Fat-free mass may play a dominant role in the association between systolic blood pressure and body composition in children and adolescents.

Systolic blood pressure (SBP) is significantly associated with body composition in children and adolescents. However, which one of the components of body composition is the dominant contributor to SBP in children and adolescents remains unclear. We, therefore, aimed to determine the dominant contributor to SBP among components of body composition in a large cohort of American children and adolescents derived from the National Health and Nutrition Examination Survey with cross-sectional analysis. In total, 13 618 children and adolescents (median age 13 years; 6107 girls) with available data on whole-body dual-emission X-ray absorptiometry measurements were included. Multiple linear regression showed that SBP was associated with higher total fat-free mass in boys (ß = 0·49, P < 0·001) and girls (ß = 0·47, P < 0·001) and with higher total fat mass only in boys (ß = 0·12, P < 0·001) after adjustment for covariates. When taking fat distribution into consideration, SBP was associated with higher trunk fat mass (boys: ß = 0·28, P < 0·001; girls: ß = 0·15, P < 0·001) but negatively associated with leg fat mass (Boys: ß = -0·14, P < 0·001; Girls: ß = -0·11, P < 0·001), in both boys and girls. Dominance analysis showed that total fat-free mass was the dominant contributor to SBP (boys: 49 %; girls: 55·3 %), followed by trunk fat mass (boys: 32·1 %; girls: 26·9 %); leg fat mass contributed the least to SBP in boys (18·9 %) and girls (17·8 %). Our findings indicated that total fat-free mass was not only associated with SBP but also the most dominant contributor to SBP variation in American children and adolescents.

Association of organ damage with predicted fat mass in a community-dwelling elderly: the Northern Shanghai study.

BACKGROUND: Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. METHODS: 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. RESULTS: All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15-1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48-2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. CONCLUSIONS: Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.

Monocyte to high-density lipoprotein ratio presents a linear association with atherosclerosis and nonlinear association with arteriosclerosis in elderly Chinese population: The Northern Shanghai Study.

BACKGROUND AND AIMS: Inflammation closely correlates with atherosclerosis and cardiovascular disease (CVD). Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammation index that can be obtained by routine blood tests. We aimed to investigate the associations between MHR and atherosclerosis and arteriosclerosis. METHODS AND RESULTS: We enrolled 2451 participants from the Northern Shanghai Study. Atherosclerosis (carotid plaque (CP), lower extremity atherosclerotic (LEA) assessed by ankle-brachial index) and arteriosclerosis (arterial stiffness (AS) assessed by carotid-femoral pulse wave velocity) were measured using standard methods. In the univariable logistic regression model, higher MHR was significantly associated with increased AS, CP, and LEA risk. In the multivariable logistic regression model, after adjustment for age, sex, hypertension, diabetes mellitus, body mass index, smoking habit, low-density lipoprotein cholesterol, and family history of premature CVD, quartile 4 (Q4) of MHR was associated with an increased risk of AS (odds ratio (OR) = 1.41; 95% confidence interval (CI):1.05-1.88; P fortrend = 0.036), CP (OR = 1.35; 95%CI:1.04-1.77; P for trend = 0.044), and LEA (OR = 2.23; 95%CI:1.49-3.35; P for trend< 0.001). Similar results were observed when MHR was analyzed as a continuous variable. The restricted cubic spline (RCS) curve showed that the association between MHR and AS was nonlinear (P nonlinear = 0.021), but not LEA (P nonlinear = 0.177) or CP (P nonlinear = 0.72). CONCLUSION: MHR presents a linear association with atherosclerosis and a nonlinear association with arteriosclerosis in the elderly Chinese population. These findings may indicate the need for early assessment and intervention for inflammation. The registration number for clinical trials: NCT02368938.

Central Versus Peripheral Artery Stiffening and Cardiovascular Risk.

