Life's Essential 8 and risk of incident heart failure in community population without cardiovascular disease: Results of the sub-cohort of China PEACE Million Persons Project.

OBJECTIVE: The American Heart Association has introduced the Life's Essential 8 metrics to evaluate and promote cardiovascular health (CVH) and we aimed to evaluate the association of CVH and incident heart failure (HF). METHODS: The China PEACE Million Persons Project is a population-based cardiovascular disease (CVD) screening study. This was a sub-cohort of the project that included individuals free of CVD at baseline. Components and classifications of CVH, including diet, physical activity, smoking status, sleep status, body mass index (BMI), non-high density lipoprotein (non-HDL), blood glucose and blood pressure, were determined based on the Life's Essential 8. CVH status was categorized as poor, intermediate and ideal status. HF cases were identified by linking hospital records. RESULTS: Among the cohort (n = 38,571, median age 54 years and women 60.5%), proportion of individuals with poor, intermediate and ideal CVH was 30.7%, 56.9% and 12.4%. After a median follow-up of 3.56 years, the incidence of HF in individuals with poor, intermediate and ideal CVH was 2.5%, 1.1% and 0.5% respectively. Compared to poor CVH, intermediate (adjusted HR: 0.52 [95% CI: 0.43-0.61]) and ideal CVH (adjusted HR: 0.38 [95% CI: 0.26-0.57]) were associated with a lower HF risk. A gradient of association between CVH and HF risk was observed (P-trend<0.001). Ideal physical activity, ideal smoking status, and intermediate and ideal status of BMI, blood glucose and blood pressure were associated with a lower HF risk. CONCLUSION: Poor CVH was associated with an increased risk of HF, and promotion of CVH may help prevent HF development.

Association between walking pace and heart failure: A Mendelian randomization analysis.

BACKGROUND AND AIM: The relationship between walking pace and heart failure (HF) has been recognized, yet the directionality and underlying mediating risk factors remain unclear. METHODS AND RESULTS: This study utilized bidirectional two-sample Mendelian randomization (MR) with genome-wide association studies (GWAS) summary statistics to assess the causal relationships between walking pace and HF. Additionally, we employed a two-step Multivariable Mendelian Randomization (MVMR) to explore potential mediating factors. We further validated our findings by conducting two-sample MR with another available GWAS summary data on heart failure. Results indicated that genetically predicted increases in walking pace were associated with a reduced risk of HF (odds ratio (OR), 0.589, 95% confidence interval (CI): 0.417-0.832). Among the considered mediators, the waist-to-hip ratio (WHR) accounts for the largest proportion of the effect (45.7%, 95% CI: 13.2%, 78.2%). This is followed by type 2 diabetes at 24.4% (95% CI: 6.7%, 42.0%) and triglycerides at 18.6% (95% CI: 4.5%, 32.7%). Furthermore, our findings reveal that genetically predicted HF risk (OR, 0.975, 95% CI: 0.960-0.991) is associated with a slower walking pace. Validated findings were consistent with the main results. CONCLUSIONS: In conclusion, MR analysis demonstrates that a slow walking pace is a reliable indicator of an elevated risk of HF, and the causal relationship is bidirectional. Interventions focusing on waist-to-hip ratio, type 2 diabetes, and triglycerides may provide valuable strategies for HF prevention in individuals with a slow walking pace.

Association between metabolic phenotypes of overweight/obesity and cardiovascular diseases in postmenopausal women.

BACKGROUND AND AIM: Obesity and metabolic abnormalities were associated with an increased risk of cardiovascular disease. However, it is unclear how metabolic weight phenotypes relate to cardiovascular diseases in postmenopausal women. This study aimed to explore the relationships in postmenopausal women. METHODS AND RESULTS: We included 15,575 postmenopausal women aged 35-75 years (median age, 60.6) without cardiovascular disease at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project. Metabolically unhealthy phenotype was defined as having ≥2 risk factors of metabolic syndrome: blood pressure ≥130/85 mm Hg or current use of antihypertensive drugs, fasting glucose ≥5.6 mmol/L or current use of antidiabetic agents, triglycerides ≥1.7 mmol/L, and high-density lipoprotein cholesterol <1.3 mmol/L. Cox regression analysis was used to evaluate the risks of cardiovascular diseases. Over a median follow-up period of 3.55 (interquartile range, 2.59-4.44) years, a total of 1354 cardiovascular events occurred. Compared to metabolically healthy normal weight, the multivariate-adjusted hazard ratios and their 95% confidence intervals were 1.41 (1.16-1.72) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.48-2.08) for metabolically unhealthy overweight/obesity. Subdividing overweight/obesity into separate groups revealed higher total cardiovascular disease risk only in metabolically unhealthy individuals across body mass index categories. CONCLUSION: In postmenopausal women, both metabolically healthy overweight/obesity and metabolically unhealthy normal weight were associated with a higher risk of cardiovascular disease compared to metabolically healthy normal weight, and the greatest risk was observed in the metabolically unhealthy overweight/obesity category.

