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INTRODUCTION
Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality across the globe,1) with respiratory viral infections, such as influenza, exerting a significant impact.2) Influenza increases the risk of developing ASCVD and the severity of existing ASCVD, leading to higher morbidity, hospitalization rates, and mortality.3) This virus also poses a considerable threat to the middle-aged working population, which is at an elevated risk of ASCVD, precipitating serious cardiac conditions within this group. Moreover, the development of ASCVD in this population group may result in substantial disability-adjusted life years (DALYs), leading to considerable socioeconomic losses in the community. Therefore, preventive measures such as influenza vaccination are crucial for middle-aged working adults at a high risk of ASCVD.
The ASCVD risk score is a pivotal tool for evaluating the possibility of ASCVD development.4) For individuals with high ASCVD risk scores, the threat of influenza is even more pronounced.5) Thus, influenza vaccination serves not only as a protective measure against the virus infection itself but also as a crucial component in the general management of cardiovascular health in individuals with high ASCVD risk scores.6)7) Furthermore, the American Heart Association and American College of Cardiology also endorse influenza vaccination as a class I recommendation for the secondary prevention of ASCVD.8) This approach aligns with international guidelines recommending annual influenza vaccination as a standard part of patient care for high-risk ASCVD populations.9) Despite this, nearly half of the individuals with ASCVD neglect their annual influenza vaccination,7) suggesting that the influenza vaccination rate is lower in individuals with an elevated risk of ASCVD. However, little information is available regarding influenza vaccination rates and related factors in individuals at an elevated risk of ASCVD.
In this study, we aimed to investigate the yearly trend of influenza vaccination and explore the factors associated with the unvaccinated status. Considering the importance of ASCVD prevention in middle-aged working adults in terms of DALYs in the community, we focused on working individuals aged between 40 and 65 years.
METHODS
Ethical statement
The study protocol was approved by the Institutional Review Board of Chungbuk National University Hospital (application No. CBNUH-2023-05-001).
Study population
The Korean National Health and Nutritional Examination Survey (KNHANES) is a population-based nationwide survey aimed at assessing the health and nutritional status of noninstitutionalized population of Korea, and conducted by the Korea Centers for Disease Control and Prevention.10)11) Data from KNHANES V (2010–2012), VI (2014–2015), VII (2016–2018), and VIII (2019–2021) were used for this study. Data from KNHANES V (2013) were excluded because vaccination data were unavailable to the public. The study population was selected using a stratified multi-stage sampling method. During the 11 years, participants aged <40 years or >65 years (n=77,302) or for whom information on weighted variables (n=10,630), 10-year ASCVD risk score (n=37,304), and vaccination variables (n=17,950) were missing were excluded, and 35,323 individuals were included in this study. Of the 35,323 participants, 14,931 had an ASCVD risk score of <7.5%, while 20,395 had a score of ≥7.5% (Figure 1).
The 10-year atherosclerotic cardiovascular disease risk
The main exposure in this study was the elevated ASCVD risk estimated using the ASCVD risk score.12) In 1976, the Framingham Heart Study revealed multiple risk factors and developed coronary heart disease risk equations for the first time.13) Since then, various equations for calculating ASCVD risk have been published in public health studies and are used in clinical practice.14)15) Among these, the equation for calculating the 10-year ASCVD risk published by the American Heart Association is the most frequently used.12) The equation allows the calculation of the 10-year risk of cardiovascular problems such as heart attack or stroke. This risk estimate considers age, sex, race, cholesterol levels, blood pressure, medication use, diabetes mellitus, and smoking status. The ASCVD risk score is expressed as a percentage. Risk scores of 0–4.9%, 5.0–7.4%, 7.5–20%, and >20% indicate low, borderline, intermediate, and high risk, respectively.12) In this study, elevated ASCVD risk was defined as a projected 10-year ASCVD risk of ≥7.5% using Pooled Cohort Equations among ASCVD-free adults.16)
Outcomes: influenza vaccination
The main outcomes of our study were the trend of influenza vaccination and the factors associated with influenza vaccination in a middle-aged working population with an elevated ASCVD risk. Influenza vaccination was investigated using the following question: “Have you ever been vaccinated against influenza in the past year?”
