Associations of long-term exposure to air pollution and physical activity with the risk of systemic inflammation-induced multimorbidity in Chinese adults: results from the China multi-ethnic cohort study (CMEC).

OBJECTIVE: Previous studies proved the effect of long-term exposure to air pollution or physical activity (PA) on the risk of systemic inflammation-induced multimorbidity (SIIM), while the evidence regarding their joint effects was rare, especially in low- and middle-income countries. Therefore, we aimed to examine the extent of interaction or joint relations of PA and air pollution with SIIM. METHODS: This study included 72,172 participants from China Multi-Ethnic Cohort.The average concentrations of ambient particulate matter pollutants (PM1, PM2.5, and PM10) were estimated using satellite-based random forest models. Self-reported information on a range of physical activities related to occupation, housework, commuting, and leisure activities was collected by an interviewer-administered questionnaire. A total of 11 chronic inflammatory systemic diseases were assessed based on self-reported lifetime diagnosis or medical examinations. SIIM was defined as having ≥ 2 chronic diseases related to systemic inflammation. Logistic regression models were used to assess the complex associations of air pollution particulate matter and PA with SIIM. RESULTS: We found positive associations between long-term air pollution particulates exposure and SIIM, with odds ratios (95%CI) of 1.07 (1.03 to 1.11), 1.18 (1.13 to 1.24), and 1.08 (1.05 to 1.12) per 10 µg/m3 increase in PM1, PM2.5, and PM10. No significant multiplicative interaction was found between ambient air pollutant exposure and PA on SIIM, whereas negative additive interaction was observed between long-term exposure to PM2.5 and PA on SIIM. The positive associations between low volume PA and SIIM were stronger among those exposed to high-level air pollution particulates. Compared with individuals engaged in high volume PA and exposed to low-level ambient air pollutants, those engaged in low volume PA and exposed to high-level ambient air pollutants had a higher risk of SIIM (OR = 1.49 in PM1 exposure, OR = 1.84 in PM2.5 exposure, OR = 1.19 in PM10 exposure). CONCLUSIONS: Long-term (3 years average) exposure to PM1, PM2.5, and PM10 was associated with an increased risk of SIIM. The associations were modified by PA, highlighting PA's importance in reducing SIIM for all people, especially those living in high-level air pollution regions.

Anemia is associated with long-term exposure to PM2.5 and its components: a large population-based study in Southwest China.

Background: Anemia is linked to PM2.5 (particulate matter with aerodynamic diameters of ⩽2.5 µm) exposure, which can increase the risk of various negative health outcomes. It remains unclear which PM2.5 components are associated with anemia and the respective contribution of each component to this association. Objective: This study aimed at investigating the association between PM2.5 and anemia in the general population and to identify the most critical PM2.5 toxic components in this association. Design: Cross-sectional study. Methods: Our study involved a large cohort of 73,511 individuals aged 30-79 from China's multi-ethnic population. We employed satellite observations and the chemical transport model (GEOS-Chem)to estimate the long-term exposure to PM2.5 and its components. Anemia was defined, according to WHO guidelines, as Hb levels below 130 g/L for men and below 120 g/L for women. Through logistic regression, we investigated the association between PM2.5 components and anemia. By utilizing weighted quantile sum (WQS) analysis, we identified key components and gained insights into their combined impact on anemia. Overall, our study sheds light on the relationship between PM2.5 exposure, its constituents, and the risk of anemia in a large cohort. Results: PM2.5 and three components, nitrate (NIT), organic matter (OM), and soil particles (SOIL), were associated with anemia. Per-standard deviation increase in the 3-year average concentrations of PM2.5 [odds ratio (OR): 1.14, 95% confidence interval (CI): 1.01, 1.28], NIT (1.20, 1.06, 1.35), OM (1.17, 1.04, 1.32), and SOIL (1.22, 1.11, 1.33) were associated with higher odds of anemia. In WQS regression analysis, the WQS index was associated with anemia (OR: 1.29, 95% CI: 1.13, 1.47). SOIL has the highest weight among all PM2.5 components. Conclusions: Long-term exposure to PM2.5 and its constituents is associated with anemia. Moreover, SOIL might be the most critical component of the relationship between PM2.5 and anemia. Our research increases the evidence of the association between PM2.5 and anemia in the general population, and targeted emission control measures should be taken into consideration to mitigate the adverse effects of PM2.5-related anemia.