Association of adiposity indices with cardiometabolic multimorbidity among 101,973 chinese adults: a cross-sectional study.

BACKGROUND: Cardiometabolic multimorbidity (CMM) and obesity represent two major health problems. The relationship between adiposity indices and CMM, however, remains understudied. This study aimed to investigate the associations of body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and conicity index (CI) with CMM among Chinese adults. METHODS: Data of 101,973 participants were collected from a population-based screening project in Southern China. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, hypertension, and diabetes. The relationship between the six adiposity indices and CMM was investigated by multivariate logistic regression and restricted cubic splines. Receiver operator characteristic curve, C-statistic and net reclassification index were used to estimate the discriminative and incremental values of adiposity indices on CMM. RESULTS: Logistic regression models showed the six adiposity indices were all significantly associated with the odds of CMM with non-linear relationships. For per SD increment, WC (Odds ratio [OR]: 1.66; 95% confidence interval (CI): 1.62-1.70) and WHtR (OR, 1.61; 95% CI, 1.58-1.65) were more significantly associated with a higher prevalence of CMM than BMI (OR, 1.55; 95% CI, 1.52-1.58) (all P < 0.05). In addition, WC, WHtR, and BRI displayed significantly better performance in detecting CMM compared with BMI (all P < 0.05). Their respective area under the curve (AUC) values were 0.675 (95% CI: 0.670-0.680), 0.679 (95% CI: 0.675-0.684), and 0.679 (95% CI: 0.675-0.684), while BMI yielded an AUC of 0.637 (95% CI: 0.632-0.643). These findings hold true across all subgroups based on sex and age. When Adding WC, WHtR, or BRI to a base model, they all provided larger incremental values for the discrimination of CMM compared with BMI (all P < 0.05). CONCLUSIONS: Adiposity indices were closely associated with the odds of CMM, with WC and WHtR demonstrating stronger associations than BMI. WC, WHtR, and BRI were superior to BMI in discriminative ability for CMM. Avoidance of obesity (especially abdominal obesity) may be the preferred primary prevention strategy for CMM while controlling for other major CMM risk factors.

The relationship between famine exposure during early life and ascending aorta dilatation in adults.

The relationship between exposure to famine in early life and the risk of ascending aorta dilatation (AAD) in adulthood is still unclear; therefore, we aimed to examine the association in the Chinese population. We investigated the data of 2598 adults who were born between 1952 and 1964 in Guangdong, China. All enrolled subjects were categorised into five groups: not exposed to famine, exposed during fetal period, and exposed during early, mid or late childhood. AAD was assessed by cardiac ultrasound. Multivariate logistic regression and interaction tests were performed to estimate the OR and CI on the association between famine exposure and AAD. There were 2598 (943 male, mean age 58·3 ± 3·68 years) participants were enrolled, and 270 (10·4 %) subjects with AAD. We found that famine exposure (OR = 2·266, 95 % CI 1·477, 3·477, P = 0·013) was associated with elevated AAD after adjusting for multiple confounders. In addition, compared with the non-exposed group, the adjusted OR for famine exposure during fetal period, early, mid or late childhood were 1·374 (95 % CI 0·794, 2·364, P = 0·251), 1·976 (95 % CI 1·243, 3·181, P = 0·004), 1·929 (95 % CI 1·237, 3·058, P = 0·004) and 2·227 (95 % CI 1·433, 3·524, P < 0·001), respectively. Subgroup analysis showed that the effect of famine exposure on the association with AAD was more pronounced in female, current smokers, people with BMI ≥ 24 kg/m2 and hypertensive patients. We observed that exposure to famine during early life was linked to AAD in adulthood.

