To the best of our knowledge, this is the first longitudinal, large-scale, population-based cohort study to investigate the association between knee OA and CVD using national health insurance data in Asian populations. Our main results are as follows: (1) knee OA was associated with an increased risk of CVD after adjusting for a wide range of potential confounders. (2) In the subgroup analysis, there was a higher risk of cardiovascular complications in those with knee OA under 65 years of age. (3) individuals with knee OA who did not exercise had an increased risk of developing cardiovascular complications, but the CVD risk of those with knee OA who exercised at least once a week or regularly was not different from those without knee OA who did not exercise.
In Korea, knee OA ranks fifth in the number of outpatients over the age of 60 (third among chronic diseases), and the total treatment cost of outpatient and inpatient care reached almost 1.14 billion dollars in 202030. In addition, deaths from CVD account for 19.2% of the total causes of death in Korea31. Therefore, it is very important to understand the relationship between knee OA and CVD, which is gaining importance in the elderly population.
The association between knee OA and CVD remains controversial, but many factors suggest that OA may be associated with increased CVD risk. First, OA and CVDs both share several risk factors. The association between OA and traditional cardiovascular risk factors such as hypertension32, diabetes33, dyslipidemia34, and obesity35 has been confirmed through several epidemiological studies. Second, NSAIDs, known to increase the risk of vascular events, are the most commonly prescribed drugs for OA patients for pain control3,36. Finally, knee OA is a major cause of disability and muscle weakness in the elderly and causes physical activity restrictions. Reduced physical activity is an important risk factor for CVD18–20.
According to the results of this study, subjects with knee OA had a 20% and 29% higher risk of MI and stroke than comparisons, respectively. In the baseline analysis, the knee OA cohort had a higher rate of comorbidities such as hypertension, diabetes, and dyslipidemia compared to the comparison cohort. However, after adjusting for 11 confounding factors including comorbidities, the still increased risk of CVD suggests that knee OA is independently associated with the occurrence of CVD. In addition, subgroup analysis confirmed that knee OA subjects under the age of 65 years, without diabetes or dyslipidemia had a higher risk of CVD. These results further support the strong association between knee OA and CVD.
Consistent with our results, in three population-based cohort studies, hip or knee OA increased the risk of developing CVD, and it was observed that the risk was further increased with the degree of disability caused by OA2,37,38. Also, in two systemic reviews and meta-analysis, Andrew et al. reported increased heart failure (relative risk (RR): 2.80; 95% CI: 2.25 to 3.49) and ischemic heart disease (RR: 1.78; 95% CI: 1.18 to 2.69)21, and Haoran et al. confirmed the CVD risk of OA patients increased by 24% compared to the comparison group9. The study of Rahman et al14 and Ong et al39 did not confirm the association between general OA or hip/knee OA and stroke, but our study did observe the relation between knee OA and stroke.
It may vary depending on whether it is caused by CVD or by all causes, there is a controversy over the mortality. Some studies have provided an increase in mortality due to CVD in patients with OA38,40. In contrast, there also exists a study in which hip/knee OA does not increase the risk of mortality41,42, and in our study, there was no evidence of an increase in all-cause death in knee OA patients. However, although not statistically significant, HR estimates of all-cause death were also higher in the knee OA cohort than in the general population.
Healthy physical activity is known as the keystone of CVD prevention and management. Exercise has been widely documented to modify potential risk factors in CVD such as obesity, diabetes, and hypertension by improving weight, glucose, and lipid control and lowering blood pressure at rest43–45. Similarly, in this study, it was observed that the risk of CVDs increased in patients with knee OA who had poor exercise habits. However, despite the widely known general benefits of exercise, there have been concerns and debates over whether exercise may cause pain or worsen symptoms in OA patients. In particular, this concern is more pronounced in knee OA because it is a major cause of elderly disability. But growing evidence dispels this concern. Regular physical activity and exercise are not the cause of OA unless injured, but rather have the benefit of reducing pain and disability46–48.
Our results warn against the ominous scenario of CVD that may come in non-exercise knee OA patients while demonstrating the CVD prevention effectiveness of exercise in knee OA patients. It is also noteworthy that the prevention effect has been confirmed even with 20–30 minutes of exercise once a week.
Aging is a strong independent predictor shared by OA and cardiovascular events. Therefore, the subgroup analysis of our study confirmed that under the age of 65 years with knee OA had a low CVD incidence, but paradoxically increased the CVD risk significantly. If OA develops at a young age, the duration of the disease increases, and if it is accompanied by poor exercise behavior, it seems that the risk of critical complications such as CVD will increases. These results advocate that lifestyle changes including steady exercise and modification of risk factors should be recommended for young knee OA patients.
This study is a large population-based cohort study evaluating the association of knee OA on CVD and mortality, and the first study to determine the effect of differences in exercise behavior in patients with knee OA on CVD. Nevertheless, there are some limitations to our study. First, due to the study design of the retrospective observational cohort study, the association between knee OA and CVD can be confirmed, but the causal relationship cannot be revealed. Second, the level of exercise collected by the self-report questionnaire cannot ignore the effect of recall bias. Also, since the contents of the questionnaire consisted mainly of aerobic exercise, information on the non-aerobic exercise performed by the subject was limited. Third, because our study was based on claims data, we could not confirm the information on the grade of knee OA. Fourth, the use of drugs that could affect the development of CVD, such as NSAIDs, was not considered. Fifth, since our research was conducted with the data of the Korean National Health Insurance Service, there may be limitations in generalizing our research results to other ethnic groups.
Knee OA is a prevalent disease in the elderly population, and both CVD and knee OA are medical burdensome diseases. Encouraging knee OA patients to maintain healthy exercise behavior helps to reduce the risk of CVD as well as knee joint health. Further research is needed in future studies on the optimal exercise method and intensity to improve CVD and mortality in knee OA patients. In addition, its effect on health costs is needed to be investigated in the future.