Non-exercise based estimation of cardiorespiratory fitness is inversely associated with metabolic syndrome in a representative sample of Korean adults

Metabolic syndrome (Mets) represents a clustering of risk factors such as central obesity, hyperglycemia, hypertension, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol [1]. Left untreated, Mets leads to the development of non-communicable diseases, such as type 2 diabetes and cardiovascular diseases (CVDs) in residents of both developed and developing countries [2, 3]. Western lifestyles characterized by obesity and physical inactivity have been blamed for the etiology of the global epidemic [1]. Along with unhealthy lifestyles, low level of cardiorespiratory fitness (CRF), which reflects the maximal capacity of the respiratory and cardiovascular systems to supply oxygen to working skeletal muscles during exercise, is another well-established risk factor of Mets [4, 5]. Low CRF is also associated with an increased risk of all- and specific-cause mortality [6‐8].

In Korea, a third of adults suffer from Mets. The prevalence of Mets is on the rise, particular in men, and in those of advancing age, with the greatest prevalence seen in elderly persons [9]. Considering continuing rise in prevalence and adverse consequences in conjunction with a rapidly aging society, Mets will continue to represent a key public health issue in Korea. Obesity and physical inactivity have been suggested as two of the primary lifestyle risk factors responsible for Mets in Korea [10]. However, less attention has been paid to investigating the impact of CRF for Mets in Korean populations. A literature review uncovered only 2 studies that examined physical fitness in relation to Mets in Korean adults. In a cross-sectional study involving 227 older adults aged 60 years and older, Hwang and Kim [11] examined the association between physical performances of a sit-up test and the Tecumseh step test as indices of muscular fitness and cardiopulmonary fitness, respectively, and they reported an inverse relationship between muscular and/or cardiopulmonary fitness and Mets. In another study involving 1007 Korean adults who underwent routine health checkups, Hong et al. [12] examined the association between a step test-based CRF and Mets, and they found that low CRF and obesity were significantly associated with an increased risk of Mets. Those previous studies recognized a prognostic role of CRF but failed to prove it in a representative sample of Korean adults. Consequently, the relationship of CRF with Mets in Korean populations remains to be confirmed.

Objectively measuring CRF is often limited by the need for specialized equipment, trained personnel, sufficient time, and other factors [8], especially in a population-based study involving a large sample size. To circumvent those limitations, Jurca et al. [13] showed that CRF can be estimated from routinely obtained health indicators with an acceptable accuracy. We previously showed that this non-exercise based estimation of CRF (eCRF) could be used an alternative tool to estimate the risk of morbidity and mortality from all and specific causes in Korean adults [14]. This study examined the association between eCRF and Mets in a representative sample of Korean adults aged 18 years and older.

Table 1 represents characteristics of study participants. Men had higher BMI (p < 0.001), waist circumference (p < 0.001), SMI (p < 0.001), physical activity (p < 0.001), eCRF (p < 0.001), resting blood pressures (p < 0.001), triglycerides (p < 0.001), fasting glucose (p < 0.001) and insulin (p < 0.001), HbA1c (p < 0.001), serum vitamin D (p < 0.001), caloric intake (p < 0.001), intakes of protein (p < 0.001), fat (p < 0.001), and carbohydrates (p < 0.001), smoking (p < 0.001), and heavy drinking (p < 0.001) but lower resting heart rate (p < 0.001) and HDL-C (p < 0.001) compared with women. No significant differences in age and HOMA-IR were observed between men and women.

Table 2 represents the prevalence of each risk factor defining Mets. Decreased HDL-C was the most frequent risk factor, followed by hypertension, hypertriglyceridemia, hyperglycemia, and central obesity. Table 3 represents the proportion of clustering of one or more risk factors for Mets. The presence of Mets was 25.7% in the total group. Men had a higher prevalence of Mets than women (28.7% vs. 23.5%) (p < 0.001). Table 4 compares physical characteristics and risk factors of those with and without Mets. As expected, individuals with Mets were older, heavier, and physically less fit and had more severe profiles of risk factors compared with individuals without Mets.

Table 5 represents the results of logistic regression analyses for Mets. An inverse and graded association between eCRF and Mets was found in women (p < 0.001) and men (p < 0.001) separately. In women, the prevalence of Mets ranged from 40.0% in the lowest quantile of eCRF (quantile 1) to 14.5% in the highest quantile of eCRF (quantile 5), and the association showed a graded response, with the quantiles 2, 3, and 4 also significantly associated with a lower prevalence of the Mets compared with the quantile 1. In men, similarly, the prevalence of Mets ranged from 46.4% in the lowest quantile to 14.8% in the highest quantile, and the association showed a graded response, with the quantiles 2, 3, and 4 also significantly associated with a lower prevalence of Mets compared with the quantile 1. The lower prevalence of Mets for the highest quantile compared with the lowest quantile remained significant in both men and women even after adjustments for age (p < 0.001 and p < 0.001 in men and women, respectively) and additionally adjustments for BMI, SMI, physical activity, smoking, heavy drinking, vitamin D, caloric intakes, and intakes of macronutrients (p < 0.05 and p < 0.05 in men and women, respectively).

In this population-based study, we examined the association between eCRF and Mets in Korean adults and found that eCRF was inversely associated with Mets, with men more likely to have a higher prevalence of Mets compared with women. This was the first study to show that the inverse association between eCRF and Mets remained statistically significant even after adjustments for all the covariates, implying a preventive role of CRF against the development of Mets in Korean adults.

