Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer-binding protein beta.

Dexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 µg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling-induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer-binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c-Jun N-terminal kinase (JNK)/p-38 signaling pathway, inhibiting microglial M1 polarization-mediated inflammation in the central nervous system.

Interactive effect of increased high sensitive C-reactive protein and dyslipidemia on cardiovascular diseases: a 12-year prospective cohort study.

BACKGROUND: Dyslipidemia and inflammation are significant factors for the onset of cardiovascular diseases (CVD); however, studies regarding their interactions on the risk of CVD are scarce. This study aimed to assess the interaction of dyslipidemia and high-sensitivity C-reactive protein (hs-CRP) on CVD. METHODS: This prospective cohort enrolled 4,128 adults at baseline in 2009 and followed them up until May 2022 for collecting CVD events. Cox-proportional hazard regression analysis estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of increased hs-CRP (≥ 1 mg/L) and dyslipidemia with CVD. The additive interactions were explored using the relative excess risk of interaction (RERI) and the multiplicative interactions were assessed with HRs (95% CI) while the multiplicative interactions were assessed by the HRs (95% CI) of interaction terms. RESULTS: The HRs of the association between increased hs-CRP and CVD were 1.42 (95% CI: 1.14-1.79) and 1.17 (95% CI: 0.89-1.53) among subjects with normal lipid levels and subjects with dyslipidemia, respectively. Stratified analyses by hs-CRP levels showed that among participants with normal hs-CRP (< 1 mg/L), TC ≥ 240 mg/dL, LDL-C ≥ 160 mg/dL, non-HDL-C ≥ 190 mg/dL, ApoB < 0.7 g/L, and LDL/HDL-C ≥ 2.02 were associated with CVD [HRs (95%CIs): 1.75 (1.21-2.54), 2.16 (1.37-3.41), 1.95 (1.29-2.97), 1.37 (1.01-1.67), and 1.30 (1.00-1.69), all P < 0.05, respectively]. While in the population with increased hs-CRP, only ApoAI > 2.10 g/L had a significant association with CVD [HR (95% CI): 1.69 (1.14-2.51)]. Interaction analyses showed that increased hs-CRP had multiplicative and additive interactions with LDL-C ≥ 160 mg/dL and non-HDL-C ≥ 190 mg/dL on the risk of CVD [HRs (95%CIs): 0.309 (0.153-0.621), and 0.505 (0.295-0.866); RERIs (95%CIs): -1.704 (-3.430-0.021 and - 0.694 (-1.476-0.089), respectively, all P < 0.05]. CONCLUSION: Overall our findings indicate negative interactions between abnormal blood lipid levels and hs-CRP on the risk of CVD. Further large-scale cohort studies with trajectories measurement of lipids and hs-CRP might verify our results as well explore the biological mechanism behind that interaction.

The variants at FLNA and FLNB contribute to the susceptibility of hypertension and stroke with differentially expressed mRNA.

BACKGROUND: Filamin A and filamin B were involved in vascular development and remodeling. Herein, it is important to explore the associations of FLNA and FLNB variants with hypertension and stroke. METHODS: The associations of two single-nucleotide polymorphisms (SNPs) at FLNA and five SNPs at FLNB with hypertension and stroke were examined in two case-control studies and a cohort study in Chinese Han population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by Logistic and Cox regression analysis respectively. In addition, filamin B, FLNA and FLNB mRNA expression were measured. RESULTS: In the case-control study of hypertension, FLNA rs2070816 (CT + TT vs. CC) and rs2070829 (CG + GG vs. CC) were significantly associated with hypertension in <55 years group (OR = 1.338, P = 0.018; OR = 1.615, P = 0.005) and FLNB rs839240 (AG + GG vs. AA) was significantly associated with hypertension in females (OR = 0.828, P = 0.041) and nonsmokers (OR = 0.829, P = 0.020). In the follow-up study, rs2070829 GG genotype carriers presented a higher risk of hypertension than CC/CG in males (HR = 1.737, P = 0.014) and smokers (HR = 1.949, P = 0.012). In the case-control study of stroke, FLNB rs1131356 variation was significantly associated with ischemic stroke (IS) and intracerebral hemorrhage (ICH), ORs of additive model were 1.342 and 1.451, with P values of 0.001 and 0.007. The FLNA transcript 2, FLNB transcript 3, transcript 4 mRNA, and filamin B expression levels were significantly different between IS cases and hypertension controls and among the genotypes of rs839240 in hypertensive individuals (P < 0.05). CONCLUSIONS: Our findings support the genetic contribution of FLNA and FLNB to hypertension, and stroke with differentially mRNA expression.

