Air pollution is associated with abnormal left ventricular diastolic function: a nationwide population-based study.

BACKGROUND: Air pollution is a growing public health concern of global significance. Till date, few studies have explored the associations between air pollutants and cardiac imaging phenotypes. In this study, we aim to explore the association of ambient air pollution and abnormal left ventricular diastolic function (ALVDF) among a large-scale free-living population. METHODS: The participants were from a national representative large-scale cross-sectional study, i.e., the China Hypertension Survey (CHS), 2012-15. After exclusion, 25,983 participants from 14 provinces and 30 districts in China were included for the final analysis. The annual average ambient PM2.5, PM10 and NO2 concentrations were obtained from the chemical data assimilation system (ChemDAS). The clinical evaluation of left ventricular function was conducted in the survey field which was based on echocardiography. Grading diastolic dysfunction was based on Recommendations for the evaluation of left ventricular diastolic function by echocardiography (2009). RESULTS: The mean age of 25,983 participants was 56.8 years, 46.5% were male, and the crude prevalence of GradeI-III ALVDF were 48.1%, 1.6% and 1.1%, respectively. The ORs (95% CI) for ALVDF in the fully adjusted model were 1.31 (1.11-1.56), 1.11 (1.01-1.21) and 1.18 (0.90-1.54) for an increase of 10 µg/m3 of PM2.5, PM10 and NO2, respectively. And for different grades of ALVDF, elevated concentration of PM2.5 and PM10 exposures significantly increased the risk of gradeIinstead of gradeII ~ III ALVDF. There was a positive linear and "J" shape concentration-response association between annual average ambient PM2.5 and NO2 and the ALVDF risk assessed by the restricted cubic spline. The exposure level of most participants to PM10 was less than 130 µg/m3, and the risk of ALVDF increased significantly with the concentration rise. CONCLUSIONS: This large-scale nationwide population study demonstrated a significantly positive association between ambient PM2.5, PM10 and NO2 with ALVDF, especially for mild ALVDF. The functional abnormality may partially explain the enhanced cardiovascular morbidity and mortality associated with air pollution, which highlights the importance of appropriate interventions to reduce ambient air pollution in China.

Long-Term Impacts of Diurnal Temperature Range on Mortality and Cardiovascular Disease: A Nationwide Prospective Cohort Study.

Previous studies have documented the associations between short-term diurnal temperature range (DTR) exposure and cardiovascular disease (CVD) via time-series analyses. However, the long-term impacts of DTR through a population-based prospective cohort have not been elucidated thoroughly. This study aimed to quantify the longitudinal association of DTR exposure with all-cause mortality and CVD in a nationwide prospective cohort and, by extension, project future DTR changes across China under climate change. We included 22,702 adults (median age 56.1 years, 53.7% women) free of CVD at baseline from a nationwide cross-sectional study in China during 2012-2015, and examined three health outcomes during a follow-up survey in 2018-2019. We estimated the chronic DTR exposure as baseline annual mean daily maximum minus minimum temperature. The Cox proportional hazards regression was adopted to assess the multivariable-adjusted hazard ratio and its corresponding 95% confidence interval (95% CI). We employed 31 downscaled global climate models under two shared socioeconomic pathways for future projection. During the median follow-up period of ~5 years, 1096 subjects died due to all causes while 993 and 597 individuals developed fatal or nonfatal CVD and fatal or nonfatal stroke, respectively. The cumulative incidence rates of all-cause mortality, CVD, and stroke were 10.49, 9.45, and 5.64 per 1000 person-years, respectively. In the fully adjusted models, the risks for all-cause mortality, CVD, and stroke would increase by 13% (95% CI: 8-18%), 12% (95% CI: 7-18%), and 9% (95% CI: 2-16%) per 1 °C increment in DTR, respectively. Moreover, linear positive associations for the concentration-response curves between DTR and mortality and CVD were observed. We also found significantly greater DTR-related mortality risks among rural residents than their urban counterparts. The DTR changes featured a dipole pattern across China under a warming climate. The southern (northern) China would experience increased (decreased) DTR exposure by the end of 21st century. The present study indicates that chronic DTR exposure can exert long-term impacts on mortality and CVD risks, which may inform future public health policies on DTR-related susceptible population and regions.

Blue sky as a protective factor for cardiovascular disease.

