Annual Health Examination Didn’t Perform a Positive Effect in the Prevention of Hyperlipidemia and Hyperglycemia Through an Eight-Year Study in China

Background: Annual health examination is recommended for the prevention and treatment of cardiovascular diseases and diabetes. However, whether it is effective for the prevention of hyperlipidemia and hyperglycemia remains unclear. Methods: A retrospective analysis of clinical samples using the laboratory information system was performed. From 2012 to 2019, 5043 participants (1755 males and 3288 females) have completed the annual health examination for 8 consecutive years, which was the follow-up group. In the same period, 136,994 participants (the control group) had a health examination only 1 time. Serum levels of fasting triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and glucose (GLU) were measured. Results: Compared with 2019 of the control group, serum TC and GLU in the 8th year of the follow-up group increased markedly in some of age groups (p < 0.001). Serum TG and TC in the 8th year were much higher compared with the 1st year of the follow-up group, especially for the female (p < 0.001). Moreover, the prevalence of hyperlipidemia and hyperglycemia in the 8th year showed signicant increase compared with the 1st year of the follow-up group and 2019 of the control group (all p < 0.05). Conclusions: Annual health examination didn’t perform a positive effect in the prevention of hyperlipidemia and hyperglycemia. Health management should be paid more attention to prevent cardiovascular disease and diabetes.


Introduction
Cardiovascular diseases (CVD) have been identi ed as the rst leading disease affecting the Chinese population [1]. It is widely known that serum hyperlipidemia, particularly elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), is strongly related with the development of CVD [2]. So, management of serum cholesterol level has been a central objective in preventing cardiovascular events [3].
Over the past three decades, the prevalence of dyslipidemia has increased remarkably in China [4]. The results of 2012 national survey showed that the prevalence of hyperglyceridemia and hypercholesterolemia in adults were 13.1% and 4.9%, respectively [5]. Projected trends in serum TC and other factors would induce an increase of approximately 21.3 million cardiovascular events and 7.7 million cardiovascular deaths over 2010 to 2030 [6]. Therefore, annual health examination was recommended for middle-aged people in the 2016 Chinese guideline for the management of dyslipidemia in adults [7].
Additionally, the prevalence of diabetes was also growing rapidly in China. Almost 25% of middle-aged and elderly rural Chinese residents had diabetes in 2010-2011 [8]. Glucose control can reduce microvascular complication of diabetes mellitus (DM) and may improve clinical outcomes for patients with DM and coronary heart disease [9]. So, early detection of hyperglycemia is necessary for early prevention and treatment of DM.
In recent years, annual health examination for the adults, especially for the middle-aged people and retired elderly, has been carried out in some companies and enterprises for over ten years [10]. Serum lipids and glucose have been detected routinely for all the health check-up people. However, whether annual measurement of serum lipids and glucose is effective for the prevention and treatment of CVD and DM, has not been proved.

Participants
All the participants came from the health examination center, Beijing Tongren Hospital, Capital Medical University. From 2012 to 2019, a total of 5043 people (1755 males and 3288 females) had a health examination for 8 consecutive years, which was the follow-up group. In the same period, the other people who went for health examination only 1 time were selected to be the control group. All the participants were divided into 10-year age classes (≤30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, ≥71 years).

Measurement
For all the participants, serum levels of TG, TC, LDL-C, HDL-C and GLU were measured after at least a 12-h overnight fasting. The measurements were performed on a Beckman system (Beckman, American) in the Department of Clinical Laboratory, Beijing Tongren Hospital. The reagents of serum TG, TC, LDL-C and HDL-C were provided by the Hitachi Chemical Diagnostics Systems Co., Ltd (Hitachi Chemical Diagnostics Systems Co., Ltd, Japan). The reagent of serum GLU was provided by the Beckman (Beckman, American).

Diagnostic criteria
According to the 2016 Chinese guideline for the management of dyslipidemia in adults [7], elevated levels of TG (≥ 2.3 mmol/L) and / or TC (≥ 6.2 mmol/L) in serum were diagnosed as hyperlipidemia. According to the criteria of Chinese diabetes society [11], increased fasting serum glucose (≥ 7.0 mmol/L) was de ned as hyperglycemia.
Approaches for evaluating the effectiveness of annual health examination to hyperlipidemia and hyperglycemia control In our study, evaluation approaches were in accordance with the three strategies used to evaluate the effectiveness of consecutive health examination, proposed by the Gan W [12]. 1) Concentrations: a. Compare the levels of serum TG, TC and GLU between the 8th year of the follow-up group and 2019 of the control group; b. Compare the levels of serum TG, TC and GLU between the 1st and the 8th health examination year of the follow-up group. 2) Prevalence: a. Compare the prevalence of hyperlipidemia and hyperglycemia between the 8th year of the follow-up group and 2019 of the control group; b. Compare the prevalence of hyperlipidemia and hyperglycemia between the 1st and the 8th health examination year of the follow-up group. 3) Calculate the numbers of participants who had a bad hyperlipidemia or hyperglycemia control during the 8 years in the follow-up group. A "bad hyperlipidemia or hyperglycemia control" is de ned as persons with fasting serum TG ≥ 2.3 mmol/L, or TC ≥ 6.2 mmol/L, or GLU ≥ 7.0 mmol/L for ≥ 3 times among the total 8 examinations.