The large elastic arteries fulfill an important role in buffering the cyclical changes in blood pressure, which result from intermittent ventricular ejection. With aging and accrual of cardiovascular risk factors, the elastic arteries stiffen, and this process holds a number of deleterious consequences for the cardiovascular system and major organs. Indeed, arterial stiffness is now recognized as an important, independent determinant of cardiovascular disease risk. Additional, important information concerning the mechanisms underlying arterial stiffening has come from longitudinal studies of arterial stiffness. More recently, attention has focused on the role of peripheral, muscular arteries in cardiovascular disease risk prediction and, in particular, the clinical consequences of reversal of the normal gradient of arterial stiffness between central and peripheral arteries, with aging and disease.

Association between organ damage and visceral adiposity index in community-dwelling elderly Chinese population: the Northern Shanghai Study.

BACKGROUND: The visceral adiposity index (VAI) is a newly developing indicator about visceral fat function and insulin resistance. This research aims to assess the association between organ damage and VAI in the community-dwelling elderly Chinese population. METHODS: In total, 3363 elderly participants were recruited between June 2014 and August 2019. VAI was used to measure visceral adipose accumulation, and organ damage was measured with standardized methods, including arterial stiffness, lower extremity atherosclerosis, carotid hypertrophy, left ventricular hypertrophy, micro-albuminuria, and chronic kidney disease. RESULTS: According to multivariable linear regression analysis, VAI was related to carotid-femoral pulse wave velocity (cf-PWV; ß = 0.047, P = 0.024), urine albumin to creatinine ratio (UACR; ß = 3.893, P = 0.008), estimated glomerular filtration rate (eGFR; ß = - 0.526, P = 0.003) and loge(ankle-to-brachial index) (ABI; ß = -0.003, P = 0.024). Using multivariable stepwise logistic regression model, higher VAI was found to be significantly related to cf-PWV > 10 m/s (OR 1.44, [95% CI 1.17-1.78]; Pfor trend < 0.001), and chronic kidney disease (CKD; OR 1.54, [95% CI 1.09-2.20]; Pfor trend = 0.015). CONCLUSIONS: Since higher VAI is related to increased risk of arterial stiffness and CKD, it may serve as a useful index for the assessment of arteriosclerosis and CKD in elderly population. TRIAL REGISTRATION: NSS, NCT02368938.

Does healthy obesity exist in the elderly? Findings from the Northern Shanghai Study.

BACKGROUND AND AIMS: Metabolic unhealthiness and obesity are both associated with an increased risk of cardiovascular disease. We aimed to investigate the significance of metabolic unhealthiness and obesity in organ damages in a community-based elderly cohort. METHODS AND RESULTS: A total of 3325 elderly participants (>65 years old) were recruited in northern Shanghai. Associations of metabolic status and obesity with organ damages were investigated. In all, 1317 (39.6%) participants were metabolically unhealthy and 481 (14.5%) were obese. Compared with metabolically healthy nonobese (MH-nonobese) individuals, metabolically healthy obese subjects had a greater left ventricular mass index (LVMI) and pulse wave velocity (PWV). Metabolically unhealthy subjects, regardless of their obesity status, had greater organ damage parameters including E/Ea, LVMI, PWV, and urine albumin-creatinine ratio (UACR) than MH-nonobese subjects (all P < 0.05). After multivariate adjustments, both metabolic unhealthiness and obesity increased the risk of left ventricular hypertrophy (LVH) (OR 1.31, 95% CI 1.10-1.57 and OR 1.63, 95% CI 1.30-2.04), diastolic dysfunction (OR 1.33, 95% CI 1.06-1.67 and OR 1.51, 95% CI 1.14-1.99), and lower extremity atherosclerosis (OR 1.44, 95% CI 1.11-1.85 and OR 2.01, 95% CI 1.49-2.70). Metabolic unhealthiness was also associated with arterial stiffness, microalbuminuria and chronic kidney disease (all P < 0.05). In a subgroup analysis, metabolic unhealthiness was associated with more organ damages in nonobese subjects, and obesity was associated with LVH and lower extremity atherosclerosis regardless of metabolic status. CONCLUSION: Both obesity and metabolic unhealthiness were associated with organ damages. Metabolic unhealthiness was associated with more organ damages, especially in nonobese individuals. Even healthy obesity was significantly associated with cardiac and vascular impairment. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT02368938.

