Improved Framingham Risk Scores of Patients with Type 2 Diabetes Mellitus in the Beijing Community: A 10-Year Prospective Study of the Effects of Multifactorial Interventions on Cardiovascular Risk Factors (The Beijing Communities Diabetes Study 22)

Diabetes is a prime risk factor for coronary heart disease [1]. Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges worldwide [2]. The International Diabetes Federation estimated that there were 150 million people aged ≥ 20 years living with diabetes in 2000 and that by 2025 this number will have risen to 300 million. Diabetes elevates the risk for cardiovascular disease (CVD) complications, particularly atherosclerotic vascular disease. CV events remain the major cause of death for those with diabetes, accounting for about 70% of all deaths in this patient population [3].

Epidemiological studies of CVD in the diabetes patient population are important in terms of being able to estimate both the magnitude and nature of the condition, to identify the risk factors for CVD in diabetic subjects, and to develop preventive measures. It should also be noted that relatively longer follow-ups may be necessary to see the benefit of diabetes therapies, as has been reported for the significant reduction of CV risk (including myocardial infarction) in patients with type 2 diabetes mellitus (T2DM) in the UK Prospective Diabetes Study (UKPDS) 10-year follow-up study [4]. To date, with the exception of the UKPDS, there have been few successful long-term prospective studies of diabetic management in a large sample of patients worldwide.

A recent survey in China showed a marked increase in the prevalence of T2DM, with a prevalence of 9.7%, representing estimated 92.4 million adults in China with diabetes in 2007. In 2007, the prevalence of T2DM in China was almost 10%, which was a three-fold increase in three decades [5]. Diabetes incidence, prevalence, and disease progression vary by ethnic group, as do dietary patterns; consequently, T2DM in the Chinese population is different from that in European and North American populations.

The Beijing Communities Diabetes Study (BCDS) is a clinical research project designed to investigate whether multifactorial interventions have a long-term effect on the risk of diabetes-related macro-vascular complications in patients with T2DM living in urban communities of Beijing. It is the first of the kind ever undertaken in China. Using this large sample of patients with T2DM in the Beijing community, our aim is to identify and investigate the predictors of CVD in Asian persons with diabetics, with a focus on the Chinese poulation, in order to provide effective guidance for preventing CVD incidence. China is a developing country, and as such its medical resources are relatively inadequate. It is therefore important to determine how to compensate for the lack of medical resources in the long-term management of T2DM in terms of CVD prevention at the community level. The major feature of our research is the joint management model of community hospitals and top tier hospitals managing a large sample of patients with diabetes during a 10-year follow-up. Our aim is to investigate whether achieving target control in patients with type 2 diabetes (blood glucose and blood pressure) can prevent CVD occurrence.

Persons with diabetes represent a special population in terms of asymptomatic cardiovascular risk assessment. Fortunately, the developmental process of CVD is slow and the incubation period is relatively long; as such, the study of cardiovascular risk assessment is of great significance for the prevention and treatment of CVD. The typical model of cardiovascular disease risk prediction was established by the Framingham Heart Study, and researchers subsequently developed a QRISK score based on the Framingham formula [6], which was then validated to be more consistent with the British population. A large prospective study published in 2009 found that the QRISK score underestimated 10-year CVD risk in subjects [7], while the Framingham risk assessment model overestimated the 10-year CVD risk in subjects. At the same time, some studies suggested that the model is not applicable in non-European countries. In order to establish a more suitable cardiovascular risk assessment model for Chinese patients, a 10-year ischemic cardiovascular disease risk assessment model and an annual risk assessment table with a simple assessment tool have been established, which have been shown to have satisfactory predictive value; these are recommended by domestic guidelines.

However, as yet there has been no research on a CVD risk assessment tool for patients with diabetes mellitus, with currently used tools often imitating or being borrowed from the above-mentioned risk assessment models. Because these earlier CVD risk assessment models were developed in the non-diabetic population and did not cover blood glucose control factors, whether the classical CVD risk assessment tool can truly reflect the CVD risk of patients with diabetes is not conclusive. In this context, it is necessary to explore CVD risk assessment tools for Chinese patients with diabetes. In the present study, we investigate the improved Framingham Risk Score (I-FRS) as a new cardiovascular risk assessment in persons with T2DM in the Beijing community and evaluate its effect on stratifying a patient’s CVD risk when the efficacy of that patient’s diabetes management is assessed.