Serum 25-hydroxyvitamin D, frailty, and mortality among the Chinese oldest old: Results from the CLHLS study.

BACKGROUND AND AIMS: In this study, the aim is to explore whether frailty status modified the associations of serum 25(OH)D levels with all-cause and cause-specific mortality in the oldest old Chinese population. METHODS AND RESULTS: A total of 1411 participants aged at least 80 years were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Information on serum 25(OH)D level, frailty status, and covariates were examined at baseline. All-cause and cause-specific mortality status were ascertained during the follow-up survey conducted in 2017-2018 by using the ICD-10 codes. Cox proportional hazard models with stratified analyses were performed to evaluate potential associations. Over a median follow-up of 3.2 years, 722 (51.2%) participants were deceased, including 202 deaths due to circulatory diseases, and 520 deaths due to noncirculatory causes. After multivariable adjustment, the lowest quartile of serum 25(OH)D levels (Hazard Ratios (95% Confidence Intervals), 1.85 (1.45-2.36), 1.85 (1.45-2.36), 1.73 (1.31-2.29), respectively) and frailty (Odd Ratios (95% Confidence Intervals), 1.91 (1.60-2.29), 2.67 (1.90-3.74), 1.64 (1.31-2.05)) were associated with significantly higher risk of all-cause mortality, circulatory mortality, and noncirculatory mortality, respectively. In addition, we observed significant interactions among 25(OH)D and frailty on the risk of all-cause and cause-specific mortality (all P-interaction < 0.001). Similar results were found in sensitivity analyses by excluding participants who died in the first year of follow-up and using clinical cutoffs of serum 25(OH)D levels. CONCLUSION: Low serum 25(OH)D levels were associated with higher risk of all-cause and cause-specific mortality among the oldest old of the Chinese population, and the associations were significantly stronger in individuals with frailty.

Early-life exposure to the Chinese famine and risk of carotid intima-media thickness increased in adulthood.

BACKGROUND AND AIMS: Little was known about the effect of famine exposure on carotid intima-media thickness (cIMT). The present study aimed to explore the relationship in a Chinese population. METHODS AND RESULTS: Participants were divided into five groups: not exposed to famine, exposed to famine in fetal, early, mid or late childhood. Elevated cIMT was defined as a thickness of >0.9 mm measured by carotid ultrasound. Multivariate logistic regression was performed to calculate odds ratio (OR) and confidence interval (CI) between famine exposure and cIMT. A total of 2637 (970 male, mean age 59.1 ± 3.65 years) participants were recruited, and 491 (18.62%) of them had elevated cIMT. When compared with the non-exposure group, the fully adjusted ORs for increased cIMT for exposure in fetal, early, mid to late childhood were 1.321 (95%CI: 0.872, 1.994, P = 0.186), 1.713 (95% CI: 1.188, 2.483, P = 0.004), 2.359 (95% CI: 1.674, 3.357, P < 0.001) and 2.485 (95% CI: 1.773, 3.518, P < 0.001), respectively. Subgroup analyses showed that the exposure to famine did not interact with body mass index, gender, smoking status, hypertension and diabetes history on its effect on cIMT. CONCLUSION: Our findings indicated that early-life exposure to the Chinese famine might be associated with an increased risk of increased cIMT in adulthood.

Relationship between body mass index and ischaemic stroke in Chinese elderly hypertensive patients.

