This is the first study to demonstrate chronic exposures to PM2.5 and transition metal components, including Mn, Fe, and Zn, are associated with subclinical atherosclerosis in young population. Although previous studies reported on the associations between traffic proximity, O3, or NOX exposures and CIMT in young population, they failed to demonstrate PM are associated with CIMT [16, 17]. There are several strengths in ours study findings. First, our exposure assessment of air pollutants and elemental constituents were conducted with LUR model which accounted for the effects of vertical distribution for high-rise buildings in urban area, thus minimizing exposure measurement error. Second, our study design largely ruled out the exposure misclassification from relocation, since our participants were invited for follow-up health examination in 2006‒2008 according to the address left at the first enrollment in the YOTA study from 1992 to 2000. Third, all participants are young population of age 12‒30 years, with less individual cardiovascular risk factors that may highlight the atherosclerotic effect of air pollutants. Although the point estimates of PM2.5 and transition metals on CIMT in this study were incremental, the results are still believed to add new insight on public health impact, even young population are less prevalent in cardiovascular comorbidities than older adults.
Though several studies have demonstrated associations between PM and CIMT in middle- or old-age population [3, 4, 13, 14, 25], our study first demonstrates the positive associations between PM2.5 and CIMT in young population. The individuals in this study exposed high annual exposure concentrations of PM2.5 (24.9 μg/m3), which is almost twice as high compared to those reported in published studies in western countries, may contribute to this particular finding. Nevertheless, the point estimate of percent difference in CIMT with PM2.5 exposure (0.77% with exposed to 4.5 μg/m3 of PM2.5) in this study is lower than a previous meta-analysis that showed a 5 μg/m3 increment of long-term exposure to PM2.5 is associated with 1.66% change in CIMT . The heterogenous findings between differernt age group may be attributable to that CIMT is chronic process in structural change and take longer time to demonstrate the measureable differences. Subroup analysis of this stuty showed significant associations between CIMT and PM2.5 only among young adults but not adolescents also support abovementioned hypothesis. Breton et al. (2012) demonstrated the effect estimate of CIMT of young adults are stonger among sbujects with cumulative O3 exposure since early childhood than those exposured in later life .
In addition to PM2.5, we further demonstrate long-term exposure to certain transition metals of PM2.5, namely Mn, Fe, and Zn, are associated with higher CIMT values. Epidemiological studies have demonstrated specific human activities, such as residing traffic proximity and cooking fuels, are associated with increased CIMT measures [11, 12, 27, 28]. Certain source-specific components of PM, including organic carbon, elemental carbon, black carbon, and S were reported to associate with increased CIMT values in elderly population [12, 28-31]. PM2.5absorbance exposure was associated to decreased carotid artery distensibility in young children . Several studies also demonstrated exposures to elemental components of PM2.5 contribute to other adverse cardiovascular effects related to atherosclerosis. Bilenko et al. (2015) demonstrated that PM10 elements, including Fe, K, and Si associated with higher diastolic BP values in children . PM2.5 metal composition, including Ni, Fe, and vanadium, were also reported to associate with higher BP values in young adults or elderly persons [33, 34]. Long-term exposures to Cu, Fe, and Zn, the transition metals of PM, may be associated with higher inflammatory biomarkers . A panel study of 17 mail carriers showed that metal compositions of PM2.5-1.0, including sodium, magnesium, calcium, strontium, manganese, and cadmium, significantly increased the cardio-ankle vascular index, a surrogate marker of arterial stiffness . These elements are emitted from multiple sources, such as Mn, Cu, Fe, and Zn from brake linings and tires; Si and Ti from road dust suspended by automobiles and wind; Ni and S from industrial or fossil fuel combustion [37, 38]. According to the regression coefficients, the strongest influence in LUR models for Fe and Zn are mainly attributed to traffic- or industry-related covariates, while Zn may also be partially emitted from population variables, such as cooking activities. Mn is primarily generated from the port activities, and partially from traffic, and industry operations. Because ship decommissioning activity does not exist in the buffers around sampling sites, Ho et al. (2015) speculated Mn possibly emitted by abrasive wear activities from ship movement in wharfs of Taipei metropolis . Our study results suggest source-specific PM2.5, primary from vehicular or industrial emissions, contribute to extra risk of subclinical atherosclerosis in young population.