Statistical analysis
All the data of clinical samples were obtained from the laboratory information system (LIS). All statistical analyses were performed using the IBM SPSS 22.0 software program. However, serum lipids and glucose concentrations didn't distribute normally and were expressed as the median (interquartile range). Differences between gender groups were assessed by 2 independent samples Mann-Whitney test. Differences among age groups were tested by Kruskal-Wallis test. Furthermore, differences of the prevalence of hyperlipidemia and hyperglycemia between the groups were assessed by the Poisson chisquare test. All p values were two-sided, and a p value < 0.05 was considered statistically signi cant.

Results
The levels of serum lipids and glucose in the control group From 2012 to 2019, 5043 people have taken part in the health examination for 8 consecutive years. In the same period, 136,994 participants (the control group) had a health examination only 1 time. The number of participants in each age group was shown in Table 1. The age of all the participants ranged from 18 to 100.  The change patterns of serum LDL-C in both genders were similar to the level of serum TC. Serum LDL-C peaked in 51-60 year group of both genders. After menopausal period, serum LDL-C of female decreased but it was always higher than the age-matched male (p < 0.001). On the contrary, serum HDL-C decreased at rst and then increased with aging, which was signi cantly different with TG, TC and LDL-C. In addition, serum HDL-C of male was always lower than that of the agematched female.
Serum GLU exhibited an age-dependent increase markedly in both genders. 1.16-and 1.17-fold higher levels for male and female were found in ≥71 year group compared with the ≤30 year group (both p < 0.001), respectively. Furthermore, during the whole life-span, serum GLU of female was always lower than that of the age-matched male, even after the age of menopause.
Effect of annual health examination on the levels of serum TG, TC and GLU in the follow-up group Because the number of participants of ≤30 year group in the 8th year of the follow-up group was small (Table 1), to avoid introducing bias in calculating the levels and the incidence rate, we merged ≤30 year group and 31-40 year group to be ≤40 year group.
The levels of serum TG, TC and GLU in 2019 of the control group, the 1st and 8th health examination year of the follow-up group were listed in Table 3  On the whole, there were no signi cant differences of serum GLU levels between the 1st and the 8th year of the follow-up (all p > 0.05).

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The prevalence of hyperlipidemia and hyperglycemia in the control group According to the diagnostic criteria, the incidence rates of hyperlipidemia in the control group from 2012 to 2019 were listed in Table 4. The incidence rates of hyperglycemia in the control group from 2012 to 2019 were listed in Table 5. The percentages of hyperglycemia also exhibited an age-dependent increase markedly in both genders. Similar to the levels of serum GLU, the percentages of hyperglycemia of male were always higher than those of the age-matched female. It should be noticed that the percentages of hyperglycemia of female increased more rapidly with aging than that of male. Such as, in 2013, the percentage of hyperglycemia of male was 4.91 folds as that of female in the ≤40 year group; but, it was only 1.28 folds as that of female in the ≥71year group. Furthermore, through the Trend chi-square test, the prevalence of hyperglycemia of male increased steadily in the ≤40 and 61-70 year groups from 2012 to 2019 (Trend chi-square 27.21 and 14.10, respectively, both p < 0.05). And the percentages of hyperlipidemia of female didn't show differences in all the age groups in the consecutive 8 years. Effect of annual health examination on the prevalence of hyperlipidemia and hyperglycemia The incidence rates of hyperlipidemia in 2019 of the control group, the 1st and 8th year of the follow-up group were listed in Table 6. Compared with the non-consecutive group in 2019, there was only a signi cant difference of the percentages of hyperlipidemia of female in the 8th year of the follow-up group in the ≤40y group (p < 0.05). Compared with the 1st year, the incidence rates of hyperlipidemia of both genders in the 8th year increased steadily in the ≤40 year group (both p < 0.05). It should be noticed that, for the female under the age of 60, the percentages of hyperlipidemia in the 8th year were signi cantly higher than those in the 1st year of the follow-up group (all p < 0.05). These were in accordance with the change pattern of serum TC in female of the follow-up group completely. As a whole, the percentages of hyperlipidemia of female in the 8th year showed signi cant increase compared with the 1st year of the follow-up group and 2019 of the control group (all p < 0.05). For the male, there were no differences of the percentages of hyperlipidemia among these three groups. The incidence rates of hyperglycemia in 2019 of the control group, the 1st and 8th year of the follow-up group were listed in Table 7.

