New-onset dyslipidemia in adult cancer survivors from medically underserved areas: a 10-year retrospective cohort study

The age-standardized incidence of all cancers per 100,000 people in Korea was 221.7 in 1999 and 295.8 in 2019 [1]. When Koreans had a life expectancy of 83 years, the cumulative cancer risk to life expectancy was 37.9% [2]. However, cancer relative survival rates are increasing. For all cancers in Korea, the 5-year relative survival rates for patients were as follows: between 2001 and 2005, 54.1%; between 2006 and 2010, 65.5%; and since 2011, 70.7% [3]. The 5-year relative survival rates for all cancers were 66.1% (prevalence 2004–2010) in the United States [4], 63% (prevalence 2006–2008) in Canada [5], and 58.6% (prevalence 2003–2005) in Japan [6, 7].

Healthy life years after cancer survival are as important as cancer treatment. The overall quality of life of cancer survivors is lower than that of the general population. The EuroQol-5 Dimension score for those > 19 years was 0.95 in the general population and 0.90 in cancer survivors [2]. The risk of complications and chronic diseases is high among cancer survivors. Cancer survivors with comorbidities have a higher risk of developing secondary cancer. However, previous studies on cancer survivors with dyslipidemia, a comorbidity, are limited [7‐9]. Although dyslipidemia is a pervasive chronic disease, its management and attention are relatively limited. The prevalence of dyslipidemia among Korean adults was 45.6% in men and 31.3% in women [10], and there was a tendency for a positive relationship with age in adults under the age of 60 [11, 12]. Dyslipidemia is a condition in which total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) in the blood are increased, or high-density lipoprotein (HDL) cholesterol is decreased. The number of new dyslipidemia cases is expected to increase as it is caused by lifestyle factors such as fat-based diets, lack of exercise, genetic factors, diseases, and drugs [13]. Although dyslipidemia can be controlled with statin drugs [14], it is difficult to cure, and most cases are asymptomatic and detected by blood tests [15].

As this chronic disease can lead to life-threatening cardiovascular diseases such as atherosclerosis, myocardial infarction, and stroke, it is a chronic disease for which prevention and management are important [16]. This dyslipidemia is important in cancer survivors for several reasons. Because a history of cancer is a risk factor for deteriorating health and disability [17]. The cancer survivor population was at high risk of chronic disease, not only in middle-aged and older adults but also in adolescents and young adults [17, 18]. This high symptom burden was also present in cancer survivors [19]. Nonetheless, previous research on the healthcare of cancer survivors includes fragmentary, therefore research areas still remain. In addition, health care for chronic diseases such as hypertension, diabetes, and dyslipidemia in cancer survivors is especially meaningful for those who have been diagnosed for more than five years. This is because patients undergoing active cancer treatment can have anorexia and cachexia due to cancer, and patients with terminal cancer can stop prescriptions with palliative care [20, 21].

In addition, medical deficiencies can be another determinant of health status. According to the World Health Organization, access to and use of health care services are key determinants of health [22]. Additionally, a lack of medical infrastructure tends to increase the risk of chronic disease [23]. Therefore, identifying the dyslipidemia status of cancer survivors according to medically underserved areas (MUA) can contribute to finding ways to reduce health inequalities.

A selective method is used to prevent and manage dyslipidemia in cancer survivors. Understanding disease onset and severity in MUA will allow for the use of limited and inelastic medical resources in a cost-effective manner [24]. The determinants of MUA include local health demand (people, income, mobility and living, health determinants), supply (medical personnel and facilities, resources), accessibility (proportion accessible within a standard time), medical use (facility utilization rate, screening rate), and health outcomes (cure, death) [25]. Although the number of medical staff in Korea is small, there are several medical activities. The number of clinicians per 1,000 people is 2.5, and that of nursing staff is 7.9 (Organization for Economic Cooperation and Development [OECD] average: 3.6 doctors, 9.4 nursing staff). Nevertheless, the number of outpatient treatments per person is 17.2 yearly, the highest among OECD countries. The total number of hospital beds is 12.4 per 1,000 people, which is approximately 2.8 times the OECD average [26]. Intensive medical practice in Korea is concentrated in metropolitan areas and large cities.

The definition of medically vulnerable areas is diverse, and it is difficult to agree on an absolute standard. Therefore, this study used data from a sample cohort to compare the level of healthcare between regions. The purpose of this study was to understand the occurrence of dyslipidemia among cancer survivors for five years or more living in medically vulnerable areas.

Table 1 shows the general characteristics of the study population following the new-onset of dyslipidemia outpatient. Of the 5,736 survivors, 1,636 developed new-onset dyslipidemia. For 2,868 non-MUA patients, the incidence rate per 1,000 person-years was 49.50 (incidence rate, 95% CI = 46.23–53.00). The incidence rate per 1,000 person-years for 2,868 patients from MUA was 57.53 (incidence rate, 95% CI = 53.77–61.55). At baseline, the sex ratio of the subjects was similar (men: 49.0%, women: 51.0%), the mean age was 63.3 years (standard deviation [SD]: 14.7), and the mean cancer survival was 10.7 years (SD: 3.2).

Table 2 shows the results of the Cox proportional hazards regression analysis of the dyslipidemia risk. Compared with non-MUA patients, MUA patients had a 1.22 times (95% CI = 1.10–1.34) higher risk of new-onset dyslipidemia. Figure 1 shows the cumulative incidence rate of new-onset dyslipidemia.

