit,for each log unit elevation in urinary MMP,the risk of hypertension in children increased by 103% (OR=2.03,95% CI: 1.32–3.12).

Passive smokingA cross-sectional analysis was performed on the data of above-mentioned 7 provincial administrative units across China in 2013 to investigate the association between exposure to parental smoking and BP in children and adolescents.[46]After adjustment for potential confounders,girls exposed to parental smoking (at least one parent smoked) were more likely to have hypertension compared with those without exposure (OR=1.11,95% CI: 1.02–1.20).No significant association was found in boys (OR=0.93,95% CI:0.86–1.01).A retrospective survey was conducted on the environmental tobacco smoke (ETS) exposure in utero in 9,354 children aged 5–17 years from 7 cities (Liaoyang,Dalian,Benxi,Anshan,Fushun,Dandong,and Shenyang) in Liaoning during 2012–2013.[47]After adjustment for a variety of confounders,such as age,sex,birth weight,BMI,and breastfeeding status,the risk of hypertension in the group of children with ETS exposure in utero was 1.36 times of that in the group without exposure (OR=1.36,95% CI: 1.18–1.57).

Green vegetationGreen vegetation can protect the cardiovascular system of human body from the damage of air pollution by purification and absorption of environmental pollutants.Further analysis was performed on the data of above-mentioned 7 provincial administrative units across China to evaluate the associations between greenness around schools and BP among children and adolescents.[48]Greenness level within 500 m of each school was estimated with 3 satellite-based indices: vegetation continuous fields (VCF),normalized difference vegetation index (NDVI),and soil adjusted vegetation index (SAVI).One IQR increase in greenness was associated with 20%,17%,and 17% reduced prevalence of hypertension for VCF (OR=0.80,95% CI: 0.77–0.82),NDVI(OR=0.83,95% CI: 0.79–0.87),and SAVI (OR=0.83,95%CI: 0.80–0.87),respectively.

Mental disorders

Mental disorders are also risk factors for hypertension in children.A survey was conducted in 2018 students aged 12–18 years (50.6% boys) from junior and senior middle schools in Suzhou to investigate the association between depression and BP.[49]Depression was assessed with the Center for Epidemiologic Studies Depression Scale.After adjustment for age,BMI,and other confounders,the risk of hypertension in the children with depression was increased by 43% (OR=1.43,95% CI:1.02–2.00) compared with those without.

Target Organ Damage in Children with Hypertension

Short-term damage

A total of 7,840 children and adolescents aged 6–17 years (52.1% boys) from Jinan were recruited in CCACH survey at baseline,of whom 333 were diagnosed as hypertensive after 3 separate visits and participated in evaluation of TOD.[50]For hypertensive children,those with overweight and obesity had a higher prevalence of elevated alanine/aspartate aminotransferase (ALT/AST)(8.0%vs.5.7%),left ventricular hypertrophy [defined as left ventricular mass index (LVMI) ≥ age-and sexspecific 95thpercentile values] (36.8%vs.8.0%),and increased carotid intima-media thickness (cIMT,defined as≥ age-and sex-specific 95thpercentile values) (48.8%vs.40.0%) than those with normal weight.Huantai Childhood Cardiovascular Health Cohort Study selected 1,515 children aged 6–11 years at baseline in Zibo City,and 1,183 (78.1%) of the participants with complete data were followed up for 2 years.[51]For children with overweight or obesity at baseline,those in the persistent elevated BP group and those in the incident elevated BP group had a 3.394 g/m2.7(95% CI: 1.689–5.099) and 1.620 g/m2.7(95%CI: 0.188–3.053) higher LVMI,respectively,at follow-up compared with those in the persistent normal BP group.However,this pattern was not observed in children with normal weight at baseline.These studies suggested that hypertensive children with overweight or obesity are more likely to develop TOD.

Long-term damage

Cardiovascular remodelingAmong 2,442 children aged 6–18 years in the Beijing Blood Pressure Cohort Study (BBS),1,259 (51.6%) were followed up over 24 years.[52]Compared to those with normal BP at baseline,children with hypertension were at 2.1 times (95% CI:1.4–3.1) likely to develop hypertension and at 1.5 times(95% CI: 1.1–1.9) likely to develop cardiovascular remodeling [defined as any increased measures of LVMI,carotid-femoral pulse wave velocity (cfPWV) or cIMT)]in adulthood.Further analysis indicated that children with higher BMI or elevated SBP were at 1.24–2.89 times likely to develop cardiovascular remodeling.[53]These findings enhanced the importance of early screening and intervention for the comorbidity of obesity and hypertension in childhood.

Renal damageThe above-mentioned BBS investigated the influence of change in BP status from childhood to adulthood on renal damage.[54]Compared with participants with persistently normal BP from childhood to adulthood,the urinary microalbumin and serum cystatin C in those with elevated BP in both childhood and adulthood increased by 0.324 (95% CI: 0.077–0.571)mg/L and 0.033 (95% CI: 0.001–0.066) mg/L,respectively.In addition,4,623 school children aged 6–15 years were enrolled at baseline Hanzhong Adolescent Hypertension Cohort,and 2,780 (60.1%) of them were followed up for 30 years.[55]BP trajectories were identified as low stable,moderate stable,high stable,and moderate increasing among 2,430 subjects.Compared with the low stable trajectory group,the SBP and DBP moderate increasing trajectory groups had 2.04 (OR=3.04) and 2.38(OR=3.38) times greater odds of experiencing subclinical renal damage in middle age,respectively (Figure 15).Visit-to-visit blood pressure variability (BPV) was assessed by standard deviation (SD) and average real variability (ARV).Further analysis indicated that per 1-unit increase of SD or ARV in SBP and DBP from childhood to adulthood were associated with 0.11–0.16 times higher risk of subclinical renal damage in adulthood (OR=1.11–1.16).[56]

Figure 15 Relationship between blood pressure trajectory from childhood to middle age and risk of subclinical kidney dam-age.Presence of subclinical renal damage was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to-creatinine ratio of at least 2.5 mg/mmol in men and 3.5 mg/mmol in women.Logistic regression model was used to adjust for sex,race,body mass index,heart rate,waist-to-hip ratio,hypertension,diabetes mellitus,hyperlipidemia,smoking,drinking,fasting plasma glucose,serum uric acid,total cholesterol,triglycerides,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol.DBP: diastolic blood pressure;SBP: systolic blood pressure.

Prevention

Prevention strategies for whole population

A national non-randomized controlled trial was conducted in 92 primary and secondary schools of 7 provincial administrative units (Ningxia,Shanghai,Chongqing,Guangdong,Tianjin,Hunan,and Liaoning) to examine the effectiveness of intervention on both obesity and hypertension in Chinese children and adolescents aged 6–18 years.[57]According to the participation willingness,45 schools were allocated to the control group (n=23,175,aged 10.9 ± 3.2 years,50.7% boys) and 47 schools to the intervention group (n=25,702,aged 11.3 ± 3.3 years,50.4% boys).The intervention strategies focused on physical activity and dietary choices,which included:creating a supportive school,family and community environment;developing specialized curriculum and class activities for health lifestyle education;promoting school physical education;and monitoring obesity-related behaviors.Six months later,the prevalence of hypertension decreased by 2.8% in the intervention group and 2.6% in the control group.After adjustment for age,sex,provinces,urban/rural areas,and the baseline disequilibrium for socio-demographic indicators,comprehensive intervention did not significantly affect the BP in all participants (OR=0.92,95% CI: 0.83–1.02).Subgroup analysis revealed that for children aged 6–9 years,the risk of hypertension in the intervention group was reduced by 22% than that in the control group (OR=0.78,95% CI:0.67–0.92).However,no effective results were found in other age groups.It was suggested that a comprehensive health lifestyle intervention targeting different age groups was needed as early as possible in school settings to reduce the risk of childhood hypertension.

On the basis of simple interventions for diet and physical activity,establishment of multi-dimensional metrics(including no smoking,healthy diet,sufficient physical activity,normal BMI,and adequate levels of BP,serum glucose,and lipids) to evaluate cardiovascular health is more meaningful for the primordial prevention of childhood hypertension.CCACH study was conducted among 12,618 children and adolescents aged 6–18 years from Chinese urban areas (Beijing,Changchun,Jinan,Yinchuan,Shanghai,Chongqing,and Chengdu) during 2013–2015.[58]Results showed that only 0.5% of the participants had all 7 ideal health metrics,0.9% had 4 ideal health behaviors (smoking,BMI,physical activity and diet),and 44.2% had 3 ideal health factors [total cholesterol (TC),BP and fasting blood glucose (FBG)].For a single metric,never smoking was the most prevalent health component (90.7%),whereas ideal health diet score was the least (8.7%).At the same time,a cross-sectional study was carried out among 15,583 participants aged 7–17 years in 7 provincial administrative units(Ningxia,Shanghai,Chongqing,Guangdong,Tianjin,Hunan,and Liaoning) across China.[59]It demonstrated that the prevalence of ideal cardiovascular health status was only 1.7% in the Chinese children and adolescents(3.1% for 4 ideal health behaviors and 53.6% for 3 ideal health factors).Therefore,comprehensive interventions to promote health and the concept of primordial prevention should be included in the whole population prevention strategies for childhood hypertension in China.

