Assessing causal relationship between non-alcoholic fatty liver disease and risk of atrial fibrillation.

Air pollution exposure and vascular endothelial function: a systematic review and meta-analysis.

Vascular endothelial dysfunction is an early stage to cardiovascular diseases (CVDs), but whether air pollution exposure has an effect on it remains unknown. We conducted a systematic review and meta-analysis to summarize epidemiological evidence between air pollution and endothelial dysfunction. We searched the database of PubMed, EMBASE, the Cochrane Library, and Web of Science up to November 10, 2022. Fixed and random effect models were used to pool the effect change or percent change (% change) and 95% confidence interval (95% CI) of vascular function associated with particulate matter (PM) and gaseous pollutants. I2 statistics, funnel plot, and Egger's test were used to evaluate heterogeneity and publication bias. There were 34 articles included in systematic review, and 25 studies included in meta-analysis. For each 10 µg/m3 increment in short-term PM2.5 exposure, augmentation index (AIx) and pulse wave velocity (PWV) increased by 2.73% (95% CI: 1.89%, 3.57%) and 0.56% (95% CI: 0.22%, 0.89%), and flow-mediated dilation (FMD) decreased by 0.17% (95% CI: - 0.33%, - 0.00%). For each 10 µg/m3 increment in long-term PM2.5 exposure, FMD decreased by 0.99% (95% CI: - 1.41%, - 0.57%). The associations between remaining pollutants and outcomes were not statistically significant. The effect of short-term PM2.5 exposure on FMD change was stronger in population with younger age, lower female proportion, higher mean body mass index and higher PM2.5 exposure. Cardiac or vasoactive medication might attenuate this effect. Our study provides evidence that PM2.5 exposure had adverse impact on vascular endothelial function, indicating the importance of air quality improvement for early CVD prevention.

Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease.

BACKGROUND:Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD.METHODS:Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators.FINDINGS:No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 = 2.07 × 10-8; OR2 = 0.57 [95% CI 0.39-0.82], p2 = 3.00 × 10-3). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 × 10-3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk.INTERPRETATION:Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects.FUNDING:Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Hourly personal temperature exposure and heart rate variability: A multi-center panel study in populations at intermediate to high-risk of cardiovascular disease.

BACKGROUND:Several studies reported temperature exposure was associated with altered cardiac automatic function, while this effect of temperature on hourly heart rate variability (HRV) among populations with cardiovascular risks was seldom addressed.METHODS:We conducted this panel study in four Chinese cities with three repeated visits among 296 participants at intermediate to high-risk of cardiovascular disease (CVD). Real-time temperature level and 24-h ambulatory electrocardiogram were monitored during each seasonal visit. Linear mixed-effects models were used to investigate associations between individual temperature and HRV parameters, and the seasonal effects and circadian effect were also evaluated.RESULTS:We found the overall downward trend of hourly HRV associated with acute exposure to higher temperature. For each 1 °C increment in temperature of 1-3 h prior to HRV measurements (lag 1-3 h), hourly standard deviation of normal-to-normal intervals (SDNN) decreased by 0.38% (95% confidence interval [CI]: 0.22, 0.54), 0.28% (95% CI: 0.12, 0.44), and 0.20% (95% CI: 0.04, 0.36), respectively. Similar inverse associations between temperature and HRV were observed in stratified analyses by temperature level. Inverse associations for cold and warm seasons were also observed, despite some effects gradually decreased and reversed in the warm season as lag times extended. Moreover, HRV showed a more significant reduction with increased temperature during daytime than nighttime. Percent change of hourly SDNN was -0.41% (95% CI: -0.62, -0.21) with 1 °C increment of lag 1 h during daytime, while few obvious changes were revealed during nighttime.CONCLUSIONS:Generally, increasing temperature was significantly associated with reduced HRV. Inverse relationships for cold and warm seasons were also observed. Associations during daytime were much more prominent than nighttime. Our findings clarified the relationship of temperature with HRV and provided evidence for prevention approaches to alleviate cardiac automatic dysfunction among populations at intermediate to high-risk of CVD.

Genetic risk modifies the effect of long-term fine particulate matter exposure on coronary artery disease.

BACKGROUND:Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood.METHODS:A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM2.5 exposures were assessed by adopting satellite-based PM2.5 estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM2.5 exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM2.5 exposure and CAD risk.RESULTS:During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM2.5 exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05-1.54) and 1.95 (1.57-2.42) among intermediate and high PM2.5 exposure groups compared to low PM2.5 exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18-1.66) and 133% (HR: 2.33, 95%CI: 1.94-2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM2.5 exposure, those with high genetic risk and high PM2.5 exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13-6.11). We observed significant multiplicative (P < 0.001) and additive interaction [relative excess risk due to interaction (95%CI): 2.75 (1.32-4.20); attributable proportion due to interaction (95%CI): 0.56 (0.42-0.70)] between genetic risk and PM2.5 exposure on CAD.CONCLUSION:This study provided evidence that long-term PM2.5 exposure might increase CAD risk, especially among people at high genetic risk. Our findings highlighted the importance of taking strategies on air quality improvement to cardiovascular disease prevention.

