Heat stress induces IL-1ß and IL-18 overproduction via ROS-activated NLRP3 inflammasome: implication in neuroinflammation in mice with heat stroke.

Heat stroke induced cerebral damage via neuroinflammation. This study aimed to approach whether heat stress would promote NOD-like receptor protein 3 (NLRP3) inflammasome via reactive oxygen species (ROS). The mice were randomly divided into the sham group, the heat stress group, and the heat stress + TEMPOL (ROS scavenger) group. And the NLRP3 -/- mice were applied and divided into the NLRP3 -/-  + sham group and the NLRP3 -/-  + heat stress group. Furthermore, the BV2 cells were divided into four groups following the intervention measures: the heat stress + TEMPOL group, the heat stress + Z-VAD-FMK (caspase-1 inhibitor) group, the heat stress group, and the control group. ROS levels were examined. The expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 were detected by western blotting and double immunofluorescence. We found that heat stress attack induced excessive ROS in microglia and subsequently activated NLRP3 inflammasome in both mice and BV2 cells. When ROS scavenged, the expression level of NLRP3 was downregulated. Furthermore, with NLRP3 inflammasome activation, the expression levels of caspase-1, IL-1ß, and IL-18 were increased. In NLRP3 -/- mice, however, the caspase-1, IL-1ß, and IL-18 were significantly declined. Further experiments showed that pretreatment of caspase-1 inhibitor decreased the expression levels of IL-1ß and IL-18. These results suggest that heat stress attack caused neuroinflammation via excessive ROS activating the NLRP3 inflammasome in microglia cells.

Atypical Legionella GTPase effector hijacks host vesicular transport factor p115 to regulate host lipid droplet.

The intracellular bacterial pathogen Legionella pneumophila uses hundreds of effector proteins to manipulate multiple processes of the host cells to establish a replicative niche known as Legionella-containing vacuole (LCV). Biogenesis of the LCV has been known to depend on host small guanosine triphosphatases (GTPases), but whether bacterial effector GTPases are also involved remains unknown. Here, we show that an ankyrin repeat containing effector LegA15 localizes directly in host lipid droplets (LDs), leading to Golgi apparatus fragmentation of the host cells by hijacking the host vesicular transport factor p115. LegA15 is a GTPase with a unique catalytic mechanism, unlike any eukaryotic small GTPases. Moreover, the effector LegA15 co-opts p115 to modulate homeostasis of the host LDs in its GTPase-dependent manner. Together, our data reveal that an atypical GTPase effector regulates the host LDs through impeding the vesicle secretion system of the host cells for intracellular life cycle of Legionella.

[Predictive value of sepsis-induced coagulopathy score on 30-day mortality in septic patients].

OBJECTIVE: To evaluate the predictive effect of sepsis-induced coagulopathy (SIC) score level on the prognosis of septic patients under sepsis 3.0 criteria. METHODS: A retrospective single-center observational study was conducted on the septic patients admitted to the department of critical care medicine and the department of emergency in Guangdong Provincial People's Hospital from August 2016 to July 2021. The baseline data, laboratory indexes and SIC scores of the patients were collected on the first and fourth (4th) day after hospitalization. Whether the patients were survival within 30 days after enrollment was recorded. Univariate and multivariate Logistic regression were used to analyze the independent risk factors for 30-day mortality in septic patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of SIC score on the 30-day prognosis of septic patients. RESULTS: A total of 173 patients met the inclusion criteria including 111 (64%) survivors and 62 (36%) non-survivors. There were significant differences in lymphocyte count (LYM), sequential organ failure assessment (SOFA), oxygenation index (PaO2/FiO2) and cardiovascular SOFA score between the survival group and the non-survival group. And there were no significant differences in other indexes. On the first day of admission, there were statistically significant differences in PaO2/FiO2, cardiovascular SOFA score, LYM, SIC score between the non-survival group and the survival group. There were significant differences in international normalized ratio (INR), prothrombin activity (PTA), prothrombin time (PT), PaO2/FiO2, cardiovascular SOFA score, LYM, C-reactive protein (CRP) and procalcitonin (PCT) between the two groups on the 4th day after admission. The mortality of septic patients increased with the increase of SIC score. Binary Logistic regression analysis showed that SIC score and LYM on the 4th day after admission were independent risk factors for 30-day mortality in septic patients (both P < 0.05). The ROC curve showed that SIC score had a certain predictive value for the 30-day prognosis of septic patients [area under the ROC curve (AUC) = 0.712, 95% confidence interval (95%CI) was 0.629-0.794, P < 0.001]. The predictive value of SIC score combined with LYM was better than that of the two alone (AUC = 0.748, 95%CI was 0.688-0.828, P < 0.001). CONCLUSIONS: The SIC score has a certain predictive value for the 30-day prognosis of septic patients. The predictive value of SIC score combined with LYM is better than that of the two alone, which is expected to be a potential indicator for early assessment of the condition and prognosis of septic patients.

