C-reactive protein (CRP) and long-term air pollution with a focus on ultrafine particles

https://doi.org/10.1016/j.ijheh.2018.01.016Get rights and content

Highlights

  • We analyzed associations of residential long-term air pollution and the inflammatory marker CRP measured by a high-sensitivity (hs) assay.

  • Air pollutants including UFP (measured as PNC) were modeled by land-use regression.

  • PNC and PM10 showed a positive association with hs-CRP in single-pollutant models.

  • PNC and PM10 were significantly associated with hs-CRP after adjustment for PM2.5.

  • Never smokers, non-obese and non-diabetic participants indicated higher effect estimates.

Abstract

Background

Long-term exposure to ambient air pollution contributes to the global burden of disease by particularly affecting cardiovascular (CV) causes of death. We investigated the association between particle number concentration (PNC), a marker for ultrafine particles, and other air pollutants and high sensitivity C-reactive protein (hs-CRP) as a potential link between air pollution and CV disease.

Methods

We cross-sectionally analysed data from the second follow up (2013 and 2014) of the German KORA baseline survey which was conducted in 1999–2001. Residential long-term exposure to PNC and various other size fractions of particulate matter (PM10 with size of <10 μm in aerodynamic diameter, PMcoarse 2.5–10 μm or PM2.5 < 2.5 μm, respectively), soot (PM2.5abs: absorbance of PM2.5), nitrogen oxides (nitrogen dioxide NO2 or oxides NOx, respectively) and ozone (O3) were estimated by land-use regression models. Associations between annual air pollution concentrations and hs-CRP were modeled in 2252 participants using linear regression models adjusted for several confounders. Potential effect-modifiers were examined by interaction terms and two-pollutant models were calculated for pollutants with Spearman inter-correlation <0.70.

Results

Single pollutant models for PNC, PM10, PMcoarse, PM2.5abs, NO2 and NOx showed positive but non-significant associations with hs-CRP. For PNC, an interquartile range (2000 particles/cm3) increase was associated with a 3.6% (95% CI: −0.9%, 8.3%) increase in hs-CRP. A null association was found for PM2.5. Effect estimates were higher for women, non‐obese participants, for participants without diabetes and without a history of cardiovascular disease whereas ex-smokers showed lower estimates compared to smokers or non-smokers. For O3, the dose-response function suggested a non-linear relationship. In two-pollutant models, adjustment for PM2.5 strengthened the effect estimates for PNC and PM10 (6.3% increase per 2000 particles/cm3 [95% CI: 0.4%; 12.5%] and 7.3% per 16.5 μg/m3 [95% CI: 0.4%; 14.8%], respectively).

Conclusion

This study adds to a scarce but growing body of literature showing associations between long-term exposure to ultrafine particles and hs-CRP, one of the most intensely studied blood biomarkers for cardiovascular health. Our results highlight the role of ultrafine particles within the complex mixture of ambient air pollution and their inflammatory potential.

Introduction

According to the WHO, ambient air pollution contributed to 3.7 million premature deaths in 2012 worldwide including 280,000 in high-income countries of Europe and is therefore the largest environmental contributor to the burden of disease (Cohen et al., 2017). This risk factor particularly affects cardiovascular and cerebrovascular causes of death since these account for 80% of mortality attributable to ambient air pollution (WHO, 2014; Lim et al., 2012). Previous studies provide consistent evidence that long-term exposure to particulate matter (PM) air pollution is associated with cardiovascular morbidity and mortality (Brook et al., 2010; Newby et al., 2015). Although the exact mechanisms behind these effects are still unclear, an inflammatory response has been hypothesized to play an important role which is also supported by several animal studies (Upadhyay et al., 2010; Araujo et al., 2008). C‐reactive protein (CRP) is a reliable measure indicating systemic inflammation and high sensitivity (hs) CRP has also been reported to be a predictor for an increased risk of cardiovascular diseases (CVD) (Koenig et al., 2006).