Prevention strategies for high-risk population

Obesity is the primary risk factor for childhood hypertension and obese children are the high-risk population for management.A non-randomized,controlled intervention study was conducted among 438 overweight and obese children aged 7–12 years (36.1% boys) from 10 primary schools in Beijing.[60]Compared with the notreatment control group,SBP significantly decreased by 4.4 mmHg in the comprehensive intervention group(95% CI: 0.3–8.4 mmHg),and so did DBP by 5.50 mmHg(95% CI: 2.2–8.8 mmHg).No statistical changes of BP were observed in physical activity only group or diet only group.

Summary

Almost half of the children with hypertension would develop adulthood hypertension if interventions were not delivered.With the prevalence of obesity and lifestyle changes,hypertension has become a common cardiometabolic abnormality in Chinese children.The BP levels in about 4% of children keep rising and have met the diagnostic thresholds for hypertension.The prevalence of hypertension at single visit of screening is 14%–20% among children and adolescents.As a key technique for early management of hypertension,the diagnostic criteria for childhood hypertension is one of the hot topics in the field of hypertension.It should be elucidated whether the diagnostic criteria for adulthood hypertension is rational and practical to be used in the teenagers who have been basically mature.If left untreated,childhood hypertension would result in short-and longterm damage in multiple target organs,such as heart,kidney,and vessels.It is urgently needed to implement comprehensive management by prevention of hypertension in the whole population and by prevention of obesity in the high-risk children on the basis of health promotion.

DYSLIPIDEMIA

Epidemiology of Dyslipidemia

Lipid level

Adults

According to the data of 179,728 participants aged ≥ 18 years eligible for analysis in China Adults Nutrition and Chronic Diseases Surveillance in 2015 (CANCDS 2015),the mean levels of TC,low density lipoprotein cholesterol (LDL-C),non-high density lipoprotein cholesterol(non-HDL-C),and triglyceride (TG) were higher than those in 2002 (Figure 16).[61]A total of 1,127 populationbased studies that measured blood lipids in 102.6 million individuals aged ≥ 18 years were pooled by Non-Communicable Disease Risk Factor Collaboration (NCDRisC) to estimate the trends from 1980 to 2018 in mean TC,non-HDL-C and high-density lipoprotein cholesterol (HDL-C) levels for 200 countries.The largest increases in non-HDL-C were found in East Asian countries (for example,China) and Southeast Asian countries.In these countries,age-standardized mean non-HDL-C increased by as much as 0.23 mmol/L per decade.As a result of these trends,China was one of the countries with the lowest average non-HDL-C levels in the world in 1980,and by 2018 it had reached or even surpassed many high-income Western countries.[62]

Figure 16 Trends in lipid level among Chinese adults aged ≥18 years over 13 years. HDL-C: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;Non-HDL-C:non-high-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

Children and adolescents

Children aged 6–18 years were enrolled in Beijing Child and Adolescent Metabolic Syndrome (BCAMS)study.Data of 1,660 participants in 2004 and 1,649 participants in 2014 indicated that the mean TC,LDL-C,non-HDL-C and TG levels in 2014 among children and adolescents were all increased compared with the estimates of 10 years ago (allP<0.001) (Figure 17).[63]

Figure 17 Trends in lipid level among children and adolescents aged 6–18 years in Beijing over 10 years.HDL-C: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;Non-HDL-C: non-high-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

“Nutrition and Health Surveillance among Children and Nursing Mothers in China” program was conducted among 11,474 children aged 12–17 years in 11 provincial administrative units across Western China (except Tibet) during 2016–2017.The level of each lipid was expressed as median and IQR (P25–P75).It was 3.53(3.12–3.97) mmol/L for TC,2.15 (1.80–2.55) mmol/L for non-HDL-C,1.91 (1.57–2.28) mmol/L for LDL-C,1.33(1.13–1.56) mmol/L for HDL-C,and 0.83 (0.64–1.11)mmol/L for TG among the participants.[64]

Prevalence

Adults

Data from CHNS 2002,[65]China National Survey of Chronic Kidney Disease (CNSCKD) 2010,[66]CHNS 2011.[67]and Report on the Status of Nutrition and Chronic Diseases of Chinese Residents 2015 showed that the overall prevalence of dyslipidemia among Chinese adults aged ≥ 18 years increased dramatically.[68]CHS 2012–2015 and China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project(China PEACE MPP) 2014–2019 reported a similar prevalence among the population aged ≥ 35 years (Figure 18).[69,70]Dyslipidemia in above studies was defined as the presence of any lipid abnormalities (including TC ≥6.22 mmol/L,LDL-C ≥ 4.14 mmol/L,HDL-C <1.04 mmol/L,or TG ≥ 2.26 mmol/L) or current use of lipidlowering agents.

Figure 18 Trends in the overall prevalence of dyslipidemia among Chinese adults during 2002–2019.

Results from the 4th CCDRFS 2013–2014,[71]CANCDS 2015,[61]China National Stroke Screening and Prevention Project (CNSSPP) 2014,[72]and China PEACE MPP 2014–2019 showed that low HDL-C and high TG were two major types of dyslipidemia among Chinese residents (Figure 19).[70]A study recruited 8,266 residents aged≥ 18 years in 1997 (38% males) and 9,756 residents in 2018 (43% males) from Shenzhen using multi-stage cluster sampling to investigate the trends of prevalence of dyslipidemia.[73]Over the observed decades,the ageadjusted prevalence of low HDL-C almost doubled in both sexes.It increased from 8.8% in 1997 to 17.5% in 2018 among women,and from 22.1% in 1997 to 39.1% in 2018 among men.The prevalence of high TG increased significantly among men,but not among women.

Figure 19 Prevalence of different forms of dyslipidemia among Chinese adults. HDL-C: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

However,it is noteworthy that the prevalence of borderline dyslipidemia (5.2 ≤ TC <6.2 mmol/L,3.4 ≤ LDLC <4.1 mmol/L,or 1.7 ≤ TG <2.3 mmol/L) was high in CCDRFS and CNSSPP,especially for TC (Figure 20).[71,72]

CCDRFS found that the prevalence peaked at the age of 60–69 years for high TC (10.7%) and high LDL-C(12.3%),at 30–39 years for low HDL-C (22.2%),and at 50–59 years for high TG (17.2%) (Figure 21).[71]

Figure 21 Prevalence of different forms of dyslipidemia among Chinese adults by age.HDL-C: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

CNSSPP demonstrated that compared with urban participants,rural residents had a higher prevalence of high TC,high LDL-C,and high non-HDL-C (allP<0.001),but a lower prevalence of low HDL-C (P<0.001).[72]The prevalence of high TG was comparable between rural and urban adults (P>0.05) (Figure 22).

Figure 22 Difference in prevalence of different forms of dyslipidemia among Chinese adults between urban and rural areas.HDLC: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;Non-HDL-C: non-high-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

CHS and CNSSP revealed that among Chinese residents,the prevalence of high TC and high LDL-C was significantly higher in women than in men,whereas the prevalence of low HDL-C and high TG was higher in men than in women except that the prevalence of high TG was slightly higher in rural women than in rural men(Figure 23).[69,72]

Figure 23 Difference in prevalence of different forms of dyslipidemia among Chinese adults by sex.HDL-C: high-density lipoprotein cholesterol;LDL-C: low-density lipoprotein cholesterol;Non-HDL-C: non-high-density lipoprotein cholesterol;TC: total cholesterol;TG: triglycerides.

Regional epidemiological surveys indicated that except for high TC in the residents of Northeastern China and high TG in the residents of Inner Mongolia,the prevalence of other forms of dyslipidemia in the two regions and that of all forms of dyslipidemia in Southwestern China (Chengdu and Chongqing) were all lower than the national estimates (Table 17).[69,70,72,74–76]

Table 17 Comparison of the prevalence of dyslipidemia in different regions with the national estimates in China.

Prevalence of familial hypercholesterolemia

General populationFrom September 2015 to August 2020,based on a typical case sampling design,China PEACE MPP screened 3,784,344 participants aged 35–75 years from 295 sites (176 rural counties and 119 urban districts) in 31 provincial administrative units across China.A total of 1,059,936 participants with complete information like LDL-C levels and family history of premature atherosclerotic cardiovascular disease (ASCVD) were included in the final analysis.Familial hypercholesterolemia (FH) was diagnosed according to the criteria from “Chinese Expert Consensus on Diagnosis of Familial Hypercholesterolemia” (CEFH criteria) in 2018.The overall prevalence of FH was 0.13% (about 1 in 769).[77]

Special populationFrom January 2013 to October 2014,China Acute Myocardial Infarction (CAMI) Registry consecutively enrolled 13,002 patients aged 18–80 years and with first-onset AMI who were naive to statin before admission.According to the Dutch Lipid Clinical Network Criteria (DLCNC),the prevalence of definite/probable FH was 0.47% (1 in 213).[78]In 2012,Dyslipidemia International Study-China (DYSIS-China) database included 23,973 out-patients with dyslipidemia who were aged ≥ 45 years and received at least one lipidlowering drug for at least 3 months.According to DLCNC,the prevalence of definite/probable FH was 0.5% (1 in 200) among the participants.[79]Based on the data of China PEACE MPP and according to the CEFH criteria,FH was screened in 26,732 patients with CAD (defined as self-reported history of AMI or coronary revascularization) and in 18,147 patients with ischemic stroke (defined as self-reported history of ischemic stroke that was diagnosed by doctors).The overall FH prevalence was 0.41% (1 in 244) in the patients with CAD and 0.35% (1 in 286) in those with ischemic stroke.[80,81]

Children and adolescentsThe diagnostic criteria of dyslipidemia for Chinese children were updated with the “Expert Consensus on Diagnosis and Management of Dyslipidemia in Children 2022”.[82]LDL-C 2.84–3.36 mmol/L is defined as borderline high,and ≥ 3.36 mmol/L as high.HDL-C 1.03–1.16 mmol/L is defined as borderline low,and <1.03 mmol/ L as low.For children aged ≤ 9 years,TG 0.84–1.12 mmol/L is defined as borderline high,and ≥ 1.12 mmol/L as high.For children aged ≥ 10 years,TG 1.01–1.46 mmol/L is defined as borderline high,and ≥ 1.46 mmol/L as high.