Among the 3232 patients with T2DM who were included in the analysis, 204 (mean age 45.2 ± 8.8 years) were categorized in the low FRS stratum (I-FRS < 10%), 2531 (mean age 63.5 ± 9.1 years ) were categorized in the medium FRS stratum (I-FRS ~ 10–20%), and 497 (mean age 72.0 ± 6.3 years) were categorized in the high FRS stratum (I-FRS > 20%). The clinical characteristics, such as the frequency of smoking and use of metformin ratios, were all significantly different among the three groups (Table 1).

This longitudinal study lasted 10 years and was based on community health center–hospital integrated management of T2DM. All treatments administered in the BCDS were in accordance with national guidelines for the management of T2DM in China. Furthermore, the inclusion of regular clinical consultations by professors in endocrinology from top tier hospitals in disease management is unique to this study. The co-operation between the systematically trained GPs and the professors in endocrinology has formed the basis for the efficient implementation of this multifactorial intervention during the last 10 years. It represents a unique healthcare model with Chinese characteristics. The joint management model of community hospitals and top tier hospitals could improve the current challenge of a lack of experts and managing a large population with T2DM and could also effectively improve the rate of achieving target control in patients with T2DM. This approach to individualized management employing a variety of treatment options may contribute to improved patient-based compliance and a reduction in the non-compliance rate.

Although excess mortality attributable to diabetes accounts for around 3 million deaths a year worldwide [11], little community-based research data are available on diabetes management in developing countries. This study is the first of the kind ever undertaken in China. The results of this study, which are similar to those of the Steno-2 study [12], provide novel data on the multifactor management of T2DM at a community level in China. Achievement of joint targets, including the achievement of targets for blood glucose, blood pressure, and lipid profiles, was 23.5%, which may be explained by the comprehensive interventions that were applied. The American Association of Clinical Endocrinologists recommendations emphasize the importance of treating LDL-cholesterol) in individuals with diabetes [13]. The LDL-cholesterol target for lipid control was LDL-cholesterol < 2.6 mmol/L (with coronary heart disease < 1.8 mmol/L).

However, during the process of management, the comprehensive compliance rate was observed to fluctuate greatly. Despite the presence of excellent doctors in the community setting, the joint target rate still fluctuated between 30 and 50%. 31.5% of patients achieved the joint target control more than three times in the Jinsong health center community. The ideal blood glucose control target was the most difficult to maintain during the long-term follow-up in relatively young patients with more social activities and obese in diabetes. Relaxation of lifestyle interventions may be the primary cause.

Some studies have found that approximately 75% of patients with T2DM are hypertensive [14]. In China, a report published in 2007 indicated that 34% of patients with T2DM had hypertension and that hypertension among those with diabetes was especially prevalent in northern China [15]. In the present study, 70.8% of the BCDS participants had hypertension. Although diabetes is itself a major cardiovascular risk factor, its presence increases the risk for other medical conditions, particularly hypertension [16]. In the United Kingdom Prospective Diabetes Study , tight blood pressure control in patients with hypertension and T2DM achieved a clinically important reduction in the risk of death and complications related to diabetes [17]. In Beijing communities, the patients in the medium and high FRS strata had higher SBP levels than those in the low FRS stratum. Thus, the need for multirisk factor control and effective community-based management for patients with T2DM and hypertension should be emphasized.

Several follow-up studies have suggested that weight change is a mechanism for reducing the incidence of diabetes [18]. The BCDS-2 study focused on the clinical characteristics of diabetic patients with metabolic syndrome and its components living in urban communities in Beijing in 2018 [19]. Visceral adipose tissue is recognized as a unique, pathogenic fat depot that confers a metabolic risk above and beyond standard anthropometric measures, such as BMI and waist circumference [20]. As an index for upper-body subcutaneous adipose tissue distribution, neck circumference seems to be a suitable parameter for use in a clinical setting as a strong indicator of central obesity and metabolic abnormalities in persons with T2DM, and this parameter has been evaluated in relation to cardiovascular risk factors [10, 21]. In our factor analyses performed to explore the variables contributing to the incidence of CVD events, we considered such variables as BMI and neck circumference as potential confounding factors. In the BCDS, a decrease in the BMI was found to be closely related to all-cause death and cardiovascular events, especially in myocardial infarction, coronary stent implantation and coronary artery bypass grafting. Despite the increasing number of studies on neck circumference and cardiovascular events, this correlation is important as it can shed some light on the pathogenesis of CVD and merits further long-term research.