Several epidemiological studies have reported associations of long-term exposure to air pollution with an increased level of CRP (Ostro et al., 2014; Hennig et al., 2014; Hoffmann et al., 2009) while others did not see an association (Dabass et al., 2016; Michikawa et al., 2016). A recent review on PM and hs-CRP did not find conclusive evidence yet (Li et al., 2012). However, previous studies mainly focused on larger particles like PM2.5 or PM10 (particulate matter with a size of <2.5 μm in aerodynamic diameter or <10 μm, respectively) whereas ultrafine particles (<100 nm) came into focus only recently. They are hypothesized to be more harmful than other particles (Delfino et al., 2005). Due to their small size they might even translocate from the lungs into the circulation which could directly lead to systemic inflammation (Araujo and Nel, 2009). Furthermore, their large surface may provide a mechanism for delivering much more potentially toxic absorbed organic material (Li et al., 2002). The California Teachers Study by Ostro et al. (Ostro et al., 2015) was the first study which investigated long-term effects of ultrafine particles on health and it prospectively included more than 100,000 participants. They reported a significant association of long-term exposure to ultrafine particles with all-cause and cardiovascular mortality. So far, only two studies have examined the association between long-term exposure to particle number concentration (PNC), as a proxy for ultrafine particles, and hs‐CRP. Viehmann et al. (2015) examined a population based prospective cohort study incorporating approximately 4800 participants finding a non-significant association whereas Lane et al. (2016) investigated 409 participants with regard to long-term exposure of near-highway ultrafine particle exposure in a cross-sectional design. The study rom the U.S. (Lane et al., 2016) also found a positive but non-significant association among all participants which even reached significance when including only the white non-Hispanic population.

To date, reliable data of chronic exposure to ultrafine particles are still lacking which in turn leads to the fact that no air quality standards are established regarding this air pollution metric. In terms of filling this gap, we examined the association of long-term exposure to air pollution and the inflammatory marker hs-CRP. We focused on ultrafine particles, but also other PM metrics, soot, nitrogen oxides and ozone were of interest. We hypothesized that long-term exposure to ambient air pollution would be positively associated with hs-CRP with ultrafine particles comprising higher toxicity.

Section snippets

Study population

This cross-sectional analysis is part of the KORA (Cooperative Health Research in the Region of Augsburg) study, a population-based, prospective cohort study conducted in southern Germany. Study participants were selected randomly from population registries in the city of Augsburg and two adjacent counties. A total of 4261 participants were examined at baseline (1999–2001) and 2279 of these participants took part in the second follow-up conducted from 2013 to 2014. The latter served as the data

Study population

Characteristics of the study population are presented in Table 1. In total, 2279 subjects participated in the study of which 25 had to be excluded due to missing data in either the outcome (N = 19), the exposure (N = 1) or the covariates (N = 5) of the main model. Two outliers were excluded after the inspection of residual plots and thus 2252 participants remained for our analyses. The study population available for analyses did not show systematic differences regarding outcome, exposure or

Summary

This cross-sectional study conducted in the city and the region of Augsburg in Germany investigated the association between long-term exposure to ultrafine particles and further ambient air pollutants and the inflammatory marker hs-CRP. Although we did not find statistically significant associations the results showed a trend to a positive association for PNC, PM10, PMcoarse, PM2.5abs, NO2 and NOx. No association was seen for PM2.5. The effect estimates were enhanced for females, non‐obese

Conclusion

Single-pollutant models showed a positive yet statistically non-significant association of long-term exposure to ultrafine particles and several other air pollutants with elevated levels of the inflammatory marker hs-CRP but no association for PM2.5 or O3. After adjustment for PM2.5, effect estimates increased for PNC and PM10 and reached significance. Our results highlight the role of ultrafine particles within the complex mixture of ambient air pollution and their inflammatory potential and

Declaration of interest

Nothing to declare.

Acknowledgements

The KORA study was initiated and financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität as part of LMUinnovative. In addition, this work was supported by intramural funding for Environmental Health projects of Helmholtz

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