The current findings of the study are in accordance with previous studies reporting an inverse association between CRF and Mets in Western populations. By analyzing the data obtained from two clinical trials involving 170 African-American postmenopausal women aged 40–65 years, for example, Adams-Campbel et al. [25] showed that individuals with very low CRF (< 18 mL·kg^− 1 ·min^− 1) had a higher prevalence of Mets, abdominal obesity, hypertriglyceridemia, and low HDL compared with individuals with moderate CRF (> 22 mL·kg^− 1 ·min^− 1), and the inverse association between CRF and Mets remained significant after adjustments for age, marital status, income, education, body composition, and other risk factors. By conducting a cohort of 3636 adults (1629 women) who participated in the Ball State Adult Fitness Program Longitudinal Lifestyle Study, Kelly et al. [26] also found an inverse and graded association between quartiles of CRF and Mets for both women and men, and the inverse association remained statistically significant even after adjustments for age at test date, physical activity, and cigarette smoking status. In addition, Ingle et al. [27] showed that fit British men had an approximately 50% lower prevalence of Mets compared with unfit British men, particularly in those aged 50 years or younger.

Similarly, an inverse association between CRF and Mets has been reported from previous studies involving Asian populations, such as Chinese women [28], Japanese women [29], and Chinese children [30]. In Korea, previous studies reported a significant association between physical fitness and Mets in older adults [11]. Similarly, parameters of muscular fitness and cardiopulmonary fitness were inversely and independently associated with the prevalence of Mets in older Korean adults [11]. Both high BMI and poor CRF were significantly associated with a higher prevalence of Mets in Korean adults [12], implying a synergistic effect of obesity and poor physical fitness on the etiology of Mets. In agreement with, Kim et al. [31] examined the relationship of visceral adiposity and CRF with Mets in a sample of 232 Korean overweight and obese adults, and found that high visceral adiposity and low CRF were additively associated with Mets. In that study, they also showed that high CRF alleviated the deleterious impact of visceral adiposity on Mets, implying CRF as a modifier in determining the relationship between visceral adiposity and Mets. Together, the findings of the current study agree with and extend the previous studies reporting eCRF as an independent predictor of Mets in Korean populations.

The preventive effects of higher eCRF quantiles against the prevalence of Mets observed in the present study represent levels that are attainable by most individuals. eCRF levels of approximately 29.9 mL/kg/min (or 8.5 METs) and 19.5 mL/kg/min (or 5.6 Mets) for men and women, respectively, represent the thresholds between the lowest quantile of eCRF and the second quantile of eCRF and are reasonably achievable through aerobic exercise. A lower prevalence of Mets was seen in those who were in the upper 4 quantiles in a dose-response manner, suggesting that further prevention against Mets can be achieved as one moves up the eCRF continuum with exercise training. In addition, the current findings show that logistic results for women and men were independent of all measured confounders, including age, markers of obesity and sarcopenia, physical activity, smoking, heavy drinking, vitamin D, caloric intake and intakes of macronutrients.

Several explanations can be given for the sex difference in the prevalence of Mets observed in the current study. First, we found that Korean men were more centrally obese than women. Central obesity is closely associated with whole body insulin resistance [9]. Consequently, central obesity-related insulin resistance, as shown by elevated levels of plasma insulin and HbA1c, is likely to have contributed to the sex difference. Second, an analysis by Oh et al. [32] of the 1988 KNHANES data showed that smoking was significantly associated with elevated TG and decreased HDL-C in conjunction with abdominal obesity in a dose-response manner. A higher rate of smoking might therefore have played a role in the sex difference we found. Lastly, other lifestyle risk factors such as heavy alcohol consumption, excessive caloric intakes, sarcopenic obesity, and physical inactivity may have played additional roles in determining the sex difference in the prevalence of Mets between Korean men and women [12, 21]. In particular, several mechanisms can be involved in the independent and inverse association between eCRF and Mets. First, CRF is positively associated with insulin sensitivity and/or insulin action in both overweight/obese [33] and normal subjects [34], implying its protective effect against Mets by enhancing insulin sensitivity. Second, high CRF provides a protective effect against Mets by suppressing pro-inflammation while enhancing anti-inflammation [35]. Third, high CRF alleviates the deleterious effects of central obesity and Mets [36]. Lastly, high CRF-induced promotion of mitochondrial biogenesis may lead to protection from Mets [37].

This study has several strengths and limitations. Strengths include a large sample size that is representative of Korean women and men over a wide range of age. To the best of our knowledge, this study represents the largest and Korean population-based study reporting an inverse association between eCRF and Mets after adjustment for a number of relevant confounders. In addition, the current findings support the use of eCRF as an alternative tool used to predict the risk of Mets. One study limitation is the inclusion of non-exercise-based estimates for CRF rather than objective measurements. The accuracy of eCRF used in the current study remains to be confirmed in a representative sample of Korean adults. The cross-sectional nature of the current study is another limitation in drawing conclusions about causation.

The current findings confirm a protective role of eCRF against the development of Mets in Korean women and men, implying that adopting a more physically active lifestyle and promoting fitness can be clinically important in upper quantiles, especially for the lowest quantile of eCRF.