BACKGROUND: Despite obesity being a major risk factor for ischaemic stroke (IS), the association between body mass index (BMI) and IS in patients with hypertension remains uncertain. OBJECTIVE: To assess the association between BMI and IS among elderly hypertensive patients in China. METHODS AND RESULTS: We recruited 3500 hypertensive patients aged ≥60 between 1 January 2010 and 31 December 2011 in China and ascertained their stroke status until December 2016. Multivariate Cox regression was used to evaluate the association between BMI and IS with interaction tests for exposure and covariates. A total of 3315 subjects (mean age 71.41±7.20 years, 44.5% were men) were included for data analysis. During an average follow-up period of 5.5 years, there were 206 onset cases (6.21%) of IS. When BMI was treated as a continuous variable, it was positively associated with the incidence of new onset IS (HR=1.14; 95% CI: 1.05 to 1.34; p=0.005) after adjusting for potential confounders. Meanwhile, when BMI was treated as a categorical variable, the highest category (≥28 kg/m2) was strongly associated with an increased risk for IS compared with normal BMI category (18.5 to 24 kg/m2) (HR=1.36, 95% CI: 1.09 to 1.80; p<0.001) in the fully adjusted model. Subgroup and interaction analysis also demonstrated that BMI independently associated with IS among males, smokers, alcohol drinkers, diabetic patients, people with uncontrolled blood pressure, decreased estimated glomerular filtration rate and those aged ≥70 years. CONCLUSION: BMI was significantly associated with IS and was an independent risk of IS in Chinese elderly hypertensive patients.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality.

BACKGROUND: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR). OBJECTIVE: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults. METHODS: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality. RESULTS: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79). CONCLUSIONS: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.

Association between pulse pressure and ischaemic stroke in elderly patients with hypertension.

BACKGROUND: The association between pulse pressure (PP) and the risk of first ischaemic stroke (IS) is inconsistent. Therefore, we evaluated the association between PP and the risk of first IS among elderly hypertensive population in China. METHODS: This was a retrospective cohort study. Patients with hypertension and aged ≥60 years were recruited. Multivariate Cox regression was performed to evaluate the association between PP and the risk of IS. We further stratified the regression models into subgroups and test for interaction to assess whether the associations were modified by other covariates. RESULTS: A total of 3315 patients with hypertension (44.49% male; mean age 71.41±7.20 years) were included, and 206 cases of IS occurred with a median follow-up of 5.5 years. The results showed that per SD mm Hg increment in PP was associated with a 17% (95% CI 1.05 to 1.40, p=0.0172) increased risk of IS. Moreover, the HR of IS for the highest quartile of PP was 1.46 (95% CI 1.18 to 1.73, p=0.0011, p for trend <0.001) comparing with the lowest quartile of PP. Subgroup analysis showed that population aged ≥70 years, male, patients with smoking or drinking habit, diabetes at baseline, being overweight, with uncontrolled blood pressure or did not take antihypertensive drugs have a higher risk for IS. CONCLUSIONS: We found that PP was significantly associated with IS and was an independent risk factor for IS.

J-shaped association between serum uric acid and acute coronary syndrome in patients with essential hypertension.

BACKGROUND: The prognostic value of serum uric acid (SUA) for incident acute coronary syndrome (ACS) in hypertensive subjects is uncertain. Therefore, the present study examined the association between SUA and incident ACS in a large cohort of Chinese hypertensive adults. METHODS: This was a retrospective cohort study, which enrolled 5473 Chinese community-dwelling hypertensive patients from 1 January 2012 to 31 December 2012. Study outcomes were ACS events, and patients were followed until 31 December 2016. Cox regression analyses were conducted to determine adjusted HRs and 95% CIs for baseline SUA tertiles (low, middle and high group) and for men and women separately. RESULTS: A total of 5473 participants were included in the analysis (median follow-up was 4.5 years). Participants were divided into tertiles based on SUA levels. During follow-up, 9 (0.49%), 14 (0.77%) and 25 (1.37%) patients developed ACS in the lowest, middle and highest tertiles, respectively. When compared with the lowest tertile of SUA, the highest tertile of SUA was associated with ACS risk in all subjects and in men and women separately (HR: 2.62, 95% CI 1.14 to 7.01, p=0.0233; 2.15, 95% CI 1.08 to 6.04, p=0.021, and 3.49, 95% CI 1.25 to 7.74, p=0.017, respectively). CONCLUSIONS: Higher SUA levels were independently associated with an elevated risk of ACS incidence. The relationship between SUA levels and ACS in hypertensive patients was J-shaped.

Relationship between diastolic blood pressure and the first ischaemic stroke in elderly patients with hypertension.