Objective: Blue sky has been considered to boost outdoor physical activity and social interaction, ameliorate work pressure and life stress, and enhance people's sense of happiness. However, the direct association between blue sky exposure and cardiovascular disease (CVD) still lacks epidemiological evidence. In this study, we aimed to quantify their relationship via a nationwide prospective cohort in China. Method: We extracted the baseline data from the China Hypertension Survey (CHS), by enrolling 22,702 participants aged ≥ 35 years without self-reported medical history of CVD from 14 provinces of China between 2012 and 2015 and followed up from 2018 to 2019. A blue day was marked out with no rain, low cloud cover ≤ climatological mean at each station, and visibility at 2 pm ≥ 21.52 km. We calculated the number of blue days at baseline survey year to evaluate the chronic individual blue day exposure. Cox proportional hazards models were employed to calculate the multivariable-adjusted hazard ratio (HR). We implemented subgroup analyses as well to identify potential effect modifications. Results: A total of 1,096, 993, and 597 incident cases of all-cause mortality, fatal or nonfatal CVD, and stroke occurred during a median follow-up around 5 years, respectively. A 10-day increase in annual blue day exposure was associated with a 3% (95% confidence interval [CI]: 1-6%) and 7% (95% CI: 5-10%) decreased risk of fatal or nonfatal CVD and stroke, respectively. Compared with those exposed to the worst tertile of blue days at baseline, subjects who exposed to the best tertile had a 32% (95% CI: 19-43%) and 43% (95% CI: 29-55%) lower likelihood of developing fatal or nonfatal CVD and stroke, respectively. Negative consistent exposure-response relationships were generally observed between them in the restricted cubic spline model. In the stratified analyses, the cardioprotective effects of blue sky were stronger for females, rural residents, and individuals residing in heavily contaminated areas. Conclusion: This study indicates that blue sky may serve as an independent environmental protective factor against CVD, and informs future policies on fighting air pollution and protecting the blue sky in China.

Left ventricular diastolic dysfunction and cardiovascular disease in different ambient air pollution conditions: A prospective cohort study.

Although previous studies indicated that the left ventricular diastolic dysfunction (LVDD) is associated with cardiovascular disease (CVD), it remains unclear whether effects would be enhanced or accelerated by long-term air pollution exposure. During 4.65 years (107,726 person-years) of follow-up, 942 cases of CVD events incident were identified among 23,143 participants from the China Hypertension Survey (CHS). Grading diastolic dysfunction was based on Recommendations for the evaluation of left ventricular diastolic function by echocardiography (2009). The annual average PM2.5, PM10 and NO2 concentrations were obtained by the chemical data assimilation system. Cox proportional hazards models were employed to estimate hazard ratios (HRs) for CVD in relation to LVDD. At baseline, the participants' mean age was 56.7 years, 46.8% were male. Compared to normal group, the HR (95% CI) of LVDD was 1.27 (1.07-1.50) after adjusting for all covariates. When stratified by ambient air pollution, we found that in middle and worst third PM2.5 areas, increased CVD risk was associated with increasing LVDD grade, both P for trend <0.05; The HRs (95% CI) of the CVD incidence were 1.52 (0.68-3.44), 4.97 (1.76-14.03) and 4.07 (1.44-11.49) for severe LVDD in the best, middle and worst third PM2.5 areas, respectively. Similar results were also presented for PM10 and NO2. In conclusion, our study highlights a stronger detectable adverse association between LVDD with CVD in worse ambient air quality assessed by any of the three primary ambient air pollutants (PM2.5, PM10 and NO2). Our study calls for appropriate interventions to reduce air pollution, which may promote great benefits to public health potentially by providing protection against the adverse CVD events.

Comprehensive characterization of lotus root polysaccharide-phenol complexes.

To explore the effects of phenolic binding on the structure and activity of lotus root polysaccharides (LRPs), five LRP-phenol complexes containing catechin (61.22 mg/g), gallic acid (9.37 mg/g), ferulic acid (29.28 mg/g), chlorogenic acid (83.80 mg/g) or caffeic acid (14.80 mg/g) were prepared via noncovalent intermolecular interaction, respectively. The interaction was confirmed by the differences among LRPs, phenols and their complexes in ultraviolet-visible and Fourier-transform infrared spectra. The phenolic binding caused significant changes in the molecular weight (MW) distribution and aggregation behavior of LRPs, particularly their average MW (34.49 kDa) increased by 3.73-8.30 times. Compared to LRPs, the complexes all showed stronger antioxidant activities. Notably, the binding of catechin improved the macrophage-stimulating effect of LRPs, specifically promoting the NO production at normal condition and inhibiting the NO overproduction induced by lipopolysaccharide. The noncovalent interaction with phenolic compounds is a promising method for the structural and functional improvement of LRPs.