Table 3 shows the subgroup analysis of the dyslipidemia risk by independent variables. New-onset dyslipidemia tended to be at greater risk in women, participants aged ≥ 80 years, high-income class, participants with disability, patients with a higher CCI, and fifth-year cancer survivor (women, HR = 1.22, 95% CI = 1.07–1.40; people ≥ 80 years old, HR = 1.40, 95% CI = 0.96–2.04; high-income class, HR = 1.25, 95% CI = 1.08–1.45; those with a disability, HR = 1.50, 95% CI = 1.09–2.06; patients with CCI two or higher, HR = 1.38, 95% CI = 1.11–1.70; fifth-year cancer survivor, HR = 11.84, 95% CI = 2.73–51.37) than each counterpart (men, younger individuals, low-income class, those without disability, no or low CCI, and cancer survivors for six years or more).

Figure 2 indicates the new-onset dyslipidemia according to cancer type in MUA. The risk of new-onset dyslipidemia in MUA compared with non-MUA was 1.20 times (95% CI = 0.87–1.66) higher in stomach cancer, 1.20 times (95% CI = 0.85–1.70) in liver cancer, 1.23 times (95% CI = 0.90–1.70) in colorectal cancer, 1.04 times (95% CI = 0.67–1.59) in lung or bronchus cancer, and 1.24 times (95% CI = 1.09–1.40) in other cancer.

This study demonstrated the impact of the occurrence of new-onset dyslipidemia in Korean adult cancer survivors for five years or more living in MUA. Cancer survivors for five years or more living from MUA have a higher risk of new-onset dyslipidemia than those from non-MUA. This higher risk was associated with women, old age, high income, disability, numerous or serious complications, and fifth-year cancer survivors. Colorectal cancer survivors of MUA tended to have a higher risk of dyslipidemia compared to other cancer types, although it was not prominent.

The annual incidence of new dyslipidemia per 1000 cancer survivors was 57.53 in MUA, 1.16 times higher than that in non-MUA. This health disparity may be attributed to chronic disease, exacerbated by cancer survivors from MUA because of poor access to healthcare. In Korea, medical institutions in rural areas account for 12.9% of those in urban areas [2]. The average number of beds per region was 1,480; however, the variation was extremely large, with a minimum of 8 and a maximum of 6,301.3 [31].

The risk of dyslipidemia in MUA was 1.22 times higher for new-onset than that in non-MUA. Dyslipidemia is treated with lifestyle changes and medication. MUA residents often use out-of-town medical care because of the disparities in medical quality. In Korea, 50.6% of medical institutions are biased toward metropolitan areas [32]. From 2010 to 2020, the proportion of non-metropolitan patients in tertiary general hospitals located in the metropolitan area increased by 3.2% among outpatients. There were 43 MUA without hospital-level regional emergency medical institutions and 93 MUA without emergency specialists [33]. In other words, dyslipidemia has the potential to lead to medical use in non-MUA or unmet medical care because of patient demand or insufficient medical resources in MUA.

Some factors were more prominent regarding the risk of dyslipidemia than their counterparts in MUA. Women tended to have a higher incidence of dyslipidemia from low-density lipoprotein cholesterol (LDL-C) [34]. Diabetes and excessive saturated fat intake are closely related to high LDL-C levels [35, 36]. In postmenopausal women, hormonal changes lead to much higher LDL-C serum levels [37]. Additionally, the percentage of women with excessive energy intake increased 1.88-fold over 9 years in South Korea (2007: 10.0%, 2015: 18.8%) [37]. Overweight and obese adults were more prevalent in lower-income groups in cities, however conversely, there were many nutritional inequalities among higher-income groups in rural areas [38]. Further research is needed to determine whether there is a difference in the factors affecting intake by sex and region.

Physical predisposing factors such as aging, disability, and comorbidities are also susceptible for dyslipidemia in MUAs. Dyslipidemia is a chronic disease, and its continuous management is important. Nevertheless, rural areas, which account for most MUAs, have inconvenient transportation to facilities, with physical distances to medical institutions being long and infrequent ships or buses. In addition, regardless of age or health status, the livelihoods of most residents in MUA are agriculture and fishing, which are physically demanding. As the physical labor group usually experiences considerable physical fatigue, the perception threshold of health deterioration is low, and, therefore, healthcare may be delayed. In addition, lack of exercise infrastructure, early bedtime, morning work, and minimal living areas can limit their exercise.

Colorectal cancer survivors tended to be at greater risk for dyslipidemia than survivors of other cancer types, although this was not statistically significant. There have been previous studies that directly or indirectly exist potential mechanisms for the relationship between colorectal cancer and dyslipidemia [8, 39]. Nevertheless, the association between colorectal cancer and dyslipidemia has not been confirmed, and the direction of association found in previous studies has changed over time [8, 40]. Dyslipidemia may be caused by the remaining eating habits of colorectal cancer survivors who had dietary problems, such as excessive intake of animal fat or saturated fat [41, 42]. However, dietary issues may not be sufficient to explain the etiology, and further studies are needed in the future.

This study had some limitations. First, the data were not adjusted for disease stage, duration, or medication regimen. Therefore, the frequency of medical use owing to dyslipidemia was not analyzed. Second, factors such as diet and genetics could not be identified because of a lack of data. Not all factors influencing the development of dyslipidemia were considered in this study.

Cancer survivors for five years or more had a higher risk of new-onset dyslipidemia in MUA. Cancer survivors of the female sex and older age in MUA, with high household income, disability, numerous complications, and fifth-year cancer survivors were extremely vulnerable to new-onset dyslipidemia. Additionally, colorectal cancer survivors tended to have a dyslipidemia risk than survivors of other types of cancer. There is a need for health measures to prevent and alleviate dyslipidemia in cancer survivors residing in MUA. In addition, a person-centered approach should be adopted, considering the demographic and disease history of cancer survivors.