Table 18 shows the prevalence of dyslipidemia among Chinese children in different regions.[64,83,84]Dyslipidemia was determined by the definition of “Expert Advice on Prevention and Treatment of Dyslipidemia in Children and Adolescents” in 2009,i.e.,TC ≥ 5.18 mmol/L,LDL-C≥ 3.37 mmol/L,HDL-C ≤ 1.03 mmol/L,TG ≥ 1.7 mmol/L,and non-HDL-C ≥ 3.75 mmol/L.

Table 18 Prevalence of dyslipidemia among Chinese children in different regions.

Awareness,treatment and control of dyslipidemia

Population with hypercholesterolemia

China National Diabetes and Metabolic Disorders Study (CNDMDS) was conducted among 46,239 adults aged ≥ 20 years from 2007 to 2008.[85]For the participants who had hypercholesterolemia,including high TC (≥6.22 mmol/L),high LDL-C (≥ 4.14 mmol/L),borderline high TC (5.18 ≤ TC <6.21 mmol/L),or borderline high LDL-C (3.37 ≤ LDL-C <4.14 mmol/L),or who reported using cholesterol-lowering drugs,the rates of awareness,treatment,and control were very low.This scenario was even worse in rural residents than in urban citizens (Figure 24) and in women than in men (Figure 25).

Figure 24 Difference in awareness,treatment,and control of dyslipidemia among Chinese adults with hy-percholesterolemia between urban and rural areas.TC: total cholesterol.

Population with type 2 diabetes mellitus

A retrospective study was conducted using the data of 942,847 outpatients aged ≥ 18 years with T2DM (53.2%men and 46.8% women) from serial cross-sectional surveys of China National HbA1c Surveillance System(CNHSS) during 2009–2013.The overall age-standardized prevalence was 43.80% for adequate LDL-C control(<2.6 mmol/L) and 44.68% for adequate TG control(<1.7 mmol/L).[86]

Population with high-or very high-risk of ASCVD

The 10-year risk for first occurrence of ASCVD was assessed in China PEACE MPP according to the recommendations by “2016 Chinese Guideline for the Management of Dyslipidemia in Adults”.[70]Results showed that 236,579 subjects (accounting for 10.2% of the total participants) had high-risk of ASCVD and 42.9% of them achieved LDL-C target (<2.6 mmol/L).The control rate was lower in women than in men (36.47%vs.49.81%).Among participants with high-risk of ASCVD and inadequate LDL-C control,only 4.5% were treated with lipidlowering drugs.In addition,71,785 subjects (accounting for 3.2% of the total participants) had very high risk of ASCVD,of whom 14.1% were treated with any lipidlowering drugs and 26.6% achieved LDL-C target (<1.8 mmol/L).The control rate was lower in women than in men (22.22%vs.30.99%) and was 44.8% among those who were treated.FH is a lifelong high risk of ASCVD.Base on the CEFH criteria,1,383 FH patients were identified out of 1,059,936 participants in China PEACE MPP.The rate of treatment with lipid-lowering drugs was 18.1% among them.None of the treated patients achieved LDL-C target (<1.8 mmol/L).[77]

Improving Care for Cardiovascular Disease in China(CCC) project enrolled 80,282 patients with ACS from 192 participating hospitals nationwide,and 6,523 of them had a history of MI or coronary revascularization.Among the 6,523 patients,50.8% were receiving lipidlowering therapy before hospitalization.In patients receiving prehospital statins,36.1% achieved LDL-C target(<1.8 mmol/L).[87]For the patients aged ≥ 75 years,the scenario was even worse.Only 33.9% of them received statins before hospitalization and 24.7% had LDL-C <1.8 mmol/L.[88]Dyslipidemia International Study II (DYSIS II)-China enrolled 1,103 patients who were hospitalized in cardiology departments for ACS from 28 tertiary hospitals between September 2017 and May 2019.[89]The LDL-C target (<1.8 mmol/L) was achieved in 41.2% of 752 patients who were on lipid-lowering therapy and with available lipid results at the 6-month follow-up(Figure 26).

Figure 26 Treatment rate with lipid-lowering drugs and LDLC control rate among Chinese population with ASCVD for secondary prevention.LDL-C: low-density lipoprotein cholesterol.

Ischemic strokePatients who had an ischemic stroke within 6–12 months were consecutively enrolled in a nationwide,multi-center,cross-sectional study from July 2013 to August 2013.[90]In all of 3,956 cases,although 79.6% received lipid-lowering drugs (statin in 97.6%),the total LDL-C control rate was still very low (27.4%) (Figure 26).

Risk Factors of Dyslipidemia

Epidemiological studies have reported that the following risk factors might be associated with dyslipidemia.

Secular trend of energy intake distributionData of 2,483 participants without dyslipidemia at baseline from the CHNS 1991–2018 were analyzed.Four trajectory groups of energy intake distribution were identified by multi-trajectory model over 27 years: “Energy evenly distributed group” (Group 1),“Lunch and dinner energy dominant group” (Group 2),“Dinner energy dominant group” (Group 3),“breakfast and dinner energy dominant group” (Group 4).Findings from a 9-year follow-up indicated that compared with Group 1,Group 3 was associated with a higher risk of dyslipidemia (RR=1.48,95% CI: 1.26–1.75),hypercholesterolemia (RR=1.96,95% CI: 1.37–2.81) and high LDL-C (RR=2.41,95% CI:1.82–3.20).[91]

Risk factors of low HDL-CA retrospective cohort study was conducted among 26,863 urban Han adults aged ≥ 18 years with records of at least 2 health check-ups over more than 1 year from 2010 to 2015.Exclusion criteria were participants with diagnosis of dyslipidemia,DM,CVDs,hepatosis,renal insufficiency or thyroid diseases on their health examination report.Results showed that men,age >65 years,BMI,TG and urea nitrogen were significant risk factors of low HDL-C.[92]A prospective study enrolled 34,260 participants without a history of dyslipidemia at baseline from the general Chinese population and followed them up every 2 years.Compared with a 7 h of sleep per night,long sleep duration (≥ 9 h) was significantly associated with a 24%higher risk of low HDL-C (HR=1.24,95% CI: 1.12–1.38).[93]

Environmental factorsA survey was conducted among 15,477 adults in Northeast China.The average PM0.1 concentration during 2006–2009 was simulated using the neural network model.After adjustment for confounders,each IQR increase in PM0.1 concentration was associated with an OR of 1.25 for overall dyslipidemias,1.41 for hypercholesterolemia,and 1.90 for hyperbetalipoproteinemia.[94]

Risk factors of dyslipidemia in childrenData from a multi-center school-based obesity intervention program 2012–2013 indicated that sugary drinks intake ≥ 1 time per week,sedentary time ≥ 10 h per day,overweight and obesity were significantly associated with the risk of dyslipidemia among children and adolescents aged 6–17 years.[83]Further analysis indicated that the prevalence of hypercholesterolemia was higher in only children than in children with siblings (5.48%vs.4.43% for high TC and 3.97%vs.2.96% for high LDL-C,allP<0.01).A higher risk of high LDL-C was found in only children after adjustment for covariates.[95]A national survey was conducted among 12,814 children aged 7–18 years in 2013.Satellite-based spatial temporal model was used to predict 3-year (2011–2013) average concentration of air pollutants.Findings indicated that the ORs of hypercholesterolemia were 2.15,1.70,and 1.43 for a 10 μg/m3increase in PM1,PM2.5,and NO2,respectively.[96]A sample of 14,755 children and adolescents aged 5–19 years were recruited in a cross-sectional survey from 7 provincial administrative units across China.Information regarding fruit consumption and other characteristics was collected by questionnaires.Participants who consumed fruits for 6–7 days per week had lower risks of high TG,dyslipidemia (defined as high LDC-C,low HDL-C,high TG,or high TC),and hyperlipidemia (defined as high TG or high TC) compared to fruit consumption of 0–2 days per week.[97]A study recruited 3,551 children and adolescents aged 6–18 years in Shandong using a multistage stratified cluster sampling method.Food Frequency Questionnaire (FFQ) was used to obtain the data of dietary factors.It was found that serum vitamin A was positively correlated with HDL-C.[98]A retrospective survey collected information on 12,701 children aged 5–6 years from electronic healthcare records.The risk of childhood hyperlipidemia was 33% higher in the participants with low birth weight than in those with appropriate birth weight.[99]

Cardiovascular Hazards of Dyslipidemia

Association between high LDL-C and ASCVDAccording to the data of GBD in 2019,61% of the burden of CVD was caused by ASCVD in China.Hypertension[theoretical minimum risk exposure level (TMREL) for SBP: 110–115 mmHg] remained the leading risk factor for ASCVD,followed by high LDL-C (TMREL: 0.7–1.3 mmol/L).[100]A prospective cohort study recruited 904 consecutive Chinese patients with ischemic stroke in Hong Kong between 2008 and 2014.Magnetic resonance angiography of the intra-and cervicocranial arteries was performed and serial post-event LDL-C measurements were obtained.The patients were followed up for a mean of 6.5 years.Results showed that the mean postevent LDL-C <1.80 mmol/L was associated with a lower risk of MACE.Similar findings were noted in patients with or without significant large-artery disease (≥50% vascular stenosis in any intra-or extra-cranial artery),with any subtype of ischemic stroke,and with age

