Diagnosis of preeclampsia using metabolomic biomarkers.

The diagnostic criteria for preeclampsia do not accurately reflect the pathophysiological characteristics of patients with preeclampsia. Conventional biomarkers and diagnostic approaches have proven insufficient to fully comprehend the intricacies of preeclampsia. This study aimed to screen differentially abundant metabolites as candidate biomarkers for preeclampsia. A propensity score matching method was used to perform a 1:1 match between preeclampsia patients (n = 70) and healthy control individuals (n = 70). Based on univariate and multivariate statistical analysis methods, the different characteristic metabolites were screened and identified. Least absolute shrinkage and selection operator (LASSO) regression analysis was subsequently used to further screen for differentially abundant metabolites. A receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of the metabolites. A total of 1,630 metabolites were identified and quantified in maternal serum samples. Fifty-three metabolites were significantly increased, and two were significantly decreased in preeclampsia patients. The area under the curve (AUC) of the model composed of isobutyryl-L-carnitine and acetyl-leucine was 0.878, and the sensitivity and specificity in detecting preeclampsia were 81.4% and 87.1%, respectively. There are significant differences in metabolism between preeclampsia patients and healthy pregnant women, and a range of novel biomarkers have been identified. These findings lay the foundation for the use of metabolomic biomarkers for the diagnosis of preeclampsia.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Risk factors and prediction model for new-onset hypertensive disorders of pregnancy: a retrospective cohort study.

Background and aims: Hypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to develop a prediction model for assessing the risk of new-onset hypertension during pregnancy. Methods: We included 446 pregnant women without baseline hypertension from Liyang People's Hospital at the first inspection, and they were followed up until delivery. We collected maternal clinical parameters and biomarkers between 16th and 20th weeks of gestation. Logistic regression was used to determine the effect of the risk factors on HDP. For model development, a backward selection algorithm was applied to choose pertinent biomarkers, and predictive models were created based on multiple machine learning methods (generalised linear model, multivariate adaptive regression splines, random forest, and k-nearest neighbours). Model performance was evaluated using the area under the curve. Results: Out of the 446 participants, 153 developed new-onset HDP. The HDP group exhibited significantly higher baseline body mass index (BMI), weight change, baseline systolic/diastolic blood pressure, and platelet counts than the control group. The increase in baseline BMI, weight change, and baseline systolic and diastolic blood pressure significantly elevated the risk of HDP, with odds ratios and 95% confidence intervals of 1.10 (1.03-1.17), 1.10 (1.05-1.16), 1.04 (1.01-1.08), and 1.10 (1.05-1.14) respectively. Restricted cubic spline showed a linear dose-dependent association of baseline BMI and weight change with the risk of HDP. The random forest-based prediction model showed robust performance with the area under the curve of 0.85 in the training set. Conclusion: This study establishes a prediction model to evaluate the risk of new-onset HDP, which might facilitate the early diagnosis and management of HDP.

Design, methodology, and baseline of eastern China student health and wellbeing cohort study.