BACKGROUND: It is uncertain how diastolic blood pressure (DBP) may associate with ischaemic stroke in elder patients with hypertension. We aimed to explore this relationship in a Chinese community. METHODS: A total of 3315 participants aged ≥60 years with essential hypertension were enrolled between January 2010 and December 2011, and being followed up until 31 December 2016. DBP levels were categorised into five groups (<60, 60-70, 70-80, 80-90 and ≥90 mm Hg), using 70-80 mm Hg as referent. We performed Cox regression analysis and subgroup analyses to evaluate the relationship between DBP and the incidence of ischaemic stroke. RESULTS: Among the 3315 participants, 44.49% were men and they were 71.4 years old on average. During a median follow-up period of 5.5 years, there were 206 onset cases of ischaemic stroke. The HRs for the first ischaemic stroke in the fully adjusted model were 1.32 (95% CI 0.73 to 2.40) for DBP <70 mm Hg, 1.50 (95% CI 1.13 to 2.73) for DBP between 80 and 89.9 mm Hg and 2.31 (95% CI 1.14 to 4.68) for DBP ≥90 mm Hg compared with DBP between 70 and 79.9 mm Hg (p=0.020 for trend). Subgroup and interaction analysis showed no significant findings. CONCLUSIONS: DBP had a non-linear association with the risk of ischaemic stroke among Chinese elderly patients with hypertension. DBP between 70 and 80 mm Hg may be an appropriate indicator for a lower stroke risk.

Relationship between serum uric acid level and all-cause and cardiovascular mortality in population with obesity.

BACKGROUND: We aimed to investigate the association between serum uric acid (SUA) and all-cause or cardiovascular mortality among participants with obesity. METHOD: All participants were included from the 1999 to 2014 National Health and Nutrition Examination Survey with follow-up mortality assessment through 31 December 2015. Cox proportional hazards models were built to estimate adjusted HRs and 95% CIs for mortality according to baseline uric acid in quartiles. Obesity was defined as body mass index ≥30 (kg/m2). Generalised additive model (GAM) and two-piecewise linear regression models were performed to explore any non-linearity in associations. RESULTS: There were 12 637 adults with obesity eligible for analysis. There were 999 (7.91%) all-cause and 147 (1.16%) cardiovascular mortality occurred during the mean follow-up of 98.11 months. Comparing with the lowest quartile of SUA, the highest SUA group did not have significant association with all-cause (HR 1.08, 95% CI 0.76 to 1.52) and cardiovascular mortality (HR 1.63, 95% CI 0.58 to 4.53) after adjusting for various confounding factors. GAM and two-piecewise linear regression model demonstrated a non-linearly relationship between SUA and all-cause mortality, and the corresponding cut-off point was 6.5 mg/dL. However, there is no significant relationship between uric acid and cardiovascular death on both sides of the cut-off value of 6.1 mg/dL. CONCLUSIONS: SUA showed a J-shaped relationship with all-cause mortality, but no significant with cardiovascular mortality in adults with obesity.

Relationship between triglyceride levels and ischaemic stroke in elderly hypertensive patients.

BACKGROUND: Although hyperlipidaemia was a well-known risk factor for ischaemic stroke, the association between triglyceride and first ischaemic stroke remains uncertain. OBJECTIVES: The present study attempted to explore the relationship between triglyceride and first ischaemic stroke in a Chinese community elderly patients with hypertension. METHODS AND RESULTS: This was a retrospective cohort study. We enrolled 3249 consecutive elderly patients with hypertension from a community in China between January 2010 and December 2011. Patients were divided into four groups based on the quartiles of triglyceride. Multivariate Cox regression analysis, subgroup and interaction test were performed to evaluate the relationship between triglyceride and first ischaemic stroke. There were a total of 3249 participants including 1455 male and 1794 female, with a mean age of 71.36±7.18 years. At an average follow-up of 5.5 years, 205 patients were identified to have first ischaemic stroke. After adjustment for potential confounders, using the lowest quartiles of triglyceride as the reference, multivariable HR (95% CI) for first ischaemic stroke increased in parallel with the quartiles of triglyceride (HRs were 1.56 (95% CI 1.07 to 2.51), 1.74 (95% CI 1.07 to 2.84) and 1.85 (95% CI 1.05 to 2.89)) from the second to the fourth quartiles, respectively (p=0.002 for trend). Subgroup and interaction analysis showed that there was no interactive effect on triglyceride and first ischaemic stroke. CONCLUSION: Triglyceride was an independent risk factor for first ischaemic stroke among Chinese elderly patients with hypertension.