The association between chemical constituents of ambient fine particulate matter and obesity in adults: A large population-based cohort study.

OBJECTIVES: Current evidence demonstrated that ambient fine particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and its constituents may be obesogenic in children, but evidence from adults is lacking. Our aim was to characterize the association between PM2.5 and its constituents and obesity in adults. METHODS: We included 68,914 participants from the China Multi-Ethnic Cohort (CMEC) baseline survey. Three-year average concentrations of PM2.5 and its constituents were evaluated by linking pollutant estimates to the geocoded residential addresses. Obesity was defined as body mass index (BMI) ≥ 28 kg/m2. Logistic regression was used to examine the relationship between PM2.5 and its constituents and obesity. We performed weighed quantile sum (WQS) regression to get the overall effect of PM2.5 and its constituents and the relative contribution of each constituent. RESULTS: Per-SD increase in PM2.5 (odds ratio [OR] = 1.43, 95% confidence interval [CI]: 1.37-1.49), black carbon (BC) (1.42, 1.36-1.48), ammonium (1.43, 1.37-1.49), nitrate (1.44, 1.38-1.50), organic matter (OM) (1.45, 1.39-1.51), sulfate (1.42, 1.35-1.48), and soil particles (SOIL) (1.31, 1.27-1.36) were positively associated with obesity, and SS (0.60, 0.55-0.65) was negatively associated with obesity. The overall effect (OR = 1.34, 95% CI: 1.29-1.41) of the PM2.5 and its constituents was positively associated with obesity, and ammonium made the most contribution to this relationship. Participants who were older, female, never smoked, lived in urban areas, had lower income or higher levels of physical activity were more significantly adversely affected by PM2.5, BC, ammonium, nitrate, OM, sulfate and SOIL compared to other individuals. CONCLUSION: Our study revealed that PM2.5 constituents except SS were positively associated with obesity, and ammonium played the most important role. These findings provided new evidence for public health interventions, especially the precise prevention and control of obesity.

The association between tea consumption and blood pressure in the adult population in Southwest China.

OBJECTIVES: Prior research on the effect of tea consumption on blood pressure (BP) generated inconsistent findings. The objective of this study was to explore the effects of different types of tea consumption on BP. METHODS: We included 76,673 participants aged 30-79 from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Binary logistic regression was used to analyze the influences of different types of tea consumption on the risk of hypertensive BP. Moreover, multiple linear regression was used to examine the association between tea drinking and BP. RESULTS: Tea consumption was associated with a reduced risk of hypertensive BP by 10% (AOR: 0.90, 95%CI: 0.86-0.94). While dark tea was related to a 1.79-5.31 mmHg reduction in systolic blood pressure (SBP) and a 0.47-1.02 mmHg reduction in diastolic blood pressure (DBP), sweet tea, regardless of the duration, frequency, or amount of consumption, significantly was associated with a reduced SBP by 3.19-7.18 mmHg. Green tea also was associated with a reduced SBP by 1.21-2.98 mmHg. Although scented tea was related to reduced SBP by 1.26-2.48 mmHg, the greatest effect came from the long duration (> 40 years:ß=-2.17 mmHg, 95%CI=-3.47 mmHg --0.87 mmHg), low frequency (1-2 d/w: ß = -2.48 mmHg, 95%CI=-3.76 mmHg--1.20 mmHg), and low amount (≤ 2 g/d: ß=-2.21 mmHg, 95%CI=-3.01 mmHg--1.40 mmHg). Additionally, scented tea was correlated to a decrease in DBP at the frequency of 1-2 d/w (ß=-0.84 mmHg, 95%CI=-1.65 mmHg--0.02 mmHg). Drinking black tea only was associated with lowered SBP. The protective effect of black tea on SBP was characterized by the long-duration (> 15 years, -2.63--5.76 mmHg), high frequency (6-7 d/w, -2.43 mmHg), and medium amount (2.1-4.0 g/d, -3.06 mmHg). CONCLUSION: Tea consumption was associated with lower SBP and a reduced risk of hypertensive BP. The antihypertensive effect varies across types of tea consumed.

Residential greenness associated with decreased risk of metabolic- dysfunction-associated fatty liver disease: Evidence from a large population-based epidemiological study.