Covariates
Data on age, sex, body mass index (BMI), smoking history, alcohol consumption, marital status, income, area of residence, education, and cardiac symptoms were obtained from the KNHANES database.17)18)19) BMI was calculated as weight in kilograms divided by height in meters squared and categorized according to Asian-specific criteria: underweight (<18.5 kg/m2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2), and obese (≥25.0–29.9 kg/m2).20) Participants who consumed >30 g/day of alcohol were classified as heavy drinkers. Comorbidities (hypertension, diabetes mellitus, dyslipidemia, atherosclerotic cardiovascular disease, and chronic kidney disease) were defined based on self-reported diagnoses by a physician. Marital status was classified as unmarried, married, or widowed/separated/divorced, and household income level was classified into four groups by quartile division. Diabetes mellitus was defined as the presence of any of the following: (1) diagnosis of diabetes mellitus by a physician, (2) fasting glucose level of ≥126 mg/dL, (3) hemoglobin A1c of ≥6.5%,21) or (4) use of oral hypoglycemic agents or insulin. Hypertension was defined as a self-reported diagnosis by a physician, use of antihypertensive medication, systolic blood pressure of ≥140 mmHg, or diastolic blood pressure of ≥90 mmHg.22) Dyslipidemia was defined as a self-reported diagnosis by a physician, the use of lipid-lowering medication, a total cholesterol level of ≥240 mg/dL, or a fasting triglyceride level of ≥200 mg/dL.
Statistical analysis
All analyses were performed using the survey commands in STATA (version 15.1; StataCorp LP, College Station, TX, USA) to account for complex sampling design and survey weights. All data are presented as weighted percentages with standard errors. The data were compared using Student’s t-test for continuous variables and Pearson’s χ2 test for categorical variables.
To evaluate factors associated with the unvaccinated status in the elevated ASCVD risk group, multivariate logistic regression analyses were performed by adjusting for variables for which the p value was <0.05 in the univariate logistic regression analyses. All tests were 2-sided, and statistical significance was set at p<0.05.
RESULTS
Baseline characteristics
Among the 35,323 participants, 20,392 were classified into the elevated ASCVD risk group (Supplementary Table 1). Of these 20,392, 36.3% were vaccinated (vaccinated group) and 63.7% were unvaccinated (unvaccinated group). As shown in Table 1, compared with the vaccinated group, the unvaccinated group was younger (mean age: 57 years vs. 54 years, p<0.001), had a smaller proportion of female individuals (57.4% vs. 43.5%, p<0.001), and a higher proportion of current smokers and heavy drinkers (22.2% vs. 38.3% and 13.5% vs. 21.6%, respectively, p<0.001 for both). Furthermore, the proportions of individuals residing in urban areas and those with higher education were higher in the unvaccinated group than in the vaccinated group. Further, a higher percentage of individuals in the unvaccinated group reported dyspnea than did those in the vaccinated group (2.4% vs. 1.2%, p=0.003). Regarding comorbidities, the unvaccinated group had a lower proportion of individuals with hypertension (41.7% vs. 46.7%), diabetes mellitus (20.4% vs. 23.1%), cardiovascular disease (3.7% vs. 5.2%), and chronic kidney disease (3.0% vs. 4.4%) than in the vaccinated group (p<0.001 for all). However, the proportion of individuals with dyslipidemia was not significantly different between the two groups (70.0% in the unvaccinated group vs. 70.8% in the vaccinated group, p=0.367).
Table 1
Baseline characteristics of individuals with an elevated cardiovascular risk (ASCVD risk score of ≥7.5%)
Influenza vaccination trend
The 11-year trend of influenza vaccination according to the ASCVD risk score is summarized in Figure 2. The overall influenza vaccination rate was 29.9% for all participants. The influenza vaccination rate was significantly higher in the elevated ASCVD risk group than in the low ASCVD risk group (33.8% vs. 25.3%, p<0.001). Until 2019, the elevated ASCVD risk group had a higher influenza vaccination rate than the low ASCVD risk group. However, thereafter, the influenza vaccination rate was not significantly different between the two groups (p<0.001).
Factors related to influenza unvaccinated status in the elevated atherosclerotic cardiovascular disease risk group
Table 2 summarizes the factors associated with influenza unvaccinated status in the elevated ASCVD risk group. The following factors were also associated with the unvaccinated status in the elevated ASCVD risk group: younger age (<50 years; adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.31–1.98), male sex (aOR, 1.43; 95% CI, 1.16–1.76), current smoker status (aOR, 1.41; 95% CI, 1.13–1.76), residence in an urban area (aOR, 1.19; 95% CI, 1.01–1.41), having higher education (aOR, 1.3; 95% CI, 1.04–1.64), and absence of dyspnea (aOR, 2.06; 95% CI, 1.23–3.44) and of hypertension (aOR, 1.19; 95% CI, 1.04–1.36).
