Tissue-resident C1q + macrophages exert anti-aging potential through the Sirt1 pathway.

OBJECTIVE: Resident immune cells are at the forefront of sensory organ-specific signals, and changes in these cells are closely related to the aging process. The Sirt pathway can regulate NAD + metabolism during aging, thereby affecting the accumulation of ROS. However, the role of the Sirt pathway in resident immune cells in aged tissues is currently unclear. METHODS: We investigated Sirt1 signalling in resident immune cells during chronic inflammation in an aged mouse model. Integrated single-cell RNA sequencing data from young and aged mice were used to refine the characterization of immune cells in aged tissues RESULTS: We found that C1q + macrophages could affect chronic inflammation during aging. C1q + macrophages acted in an opposing manner to Il1b + macrophages and were responsible for anti-inflammatory effects during aging. Sirt1 agonists inhibited the decrease in C1qb in macrophages during aging, and anti-aging drugs could affect the expression of C1qb in macrophages via the Sirt1 pathway. CONCLUSIONS: In this study, we first identified the relevance of C1q + macrophages in chronic inflammation during aging. The potential anti-aging effect of C1q + macrophages was mediated by the Sirt1 pathway, suggesting new strategies for aging immunotherapy.

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Relationship between normal weight central obesity and arterial stiffness in Chinese adults with hypertension.

BACKGROUND AND AIMS: Normal weight central obesity (NWCO) is a category of obesity that is characterized by having a normal BMI and presence of abdominal obesity. Recently, studies have reported that NWCO was associated with the cardiovascular diseases. The researches exploring the relationship between NWCO and arterial stiffness are limited. So this study intended to investigate the relationship between NWCO and arterial stiffness in Chinese adults with hypertension. METHODS AND RESULTS: This study is a sub-study of the China H-type Hypertension Registry Study. We included 8580 Chinese hypertensive patients with normal weight (18.5 kg/m2 ≤BMI <24 kg/m2). Central obesity was defined as waist-height ratio ≥0.5, and participants were categorized into two groups: NWCO and normal weight and no central obesity (NWNO). Using the brachial-ankle pulse wave conduction velocity (baPWV) assessed the arterial stiffness. Multiple linear regression analysis was used to evaluate relationship between NWCO and baPWV. Multiple logistic regression analysis was used to evaluate relationship between NWCO and arterial stiffness. Of 8580 participants, 4327 (50.4 %) were NWCO. The multiple linear regression analysis demonstrated that people with NWCO had higher baPWV value (total people: ß = 38.33, 95%CI 22.82-53.84; men: ß = 39.87, 95%CI 18.43-61.32; women: ß = 29.65, 95%CI 7.20-52.09) compared with NWNO. The baPWV ≥1800 cm/s was defined as arterial stiffness, and the multiple logistic regression analysis showed that people with NWCO associated higher arterial stiffness risk (total people: OR = 1.25, 95%CI 1.12-1.39; men: OR = 1.29, 95%CI 1.11-1.50; women: OR = 1.18, 95%CI 1.01-1.38). CONCLUSION: NWCO is significantly related to increased risk of arterial stiffness in Chinese adults with hypertension.

Sleep Patterns Modify the Association between Vitamin D Status and Coronary Heart Disease: Results from NHANES 2005-2008.