Association of heating fuel types with mortality and cardiovascular events among non-smokers in China.

Only a few prospective studies have investigated the relationship between solid fuel use and cardiovascular disease (CVD) and mortality, and they have reported inconsistent conclusions. This study aimed to investigate the effect of solid fuel heating on the risk of CVD events and all-cause mortality among non-smokers. Data of this sub-study were obtained from the China Hypertension Survey (CHS), and 13,528 non-smoking participants aged 35 or above without self-reported medical history of CVD were enrolled between October 2012 and December 2015. CVD events and all-cause mortality were followed up in 2018 and 2019. The type of primary heating fuel was categorized as clean fuel (natural gas and electricity) and solid fuel (coal, wood, and straw). Cox regression was applied to evaluate the relationship between solid fuel use and CVD events and all-cause mortality. Of the 13,528 non-smoking participants, the mean age was 55.4 ± 13.1 years. During the median follow-up of 4.93 years, 424 participants developed fatal or nonfatal CVD (stroke, 273; coronary heart disease, 119; and other cardiovascular events, 32) and 288 died from all causes. The cumulative incidence of fatal and nonfatal CVD and all-cause mortality were 6.78 and 4.62 per 1000 person-years, respectively. Solid fuel heating was independently associated with an increased risk of fatal or nonfatal stroke and all-cause mortality compared with the use of clean fuels, the fully adjusted hazard ratios (HRs), and 95% confidence intervals (CI) were 1.44 (1.00-2.08) and 1.55 (1.10-2.17), respectively. The relationship between solid fuel heating and fatal and nonfatal CVD events was non-significant (HR = 1.19; 95% CI: 0.89-1.59). Solid fuel heating is longitudinally associated with a higher risk of stroke and all-cause mortality in non-smoking Chinese. Switching to cleaner energy sources for heating may be important for reducing the risk of CVD and mortality.

Long-term temperature variability and the incidence of cardiovascular diseases: A large, representative cohort study in China.

In the context of global climate change, far less is known about the impact of long-term temperature variability (TV), especially in developing countries. The current study aimed to estimate the effect of long-term TV on the incidence of cardiovascular disease (CVD) in China. A total of 23,721 individuals with a mean age of 56.15 years were enrolled at baseline from 2012 to 2016 and followed up during 2017-2019. TV was defined as the standard deviation of daily temperatures during survey years and was categorized into tertiles (lowest≤ 8.78 °C, middle = 8.78-10.07 °C, highest ≥ 10.07 °C). The Cox proportional hazards regression was used to estimate the multivariable-adjusted hazard ratio (HR) between TV and CVD. During the median follow-up of 4.65 years, we ascertained 836 cases of incident CVD. For per 1 °C increase in TV, there was a 6% increase of CVD (HR = 1.06 [95% confidence interval (CI): 1.01-1.11]). A significant positive trend was observed between CVD risk and increasing levels of TV compared to the lowest tertile [HR = 1.34 (95% CI: 1.13-1.59) for the medium tertile, HR = 1.72 (95% CI: 1.35-2.19) for the highest tertile, Ptrend < 0.001]. Exposure to high TV would lose 2.11 disease-free years for the population aged 35-65 years and 66 CVD cases (or 7.95% cases) could been attributable to TV higher than 8.11 °C in the current study. The current findings suggested that long-term TV was associated with a higher risk of CVD incidence, it is needed to reduce the TV-related adverse health effect.

Habitation Altitude and Left Ventricular Diastolic Function: A Population-Based Study.