Purpose: To describe the study design, methodology, and cohort profile of the Eastern China Student Health and Wellbeing Cohort Study. The cohort baseline includes (1) targeted disease (myopia, obesity, elevated blood pressure, and mental health) and (2) exposures (individual behaviors, environment, metabolomics, and gene and epigenetics). Participants: Annual physical examination, questionnaire-based survey, and bio-sampling have been carried out in the study population. In the first stage (2019-2021), a total of 6,506 students in primary schools are enrolled in the cohort study. Findings to date: Of all the cohort participants, the ratio of male to female is 1.16 among a total of 6,506 student participants, of which 2,728 (41.9%) students are from developed regions and 3,778 (58.1%) students are from developing regions. The initial age of observation is 6-10 years, and they will be observed until they graduate from high school (>18 years of age). (1) Targeted diseases: The growth rates of myopia, obesity, and high blood pressure vary by regions, and for developed regions, the prevalence of myopia, obesity, and elevated blood pressure is 29.2%, 17.4%, and 12.6% in the first year, respectively. For developing regions, the prevalence of myopia, obesity, and elevated blood pressure is 22.3%, 20.7%, and 17.1% in the first year, respectively. The average score of CES-D is 12.9 ± 9.8 in developing regions/11.6 ± 9.0 in developed regions. (2) Exposures: ① The first aspect of individual behaviors: the questionnaire topics include diet, physical exercise, bullying, and family. ② The second aspect of environment and metabolomics: the average desk illumination is 430.78 (355.84-611.56) LX, and the average blackboard illumination is 365.33 (286.83-516.84) LX. Metabolomics like bisphenol A in the urine is 0.734 ng/ml. ③ The third aspect of gene and epigenetics: SNPs (rs524952, rs524952, rs2969180, rs2908972, rs10880855, rs1939008, rs9928731, rs72621438, rs9939609, rs8050136 and so on) are detected. Future plans: Eastern China Student Health and Wellbeing Cohort Study is aiming to focus on the development of student-targeted diseases. For children with student common diseases, this study will focus on targeted disease-related indicators. For children without targeted disease, this study aims to explore the longitudinal relationship between exposure factors and outcomes, excluding baseline confounding factors. Exposure factors include three aspects: (1) individual behaviors, (2) environment and metabolomics, and (3) gene and epigenetics. The cohort study will continue until 2035.

Association between the triglyceride-glucose index and albuminuria in hypertensive individuals.

BACKGROUND: Previous studies have demonstrated that the triglyceride-glucose (TyG) index is significantly associated with vascular damage. Albuminuria is a marker of hypertension-mediated organ damage (HMOD) and has been linked to a greater risk of cardiovascular disease (CVD). However, the association between the TyG index and albuminuria in patients with hypertension is not clear. This population research focused on subjects with hypertension to investigate the association between an elevated TyG index and albuminuria. METHODS: From September 2019 to November 2019, 789 hypertensive participants were involved in our research. Logistic regression models were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for albuminuria according to the quartiles of the TyG index. RESULTS: Multivariate logistic regression analysis revealed that the TyG index was significantly associated with albuminuria. Using the lowest TyG index quartile as the reference, the fully adjusted ORs (95% CIs) for albuminuria for TyG index quartile II, quartile III, and quartile IV were 1.90 (1.17-3.12), 1.81 (1.07-3.07), and 3.46 (2.06-5.91), respectively. The results in the subgroup analysis were similar to the main analyses except for the smokers. Restricted cubic spline curves based on logistic regression models evaluated the linear association between the TyG index and albuminuria (P for nonlinear = 0.831). CONCLUSION: The TyG index was positively associated with albuminuria among hypertensive participants.

Perirenal adipose afferent nerves sustain pathological high blood pressure in rats.

Hypertension is a pathological condition of persistent high blood pressure (BP) of which the underlying neural mechanisms remain obscure. Here, we show that the afferent nerves in perirenal adipose tissue (PRAT) contribute to maintain pathological high BP, without affecting physiological BP. Bilateral PRAT ablation or denervation leads to a long-term reduction of high BP in spontaneous hypertensive rats (SHR), but has no effect on normal BP in control rats. Further, gain- and loss-of-function and neuron transcriptomics studies show that augmented activities and remodeling of L1-L2 dorsal root ganglia neurons are responsible for hypertension in SHR. Moreover, we went on to show that calcitonin gene-related peptide (CGRP) is a key endogenous suppressor of hypertension that is sequestered by pro-hypertensive PRAT in SHRs. Taken together, we identify PRAT afferent nerves as a pro-hypertensive node that sustains high BP via suppressing CGRP, thereby providing a therapeutic target to tackle primary hypertension.

Interleukin 10 Attenuates Angiotensin II-Induced Aortic Remodelling by Inhibiting Oxidative Stress-Induced Activation of the Vascular p38 and NF-κB Pathways.