HTRA1 Variants and the Interaction with Smoking Confer the Genetic Susceptibility to Ischemic Stroke.

High temperature requirement protein A1 (HtrA1) was identified as the causative gene of autosomal recessive arteriopathy and associated with lacunar ischemic stroke (IS) in European. This study aimed at evaluating the association of HTRA1 with IS and four tagging single-nucleotide polymorphisms (SNPs) were genotyped in a cohort of 4,098 Chinese. The mRNA level of HTRA1 in 72 IS cases and 72 hypertension controls were measured and compared. In whole population, SNP rs2268350 (C>T) was significantly associated with IS incidence (P=0.034). Stratification analysis observed significant association of rs2268350 in male, smoking and drinking populations, rs2672587 (C>G) in smoking and nonsmoking populations and rs3793917 (C>G) in smoking, nonsmoking and nondrinking populations with stroke respectively (P<0.05). The additive interaction and multiplicative interaction between rs2268350 and smoking were both of significant (P<0.05) after adjustment for the covariates. There was a cumulated risk of IS among genotypes of rs3793917 (P=0.009) and rs2672587 (P=0.047) in smoking population. The mRNA level of HTRA1 in non-smokers with rs2268350 CC was significantly higher than smokers with rs2268350 CT/TT (P=0.046) in IS cases. Our findings support that HTRA1 confers the genetic susceptibility to IS and smoking might modify the genetic effect of HTRA1 on IS by suppressing HTRA1 mRNA expression.

The variant at TGFBRAP1 is significantly associated with type 2 diabetes mellitus and affects diabetes-related miRNA expression.

While the transforming growth factor-ß1 (TGF-ß1) regulates the growth and proliferation of pancreatic ß-cells, its receptors trigger the activation of Smad network and subsequently induce the insulin resistance. A case-control was conducted to evaluate the associations of the polymorphisms of TGF-ß1 receptor-associated protein 1 (TGFBRAP1) and TGF-ß1 receptor 2 (TGFBR2) with type 2 diabetes mellitus (T2DM), and its genetic effects on diabetes-related miRNA expression. miRNA microarray chip was used to screen T2DM-related miRNA and 15 differential expressed miRNAs were further validated in 75 T2DM and 75 normal glucose tolerance (NGT). The variation of rs2241797 (T/C) at TGFBRAP1 showed significant association with T2DM in case-control study, and the OR (95% CI) of dominant model for cumulative effects was 1.204 (1.060-1.370), Bonferroni corrected P < 0.05. Significant differences in the fast glucose and HOMA-ß indices were observed amongst the genotypes of rs2241797. The expression of has-miR-30b-5p and has-miR-93-5p was linearly increased across TT, TC, and CC genotypes of rs2241797 in NGT, Ptrend values were 0.024 and 0.016, respectively. Our findings suggest that genetic polymorphisms of TGFBRAP1 may contribute to the genetic susceptibility of T2DM by mediating diabetes-related miRNA expression.

Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.

OBJECTIVES: Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis. METHODS: A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis. RESULTS: During a median follow-up time of 5.01 years, 98 CHD incidence was identified (47.03/104 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08 mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ≥1.08 mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with < 1.08 mg/L, the adjusted HR (95% CI) was 1.69 (1.11-2.60) with a P value of 0.016. No significant casual association was observed between hs-CRP and CHD with a P value of 0.777. CONCLUSIONS: The association between hs-CRP and CHD is unlikely to be causal, hs-CRP might be a predictor for incidence of CHD in general population.

Comparison of the Correlates Between Body Mass Index, Waist Circumference, Waist-to-Height Ratio, and Chronic Kidney Disease in a Rural Chinese Adult Population.