Discussion
Regular physical examination is recommended in China to protection and treatment of CVD and DM, but its effectiveness in the control of hyperlipidemia and hyperglycemia has not been proved. So, we rstly investigated the changing pattern of serum lipids and glucose in the general population with aging. Since the concentrations of serum lipids and glucose in some groups didn't distribute normally, all the results were expressed as the median (interquartile range). It was found that serum TG of male exhibited the pattern of rst increase, then decrease. serum TG of female showed an obvious increase with aging, similar to the report of Gan [12]. The change pattern of serum LDL-C was in accordance with serum TC in both genders, which peaked in 51-60y group and decreased after menopausal period. Serum HDL-C followed the pattern of rst decrease and then increase with aging. Serum glucose in both genders demonstrated an age-dependent increasing pattern, consistent with the previous reports [13][14]. Our research further con rmed that the highest increase of serum lipids and glucose in women took place during the menopausal period. Therefore, annual health examination was also recommended for the female after menopausal period to prevent and treat the CVD and DM.
We evaluated the effectiveness of annual health examination to hyperlipidemia and hyperglycemia control through 3 approaches. After 8 years' consecutive health examination, the levels of serum lipids and glucose in the follow-up group was not lower than those of the control group in 2019. Additionally, our results showed that serum TG and TC of the 8th year increased signi cantly compared with the 1st year of the follow-up group, which was consistent with the report of Gan [12]. However, we demonstrated that there was no signi cant difference of serum GLU between the 8th and the 1th year of the follow-up group, which was unlike with the result of Gan. In our study, serum GLU in the 1th year of the follow-up group were similar to those of the control groups in all the age groups, but serum GLU in the 1th year of the follow-up group were much lower than those in 2016 of the control groups in Gan [12].
All these results suggested that annual health examination didn't reduce the levels of serum TG, TC and GLU and prevent the development of CVD and DM. Moreover, the percentages of hyperlipidemia and hyperglycemia in the 8th year showed signi cant increase compared with the 1st year of the follow-up group and 2019 of the control group (all p < 0.05). Therefore, these results indicated that after 8 years' consecutive health examination, annual health examination didn't perform a positive effect in the prevention of hyperlipidemia and hyperglycemia.
With the development of economy, the prevalence of adult obesity and central obesity increased annually from 1997 to 2011 [15].  [20]. These ndings further con rmed that the long-term of lifestyle intervention induced clinical bene ts for patients with impaired glucose tolerance and lifestyle interventions should be as public health measures to control the consequences of diabetes. Therefore, American Diabetes Association established Lifestyle Management: Standards of Medical Care in Diabetes-2019 in 2019 [21].
It is widely known that the purpose of annual health examination is to nd and treat the diseases as early as possible. Early or mild hyperlipidemia and hyperglycemia will not lead to any discomfort to the body. Once one patient is diagnosed as hyperlipidemia or hyperglycemia, diet control and lifestyle improvement have been the basic measures for the treatment of dyslipidemia and diabetes. However, for a health examination participant, compliance of diet control and lifestyle management was usually poor, which has become a common problem at present. Our results also indicated that more than half participants diagnosed as hyperlipidemia and hyperglycemia had a bad control. Consistent with our results, Lau et al. found that a general population to participate in a repeated screening and lifestyle counselling programme over ve years did not result in lower incidence of diabetes after 10years of follow-up [22]. So, it is necessary to perform a population-based education on health eating and physical activity. Health management should be paid more attention to prevent cardiovascular disease and diabetes.

Conclusions
In conclusion, our data showed that annual health examination didn't show a positive effect in the prevention of hyperlipidemia and hyperglycemia. Health management should be paid more attention to prevent cardiovascular disease and diabetes.

Availability of data and materials
The data used in the study were available from the LIS of Department of Clinical Laboratory of Beijing Tongren Hospital a liated Capital Medical University.

Competing interests
Xiaohong Zhang, Xiaokui He, Xuehong Zhou, Hongyan Geng and Xiangyi Liu declare that they have no con ict of interest.
Funding Not applicable.

Authors' contributions
Xiaohong Zhang designed the experiments, analyzed the data and wrote the manuscript. Xiaokui He, Xuehong Zhou and Hongyan Geng took part in the detection of samples. XiangYi Liu contributed to interpretation of results and reviewed drafts of the manuscript. All authors read and approved the nal manuscript.