ELEVATED PD-1/CD28 RATIO RATHER THAN PD-1 EXPRESSION IN CD8+ T CELLS PREDICTS NOSOCOMIAL INFECTION IN SEPSIS PATIENTS: A PROSPECTIVE, OBSERVATIONAL COHORT STUDY.

ABSTRACTBACKGROUND: The expression of programmed cell death 1 receptor (PD-1) and CD28 on CD8+ T cells is considered to be related to immune function and prognosis markers in patients with sepsis. However, the relationship between the ratio of PD-1/CD28 and nosocomial infection has not been elucidated. Methods: A prospective, observational cohort study was conducted in a general intensive care unit. Patients were enrolled according to the sepsis-3 criteria and peripheral blood samples were collected within 24 hours of enrollment. Programmed cell death 1 receptor and CD28 expression on CD8+ T cells was assayed on day 1. Patients were followed up until 28 days. Multivariate regression analysis was used to assess independent risk factors for nosocomial infection. The accuracy of biomarkers for nosocomial infection and mortality was determined by the area under the receiver operating characteristic curve analysis. The association between biomarkers and 28-day mortality was assessed by Cox regression survival analysis. Results: A total of 181 patients were recruited, and 68 patients were finally included for analysis. Of these, 19 patients (27.9%) died during 28 days and 22 patients (32.4%) acquired nosocomial infection. The PD-1/CD28 ratio of patients with nosocomial infection was significantly higher than those without (0.27 [0.10-0.55] vs. 0.15 [0.08-0.28], P = 0.025). The PD-1/CD28 ratio in CD8+ T cells (odds ratio, 53.33; 95% confidence interval, 2.39-1188.22, P = 0.012) and duration of mechanical ventilation (odds ratio, 1.14; 95% confidence interval, 1.06-1.24; P = 0.001) were independently associated with nosocomial infection. The area under the receiver operating characteristic curve of PD-1/CD28 ratio in CD8+ T cells was 0.67 (0.52-0.82). The PD-1/CD28 ratio in CD8+ T cells of the nonsurvivors was significantly higher than the survivors (0.23 [0.15-0.52] vs. 0.14 [0.07-0.32]); Cox regression analysis showed that the survival time of patients with PD-1/CD28 ratio in CD8+ T cells of 0.13 or greater was shorter compared with patients with lower levels (hazard ratio, 4.42 [1.29-15.20], χ2 = 6.675; P = 0.010). Conclusions: PD-1/CD28 ratio in CD8+ T cells at admission may serve as a novel prognostic biomarker for predicting nosocomial infection and mortality.

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy.

BACKGROUND: Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis-associated encephalopathy (SAE) remains unclarified. METHODS: Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood-brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro-inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes. RESULTS: Rats in the CLP group presented increased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase-1 expression and IL-1ß secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase-1 and reduced release of IL-1ß into CNS. CONCLUSION: Collectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1ß into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.

Comparison of clinical characteristics in patients with coronavirus disease and influenza A in Guangzhou, China.

