This study had three principal findings. Firstly, in a time-updated model, three MRF (SBP ≥140 mmHg, obesity with central obesity, and inactivity) were significant in the midlife general population. Secondly, participants who maintained or achieved an optimal risk factor profile had a significantly reduced risk of AF. These findings highlight the potential population and individual level impact of risk factor modification on AF risk. Thirdly, decreased MRF burden was associated with a decreased risk of AF. Our study shows that reducing the MRF burden and maintenance or achievement of MRF ≤1 plays a crucial role in reducing the risk of AF.
Worldwide, a rapid upward trajectory of prevalence and incidence of AF is occurring (12). The global burden-of-disease study highlighted an alarming twofold increase in AF-related mortality between 1990 and 2010 (7), as well as estimated death rates of 20% and 50%, one and five years, respectively, after initial diagnosis of AF in older adults (13). The burden of AF in Asia is rapidly increasing given the proportional increase in the older population (14, 15). In Korea, a large sample cohort study based on nationwide health insurance data showed that the prevalence of AF increased from 0.36% in 2003 to 0.89% in 2013 (16). In addition, hospitalization rates and costs for AF have increased exponentially over the past 10 years, with a decrease in mortality associated with AF hospitalizations (17). AF will represent a significant public health burden in the near future. Thus, strategies for AF prevention are of paramount importance to prevent morbidity, mortality, and complications associated with AF.
Studies have reported that the independent risk factors for incident AF include aging, hypertension, congestive heart failure, coronary artery disease, valvular heart disease, diabetes mellitus, male sex, obesity, and excessive alcohol use (8, 18). Furthermore, increased numbers of unhealthy lifestyle factors, including current smoking, heavy drinking (30 g/day) and lack of regular exercise, were associated with a higher risk of incident AF (19). These risk factors play a crucial role in abnormal atrial remodelling, disease progression, and recurrence (20). Similarly, the current study showed that an SBP of more than 140 mmHg, obesity with central obesity, inactivity for leisure time, aging, male sex, and CVD were significant risk factors for AF incidence. Particularly, 81.2% of all participants had at least one MRF, and 72.2% (n = 6535) had leisure-time inactivity. In addition, 28.7% of incident AF appears to be attributable to these three MRF, with inactivity during leisure time being the greatest contributing risk factor, indicating the importance of MRF management, especially increasing LTPA.
Although studies for risk prediction and treatment of AF have been extensive, AF prevention has received relatively little attention (7–10). Current international guidelines recommend modifying an inappropriate diet, quitting smoking, abstaining from alcohol and recreational drugs, and participating in regular physical activity programs as key health behaviours to prevent the development of AF (10). However, many earlier studies also usually assessed risk factors and risk prediction of AF using a single measurement for risk factors (baseline cox model) and provided no information regarding risk factor changes during the follow-up period. These results may have immortal time bias, which can lead to overestimation of the outcome event rate in the unexposed group, underestimation of the event rate in the exposed group, or both (21, 22). When incorporating time-updated assessments of directly significant MRF, there is limited information on the association between optimal levels of risk factors and AF risk reduction. Our results showed that maintaining or achieving MRF ≤1 significantly reduced the risk of AF. In particular, we identified a consistent decrement in AF risk with progressively optimal risk factor profiles, with a striking 71% lowering of AF risk with optimal levels of MRF (reversing SBP of more than 140 mmHg, obesity with central obesity and inactivity for leisure time). Our study suggests that risk factor improvement may decrease AF risk in general population. Similarly, Du X et al. reported that a high proportion of AF can be prevented by combining strategies, focusing on the high-risk population for better risk factor management, and emphasizing healthy lifestyle choices in the whole population (6). Our findings indicate that it is possible to prevent approximately 29% of AF cases through risk factor modification. Unfortunately, we did not find significant associations between MRF combinations and AF risk, as the sample size was too small and statistical power was too low to analyse these outcomes. However, we believe that our findings provide firmer evidence to establish strategies for AF prevention in the general population.
Although the Framingham Heart Study reported that the risk factor burden, comprising modifiable risk factors, and having multiple morbidities play a crucial role in the lifetime risk of AF, associations between MRF burden and incidence of AF have not been previously reported (23). Our findings showed that the risk of AF progressively decreases according to the decrease in the proportion of visits with more than two MRF during the follow-up period. These results indicate that even if the durations of exposure to MRF are the same, the risk of AF may be lower in those who have a longer period of non-exposure to MRF. We suggest that lengthening the period of non-exposure to MRF (especially when the number of MRF is one or less) during a lifetime could help reduce the risk of AF. Moreover, a log-linear association of high SBP burden with AF incidence suggests that there are cumulative effects of high SBP on the risk of AF. Although we did not find a progressive decrease according to the decreases in the burdens of obesity with central obesity and that of inactivity, an MRF burden of < 72% for high SBP, 89% for obesity with central obesity, and 88% for inactivity lowered the risk of incident AF more than 50%, compared with an MRF burden of 100%. Therefore, minimizing the MRF burden by early intervention and control could reduce the incidence of AF. There is also potential for the burden and costs of AF to be reduced. Our findings provide a necessary evidence base to support future investment in intervention trials aimed at modification of risk factors for AF in the general population without AF.
Strengths and limitations
This study had several limitations that need to be addressed. First, the study population comprised healthy and middle-aged subjects recruited from two specific communities in Korea (Ansan and Ansung). Thus, the PAF estimated in this study, which is population-specific, may not be applicable to the general Korean population. Second, self-reporting questionnaires may not have accurately reflected the level of LTPA. In addition, the LTPA was divided into only two groups (inactive vs. active), because the majority of the study population had 0 min/week of LTPA (inactivity) and a small event size when categorizing the active group. Thus, we could not assess the association between LTPA intensity and incidence of AF. Third, information regarding some AF risk factors (e.g., smoking, drinking and sleep apnoea) were not available, due to missing data. We also conducted multivariate model analysis for these factors after excluding missing data, but significant associations between these factors and incident AF were not found. Fourth, AF was identified biennially using a standard 12-lead ECG, therefore some cases of paroxysmal AF could have been missed. Instead, we additionally analysed the incidence of AF using the Korean Classification of Diseases-7 (KCD-7) codes, which is similar to the International Classification of Diseases-10 (ICD-10), for 7,620 participants who consented to data linkage between KoGES and the Korean National Health Insurance Service (NHIS) database. We confirmed that the overall incidence rate of AF using KCD-7 codes was 2.5%, which was similar to our results (2.0%).
However, the study had several strengths. The main strengths were its community-based prospective design and the long follow-up period. In addition, to our knowledge, this is the first study to investigate the association between MRF for incident AF using a time-updated model and assessing the cumulative effects of MRF burden on AF risk in South Korea.