U-shaped association between low-density lipid cholesterol and diabetes mellitus in patients with hypertension.

BACKGROUND: The magnitude and direction of association of low-density lipid cholesterol (LDL-C) with diabetes mellitus (DM) might differ by hypertensive status, but there is limited epidemiological evidence in China. METHODS: We examined the association between LDL-C levels and DM in 9892 participants with hypertension using logistic regression. Participants were stratified into three groups according to LDL-C levels (desirable, borderline high or high), then further divided into quartiles. Restricted cubic spline regression models, subgroup analysis and interaction tests were also conducted to evaluate the shape of association. RESULTS: After adjusting for covariates, lower LDL-C had a significant and inverse association with the likelihood of DM in all participants (OR: 0.944, 95% CI = 0.893, 0.998). In participants with desirable LDL-C concentrations (< 3.4 mmol/L), LDL-C protected against DM (OR = 1.240, 95% CI = 1.076, 1.429 per 1 mmol/L decrease). In participants with higher LDL-C concentrations (> 4.1 mmol/L), LDL-C increased the DM likelihood (OR = 1.536, 95% CI = 1.126, 2.096 per 1 mmol/L increase). Restricted cubic spline regression also found a U-shaped association between LDL-C levels and DM prevalence. CONCLUSIONS: There was a U-shaped association between LDL-C levels and DM in Chinese patients with hypertension.

Potential therapeutic targets for hypoxia-induced pulmonary artery hypertension.

BACKGROUND: Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction. Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of factors responsible for the proliferation of hypoxic pulmonary arterial smooth muscle cells (PASMCs), although the exact mechanisms remain unclear. METHODS: Pulmonary artery hypertension was induced in rats with or without 5-hydroxydecanoate (5-HD). The mean pulmonary artery pressure, morphologic changes, mRNA and protein expressions of voltage-gated potassium channels (Kv1.5 channel), were measured. The concentrations of monocyte chemo-attractant protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-ß1) were detected. Furthermore, pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured with or without hypoxia pretreated with or without 5-HD or/and Kv1.5 inhibitor 4-aminopyridine (4-AP). Mitochondrial membrane potential (Δψm) and the proliferation of PASMCs were detected. RESULTS: 5-HD significantly prevented the development of PAH by blocking the mitochondrial membrane depolarization, increased the expression of voltage-gated potassium channels, and reduced pulmonary hypertension mediated by TGF-ß1 or MCP-1 signaling pathway. CONCLUSION: The MitoKATP plays an important role in the development of PAH and may be therapeutic target for the treatment of disease.

Early activation of pulmonary TGF-ß1/Smad2 signaling in mice with acute pancreatitis-associated acute lung injury.

Acute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-ß (TGF-ß) is involved in the resolution of lung injury in later phases of the disease. Some evidence exists demonstrating that TGF-ß not only is involved in the late stages, but also contributes to lung injury early on in the progress of the disease. Acute pancreatitis was induced using ductal ligation in mice. TGF-ß1, 2, and 3, TßRII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were analyzed at 9 and 24 h. We demonstrate that TGF- ß1 levels in the lungs of mice with acute pancreatitis increase as early as 9 h after induction. We observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24 h. Inhibitory Smad7 expression was transiently increased at 9 h in acute pancreatitis, but reduced later at 24 h, with a concomitant increased nuclear translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF-ß signaling in the lungs as early as 24 h after acute pancreatitis, suggesting that TGF-ß may represent a potential therapeutic candidate in acute pancreatitis-induced acute lung injury.

Social Determinants of Health, Cardiovascular Health, and Outcomes in Community-Dwelling Adults Without Cardiovascular Disease.

