Although subjects had not been prescribed antidyslipidemic drugs and had health checkup results indicating an uncontrolled lipid status in the baseline year (2015), most subjects remained untreated with antidyslipidemic drugs, and more than 75% continued to have uncontrolled lipid levels in 2016 and 2017 in this study.
Theoretically, all residents in Japan are covered by public medical insurance and have the freedom to receive treatment at any of the healthcare institutions, generally with a small out-of-pocket expense. Even under this condition, our results describe a ‘real-world’ situation wherein approximately 95% of subjects were not prescribed antidyslipidemic drugs, despite checkup results suggesting dyslipidemia. Furthermore, our analysis revealed a gap between accumulated evidence of antidyslipidemic medication benefits and the reality of controlling lipid parameters. A meta-analysis of 27 randomized controlled trials of statin treatment reported that lowering LDL-c by approximately 1 mmol/L (~ 39 mg/dL) yielded a 21% reduction in major vascular events, irrespective of baseline risks of major vascular events . In the present study, in subjects who started antidyslipidemic drugs in 2016 and 2017, LDL-c was reduced by approximately 40 mg/dL in the same year. However, 27.1% of the patients discontinued the treatment in 2017. Overall, most subjects did not receive antidyslipidemic drug prescriptions, and more than three quarters of subjects without the prescription failed to achieve lipid control, as substantiated in the poor lipid control status in previous studies [17,18,19]. Although nearly half of the subjects prescribed antidyslipidemic drugs for 2 years remained with an uncontrolled lipid status, our analysis, coupled with previous findings, may underscore the importance of pharmacological treatment for lipid control.
Difficulty in changing the checkup recipient’s behavior was also supported by the lack of change in secondary measures (BMI and smoking status) as in previous studies. Another report on blood pressure control, utilizing the same MinaCare database, showed a substantial proportion, albeit smaller than dyslipidemia, of subjects who did not receive proper treatment despite the checkup results indicating hypertension (, in press). In another Japanese statutory health checkup targeting metabolic syndrome, recipients with an increase in visceral fat with one or more additional risks are recommended to participate in the subsequent health guidance program to support behavioral modification. A database study of this checkup program revealed that most recipients eligible did not attend these programs, despite the results and recommendations calling for change [24, 25]. One possible scenario for the lack of change in antidyslipidemic drug prescription status in the present study population is that even though the subjects sought treatment, some physicians may have prioritized lifestyle improvement over medication according to therapeutic guidelines for dyslipidemia , particularly for subjects who had uncontrolled HDL-c levels. However, this may have been the case for only a certain proportion of subjects, considering that only about 12.5% of the subjects had abnormal findings in HDL-c levels alone or with the other parameters at baseline, and thus might not affect the overall trend of the drug prescription status observed in this study. The absence of subjective symptoms, particularly in the earlier stages of dyslipidemia, may also serve as a barrier to initiate behavioral changes. This may be particularly the case for younger checkup recipients, marked with a smaller antidyslipidemic drug prescription proportion. Moreover, considering the lower awareness of dyslipidemia (compared with hypertension) suggested in a previous study in Japan  and in comparison with the aforementioned report on BP , the fact that lipid parameter values are measured only on blood examinations, in contrast to the wide availability of BP self-monitoring devices, may also contribute to forming a barrier.
Although the barriers to behavioral change among subjects who received unfavorable health checkup results are still unclear, warranting further studies, our results suggest that additional approaches are required to encourage the recipients to change their behavior. Employers are required to strive to provide employees who have abnormal findings during checkups with health instructions and recommendations for secondary examinations. In reality, however, more than 30% of employers did not encourage their employees to undergo a secondary work-up or provide health instructions, according to the national survey . Theoretically, all Japanese employees and their dependents undergo regular health checkups annually. Therefore, maximizing this opportunity with a more intensive approach, including education and regular reminders, may elicit behavioral change and ultimately prevent CVD and other NCDs at a population level.