BACKGROUND: This study aims to compare the epidemiological, clinical and laboratory characteristics between patients with coronavirus disease (COVID-19) and influenza A (H1N1), and to develop a differentiating model and a simple scoring system. METHODS: We retrospectively analyzed the data from patients with COVID-19 and H1N1. The logistic regression model based on clinical and laboratory characteristics was constructed to distinguish COVID-19 from H1N1. Scores were assigned to each of independent discrimination factors based on their odds ratios. The performance of the prediction model and scoring system was assessed. RESULTS: A total of 236 patients were recruited, including 20 COVID-19 patients and 216 H1N1 patients. Logistic regression revealed that age >34 years, temperature ≤37.5 °C, no sputum or myalgia, lymphocyte ratio ≥20% and creatine kinase-myocardial band isoenzyme (CK-MB) >9.7 U/L were independent differentiating factors for COVID-19. The area under curves (AUCs) of the prediction model and scoring system in differentiating COVID-19 from H1N1 were 0.988 and 0.962, respectively. CONCLUSIONS: There are certain differences in clinical and laboratory features between patients with COVID-19 and H1N1. The simple scoring system may be a useful tool for the early identification of COVID-19 patients from H1N1 patients.

Urinary Trypsin Inhibitor Protects Tight Junctions of Septic Pulmonary Capillary Endothelial Cells by Regulating the Functions of Macrophages.

BACKGROUND: Our previous study found that urinary trypsin inhibitor (ulinastatin, UTI) protected tight junctions (TJs) of lung endothelia via TNF-α inhibition, thereby alleviating pulmonary capillary permeability in septic rats. As the activated macrophage is the main source of TNF-α in sepsis, we speculate that UTI may exert the above effects by regulating the functions of macrophages. METHODS: Bone-marrow derived macrophages (BMDM) were divided into control, lipopolysaccharide (LPS), UTI+LPS and UTI groups. TNF-α, TGF-ß, IL-10, CD86, CD206 and MCP-1 expression were assessed by Western blot. The phagocytosis and migration of BMDM were detected. Pulmonary microvascular endothelial cells (PMVECs) were cultured with the conditioned medium (CM) from each group of BMDM above. Sprague-Dawley rats were divided into sham, cecal ligation and puncture (CLP), and UTI+CLP groups. Western blot and immunofluorescence were used to detected zonula occludens-1 (ZO-1), occludin and claudin-5 expression in PMVECs, as well as TNF-α, TGF-ß, iNOS, CD86 and CD206 expression in lungs. Pulmonary capillary permeability was assessed by extravasated Evans blue, lung injury score (LIS), wet-to-dry weight ratio and electron microscope. RESULTS: TNF-α and CD86 expression were increased in LPS-treated BMDM, but were reversed by UTI pretreatment. TGF-ß, IL-10 and CD206 expression were the opposite. UTI markedly decreased phagocytosis and migration of LPS-treated BMDM. ZO-1, occludin and claudin-5 expression were markedly decreased in PMVECs of the CM-LPS group, but significantly increased in the CM-UTI+LPS group. TNF-α, iNOS and CD86 expression were increased in the lungs of CLP-rats but decreased with UTI pretreatment, while TGF-ß and CD206 expression were the opposite. UTI markedly ameliorated the lung EB leakage, improved LIS, reduced the wet-to-dry ratio and revised the damaged TJs of PMVECs in CLP-rats. CONCLUSION: UTI effectively inhibits the conversion of M1 macrophage but increases M2, reduces the phagocytosis and migration, which helps to protect endothelia TJs and reduce pulmonary capillary permeability during sepsis.

PD-1 in Tregs predicts the survival in sepsis patients using sepsis-3 criteria: A prospective, two-stage study.

BACKGROUND: The expression of Tregs co-signaling molecules serves as the marker of immune dysfunction. The present study aimed to verify their predictive role in the 28-day mortality of sepsis patients. METHODS: A prospective, observational, two-stage cohort study was conducted. The patients who fulfilled the sepsis-3 criteria were enrolled, and peripheral blood samples were collected within 24 h post-enrollment. The expression of the four co-signaling molecules of Tregs, namely, PD-1, CD28, PD-L1 and CD86, was measured, and sequential organ failure assessment (SOFA) scores were recorded on day 1 of inclusion. Patients were followed up for 28 days or, otherwise, deceased. Multivariate regression analysis was used to assess the independent risk factors for 28-day mortality, and a prognostic prediction model was established, which was verified in the validation set. RESULTS: A total of 292 patients were recruited in the study, of which 120 patients were finally included in the analysis, that is 58 patients in stage I (test set) and 62 patients in stage II (validation set). In stage I, 14 (24.1%), patients died during 28 days, and the expression of PD-1 in Tregs (OR:1.037;95%CI:1.003-1.071) and SOFA scores(OR:1.262;95%CI:1.046-1.524) were independent risk factors for 28-day mortality. The ability of Tregs PD-1 in predicting 28-day mortality was validated in stage II (AUC = 0.792). CONCLUSION: PD-1 overexpression in Tregs was associated with poor outcomes, and PD-1 in Tregs is considered to be a valuable tool for the prediction of prognosis in septic patients using sepsis-3.0 criteria.