BACKGROUND: Numerous studies have shown that residential greenness positively correlates with enhanced health. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects about a quarter of the population while lacking specific treatments. Given that the association between green space and MAFLD is still unknown, we explored the association between residential greenness and MAFLD as well as the potential mechanisms based on the baseline survey of the China Multi-Ethnic Cohort (CMEC). METHODS: Residential greenness was expressed as normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). MAFLD was assessed through hepatic steatosis, the presence of overweight/obesity, type 2 diabetes mellitus, and evidence of metabolic dysregulation. We used logistic regression to examine the association between NDVI/EVI and the prevalence of MAFLD. Moreover, we utilized causal mediation analyses to explore the role of physical activity and ambient particulate matters (PM1, PM2.5, and PM10) on the association between residential greenness and MAFLD. RESULTS: We included 72,368 participants from the CMEC and found that residential greenness was negatively associated with the prevalence of MAFLD. For an interquartile range (IQR) increase in NDVI500 m and EVI500 m, the odds ratio (OR) of MAFLD were 0.78 (95 %CI: 0.75, 0.81) and 0.81 (95 %CI: 0.78, 0.84), respectively. Greater association between residential greenness and MAFLD was observed among males. Air pollutants and physical activity could mediate a partial effect (8.5-22.9 %) of residential greenness on MAFLD. CONCLUSION: Higher residential greenness was associated with decreased risk of MAFLD. Moreover, the association was greater among males. The protective effects of residential greenness may be achieved by mitigating the hazardous effects of air pollutants and encouraging physical activity.

Associations and pathways between residential greenness and hyperuricemia among adults in rural and urban China.

BACKGROUND: Residential greenness may decrease the risk for hyperuricemia in rural areas, but the urban-rural disparities in this association and underlying pathways have not been studied. OBJECTIVES: To investigate the associations and potential pathways between residential greenness and hyperuricemia in urban and rural areas. METHODS: The baseline survey of the China Multi-Ethnic Cohort (CMEC) was used. Hyperuricemia was defined as serum uric acid (SUA) > 417 µmol/L for men and >357 µmol/L for women. The satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were used to capture residential greenness. A propensity score inverse-probability weighting method was used to assess urban-rural differences in the associations between residential greenness and hyperuricemia, with possible mediation effects of physical activity (PA), body mass index (BMI), PM2.5, and NO2 examined by causal mediation analyses. RESULTS: A total of 72,372 participants were included. The increases in the EVI500m and NDVI500m residential greenness were associated with a decreased risk for hyperuricemia and the SUA level in both urban and rural areas. For example, each 0.1-unit increase in EVI500m was associated with a decreased hyperuricemia risk of 7% (OR = 0.93 [0.91, 0.96]) and a decreased SUA level of -1.77 µmol/L [-2.60, -0.93], respectively; such associations were stronger in urban areas for both the risk for hyperuricemia (OR = 0.84 [0.83, 0.86]) and SUA level (-7.18 µmol/L [-7.91, -6.46]). The subgroup analysis showed that the greenness-hyperuricemia/SUA association varied by age, sex, and annual household income. The percentage of the joint mediation effect of PA, BMI, PM2.5, and NO2 on the association between EVI500m and the risk for hyperuricemia was higher in urban (34.92%) than rural areas (15.40%). BMI, PM2.5, and PA showed significantly independently mediation effects for the greenness-hyperuricemia association in both rural and urban areas. CONCLUSIONS: Exposure to residential greenness was associated with a decreased risk for hyperuricemia, partially through the pathways of PA, BMI, PM2.5, and NO2, which varied in urban and rural areas.

The role of lipid profile in the relationship between particulate matters and hyperuricemia: A prospective population study.