OBJECTIVE: The aim of the article was to evaluate and compare the correlates of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with chronic kidney disease (CKD) among a rural Chinese adult population. DESIGN: This was a case-control study. METHODS: A total of 4,221 adults, aged 27 to 95 years, were divided into different groups based on the standard of CKD stages. A receiver operating characteristic curve was performed to evaluate and compare the predictive values of BMI, WC, and WHtR for CKD. Multiple logistic regression model and ordinal logistic regression model were used to estimate the association between BMI, WC, WHtR, and CKD. MAIN OUTCOME MEASURES: The main outcome variable was stage of CKD. RESULTS: The abnormality in BMI, WC, and WHtR was associated with the cumulative risk of CKD after adjusting for age, gender, smoking, and drinking, and corresponding odds ratios (ORs) (95% confidence intervals [CIs]) were 1.154 (1.009-1.319), 1.240 (1.077-1.428), and 1.191 (1.030-1.378). After further adjustment for blood lipid, hypertension, type 2 diabetes mellitus, and use of antihypertensive and antidiabetic agents, the association of WC and CKD remained statistically significant (adjusted OR = 1.220, 95% CI: 1.052-1.415). Both WC and WHtR were significantly associated with the risk of CKD in females, crude ORs (95% CIs) of cumulative effect of WC and WHtR with CKD were 1.534 (1.296-1.816) and 1.981 (1.683-2.331), respectively. The area under the curves of BMI, WC ,and WHtR for CKD Stage 3 were 0.531, 0.579, and 0.614, and pairwise comparisons showed the area under the curve of WHtR was significantly higher than BMI and WC (P < .001 and P = .002). CONCLUSION: Our findings suggested that abnormality in BMI, WC, and WHtR was associated with CKD in rural population, and WHtR was better in CKD prediction, especially in female.

Common variants of ROCKs and the risk of hypertension, and stroke: Two case-control studies and a follow-up study in Chinese Han population.

The Rho kinases (ROCKs) are recognized as a critical regulator of vascular functions in cardiovascular disorders. It is crucial to illustrate the association of ROCKs genetic variation and hypertension and/or stroke events. Herein we aimed at investigating the association of ROCK1 and ROCK2 with hypertension and stroke in Chinese Han population. Seven tagSNPs at ROCK1 and ROCK2 were genotyped in a community-based case-control study consisting of 2012 hypertension cases and 2210 normotensive controls and 4128 subjects were further followed up. In stroke case-control study, 1471 ischemic stroke (IS) inpatients and 607 hemorrhagic stroke (HS) inpatients were collected, and 2443 age-matched controls were selected from the follow-up population. Risks were estimated as odds ratio (OR) and hazard ratio (HR) by logistic and Cox regression. The community-based case-control study didn't identify any significant tagSNPs associated with hypertension even after adjustment for covariates. The follow-up analysis showed that rs1481280 of ROCK1 significantly associated with incident hypertension (HR=1.130, P=0.048) after adjusting for covariates. rs7589629 and rs978906 of ROCK2 were significantly associated with incident IS (HR=1.373, P=0.004; HR=1.284, P=0.026) respectively. In stroke case-control study, rs288980, rs1481280 and rs7237677 were significantly associated with IS and the adjusted ORs (P values) of additive model were 0.879 (0.010), 0.895 (0.036) and 0.857 (0.002) respectively. Furthermore, rs288980, rs7237677 and rs978906 were significantly associated with HS and the adjusted ORs (P values) of additive model were 0.857 (0.025), 0.848 (0.018) and 0.856 (0.027) respectively. Our findings suggest that ROCK1 and ROCK2 contribute to the genetic susceptibility of hypertension and stroke.

Evaluation of genetic effect of NOS3 and G×E interaction on the variability of serum bilirubin in a Han Chinese population.

Bilirubin was shown to be related to the generation and functional exertion of endothelial nitric oxide synthase (eNOS) whilst the genetic effect of NOS3 on bilirubin variability was rarely reported. Herein we assessed the associations of three single nucleotide polymorphisms (SNPs) of NOS3 (rs4496877, rs1808593, and rs3918186) with bilirubin elevation in 2077 adults. The results showed that rs1808593 was significantly associated with bilirubin elevation, and odds ratios (ORs) of dominant model for the elevation of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IDBIL) were 0.837, 0.821 and 0.754, respectively (P < 0.05 for all). Stratification analysis indicated that rs3918186 was significantly associated with the elevation of TBIL and IDBIL in the males, and ORs of dominant model were 1.505 and 1.440 with P < 0.05 for all. In the smoking group, significant associations of rs4496877, rs1808593, and rs3918186 with TBIL elevation were observed, and ORs of dominant model were 1.739, 0.758 and 1.626 (P < 0.05 for all). rs4496877 and rs3918186 were both associated with TBIL elevation in the drinking group, and ORs were 1.557 and 1.769 with P < 0.05 for all. In the ≥55 year-old group, rs4496877 and rs1808593 were significantly associated with DBIL and IDBIL elevations, and ORs were 1.340 and 0.790 (P < 0.05). Meanwhile, rs4496877, rs1808593, rs3918186, smoking, and drinking were shown to have a notable interaction effects on the TBIL elevation. Our findings supported that NOS3 harbors the genetic susceptibility to the bilirubin elevation. Age, gender, smoking, and drinking could be involved in the genetic modification of NOS3 on the bilirubin variability.