Ulinastatin Ameliorates Pulmonary Capillary Endothelial Permeability Induced by Sepsis Through Protection of Tight Junctions via Inhibition of TNF-α and Related Pathways.

Background: Increased permeability of pulmonary capillary is a common consequence of sepsis that leads to acute lung injury. In this connection, ulinastatin, a urinary trypsin inhibitor (UTI), is used clinically to mitigate pulmonary edema caused by sepsis. However, the underlying mechanism of UTI in alleviating sepsis-associated pulmonary edema remains to be fully elucidated. As tight junctions (TJs) between the pulmonary microvascular endothelial cells (PMVECs) play a pivotal role in the permeability of pulmonary capillary, this study investigated the effect of UTI on expression of junctional proteins in PMVECs during sepsis. Methods: Male adult Sprague Dawley rats were subjected to cecal ligation and puncture (CLP) and divided into sham, CLP, and UTI+CLP groups. UTI was administered every 8 h for 3 days before CLP. At 48 h after surgery, Evans blue (EB) was administered to evaluate the pulmonary vascular leakage. Histological staining was used for evaluation of lung injury score. Using immunofluorescence staining and Western blot, the expression of junctional proteins (occludin, claudin-5, and ZO-1) in pulmonary endothelia was assessed. In vitro, PMVECs were divided into control, lipopolysaccharide (LPS), and UTI+LPS groups for examination of expression of junctional proteins and TNF-α as well as inhibitor of NF-κB (IκB), p38 mitogen-activated protein kinases (p38 MAPKs), c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs) signaling pathways. Additionally, the expression of various junctional proteins was determined in PMVECs of control, LPS, and TNF-α receptor antagonist-LPS groups. PMVECs were also treated with TNF-α and TNF-α receptor antagonist and the expression of various junctional proteins was assessed. Results: Compared with the CLP group, UTI markedly decreased EB leakage and lung injury score. The expression of occludin, claudin-5, and ZO-1 was decreased in both CLP rats and LPS-treated PMVECs, but it was reversed by UTI and TNF-α receptor antagonist. TNF-α expression was vigorously elevated in the lung of CLP rats and in LPS-challenged PMVECs, which were suppressed by UTI. In addition, TNF-α also reduced occludin, claudin-5, and ZO-1 expression in PMVECs, but these effects of TNF-α were antagonized by pretreatment with TNF-α receptor antagonist. Furthermore, UTI inhibited LPS-induced activation of NF-κB and mitogen-activated protein kinases (MAPKs) pathways in PMVECs. Conclusion: UTI effectively protects TJs and helps to attenuate the permeability of pulmonary capillary endothelial cells during sepsis through inhibiting NF-κB and MAPKs signal pathways and TNF-α expression.

Evaluation of a combination "lymphocyte apoptosis model" to predict survival of sepsis patients in an intensive care unit.

BACKGROUND: A major challenge in sepsis intervention is unclear risk stratification. We postulated that a panel of biomarkers of lymphocyte apoptosis and immune function, termed the "lymphocyte apoptosis model," would be an effective tool for predicting 28-day survival for sepsis patients. METHODS: A total of 52 consecutive sepsis patients were enrolled. Peripheral blood samples were collected on day 1 of admission for quantification of biomarkers of lymphocyte apoptosis and immune function, including lymphocyte count, lymphocyte apoptotic percentage, expression on monocyte HLA-DR, CD4+/CD8+ T cell ratio, T helper type 1 to type 2 ratio (Th1/Th2), cytochrome c levels, and various proinflammatory cytokine levels. Sepsis severity was classified using Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Survival was assessed at 28 days. RESULTS: Compared with survivors, non-survivors had significantly higher lymphocyte apoptotic percentages and plasma cytochrome c levels and significantly lower lymphocyte counts, Th1/Th2 ratios, and HLA-DR expression on day 1 of admission. Multivariate analysis identified cytochrome c levels (odds ratio [OR]1.829, p = 0.025), lymphocyte apoptotic percentage (OR 1.103, p = 0.028), lymphocyte count (OR 0.150, p = 0.047), and HLA-DR expression (OR 0.923, p = 0.021) as independent predictors of 28-day mortality. A logistic regression equation incorporating the independent risk factors predicted 28-day mortality with greater accuracy than did the APACHE II score or single components biomarkers. CONCLUSIONS: The "lymphocyte apoptosis model" may be useful for risk stratification and predicting prognosis of sepsis patients.