BACKGROUND: Although an increased risk of coronary heart disease (CHD) has been reported in individuals with low vitamin D status, this remains controversial. Growing evidence suggests that sleep behaviors may influence vitamin D endocrine functions. OBJECTIVES: We explored the association between serum 25-hydroxyvitamin D [[25(OH)D] concentrations and CHD and whether sleep behaviors modify this relationship. METHODS: A cross-sectional analysis of 7511 adults aged ≥20 y in 2005-2008 National Health and Nutrition Examination Survey (NHANES) that included serum 25(OH)D concentrations and provided information on sleep behaviors and history of CHD was performed. Logistic regression models were used to assess the association between serum 25(OH)D concentrations and CHD, whereas stratified analyses and multiplicative interaction tests were used to evaluate the modification effect of overall sleep patterns and each sleep factor on this relationship. The overall sleep patterns integrated 4 sleep behaviors (sleep duration, snoring, insomnia, and daytime sleepiness) in the form of healthy sleep score. RESULTS: Serum 25(OH)D concentrations were inversely associated with risk of CHD (P < 0.01). Hypovitaminosis D [serum 25(OH)D <50nmol/L] was associated with a 71% increased risk of CHD (OR: 1.71; 95% CI: 1.28, 2.28; P < 0.01) compared with that in participants with sufficient vitamin D [serum 25(OH)D ≥75nmol/L], and the association was more evident and stable among participants with poor sleep patterns (P-interaction < 0.01). Among the individual sleep behaviors, sleep duration had the strongest interaction with 25(OH)D (P-interaction < 0.05). The association between serum 25(OH)D concentrations and risk of CHD was more pronounced in participants with sleep duration <7 h/d or >8 h/d compared with those with sleep duration 7-8 h/d. CONCLUSIONS: These findings suggest that the influence of lifestyle-related behavioral risk factors, such as sleep behaviors (especially sleep duration), need to be considered when evaluating the association between serum 25(OH)D concentrations and CHD as well as the clinical benefits of vitamin D supplementation.

A Body Shape Index is positively associated with all-cause and cardiovascular disease mortality in the Chinese population with normal weight: A prospective cohort study.

BACKGROUND AND AIM: A body shape index (ABSI) is a valuable predictor of mortality in the Western population, but similar evidence in the general Chinese population is limited. This study aims to evaluate the association between the ABSI and all-cause and cardiovascular disease (CVD) mortality in the Chinese population with normal weight. METHODS AND RESULTS: 9046 participants with normal BMI (18.5-24.9 kg/m2) from the China Hypertension Survey were enrolled. The baseline ABSI was calculated as waist circumference/(BMI2/3height1/2). Cox proportional hazards regression was performed to evaluate the association of the ABSI with all-cause and CVD mortality. Over an average follow-up of 5.4 years, 686 all-cause and 215 CVD deaths occurred. A 0.01-unit increment in the ABSI was associated with a 31% greater risk of all-cause mortality (hazard ratio [HR], 1.31; 95% CI: 1.12, 1.48) and CVD mortality (HR, 1.30; 95% CI: 1.08, 1.58). Compared with quartile 1 of the ABSI, the adjusted HRs of all-cause mortality for quartiles 2-4 were, respectively, 1.25 (95% CI: 0.98, 1.59), 1.28 (95% CI: 0.99, 1.67), and 1.54 (95% CI: 1.17, 2.03) (Ptrend = 0.004), and those of CVD mortality for quartiles 2-4 were, respectively, 1.28 (95% CI: 0.88, 1.83), 1.42 (95% CI: 0.97, 2.08), and 1.45 (95% CI: 0.98, 2.170) (Ptrend = 0.043). The dose-response analysis showed a linear positive association of the ABSI with all-cause (Pnonlinearity = 0.158) and CVD mortality (Pnonlinearity = 0.213). CONCLUSION: The ABSI was positively associated with all-cause and CVD mortality among the general Chinese population with normal BMI. The data suggest that the ABSI may be an effective tool for central fatness for mortality risk assessment.

Associations between dietary copper intake and hypertriglyceridemia among children and adolescents in the US.

BACKGROUND AND AIMS: A relationship exists between dietary copper intake and hypertriglyceridemia in the United States (US). However, children and adolescents have there is limited research data for children and adolescents, who have not been thoroughly investigated. This study aimed to carefully evaluate this relationship. METHODS AND RESULTS: This cross-sectional study included 3982 children and adolescents who participated in the US National Health and Nutrition Examination Survey 1999-2006. The outcome variable was hypertriglyceridemia, defined as a triglyceride (TG) concentration >150 mg/dL. Multivariate and binary logistic regression models were applied in this study. The median (Q1-Q3) copper intake and TG levels were 0.98 (0.71-1.32) mg/d and 72.00 (53.00-100.00) mg/dL, respectively. The smoothing curve showed an inverted L-shaped relationship between copper intake and the prevalence of hypertriglyceridemia in American children and adolescents. A binary logistic regression model was developed to evaluate the relationship between copper intake and the prevalence of hypertriglyceridemia, and the inflection point was 0.76 mg/d. The odds of developing hypertriglyceridemia significantly increased with increasing levels of copper intake (odds ratio (OR), 2.00; 95% confidence interval (CI): 1.39-2.86) in participants with copper intake >0.76 mg/d (P for log likelihood ratio test = 0.032). The association between high copper intake and increased hypertriglyceridemia risk was significantly stronger in participants with a high body mass index (BMI; ≥23 kg/m2) (OR: 2.09; 95% CI: 1.42-3.07) than in those with a low BMI (tertile 1-2) (p for interaction = 0.048). Moreover, the increase in copper intake in adolescents aged 13-18 years significantly increased the prevalence of hypertriglyceridemia (OR: 1.95; 95% CI: 1.38-2.76; p for interaction = 0.001). CONCLUSION: Higher dietary copper intake increases the prevalence of hypertriglyceridemia, especially among US adolescents with a BMI ≥23 kg/m2.