Association study of NOS3 gene polymorphisms and hypertension in the Han Chinese population.

BACKGROUND: Recent studies have reported that NOS3 plays an important role in cardiovascular pathology, whereas the association of NOS3 and hypertension (HT) has been controversial between African Americans and European whites. Here, we aimed to further investigate the genetic effect of unexplored loci at NOS3 on the susceptibility of HT in the Han Chinese population. METHODS AND RESULTS: The association of three polymorphisms; rs4496877, rs1808593 and rs3918186 to HT was tested in a case control study that included 2012 HT cases and 2210 controls. Association analysis showed that there was no significant association between rs4496877, rs1808593 and rs3918186 of NOS3 and HT in the whole study population. Stratification analysis indicated that rs3918186 was significantly associated with HT in the ≥55-year-old population (OR = 1.245, 95% CI = 1.010-1.534, P = 0.04). The rs4496877 and rs1808593 were significantly associated with HT in the male population (P = 0.015) and <55-year-old population (P = 0.025), respectively (OR = 3.254, 95% CI = 1.257-8.425 and OR = 1.683, 95% CI = 1.066-2.657, respectively). Quantitative trait analysis showed that there were significant differences in systolic blood pressure (SBP) among the genotypes (AA, AT and TT) of rs3918186 in the non-intervention populations (P = 0.016). GMDR analysis showed that drinking and rs3918186 had significant interaction effects for risk of HT. CONCLUSIONS: The findings of this study indicated that the rs4496877, rs1808593 and rs3918186 polymorphisms of NOS3 contribute to the genetic susceptibility of HT and that rs3918186 was associated with SBP in the Chinese population. Age and gender might modify the genetic effect of NOS3 on HT, and drinking significantly interacts with rs3918186.

Polymorphisms of the TGFBRAP1 gene in relation to blood pressure variability and plasma TGF-ß1.

TGF-ß receptor-associated protein 1 (TGFBRAP1), as a chaperone, binds Smad4 to participate in vascular development and remodeling which is closely related to the aetiology of essential hypertension (EH). Herein, the main aim of this study is to investigate the genetic susceptibility of TGFBRAP1 to hypertension. A case-control study comprising 2012 hypertension cases and 2210 controls was used to generate the hypothesis of the association of TGFBRAP1 gene with EH and another case-control study in a children population then proceeds to further replicate the association. Logistic regression model was used to adjust confounding factor for EH and general linear model (GLM) was applied to compare blood pressure levels and plasma TGF-ß1 levels between genotypes in cases and controls. There was no statistical association with EH after the covariates were controlled for. However, quantitative trait analysis indicated that DBP had a linear decrease with the variations of rs2679860 (p = 0.005) after adjustment for confounding factor but the direction of this genetic effect was opposite of that in the children population. And normally distributed square root of TGF-ß1 (pg/ml) had a linear increased with the variations of rs2679860 (p = 0.042) after adjusting covariates. Our finding supports the association of rs2679860 polymorphisms of TGFBRAP1 and DBP variation as well as plasma levels of TGF-ß1 and that suggests the variation of rs2679860 might influence the direct modulatory effect of TGF-ß1 on the blood pressure by regulating the plasma levels of TGF-ß1.

HMGB1 gene polymorphism is associated with hypertension in Han Chinese population.

