Circulating trimethylamine N-oxide is correlated with high coronary artery atherosclerotic burden in individuals with newly diagnosed coronary heart disease.

BACKGROUND: Trimethylamine N-oxide (TMAO) is a metabolite derived from the gut microbiota and has been reported to be correlated with cardiovascular diseases. Although TMAO is associated with the severity of coronary artery disease in subjects with coronary heart disease (CHD) history. However, the correlation between TMAO and the atherosclerotic burden in newly diagnosed cases of CHD is unknown. METHODS: In this hospital-based study, we enrolled 429 individuals newly diagnosed with CHD undergoing coronary angiography. Plasma TMAO was assessed before coronary angiography. SYNTAX score was computed during coronary angiography to estimate the coronary artery atherosclerotic burden. Both linear and logistic regression analyses were conducted to explore the correlation between plasma TMAO levels and SYNTAX score in newly diagnosed CHD population. RESULTS: The TMAO in patients with SYNTAX ≥ 33 and subjects with SYNTAX < 23 were 6.10 (interquartile range [IQR]: 3.53 to 9.15) µmol/L and 4.90 [IQR: 3.25 to 7.68] µmol/L, respectively. Linear regression adjusting for traditional risk factors showed TMAO level was positively correlated with SYNTAX score (ß = 0.179; p = 0.006) in CHD population. When TMAO was added to models with traditional risk factors, the predictive value improved significantly, with the receiver operating characteristic curve (AUC) increased from 0.7312 to 0.7502 (p = 0.003). Stratified analysis showed that the correlations did not hold true for subjects who were non-smoker or with histories of diabetes. None of the stratifying factors significantly altered the correlation (all p for interaction < 0.05). CONCLUSIONS: We found a positive linear correlation between plasma TMAO and SYNTAX score among newly diagnosed CHD individuals in Chinese population.

PM2.5 associates with blood pressure: a Mendelian randomization analysis.

The relationship between fine particulate matter (PM2.5) and blood pressure (BP) is a controversial issue. We conducted a two-sample Mendelian randomization (MR) analysis and identified 58 genome-wide significant single-nucleotide polymorphisms associated with PM2.5 as instrument variables. Inverse-variance weighted (IVW) was used as the primary analysis approach. MR-Egger, weighted median, simple model, and weighted model methods were selected for quality control. We found a significant negative causal association of higher genetically predicted PM2.5 levels with lower systolic BP (SBP), while no causal relationship was identified between PM2.5 and diastolic BP (DBP). For each 1 standard deviation increase in genetically predicted PM2.5 levels, the beta value (95% CI) of SBP was -0.14 (-0.25, -0.03) for IVW (p=0.02), and -0.13 (-0.22, -0.04) for weighted median (p=0.005). Increased PM2.5 concentrations can lead to decreased SBP levels. Our findings provided novel insights into the controversial topic on the causal relationship between PM2.5 and BP.

Comparison of BP variability, cumulative BP, and BP trajectory for predicting cardiovascular events in the general population.

OBJECTIVE: Systolic blood pressure variability (SBPV), cumulative systolic BP (cumSBP), and systolic blood pressure trajectory (trajSBP) are major indices describing characteristics of BP changes. The aim of this study was to compare their discrimination abilities for cardiovascular (CV) events. METHODS: In 51698 subjects, associations were assessed using Cox regression in the overall cohort and Framingham risk score (FRS) stratified groups. Individuals with <10%, 10%-20%, and >20% 10-year CV risk were categorized into the low-, intermediate-, and high-risk group, respectively. Discrimination capabilities were evaluated using the area under curve (AUC), Harrell's C index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: Within a mean follow-up of 6.83 ± 0.89 years, 2330 participants had CV events, and all three markers were significantly associated with CV events. TrajSBP provided the best additional discriminative value for CV events, with improvements of 1.54% in AUC%, 0.01 in Harrell's C, 37.52% in NRI%, and 0.59% in IDI%. CumSBP had good additional discriminative capability in the intermediate to high FRS groups, but the effect sizes were smaller than those of trajSBP. Although, SBPV improved the predictive capabilities in the low-to intermediate-risk groups, the effect sizes were much smaller than those of the other indices. Sensitivity analyses excluding patients who underwent antihypertensive therapy revealed similar patterns but higher effect sizes than in the overall population. CONCLUSION: TrajSBP provides the best additional discrimination capabilities based on traditional risk profiles and may assist the risk stratification and individual prediction for future CV events.