Positive association between weight-adjusted-waist index and dementia in the Chinese population with hypertension: a cross-sectional study.

PURPOSE: The links between obesity and dementia remain equivocal. Therefore, this study aimed to explore the association between weight-adjusted waist index (WWI), a new anthropometric indicator reflecting obesity, and dementia in the Chinese population with hypertension. METHODS: A total of 10,289 participants with hypertension were enrolled in this cross-sectional study, a subset of the China H-type hypertension registry study. WWI was calculated as waist circumference (WC) divided by the square root of bodyweight. Mini-mental state examination (MMSE) scale was performed to evaluate the cognitive function. According to educational background, different MMSE cut-off values were applied to define dementia: < 24 for participants with ≥ 7 years of education, < 20 for those with 1-6 years of education, and < 17 for illiterate participants. Multivariable linear regression and multivariable binary logistic regression analyses were conducted to assess the associations between WWI and MMSE and dementia, respectively. RESULTS: Overall, the mean age was 63.7 ± 9.7 years, and 49.0% were males. Multivariate linear regression analyses showed that WWI was negatively associated with MMSE (ß, -1.09; 95% confidence interval [CI]: -1.24, -0.94). Consistently, multivariable binary logistic regression analyses found a positive association between WWI and the risk of dementia (odds ratio [OR], 1.45; 95% CI: 1.35, 1.56). Compared with individuals in quartile 1 of WWI, the adjusted ß and OR values of WWI for MMSE and dementia were -2.28 (95% CI: -2.62, -1.94) and 2.12 (95% CI: 1.81, 2.48), respectively. Results of smoothing curve fitting confirmed the linear association between WWI and MMSE and dementia. Subgroup analysis showed a stronger association between WWI and dementia in participants with hypertension with midday napping. CONCLUSION: WWI was independently and positively associated with dementia among the population with hypertension, especially in those with midday napping. The data suggests that WWI may serve as a simple and effective tool for the assessment of the risk of dementia in clinical practice.

The Association of Malnutrition With Chronic Kidney Disease in the Older Chinese Population With Hypertension: Evidence From the China H-type Hypertension Registry Study.

OBJECTIVE: Current evidence of the dose-response association between the geriatric nutritional risk index (GNRI) and chronic kidney disease (CKD) is limited. Hence, this study aimed to determine the association between GNRI and CKD in the elderly Chinese population with hypertension. METHODS: Data were derived from the China H-type Hypertension Registry. A total of 9,897 elderly patients with hypertension were included in the cross-sectional analysis. GNRI was calculated using the serum albumin and weight loss and the specific formula was as follows: GNRI = [1.489 × serum albumin (g/L)] + [41.7 × (actual weight/ideal weight)]. The outcome of our study was CKD, which was defined as an estimated glomerular filtration rate value of <60 mL/minute/1.73 m2. The association between the GNRI and CKD was analyzed using multivariate logistic regression. RESULTS: The present study population was composed of 9,897 participants with an average age of 68.67 (6.10) years. In particular, it was consisted of 4,683 (47.32%) male and 5,214 (52.68%) female participants. Overall, there was a significantly negative association between GNRI and CKD prevalence (per 1 increment; adjusted odds ratio [OR], 0.96; 95% confidence interval [CI]: 0.95-0.97). In a fully adjusted model, compared with the participants in the highest group tertiles 3 (GNRI ≥112), the participants in group tertiles 1 (GNRI <106) and group tertiles 2 (GNRI ≥106 ≤ 112) increased the prevalence of CKD by 57% (OR 1.57, 95% CI: 1.28-1.93) and 5% (OR 1.05, 95% CI: 0.86-1.28), respectively. Moreover, similar results were observed when the GNRI was assessed as a categorical variable based on the clinical cutoff values. CONCLUSION: This cross-sectional analysis found a significant negative association between GNRI and CKD among the elderly Chinese adults with hypertension.

[Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population].

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

[Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population].

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

[Relationship of Cognitive Function With Menarche Age,Menopause Age, and Reproductive Period in Female Patients With Hypertension].

Objective To explore the relationship of menarche age,menopause age,and reproductive period with cognitive function in the female patients with hypertension.Methods Hypertension screening was carried out in Wuyuan county of Jiangxi province from July to August in 2018.Data were collected through a face-to-face questionnaire survey,physical measurement,and biochemical tests.The cognitive function was scored according to the mini-mental state examination(MMSE)scale.Multiple linear regression and Logistic regression were employed to analyze the effects of menarche age,menopause age,and reproductive period on cognitive function,and the penalized spline regression to fit the curves.Results A total of 4595 postmenopausal women with hypertension were included in the analysis,with the mean age of(65.1±8.4)years,mean menarche age of(16.6±2.2)years,mean menopause age of(48.2±5.0)years,mean reproductive period of(31.7±5.5)years,mean MMSE score of(19.0±6.3)points,and total cognitive impairment detection rate of 40.4%(1859/4595).The detection rates of cognitive impairment were 28.4%,39.1%,and 45.8% in the females with the menarche ages of <15,15-16,and ≥17 years,47.9%,39.7%,and 38.3% in the females with the menopausal ages of <45,45-49,and ≥50 years,and 56.0%,44.4%,40.6%,and 32.6% in the females with the reproductive periods of <25,25-29,30-34,and ≥35 years,respectively.Moreover,the detection rates of cognitive impairment among different age groups were statistically significant(all P<0.05).Compared with the group with the menarche age <15 years,the groups with the menarche ages of 15-16 years and ≥17 years showed increased detection rates of cognitive impairment(OR=1.45,95%CI=1.19-1.75,P<0.001;OR=1.65,95%CI=1.37-1.98,P<0.001).Compared with the group with the menopausal age <45 years,the groups with the menopausal ages of 45-49 years and ≥50 years showed decreased detection rates of cognitive impairment(OR=0.80,95%CI=0.66-0.95,P=0.013;OR=0.78,95%CI=0.65-0.93,P<0.001).Compared with the group with the reproductive period <25 years,the groups with the reproductive periods of 25-29,30-34,and ≥35 years showed decreased detection rates of cognitive impairment(OR=0.66,95%CI=0.52-0.84,P<0.001;OR=0.62,95%CI=0.50-0.76,P<0.001;OR=0.51,95%CI=0.41-0.63,P<0.001).Conclusion The detection rate of cognitive impairment had a positive correlation with menarche age and negative correlations with menopause age and reproductive period in the female patients with hypertension.

[Association Between Plasma Homocysteine Level and Hyperuricemia in Elderly Patients With Hypertension].

Objective To explore the association between plasma homocysteine (Hcy) level and hyper-uricemia (HUA) in the elderly patients with hypertension.Methods From March to August in 2018,9902 hypertensive patients ≥ 60 years were routinely tested for blood biochemical indicators in Wuyuan county,Jiangxi province.The patients were assigned into a HUA group and a normal uric acid group.Multivariate Logistic regression was adopted to analyze the relationship between Hcy level and the risk of HUA.Results Compared with the normal uric acid group,the HUA group showed increased incidence of hyperhomocysteinemia (99.9% vs.98.7%,P<0.001) and elevated Hcy level[16.8 (13.8-21.5) µmol/L vs.14.4 (12.3-17.7) µmol/L,P<0.001].The multivariate Logistic regression analysis showed that after adjusting for influencing factors,the risk of HUA in the patients with hyperhomocysteinemia was 2.92 times of that in the patients with a normal Hcy level.The threshold effect analysis showed that the Hcy level was positively correlated with the occurrence of HUA in the case of Hcy<20 µmol/L (OR=1.05,95%CI=1.04-1.07,P<0.001).In the case of Hcy ≥ 20 µmol/L,there was no correlation between Hcy level and HUA (OR=1.00,95%CI=0.99-1.00,P=0.055),and the likelihood ratio test showed statistically significant results (P<0.001).Conclusion The elderly with hypertension should pay attention to control the Hcy level,which will be helpful to prevent the occurrence of HUA.