Table 2
Factors associated with influenza unvaccinated status in individuals with an elevated cardiovascular risk (ASCVD risk score of ≥7.5%)
DISCUSSION
This study evaluated the recent trend in influenza vaccination and factors associated with the unvaccinated status among middle-aged working adults (aged 40–64 years) with an elevated ASCVD risk in Korea. We found that the influenza vaccination rate was 33.8% in the elevated ASCVD risk group, which was significantly higher than that in the low ASCVD risk group (25.3%). We also found that factors related to the unvaccinated status in this population included younger age, male sex, current smoking status, and higher education status.
Various factors, including healthcare accessibility and socioeconomic status, can influence influenza vaccination rates. These factors are particularly important in understanding vaccination trends among individuals with elevated ASCVD risk. This study focused on middle-aged working adults, who represent a critical demographic for ASCVD prevention. However, it is essential to consider how healthcare access and socioeconomic factors may affect the likelihood of an influenza vaccine, potentially confounding the relationship between vaccination and cardiovascular outcomes. In South Korea, influenza vaccination policies play a significant role in vaccination rates. Specifically, individuals aged 65 and above are eligible for free vaccination under the national public health policy. Given that this policy introduces a substantial difference in vaccine access for those aged 65 and older, we excluded individuals aged 65 and above from the analysis to control this confounding factor. By focusing on individuals under 65, we aimed to reduce the potential bias introduced by the free vaccination policy and better understand vaccination trends in the general population at elevated risk for ASCVD.
The trend of influenza vaccination in the general population and those with an established ASCVD diagnosis has been well documented.23)24) For example, Al Rifai et al.25) reported that the influenza vaccination rate was 38% among the overall population in the US and 51% among participants who self-reported ASCVD. In Korea, Kim et al.26) showed that the influenza vaccination rate ranged from 53% to 74% in patients with ASCVD between 2007 and 2019, which was higher than that in those without ASCVD (28–40%). However, information on the trend of influenza vaccination in middle-aged working adults with an elevated ASCVD risk is scarce. Considering that influenza can trigger acute coronary syndrome in individuals with an elevated ASCVD risk, and that influenza vaccination prevents this, data on the influenza vaccination rate in this population would be very informative in terms of public health management. Although the influenza vaccination rate was higher in middle-aged working adults with an elevated ASCVD risk than in those with a low ASCVD risk, the vaccination rate was relatively low; only approximately one in 3 individuals received the influenza vaccination.
Except in 2020, the influenza vaccination rate was higher in the elevated ASCVD risk group than in the low ASCVD risk group during the study periods. Until 2019, influenza vaccination numbers were significantly higher in the elevated ASCVD risk group than in the low ASCVD risk group. From 2019 onward, the influenza vaccination rate sharply increased in the low ASCVD risk group, which can be attributed to the pandemic of coronavirus disease 2019 (COVID-19). In the 2020–2021 season, free influenza vaccinations have been expanded to 62 and older as part of the national health policies. This temporary assistance led by the government could have led to increased vaccination rates. Also, increased public awareness of the need for influenza vaccination during this period may be linked to this phenomenon. Although the influenza vaccination rate increased from 2019 to 2021 in the elevated ASCVD risk group, the delta was not as large as that in the low ASCVD risk group. In 2021, the influenza vaccination rate reached approximately 40% in both groups. As the recent increase in influenza vaccination rates could be a temporary phenomenon similar to that during the COVID-19 pandemic, vigilant surveillance of influenza vaccination is needed.
Vaccination rates were significantly lower in certain groups: younger individuals (those aged <50 years), male individuals, current smokers, those living in urban areas, and those with higher education. Age and sex are known to affect influenza vaccination; however, their effects are highly conflicting.27) As in the current study, a lower influenza vaccination rate has been consistently observed in men in Korea.26)28) Although the reasons for this observation are unknown, considering the higher adherence to mediation in women than in men in Korea,29) women may have been more likely than men to adhere to clinicians’ recommendations for influenza vaccination. For individuals with higher odds of receiving influenza vaccination, positive health-seeking behaviors and motivations in never-smokers, as well as negative health-seeking behaviors in current smokers who have quit, could be contributing factors.26)
Generally, education level is positively associated with the influenza vaccination rate.23) However, in our study, the educational status of college graduates and residents in urban areas was the other determinant of the lack of influenza vaccination in the elevated ASCVD risk group. Considering the higher accessibility to medical information, more health knowledge, and more stable economic status in individuals with high education levels and residing in urban areas compared with their counterparts, this finding was unexpected. The reasons for this phenomenon are unclear. However, considering that many previous Korean studies evaluating different populations have shown similar results,11)26) a population-specific factor may exist. For example, some local governments in Korea provide free influenza vaccination to individuals with lower income levels, which is correlated with education level and residential area. This finding suggests that financial support from the government may influence health-seeking behaviors in terms of influenza vaccination in potential risk groups of unvaccinated individuals.