Background Although numerous studies have been published evaluating the positive or negative effects of altitude on cardiovascular disease, many of them are conflicting. Methods and Results Data come from 2 cross-sectional surveys using a similar method in China; and a total of 34 215 residents, aged ≥35 years, were eligible and recruited in the study. Left ventricular diastolic dysfunction (LVDD), according to the 2009 American Society of Echocardiography guidelines, was defined and evaluated. Altitude was divided into low (<1500 m), middle (1500-3500 m), and high (≥3500 m) level groups. Among the 34 215 participants (aged 55.87 years; men, 45.92%; altitude ranging from 3.1 ~ 4507 m), 15 099 (crude prevalence, 44.13%), 517 (crude prevalence, 1.51%), and 272 (crude prevalence, 0.79%) were diagnosed as having grades I, II, and LVDD, respectively. Compared with low-level group, the odds ratios (ORs) (95% CIs) of LVDD for middle- and high-level groups were 1.65 (1.49-1.82) and 1.89 (1.63-2.19), respectively (Ptrend<0.001). The ORs (95% CI) were 1.43 (1.31-1.56) and 2.03 (1.67-2.47) per 500-m increment for middle- and high-level groups. There was a nonlinear relationship (upward-sloping "W" shape) between altitude and the risk of LVDD, assessed by the restricted cubic spline. For each LVDD grade, ORs (95% CIs) of grade I LVDD for middle- and high-level groups were 1.75 (1.59-1.92) and 1.95 (1.69-2.25), respectively; for grade II, ORs (95% CIs) for middle- and high-level groups were 6.19 (3.67-10.42) and 5.27 (2.18-12.74), respectively. The stratified analyses indicated that LVDD was much more remarkably influenced by elevated altitude in men (Pinteraction=0.0019). Conclusions Higher altitude is associated with increased risk of LVDD among people living over 1500 m, especially for men.

Air temperature variability and high-sensitivity C reactive protein in a general population of China.

BACKGROUND: Along with global climate change, the relationship between temperature variability (TV) and cardiovascular hospitalization and deaths have been well established. However, limited studies were conducted to reveal the underlying mechanism for TV-related cardiovascular diseases. OBJECTIVES: In the current study, a novel TV calculation, taking account for both interday and intraday TV as well as lag effects, was used to investigate the effect of short-term TV on the level of high-sensitivity C reactive protein (hs-CRP), which is a crucial preclinical predictor for cardiovascular disease (CVD). RESULTS: Among the 11,623 Chinese population (46.0% male; mean age 49.8 years), the average hs-CRP was 1.4 mg/ L (standard deviation 1.6 mg/L). Statistical significance between TV and hs-CRP was observed for different TV exposure days (TV01-TV07) in adjusted model, with highest effect for TV06. Specifically, per 1 °C increase in TV06 led to 2.241% (95%CI: 1.552%-2.935%) increase in hs-CRP. Female, obesity and elderly population were more susceptible to TV. The largest mediator for the association of TV and hs-CRP was lipoprotein(a), accounting for 8.68%, followed by smoking status (4.78%), alcohol use (3.95%) and systolic BP (3.20%). CONCLUSION: Short-term TV will significantly increase the level of hs-CRP, suggesting hs-CRP to be the potential biologic mechanisms underlying the cardiovascular effects of TV. And more attention should be paid to unstable weather in the global climate change context. Further developing efficient public health policies on climate change may benefit for global heath.

Disentangling loosening from softening: insights into primary cell wall structure.

How cell wall elasticity, plasticity, and time-dependent extension (creep) relate to one another, to plant cell wall structure and to cell growth remain unsettled topics. To examine these issues without the complexities of living tissues, we treated cell-free strips of onion epidermal walls with various enzymes and other agents to assess which polysaccharides bear mechanical forces in-plane and out-of-plane of the cell wall. This information is critical for integrating concepts of wall structure, wall material properties, tissue mechanics and mechanisms of cell growth. With atomic force microscopy we also monitored real-time changes in the wall surface during treatments. Driselase, a potent cocktail of wall-degrading enzymes, removed cellulose microfibrils in superficial lamellae sequentially, layer-by-layer, and softened the wall (reduced its mechanical stiffness), yet did not induce wall loosening (creep). In contrast Cel12A, a bifunctional xyloglucanase/cellulase, induced creep with only subtle changes in wall appearance. Both Driselase and Cel12A increased the tensile compliance, but differently for elastic and plastic components. Homogalacturonan solubilization by pectate lyase and calcium chelation greatly increased the indentation compliance without changing tensile compliances. Acidic buffer induced rapid cell wall creep via endogenous α-expansins, with negligible effects on wall compliances. We conclude that these various wall properties are not tightly coupled and therefore reflect distinctive aspects of wall structure. Cross-lamellate networks of cellulose microfibrils influenced creep and tensile stiffness whereas homogalacturonan influenced indentation mechanics. This information is crucial for constructing realistic molecular models that define how wall mechanics and growth depend on primary cell wall structure.

Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast.