Our results suggest the importance of pharmacological LDL-c management in lipid control. Among the various factors found to be associated with uncontrolled lipid status using logistic regression, high LDL-c (LDL-c ≥ 140 mg/dL) was the greatest risk, increasing the odds of lipid control failure without antidyslipidemic drug prescription by five-fold. Meanwhile, in subjects who started antidyslipidemic drugs, LDL-c levels ≥ 140 mg/dL decreased the odds of lipid control failure. In contrast, abnormal TG and HDL-c levels remained as risk factors for uncontrolled lipid status regardless of the presence or absence of antidyslipidemic drug prescription. Moreover, when the lipid control status was stratified based on the target achievement of each lipid parameter as well as sex and age, more subjects with antidyslipidemic drug prescription achieved lipid control than those without the prescription, regardless of sex and age, but only in the subgroups with LDL-c ≥ 140 mg/dL, HDL ≥ 40 mg/dL, or TG < 150 mg/dL. Based on the definition of lipid control as abnormal values in at least one of the lipid parameters (LDL-c, HDL-c, and TG), all three subgroups (LDL-c ≥ 140 mg/dL, HDL ≥ 40 mg/dL, and TG < 150 mg/dL) commonly included subjects with LDL-c ≥ 140 mg/dL at baseline. It is inferred that more patients who had elevated LDL-c levels may have achieved lipid control with antidyslipidemic drug prescription than those without, and this may not always be applicable to those who had normal LDL-c but abnormal HDL-c and/or TG values. These results may reflect the actual situation in which most subjects with dyslipidemia had abnormal LDL-c levels (70.8% at baseline), while smaller proportions had abnormal HDL-c or TG levels (12.5% and 44.5%, respectively, at baseline). In addition, considering the predominance of LDL-c-lowering agents in antidyslipidemic drugs marketed in Japan, many subjects are considered to have received pharmacological treatment targeted at lowering LDL-c levels and regaining lipid control, leading to an apparent negative association between uncontrolled lipid levels and baseline LDL-c ≥ 140 mg/dL. However, those with normal LDL-c but abnormal HDL-c or TG values may not benefit from LDL-c-lowering agents or, for some reason, antidyslipidemic drugs prescribed to improve HDL-c or TG levels may have failed to exert the expected effects.
Nevertheless, the results also suggest the importance of comprehensive lipid management that encompasses other risks of lipid control failure, that is, BMI ≥ 25.0 kg/m2 and smoking status, albeit with relatively small OR, as well as HDL-c < 40 mg/dL and TG ≥ 150 mg/dL. The Japan Atherosclerosis Society guidelines recommend lifestyle modification first for those without a history of coronary artery disease, and in cases where lifestyle management only cannot control the lipid status, pharmacological treatment and lifestyle management are recommended . However, in most subjects with obesity and a smoking habit at baseline, these states did not change the next year, suggesting that they did not engage in necessary lifestyle modifications. Recently, total cholesterol levels have been reported to be surging in Japan, possibly as a consequence of the westernization of lifestyles . Furthermore, amid the demographic shift to a highly aging population, which is associated with more CV events, CVD, and the ensuing burden, over 30% of the Japanese population is projected to be over 65 years in 2025 . For the aging population to live healthy and independent lives, there is an imminent need for comprehensive CVD prevention and management as well as boosting the motivation for behavioral alteration from the bottom up, starting with the younger generations.
This study has several limitations. First, the database was limited to Japanese employees and their dependents covered by employment-based insurance and therefore may not fully represent the entire population in Japan. The database includes a relatively small proportion of elderly people over 70 years and excludes workers of specific sectors (e.g., self-employment) that were not covered by the employment-based insurance. However, the proportion of checkup recipients in these populations are smaller than working generations (25–64 years) and corporate employees , all of whom are supposed to receive compulsory checkups under the obligation imposed on their employers. However, with a large sample size and relatively wide age distribution, the database is considered to reflect the individuals insured by employment-based health insurance. Indeed, a previous study using the MinaCare database reported data consistent with two national data reports . This may rationalize the use of this database for the present study. Second, the definition of antidyslipidemic drugs included all antidyslipidemic drugs, not classified by the indication for each parameter. That is, LDL-c-lowering agents and TG-lowering agents were both defined as ‘antidyslipidemic drugs’ (Supplementary Table 1, see ESM). Finally, the nature of the database study was such that antidyslipidemic drug prescriptions were the main means of the subjects’ behavioral changes for CV management as well as BMI and smoking status. Checkup recipients who consulted health care professionals and were instructed and engaged in lifestyle modification without drug prescription were not explicitly captured in the data, although most included subjects failed to achieve lipid control without the prescription. Prospective cohort studies would allow a wider range of methods/outcomes to assess subjects’ ‘behaviors’ more directly. These limitations should be noted upon interpretation. Nevertheless, prescription data allowed us to accurately capture the pharmacological dyslipidemia management in Japan, as it was not dependent on self-report data, which is more prone to recall bias. Furthermore, to the best of our knowledge, this study is important to gain insight into the effectiveness of health checkup and guidance programs on CV risk management behaviors in workers in Japan, the main supporters of the economy and super-aging society, and may warrant further studies on this issue.