Background: Limited data exist regarding the prognostic implications of social determinants of health (SDOH) and cardiovascular health (CVH) in Chinese community populations. Objectives: The aim of this study was to evaluate the associations of SDOH and CVH with major adverse cardiovascular events (MACE) and all-cause death. Methods: Individuals without cardiovascular disease were obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project. SDOH (educational attainment, economic stability, health care access, social support, and neighborhood) and CVH components were extracted. Participants were divided into groups with low and high burden of unfavorable SDOH and groups with poor, intermediate, and ideal CVH. MACE (a composite of coronary heart disease or myocardial infarction, stroke, heart failure, and cardiovascular death) and all-cause death were identified by linking hospital records with resident identity card number. Results: Among the cohort (n = 38,571, median age 54 years, 60.5% women), the proportion of individuals with a high burden of unfavorable SDOH was 68.9%, and that with poor CVH was 30.7%. In reference to the group with a low burden of unfavorable SDOH, the adjusted HRs for MACE and all-cause death in the high burden group were 1.18 (95% CI: 1.08-1.30) and 1.35 (95% CI: 1.09-1.68), respectively. In reference to the group with ideal CVH, poor CVH was associated with higher risks for MACE and all-cause death. A high burden of unfavorable SDOH and poor CVH exerted joint effects on all-cause death (HR: 2.20; 95% CI: 1.08-4.48). Conclusions: A high burden of unfavorable SDOH and poor CVH were associated with increased risks for MACE and mortality. Dedicated efforts are needed to address these health disparities.

Household use of solid fuel and sarcopenia among middle-aged and older adults: The China Health and Retirement Longitudinal Study.

OBJECTIVE: Few studies have examined the effects of air pollution on the risk of sarcopenia, especially pollution in indoor settings. We explored the cross-sectional and longitudinal associations of household use of solid fuel for cooking and heating, separately and simultaneously, with risk of sarcopenia. METHODS: Cross-sectional and follow-up data from the China Health and Retirement Longitudinal Study were used. Multivariable-adjusted generalized linear models and Cox proportional hazards regression models were performed to estimate the odds ratio and hazard ratio for sarcopenia, respectively. RESULTS: 11,494 (median age: 57.0 years; 47.4 % males) and 7483 (median age: 57.0 years; 46.9 % males) participants were included in the cross-sectional and longitudinal study, respectively. After fully adjusting for covariates, including outdoor concentration of particulate matter (PM2.5), both the use of solid fuels for cooking and use for heating were positively associated with incident sarcopenia in the longitudinal analyses, with hazard ratios (95 % confidence interval) of 1.56 (1.28-1.89) and 1.26 (1.04-1.52), respectively. Moreover, significant multiplicative and/or additive interactions were observed between age, smoking and cooking with solid fuel and risk of sarcopenia (all P for interaction <0.05). Similar results were found in the cross-sectional analyses. CONCLUSIONS: Household use of solid fuel was significantly associated with a higher risk of sarcopenia, while ageing and smoking had synergetic effects with burning solid fuels on the risk of sarcopenia. Our results highlight the importance of taking multi-pronged measures with respect to both air pollution and healthy lifestyle to prevent sarcopenia and promote healthy ageing.

Positive additive interaction effects of age, sex, obesity, and metabolic syndrome on left ventricular dysfunction.

OBJECTIVE: This study aims to explore the association between metabolic syndrome (MetS) and left ventricular diastolic dysfunction (LVDD) and systolic dysfunction (LVSD), defined by impaired global longitudinal strain (GLS), and assess additive and multiplicative interactions among age, sex, obesity, and MetS regarding LVDD and LVSD. METHODS: We prospectively recruited 5503 participants from the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project with complete echocardiography exam. Multivariable logistic models were used to calculate adjusted odds ratios to evaluate both additive and multiplicative interactions. RESULTS: The mean age was 56.59 years; 59.4% were women, 46.7% had MetS, 26.6% had left ventricular hypertrophy, 46.3% had LVDD, and 12.50% had impaired GLS. Compared to the non-MetS, the odds ratio (OR) of LVDD and impaired GLS in MetS were 1.40 (1.20-1.64) and 1.26 (1.03-1.54), respectively. For LVDD, relative excess risk due to additive interaction (RERI) for women and MetS, elderly and MetS, obesity and MetS were 0.76 (0.02-1.50), 35.65 (17.51-53.79), and 2.14 (0.66-3.62), respectively, thus suggesting additive interactions. For impaired GLS, RERI for obesity and MetS was 3.37 (0.50-6.24), thus suggesting additive interactions. CONCLUSIONS: The MetS is independently associated with LVDD and impaired GLS. From the public health implications, prevention of MetS in women, elderly, and obese individuals might result in a greater reduction of LVDD and LVSD risk in cardiovascular high-risk population.