Longitudinal association between air pollution and green space with cardiometabolic risk factor clustering among children

Cardiometabolic risk factors are the largest contributors to the global disease burden, overall and for disease-related mortality [1,2]. Approximately, 63% of the deaths from cardiometabolic diseases (CMDs) were attributed to the combined effect of high blood pressure (BP), body mass index (BMI), blood glucose, and cholesterol in 2010 [1]. In terms of disability-adjusted life-years, high BP, BMI, blood glucose, and cholesterol were among the top 10 risk factors in 2016 [2]. Although CMDs occur most frequently among middle-aged adults, many cardiometabolic risk factors have been shown to be stable from childhood into adulthood [3]. And importantly, early-life exposures have later life consequences [4]. 
Air pollution and green space are important risk factors of cardiometabolic alterations among children [5–8]. Exposure to higher levels of air pollution may negatively impact cardiometabolic health through autonomic nervous system imbalance, pulmonary and systemic inflammation and oxidative stress [5,6]. Children are more vulnerable to the harmful effects of air pollutants than adults because their defense mechanisms are still evolving and because they inhale a higher volume of air pollutants per body weight than adults [9]. On the contrary, green space may improve cardiometabolic health by its restoring and building capacities [7,8]. For restoring, time in green space was shown to be associated with a higher level of cardioprotective factors like didehydroepiandrosterone and a lower level of risk factors like inflammatory cytokines [8]. For building, the green space release certain chemical agents with cardiometabolic health implication (e.g. phytoncides) [8]. It can also reduce harm from air pollution, heat, and noise [7]. 
Previous evidence of the association between air pollution, green space and cardiometabolic risk among children is limited and inconsistent. A nationwide school-based study in Iran investigated the association between air quality and individual cardiometabolic risk factors, and found significant positive associations for systolic BP, total cholesterol, and triglycerides [10]. A study in Spain showed that the distance from home to green space was not significantly associated with cardiometabolic risk levels in primary students [11]. Another study investigated the association between air pollution, green space and cardiometabolic risk in Dutch adolescents [12]. This study did not provide evidence for beneficial effects of green space or adverse effects of air pollution on cardiometabolic health in adolescents [12]. To our knowledge, previous studies are all based on cross-sectional design and thus meriting further longitudinal study to provide evidence of a temporal relationship. 
Previous studies focused on individual cardiometabolic risk factors or sum of z-scores [10–12], which are not good indicators of overall cardiometabolic risk [13]. An alternative indicator is metabolic syndrome (MetS), a standardized measure in adults referring to the presence of at least three of the following five medical conditions: abdominal obesity, high BP, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein (HDL-C) [14]. But, it has been suggested that MetS is rather controversial in pediatrics [13]. First, many definitions of pediatric MetS have been proposed but no consensus reached [13]. Second, pediatric MetS is highly unstable throughout childhood, and thus the predictive value of future risk is unclear [13]. 
Therefore, the American Academy of Pediatrics has recently recommended to focus more on cardiometabolic risk clustering [13], a continuous latent variable of cardiometabolic risk score (MetScore) rather than cutoff points [13]. The MetScore can better predict adult risk from early adolescence [3,13,15]. To our knowledge, this new approach has not been used in previous research to analyze the association between air pollution, green space, and cardiometabolic risk factors. The present study extends previous research and aims to examine the longitudinal association between air pollution, green space, and cardiometabolic risk factor clustering among children.