Interleukin 10 (IL-10) is a probable anti-inflammatory factor that can attenuate hypertrophic remodelling caused by overloaded pressure and improve cardiac function. In this study, IL-10 was decreased in both the plasma of hypertensive patients and the aortic vessels of angiotensin II (Ang II)-induced hypertensive mice. IL-10 was unable to alter blood pressure in the case of Ang II-induced hypertension. The aortic thickness, collagen deposition, and the levels of fibrosis-associated markers, including collagen type I α 1 (Col1α1), connective tissue growth factor (CTGF), transforming growth factor-ß (TGF-ß), and matrix metalloproteinase 2 (MMP2), were significantly reduced in the IL-10 treatment group compared with the vehicle group after Ang II treatment. Moreover, IL-10 treatment significantly inhibited the number of CD45+ positive cells and the mRNA expression levels of proinflammatory cytokines in the vascular tissue of Ang II-infused mice. Furthermore, dihydroethidium (DHE) and 4hydroxynonenal (4-HNE) staining showed that IL-10 decreased Ang II-induced vascular oxidative stress and lipid peroxidation. Furthermore, IL-10 suppressed Ang II-induced proliferation, fibrosis, and inflammation of mouse vascular adventitial fibroblasts (mVAFs). Mechanistically, IL-10 suppressed the phosphorylation of p38 mitogen-activated protein (MAP) kinase and nuclear factor-κB (NF-κB) in Ang II-induced vascular fibrosis. In summary, our data indicated that IL-10, as a potential therapeutic target treatment, could limit the progression of Ang II-induced aortic remodelling.

Omental Adipose Removal Decreases High Blood Pressure in Hypertensive Patients Independent of Body Mass Index.

AIM: Several studies have demonstrated that increased omental adipose is a risk factor for obesity and metabolic syndrome. It remains unclear whether it is responsible for hypertension as an independent risk. This study was designed to assess the impact of omental adipose removal by surgery on blood pressure in cancer patients with or without hypertension. METHODS AND RESULTS: In this prospective observational study, 133 patients with gastric or gynecological cancer were divided into 3 groups: non-hypertensive and omentum removed (NH&OR), hypertensive and omentum removed (H&OR), and hypertensive and omentum present (H&OP). Patients were followed up with systolic and diastolic blood pressure (SBP and DBP), changes in related body mass index and metabolic indices. The time points of the 2 follow-up visits were 1 month ± 7 days after the operation before the start of chemotherapy and the endpoint of 8 ± 1 month. Omental adipose tissues from both non-hypertensive and hypertensive patients in surgery were collected. We included 133 patients (84.2% female, 20.3% malignant gastric cancer and 79.7% malignant gynecological cancer, 78.2% omentum removal, 48.9% hypertensive), and all completed follow-up. H&OR group showed significant reductions in systolic and diastolic blood pressure compared with the baseline at 1-m (-16.94/-10.50 mmHg, both P < 0.001) and 8-m end point (-16.00/-5.50 mmHg, P < 0.001 and P = 0.004). Little reductions were observed with the body mass index of patients in 3 groups till the endpoint of study (H&OR group: 24.60 kg/m2 to 23.57 kg/m2, NH&OR group: 23.45 kg/m2 to 23.25 kg/m2, H&OP group: 25.74 kg/m2 to 25.24 kg/m2, all P > 0.05). No correlation was found between the baseline body mass index and 8-m change of systolic and diastolic blood pressure in omentum removed groups. In both groups, triglyceride levels were significantly increased at 4 ± 1 week after surgery (NH&OR 0.32 mmol/L, P = 0.006; H&OR 0.40 mmol/L, P = 0.010). CONCLUSION: Resection of omental adipose tissue represents an effective strategy for reducing systolic and diastolic blood pressure at 8 months in hypertensive patients, even in the non-obese hypertensive population.

Comparative Study of Metabolite Changes After Antihypertensive Therapy With Calcium Channel Blockers or Angiotensin Type 1 Receptor Blockers.