Association between high non-HDL-C and CVDA cohort of 47,262 participants from Prospective Urban Rural Epidemiology study in China (PURE-China) were followed up for a median duration of 11.9 years.Results showed that high non-HDL-C was the third metabolic risk factor for CVD (PAF of 7.8%),next to hypertension and low education.As for MI,high non-HDL-C was the second risk factor (PAF of 11.0%),next only to hypertension.Compared with non-HDL-C ≤ 3.2 mmol/L,non-HDL-C >4.0 mmol/L was associated with an adjusted HR of 1.26 for CVD,1.42 for MI,and 1.25 for stroke.[102]

Association between HDL-C and first ischemic strokeA nested case-control study was conducted among 2,463 first incident cases of ischemic stroke and 2,463 controls.The participants were hypertensive patients from the “H-type Hypertension Prevention and Control Public Service Project (HHPCP)”.They were matched by age,sex,and region.None of them had a history of stroke at baseline.After adjustment for potential confounders,HDL-C,as a continuous variable or a categorical variable in tertiles,was inversely associated with first ischemic stroke.Compared to HDL-C <1.37 mmol/L,HDL-C ≥ 1.69 mmol/L was associated with a significant reduction of first ischemic stroke by 18%.However,this association was no longer present when HDL-C was categorized according to the current clinical criteria.An increased risk of first ischemic stroke was only found in the presence of low HDL-C (<1.37 mmol/L) when LDL-C and TG were combined with HDL-C for analysis.The adjusted ORs were 1.66 for LDL-C >3.58 mmol/L and 1.47 for TG >1.59 mmol/L.[103]

Association between triglyceride-glucosey index and first ischemic strokeTriglyceride-glucosey (TyG) index=Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2].A total of 11,777 participants aged ≥ 40 years living in Xin’an county in Luoyang,Henan Province were enrolled in the Rural Chinese Cohort Study during 2007–2008.They were free of stroke and CVD at baseline and were followed up for a median of 6 years.It was found that the risk of ischemic stroke increased with each TyG index quartile.Compared with TyG Q1 group,the adjusted RRs were 1.33,1.57 and 1.95 in Q2,Q3 and Q4 groups,respectively.[104]

Association between TC variability and cognitivefunctionTC levels and cognitive function were assessed among 6,377 participants in 2 waves of CHARLS(2011 and 2015).TC variability was defined as the intraindividual standard deviation over two blood tests.After adjustment for potential confounders,higher visit-tovisit TC variability was associated with a lower cognitive function in middle-aged and elderly men,but not in women.[105]

Intervention Measures,Significance and Guidelines for Dyslipidemia

Evidence of clinical trial on new lipid-lowering drugsA multi-center,randomized,placebo-controlled trial was conducted among 248 patients with high TG(2.26 mmol/L

Evidence of lipid-lowering therapy in real worldA total of 99,655 adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥ 2 prescriptions of statins from 2012 through 2013 were divided into primary (n=34 372) and secondary (n=65,283) prevention subgroups in a retrospective study.Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up.The mean PDC of all statin users was 0.20,65.5% patients with PDC <0.20,and only 5.9% patients with PDC ≥0.50.The patients with PDC ≥ 0.5 had a 37% lower risk of 2-year MACE compared with those with PDC <0.50.Findings from this study suggested that statin adherence was very poor in both primary and secondary prevention of CVD in China and highlighted the importance of improving this situation.[107]A total of 104,516 inpatients with ACS from multiple centers were recruited in the CCC project during 2014–2019.Among them,75.1% met the criteria of extreme high-risk,which was proposed by“Chinese Expert Consensus on Lipid Management of Extreme High-risk ASCVD Patients” of Chinese Society of Cardiology (CSC).Only 6.6% of the extreme high-risk patients achieved LDL-C target (<1.4 mmol/L).Among 40,875 patients with information about discharge prescription,95.1% received statin monotherapy.[108]Data from DYSIS II-China indicated that among 752 ACS patients on lipid-lowering therapy and with available lipid results at the 6-month follow-up,58.8% failed to achieve the LDL-C target,the distance to target was 0.7 ± 0.7 mmol/L,and 91.4% received statin monotherapy.[89]The latter two studies suggested that the strategies to achieve LDL-C target among patients with ASCVD should be optimized in China and the combination therapy was insufficient to lower lipid in the clinical practice.

New guidelines,consensus,and recommendations“Expert Consensus on the Comprehensive Management of Blood Pressure and Dyslipidemia in Chinese Hypertensive Patients” was released by Hypertensive Group of Chinese Society of Cardiology of Chinese Medical Association in 2021.[109]It stressed that all hypertensive patients should be assessed for the risk of ASCVD in addition to management of hypertension.The LDL-C target should be determined and managed to achieve according to the risk stratification.In the same year,“Expert Statement on the Relationship Between Lipoprotein (a)and Cardiovascular Disease Risk and Clinical Management” was published by Beijing Heart Association.[110]It suggested that lipoprotein (a) ≥ 30 mg/dL (or 75 nmol/L)should be regarded as the cutoff point to increase the risk of CVD,and specifically pointed out that comprehensive management of CVD risk should be reinforced for patients with high lipoprotein (a) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor should not be recommended if the primary goal was to reduce lipoprotein (a).“Chinese Expert Consensus on non-Traditional Blood Lipid Parameters to Control the Risks of Arteriosclerotic Cardiovascular Disease” was issued by the Specialist Committee on Laboratory Medicine of Chinese Association of Integrative Medicine in 2022.[111]It made recommendations for the detection and clinical application of non-HDL-C,ApoB,lipoprotein (a),lipoprotein residue,and non-fasting blood lipid.

Summary

The lipid level and prevalence of dyslipidemia among Chinese adults and children demonstrate an upward trend.Among individuals aged ≥ 18 years,the prevalence is 5.8% for high TC,7.2% for high LDL-C,24.9% for low HDL-C,and 15% for high TG.High TG and low HDL-C are the major types of dyslipidemia among children aged 6–17 years,with the prevalence of 15.7% and 13.5%,respectively.The prevalence of FH is 0.13% (about 1 in 769) among adults aged 35–75 years.The awareness,treatment,and control of hypercholesterolemia are very low among Chinese adults.This scenario is even worse in rural residents than in urban citizens and in women than in men.High LDL-C is the 2nd risk factor for ASCVD in China,but the control rate remains quite low in the population with high-or very high-risk of ASCVD.China has a high rate of statin monotherapy and a low rate of combined lipid-lowering therapy.It is urgent to optimize lipid-lowering strategies to improve the achievement of LDL-C target.Large scale clinical trials on lipid-lowering therapy are insufficient in China.They should be performed on new drugs among specific population in multi-centers and provide high-quality clinical evidence to improve the management of ASCVD.

DIABETES MELLITUS

Prevalence of Diabetes and Prediabetes in Chinese Population

The prevalence of diabetes in Chinese population is increasing significantly (Figure 27).A cross-sectional studyamong 75,880 participants aged ≥ 18 years across 31 provincial administrative units in China from 2015 to 2017 showed that the weighted prevalence rates of total diabetes,[112]self-reported diabetes,newly diagnosed diabetes,and prediabetes diagnosed by the American Diabetes Association (ADA) criteria were 12.8% (95% CI:12.0%–13.6%),6.0% (95% CI: 5.4%–6.7%),6.8% (95% CI:6.1%–7.4%),and 35.2% (95% CI: 33.5%–37.0%),respectively.It was higher among adults aged ≥ 50 years and among men.The prevalence of total diabetes in 31 provincial administrative units ranged from 6.2% in Guizhou to 19.9% in Inner Mongolia.Han ethnicity had the highest prevalence of diabetes and Hui ethnicity had the lowest among 5 investigated ethnicities.According to the WHO diagnostic criteria,the weighted prevalence of total diabetes was 11.2% (95% CI: 10.5%–11.9%) in China.The total number of patients with diabetes in China is estimated to be 129.8 million (70.4 million men and 59.4 million women).The proportion of patients who were aware of their diabetes was higher in the older population,and the proportion of patients who controlled their HbA1c levels well was higher in younger urban residents.

Figure 27 Prevalence of diabetes in China in previous surveys. ＊Prevalence of diabetes in urban residents.

Cardiovascular Risk in Patients with Diabetes

Using the national Hospital Quality Monitoring System (HQMS) database,the prevalence of microvascular and macrovascular complications among inpatients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in tertiary hospitals in China was evaluated.[113]A total of 92,413 inpatients with T1DM and 6,094,038 inpatients with T2DM were enrolled for analysis.The proportions of inpatients with macrovascular complications in inpatients with T1DM and T2DM increased from 7.3% and 14.5% in 2013 to 13.2% and 18.4%in 2017,respectively.The proportions of inpatients with microvascular complications in inpatients with T1DM and T2DM increased from 29.9% and 19.0% in 2013 to 31.6% and 21.0% in 2017,respectively.Hypertension and hyperlipidemia were risk factors for both microvascular and macrovascular complications.Among inpatients with T1DM,the adjusted ORs of microvascular complications increased in 40–49 age group and Northeast region,while older age,male and North region were risk factors for macrovascular complications.Among inpatients with T2DM,the OR of microvascular complications increased in 40–49 age group,female,urban and North region,while older age,male,urban and Southwest region were risk factors for macrovascular complications.