The stratified analyses show that associations of combined CCA IMT values with PM2.5, Mn, Fe, or Zn are stronger in subjects who are females or lower household incomes than those with contrary stratum, which may suggest females or subjects with lower socioeconomic (SES) status are more vulnerable to exposure of air pollution, resulting in the acceleration of subclinical atherosclerosis. Existing research support our finding that carotid arterial wall thickness is more pronounced in females exposed to PM2.5 [8, 25, 39]. This observed vulnerability among females could be due to females having smaller airways, resulting in enhanced deposition of fine particles. More frequent exposures to cooking fuel among women may further contribute to the stronger associations of PM2.5 exposures with Taiwanese females. The epidemiological study in India showing associations between use of unvented stove and higher CIMT values, especially in women , further support our findings. The mediation effect of SES on relationships between air pollution and cardiovascular health still remains inconclusive ; however, several studies reported lower individual or neighborhood SES status may enhance the air pollution-related cardiovascular risk. Higher risk estimates of cardiovascular events with exposure to PM2.5 were observed among participants living in low-SES neighborhoods . Dragano et al. (2009) observed that women in the lowest income stratum have a significantly higher level of coronary artery calcification (CAC) associated with pollution exposure compared to women in the highest income stratum . Diez Roux et al. (2004) reported that low SES status also suffer from worse health outcomes resulting from psychosocial stress, which may mediate the effect of air pollution-related atherosclerosis . The higher air pollution and noise exposures in subjects with lower SES due to their residency proximity to traffic- or industrial-area may also contribute to the mediation between air pollution and subclinical atherosclerosis .
Stratified analyses of this study further demonstrate the vulnerability to air pollution in low cardiovascular risk subjects of non-smoking, normal weight, non-hypertensive, non-hyperglycemic, or non-hypercholesterolemic young population. Some other studies also agree with our findings. Kauffman et al. (2016) reported that the progression of coronary artery calcification with exposures to PM2.5 and NOX might be greater in non-diabetic, non-obese, non-hypercholesterolemic subjects . Epidemiological studies also reported that associations between PM and decreased renal function are stronger in non-diabetic subjects, which may share atherosclerotic change as the common pathophysiologic pathway [44, 45]. Our previous study also observed that CIMT values are associated with perfluorinated chemicals in healthy young subgroups . One possible explanation to the stronger effect of air pollution-related atherosclerosis in healthier young subjects is that the effect of air pollution on CIMT is weaker than the traditional cardiovascular risk factors such as obesity, smoking, hypertension, hyperglycemia, or hypercholesterolemia, which results in findings of insignificant air pollution-related atherosclerosis on subjects with unhealthy lifestyle or comorbidities. In other words, healthy young population must be more aware of air pollution-related atherogenic effect.
Several study limitations should be addressed. First, the lag time existed between health examination (performed during 2006‒2008) and exposure concentration estimation (LUR developed in 2009‒2010). The annual average concentrations of PM2.5 in Taipei metropolis during 2006‒2010 slightly decreased in trend (46), which could result in underestimation of personal annual mean exposures and effect estimates. Second, the R2 validations for several elemental constituents, including Si, S, Ti, Ni, and Zn, are less than 0.40 (Supplemental Table 2), which could possibly influence the accuracy of model prediction. Third, the results of stratified analyses may be biased under multiple comparisons, and insignificant findings among comorbid groups may be attributed to small sample size and wide confidence intervals. More studies are necessary to elucidate the population susceptibility of subclinical atherosclerosis to air pollution. Other possible unmeasured confounders are ambient or traffic noise, and endocrine disrupting chemicals such as perfluorinated compounds and phthalates, which have been shown to associate with atherosclerosis [47, 48].