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.

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.

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.

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.

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.

Stage 1 hypertension defined by the 2017 ACC/AHA blood pressure guideline and cardiometabolic multimorbidity in Chinese adults.

The association of blood pressure (BP) classification defined by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline with cardiometabolic multimorbidity (CMM) remains unclear. The present study aimed to investigate this research gap in the Chinese adults. Cross-sectional data were collected from a population-based cohort conducted in Southern China. Participants were categorized as having normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension according to the 2017 ACC/AHA guideline. CMM was defined as having two or more of the following diseases: coronary heart disease, stroke, and diabetes. The relationship between the BP classifications and CMM was examined by multivariate logistic regression. A total of 95 649 participants (mean age: 54.3 ± 10.2 years, 60.7% were women) were enrolled in this study. Multivariable-adjusted logistic regression models revealed that stage 1 hypertension (odds ratio [OR], 1.35; 95% confidence interval [CI], 1.03-1.78) and stage 2 hypertension (OR, 3.53; 95% CI, 2.82-4.47) were significantly associated with a higher prevalence of CMM compared with normal BP. The association between stage 1 hypertension and CMM were profound in women (OR, 1.76; 95% CI, 1.17-2.67) and in the middle-aged group (OR, 1.53; 95% CI, 1.02-2.35) compared with men and older individuals, respectively. Our study showed that among Chinese adults, stage 1 hypertension defined by the 2017 ACC/AHA guideline was already associated with higher odds of CMM compared with normal BP, particularly in women and middle-aged participants. Managing stage 1 hypertension may be an important measure to prevent CMM in Chinese adults.

Association of apolipoprotein B with all-cause and cardiovascular mortality among adults: Results from the National Health and Nutrition Examination Surveys.

BACKGROUND: Apolipoprotein B (apoB) is a crucial component that directly reflects the number of atherogenic lipoprotein particles and is closely related to atherosclerosis. However, there was an inconsistency among previous studies in its relationship with mortality. Using nationally representative data, we aimed to investigate the association of apoB with cardiovascular and all-cause mortality. METHODS: We retrospectively included participants from the National Health and Nutrition Examination Survey (2007-2014), and mortality was ascertained through December 31, 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) of apoB in quartiles (Q1-Q4) for mortality risk were calculated using multivariable-adjusted Cox proportional hazards models, and restricted cubic spline regressions were performed to test dose relationships. RESULTS: We enrolled 10,375 participants with a mean age of 46.3 years, of which 47.88% were men. During a mean follow-up time of 69.2 months, 533 (5.14%) and 91 (0.88%) deaths were due to all causes and cardiovascular disease, respectively. After adjusting for confounders, per SD, increment of apoB was associated with an elevated risk of cardiovascular mortality (HR, 1.13; 95% CI, 1.03-1.24). The risk of all-cause mortality was significantly reduced in the third quartile (Q3) of apoB (HR, 0.71; 95% CI, 0.56-0.91) compared with the reference quartile (Q1). Moreover, spline analyses showed that the relationship of apoB with all-cause mortality was U-shaped, and the threshold value was 108 mg/dL. CONCLUSIONS: ApoB was linearly associated with increased risk of cardiovascular mortality and non-linearly associated with all-cause mortality in a U-shaped manner, independently of other cardiovascular risk factors.

Association of adiposity indices with prehypertension among Chinese adults: A cross-sectional study.

The association of adiposity indices with prehypertension remains unclear in the Chinese non-hypertensive population. This study aimed to compare the association of adiposity indices, including waist circumference (WC), waist-to-height ratio, body roundness index (BRI), a body shape index (ABSI), and conicity index (CI), and prehypertension in the Chinese population. We recruited 61 475 participants from a population-based screening project in Guangdong province, China. Multiple logistic regression analyses were performed to detect the association between the six adiposity indices and prehypertension. Receiver operator characteristic curve (ROC) analysis was used to evaluate the predictive values of adiposity indices to prehypertension. The individuals were divided into two categories by blood pressure (BP) levels: normotension (<120/80 mmHg) and prehypertension (120-139/80-89 mmHg). A total of 33 233 people had prehypertension, with a prevalence of 54.04% and 42% males. Both logistics regression models presented a positive association between each adiposity index and prehypertension (p < .05), except for ABSI. The body mass index (BMI) was slightly more correlated with prehypertension than any other index. The standardized ORs for the six indices were 1.392, 1.361, 1.406, 1.039, 1.372, and 1.151, respectively. Compared to other adiposity indices, the WC had a significantly higher area under the curve (AUC) for predicting prehypertension (AUC: .619, sensitivity: 57%, specificity: 60.6%). In conclusion, WC and BMI might be the best indicators for prehypertension. Increasing evidence supports avoiding obesity as a preferred primary prevention strategy for prehypertension while controlling other major hypertension risk factors.