Renal Artery Stenosis Complicated with Primary Aldosteronism.

Primary aldosteronism (PA) is a typical example of low renin hypertension, whereas renal artery stenosis (RAS) is a classic form of high renin hypertension. PA and RAS occurring simultaneously in a patient is challenging to diagnose. We report a 32-year-old woman with a 12-year history of resistant hypertension. She was identified to have elevated plasma aldosterone and renin levels with normal aldosterone/renin ratio (ARR). Imaging examinations identified bilateral adrenal thickening and subtotal occlusion of the anterior segment of the left renal artery. Adrenal venous sampling was performed and indicated the existence of unilateral aldosterone over-secretion. It may suggest that even though RAS led to non-suppressed renin, adrenal venous sampling remains to be an applicable approach to establish the diagnosis of aldosterone-producing adenomas, although the diagnostic value of ARR may be compromised due to non-suppressed renin level. The patient underwent a two-stage treatment. First, stenosis of the left renal artery was dilated by percutaneous transluminal renal balloon angioplasty. Two months later, laparoscopic complete left adrenalectomy was performed. Hematoxylin-eosin staining and CYP11B2 immunostaining suggested that this tumor was an aldosterone-producing adenoma. After the two-stage treatment, her blood pressure decreased to a normal level without antihypertensive drugs. This case report raises our awareness of the simultaneous occurrence of RAS and PA. Under this condition, ARR could lead to a false-negative PA. Adrenal venous sampling is warranted to achieve a confirmed diagnosis. For subjects with complex etiologies of secondary hypertension, multi-stage treatment may be required.

Corrigendum: Case report: Primary aldosteronism and subclinical cushing syndrome in a 49-year-old woman with hypertension plus hypokalaemia.

[This corrects the article DOI: 10.3389/fcvm.2022.911333.].

Identification of potential lncRNA-miRNA-mRNA regulatory network contributing to aldosterone-producing adenoma.

Aldosterone-producing adenoma (APA) is a common cause of secondary hypertension. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network to uncover molecular mechanism underlying APA. The mRNA and lncRNA expression data of APA and adjacent adrenal gland (AAG) from GSE60044, GSE64957 and GSE101894 were obtained from the Gene Expression Omnibus (GEO) database to analyse differentially expressed genes (DEGs) and lncRNAs (DElncs). Hub genes were identified by robust rank aggregation (RRA) and protein-protein interaction (PPI) network analysis. The miRcode and miRWalk network tools were used to construct the ceRNA network. 1526 upregulated and 1512 downregulated DEGs were identified, which are mainly enriched in extracellular matrix and Ca2 + -related GO terms. In the KEGG pathway analysis, Ca2+ signalling and the aldosterone synthesis and secretion pathways were enriched. ceRNA network included 2 lncRNAs, 9 miRNAs, and 13 mRNAs. The lncRNAs are MEG3 and LINC00115. The mRNAs included CCND1, TP53, GPRC5B, BMI1, COMMD3-BMI1, ADAMTS15, STAT3, MMP2, SCN2B, CXCL12, HGF, FOS, and THBS1. Overall, this study conducted a ceRNA regulatory network analysis and identified that 2 lncRNAs and 13 mRNAs may contribute to the development of APA. These findings may provide novel diagnostic and intervention targets for APA.

Case Report: Primary Aldosteronism and Subclinical Cushing Syndrome in a 49-Year-Old Woman With Hypertension Plus Hypokalaemia.

Background: Coexisting primary aldosteronism (PA) and subclinical Cushing's syndrome (SCS) caused by bilateral adrenocortical adenomas have occasionally been reported. Precise diagnosis and treatment of the disease pose a challenge to clinicians due to its atypical clinical manifestations and laboratory findings. Case Summary: A 49-year-old woman was admitted to our hospital due to fatigue, increased nocturia and refractory hypertension. The patient had a history of severe left hydronephrosis 6 months prior. Laboratory examinations showed hypokalaemia (2.58 mmol/L) and high urine potassium (71 mmol/24 h). Adrenal computed tomography (CT) showed bilateral adrenal masses. Undetectable ACTH and unsuppressed plasma cortisol levels by dexamethasone indicated ACTH-independent Cushing's syndrome. Although the upright aldosterone-to-renin ratio (ARR) was 3.06 which did not exceed 3.7, elevated plasma aldosterone concentrations (PAC) with unsuppressed PAC after the captopril test still suggested PA. Adrenal venous sampling (AVS) without adrenocorticotropic hormone further revealed hypersecretion of aldosterone from the right side and no dominant side of cortisol secretion. A laparoscopic right adrenal tumor resection was performed. The pathological diagnosis was adrenocortical adenoma. After the operation, the supine and standing PAC were normalized; while the plasma cortisol levels postoperatively were still high and plasma renin was activated. The patient's postoperative serum potassium and 24-h urine potassium returned to normal without any pharmacological treatment. In addition, the patient's blood pressure was controlled normally with irbesartan alone. Conclusion: Patients with refractory hypertension should be screened for the cause of secondary hypertension. AVS should be performed in patients in which PA is highly suspected to determine whether there is the option of surgical treatment. Moreover, patients with PA should be screened for hypercortisolism, which can contribute to a proper understanding of the AVS result.

Influence of Hypersensitive C-Reactive Protein on the Effect of Continuous Antihypertensive Pharmacological Therapy.

ABSTRACT: Systemic chronic inflammation, represented by hypersensitive C-reactive protein (hsCRP), is an essential contributing factor to hypertension. However, the influence of hsCRP levels on the effect of antihypertensive pharmacological therapy remains unknown. We evaluated hsCRP levels in 3756 newly diagnosed, untreated hypertensive subjects. Participants were grouped by tertiles of hsCRP and were randomly treated with nitrendipine + captopril, nitrendipine + spironolactone hydrochlorothiazide + captopril, and hydrochlorothiazide + spironolactone. Blood pressure (BP) was recorded every 2 weeks. A multivariate mixed linear model was used to evaluate the impact of baseline hsCRP levels on the continuous antihypertensive effect. After 3, 6, 9, and 12 months of continuous antihypertensive treatment, no significant difference was observed in BP decline among the different hsCRP groups. We identified interactions between baseline hsCRP levels and follow-up time. After adjusting for conventional risk factors and the interactions between hsCRP and follow-up time, there was no significant association between baseline hsCRP level and antihypertensive effects at 0-6 months of follow-up. However, from 6 to 12 months, subjects with higher baseline hsCRP levels exhibited a more marked BP-lowering effect ( P < 0.001 at 9 months, P = 0.002 at 12 months). Overall, there exist interaction effects between baseline hsCRP levels and follow-up time. Individuals with higher baseline hsCRP levels may exhibit a better response to antihypertensive therapy.

Exome-Wide Association Study Identifies East Asian-Specific Missense Variant MTHFR C136T Influencing Homocysteine Levels in Chinese Populations RH: ExWAS of tHCY in a Chinese Population.

Plasma total homocysteine (tHCY) is a known risk factor of a wide range of complex diseases. No genome scans for tHCY have been conducted in East Asian populations. Here, we conducted an exome-wide association study (ExWAS) for tHCY in 5,175 individuals of Chinese Han origin, followed by a replication study in 668 Chinese individuals. The ExWAS identified two loci, 1p36.22 (lead single-nucleotide polymorphism (SNP) rs1801133, MTHFR C677T) and 16q24.3 (rs1126464, DPEP1), showing exome-wide significant association with tHCY (p < 5E-7); and both loci have been previously associated with tHCY in non-East Asian populations. Both SNPs were replicated in the replication study (p < 0.05). Conditioning on the genotype of C677T and rs1126464, we identified a novel East Asian-specific missense variant rs138189536 (C136T) of MTHFR (p = 6.53E-10), which was also significant in the replication study (p = 9.8E-3). The C136T and C677T variants affect tHCY in a compound heterozygote manner, where compound heterozygote and homozygote genotype carriers had on average 43.4% increased tHCY than had other genotypes. The frequency of the homozygote C677T genotype showed an inverse-U-shaped geospatial pattern globally with a pronounced frequency in northern China, which coincided with the high prevalence of hyperhomocysteinemia (HHCY) in northern China. A logistic regression model of HHCY status considering sex, age, and the genotypes of the three identified variants reached an area under the receiver operating characteristic curve (AUC) value of 0.74 in an independent validation cohort. These genetic observations provide new insights into the presence of multiple causal mutations at the MTHFR locus, highlight the role of genetics in HHCY epidemiology among different populations, and provide candidate loci for future functional studies.

Genetic variants in Chinese patients with sporadic Stanford type A aortic dissection.

BACKGROUND: Genetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD. METHODS: We analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients. RESULTS: In total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 vs. 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% vs. 66.7%, P=0.007). Patients with fibrillin-1 (FBN1) mutations were younger than patients without FBN1 mutations (44.7±11.0 vs. 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% vs. 10.5%, P=0.029) but only in patients who received conservative treatment. CONCLUSIONS: Half of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.

Extracellular matrix-based biomaterials for cardiac regeneration and repair.

The spectrum of ischemic heart diseases, encompassing acute myocardial infarction to heart failure, represents the leading cause of death worldwide. Although extensive progress in cardiovascular diagnoses and therapy has been made, the prevalence of the disease continues to increase. Cardiac regeneration has a promising perspective for the therapy of heart failure. Recently, extracellular matrix (ECM) has been shown to play an important role in cardiac regeneration and repair after cardiac injury. There is also evidence that the ECM could be directly used as a drug to promote cardiomyocyte proliferation and cardiac regeneration. Increasing evidence supports that applying ECM biomaterials to maintain heart function recovery is an important approach to apply the concept of cardiac regenerative medicine to clinical practice in the future. Here, we will introduce the essential role of cardiac ECM in cardiac regeneration and summarize the approaches of delivering ECM biomaterials to promote cardiac repair in this review.

Optimized Langendorff perfusion system for cardiomyocyte isolation in adult mouse heart.

With the rapid development of single-cell sequencing technology, the Langendorff perfusion system has emerged as a common approach to decompose cardiac tissue and obtain living cardiomyocytes to study cardiovascular disease with the mechanism of cardiomyocyte biology. However, the traditional Langendorff perfusion system is difficult to master, and further, the viability and purity of cardiomyocytes are frequently unable to meet sequencing requirements due to complicated devices and manipulate processes. Here, we provide an optimized Langendorff perfusion system with a simplified and standardized operating protocol which utilizes gravity as the perfusion pressure, includes a novel method for bubbles removing and standardizes the criteria for termination of digestion. We obtained stable cardiomyocyte with high viability and purity after multiple natural gravity sedimentation. The combination of the optimized Langendorff perfusion system and the multiple natural gravity sedimentation provides a stable system for isolating adult mouse heart, which will provide higher-quality cardiomyocytes for further experiments.

Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting.

BACKGROUND: Monogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension. METHODS: We performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays. RESULTS: 21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%). CONCLUSION: Molecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation.

Blood Pressure Variability Is Associated with Hearing and Hearing Loss: A Population-Based Study in Males.

Blood pressure (BP) has been well documented to be associated with hearing loss previously. However, the role of blood pressure variability (BPV, representing BP fluctuation over a time period) on hearing remains unknown. We aimed to evaluate the relationship between BPV and hearing in Chinese population. We included 8646 male subjects from a population-based study (the Kailuan study). BP was measured every two years at routine physical examinations from 2006 to 2015. Based on five annual BP measurements, BPV was estimated by standard deviation of BP (SD), coefficient of the variation of BP (CV), and variation independent of mean of BP (VIM). Hearing was estimated by pure-tone average threshold (PTA) at low, intermediate, and high frequencies in the year of 2014. Regression models were used to evaluate the relationship between BPV and hearing. The results showed that PTAs and percentages of hearing loss at low, intermediate, and high frequencies grew gradually with increasing systolic SD (SSD) (p<0.05). After adjusting for multiple covariates, multivariate regression analyses demonstrated that variations of SBP (SSD, SCV, and VIMSBP) were all positively correlated with PTA at intermediate and high frequencies (p<0.05). Each SD increase in SSD, SCV, and VIMSBP was also positively associated with hearing loss at intermediate and high frequencies. No significant correlation was observed between variations of DBP and hearing. These findings suggest that increase in long-term BPV is associated with hearing and hearing loss. Trial registration number: Kailuan study (ChiCTRTNC-11001489).