Some scholars used the data from the basic medical insurance database for urban employees in Beijing to monitor the incidence of ischemic stroke in patients newly diagnosed with T2DM between 2010 and 2017 with a prospective design method.[114]A total of 185,813 newly diagnosed T2DM patients were enrolled,with an average age of (58.5 ± 13.2) years,and 49.0% were male.During 7-year follow-up,10,393 newly diagnosed ischemic stroke occurred,with a cumulative incidence of 5.6%.The cumulative incidence increased with age (P<0.05).It was 1.5% (95% CI: 1.3%–1.6%) in group ≤ 44 years old,3.6% (95% CI: 3.4%–3.7%) in group 45–54 years old,5.4% (95% CI: 5.2%–5.5%) in group 55–64 years old and 9.2% (95% CI: 9.0%–9.4%) in group ≥ 65 years old.The cumulative incidence was higher in males(6.8 %,95% CI: 6.7%–7.0%) than in females (4.4%,95% CI:4.3%–4.6%).Among patients <80 years old,the cumulative incidence was higher in males than in females in all age groups,but in group ≥ 80 years old,females had a higher cumulative incidence than males (9.2%vs.7.9%).Further analysis revealed that coronary artery disease(CAD) (OR=3.18,95% CI: 2.72–3.72),heart failure (OR=1.53,95% CI: 1.32–1.79) and renal failure (OR=1.45,95%CI: 1.20–1.75) were associated with ischemic stroke in patients with T2DM.

The prevalence of CAD and cardiovascular risk factors in Chinese patients with T2DM was investigated among 30,693 inpatients with T2DM treated from 2013 to 2018.[115]The crude prevalence of CAD was estimated to be 23.5% and age-standardized prevalence based on data from the Chinese population census in 2010 was 13.9%(16.0% in men and 11.9% in women).More than half of patients with CAD have four or more of the five traditional risk factors.The diabetes duration,hypertension,smoking,underweight,overweight,obesity and hypoglycaemia were significantly associated with increased risk of CAD (allP<0.05).The ORs of CAD in patients with three,four and five defined CAD risk factors (i.e.,diabetes,hypertension,dyslipidemia,overweight or obese,and smoking) were 2.35 (95% CI:1.81–3.04),2.96 (95% CI: 2.28–3.85) and 5.29 (95% CI:4.04–6.93),compared with diabetes patients without any other risk factors.

Lifestyle Interventions to Prevent Diabetic Cardiovascular Complications

Da Qing Diabetes Prevention Outcome Study is the earliest and longest lifestyle study on lifestyle intervention to prevent diabetes in the world.577 adults with impaired glucose tolerance (IGT)diagnosed by use of 75 g oral glucose tolerance tests from 33 clinics in China were randomized to the control group or one of the three lifestyle intervention groups (diet,exercise,diet plus exercise) and the intensive lifestyle intervention lasted from 1986 to 1992.During the 30-year follow-up,compared with control,the combined intervention group had a median delay in diabetes onset of 3.96 years,26% fewer cardiovascular disease events (HR=0.74,95% CI:0.59–0.92),35% lower incidence of microvascular complications (HR=0.65,95% CI: 0.45–0.95),33% fewer cardiovascular disease deaths (HR=0.67,95% CI:0.48–0.94),26% fewer all-cause deaths (HR=0.74,95% CI:0.61–0.89),and an average increase in life expectancy of 1.44 years.The cumulative incidence of stroke and severe retinopathy was 25% (HR=0.75,95% CI: 0.59–0.96) and 40% (HR=0.60,95% CI: 0.38–0.95) lower in the intervention group than in the control group,as were the incidence rates of CAD,hospitalization for heart failure,nephropathy and neuropathy,though which did not reach significant differences.[116]These new findings provide further evidence that lifestyle intervention for people with IGT can reduce chronic complications of diabetes and diabetes related mortality (Figure 28).

Figure 28 Comparison of CVD events (A) and CVD mortality (B) between lifestyle intervention group and con-trol group during the 30-year follow-up in Da Qing Diabetes Prevention Outcome Study (1986–2016).CVD: cardiovascular disease.

Da Qing Diabetes Prevention Outcome Study published new results in 2021.[117]At the end of the 6-year trial,of 540 participants with IGT,252 participants had developed diabetes,114 had remained with IGT and 174 had regressed to normal glucose tolerance (NGT).Participants were then followed for 24 years after completion of the trial.Compared with those who developed diabetes during the trial,the median time to onset of diabetes was delayed by 14.9 years in the NGT and 9.9 years in the IGT groups.After completion of the trial,among those with diabetes,IGT and NGT,the 24-year cumulative incidence of CVD was 64.5%,48.5% and 45.1%,respectively.Compared with participants who had progressed to diabetes during the trial,those who regressed to NGT had a 37% (HR=0.63;95% CI: 0.47–0.85) reduction in CVD incidence,and those who remained with IGT had a 34% (HR=0.66;95% CI: 0.47–0.91) lower CVD incidence.The study suggested that people with IGT who reverted to NGT or remained with IGT by lifestyle intervention had significantly lower incidence of CVD than those who had developed diabetes (Figure 29).

Figure 29 24-year cumulative incidence of first CVD events --30-year results of the Da Qing Diabetes Prevention Outcome Study (1986–2016). CVD: cardiovascular disease;DM: diabetes mellitus;IGT: impaired glucose tolerance;NGT: normal glucose tolerance.

Guidelines,Consensus and Suggestions

In May 2021,the Expert Consensus on the Diagnosis and Treatment of Diabetes Patients with CVD was published,[118]which was elaborated from the perspective of CVD and diabetes management,covering the diagnosis,drug treatment and risk factor management of diabetes patients with CVD [mainly including atherosclerotic cardiovascular disease (ASCVD) and heart failure],aiming to strengthen the comprehensive management of patients and ultimately improve the prognosis of patients.The management of CVD mainly includes blood pressure and blood lipid control,antithrombotic therapy,antimyocardial ischemia,and anti-ventricular remodeling.The management of diabetes mainly includes lifestyle intervention,glucose-lowering treatment,blood glucose monitoring and treatment,and hypoglycemia prevention.The glucose-lowering pathway for T2DM patients with CVD is outlined in Figure 30.

In recent years,due to the ample evidence of cardiovascular benefits provided by cardiovascular outcome trials of novel glucose-lowering drugs such as GLP-1RA and SGLT2i,some international guidelines have successively updated the recommended content.The European Society of Cardiology (ESC) 2019/European Association for the Study of Diabetes (EASD) guidelines took the lead in proposing that for newly treated T2DM patients,if ASCVD or high-risk/very high-risk cardiovascular risk is complicated,SGLT2i or GLP-1RA monotherapy is preferred.[119]When HbA1c is above the target,Metformin should be used in combination.If there is no concomitant ASCVD or high-risk/very highrisk cardiovascular risk,Metformin remains the first line of choice.For T2DM patients who have already received Metformin treatment and have concomitant ASCVD or high-risk/very high-risk cardiovascular risk,SGLT-2i or GLP-1RA should be used in combination,irrespective of HbA1c levels.

In 2022,the American Diabetes Association (ADA)/EASD consensus on hyperglycemia management updated the treatment pathway for T2DM to recommend different “treatment goals” according to the patient’s own characteristics.[120]Treatment goal 1: T2DM patients with high risk of heart and kidney disease,with the goal of “reducing adverse events of heart and kidney disease”;Treatment goal 2: T2DM does not involve high-risk individuals with heart and kidney disease,with the goal of achieving and maintaining blood glucose and weight standards.

Summary

The treatment strategy of T2DM should be comprehensive,including the control of blood glucose,blood pressure,blood lipid and body weight,antiplatelet treatment and lifestyle modification.CVD is the main cause of disability and death in T2DM.Diabetes patients need comprehensive treatment for cardiovascular risk factors,which is the main measure to reduce cardiovascular events.In addition to the population of diabetes ranking first in the world,the population of prediabetes in China accounts for one third of the total population.For this part of the population,we should actively respond to the national strategy of moving forward the threshold of chronic disease prevention and control and carry out lifestyle intervention to prevent diabetes and subsequent long-term cardiovascular complications,reduce mortality,improve people’s quality of life,and extend life span.

CHRONIC KIDNEY DISEASE

Chronic kidney disease (CKD) is defined as renal damage caused by any reason or estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2for more than 3 months.Renal damage refers to the appearance of pathological changes,abnormal blood or urine composition,and abnormal imaging manifestation.