Association between triglyceride glucose-body mass index and hypertension in Chinese adults: A cross-sectional study.

The triglyceride glucose-body mass index (TyG-BMI) has been considered an alternative marker of insulin resistance (IR). This cross-sectional study was designed to mainly investigate the association between TyG-BMI, triglyceride glucose combined with body mass index, and hypertension in Chinese adults. The relationship between TyG-BMI and hypertension was examined by multivariate logistic regression and restricted cubic spline model. Multiple logistic regression models were also performed to examine the associations between the individual components of TyG-BMI (BMI, TyG index, TG and FBG) and hypertension. The incremental ability of TyG-BMI versus its individual components for hypertension discrimination was evaluated by C-statistic and net reclassification index. Subgroup analysis was performed to examine potential interactions. A total of 92,545 participants (38.9% men, mean age 53.7 years) were included for final analysis. Logistic regression models showed TyG-BMI and its individual components were all significantly associated with the odds of hypertension (p for trend < .001). The restricted cubic spline regression manifested a linear association between TyG-BMI and hypertension (p for non-linear = .062). The addition of TyG-BMI, in comparison with each individual component, exhibited the maximum incremental value for the discrimination of hypertension on the basis of base model (C-statistic: 0.679, 95% CI: 0.675-0.683 for base model vs. 0.695, 95% CI: 0.691-0.699 for base model + TyG-BMI; net reclassification index: 0.226, 95% CI: 0.215-0.234). TyG-BMI was significantly associated with the odds of hypertension and can be a better discriminator of hypertension.

Prenatal exposure to the Chinese famine of 1959-62 and risk of cardiovascular diseases in adulthood: findings from the China PEACE million persons project.

AIMS: Much remains unknown about the role of prenatal exposure to environmental stressors in the development of cardiovascular diseases (CVD). The current study aimed to investigate whether exposure to famine early in life was associated with a higher risk of CVD in adulthood. METHODS AND RESULTS: Among 71 667 men and women participated in the Patient-centred Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project in southern China, specific years of birth were used to define two cohorts: the exposed group (born during the famine of 1959-62) and the non-exposed group [born before the famine (1949-58) or after the famine (1963-72)]. Multivariable-adjusted generalized linear models were used to examine the associations of famine exposure with the risk of developing CVD, as well as with the 10-year CVD risk defined by well-established risk scores. Compared with the non-famine group, early-life exposure to the Chinese famine was significantly associated with increased risks of total CVD (odds ratio, OR = 1.28, 95% confidence interval: 1.16-1.41), coronary heart disease [OR: 1.23 (1.07-1.41)], acute myocardial infarction [OR: 1.32 (1.01-1.70)], heart failure [OR: 2.01 (1.53-2.60)], and stroke [OR: 1.28 (1.12-1.45)] in adulthood. In those without established CVD, early-life exposure to the famine was associated with higher levels of total cholesterol, systolic blood pressure, waist circumference, risk of diabetes, and therefore 10-year CVD risk. CONCLUSION: Early-life exposure to the Chinese famine is associated with an elevated CVD risk later in life, independent of known risk factors.

Association between famine exposure in early life and risk of hospitalization for heart failure in adulthood.

Background: Few studies have reported the association of early life exposure to famine with the risk of heart failure. The current study aimed to investigate whether exposure to famine in early life is associated with a higher risk of hospitalization for heart failure in adulthood. Methods: We used data from participants included in the sub-cohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project in Guangdong Province. Specific years of birth were used to define the famine-exposed group (born during the famine of 1959-1962), the pre-famine group (born before the famine [1954-1957], and the post-famine group (born after the famine [1964-1967]). Multivariable-adjusted generalized linear models were used to examine the associations of early life famine exposure with the risk of hospitalization for heart failure. Results: A total of 36,212 participants were enrolled in this analysis with a median age of 57.4 years and 37.5% of them were men. Compared with the post-famine group, famine births and pre-famine births were associated with increased risk of heart failure (OR: 1.96 [1.56-2.48] and OR: 1.62 [1.07-2.47], respectively). When compared with the age-balanced non-exposed group, the famine-exposed group was also significantly associated with increased risk of heart failure (OR: 1.32 [1.11-1.57]). The associations were stronger in participants with better economic status and in participants with hypertension, diabetes, and dyslipidemia (P for interaction < 0.05). Conclusion: Early life exposure to the Chinese famine is associated with an elevated risk of hospitalization for heart failure in adulthood.

Specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFNτ directs normal uterine fate for bovine early implantation.

Interferon-tau (IFNτ), as an antiluteolytic factor secreted by trophoderm during the pregnancy of ruminants, actually functions by activating the IFNτ receptor 1 (IFNAR1) and IFNτ receptor 2 (IFNAR2). However, it has not been clearly understood how IFNτ-IFNAR cascade regulation processes between the embryo and uterine epithelial cells in ruminants. In this study, we found the expression and location of IFNτ in the bovine blastocysts from different production sources. IFNτ, IFNAR1 and IFNAR2 were all located in the trophoblast cells of the blastocyst. However, the fluorescence intensity of IFNAR1 was consistent with that of IFNτ. Antagonizing the expressions of IFNAR1 and IFNAR2 in embryos and co-culture with endometrial epithelium cells (EECs) reduced the expressions of Integrin αv ß3, WNT7A, and ISG15 in EECs. Knocking out IFNAR1 and IFNAR2 reduce the expressions of Integrin αv ß3 and WNT7A in EECs, the deletion of IFNAR2 gene has a greater impact than that of IFNAR1 gene. IFNAR1-/IFNAR2+ and IFNAR1+/IFNAR2- EECs were co-cultured with IVF embryos, the expression of Integrin αv ß3 was inhibited, and the inhibition of IFNAR1+/IFNAR2- was much stronger, and the expression of WNT7A was not inhibited. The expressions of Integrin αv ß3 and WNT7A did not change significantly after IFNAR1-/IFNAR2+ and IFNAR1+/IFNAR2- co-culture with PA embryos. All of these results strongly suggest that specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFNτ directs normal uterine preparation for bovine early implantation.

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.

Evolutionary epigenomic analyses in mammalian early embryos reveal species-specific innovations and conserved principles of imprinting.

While mouse remains the most popular model, the conservation of parental-to-embryonic epigenetic transition across mammals is poorly defined. Through analysis of oocytes and early embryos in human, bovine, porcine, rat, and mouse, we revealed remarkable species-specific innovations as no single animal model fully recapitulates the human epigenetic transition. In rodent oocytes, transcription-dependent DNA methylation allows methylation of maternal imprints but not intergenic paternal imprints. Unexpectedly, prevalent DNA hypermethylation, paralleled by H3K36me2/3, also occurs in nontranscribed regions in porcine and bovine oocytes, except for megabase-long "CpG continents (CGCs)" where imprinting control regions preferentially reside. Broad H3K4me3 and H3K27me3 domains exist in nonhuman oocytes, yet only rodent H3K27me3 survives beyond genome activation. Coincidently, regulatory elements preferentially evade H3K27me3 in rodent oocytes, and failure to do so causes aberrant embryonic gene repression. Hence, the diverse mammalian innovations of parental-to-embryonic transition center on a delicate "to-methylate-or-not" balance in establishing imprints while protecting other regulatory regions.

Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients.

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients. Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity. Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 µmol/L; middle (SUA stable): ≥-32.6 µmol/L, <40.2 µmol/L; high (SUA increase substantially): ≥40.2 µmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially. Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

Association of Circulating, Inflammatory-Response Exosomal mRNAs With Acute Myocardial Infarction.

Background: Although many cardiovascular disease studies have focused on the microRNAs of circulating exosomes, the profile and the potential clinical diagnostic value of plasma exosomal long RNAs (exoLRs) are unknown for acute myocardial infarction (AMI). Methods: In this study, the exoLR profile of 10 AMI patients, eight stable coronary artery disease (CAD) patients, and 10 healthy individuals was assessed by RNA sequencing. Bioinformatic approaches were used to investigate the characteristics and potential clinical value of exoLRs. Results: Exosomal mRNAs comprised the majority of total exoLRs. Immune cell types analyzed by CIBERSORT showed that neutrophils and monocytes were significantly enriched in AMI patients, consistent with clinical baseline values. Biological process enrichment analysis and co-expression network analysis demonstrated neutrophil activation processes to be enriched in AMI patients. Furthermore, two exosomal mRNAs, ALPL and CXCR2, were identified as AMI biomarkers that may be useful for evaluation of the acute inflammatory response mediated by neutrophils. Conclusions: ExoLRs were assessed in AMI patients and found to be associated with the acute inflammatory response mediated by neutrophils. Exosomal mRNAs, ALPL and CXCR2, were identified as potentially useful biomarkers for the study of AMI.

