Prevalence of Dyslipidemia and Availability of Lipid-Lowering Medications Among Primary Health Care Settings in China

1China is in the midst of an epidemiological transition in which cardiovascular diseases (CVDs) have replaced infectious diseases as the leading cause of death. Currently, CVD in China accounts for more than 40% of the causes of death. There are concerns that dyslipidemia, the prevalence of which historically was low in China, is emerging as the second leading yet often unaddressed factor associated with the risk of CVD.

2Recent national studies, have assessed the overall prevalence of dyslipidemia and achievement of low-density lipoprotein cholesterol (LDL-C) lowering targets in the Chinese population. However, they did not assess the treatment rate and control rate of elevated LDL-C in both primary and secondary prevention populations. In addition, data are lacking on the availability of lipid-lowering medications in primary care institutions, which play an important role in preventing and managing chronic diseases. Assessing the prevalence, treatment, and control patterns of dyslipidemia and associated characteristics in community residents can help identify subgroups of individuals who will be the target population for interventions to reduce cardiovascular risk. Moreover, assessing the availability of lipid-lowering medications in primary care institutions is critical for assisting the development of policies to mitigate the burden of dyslipidemia.

3The China-PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project (MPP), a large-scale population-based screening project, is an ideal platform to study dyslipidemia in Chinese adults, given the large size of this data set and the recruitment of participants at the community level. Accordingly, in this cross-sectional study, we leveraged the China-PEACE MPP and a national survey of primary care institutions to describe the prevalence, treatment, and control of dyslipidemia and the availability of lipid-lowering medications in primary care institutions.

4The central ethics committee at the China National Center for Cardiovascular Disease and the institutional review board at Yale University approved this project. All enrolled participants provided written informed consent. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cross-sectional studies.

5From December 2014 to May 2019, we used a purposive sampling method to select 189 sites (114 rural counties, 75 urban districts) across all 31 provinces in China. Sites were selected purposefully to reflect the diversity in geographical distribution, economic development, and population structure across the country (see details in eAppendix 1 in Supplement 1). At each site, participants were recruited by local staff via extensive publicity campaigns on television and in newspapers and were enrolled if they were aged 35 to 75 years and currently residents in the selected region. Participants were then screened for high risk of CVD using measurements of blood pressure, blood lipids, blood glucose, height, and weight; a questionnaire assessing cardiovascular-related health status was also administered. Of the 2 660 666 participants enrolled, 322 814 (12.1%) were excluded from this analysis because they lacked fasting blood lipid measurements or had implausible lipid values, and 23 314 (0.8%) were excluded because of missing data for other covariates (eFigure 1 in Supplement 1).

6From November 2016 to May 2017, we conducted a nationwide survey in 3529 primary care institutions in the China-PEACE MPP network. These institutions included 188 community health centers and 490 community health stations from the urban areas, and 286 township health centers and 2565 village clinics from the rural areas. In China, primary health care services are provided by community health centers and community health stations (1 level below) in urban areas and by township health centers and village clinics (1 level below) in rural areas. The distribution of sampled primary care institutions across rural and urban areas reflected the national ratio of rural to urban institutions.

7At the initial screening of China-PEACE MPP, participants underwent a lipid blood test performed by a rapid lipid analyzer using whole blood samples (CardioChek PA Analyzer; Polymer Technology Systems). Participants were considered in a fasting state if their last meals were taken more than 8 hours before. Total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) were measured. LDL-C was calculated with the Friedewald equation after excluding participants with TG greater than 400 mg/dL (to convert TG to millimoles per liter, multiply by 0.0113).

8Dyslipidemia was defined as TC greater than or equal to 240 mg/dL (to convert to millimoles per liter, multiply by 0.0259), LDL-C greater than or equal to 160 mg/dL (to convert to millimoles per liter, multiply by 0.0259), HDL-C less than 40 mg/dL (to convert to millimoles per liter, multiply by 0.0259), or TG greater than or equal to 200 mg/dL, or self-reported use of lipid-lowering medications, in accordance with the 2016 Chinese Adult Dyslipidemia Prevention Guideline. We used the same definition among secondary prevention population to be consistent with previous national studies in China., Participants were considered as being treated for dyslipidemia if they reported using lipid-lowering medication (Western medicines or traditional Chinese medication [TCM]) within the last 2 weeks. Control of LDL-C was defined on the basis of atherosclerotic cardiovascular disease (ASCVD) risk stratification in accordance with the Chinese guideline (see details in eAppendix 2 in Supplement 1). Specifically, participants were considered as achieving LDL-C control targets if they had established ASCVD (ie, coronary heart disease or stroke) and LDL-C less than or equal to 70 mg/dL, or if they had an estimated 10-year ASCVD risk of greater than or equal to 10% and LDL-C less than or equal to 100 mg/dL, or if they had an estimated 10-year ASCVD risk of less than 10% and LDL-C less than or equal to130 mg/dL.