Hypertonic saline regulates microglial M2 polarization via miR-200b/KLF4 in cerebral edema treatment.

BACKGROUND: Hypertonic saline (HS) has been used clinically for treatment of cerebral edema for decades. Previously we have demonstrated that HS alleviates cerebral edema via regulating water/ion channel protein and attenuating neuroinflammation. However, whether HS treatment triggers microglia polarization and its regulatory mechanism during this process is unclear. METHODS AND RESULTS: The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery occlusion (MCAO) were used for assessment of neuroinflammation and microglia functions. Treatment of 10% HS not only significantly reduced infarct size and ipsilateral ischemic hemispheric brain water content (BWC) via attenuating ischemia-induction of TNF-α, IL-1ß, microglia M1 markers (iNOS, CD86) and miR-200b, but also increased neurotrophic factors such as IL-10 and IL-4, microglia M2 markers (Arg1, CD206) and Krüppel-like factor 4 (KLF4). Similar changes were confirmed in primary microglial cells subjected to hypoxia with/without HS in vitro. Importantly, overexpression of miR-200b was able to induce microglia M1 polarization via directly targeting KLF4. Restoring KLF4 expression abolished this effect. On the contrary, miR-200b inhibitor or KLF4 overexpression led to microglia M2 polarization. Mechanistically, KLF4 directly binds to promoter region of Agr1, thus inducing its transcription. Similar to treatment of HS, experimental overexpression of KLF4 in vivo exerted significant beneficial effects on ischemia-induced cerebral edema. However, knockdown of KLF4 abrogated the benefits of HS. CONCLUSIONS: Hypertonic saline regulates microglial M2 polarization via miR-200b/KLF4 during its treatment of cerebral edema. This study may provide new insights of HS-related therapy for cerebral edema.

Hypercapnia induces IL-1ß overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats.

BACKGROUND: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1ß) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1ß secretion outside the central nervous system (CNS). However, the underlying mechanism of hypercapnia aggravating cognitive impairment under hypoxia has remained uncertain. This study was aimed to explore whether hypercapnia would partake in increasing IL-1ß secretion via activating the NLRP3 (NLR family, pyrin domain-containing 3) inflammasome in the hypoxic CNS and in aggravating cognitive impairment. METHODS: The Sprague-Dawley (SD) rats that underwent hypercapnia/hypoxemia were used for assessment of NLRP3, caspase-1, IL-1ß, Bcl-2, Bax, and caspase-3 expression by Western blotting or double immunofluorescence, and the model was also used for Morris water maze test. In addition, Z-YVAD-FMK, a caspase-1 inhibitor, was used to treat BV-2 microglia to determine whether activation of NLRP3 inflammasome was required for the enhancing effect of hypercapnia on expressing IL-1ß by Western blotting or double immunofluorescence. The interaction effects were analyzed by factorial ANOVA. Simple effects analyses were performed when an interaction was observed. RESULTS: There were interaction effects on cognitive impairment, apoptosis of hippocampal neurons, activation of NLRP3 inflammasome, and upregulation of IL-1ß between hypercapnia treatment and hypoxia treatment. Hypercapnia + hypoxia treatment caused more serious damage to the learning and memory of rats than those subjected to hypoxia treatment alone. Expression levels of Bcl-2 were reduced, while that of Bax and caspase-3 were increased by hypercapnia in hypoxic hippocampus. Hypercapnia markedly increased the expression of NLRP3, caspase-1, and IL-1ß in hypoxia-activated microglia both in vivo and in vitro. Pharmacological inhibition of NLRP3 inflammasome activation and release of IL-1ß might ameliorate apoptosis of neurons. CONCLUSIONS: The present results suggest that hypercapnia-induced IL-1ß overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.