Disparities in Secondary Prevention between Stroke and Coronary Heart Disease in China: Cross-Sectional Community-Based Study, 2014-2016.

BACKGROUND: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China. METHODS: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models. RESULTS: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups. CONCLUSION: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps.

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy.

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

Association between plasma copper levels and first stroke: a community-based nested case-control study.

BACKGROUND AND AIMS: Uncertainty remains regarding the association between the risk of stroke and plasma copper levels in population with copper mostly in normal range due to limited data. We examined the association between baseline plasma copper and risk of first stroke in Chinese community-dwelling population. METHODS: We conducted a nested case control study from 'H-type Hypertension and Stroke Prevention and Control Project'. A total of 1255 first stroke cases and 1255 controls matched for age, sex and study site were included in the analysis. Conditional logistic regression analyses were performed to evaluate the association between plasma copper and first stroke. RESULTS: The overall mean of copper was 15.90 (2.66) µmol/L. In total, 94.26% participants' copper concentration was in the normal range by Mayo Clinic laboratory reference values. Smoothing curve showed that the associations of plasma copper with first stroke and its subtypes were linear. Each standard deviation (SD) increment of plasma copper was independently and positively associated with risk of first stroke [odds ratio (OR): 1.17, 95% confidence interval (CI): 1.07-1.28]. The multivariable ORs with 95% CIs for total stroke, ischemic stroke and hemorrhagic stroke in the highest versus the lowest quartile of plasma copper were 1.49 (1.16-1.90; P-trend = 0.001), 1.46 (1.12-1.92; P-trend = 0.004) and 2.05 (0.95-4.38; P-trend = 0.050), respectively. CONCLUSIONS: Baseline plasma copper was positively associated with risk of first ischemic stroke in an approximately linear fashion among Chinese community population (80.32% hypertensives), although their copper levels were mostly within the normal range according to current reference values. Our findings warrant additional investigation.

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in China: A prospective cohort study.

BACKGROUND AND AIMS: As a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China. METHODS AND RESULTS: A total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1-3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke). CONCLUSION: Higher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.

Association of marital status with cognitive function in Chinese hypertensive patients: a cross-sectional study.

PURPOSE: The aim of this study was to evaluate the association of marital status with cognitive function and to examine the potential effect modifiers in Chinese hypertensive populations. METHODS: A total of 9,525 adult Chinese hypertensive patients were enrolled in this cross-sectional study. Cognitive function, as the dependent variable in our study, was assessed by the Chinese version of the Mini-Mental State Examination (MMSE). We adjusted for potential confounding factors in multiple linear regression models to examine the relationship of marital status with cognitive function. In addition, we divided the population according to sex to explore whether there were sex-specific differences. RESULTS: Among the 9,525 study participants, the mean (SD) age for men was 63.5 (10.3) years, and the mean MMSE score was 24.9 ± 5.0, whereas for women, the mean (SD) age was 63.8 (9.3) years, and the mean MMSE score was 19.4 ± 6.4. Unmarried persons had lower scores on the MMSE and lower subscores in each of the cognitive domains. A stronger correlation between marital status and a lower MMSE score was statistically significant in men (unmarried men: ß = -1.55; 95% CI: -1.89, -1.21) but not women (unmarried women: ß = -0.22; 95% CI: -0.56, 0.12; p interaction = 0.006). Compared to men who were widowed or divorced, never married men were more likely to have lower MMSE scores (ß = -2.30, 95% CI -3.10,-1.50; p < 0.001). CONCLUSIONS: Our study demonstrated that being unmarried is an extremely important but neglected social risk factor for cognitive function. Sex was a strong effect modifier: being unmarried was correlated with a higher risk of cognitive decline than being married in Chinese hypertensive men, especially among older men, but this correlation was not observed among women. Moreover, never married men showed poorer cognitive function than those who were divorced or widowed.

Association Between Hyperhomocysteinemia Combined with Metabolic Syndrome and Higher Prevalence of Stroke in Chinese Adults Who Have Elevated Blood Pressure.

BACKGROUND Hyperhomocysteinemia (HHcy) and metabolic syndrome (MS) are established cardiovascular risk factors of stroke and are frequently associated with hypertension. However, studies on the association between HHcy combined with MS and stroke risk in hypertensive patients were absent. MATERIAL AND METHODS In 14 059 selected participants with elevated blood pressure, we assessed the prevalence of the MS and stroke. We defined HHcy as plasma total homocysteine >15 µmol/L. MS was defined according to the Chinese Diabetes Society (CDS) criterion. Multivariable analysis was used to examine the association of HHcy or (and) MS with stroke risk in different models. RESULTS The prevalence rates of HHcy and MS were 49.96% and 42.21%, respectively. Patients with stroke had higher plasma total homocysteine levels and a higher prevalence of MS (P<0.001). Multivariable analyses indicated that HHcy and MS are independently associated with higher prevalence of stroke (adjusted-odds ratio (OR): 1.36, 95% CI 1.17 to 1.58, P<0.001; adjusted-OR: 1.68, 95% CI 1.44 to 1.96, P<0.001, respectively). Those with combined HHcy and MS had higher odds of stroke than those with isolated HHcy or MS (adjusted-OR: 1.78, 95% CI 1.47 to 2.15, P<0.001; adjusted-OR: 1.39, 95% CI 1.13 to 1.70, P=0.002, respectively). CONCLUSIONS HHcy combined with MS was associated with higher prevalence of stroke in Chinese adults with elevated blood pressure.

Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China.

BACKGROUND: Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China. METHODS: A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs. RESULTS: Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)-lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65-0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56-0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45-0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52-0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14-1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57-0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24-17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61-2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38-0.55]; OR, 0.60 [95% CI, 0.52-0.69]; OR, 0.55 [95% CI, 0.48-0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01-1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level. CONCLUSIONS: Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.

Visceral Adiposity Index Is Inversely Associated with Renal Function in Normal-Weight Adults with Hypertension: The China H-Type Hypertension Registry Study.

BACKGROUND: Risk of chronic kidney disease (CKD) is higher in normal-weight metabolically unhealthy people, especially when combined with hypertension. In this context, whether the visceral adiposity index (VAI), which reflects body fat distribution and metabolism, can be used to identify the risk of CKD among normal-weight hypertensive patients is unclear. OBJECTIVES: This study aimed to evaluate the association between VAI and renal function in normal-weight hypertensive patients. METHODS: In this cross-sectional study, 8591 hypertensive patients with normal BMI from the China H-type Hypertension Registry Study were analyzed. The VAI was calculated with serum triglycerides, serum HDL cholesterol, waist circumference, and BMI. VAI was ln-transformed for analysis on account of the skewed distribution. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL · min-1 · 1.73 m-2. Multivariable linear and multivariable logistic regression analyses were performed to evaluate the association of VAI with eGFR and CKD. RESULTS: The prevalence rate of CKD was 10.1%. Multivariable linear regression analyses showed that an elevated lnVAI reduced eGFR by 2.63 mL · min-1 · 1.73 m-2 (95% CI: -3.54, -1.72 mL · min-1 · 1.73 m-2). Multivariable logistic regression analysis showed that an elevated lnVAI was independently associated with the prevalence of CKD (OR: 1.59; 95% CI: 1.31, 1.93). As possible confounding factors were removed the association became greater. The higher the VAI was, the greater the decrease in eGFR and the higher the risk of CKD. No significant interactions were found in any of the subgroups (age, sex, physical activity, current smoking, current drinking, fasting glucose, LDL cholesterol, blood pressure, and antihypertensive drugs). CONCLUSIONS: VAI, as a simple surrogate measure of visceral fat accumulation, is independently and inversely associated with renal function in normal-weight Chinese hypertensive adults.This trial was registered at chictr.org.cn as ChiCTR1800017274.