The budding yeast actin cables and contractile ring are important for polarized growth and division, revealing basic aspects of cytoskeletal function. To study these formin-nucleated structures, we built a three-dimensional (3D) computational model with actin filaments represented as beads connected by springs. Polymerization by formins at the bud tip and bud neck, crosslinking, severing, and myosin pulling, are included. Parameter values were estimated from prior experiments. The model generates actin cable structures and dynamics similar to those of wild type and formin deletion mutant cells. Simulations with increased polymerization rate result in long, wavy cables. Simulated pulling by type V myosin stretches actin cables. Increasing the affinity of actin filaments for the bud neck together with reduced myosin V pulling promotes the formation of a bundle of antiparallel filaments at the bud neck, which we suggest as a model for the assembly of actin filaments to the contractile ring.

Dynamic network morphology and tension buildup in a 3D model of cytokinetic ring assembly.

During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes and bundled by cross-linking proteins. The myosin motors exert forces on the actin filaments, resulting in a net pulling of the nodes into a contractile ring, while cross-linking interactions help align actin filaments and nodes into a single bundle. We used these mechanisms in a three-dimensional computational model of contractile ring assembly, with semiflexible actin filaments growing from formins at cortical nodes, capturing of filaments by neighboring nodes, and cross-linking among filaments through attractive interactions. The model was used to predict profiles of actin filament density at the cell cortex, morphologies of condensing node-filament networks, and regimes of cortical tension by varying the node pulling force and strength of cross-linking among actin filaments. Results show that cross-linking interactions can lead to confinement of actin filaments at the simulated cortical boundary. We show that the ring-formation region in parameter space lies close to regions leading to clumps, meshworks or double rings, and stars/cables. Since boundaries between regions are not sharp, transient structures that resemble clumps, stars, and meshworks can appear in the process of ring assembly. These results are consistent with prior experiments with mutations in actin-filament turnover regulators, myosin motor activity, and changes in the concentration of cross-linkers that alter the morphology of the condensing network. Transient star shapes appear in some simulations, and these morphologies offer an explanation for star structures observed in prior experimental images. Finally, we quantify tension along actin filaments and forces on nodes during ring assembly and show that the mechanisms describing ring assembly can also drive ring constriction once the ring is formed.

Actin cable distribution and dynamics arising from cross-linking, motor pulling, and filament turnover.

The growth of fission yeast relies on the polymerization of actin filaments nucleated by formin For3p, which localizes at tip cortical sites. These actin filaments bundle to form actin cables that span the cell and guide the movement of vesicles toward the cell tips. A big challenge is to develop a quantitative understanding of these cellular actin structures. We used computer simulations to study the spatial and dynamical properties of actin cables. We simulated individual actin filaments as semiflexible polymers in three dimensions composed of beads connected with springs. Polymerization out of For3p cortical sites, bundling by cross-linkers, pulling by type V myosin, and severing by cofilin are simulated as growth, cross-linking, pulling, and turnover of the semiflexible polymers. With the foregoing mechanisms, the model generates actin cable structures and dynamics similar to those observed in live-cell experiments. Our simulations reproduce the particular actin cable structures in myoVΔ cells and predict the effect of increased myosin V pulling. Increasing cross-linking parameters generates thicker actin cables. It also leads to antiparallel and parallel phases with straight or curved cables, consistent with observations of cells overexpressing α-actinin. Finally, the model predicts that clustering of formins at cell tips promotes actin cable formation.

INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.

During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin motors exert forces that pull nodes together into a contractile ring. Cross-linking interactions help align actin filaments and nodes into a single bundle. Mutations in the myosin motor domain and changes in the concentration of cross-linkers alpha-actinin and fimbrin alter the morphology of the condensing network, leading to clumps, rings or extended meshworks. How the contractile tension developing during ring formation depends on the interplay between network morphology, myosin motor activity, cross-linking and actin filament turnover remains to be elucidated. We addressed this question using a 3D computational model in which semiflexible actin filaments (represented as beads connected by springs) grow from formins, can be captured by myosin in neighboring nodes, and get cross-linked with one another through an attractive interaction. We identify regimes of tension generation between connected nodes under a wide set of conditions regarding myosin dynamics and strength of cross-linking between actin filaments. We find conditions that maximize circumferential tension, correlate them with network morphology and propose experiments to test these predictions. This work addresses "Morphogenesis of soft and living matter" using computational modeling to simulate cytokinetic ring assembly from the key molecular mechanisms of viscoelastic cross-linked actin networks that include active molecular motors.