Prevalence

A national cross-sectional survey was conducted between September,2009 and September,2010 among 47,204 adults aged ≥ 18 years from 13 provincial administrative units in China to investigate the prevalence of CKD.The overall prevalence of CKD was 10.8%,therefore the number of patients with CKD in China was estimated to be about 120 million.The prevalence of eGFR<60 mL/min per 1.73 m2was 1.7%,and that of albuminuria defined as a urinary albumin to creatinine ratio>30 mg/g was 9.4%.Age,gender,hypertension,diabetes,cardiovascular history,hyperuricemia,place of residence and economic status were independent risk factors for CKD.[121]

CHARLS included 6,706 adults aged ≥ 60 years from 2015–2016 to investigate the prevalence of reduced kidney function in Chinese old adults.The study results revealed that the prevalence of reduced kidney function was 10.3% (95% CI: 9.3%–11.2%).Reduced kidney function is defined as an eGFR of less than 60 mL/min per 1.73 m2.The prevalence increased with advancing age(3.3% for persons aged 60–64 years,6.4% for 65–69 years,11.4% for 70–74 years,22.2% for 75–79 years,and 33.9%for those aged ≥ 80 years).[122]

China Kidney Disease Network (CK-NET) 2016 Annual Data Report indicated that the patients with CKD constituted 4.86% of all admissions in tertiary hospitals in China.The prevalence of CKD varied among different patients.It was 13.90%,11.41%,and 7.96% for diabetes,hypertension,and CVD,respectively.[123]

CKD and Revascularization Therapy for CAD

A retrospective single-center study from Anzhen hospital compared the long-term outcomes of coronary artery bypass grafting (CABG)vs.percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for CAD patients with CKD.The primary endpoint was the occurrence of all-cause death.The secondary endpoints were major adverse cardiovascular events (MACE),such as death,myocardial infarction (MI),stroke and repeat revascularization.A total of 1,485 patients with reduced kidney function (eGFR <60 mL/min per 1.73 m2) who underwent CABG (n=533) or PCI with DES (n=952)from 2013 to 2020 were enrolled.After propensity score matching (PSM),399 patients were well matched in each group.The median follow-up duration was 55.6 months(interquartile range 34.3–74.7 months).At the 1-year follow-up,CABG was associated with a lower survival rate than PCI (94.2%vs.98.0%,HR=3.72,95% CI:1.63–8.49,P<0.01).At the end of the 5-year follow-up,CABG had a higher cumulative survival rate (68.4%vs.66.0%) but without a statistically significant difference (HR=0.92,95% CI: 0.67–1.27) compared with that of PCI.In terms of secondary endpoints,the freedom from MI and the freedom from repeated revascularization were both better in the CABG group compared to the PCI group (89.1%vs.81.7%,HR=0.59,95% CI: 0.38–0.92,P=0.019;86.9%vs.73.8%,HR=0.54,95% CI: 0.36–0.81,P=0.003,respectively).Furthermore,the freedom from MACE was also better in the patients of CABG compared with the patients of PCI (58.5%vs.51.3%,HR=0.71,95% CI: 0.55–0.91,P=0.030).[124]

Atrial Fibrillation and in-Hospital Outcomes in CKD Patients with ACS

In a retrospective study,a total of 16,533 CKD patients with ACS between November 2014 and December 2018 were included based on the CCC-ACS project.Patients were divided into an AF group and a non-AF group according to the discharge diagnosis.A total of 1,418 (8.6%)patients had clinically recognized AF during hospitalization,654 of whom had an eGFR of 45 to <60 mL/min per 1.73 m2,and 764 had an eGFR <45 mL/min per 1.73 m2.Compared with the non-AF group,the AF group had a higher risk of in-hospital mortality (OR=1.250,95% CI: 1.001–1.560,P=0.049) and MACE (OR=1.361,95% CI: 1.197–1.547,P<0.001).MACE was defined as a composite of reinfarction,heart failure,cardiogenic shock,cardiac arrest,stent thrombosis,and stroke.Compared with patients with eGFR 45 to <60 mL/min per 1.73 m2,patients with eGFR <45 mL/min per 1.73 m2had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACE.The study results suggested that AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population.Furthermore,the lower the eGFR,the higher the risk of in-hospital mortality and MACE in CKD patients with ACS.[125]

Echocardiographic Parameters and Cardiovascular Outcomes and Mortality among Patients with CKD

A total of 2020 patients with CKD stages 1–4 from Chinese Cohort Study of CKD (CSTRIDE) were enrolled to evaluate the relationship between left ventricular hypertrophy and impaired systolic and diastolic function and cardiovascular outcomes.Left ventricular hypertrophy was defined by left ventricular mass index >49.2 g/m2.7in men and >46.7 g/m2.7in women.Ejection fraction (EF) of 55% and mitral E wave to A wave (E/A,peak velocity flow in early to late diastole) ratio of 0.75 were determined as thresholds for analysis of systolic and diastolic function,respectively.After a median follow-up of 4.5 years,53 heart failure,76 non-heart failure cardiovascular events (non-fatal acute myocardial infarction,unstable angina,cerebrovascular events and PAD) and 82 deaths occurred.No overall association was found between left ventricular hypertrophy and subsequent heart failure,but the relationship was significant among patients without diabetes with the multivariable adjusted hazard ratio of 3.66 (95% CI: 1.42–9.46).EF <55% was associated with both heart failure and non-heart failure cardiovascular events with hazard ratios of 3.16 (95% CI: 1.28–7.77) and 2.76 (95% CI:1.08–7.04),respectively.E/A ratio ≤ 0.75 was associated with non-heart failure cardiovascular events (HR=2.03,95% CI: 1.09–3.80),compared with E/A ratio of 0.76–1.49.This study confirmed that impaired left ventricular systolic and diastolic function was associated with cardiovascular outcomes in a Chinese cohort of CKD.[126]

Diabetic Kidney Disease and All-Cause Mortality and Cardiovascular and Kidney Outcomes

A total of 19,025 Chinese adults with type 2 diabetes were enrolled in the Hong Kong Diabetes Biobank.Diabetic kidney disease (DKD) phenotypes were defined by baseline eGFR and albuminuria: no DKD (no decreased eGFR or albuminuria),albuminuria without decreased eGFR,decreased eGFR without albuminuria,and albuminuria with decreased eGFR.Mean participant age was 61.1 years,58.3% were male,and mean diabetes duration was 11.1 years.During 54,260 personyears of follow-up,438 deaths,1,076 CVD events,298 hospitalizations for HF,and 1161 episodes of CKD progression occurred.CVD was defined as the first occurrence of CAD (myocardial infarction,ischemic heart disease,or angina pectoris),stroke (ischemic stroke except transient ischemic attack,hemorrhagic stroke,or acute but ill-defined cerebrovascular disease),or PAD (amputation,gangrene,or peripheral revascularization).CKD progression was defined as the first occurrence of chronic dialysis,kidney transplant,and sustained eGFR ≤ 15 mL/min per 1.73 m2in 90 days apart or ≥ 40% reduction compared with baseline in 90 days apart.Compared with the no-DKD subgroup,the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (HR=1.59,95% CI: 1.04–2.44),hospitalization for HF (HR=3.08,95% CI: 1.82–5.21),and CKD progression (HR=2.37,95% CI: 1.63–3.43).The risks of death,CVD,hospitalization for HF,and CKD progression were higher in the setting of albuminuria with or without decreased eGFR.[127]

Summary

CKD is a kind of chronic progressive disease with a high prevalence that deserves attention,and it is associated with a variety of chronic non-infectious diseases,such as diabetes,hypertension and CVD.DKD has become the leading cause of CKD in China,with a high risk of disease progression,occurrence of CVD events,and death.There is an urgent need for targeted disease screening,classification,and treatment methods.CVD is not only a risk factor for CKD,but also a common complication in CKD patients,and is associated with mortality and poor cardiovascular prognosis in CKD patients.Meanwhile,the decreased eGFR also affects the response and prognosis of CKD patients to CVD related treatments.Therefore,CKD patients,as a CVD high-risk group with their own characteristics,should strengthen targeted research and intervention in the prevention and treatment of CVD.

METABOLIC SYNDROME

The development process of CVD is affected by metabolic factors.Multiple metabolic disorders such as body weight,blood pressure,blood glucose,blood lipid and uric acid are important risk factors for CVD.Abnormal aggregation of obesity,impaired glucose tolerance,diabetes,hypertension and lipid metabolic disorder in the same individual is defined as metabolic syndrome (MS).

Diagnostic Criteria for MS

Adults

At present,the diagnostic criteria for adult MS include the China Diabetes Society (CDS) MS criterion,Joint Committee for Developing Chinese Guidelines on prevention and treatment of dyslipidemia in adults (JCDCG) MS criterion,National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) MS criterion and its revision,Joint International multi-societies (IDF and AHA/NHLBI) Statement (JIS) MS criterion.

Children and adolescents

At present,there are three diagnostic criteria for MS in children: Cook in 2003,IDF in 2007,and the diagnostic criterion for MS in children and adolescents formulated by Chinese Pediatric Society in 2012.

Prevalence of MS

Prevalence of MS in adults

In the 2002 and 2010–2012 surveys on the China National Health and Nutrition Surveillance Project,[128,129]a cluster random sampling method was used to include 48,556 and 104,098 subjects aged ≥ 18 years.According to the CDS diagnostic criteria,the prevalence of MS increased from 6.6% in 2002 to 15.4% in 2012.

Prevalence of MS in children and adolescents

Analysis of the data from 16,872 adolescents aged 10–17 years in China National Health and Nutrition Surveillance (2010–2012) Project from 150 monitoring sites in 31 provincial administrative units indicated that the prevalence of MS in children and adolescents was 2.4%based on the criterion of Chinese Pediatric Society and Chinese Medical Association,but was 4.3% based on Cook criterion.[130]

Prevalence of MS in special population

ElderlyA meta-analysis was conducted on the epidemiological survey literature of MS among the elderly population aged ≥ 60 years in China from 2005 to 2021.A total of 21 articles and 77,190 study subjects were included.Based on CDS diagnostic criterion,the prevalence of MS in Chinese elderly was 23.9% (95% CI:21.8%–26.1%),21.6% (95% CI: 19.5%–23.8%) in males and 26.1% (95% CI: 23.6%–28.6%) in females.[131]

Medical staffFrom June to December 2020,3,046 medical staff from 3 hospitals in Nanjing were investigated for the prevalence of MS.Based on CDS diagnostic criterion,the overall prevalence was 13.6%,18.09% in males and 9.66% in females.The prevalence of MS increased with age (P<0.001).[132]

Tibetan dwellingsThe prevalence of MS was investigated among 920 Tibetan pastoralists aged 18–90 years in transition from high altitude nomadic to settled urbanized environment in Qinghai in 2018.The prevalence of MS was 32.8%,33.7% in males and 32.1% in females,and increased with age significantly (P<0.001).[133]

Influencing Factors of MS

Life style

Four continuous cross-sectional surveys in 8–15 counties/districts of Szechuan in West China were conducted by Szechuan CDC in 2010,2013,2015 and 2018,respectively.A total of 23,708 adults were included in the analysis.The study found that the ORs of MS in people smoking at least 20 cigarettes per day and eating more than 100 g/d of red meat were 1.10 (95% CI: 0.98–1.22)and 1.16 (95% CI: 1.09–1.25),respectively.Taking the group consuming fruit or vegetable juice weekly as a reference,the group with a lower frequency of intake had a 19% increased risk of MS (OR=1.19,95% CI;1.01-1.40),and the group that did not consume fruit or vegetable juice at all had a 27% increased risk (OR=1.27,95% CI:1.09–1.48).

The MS risk of groups with medium and low levels of physical activity was 1.24 (95% CI: 1.15–1.34) and 1.35(95% CI: 1.24–1.46) times that of the group with a high level of physical activity.The groups with sedentary time outside of work of 1.2–2.0 h,2.0–3.1 h and more than 3.1 h had a greater risk of MS than the group with less than 1.2 h.In particular,the risk in the upper quartile group was 1.19 (95% CI: 1.08–1.31) times that in the lower quartile group.[134]

A cross-sectional study was performed among 4,424 residents in Suzhou.The study revealed that the OR for the highestvs.lowest quartiles of consumption was 1.23(95% CI: 1.02–1.48) for red meat,0.83 (95% CI: 0.72–0.97)for fish and 0.93 (95% CI: 0.74–1.18) for poultry.[135]

Parental overweight and obesity

A cross-sectional survey included a total of 11,784 Chinese children and adolescents aged 7–18 years and showed that children with overweight fathers,mothers and both had 2.17 times (95% CI: 1.65–2.85),2.89 times(95% CI: 2.03–4.11) and 2.81 times (95% CI: 1.91–4.15)higher risk of MS,respectively.[136]

Weight gain

437,849 participants aged 35–64 years were included in a national cross-sectional project.Larger weight gains from young to middle adulthood were associated with higher odds of MS at middle adulthood,with ORs of 2.01 (95% CI: 1.98–2.05),1.93 (95% CI: 1.92–1.94),and 1.67(95% CI: 1.64–1.70) per 5 kg weight gain across participants who were underweight,normal-weight,and overweight/obese at young adulthood aged 25 years,respectively.[137]

Hyperhomocysteinemia (HHcy) and abdominal obesity

A 7-year follow-up study starting in 2013 included 3,675 elderly individuals aged ≥ 65 years in the community.All participants were grouped into normal waist circumference (NWC) and abdominal obesity (HWC) by waist circumference (WC).The prevalence of HHcy (Hcy>15 μmol/L),HWC and MS (based on IDF criterion) in elderly Chinese community residents at baseline was 40.1%,59.3%,and 41.4%,respectively.HHcy and abdominal obesity increased the risk of MS (Table 19).[138]

Table 19 MS risk and CVD death associated with WC/HHcy.

High-sensitive C reactive protein (hs-CRP) and MS

In the 2011–2012 China Health and Retirement Longitudinal Study (CHRLS),participants aged ≥ 45 years without baseline MS were selected and followed up from 2015 to 2016.A total of 4,116 cases were included in the analysis.Participants were divided into 4 groups according to the interquartile range of hs-CRP: <0.48 mg/L,0.48–0.81 mg/L,0.81–1.63 mg/L and ≥ 1.63 mg/L.Compared with the participants with hs-CRP in the lowest quartile,those with hs-CRP in the second,third,and highest quartiles had higher odds of MS,with OR of 1.51(95% CI: 1.12–2.06),1.50 (95% CI: 1.11–2.04),and 1.83(95% CI: 1.37–2.47),respectively.One unit (log of 1 mg/L) increase in hs-CRP was associated with 23%higher risk of MS (OR=1.23,95% CI: 1.10–1.38).[139]

MS and CVD

A total of 2,644 Kazakh individuals in remote rural areas of Xinjiang completed the baseline data collection from 2010 to 2012 and were followed up in 2016.Participants with 1 to 5 MS components had an increased HR for developing CVD,from 1.82 to 8.59 (P<0.001 for trend),compared with those with no MS components.[140]

A prospective study included 72,986 participants without MS and CVD at baseline.During the median follow-up of 8.47 years,26,411 cases developed MS.As MS onset age increased,CVD hazards gradually decreased after adjusting for potential confounders.Compared with non-MS controls,the HR for CVD was 1.84(95% CI: 1.31–2.57) in the MS onset age <45 years group,1.67 (95% CI: 1.42–1.95) for the 45–54 years group,1.36(95% CI: 1.18–1.58) for the 55–64 years group,and 1.28(95% CI: 1.10–1.50) for the ≥ 65 years group,respectively.[141]

A total of 1,157 patients with obstructive sleep apnea(OSA),aged ≥ 60 years,no myocardial infarction,and hospitalization for unstable angina or heart failure at baseline were enrolled.During the median follow-up of 42 months,MS was present in 703 out of 1,157 (60.8%)elderly patients with OSA.MS was associated with an incidence risk for MACE (defined as cardiovascular death,myocardial infarction,and hospitalization for unstable angina or heart failure) (HR=1.86,95% CI:1.17–2.96) and hospitalization for unstable angina (HR=2.01,95% CI: 1.04–3.90).[142]

The Kailuan cohort study analyzed the relationship between dynamic changes of MS and CVD risks in 31,481 subjects aged 18–98 who were included from 2006 to 2007 and were followed up at baseline,2008,and 2010,respectively.[143]The average follow-up period was 7.1 years.Compared with the MS-free group,MS-stable group had the highest risk of CVD (defined as myocardial infarction,stroke and heart failure) (HR=2.31,95%CI: 2.03–3),followed by MS-developed group (HR=1.92,95% CI: 1.64–2.25),and MS-recovery (converted to MS-free) group had the lowest CVD risk (HR=1.42,95%CI: 1.17–1.72).The association of MS dynamic change with CVD is listed in Table 20.

Table 20 Risks of CVD by the dynamic pattern of MS.

Summary

The prevalence of MS among adults in China is on the rise.Unhealthy lifestyle,weight gain from young to middle adulthood,and parents’ overweight and obesity are closely related to MS.MS increases the risk of developing CVD,while improving MS may reduce the risk of developing CVD.

AIR POLLUTION

Ambient air pollution ranked the 3rdand household air pollution ranked the 13thin terms of the disability-adjusted life year (DALY) and death burden in China.The total deaths and DALY attributable to household pollution decreased by 72.7% and 80.2%,respectively,from 1990 to 2019 in China.[144]

Air Pollution in China

According to the Report on the State of the Ecology and Environment in China,in 2021,the ambient air quality in 218 (64.3%) out of 339 cities met the targets in China,which was 3.5% higher than in 2020.In comparison with the data in 2020,concentrations of 6 air pollutants (PM2.5,PM10,SO2,NO2,CO,O3) were on the decline(Table 21).PM2.5as the major pollutant accounted for 39.7% of the days with heavy and severe pollution.Longterm average (from 2000 to 2016) of high resolution (1 km × 1 km) ambient PM2.5concentrations were evaluated using satellite remote sensing inversion technique,the results showed that the Beijing-Tianjin-Hebei metropolitan region has the most severe PM2.5pollution.[145]The formation of ambient air pollution is affected by temperature,humidity,wind speed,wind direction and other meteorological factors.

Table 21 Trends in the changes of six major air pollutants from 2013 to 2021.

Ambient Air Pollution and CVD

Short-term effect of ambient air pollution on CVD

A large number of epidemiological studies have confirmed the adverse effects of ambient air pollution on the cardiovascular system and found a significant correlation between ambient air pollutants concentration and CVD mortality and morbidity.A nationwide daily timeseries analysis in 272 Chinese cities from 2013 to 2015 revealed that the mortality of CVD,CAD and hypertension increased with the elevated concentration of PM2.5,coarse particulate matter (with aerodynamic diameter between 2.5–10 μm),O3,SO2,NO2and CO.[145–150]Anoth-er time-series study was conducted in 250 Chinese counties from 2013 to 2018.The risk of mortality during the period of heavy PM2.5pollution events increased by 1.09% (95% CI: 0.58%–1.60%) for CVD.[151]

One study evaluated the associations between shortterm exposure to PM2.5and the risks of acute incidence of stroke on the same spatiotemporal scale in 10 Chinese counties.With a 10 μg/m3increase in the PM2.5concentration,the acute incidence risk increased by 0.37% (95%CI: 0.15%–0.60%) for stroke,0.46% (95% CI: 0.21%–0.72%) for ischemic stroke.[152]One study explored the associations of short-term exposure to ambient air pollution with the onset of ACS and its subtypes in 318 Chinese cities between 2015 and 2020.It found that acute exposures to PM2.5,NO2,SO2,and CO were each associated with the onset of ACS and its subtypes.An interquartile range (IQR) increase in concentrations of PM2.5(36.0 μg/m3),NO2(29.0 μg/m3),SO2(9.0 μg/m3),and CO (0.6 mg/m3) was significantly associated with 1.32% (95% CI: 1.07%–1.57%),3.89% (95% CI:3.41%–4.37%),0.67% (95% CI: 0.47%–0.86%),and 1.55%(95% CI: 1.22%–1.88%) higher risks of ACS onset,respectively.[153]Time series study in 184 major Chinese cities showed that an increase of 10 μg/m3in PM2.5was associated with a 0.26% (95% CI: 0.17%–0.35%) increase in hospital admissions on the same day for CVD.[154]Another study conducted in 62 Chinese cities investigated the relationship between short-term exposure to NO2and hospital admissions for heart failure.The study showed that an increase of 10 μg/m3in NO2was associated with a 2.2% (95% CI: 1.2%–3.1%) increase in hospital admission for heart failure.[155]

One multi-center,case-control study performed in 21 cities,Southern China demonstrated that maternal exposure to greater levels of air pollutants (PM1,PM2.5,PM10,and NO2) during the pregnancy,especially the first trimester,was associated with higher odds of congenital heart defects (CHD)in offspring.An IQR (13.3 μg/m3)increase in PM1was associated with 1.09-fold (95% CI:1.01–1.18) greater odds of CHD.[156]A nationwide population-based study conducted in 64 Chinese counties in 30 provincial administrative units examined the relationship between maternal exposures to four species of air pollutants (NO2,O3,SO2,and CO) and atrial septal defect (ASD).The study confirmed significantly positive associations between ASD and maternal exposures to NO2,O3,SO2,and CO during entire pregnancy,first-,second-,and third-trimester.The adjusted odds ratios(aOR) for each 10 μg/m3increment of NO2,O3,SO2were 1.33 (95% CI: 1.22–1.45),1.13 (95% CI: 1.10–1.16),1.28(95% CI: 1.20–1.35),respectively;the aOR for each 100 μg/m3increment of CO was 1.10 (95% CI: 1.06–1.15).[157]The short-term effects of air pollution on CVD are shown in Table 22.

Table 22 Short-term effects of ambient air pollution on CVD hospitalization and years of life lost.

Long-term Effect of Ambient Air Pollution on CVD

Compared to short-term exposure to outdoor air pollution,long-term exposure to outdoor air pollution has a greater impact on health.From 2000 to 2016,China had over 30 million excess deaths attributed to long-term exposure to PM2.5,with an annual excess death toll of 1.5 million to 2.2 million.[145]It was estimated that ambient air pollution resulted in 1.42 million deaths in 2019,among them,90 thousand deaths attributed to O3.[144]China-PAR is a cohort study among 120,000 adults in 15 provincial administrative units.Both China-PAR and another cohort study in Taiwan demonstrated that exposure to PM2.5increased the risk of all-cause mortality.[158,159]Exposure to PM2.5also increased the risk of incidence and death for CVD and stroke,[160–165]increased the incidence of CAD and the risk of peripheral arterial occlusive disease (Table 23).[166–168]

Table 23 Long-term effects of air pollution on CVD incidence and mortality.

Ambient air pollution and cardiovascular risk factors

Panel studies conducted in Beijing and Shanghai found that short-term exposure to PM2.5and its constituents (SO42-,Cl-,K+,etc.) were positively associated with the significant alterations of systemic inflammatory biomarkers,such as soluble ST2,insulin,interleukin-17A,tumor necrosis factor-α (TNF-α),interleukin-8 and monocyte chemoattractant protein-1.[169,170]Panel study among 76 seniors in Jinan revealed that exposure to PM2.5was correlated with an increased risk of higher insulin resistant index and serum insulin level.[171]A multicity panel study among individuals at high-risk of CVD showed the adverse impact of short-term PM2.5exposure on BP,variability of BP and heart rate,and lung function.However,the impact was attenuated or diminished by blood pressure control.[172–175]A time-series study concluded that the short-time exposure to PM2.5increased the incidence of dyslipidemia in Chengdu.[176]A study conducted in 22 communities in Guangzhou showed that daily mean and hourly-peak of PM2.5were significantly associated with daily outpatient clinic visits for hypertension.[177]A longitudinal study in Nanjing demonstrated that the short-term exposure to PM2.5elevated the fasting blood glucose.[178]It can also induce early cardiovascular effects in general population,in-cluding myocardial injury,increased blood viscosity and vascular stiffness as confirmed in a study performed in 15 cities in China.[179]

Long-term exposure to fine particulate matter increases the incidence of hypertension,diabetes and overweight/obesity.Data from the China-PAR project (a large prospective cohort study) found that each 10 μg/m3increment of PM2.5could increase 11% (95% CI:5%–17%) risk of hypertension,15.66% (95% CI: 6.42%–25.70%) risk of diabetes and 13.5% (95% CI: 12.8%–14.3%) risk of overweight/obesity.[180–182]China-PAR project also found that PM2.5modified the relationship between physical activity and hypertension incidence.Increased physical activity volume was negatively associated with incident hypertension in the low PM2.5level(<59.8 μg/m3).However,the health benefits were not observed in the high PM2.5level (≥ 59.8 μg/m3).[183]The cohort study on chronic disease of communities’ natural population in Beijing-Tianjin-Hebei metropolitan region detected a positive significant association between longterm exposure to PM2.5and incidence of stage 1 hypertension (according to the 2017 ACC/AHA Hypertension Guideline,SBP 130–139 mmHg or DBP 80–89 mm-Hg is defined as stage 1 hypertension).[184]Exposure to PM2.5was found to lead to abnormal cardiac conduction,i.e.,prolonged QRS and QTc intervals.[185,186]Data from 33 communities in Northeast China found that each IQR increase in PM0.1concentration was associated with a 5.75(95% CI: 3.24–8.25) mg/dl and a 6.05 (95% CI: 2.85–9.25)mg/dl increase in the serum level of TC and LDL-C,respectively.[187]A cross-sectional investigation in China suggested that long-term exposure to PM2.5mass and specific PM2.5components were significantly associated with elevated blood pressure and a higher hypertension prevalence in Chinese children and adolescents.[188,189]

Household air pollution and CVD

A prospective cohort study among 226,000 urban residents in China showed that cooking with solid fuels significantly increased the risk of cardiopulmonary diseases and all-cause mortality.Compared with persistentclean fuel users,persistent solid fuel users had 19% (95%CI: 10%–28%),24% (95% CI: 10%–39%) and 43% (95% CI:10%–85%) higher risks of all-cause mortality,CVD mortality and respiratory mortality,respectively.[190]Stove upgrading and energy switching resulted in the reduction of premature deaths from cardiopulmonary diseases.[191]CHS sub-study revealed that solid fuel heating was independently associated with an increased risk of stroke and all-cause mortality compared with the use of clean fuels,the fully adjusted HRs were 1.44 (95% CI:1.00–2.08) and 1.55 (95% CI: 1.10–2.17),respectively.[192]

Air Pollution Intervention Measures and Strategies

Since the 1980s,China has proposed measures to address air pollution and environmental health issues at various levels,including national policies,regulations,action plans,and national standards.In 2013 and 2018,the State Council issued the “Ten Principles of Atmosphere” and the “Three Year Action Plan to Win the Blue Sky Defense War”,respectively,setting quantitative air quality improvement goals and reducing the total emissions of major air pollutants.The new version of the National Environmental Air Quality Standard in 2013 added PM2.5pollution monitoring indicators,lowered the concentration limits of indicators such as NO2and PM10,and established an air quality monitoring network nationwide.After decades of development,China’s air pollution related policies and regulations have become increasingly perfect,and air quality has significantly improved.A study conducted at the national level on longterm exposure to PM2.5and related disease burden assessment showed that from 2000 to 2016,the number of deaths attributed to PM2.5pollution in China reached 30.8 million.Since 2013,the total number of deaths caused by PM2.5exposure in China has been gradually decreasing.[145]According to a study conducting in 72 cities in China,it is estimated that achieving the 2005 WHO PM2.5daily average ambient air quality standard (25 μg/m3) and China’s 2012 PM2.5daily average ambient air quality standard (75 μg/m3) can avoid life loss of 168,065 and 68,684 years,respectively.[193]At the same time,in the process of China’s gradual realization of the carbon neutrality goal,combining the strict clean air policy with the climate policy will help reduce the level of air pollution and protect public health.[194]A study focusing on the economic costs and health benefits of different carbon reduction pathways found that carbon reduction could avoid approximately 118,000 and 614,000 PM2.5attributable deaths in 2030 and 2050,respectively.[195]The study on the benefits of China’s carbon and air quality pollution prevention policies on human health predicts that the number of deaths related to PM2.5and O3in the country is expected to decrease by 235.2 (95% CI:185.3–292.8) thousand and 53.4 (95% CI: 34.9–67.5) thousand by 2030,respectively.[196]

Summary

Both short-term and long-term exposure to air pollution can cause damage to the cardiovascular system,making it one of the risk factors for CVD.In recent years,with the implementation of air pollution control policies and measures in China,air quality has significantly improved,but it has not yet reached the standards recommended by the WHO.Heavy pollution weather events occur frequently,and the CVD hazards related to air pollution still exist.Medical personnel still need to be aware of the CVD risks associated with air pollution,in order to prepare for corresponding medical care in the event of air pollution,especially severe weather conditions.