Genetic screening for Bartter syndrome and Gitelman syndrome pathogenic genes among individuals with hypertension and hypokalemia.

PURPOSE: Bartter syndrome (BS) and Gitelman syndrome (GS) are hereditary diseases characterized by hypokalemia with decreased or normal blood pressure (BP). However, BS or GS patients who present with elevated BP levels have been increasingly reported recently. Therefore, this study aimed to investigate the presence of BS and GS among individuals with unexplained hypokalemia with hypertension in a clinical setting. METHODS: Patients presented with unexplained hypertension and hypokalemia admitted to Hypertension Center of Fuwai Hospital from November 2015 to February 2017 were enrolled. High-throughput sequencing for five BS and GS causative genes were performed. Variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. RESULTS: Thirty-four patients with unexplained hypertension and hypokalemia were included for genetic analysis. A total number of 10 rare variants were identified in six individuals (mutation detection rate, 17.65%). One homozygous variant carried by one of the 34 patients, KCNJ1 c.941A> G (p.Tyr314Cys), were categorized as likely pathogenic variant and resulted in a diagnostic yield of 2.94%. Eight of the remaining nine variants were predicted to be deleterious by ≥ three bioinformatics software and may give additional potential diagnostic yields. CONCLUSIONS: This is the first study performing combined genetic screening for BS and GS pathogenic genes among individuals with unexplained hypertension and hypokalemia. Our data suggested that BS or GS may contribute to the etiology of patients presented with hypertension and hypokalemia. Genetic testing for BS and GS pathogenic genes are recommended to facilitate precision diagnoses and targeted treatment.

Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients.

Previous studies suggested a possible gut microbiota dysbiosis in chronic heart failure (CHF). However, direct evidence was lacking. In this study, we investigated the composition and metabolic patterns of gut microbiota in CHF patients to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF. We enrolled 53 CHF patients and 41 controls. Metagenomic analyses of faecal samples and metabolomic analyses of faecal and plasma samples were then performed. We found that the composition of gut microbiota in CHF was significantly different from controls. Faecalibacterium prausnitzii decrease and Ruminococcus gnavus increase were the essential characteristics in CHF patients' gut microbiota. We also observed an imbalance of gut microbes involved in the metabolism of protective metabolites such as butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients. Metabolic features of both faecal and plasma samples from CHF patients also significantly changed. Moreover, alterations in faecal and plasma metabolic patterns correlated with gut microbiota dysbiosis in CHF. Taken together, we found that CHF was associated with distinct gut microbiota dysbiosis and pinpointed the specific core bacteria imbalance in CHF, along with correlations between changes in certain metabolites and gut microbes.

AK098656, a Novel Vascular Smooth Muscle Cell-Dominant Long Noncoding RNA, Promotes Hypertension.

Recent studies reported some long noncoding RNAs (lncRNAs)-mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs. AK098656 promoted VSMCs synthetic phenotype evidenced by increasing VSMC proliferation and migration, elevating extracellular matrix proteins, whereas lowering contractile proteins. Furthermore, AK098656 was demonstrated to directly bind with the VSMCs-specific contractile protein, myosin heavy chain-11, and an essential component of extracellular matrix, fibronectin-1, and finally lowered these protein levels through protein degradation. AK098656 was also shown to bind with 26S proteasome non-ATPase regulatory subunit 11 and facilitated myosin heavy chain-11 to interact with this protein. In vivo, AK098656 transgenic rats showed spontaneous development of hypertension, with elevated VSMCs synthetic phenotype and narrowed resistant arteries. Transgenic rats also showed slight cardiac hypertrophy without other complications, which was similar with early pathophysiological changes of hypertension. All these data indicated AK098656 as a new human VSMC-dominant lncRNA, which could promote hypertension through accelerating contractile protein degradation, increasing VSMC synthetic phenotype, and finally narrowed resistance arteries.

[Preparation and chiral recognition of heterosubstituted amylose derivatives-based chiral stationary phases].

Two novel amylose derivatives, namely amylose 2-benzoate-3-(4-methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate) and amylose 2-benzoate-3-(3,5-dichlorophenylcarbamate)-6-(4-methylphenylcarbamate), were prepared utilizing a serial regioselective process. After coated onto aminopropyl silica gel, they were utilized as chiral stationary phases (CSPs) for high performance liquid chromatography. Investigations indicated that the CSPs exhibited characteristic chiral recognition and their chiral recognition abilities were much higher than those of amylose tris(3,5-dichlorophenylcarbamate) (ADCPC), a homosubstituted derivative. The nature and position of the substituents at 3-, and 6-positions of a glucose unit had great influence on the chiral resolution abilities of the amylose derivatives. Some chiral compounds which were not effectively resolved on the commercial column Chiralpak AD were effectively separated on the new CSPs. Moreover, with all the eight tested racemates resolved, amylose 2-benzoate-3-(4-methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate) exhibited relatively high chiral recognition and might be a potential useful CSP.

Genome Wide Association Study Identifies L3MBTL4 as a Novel Susceptibility Gene for Hypertension.

Hypertension is a major global health burden and a leading risk factor for cardiovascular diseases. Although its heritability has been documented previously, contributing loci identified to date account for only a small fraction of blood pressure (BP) variation, which strongly suggests the existence of undiscovered variants. To identify novel variants, we conducted a three staged genetic study in 21,990 hypertensive cases and normotensive controls. Four single nucleotide polymorphisms (SNPs) at three new genes (L3MBTL4 rs403814, Pmeta = 6.128 × 10(-9); LOC729251, and TCEANC) and seven SNPs at five previously reported genes were identified as being significantly associated with hypertension. Through functional analysis, we found that L3MBTL4 is predominantly expressed in vascular smooth muscle cells and up-regulated in spontaneously hypertensive rats. Rats with ubiquitous over-expression of L3MBTL4 exhibited significantly elevated BP, increased thickness of the vascular media layer and cardiac hypertrophy. Mechanistically, L3MBTL4 over-expression could lead to down-regulation of latent transforming growth factor-ß binding protein 1 (LTBP1), and phosphorylation activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which is known to trigger the pathological progression of vascular remodeling and BP elevation. These findings pinpointed L3MBTL4 as a critical contributor to the development and progression of hypertension and uncovers a novel target for therapeutic intervention.

Relationship between cardiovascular health score and year-to-year blood pressure variability in China: a prospective cohort study.

OBJECTIVES: On the basis of cardiovascular health factors and behaviours, the American Heart Association proposed the Cardiovascular Health Score (CHS). It has been widely used to estimate the cardiovascular health status of individuals. The aim of this study was to investigate the relationship between CHS and year-to-year blood pressure variability (BPV). DESIGN: Prospective cohort study. SETTINGS: We stratified participants into two groups by gender: first group, female group; second group, male group. The relationship between CHS and year-to-year blood pressure variability were analysed. PARTICIPANTS: A total of 41,613 individuals met the inclusion criteria (no history of stroke, transient ischaemic attack, myocardial infarction, malignant tumour or atrial fibrillation) and had complete blood pressure data. RESULTS: The coefficient of the variation of systolic blood pressure (SCV) was 8.33% in the total population and 8.68% and 8.22% in female and male groups, respectively (p<0.05). Multivariable linear regression analysis revealed that higher CHS was inversely associated with increasing year-to-year BPV, which persisted after adjusting for baseline systolic blood pressure and other risk factors. Each SD increase in CHS could lead to a 0.016SD decrease in SCV (p<0.05). CONCLUSIONS: In summary, CHS was inversely related to year-to-year BPV, which suggested that a healthy lifestyle may contribute to better blood pressure management.