9Information on the participants’ sociodemographic characteristics, health behaviors, medical history, and cardiovascular risk factors was recorded during in-person interviews as described elsewhere. Height and weight were collected using standard protocols, and body mass index was calculated by dividing the weight in kilograms by the square of height in meters. Obesity was defined as a body mass index of at least 28, in accordance with the recommendations of the Working Group on Obesity in China.

10The availability of lipid-lowering medications, including statins, nonstatins, and TCMs (see a complete list in eAppendix 3 in Supplement 1), was obtained from each primary care institution participating in the China-PEACE primary health care survey. We collected lists of medications in stock at the time of the survey from each participating primary care institution. For each medication on the list, we collected its generic name, brand name, and dosage.

11We described the prevalence of dyslipidemia in the overall study population and stratified by ASCVD risk. Because the indication of lipid-lowering therapy is based on ASCVD risk in current clinical guidelines, we described the treatment and control rates of LDL-C among participants with established ASCVD and high risk of ASCVD, respectively. Both groups were recommended by clinical guidelines to achieve LDL-C control targets to lower the risk of ASCVD. In a sensitivity analysis, we determined the age-standardized prevalence of dyslipidemia by adjusting observation weights to match the age and sex distributions in the 2010 Chinese Census.

12We developed multivariable mixed models with a logit link function and township-specific random intercepts (to account for geographical autocorrelation) to identify individual characteristics associated with the prevalence of dyslipidemia among all study participants and the control of LDL-C among participants with established and high risk of ASCVD, respectively. Finally, we assessed the availability of lipid-lowering medications in primary care institutions by calculating the proportion of participating institutions with a specific type of lipid-lowering medication in stock. We examined the availability by type of primary care institutions and region.

13All analyses were conducted with R statistical software version 3.33 (R Project for Statistical Computing). All statistical testing was 2-sided, at a significance level of P <.05. Data analysis was performed from June 2019 to March 2021.

14Our final sample of China-PEACE MPP included 2 314 538 participants (1 389 322 women [60.0%]; mean [SD] age, 55.8 [9.8] years) (eFigure 1 in Supplement 1), 1 369 160 of whom (59.2%) were from rural areas (Table 1). Overall, 781 865 participants (33.8%) had dyslipidemia, 71 785 (3.2%) had experienced prior cardiovascular events, and 236 579 (10.2%) had high risk of ASCVD.

15The prevalence of high TC was 7.1% (164 201 participants), that of high LDL-C was 4.0% (91 683 participants), that of high TG was 16.9% (390 244 participants), and that of low HDL-C was 15.6% (361 395 participants). Low HDL-C and high TG levels were the most common lipid abnormalities (46.2% [361 395 participants] and 49.9% [390 244 participants] of individuals with dyslipidemia, respectively), with mean (SD) HDL-C of 55.9 (15.9) mg/dL and mean (SD) TG of 139.9 (69.3) mg/dL (eFigure 2 in Supplement 1 and Figure 1). Using the 2010 Chinese Census data, we reported the age- and sex-standardized rate of overall dyslipidemia to be 34.1%.

16In multivariable regression analysis, we identified that advanced age, female sex, nonfarmer occupation, higher income, higher education level, smoking, alcohol consumption, prior cardiovascular events, diabetes, and obesity were associated with higher risk of TC greater than or equal to 240 mg/dL, LDL-C greater than or equal to 160 mg/dL, or TG greater than or equal to 200 mg/dL. However, younger age, male sex, nonfarmer occupation, higher income, higher education level, smoking, no alcohol consumption, prior cardiovascular events, diabetes, and obesity were associated with higher risk of HDL-C less than 40 mg/dL (Table 2).