Although the influenza vaccination rate was higher in the elevated ASCVD risk group than in the low ASCVD risk group, it remained unsatisfactory. The benefits of annual influenza vaccination among those with ASCVD have been well-established.30) A meta-analysis involving 6,735 patients from 6 studies showed that the influenza vaccination reduced 36% of the risk of composite CV events in patients with high ASCVD risk.30) Influenza vaccination also reduces the risk of acute myocardial infarction and stroke in patients with hypertension without prevalent coronary artery disease or previous stroke, leading to improved outcomes and reduced mortality. In addition, patients with diabetes who are at an elevated risk of ASCVD are strongly recommended to be vaccinated against influenza according to the diabetes guidelines.9) Despite the relevant evidence for the benefits of influenza vaccination in individuals with elevated ASCVD risk, the current guidelines, including those of the American Heart Association and American College of Cardiology do not mention any recommendations about influenza vaccination in individuals with an elevated ASCVD risk, while the guidelines of the American Heart Association and American College of Cardiology have made influenza vaccination a class I recommendation for the secondary prevention of ASCVD.21) The influenza vaccine is likely beneficial not only for patients with documented ASCVD but also for individuals with an elevated ASCVD risk. Hence, influenza vaccination should be emphasized in individuals with an elevated ASCVD risk. In addition, this low rate is likely influenced by barriers to healthcare access and vaccine hesitancy. Government policies, particularly financial support through publicly funded vaccination programs, play a crucial role in increasing vaccination rates. Since 2019, expanded eligibility for free vaccinations has contributed to higher vaccination rates among the elevated ASCVD risk group, but middle-aged adults with elevated ASCVD risk, who are not always included in these programs, remain underserved. Expanding the national vaccination program to cover this group, along with addressing vaccine hesitancy, could significantly improve vaccination rates and help reduce cardiovascular events triggered by influenza. Further research should explore the potential impact of such interventions and assess whether expanded vaccination coverage would lead to improved cardiovascular outcomes in this population.
This study has three important clinical implications. First, by showing the relatively low influenza vaccination rate in middle-aged working adults with an elevated ASCVD risk, our study highlights the importance of public awareness about influenza vaccination in this population. Second, because our study reveals various factors associated with the unvaccinated status, our results can help formulate risk-stratified strategies to improve influenza vaccination in middle-aged working adults with an elevated ASCVD risk. For example, current smokers with an elevated ASCVD risk were associated with a high likelihood of being unvaccinated. Thus, government campaigns or encouragement from healthcare providers should be provided to this group. Third, emphasizing the importance of influenza vaccination in middle-aged working adults with an elevated ASCVD risk may contribute to reducing serious DALYs by preventing influenza itself as well as influenza-induced ASCVD.
This study had some limitations. First, recall bias might have affected the results because of self-reported influenza vaccination information in the KNHANES database. Second, due to the absence of data on psychological factors or personal health perceptions that could influence vaccination behavior, this study could not include this information. Since these factors are known to play a role in shaping an individual’s decisions to receive or avoid vaccination, future studies should consider including these variables, perhaps through surveys or interviews, to provide more comprehensive results. Third, although the ASCVD risk score is primarily used for preventive interventions of ASCVD, this study included patients with a history of ASCVD. However, as the number of individuals with pre-existing ASCVD was small, this would not have had a significant impact on our results. Finally, influenza vaccination policies may differ among countries. Therefore, our results may not apply to other countries with different influenza vaccination policies.
In conclusion, despite the potential benefits of influenza vaccination against ASCVD in middle-aged working adults with elevated ASCVD risk, the influenza vaccination rate in this population was still as low as approximately 30%. Unvaccinated status was associated with younger age, male sex, current smoking status, residence in an urban area, and higher education level. Clinicians should provide in-depth counseling on influenza vaccination to the working middle-aged population with an elevated ASCVD risk and encourage them to receive it.
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