BACKGROUND: High-mobility group box 1 protein (HMGB1) acts as a proinflammatory cytokine by activating pattern recognition receptors (PRRs), including Toll-like receptor 4 (TLR4) and the receptor of AGE (AGER) with oxidative injury. Animal study proved that HMGB1 contributed to the pathogenesis of experimental pulmonary hypertension (HT) via activation of TLR4. The aim of this study is to test whether HMGB1 harbor genetic susceptibility to HT in a Chinese population. METHODS: A case-control study comprising 2012 HT cases and 2210 controls was used to evaluate the association of three tagging single nucleotide polymorphism (tagSNPs) in HMGB1 gene with HT and blood pressure. Logistic regression model was used to adjust confounding factor for HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes in cases and controls. RESULTS: Single locus analysis showed that there was no statistical association of three tagSNPs with HT after adjustment for the covariates. Further stratification analysis found that rs2249825 was significantly associated with HT in ≥55 years groups, ORs (95% CI) of additive model and dominant model were 1.208 (1.029-1.417) and 1.212 (1.020-1.441), and p values were 0.021 and 0.029, respectively. Quantitative trait analysis indicated that DBP had a linear decrease with the variations of rs2249825 in both untreated HT group (p=0.002) and control group (p=0.034) respectively. CONCLUSIONS: Our finding suggests that rs2249825 of HMGB1 genetic polymorphisms are significantly associated with HT and diastolic blood pressure, and the genetic effect on HT is modulated by age.

CRP gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population.

C-reactive protein (CRP), an inflammatory marker that statistically predicts future cardiovascular risk, has been reported to be associated with plasma lipid level changes. Whether CRP genetic variants affect lipid metabolism is of importance to investigate. A community-based study population including 2,731 adult subjects aged 18-62 years was used to evaluate the association of CRP gene with dyslipidemia and five tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to further evaluate relationships between the SNPs and lipid metabolism abnormality and general linear model was applied to compare plasma lipid levels between genotypes. Association analyses indicated that recessive model of SNPs rs876537 and rs4285692 had significant association with elevated HDL after adjustment for covariates. Odds ratio (OR) of rs876537 were 0.60 for HDL > 1.54 versus 1.04-1.54 mmol/L (P = 0.011), as well as, ORs were 0.617 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.002) and 0.724 for HDL = 1.59-1.83 versus ≤1.35 mmol/L (P = 0.028) respectively. OR of rs4285692 was 0.634 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.027). Further stratification analysis found significant associations of rs10737175 with elevated HDL (>1.54 vs. 1.04-1.54 mmol/L, OR 0.629 and P = 0.027) and elevated TG (≥1.70 vs. <1.70 mmol/L, ORs of additive and dominant models were 0.628, 0.545 and P values were 0.006, 0.003 respectively) in female. rs4285692 was significantly associated with elevated LDL (≥3.37 vs. <3.37 mmol/L), ORs equaled to 1.532, 2.281 for additive model and recessive model and P values were 0.028, 0.024 respectively in male. Furthermore, quantitative trait analysis indicated the variation T to C of rs876537 significantly affect decreased plasma HDL level (P = 0.014). Our findings suggest that CRP genetic polymorphisms independently had positive association with the risk of HDL, LDL and TG elevating and further replication in other large population and biological function research would be warranted.

Association study of common variations of FBN1 gene and essential hypertension in Han Chinese population.

Fibrillin-1 (FBN1) was reported to have impact on the physiological arterial stiffness and vascular remodeling with hypertension of recent years. In the previous study we reported the association of four functional single nucleotide polymorphisms (SNPs) of FBN1 gene and hypertension. Here, we further investigate the association of four tagging SNPs (tagSNPs) which covered remain genetic variation blocks of FBN1 gene with hypertension, blood pressure and efficacy of antihypertensive in a South Han Chinese population. A case-control study including 2,012 hypertension cases and 2,116 controls age- and sex-matched controls was conducted from a community-based population and four candidate tagSNPs of the FBN1 gene were genotyped. Association analysis by multiple logistic regression was conducted for allele, genotype and haplotype and hypertension, blood pressure trait and control status with antihypertensive. General linear model was applied to compare blood pressure levels between genotypes. The association of rs17361868 and hypertension was statistically significant and that was further observed in female, ≥55 years, non-smoking and non-drinking populations (P < 0.05). Significant association of rs668842, rs11635140 and hypertension were observed in <55 years population as well as the later in female and non-smoking populations respectively. Haplotype G-T constructed of rs668842 and rs11635140 was significantly associated with hypertension comparing to reference haplotype A-C (P = 0.022). Normally distributed square root of TGF-ß1 (pg/ml) of hypertension cases (148.56 ± 66.46) was significantly higher than that of control (128.52 ± 65.11), P = 0.008. Furthermore, TGF-ß1 was significantly correlated with SBP (r = 0.135, P = 0.018) and DBP (r = 0.154, P = 0.007) respectively whereas no statistical difference of blood pressure or TGF-ß1 was observed between genotypes. Remarkably, rs17361868 were significantly associated with the status of blood pressure in the patients taking three of the antihypertensive drugs, Zhen Ju Jiang Ya tablets, Jiang Ya tablet and compound reserpine (P < 0.05). The present study provides further association evidence of FBN1 gene polymorphisms and hypertension, antihypertensive efficacy. Further replication of these results via association or prospective studies conducted in other populations is warranted.