ABSTRACT: The high prevalence of hypertension contributes to an increased global burden of cardiovascular diseases. Calcium channel blockers (CCBs) and angiotensin type 1 receptor blockers (ARBs) are the most widely used antihypertensive drugs, and the effects of these drugs on serum metabolites remain unknown. Untargeted metabolomics has been proved to be a powerful approach for the detection of biomarkers and new compounds. In this study, we aimed to determine the changes in metabolites after single-drug therapy with a CCB or ARB in patients newly diagnosed with mild to moderate primary hypertension. We enrolled 33 patients and used an untargeted metabolomics approach to measure 625 metabolites associated with the response to a 4-week treatment of antihypertensive drugs. After screening based on P < 0.05, fold change > 1.2 or fold change < 0.83, and variable importance in projection > 1, 63 differential metabolites were collected. Four metabolic pathways-cysteine and methionine metabolism, phenylalanine metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism-were identified in participants treated with ARBs. Only taurine and hypotaurine metabolism were identified in participants treated with CCBs. Furthermore, homocitrulline and glucosamine-6-phosphate were relevant to whether the blood pressure reduction achieved the target blood pressure (P < 0.05). Our study provides some evidence that changes in certain metabolites may be a potential marker for the dynamic monitoring of the protective effects and side effects of antihypertensive drugs.

Inhibition of acetylation of histones 3 and 4 attenuates aortic valve calcification.

Aortic valve calcification develops in patients with chronic kidney disease who have calcium and phosphate metabolic disorders and poor prognoses. There is no effective treatment except valve replacement. However, metabolic disorders put patients at high risk for surgery. Increased acetylation of histones 3 and 4 is present in interstitial cells from human calcific aortic valves, but whether it is involved in aortic valve calcification has not been studied. In this study, we found that treating cultured porcine aortic valve interstitial cells with a high-calcium/high-phosphate medium induced calcium deposition, apoptosis, and expression of osteogenic marker genes, producing a phenotype resembling valve calcification in vivo. These phenotypic changes were attenuated by the histone acetyltransferase inhibitor C646. C646 treatment increased the levels of class I histone deacetylase members and decreased the acetylation of histones 3 and 4 induced by the high-calcium/high-phosphate treatment. Conversely, the histone deacetylase inhibitor suberoylanilide hydroxamic acid promoted valve interstitial cell calcification. In a mouse model of aortic valve calcification induced by adenine and vitamin D treatment, the levels of acetylated histones 3 and 4 were increased in the calcified aortic valves. Treatment of the models with C646 attenuated aortic valve calcification by restoring the levels of acetylated histones 3 and 4. These observations suggest that increased acetylation of histones 3 and 4 is part of the pathogenesis of aortic valve calcification associated with calcium and phosphate metabolic disorders. Targeting acetylated histones 3 and 4 may be a potential therapy for inoperable aortic valve calcification in chronic kidney disease patients.

Hydralazine protects against renal ischemia-reperfusion injury in rats.

In this study, we investigated whether hydralazine could reduce renal ischemia and reperfusion (I/R) injury in rats. Renal I/R was induced by a 70-min occlusion of the bilateral renal arteries and a 24-h reperfusion, which was confirmed by the increased the mortality, the levels of blood urea nitrogen (BUN), blood creatinine (Cr), renal tissue NO and the visible histological damage of the kidneys. Apoptosis was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, the serum levels of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were significantly elevated in renal I/R group, while the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels were suppressed. However, intragastric pretreatment with hydralazine at doses of 7.5-30 mg/kg before renal I/R significantly limited the increase in mortality, BUN, Cr, oxidative stress, inflammatory factors, histological damage and apoptosis in the kidneys. In addition, hydralazine also increased p-AKT, Bcl-2 expression and decreased iNOS, Bax, cleaved caspase-3 expression in the kidneys. In conclusion, hydralazine reduced renal I/R injury probably via inhibiting NO production by iNOS/NO pathway, inhibiting oxidative stress, inflammatory response and apoptosis by a mitochondrial-dependent pathway.