The association of four-limb blood pressure differences with cardiovascular risk factors and target organ changes in elderly Chinese: The Northern Shanghai Study.

Background: The association of four-limb systolic blood pressure differences (SBPDs) including inter-arm (IASBPD), inter-leg (ILSBPD) and ankle-brachial index (ABI) with cardiovascular risk factors and target organ changes (TOCs) remains controversial. This study aims at investigating the association of those parameters with cardiovascular risk factors and TOCs in an elderly Chinese population.Methods: A total of 1528 subjects derived from the Northern Shanghai Study were studied. Four-limb BPs were simultaneously measured by VP-1000 device. Cardiovascular risk factors and TOCs including parameters of left ventricular structure and function, carotid intima-media thickness, carotid-femoral pulse-wave velocity (CF-PWV), estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio, were evaluated with standardized methods.Results: ABI significantly associated age (ß = -0.004, p < .01), female gender (ß = 0.02, p < .01), body mass index (ß = -0.004, p < .01), smoking (ß = -0.04, p < .01), high-density lipoprotein (ß = 0.04, p < .01), low-density lipoprotein (ß = -0.01, p = .01) and diabetes mellitus (ß = -0.02, p < .01), while the fourth root of IASBPD significantly associated with body mass index (ß = 0.03, p < .01), high-density lipoprotein (ß = -0.10, p = .02) and brachial SBP (ß = 0.003, p < .01); the fourth root of ILSBPD significantly associated with high-density lipoprotein (ß = -0.12, p < .01) and diabetes mellitus (ß = 0.09, p = .01). IASBPD, ILSBPD, and ABI all significantly associated with CF-PWV and eGFR (all p < .05) in either unadjusted or adjusted models, but not with other TOCs.Conclusion: Four-limb SBPDs, namely ABI, IASBPD, and ILSBPD, bore various burdens of cardiovascular risk factors and significantly and independently associated with CF-PWV and eGFR.

Association between macro- and microvascular damage and the triglyceride glucose index in community-dwelling elderly individuals: the Northern Shanghai Study.

BACKGROUND: It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index. METHODS: A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle-brachial index (ABI), carotid intima-media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated. RESULTS: In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI < 0.9, microalbuminuria (MAU) and chronic kidney disease (CKD). In multivariable logistic regression, there was a significant increase in the risk of cf-PWV > 10 m/s (OR = 1.86, 95% confidence interval [95% CI] 1.37-2.53, Pfor trend < 0.001), ba-PWV > 1800 cm/s (OR = 1.39, [95% CI] 1.05-1.84, Pfor trend= 0.02), MAU (OR = 1.61, [95% CI] 1.22-2.13, Pfor trend < 0.001) and CKD (OR = 1.67, [95% CI] 1.10-1.50, Pfor trend= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque. CONCLUSION: An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.

Comparison of various lipid parameters in association of target organ damage: a cohort study.

BACKGROUND: Recommendations of non-HDL amplification varied from different guidelines. We aim to test the relationships between various lipid parameters and target organ damage (TOD) including aortic stiffness, peripheral arterial disease and chronic kidney disease in a community-based elderly cohort. METHODS: 1599 (aged 71.4 ± 6.1 years) participants were recruited. Eight lipid parameters, including total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, non-HDL-C, TC/HDL ratio, TG/HDL ratio and LDL/HDL ratio, together with other plasma biomarkers like creatinine were measured. Pulse wave velocity (PWV) was measured by the SphygmoCor device, and ankle-brachial index (ABI) was assessed by Omron VP-1000 device. RESULTS: Four individual lipid parameters (TC, TG, LDL-C and HDL-C) significantly correlated with most, but not all, TOD indices. Meanwhile, 4 combined lipid parameters, namely non-HDL-C, TC/HDL, TG/HDL and LCL/HDL, significantly correlated with all TOD (P ≤ 0.033). In multiple linear regression analyses, 4 combined lipid parameters also significantly associated with TOD (P ≤ 0.027), while none of individual lipid parameters significantly associated with all TOD indices. In multiple logistic regression analyses, only non-HDLC and TC/HDL significantly associated with TOD (P ≤ 0.039), and other lipid parameters did not significantly associate with TOD. CONCLUSION: In an elderly community sample, non-HDLC and TC/HDLC were better associated with TOD than other lipid parameters. This finding should be considered in future clinical lipid-lowing therapy. TRIAL REGISTRATION: This trial was retrospectively registered in ClinicalTrials.gov (No. NCT02368938 , registered on 15 Feb 2015).