The importance of individualized risk assessment is receiving ever more attention. Many studies have shown that the use of different cardiovascular risk assessment tools for the same individual can result in the risk of CVD over a 10-year period being very different or the prediction even placing the individual in a different risk stratification. Tools are valuable to clinics, where it is important to define the risks for a specific individual and then develop interventions in individuals. Therefore, the availability of more accurate risk predicts tools will facilitate more effective intervention. At present, there is a lack of comprehensive, individualized and more economical CVD risk assessment tools in China. Therefore, it is necessary to discuss the CVD risk assessment tools suitable for Chinese patients with diabetes.

As complications related to CVD are still a very important health problem, the FRS has become a widely used method to predict the occurrence of CVD over a 10-year period, and its usefulness in this regard has been demonstrated [6]. Studies have also shown that the higher the risk for developing CVD, the greater the efficacy of the intervention that is needed. Several primary prevention trials have demonstrated a significant effect of interventions on cardiovascular events in patients with lower risk scores [22].

In our study, patients in medium and high FRS strata were more likely to be older and have a longer duration of diabetes and higher blood pressure than those in the low FRS stratum. At the end of the 10-years of follow-up, the I-FRS was significantly lower in the low, medium and high FRS strata (P  < 0.001). In addition, at baseline and after 10-years of follow-up, the post-intervention I-FRS was significantly lower than the baseline score in the HTN group and CVD group (P  < 0.01 for each); in contrast, at the end of the 10-years of follow-up, there was no significant difference in the I-FRS of the DM group when compared with baseline data. Thus, it is likely that a multifactorial intervention for CVD risk factors will have a positive, long-term effect on the I-FRS for patients with T2DM in the community, especially those in the high FRS stratum. It appears that paying more attention to patients with T2DM with hypertension or CVD disease will be more effective during the multifactorial intervention. Some indicators for calculating the FRS can be changed, and some cannot be changed, such as age. During the multifactor intervention, metabolic indicators can be changed by treatment and, therefore, the prevention of these indicators will have important value for CVD prevention in practice.

Despite the effects of multifactorial interventions on the I-FRS, we detected an increased incidence of cardiovascular events during the 10-year follow-up period. The 10-year HRs for CVD events in diabetic patients with an I-FRS score > 20% was 12.5-fold higher than that of patients with an I-FRS score < 10%. The cumulative CVD event rate was significantly higher among patients in the medium and high FRS strata among those in the low FRS strata. The 10-year HRs for death caused by CVD events in diabetic patients with FRS score > 20% was 2.91-fold higher than that of patients with an I-FRS score < 10%. The observation that CVD events seem to have a reduced incidence in people who had received specific interventions during the follow-up period is encouraging.

This study was a prospective one, and the dataset used for the analyses has considerable strength. A large, ethnically-diverse community population was enrolled, detailed clinical and metabolic characterization of the cohort was achieved, and important data were centralized and tested in a central laboratory.

In summary, increased blood pressure, abnormal lipid profiles, and elevated plasma glucose concentrations were highly significantly associated with CVD in the study population. Moreover, it was evident that the I-FRS was more suitable in patients with T2DM and was found to be a useful tool for estimating the beneficial effects of multifactorial treatments in the DM, HTN, and CVD groups. Especially for diabetic patients with a risk score of > 20%, multifactorial treatment could be effective in improving the I-FRS. Thus, multifactorial interventions for CVD risk factors in the community are important to reduce the incidence of endpoint events in Chinese diabetic patients with hypertension or CVD. Certain groups of patients may benefit from I-FRS estimate as a tool to aid decision-making regarding overall risk reduction. Hence, we suggest the use of the I-FRS to stratify patients’ CVD risk when analyzing the efficacy of management at regular intervals. Aggressive risk reduction should be focused on those individuals who had a high I-FRS and to achieving individualized risk assessment and improving the effectiveness and price ratio of the intervention.