The U-Shaped Association of Non-High-Density Lipoprotein Cholesterol Levels With All-Cause and Cardiovascular Mortality Among Patients With Hypertension.

Background: Non-high-density lipoprotein cholesterol (non-HDL-C) is a valuable indicator in routine blood lipid tests, but the associations of non-HDL-C with mortality in hypertensive population still remain uncertain. Methods: In the National Health and Nutrition Examination Surveys from 1999 to 2014, participants having hypertension were included and grouped by non-HDL-C levels (<130, 130-159, 160-189, 190-219, and ≥220 mg/dl). Multivariate Cox regression was conducted for calculation of hazard ratios (HR) and 95% confidence interval (CI). To reveal the relationship between non-HDL-C and mortality, Kaplan-Meier survival curves, restricted cubic spline, linear regression, and subgroup analysis were also applied. Results: A total of 12,169 participants (47.52% males, mean age 57.27 ± 15.79 years) were included. During average follow-up of 92.5 months, 1,946 (15.99%) all-cause deaths and 422 (3.47%) cardiovascular deaths occurred. After adjusting for confounders, the association of non-HDL-C with mortality was detected as U-shaped. Threshold values were observed at 158 mg/dl for all-cause mortality and 190 mg/dl as to cardiovascular mortality. Below the threshold, every 10 mg/dl increment in non-HDL-C attributed to relatively low all-cause mortality significantly (HR = 0.94, 95% CI: 0.92-0.96). Above the threshold, non-HDL-C has significant positive associations with both all-cause (HR = 1.03, 95% CI: 1.01-1.05) and cardiovascular mortality (HR = 1.09, 95% CI: 1.05-1.14). For subgroups analysis, similar results were found among participants age <65 years old, non-white population, those were not taking lipid-lowering drugs, and subjects with body mass index (BMI) ≥25 kg/m2. Conclusion: The U-shaped association was detected between non-HDL-C and mortality among hypertensive population.

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.

Association Between Vascular Overload Index and New-Onset Ischemic Stroke in Elderly Population with Hypertension.

BACKGROUND: Vascular overload index (VOI) is a marker of arterial stiffness and arteriolar resistance, which predicts the increasing risks of cardiovascular and cerebrovascular disease. This study aimed to evaluate the association between VOI and new-onset ischemic stroke in an elderly population with hypertension. METHODS: This retrospective cohort study included 3315 hypertensive participants aged 60 years or more. Ischemic stroke was diagnosed according to cranial computed tomography, magnetic resonance imaging of the brain or cerebrovascular angiography. The calculation of VOI was based on systolic and diastolic blood pressure. VOI was divided by quartiles (<7.88 mmHg, 7.88-16.10 mmHg, 16.10-27.14 mmHg, ≥27.14 mmHg) and evaluated the association with new-onset ischemic stroke by multivariable Cox regression models. RESULTS: A total of 3315 participants (55.5% female) aged 71.4±7.20 years were included in the analysis. The median follow-up period was 5.5 years, and 206 participants reached the endpoint, new-onset ischemic stroke. With per standard deviation increment in VOI, the risks of new-onset ischemic stroke increased in non-adjusted model (Hazard ratio [HR], 1.11; 95% confidence interval [CI]: 1.03-1.22; p = 0.001), adjusted model (HR, 1.11; 95% CI: 1.04-1.22; p = 0.003) and fully-adjusted model (HR, 1.15; 95% CI: 1.08-1.26; p<0.001), respectively. In multivariate fully adjusted model, the risks of ischemic stroke increased in higher quartiles in comparison to the first quartiles (p for trend <0.001). CONCLUSION: In an elderly hypertensive population, VOI is significantly associated with the incidence of new-onset ischemic stroke. Elevated VOI is the cardiovascular risk factor and increases the probability of new-onset ischemic stroke.