Blood pressure goal for the elderly Chinese: the findings from the Northern Shanghai Study.

BACKGROUND: The Eighth Joint National Committee Panel (JNC8) recommended a novel blood pressure (BP) goal for individuals with hypertension, which was less stringent than the Seventh Joint National Committee (JNC7) guideline and is still under debate. In our study, we aimed at finding a better BP goal for the elderly Chinese. METHODS: About 1599 community-based elderly participants were recruited in the northern Shanghai and were classified by chronic kidney disease or diabetes mellitus to investigate their BP control conditions based on both the JNC7 and JNC8. Then, participants were categorized into four groups: normotensive individuals (Group 1), individuals at BP goal by JNC7 (Group 2), individuals at BP goal by JNC8 but not by JNC7 (Group 3), and individuals not at-goal by both guidelines (Group 4). Patients' hypertensive target organ damages as left ventricular mass index (LVMI), peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), pulse wave velocity (PWV), etc. were evaluated. RESULTS: According to the JNC8, 19.0% of the population were reclassified as at-goal. Group 4 had significantly greater LVMI than Group 2 (96.5 vs 91.5 g/m2, p < 0.05) and also had significantly greater E/Ea (10.3 vs 9.7 and 10.3 vs 9.7, p < 0.05) and PWV (10.3 vs 9.3 m/s and 10.3 vs 9.7 m/s, p < 0.05) than both Group 2 and Group 3; however, there were no significant differences of these variables between Group 2 and Group 3. CONCLUSION: In the community-based elderly Chinese, the JNC8 hypertension guideline may set a better BP goal than the JNC7 in identifying patients' left ventricular diastolic dysfunction and arterial stiffening.

Incidence and prognosis of cardiac conduction system diseases in hypertension: the STEP trial.

Patients with cardiac conduction system diseases (CSD) may have increased incidence and mortality of cardiovascular events. Here we report a post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) randomized clinical trial (ClinicalTrials.gov number, NCT03015311) concerning the effect of intensive blood pressure (BP) control on the incidence of new-onset CSD and the prognostic implications of preexisting or new-onset CSD. The incidence of new-onset CSD was similar in the intensive (n = 205, 6.42%) and standard (n = 188, 5.94%) treatment arms. Participants with preexisting CSD had a higher risk for acute decompensated heart failure. Increased age, male sex and increased body mass index were independently associated with increased risk for new-onset CSD. Our results suggest that intensive BP control may not reduce the incidence of new-onset CSD compared with standard BP control.

Vasculopathy Augments Cardiovascular Risk in Community-Dwelling Elderly with Left Ventricular Hypertrophy.

This study aimed to investigate the impact of various vasculopathies alongside left ventricular hypertrophy (LVH) on cardiovascular risk in the elderly. This prospective cohort study included 3339 older adults from the Northern Shanghai Study, classified into four mutually exclusive left ventricular (LV) geometry groups based on echocardiographic data: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Vasculopathy was categorized into three primary types: arteriosclerosis, atherosclerosis, and renal senescence. Major adverse cardiovascular events (MACEs) were defined as non-fatal acute myocardial infarction, non-fatal stroke, and cardiovascular deaths according to ICD-10 codes. Over a median follow-up period of 5.7 years, 221 incident cases of MACEs were identified. Concentric hypertrophy exhibited the highest prevalence of hypertension, the most significant increase in vascular stiffness, and the highest rate of MACEs. The adjusted Cox regression analysis showed that eccentric hypertrophy is associated with an increased risk of MACEs (HR: 1.638 [95% CI: 1.151-2.331], p = 0.006), while concentric hypertrophy shows an even higher risk (HR: 1.751 [95% CI: 1.127-2.721], p = 0.013). Conversely, concentric remodeling was not significantly associated with an increased risk of MACEs. Renal senescence presents a moderate but significant risk for MACEs, with an HR of 1.361 (95% CI: 1.019-1.819; p = 0.037) when adjusted for LVH. The Kaplan-Meier analysis showed that patients with LVH and multiple vasculopathies experience the most significant decrease in survival probability (log-rank p < 0.001). The subgroup analysis revealed that LVH significantly raises the risk of MACEs, especially in older males with hypertension, diabetes, or vasculopathy. This study reinforces the importance of LVH as a predictor of adverse cardiovascular outcomes and underscores the compounded risk associated with the presence of multiple vasculopathies. Additionally, it highlights renal senescence as a distinct and independent risk factor for MACEs, separate from LVH.