A pilot clinical study of adjunctive therapy with selective intracoronary hypothermia in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We aimed to assess the effect of selective intracoronary hypothermia on outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND: Intracoronary hypothermia, the feasibility and safety of which has been validated in humans, induced by selective trans-coronary infusion of saline at different temperatures can reduce infarct size (IS) prior to reperfusion in animal models of STEMI. METHODS: Sixty STEMI patients presenting with thrombolysis in myocardial infarction (TIMI) flow grade 0/1 were randomized after coronary artery angiography. Intracoronary hypothermia was induced by selective trans-coronary infusion of saline at 4°C to the endangered myocardium in the 30 patients. The primary endpoint, absolute IS expressed as IS/myocardium at risk (MaR), was assessed by cardiac magnetic resonance imaging at day 7 post-PPCI in 50 patients. Clinical follow-up was undertaken at day 30 after procedure. RESULTS: Intracoronary hypothermia was successfully performed in hypothermia group, without increase in arrhythmia or hemodynamic instability. The mean temperature reduction of 5.8 ± 1.1°C in distal coronary artery was achieved before reperfusion. Mean IS/MaR was predominantly reduced in the hypothermia group (44.85 ± 5.89% vs. 50.69 ± 10.75%, P = 0.022), especially in the anterior STEMI subgroup (46.12 ± 7.54% vs. 55.27 ± 11.175%, P = 0.023). The clinical events appeared no statistical difference between the two groups at the 30-day follow-up. CONCLUSION: The statistical difference in IS/MaR by intracoronary hypothermia as adjunctive therapy to PPCI is an important observation and warrants a larger pivotal trial fully powered for efficacy.

Smoking, Hypertension, and Their Combined Effect on Ischemic Stroke Incidence: A Prospective Study among Inner Mongolians in China.

OBJECTIVE: We intended to investigate the combined effect of smoking and hypertension on ischemic stroke incidence based on a 10-year prospective study among Inner Mongolians in China. METHODS: A prospective cohort study from June 2003 to July 2012 was conducted among 2589 participants aged 20 years and older from Inner Mongolia, China. We categorized the participants into 4 subgroups according to the status of smoking and hypertension. The cumulative incidence rates of ischemic stroke among the 4 subgroups were estimated using Kaplan-Meier curves and compared by log-rank test. Cox proportional hazard model was used to compute hazard ratios of ischemic stroke across the 4 subgroups after adjusting for important confounding factors. RESULTS: The cumulative incidence rates of ischemic stroke were .85%, 2.05%, 3.19%, and 8.14% among non-hypertension/non-smokers, non-hypertension/smokers, hypertension/non-smokers, and hypertension/smokers, respectively. The multivariable-adjusted hazard ratios [95% confidence intervals] of ischemic stroke for hypertension and smoking were 1.84 [1.05-3.23] and 1.89 [1.11-3.22], respectively. The hazard ratios [95% confidence intervals] of ischemic stroke for non-hypertension/smokers, hypertension/non-smokers, and hypertension/smokers were 1.37 [.56-3.33], 1.34 [.54-3.29], and 2.93 [1.26-6.83], respectively, compared with the non-hypertension/non-smokers. Significant interaction was detected between smoking and hypertension on the risk of ischemic stroke. CONCLUSIONS: Our study indicated that participants with coexistence of smoking and hypertension were at the highest risk for ischemic stroke. There was a significant interaction between smoking and hypertension on the risk of ischemic stroke.

YKL-40 is a novel biomarker for predicting hypertension incidence among prehypertensive subjects: A population-based nested case-control study in China.

BACKGROUND AND AIMS: The previous study suggested that Human cartilage glycoprotein-39 (YKL-40) was positively associated with hypertension incidence in certain high-risk groups of hypertension. We aimed to investigate that whether YKL-40 is an effective biomarker for predicting hypertension incidence among prehypertensive subjects. METHODS: In a 1:1 matched case-control study of 700 pairs with available YKL-40 levels nested in a prospective cohort of initially healthy Chinese subjects, 294 pairs additionally have matched baseline BP status (prehypertensive or normotensive). Multivariable conditional logistic regression analyses were used to calculate the odds ratios (95% confidential intervals) of hypertension associated with higher levels of YKL-40 in both prehypertensive and normotensive subgroups, respectively. RESULTS: In the prehypertensive subgroup, the subjects in the highest quartile of plasma YKL-40 levels had a significantly higher risk of hypertension incidence, compared with those in the lowest quartile. The odds ratio (95% confidential intervals) is 2.01 (1.05-3.85). A positive association between YKL-40 levels and hypertension incidence was found (P for trend<0.05). However, this significant association was not observed in the normotensive subgroup. CONCLUSIONS: Higher YKL-40 levels at baseline were positively associated with hypertension incidence among prehypertensive subjects. YKL-40 may represent a novel biomarker for predicting hypertension risk in prehypertension population.

Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China.

BACKGROUND: Atrial natriuretic peptide (ANP) and its prohormone activating enzyme are associated with central obesity, suggesting there may be a potential relationship between proANP1-98 and central obesity. However, the association is still lack of population-based evidence. We explored the association in a general population of China. METHODS: We measured plasma proANP1-98, waist circumference and other traditional biomarkers in 2203 participants aged≥30y. Multivariate logistic regression models were used to determine the association between plasma proANP1-98 and central obesity, and odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: High proANP1-98 was significantly associated with increased risk of central obesity in participants, and the multivariate adjusted OR (95% CI) of central obesity associated with the second, third and fourth quartiles of proANP1-98 were 1.33 (1.03-1.72), 1.69 (1.31-2.19) and 1.76 (1.35-2.29), respectively, compared with the lowest quartile of proANP1-98. There was a dose-response relationship between proANP1-98 and risk of central obesity among the participants (Ptrend<0.001). Sensitivity analyses further confirmed these associations. Adding proANP1-98 to a model containing conventional risk factors improved discriminatory power of central obesity (as shown by significant improvement in continuous NRI and IDI). CONCLUSIONS: Contrary to known reduced ANP levels in central obesity, we found that plasma proANP1-98 was positively associated with central obesity, suggesting that elevated plasma proANP1-98 may be a marker or a risk factor for central obesity.

Association between plasma proANP and hyperuricemia in Chinese Han women: a cross-sectional study.

BACKGROUND: Association between pro-atrial natriuretic peptide (proANP) and hyperuricemia has not yet been investigated in population. This study aimed to examine the association in Chinese Han women. METHODS: We measured plasma proANP, serum uric acid, and other traditional biomarkers in 1360 women older than 30 years residing in the Gusu district of Suzhou City. Association between plasma proANP and hyperuricemia was analyzed in women aged ≥45 years and those aged <45 years, respectively. RESULTS: In women aged ≥45 years, the odds ratio (OR) [95% confidence interval (CI)] of hyperuricemia with high proANP (over the median) was 0.57 (0.34-0.97) compared to those with low proANP (p=0.040). After adjustment for age and other potential covariates, a high plasma proANP was associated with a decreased risk of hyperuricemia in women aged ≥45 years (OR 0.40; 95% CI, 0.19-0.84), when the highest and lowest categories were compared. In contrast, there was no association between plasma proANP and hyperuricemia in women aged <45 years. We did not observe a significant interaction between age and proANP (pinteraction=0.113). Sensitivity analyses further confirmed these age-specific findings. CONCLUSIONS: Plasma proANP was significantly and inversely associated with hyperuricemia in Chinese Han women aged ≥45 years. This study suggests that an increased plasma proANP should be a protective factor of hyperuricemia among middle-aged and old women.

Copeptin as a biomarker for prediction of prognosis of acute ischemic stroke and transient ischemic attack: a meta-analysis.

This meta-analysis aimed to investigate the predictive effect of copeptin as a biomarker for the prognosis of acute ischemic stroke and transient ischemic attack. Electronic databases including PubMed, Medline, EMBASE, Web of Science and Cochrane Central were searched for studies assessing the association of copeptin level on admission with prognosis of acute ischemic stroke and transient ischemic attack. The Newcastle-Ottawa Quality assessment scale for cohort study was used to evaluate quality. A total of 1976 acute ischemic stroke patients from 6 studies were included, and 59% of patients were male. Patients with poor outcomes and nonsurvivors had a higher copeptin level at admission (P<0.0001). Copeptin combined with an admission National Institutes of Health Stroke Scale score significantly improved the discriminatory accuracy of functional outcome and mortality compared with the National Institutes of Health Stroke Scale alone. Elevation in plasma copeptin level carried a higher risk of all-cause mortality (odds ratio=4.16; 95% CI: 2.77-6.25) and poor functional outcome (odds ratio=2.56; 95% CI: 1.97-3.32) after acute ischemic stroke. In addition, copeptin improved the prognostic value of the ABCD2 (age, blood pressure, clinical features of transient ischemic attack, duration of symptoms and presence of diabetes mellitus) score for a recurrent cerebrovascular event in transient ischemic attack. Copeptin seems to be a promising independent biomarker for predicting the functional outcome and all-cause mortality within 3 months or 1 year after acute ischemic stroke, and it could also be a powerful tool for early risk stratification for patients with transient ischemic attack.