Assessing causal relationship between non-alcoholic fatty liver disease and risk of atrial fibrillation.

Air pollution exposure and vascular endothelial function: a systematic review and meta-analysis.

Vascular endothelial dysfunction is an early stage to cardiovascular diseases (CVDs), but whether air pollution exposure has an effect on it remains unknown. We conducted a systematic review and meta-analysis to summarize epidemiological evidence between air pollution and endothelial dysfunction. We searched the database of PubMed, EMBASE, the Cochrane Library, and Web of Science up to November 10, 2022. Fixed and random effect models were used to pool the effect change or percent change (% change) and 95% confidence interval (95% CI) of vascular function associated with particulate matter (PM) and gaseous pollutants. I2 statistics, funnel plot, and Egger's test were used to evaluate heterogeneity and publication bias. There were 34 articles included in systematic review, and 25 studies included in meta-analysis. For each 10 µg/m3 increment in short-term PM2.5 exposure, augmentation index (AIx) and pulse wave velocity (PWV) increased by 2.73% (95% CI: 1.89%, 3.57%) and 0.56% (95% CI: 0.22%, 0.89%), and flow-mediated dilation (FMD) decreased by 0.17% (95% CI: - 0.33%, - 0.00%). For each 10 µg/m3 increment in long-term PM2.5 exposure, FMD decreased by 0.99% (95% CI: - 1.41%, - 0.57%). The associations between remaining pollutants and outcomes were not statistically significant. The effect of short-term PM2.5 exposure on FMD change was stronger in population with younger age, lower female proportion, higher mean body mass index and higher PM2.5 exposure. Cardiac or vasoactive medication might attenuate this effect. Our study provides evidence that PM2.5 exposure had adverse impact on vascular endothelial function, indicating the importance of air quality improvement for early CVD prevention.

Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease.

BACKGROUND:Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD.METHODS:Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators.FINDINGS:No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 = 2.07 × 10-8; OR2 = 0.57 [95% CI 0.39-0.82], p2 = 3.00 × 10-3). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 × 10-3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk.INTERPRETATION:Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects.FUNDING:Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).

Hourly personal temperature exposure and heart rate variability: A multi-center panel study in populations at intermediate to high-risk of cardiovascular disease.

BACKGROUND:Several studies reported temperature exposure was associated with altered cardiac automatic function, while this effect of temperature on hourly heart rate variability (HRV) among populations with cardiovascular risks was seldom addressed.METHODS:We conducted this panel study in four Chinese cities with three repeated visits among 296 participants at intermediate to high-risk of cardiovascular disease (CVD). Real-time temperature level and 24-h ambulatory electrocardiogram were monitored during each seasonal visit. Linear mixed-effects models were used to investigate associations between individual temperature and HRV parameters, and the seasonal effects and circadian effect were also evaluated.RESULTS:We found the overall downward trend of hourly HRV associated with acute exposure to higher temperature. For each 1 °C increment in temperature of 1-3 h prior to HRV measurements (lag 1-3 h), hourly standard deviation of normal-to-normal intervals (SDNN) decreased by 0.38% (95% confidence interval [CI]: 0.22, 0.54), 0.28% (95% CI: 0.12, 0.44), and 0.20% (95% CI: 0.04, 0.36), respectively. Similar inverse associations between temperature and HRV were observed in stratified analyses by temperature level. Inverse associations for cold and warm seasons were also observed, despite some effects gradually decreased and reversed in the warm season as lag times extended. Moreover, HRV showed a more significant reduction with increased temperature during daytime than nighttime. Percent change of hourly SDNN was -0.41% (95% CI: -0.62, -0.21) with 1 °C increment of lag 1 h during daytime, while few obvious changes were revealed during nighttime.CONCLUSIONS:Generally, increasing temperature was significantly associated with reduced HRV. Inverse relationships for cold and warm seasons were also observed. Associations during daytime were much more prominent than nighttime. Our findings clarified the relationship of temperature with HRV and provided evidence for prevention approaches to alleviate cardiac automatic dysfunction among populations at intermediate to high-risk of CVD.

Genetic risk modifies the effect of long-term fine particulate matter exposure on coronary artery disease.

BACKGROUND:Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood.METHODS:A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM2.5 exposures were assessed by adopting satellite-based PM2.5 estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM2.5 exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM2.5 exposure and CAD risk.RESULTS:During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM2.5 exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05-1.54) and 1.95 (1.57-2.42) among intermediate and high PM2.5 exposure groups compared to low PM2.5 exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18-1.66) and 133% (HR: 2.33, 95%CI: 1.94-2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM2.5 exposure, those with high genetic risk and high PM2.5 exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13-6.11). We observed significant multiplicative (P < 0.001) and additive interaction [relative excess risk due to interaction (95%CI): 2.75 (1.32-4.20); attributable proportion due to interaction (95%CI): 0.56 (0.42-0.70)] between genetic risk and PM2.5 exposure on CAD.CONCLUSION:This study provided evidence that long-term PM2.5 exposure might increase CAD risk, especially among people at high genetic risk. Our findings highlighted the importance of taking strategies on air quality improvement to cardiovascular disease prevention.