CONTEXT: Recent studies in specific population subgroups (e.g., pregnant women) have suggested PM exposure increases the risk of hyperuricemia. However, no studies have examined this in the general population. Furthermore, the underlying mechanism through which PM impacts hyperuricemia risk is poorly understood. OBJECTIVE: To assess the association between long-term exposure to PM and risk of hyperuricemia and whether this association is mediated by lipid profile. METHODS: We included 5939 participants in Southwest China from the China Multi-Ethnic Cohort (baseline 2018-2019, follow-up 2020-2021). Long-term PM pollutants (PM1, PM2.5, PM10) exposure for each individual was represented by the three-year average PM levels before the baseline survey. Hyperuricemia at follow-up was defined as the serum uric acid above 7.0 mg/dL in men and 6.0 mg/dL in women. Serum lipids were measured at baseline including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). The association of PM with hyperuricemia was accessed through logistic regression. The potential mediation effects of serum lipids were evaluated through causal mediation analyses. RESULTS: A total of 837 participants were newly diagnosed with hyperuricemia. The odds ratios of hyperuricemia associated with an interquartile range (IQR) increase in PM1, PM2.5, and PM10 (IQR: 21.10, 25.78, 30.43 µg m-3) were 1.72 (95% CI: 1.23, 2.39), 2.68 (95% CI: 1.59, 4.49), and 1.81 (95% CI: 1.20, 2.72), respectively. The association between PM2.5, PM1, and PM10 on hyperuricemia was mediated by HDL-C (10%) and LDL-C (3%). CONCLUSION: Higher particulate matter exposure was associated with higher hyperuricemia incidence. The decline in HDL-C and rise in LDL-C partially mediated this association. These findings were conducive to scientific research about the underlying mechanism of PM on hyperuricemia.

[Impact of plateau environment on seminal characteristics of native Tibetans and immigrated Tibetan Hans].

OBJECTIVE: To investigate the characteristics of the semen parameters of native Tibetans and immigrated Tibetan Hans in the high-altitude area and analyze the influence of altitude adaptation on male fertility. METHODS: This study included 1 563 infertile male patients, including 698 native Tibetans and 865 immigrated Tibetan Hans, and 56 normal fertile men, including 33 native Tibetans and 23 Tibetan Hans. We obtained semen samples from the subjects for routine semen analysis and sperm DNA fragmentation index (DFI) examination and collected peripheral blood for determination of the reproductive hormone levels. RESULTS: In the infertile patients, the native Tibetans, as compared with the immigrated Hans, showed significantly higher incidence rates of azoospermia (5.87% vs 2.89%, P <0.05), severe oligozoospermia (3.15% vs 1.73%, P <0.05) and abnormal seminal viscosity (43.12% vs 25.89%, P<0.01), but no statistically significant differences in the percentages of normozoospermia (81.08% vs 87.39%, P >0.05), oligozoospermia (5.44% vs 3.93%, P >0.05), severe asthenozoospermia (4.44% vs 4.04%, P >0.05) or severe teratozoospermia (4.58% vs 6.59%, P >0.05). In the normal fertile men, there were no statistically significant differences between the native Tibetans and immigrated Hans in age (ï¼»32.42 ± 4.82ï¼½ vs ï¼»34.57 ± 6.01ï¼½ yr, P >0.05), sperm concentration (ï¼»143.69 ± 85.74ï¼½ vs ï¼»155.11 ± 82.56ï¼½ ×106/ml, P >0.05), straight line velocity (ï¼»25.74 ± 3.94ï¼½ vs ï¼»27.24 ± 3.46ï¼½ µm/s, P >0.05), percentage of morphologically normal sperm (ï¼»8.22 ± 4.35ï¼½ vs ï¼»7.28±2.46ï¼½ %, P >0.05), total testosterone concentration (ï¼»17.97 ± 2.98ï¼½ vs ï¼»15.72 ± 6.38ï¼½ nmol/L, P >0.05), or follicle stimulating hormone level (ï¼»5.51 ± 1.62ï¼½ vs ï¼»4.17 ± 2.08ï¼½ IU/L, P >0.05). However, the immigrated Hans, in comparison with the native Tibetans, exhibited a higher sperm motility (ï¼»79.75 ± 14.67ï¼½ vs ï¼»66.58 ± 17.21ï¼½%, P <0.05), a lower curvilinear velocity (ï¼»60.97 ± 2.71ï¼½ vs ï¼»71.14 ± 82.13ï¼½ µm/s, P <0.05) and a lower level of luteinizing hormone (ï¼»4.28 ± 1.20ï¼½ vs ï¼»5.84 ± 1.15ï¼½ IU/L, P <0.05). CONCLUSIONS: During the acclimatization to the plateau hypoxia environment, the immigrated Tibetan Hans undergo adaptive changes in sperm concentration and motility and have lower incidence rates of azoospermia and severe oligozoospermia than native Tibetan males.

GCH1 plays a role in the high-altitude adaptation of Tibetans.

Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene ( GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase (NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.