YKL-40 Level and Hypertension Incidence: A Population-Based Nested Case-Control Study in China.

BACKGROUND: Human cartilage glycoprotein-39 (YKL-40) has been suggested to be a new marker of inflammation, atherosclerosis, and endothelial dysfunction. However, whether a higher level of YKL-40 is an independent risk factor for hypertension incidence is still unknown. METHODS AND RESULTS: In a nested case-control study within a prospective cohort of 12 423 initially healthy Chinese adults, we measured baseline plasma concentrations of YKL-40 among 700 new-onset hypertension cases and 700 age- and sex-matched controls. Multiple conditional logistic regression analyses were used to calculate the odds ratios (95% CIs) of hypertension associated with higher levels of YKL-40 both in the total population and in the age- (>55 and ≤55 years) and sex-matched subgroups. Among the total population, YKL-40 levels were not associated with hypertension risk. In the subgroup older than 55 years, odds ratios (95% CIs) of hypertension for those in the two higher tertiles of YKL-40 were 1.23 (0.77-1.97) and 1.59 (0.99-2.55) (P for linear trend=0.05). In the male subgroup, odds ratios (95% CIs) of hypertension for those in the two higher tertiles of YKL-40 were 1.55 (0.88-2.72) and 2.09 (1.14-3.82) (P for linear trend=0.02). An interaction effect was observed between YKL-40 and sex (P for interaction <0.01) but not between YKL-40 and age (P for interaction=0.21). High YKL-40 level significantly increased hypertension risk in men but decreased hypertension risk with a trend although not significant in women. CONCLUSIONS: This study suggests that YKL-40 is associated with hypertension incidence only among men. The study findings need to be further verified by prospective cohort studies or clinical trials.

Clustering of cardiovascular risk factors and stroke: a prospective cohort study in Inner Mongolia.

OBJECTIVE: This study aimed to evaluate the effect of clustering of cardiovascular risk factors (CVRF) on stroke incidence and find some high predictive clusters among Inner Mongolians in China. METHODS: A prospective cohort study was conducted among 2589 participants aged 20 and older from Inner Mongolia, China. The participants were divided into four groups according to the number of CVRFs and followed up from June 2002 to July 2012. Cox proportional hazards model was used to evaluate the clustering of CVRFs on the incidence of stroke. Area under curve was used to compare the effect of every cluster on stroke and find those having higher predictive value. RESULTS: A total of 124 stroke occurred during the follow-up period. The incident stroke cases tended to be older and male; had higher prevalence of smoking, drinking, and family history of cardiovascular diseases (FHCVD); had greater waist circumference, higher systolic and diastolic blood pressure, and C-reactive protein levels at baseline compared with those who did not experience stroke. Unadjusted hazard ratio (HR) (95% confidence interval) of stroke in the participants with at least three CVRFs was 5.230 (2.646-10.336), compared with those without CVRF. After multiple adjustments, the result remained statistically significant (HR, 3.388; 95% confidence interval: 1.678-6.840). On the basis of FHCVD, clustering of hypertension with other CVRFs and clustering of diabetes with tachycardia had higher predictive value than other clustering. CONCLUSION: The clustering of CVRFs increased the risk of stroke. On the basis of FHCVD, the clustering of hypertension with other CVRFs and the clustering of diabetes with tachycardia had higher predictive value for stroke than other cluster.