Photocatalyzed Oxidative Tandem Reaction Mediated by Bipyridinium for Multifunctional Derivatization of Alcohols.

The multifunctional derivatization of alcohols has been achieved by the bipyridinium-based conjugated small molecule photocatalysts with redox center and Lewis acid site. Besides exhibiting high activity in the selective generation of aldehydes/ketones, acids from alcohols through solvent modulation, this system renders the first selective synthesis of esters via an attractive cross-coupling pattern, whose reaction route is significantly different from the traditional condensation of alcohols and acids or esterification from hemiacetals. Following the oxidization of alcohol to aldehyde via bipyridinium-mediated electron and energy transfer, the Lewis acid site of bipyridinium then activates the aldehyde and methanol to obtain the acetal, which further reacts with methanol to generate ester. This method not only demonstrates a clear advantage of bipyridinium in diverse catalytic activities, but also paves the way for designing efficient multifunctional small molecule photocatalysts. This metal- and additive-free photocatalytic esterification reaction marks a significant advancement towards a more environmentally friendly, cost-effective and green sustainable approach, attributed to the utilization of renewable substrate alcohol and the abundant, low-cost air as the oxidant. The mildness of this esterification reaction condition provides a more suitable alternative for large-scale industrial production of esters.

The lncRNA GAS5 upregulates ANXA2 to mediate the macrophage inflammatory response during atherosclerosis development.

Inflammatory macrophages play a crucial role in atherosclerosis development. The long non-coding RNA growth arrest-specific 5 (GAS5) regulates THP-1 macrophage inflammation by sponging microRNAs. The purpose of this study was to investigate the regulatory mechanism of GAS5 in atherosclerosis development. GSE40231, GSE21545, and GSE28829 datasets from the Gene Expression Omnibus database were integrated after adjusting for batch effect. Differential analysis was performed on the integrated dataset and validated using the Genotype-Tissue Expression and GSE57691 datasets. Potential biological functions of GAS5 and annexin A2 (ANXA2) were identified using gene set enrichment analysis (GSEA). ssGSEA, CIBERSORTx, and ImmuCellAI algorithms were used to identify immune infiltration in plaque samples. GAS5 and ANXA2 expression levels in RAW264.7 cells treated with oxidized low-density lipoprotein (ox-LDL) were measured by qRT-PCR and Western blot. Small interfering and short hairpin RNA were used to silence GAS5 expression. Plasmids of ANXA2 were used to establish ANXA2 overexpression. Apoptosis and inflammatory markers in macrophages were detected by Western blot. Aortic samples from APOE-/- mice were collected to validate the expression of GAS5 and ANXA2. GAS5 expression was significantly increased during atherosclerosis. GAS5 expression was positively correlated with macrophage activation and ANXA2 expression in plaques. Furthermore, ANXA2 upregulation was also related to the activation of macrophage. GSEA indicated similar biological functions for GAS5 and ANXA2 in plaques. Moreover, in vitro experiments showed that both GAS5 and ANXA2 contributed to macrophage apoptosis and inflammation. Rescue assays revealed that the inflammatory effects of GAS5 on macrophages were ANXA2-dependent. In vivo experiments confirmed the highly expression of Gas5 and Anxa2 in the plaque group. We identified the atherogenic roles of GAS5 and ANXA2 in the inflammatory response of macrophages. The inflammatory response in ox-LDL-treated macrophages was found to be mediated by GAS5-ANXA2 regulation, opening new avenues for atherosclerosis therapy.