Comparison of body mass index with body fat percentage in the evaluation of obesity in Chinese.

OBJECTIVE: To evaluate the present Chinese body mass index (BMI) criteria with body fat percentage (BF%) in determining obesity in Chinese population. METHODS: A total of 4 907 subjects (age: 20-90 yrs) were enrolled in the baseline survey of a longitudinal epidemiological study, and 2 638 of them were reevaluated in 5.5 years later. The Chinese BMI and WHO BF% were used to define obesity, respectively. RESULTS: The diagnostic agreement between the Chinese BMI and WHO BF% definitions for obesity was poor for both men (kappa: 0.210, 95% CI: 0.179-0.241) and women (kappa: 0.327, 95% CI: 0.296-0.358). However, BMI had a good correlation with BF% both in men (r: 0.785, P<0.01) and women (r: 0.864, P<0.01). The age and sex-adjusted relative risks (RR) for incidence of type 2 diabetes (T2DM) were significantly higher in subjects with intermediate BF% (BF%:20.1%-25% for men, 30.1%-35% for women) (RR: 2.35, 95% CI: 1.23-4.48) and high BF%(BF%>25% for men and > 35% for women)(RR: 2.89, 95% CI: 1.43-5.81), or in subjects with high BMI (BMI>or=28 kg/m(2)) (RR: 2.46, 95% CI: 1.31-4.63) when compared to those with low BF% (BF%

The metabolic syndrome increased risk of cardiovascular events in Chinese--a community based study.

BACKGROUND: Whether metabolic syndrome (MetS) could serve as a valid indicator for cardiovascular disease (CVD) is in controversy. The aim of the study was to prospectively evaluate the predictive value of the MetS for CVD events in Chinese population by different MetS definitions. METHODS: This was a community-based cohort study. MetS was defined according to the World Health Organization (WHO), the International Diabetes Federation (IDF), the National Cholesterol Education Program Adult Treatment Panel III (NCEPIII) and Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (JCDCG), respectively. 2788 subjects were included. The incidence of CVD events was monitored during a 5.5-year period. RESULTS: The proportion of MetS defined by the WHO, IDF, NCEPIII and JCDCG criteria was 25.9%, 15.4%, 22.0% and 26.1%, respectively in men, and 24.5%, 28.0%, 31.1% and 23.0%, respectively in women. After adjusting for age, all four definitions were associated with increased risk of CVD events in women, but not in men. The corresponding hazard ratios (HRs) [95% confidence intervals (CIs)] in women were 2.13 (1.44-3.16), 1.49 (1.01-2.19), 1.50 (1.02-2.21) and 2.10 (1.41-3.11). The HRs remained significant with WHO and JCDCG definitions, not with the IDF and NCEPIII definitions, when factors of LDL cholesterol, and smoking were adjusted. CONCLUSION: The MetS by the WHO and JCDCG definition was associated with increased risk of CVD events in Chinese women after adjustment for age, total cholesterol, LDL cholesterol, and smoking.

Serum C-reactive protein and risk of cardiovascular events in middle-aged and older chinese population.

The purpose of the present study was to investigate the effect of high-sensitivity C-reactive protein (hs-CRP) on the risk of cardiovascular disease (CVD) in a Chinese population. A total of 2,656 participants (aged 30 to 95 years) with baseline hs-CRP levels available were monitored for the incidence of a composite of CVD events (stroke and coronary heart disease) during a 5.5-year period. With increasing quartiles of hs-CRP (<0.47, 0.47 to 0.97, 0.97 to 2.09, and >or=2.09 mg/L), the incidence of CVD increased progressively (11.7, 16.4, 24.7, and 36.5 per 1,000 person-years, respectively). In a Cox model adjusted for other traditional risk factors (e.g., age, blood pressure, diabetes mellitus, lipids, body mass index, smoking status), elevated hs-CRP (>or=2.0 mg/L) independently predicted the risk of CVD (hazard ratio 1.39; 95% confidence interval 1.04 to 1.87). The effect was especially significant for stroke (hazard ratio 1.58; confidence interval 1.08 to 2.31). In conclusion, the results of our study suggest that elevated hs-CRP (>or=2.0 mg/L) is an effective predictor of CVD in a Chinese population.