17A total of 71 785 participants had established ASCVD and were recommended for lipid-lowering medications regardless of LDL-C levels, of whom 10 120 (14.1%) were treated and 61 665 (85.9%) were untreated with any lipid-lowering medications. The control rate of LDL-C (≤70 mg/dL) among adults with established ASCVD was 26.6% (19 087 participants), with the control rate being 44.8% (4535 participants) among those who were treated and 23.6% (14 552 participants) among those who were untreated (Figure 2).

18A total of 236 579 participants had high risk of ASCVD, of whom 101 474 (42.9%) achieved LDL-C control targets (≤100 mg/dL). Among 135 105 participants who had high risk of ASCVD and LDL-C greater than 100 mg/dL, 6044 (4.5%) were treated with lipid-lowering medications (Figure 2). Among 769 722 participants with low or moderate risk of ASCVD, the overall treatment and control rates of LDL-C were 2.2% (17 087 participants) and 55.7% (428 588 participants), respectively.

19In multivariable regression analysis, we identified that advanced age (age 65-75 years, odds ratio [OR], 0.63; 95% CI, 0.56-0.70), female sex (OR, 0.56; 95% CI, 0.53-0.58), lower income (reference category), smoking (OR, 0.89; 95% CI, 0.85-0.94), alcohol consumption (OR, 0.87; 95% CI, 0.83-0.92), and no diabetes (reference category) were associated with lower control of LDL-C among participants with established ASCVD. Younger age (reference category) and female sex (OR, 0.58; 95% CI, 0.56-0.59) were associated with lower control of LDL-C among participants with high risk of ASCVD (Table 3).

20Of the 3529 primary care institutions surveyed, 3041 with completed medication availability data were included in the final analysis. These institutions included 145 community health centers and 384 community health stations from the urban areas, 243 township health centers and 2269 village clinics from the rural areas (eTable 1 in Supplement 1).

21Of 3041 primary care institutions included in the analysis, 1512 (49.7%) stocked statins, 584 (19.2%) stocked nonstatins, and 467 (15.4%) stocked lipid-lowering TCM. Xuezhikang, the only TCM that had evidence of secondary prevention for CVD, was stocked in 311 primary care institutions (10.2%). Among the 4 types of institutions, community health centers had the highest statin availability (114 centers [78.6%]), whereas village clinics had the lowest statin availability (991 clinics [43.7%]) (eFigure 3 in Supplement 1). Simvastatin was the most commonly stocked statin (1422 clinics [46.8%]), followed by atorvastatin (808 clinics [26.6%]), and rosuvastatin (559 clinics [18.4%]) (eTable 2 in Supplement 1).

22This large, national cross-sectional study found that dyslipidemia is highly prevalent in China but commonly undertreated and uncontrolled. Even among people with established ASCVD and high risk of ASCVD, only 26.6% and 42.9%, respectively, achieved LDL-C control targets. Moreover, statins, the evidence-based lipid-lowering medications recommended by the guideline, are not available in almost one-half of the primary care institutions, with the lowest availability in rural village clinics.

23Our study extends the literature in several important ways. First, our study is one of the largest and most recent studies to show the nationwide characteristics of the dyslipidemia epidemic in China. Although the prevalence of dyslipidemia was consistent with previous studies and meta-analyses,,,,, the large size of our study allowed us to draw robust conclusions across a wide variety of subgroups. Our results reveal that dyslipidemia has become a major factor associated with the risk of CVD in China overall and across diverse population subgroups, suggesting that a national approach is warranted to mitigate dyslipidemia and the resulting burden of CVD. In addition, low HDL-C and high TG levels have become the dominant components of dyslipidemia, which are different than the high TC and LDL-C levels found in the US and European countries.,, This finding calls for attention to HDL-C and TG management in addition to LDL-C control emphasized in most of the current guidelines. Icosapent ethyl, a new TG-lowering drug, has been shown to have a substantial benefit with respect to major adverse cardiovascular events in the recent REDUCE-IT trial, and was granted priority review by the US Food and Drug Administration. China may consider adopting new treatments to control TG as they become available. Moreover, lifestyle modifications endorsed by guidelines to improve HDL-C and TG may be particularly relevant to the Chinese population and should be promoted.

24Second, we showed that despite the low prevalence of increased LDL-C, the absolute number of people with elevated LDL-C is still large, yet its treatment and control are far from optimal. In particular, for patients with established ASCVD, statins were recommended as first-line medications for risk reduction irrespective of LDL-C levels according to the secondary prevention guidelines., However, only 14.1% of patients with established ASCVD in our study were treated with lipid-lowering medications and the use of statins was even lower. We further identified that younger age and female sex were associated with lower control of LDL-C among people with high risk of ASCVD, indicating that preventive interventions to control LDL-C should be targeted to these subgroups for optimal outcomes.

25Third, to our knowledge, this study is the first national study to assess the availability of lipid-lowering medications in primary care institutions from all 31 provinces in China. Previous studies were limited to specific regions, populations, or data sources.,,,,,, We found that evidence-based medications, such as statins, were stocked in only one-half of the primary care institutions. One of the commonly stocked TCMs, xuezhikang, was endorsed by the Chinese guideline because studies showed it had a lipid-lowering effect similar to that of statins.,, However, the safety and efficacy of other TCMs stocked in primary care institutions were unclear and need additional evaluation.

26Our study found that the associations between different forms of dyslipidemia and some risk factors, including age, sex, and alcohol consumption, may be different. The differential association may be associated with different sex hormones in men and women. It has been shown that menopause leads to changes in lipid profile through reducing HDL-C and increasing TC, TG, and LDL-C. Our study also supports a previous study reporting that lower alcohol consumption was associated with higher HDL-C levels. Studies have shown that alcohol reduces the activity of cholesterol ester transformation from HDL to atheromatic molecules, subsequently increased the circulating levels of HDL-C.

27Our study has important policy implications. Despite historically low lipid levels in the Chinese population, marked changes in diet and physical activity, especially increased dietary energy intake and sedentary behaviors, has increased the rate of dyslipidemia, a factor substantially associated with the risk of CVD.,, If China seeks to mitigate increasing prevalence of CVD, reducing dyslipidemia is a potential good target. An important step is to increase the capacity of primary care institutions to screen, diagnose, and treat dyslipidemia in community residents. The Chinese health reform in 2009 emphasized the role of primary health care as the gatekeeper to health care system. However, routine screening programs for blood lipid levels are still not provided in primary care institutions, limiting the detection and treatment of dyslipidemia. In addition, it is important to ensure that effective lipid-lowering medications are available in primary care institutions where basic medical services are provided. The marked deficiencies in statin availability at primary care institutions are not consistent with the health needs of the people and have implications for patients’ health. The 2018 National Essential Medicines List has included more evidence-based lipid-lowering medications and could facilitate the provision of these medications; however, this program is in the early stages of implementation. Finally, effective community-based prevention strategies that promote lifestyle modification (eg, regular physical activity and dietary improvement) are needed to control dyslipidemia, particularly HDL-C and TG levels, in the Chinese population.

28Our study had some limitations. First, our study used a purposeful, rather than random, sampling strategy. However, participants from all ethnic groups across all provinces in China were included, and the ratios of participants in rural to urban areas in each province were comparable to national census data. Compared with the age and sex distribution of national census data, this study has more women and more adults in the older age group, which may result in overestimating the prevalence of dyslipidemia. However, we calculated the age- and sex-standardized estimates for dyslipidemia prevalence according to the 2010 Chinese Census data, and the estimates closely resemble our main results. In addition, use of lipid-lowering medications was self-reported, which could be subject to recall bias. We asked a subset of participants to bring in the bottle of mediations for validation purpose and found that self-reported data may tend to underestimate the overall treatment rate, because some participants who received treatment could not recall the name of lipid-lowering medications. Nevertheless, ongoing rates of dyslipidemia in those taking lipid-lowering medications reflect that it is likely few were taking effective medications. Furthermore, we defined diabetes according to physician diagnosis only, which tends to underestimate the overall prevalence of diabetes given the large proportion of people with undiagnosed diabetes. Because people with diabetes are considered at high risk of ASCVD and require lipid-lowering therapy for risk reduction, our analysis tends to underestimate the proportion of participants with high risk of ASCVD.

29In conclusion, the findings of this study suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled. Statins were available in less than one-half of the primary care institutions, with the lowest availability in rural village clinics. A focus on lipid management, in addition to other emerging risk factors, including hypertension, smoking, and air quality, represents immense opportunities for China to stem an increasing population threat of cardiovascular diseases.