Northern Shanghai Study II: systematic assessment and management of early organ damage and its role in preventing and reducing cardiovascular risk-protocol of a prospective study.

INTRODUCTION: Cardiovascular diseases are the leading cause of death and disease burden in China. However, there is a lack of prospective cohort studies suitable for evaluating early organ damage and its role in preventing and reducing cardiovascular risk among Chinese residents. This study intends to establish the first database based on the phenotypes of all early structural and functional damage of cardiovascular organs in Chinese population. Moreover, a digital follow-up mechanism will be formed, a prospective population cohort will be established, a biological sample bank for early cardiovascular organ damage will be established, and an intervention and management system for early damage of cardiovascular organs will be explored. METHODS AND ANALYSIS: This study is a prospective cohort study built on the foundation of the Northern Shanghai Study I. People aged 18-75 years are enrolled. After the recruitment, first, corresponding physical measurements and clinical examinations are conducted to collect cardiovascular risk factors and establish the demographic baseline of the study population. Next, the latest equipment is used to evaluate early structural and functional cardiovascular organ damage including heart, macrovessels, microcirculation, renal function and fundus. Meanwhile, the blood, urine, faeces and other biological samples of participants are collected to establish the cardiometabolic and gut microbiota analysis databases. The population is followed up every 2 years. Comprehensive assessment of early organ damage will be used to predict cardiovascular risk, guide people to change lifestyles to achieve early prevention and provide corresponding treatment recommendations. ETHICS AND DISSEMINATION: This study was approved by the Shanghai Tenth People's Hospital Institutional Review Board. All participants signed a written consent form. The results of this study will be disseminated in peer-reviewed journals. Ethics approval: SHYS-IEC-5.0/22k148/P01. TRIAL REGISTRATION NUMBER: NCT05435898.

Immature neutrophil is associated with coronary plaque vulnerability based on optical coherence tomography analysis.

INTRODUCTION: High neutrophil to lymphocyte ratio is considered to predict poor prognosis of acute coronary syndrome (ACS). However, the association of neutrophil subpopulation with plaque vulnerability and the incidence of ACS remains unknown. METHODS AND RESULTS: Blood samples from 48 patients with unstable angina (UA), 31 with ST-segment elevation myocardial infarction (STEMI) and 33 healthy controls were collected at admission. The morphology of coronary plaques in 48 UA patients were further evaluated by optical coherence tomography (OCT). According to maturation stages of neutrophils and the expression of CD10 and CD101, circulating neutrophils could be divided into pre-neutrophils (CD101-CD10-), immature neutrophils (CD101+CD10-) and mature neutrophils (CD101+CD10+). While the number of pre-neutrophil was quite low in blood and comparable among three groups, the absolute counts and percentage of CD10- immature neutrophils were higher in peripheral bloods of UA and STEMI patients compared with those in healthy controls. The concentration of plasma myeloperoxidase was positively associated with the percentage of CD10- immature neutrophils. Furthermore, UA patients with thin-cap fibroatheroma (TCFA) observed by OCT had a higher proportion and larger number of immature neutrophils as compared to those without TCFA. The percentage of immature neutrophils also closely correlated with plaque rupture and the feature of vulnerable plaque, including thinner fibrous cap and larger lipid core, but did not associate with percent lumen stenosis. CONCLUSION: Our findings emphasize that the abnormally increased level of CD10- immature neutrophils may sever as a promising marker of the incidence of ACS and plaque vulnerability.

Etiological Diagnosis and Personalized Therapy for Hypertension: A Hypothesis of the REASOH Classification.