Sex and age differences in the association between high sensitivity C-reactive protein and all-cause mortality: A 12-year prospective cohort study.

To explore the influence of age on hs-CRP among men and women and investigate the impact of hs-CRP on all-cause death, this prospective cohort enrolled 4128 community adults from 2009 to 2022 for all-cause death. Age and sex-specific hs-CRP percentile curves were generated using the GAMLSS method. Cox-proportional hazard regression analysis was applied to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs). During the follow-up with a median of 12.59 years, 701 cases of all-cause death were identified. Among men, the smoothed centile curves of hs-CRP gradually increased from age 35 onwards whereas, the smoothed centile curves of hs-CRP continuously increased as age increased among women. Compared with the reference group, the adjusted HR of the association between elevated hs-CRP and all-cause death was 1.33 (95 % CI: 1.11-1.61). The adjusted HRs of the associations between elevated hs-CRP and all-cause death were higher in women [1.40 (95 % CI: 1.07-1.83)] than men [1.28 (95 % CI: 0.99-1.65) and in subjects aged < 65 years [1.77 (95 % CI: 1.19-2.62)] than in subjects aged ≥ 65 years [1.27 (95 % CI: 1.03-1.57)]. Our findings highlight the need of investigating sex and age differences in biological pathways that link inflammation and mortality.

[An association study between transforming growth factor-ß1 receptor 2 gene polymorphisms and essential hypertension].

OBJECTIVE: To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-ß1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population. METHODS: The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension. RESULTS: The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05). CONCLUSION: SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Interaction Analysis of Abnormal Lipid Indices and Hypertension for Ischemic Stroke: A 10-Year Prospective Cohort Study.

Background: Dyslipidemia and hypertension are two important independent risk factors for ischemic stroke (IS); however, their combined effect on IS remains uncertain. Objectives: This present study aimed to evaluate the interaction effect of hypertension and abnormal lipid indices on IS in a 10-year prospective cohort in Chinese adults. Methods: The cohort study of 4,128 participants was conducted in May 2009 and was followed up to July 2020. All qualified participants received a questionnaire survey, physical examination, and blood sample detection. Cox regression was used to evaluate the association of dyslipidemia and hypertension with IS, and calculate the hazard ratio (HR) and 95% confidence interval (CI). The relative excess risk of interaction (RERI) and the HR (95%CI) of interaction terms were used to examine additive and multiplicative interactions. Results: In the hypertensive population, Non-HDL-C ≥190 mg/dl, LDL-C/HDL-C ≥2 and HDL-C ≥60 mg/dl were statistically associated with IS, and after adjusting for covariates, HRs (95%CIs) were 1.565 (1.007-2.429), 1.414 (1.034-1.933) and 0.665 (0.450-0.983), respectively. While in the non-hypertension population, no significant association of Non-HDL-C ≥190 mg/dl, LDL-C/HDL-C ≥2, and HDL-C ≥60 was detected with IS (P > 0.05). There was a significant association between TC/HDL-C ≥ 3.6 and the decreased risk of IS in the non-hypertension population, and the HR (95%CI) was 0.479 (0.307-0.750). Whereas, a similar association was not observed in the hypertensive population. HDL-C ≥ 60 mg/dl, Non-HDL-C ≥ 190 mg/dl, TC/HDL-C ≥ 3.6, and TG/HDL-C ≥ 1 have additive and multiplicative interactions with hypertension (P < 0.05). The RERIs (95% CIs) of the additive interaction are -0.93 (-1.882-0.044), 1.394 (0.38-2.407), 0.752 (0.354-1.151) and 0.575 (0.086-1.065), respectively. The HRs (95% CIs) of the multiplicative interaction terms were 0.498 (0.272-0.911), 4.218 (1.230-14.464), 2.423 (1.437-4.086) and 1.701 (1.016-2.848), respectively. Conclusion: High concentration of HDL-C reduces the impact of hypertension on IS, while the high concentration of Non-HDL-C, TC/HDL-C, and TG/HDL-C positively interact with hypertension affecting the incidence of IS. This study provides useful evidence for the combined effects of dyslipidemia and hypertension in predicting IS.

Gender Specificity and Local Socioeconomic Influence on Association of GHR fl/d3 Polymorphism With Growth and Metabolism in Children and Adolescents.

Objective: Growth hormone receptor (GHR) mediates most GH biological actions. This study is aimed to evaluate whether GHR fl/d3 polymorphism contributes to the inter-individual variability of growth and metabolism in healthy children and adolescents. Methods: A total of 4,730 students aged 6-16 years from Yixing and Suqian City in China were included in this cross-sectional study. Height and body mass index (BMI) were transformed into the form of z-score corresponding to age and gender. Logistic regression was used to evaluate the associations of GHR fl/d3 polymorphism with height, BMI, metabolic traits, and hypertension by estimating the odds ratios (ORs) and 95% confidence intervals (CIs). Results: GHR d3 allele was inversely associated with overweight, total cholesterol (TC) and triglyceride (TG) levels (OR [95% CI] for overweight: 0.754 [0.593-0.959], P = 0.021; OR [95% CI] for TC: 0.744 [0.614-0.902], P = 0.003; OR [95% CI] for TG: 0.812 [0.654-0.998], P = 0.047). GHR d3 allele was associated with decreased odds of pre-hypertension in boys (OR [95% CI]: 0.791 [0.645-0.971], P = 0.025), but associated with increased odds of pre-hypertension and hypertension in girls (ORs [95% CIs]: 1.379 [1.106-1.719], P = 0.004; OR [95% CI]: 1.240 [1.013-1.519], P = 0.037). Interaction of GHR fl/d3 polymorphism with gender contributed to increased odds of pre-hypertension and hypertension (interactive ORs [95% CIs]: 1.735 [1.214-2.481], P = 0.003; OR [95% CI]: 1.509 [1.092-2.086], P = 0.013). Stratification analysis showed that the correlation tendencies of GHR fl/d3 polymorphism and BMI with age were different between two cities with discrepant economic development levels. Conclusion: GHR fl/d3 polymorphism is associated with growth, metabolism, and hypertension in children and adolescents with the gender specificity, and the genetic effect of GHR fl/d3 may be modified by the local socioeconomic levels.

The relationship between lipid risk score and new-onset hypertension in a prospective cohort study.

Background: Dyslipidemia and hypertension are both important risk factors for atherosclerotic cardiovascular diseases. However, the relationship between dyslipidemia and incident hypertension remains to be elucidated comprehensively. The main purpose of this study was to construct the lipid risk score to explore the risk prediction effect of integrated lipid indices on new-onset hypertension. Methods: This prospective cohort study with 2116 non-hypertensive subjects was conducted from 2009 to 2020. New hypertension events during the follow-up period were recorded and verified. The lipid risk score was calculated by summing coded total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol weighted with corresponding effect sizes. Cox regression analysis was used to estimate the association between the lipid risk score or lipid indices and incident hypertension in the subgroup of age (< 55 and≥ 55 years at baseline). Results: After a median of 10.75-year follow-up, 637 incident hypertension cases were identified. The restricted cubic spline showed that the lipid risk score had a positive linear correlation with hypertension (P< 0.001). Among people< 55 years, with every increase of 0.94 in lipid risk score, the risk of hypertension increased by 37% (adjusted HR [95%CI]: 1.369 [1.164-1.610]). This association was not modified by overweight or obesity. Conclusions: The integrated lipid risk score, independent of traditional risk factors, has a significantly predictive effect on hypertension in people younger than 55 years. This finding may aid in identifying high-risk individuals for hypertension, as well as facilitating early intervention and management to reduce adverse cardiovascular events. Comprehensive lipid management should be attached importance in the prevention and control of hypertension.