With the epidemic of risk factors such as unhealthy lifestyle, obesity and mental stress, the prevalence of hypertension continues to rise across the world. Although standardized treatment protocols simplify the selection of antihypertensive drugs and ensure therapeutic efficacy, the pathophysiological state of some patients remains, which may also lead to the development of other cardiovascular diseases. Thus, there is an urgent need to consider the pathogenesis and selection of antihypertensive drug for different type of hypertensive patients in the era of precision medicine. We proposed the REASOH classification, based on the etiology of hypertension, including renin-dependent hypertension, elderly-arteriosclerosis-based hypertension, sympathetic-active hypertension, secondary hypertension, salt-sensitive hypertension and hyperhomocysteinemia hypertension. The aim of this paper is to propose a hypothesis and provide a brief reference for the personalized treatment of hypertensive patients.

Short Sleep Duration Was Associated with Increased Regional Body Fat in US Adults: The NHANES from 2011 to 2018.

Background: The relationship between sleep duration and different regional fat is unclear. We aimed to investigate the association between sleep duration and different regional fat mass (FM) among a population of US adults. Methods: 9413 participants were included from the National Health and Nutrition Examination Survey (NHANES), from 2011 to 2018. The sleep duration was divided into short sleep (<7 h/day), normal sleep (7−9 h/day) and long sleep (>9 h/day). Different regional FM was measured by dual-energy X-ray absorptiometry, including trunk FM, arms FM and legs FM. Fat mass index (FMI) was obtained by dividing FM (kg) by the square of body height (m2). Multiple linear regression was used to evaluate the relationship between sleep duration and regional FMI. Results: The mean sleep duration was 7.1 ± 1.5 h/day. After adjusting for socio-demographic, lifestyle information, comorbid diseases and medications, short sleepers had higher trunk FMI (ß = 0.134, 95% confidence interval (CI): 0.051−0.216, p = 0.001), arms FMI (ß = 0.038, 95% CI: 0.016−0.06, p < 0.001) and legs FMI (ß = 0.101, 95% CI: 0.044−0.158, p < 0.001) compared to normal sleepers, whereas no significant difference was found in long sleepers. The similar results were also observed in men, while short sleepers only had higher arms FM in women (all p < 0.01). In addition, compared to normal sleepers, short sleepers had higher arms FMI and legs FMI in the obese group (all p < 0.05), while no relationship was observed in non-obese group. Conclusions: Short sleep duration, but not long sleep duration, was independently related to the increased different regional body fat in US adults, especially in men and those with obesity.

The impact of body composition and fat distribution on blood pressure in young and middle-aged adults.

Background: The relative contributions of each component of body composition to blood pressure (BP) remain unclear. Objective: We aimed to comprehensively investigate the impact of body composition and fat distribution on BP and quantify their relative contributions to BP in a large cohort with young and middle-aged adults. Methods: 14,412 participants with available data on whole-body DXA measurement from the National Health and Nutrition Examination Survey were included. Multiple stepwise linear regressions of BP on components of body composition and fat distribution were built. Then, relative importance analysis was performed to quantify the contributions of each component to BP. Results: The median age of participants was 36 years and there were 50.7% women. Linear regression with mutual adjustment showed that total fat mass, total muscle mass, and trunk fat mass significantly and positively associated with BP; however, arm and leg fat mass significantly and negatively associated with BP. In men, after further adjusted for potential covariates, SBP were significantly determined by trunk fat mass (ß = 0.33, P < 0.001), leg fat mass (ß = - 0.12, P < 0.001), and total muscle mass (ß = 0.10, P < 0.001); and DBP were significantly determined by trunk fat mass (ß = 0.52, P < 0.001), leg fat mass (ß = -0.15, P < 0.001), arm fat mass (ß = -0.23, P < 0.001), and total muscle mass (ß = 0.06, P < 0.001). Similar results were observed in women. Relative importance analysis showed that trunk fat mass was the major contributor (38-61%) to both SBP and DBP; meanwhile, total muscle mass also made relatively great contribution (35-43%) to SBP. Conclusion: Both fat mass and muscle mass independently associated with and substantially contributed to SBP in both men and women. After full adjustment, trunk fat mass positively associated with both SBP and DBP, and was the most dominant contributor to BP; however, leg fat mass negatively associated with both SBP and DBP.

Extraction Optimization, Structural Characterization, and Anti-Hepatoma Activity of Acidic Polysaccharides From Scutellaria barbata D. Don.

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and ß-glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro, and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide.