Influence of multiple risk factor control level on cardiovascular outcomes in hypertensive patients.

OBJECTIVE: The relationship between the level of baseline risk factor control and cardiovascular outcomes in hypertensive patients with blood pressure intervention is not well understood. It is also unclear whether the level of baseline risk factor control is persuasively associated with cardiovascular outcomes in hypertensive patients with blood pressure lowering strategy. METHOD: We performed an analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Participants without complete baseline risk factor data were excluded. The primary outcome was a composite of cardiovascular events and all-cause mortality. Cox proportional hazard models were used to calculate the hazard ratio (HR) and estimate association between risk factor control levels (≥6, 5, 4, and ≤ 3) and cardiovascular outcomes. RESULTS: A total of 8337 participants were involved in the analysis and the median follow-up period was 3.19 years. Each additional risk factor uncontrolled was associated with a 24% higher cardiovascular risk (HR 1.24, 95% CI 1.11-1.37). Compared with participants with optimal risk factor control, those with ≤ 3 factors control exhibited 95% higher cardiovascular risk (HR 1.95, 95% CI 1.37-2.77). The corresponding protective effects of multiple risk factor modification were not influenced by intensive or standard antihypertensive treatment (P for interaction = 0.71). CONCLUSIONS: A stepwise association was observed between cardiovascular risk and the number of risk factor control in hypertensive patients. The more risk factor was modified, the less cardiovascular risk was observed, irrespective of different blood pressure lowering strategies. Comprehensive risk factor control strategies are warranted to reduce cardiovascular disease risk in hypertensive patients. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Impact of Hypertension Duration on the Cardiovascular Benefit of Intensive Blood Pressure Control.

BACKGROUND: The optimal timing for initiating intensive systolic blood pressure (SBP) treatment remains unclear. While longer hypertension duration is positively associated with increased cardiovascular disease risk, it is unknown whether patients with prolonged hypertension can derive similar benefits from intensive SBP treatment. METHODS: From the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients), 8442 participants with complete hypertension duration data were categorized by hypertension duration ≤5 years, 5 to 10 years, 10 to 15 years, and >15 years. The primary outcome was a composite of cardiovascular events. Hazard ratios were calculated using the Fine-Gray subdistribution hazard model. RESULTS: The incidences of the primary outcome increased significantly in patients with hypertension over 15 years than those <5 years in the standard SBP treatment group (adjusted hazard ratios, 1.68 [95% CI, 1.11-2.56]) but not in the intensive treatment group. Each 1-year increase in hypertension duration continuously increased the adjusted risk of major cardiovascular events by 4% (95% CI, 1.01-1.08) up to 20 years, plateauing at an adjusted hazard ratio of 2.27 (95% CI, 1.28-4.04). After intensive SBP treatment, the incidences of major cardiovascular events were similar across different hypertension duration groups, which were 2.22%, 1.69%, 3.02%, and 2.52%, respectively (P>0.05). Subgroup analyses indicated a potential sex difference in this relationship between hypertension duration and the primary outcome in the standard SBP treatment group (Pinteraction=0.05). CONCLUSIONS: Initiating intensive SBP treatment at any stage of hypertension duration could reduce cardiovascular disease risk to a comparable level. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03015311.

Association of intensive blood pressure management with cardiovascular outcomes in patients using multiple classes of antihypertensive medications: a post-hoc analysis of the STEP Trial.

High medication burden is associated with poor treatment effect and high risk of cardiovascular outcomes. This study aimed to investigate the association between the antihypertensive medication burden and cardiovascular outcomes in the STEP trial. This post-hoc analysis of the STEP trial enrolled 8511 participants, including 8041 with low burden and 470 with high burden. High antihypertensive medication burden was defined as being treated with ≥3 different classes of prescribed antihypertensive medications. The primary outcome was a composite of cardiovascular outcomes. Fine-Gray model was used in this study. Among all participants, high antihypertensive medication burden was associated with a higher risk of the primary outcome compared with low medication burden (HR, 1.52; 95% CI, 1.03-2.24), which was consistent in the standard group (HR, 1.95; 95% CI, 1.20-3.18) and the intensive group (HR, 1.10; 95% CI, 0.57-2.13; Pinteraction = 0.18). The beneficial effects of intensive systolic blood pressure (SBP) control on the primary outcome remained significant in the high burden group (HR, 0.42; 95% CI, 0.19-0.95) and the low burden group (HR, 0.79; 95% CI, 0.63-0.98; Pinteraction = 0.18). At 24 months, the percentage of participants achieving the target SBP was lower in the high medication burden group (risk ratio, 0.93; 95% CI, 0.89-0.98). In both standard and intensive treatment groups, participants with a high medication burden were harder to achieve the target SBP (Pinteraction = 0.65). High antihypertensive medication burden was associated with worse SBP control and a greater risk of cardiovascular events. Intensive SBP control showed cardiovascular benefits in both medication burden groups. Trial registration: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Visit-to-Visit Blood Pressure Variability and Cardiovascular Outcomes in Patients Receiving Intensive Versus Standard Blood Pressure Control: Insights From the STEP Trial.

BACKGROUND: The clinical prognostic value of visit-to-visit blood pressure (BP) variability (BPV) is debatable, and relative studies among patients receiving BP control to achieve lower BP targets are limited. METHODS: We analyzed a dataset from the STEP trail (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) to investigate the relationship between visit-to-visit BPV and cardiovascular events in patients with hypertensive aged 60 to 80 years. Visit-to-visit BPV was defined as the coefficient of variation, SD, delta, average real variability, and variability independent of the mean of BP measured at 6-, 9-, 12-, 15-, and 18-month follow-up visits. We computed hazard ratios for the risks associated with a 1-SD increase in BPV indexes in multivariable cox regression models. RESULTS: Among 7678 patients from the STEP trial, after adjustment for multiple confounders, diastolic BPV indexes were significantly associated with the primary composite end point (hazard ratios ≥1.21; P≤0.029) in the standard group, while there was no association between the clinical outcomes and systolic BPV (P≥0.091). In the intensive treatment group, either systolic or diastolic BPV was no association with clinical outcomes(P≥0.30). Sensitivity analyses using an alternative method to calculate BPV based on 7 BP records generated confirmatory results. CONCLUSIONS: In older adults with hypertension, visit-to-visit diastolic BPV is an independent predictor of adverse health outcomes in the standard treatment group. However, BPV did not have prognostic value in the intensive treatment group. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03015311.

Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension.

BACKGROUND: There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. METHODS: The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. RESULTS: During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. CONCLUSIONS: NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Impact of baseline blood pressure on all-cause mortality in patients with atrial fibrillation: results from a multicenter registry study.

BACKGROUND: The ideal blood pressure (BP) target for patients with atrial fibrillation (AF) is still unclear. The present study aimed to assess the effect of the baseline BP on all-cause mortality in patients with AF. METHODS: This registry study included 20 emergency centers across China and consecutively enrolled patients with AF from 2008 to 2011. All participants were followed for 1 year ±â€Š1 month. The primary endpoint was all-cause mortality. RESULTS: During the follow-up, 276 (13.9%) all-cause deaths occurred. Kaplan-Meier curves showed that a systolic blood pressure (SBP) ≤110 mmHg or >160 mmHg was associated with a higher risk of all-cause mortality (log-rank test, P  = 0.014), and a diastolic blood pressure (DBP) <70 mmHg was associated with the highest risk of all-cause mortality (log-rank test, P  = 0.002). After adjusting for confounders, the multivariable Cox regression model suggested that the risk of all-cause mortality was increased in the group with SBP ≤110 mmHg (hazard ratio [HR], 1.963; 95% confidence interval [CI], 1.306-2.951), and DBP <70 mmHg (HR, 1.628; 95% CI, 1.163-2.281). In the restricted cubic splines, relations between baseline SBP or DBP and all-cause mortality showed J-shaped associations (non-linear P <0.001 and P  = 0.010, respectively). The risk of all-cause mortality notably increased at a lower baseline SBP and DBP. CONCLUSIONS: Having a baseline SBP ≤110 mmHg or DBP <70 mmHg was associated with a significantly higher risk of all-cause mortality in patients with AF. An excessively low BP may not be an optimal target for patients with AF.

Stage 1 Hypertension and the 10-Year and Lifetime Risk of Cardiovascular Disease: A Prospective Real-World Study.

Background The 10-year and lifetime cardiovascular disease risk in the population with stage 1 hypertension and the effects of recovery from and progression of stage 1 hypertension remain undetermined. Methods and Results This prospective cohort study included 96 268 individuals with blood pressure measurements obtained in 2006 and again in 2010. The 10-year cardiovascular disease risk was estimated using the multivariable Cox proportional hazards model, and the lifetime risk was calculated using a modified survival analysis that accounted for the competing risk of death. Stage 1 hypertension was detected in 30.83% of the cohort. The 10-year cardiovascular disease risk was 2.80%, and the lifetime risk was 16.61%. Compared with the normal blood pressure group, the stage 1 hypertension group had a 35% higher 10-year risk (hazard ratio [HR], 1.35 [95% CI, 1.19-1.52]) and a 36% higher lifetime risk (HR, 1.36 [95% CI, 1.25-1.49]). By 2010, 12.57% of the participants with stage 1 hypertension had progressed to stage 2, with a significant 156% increase in 10-year risk (HR, 2.56 [95% CI, 2.11-3.11]) and an increased lifetime risk of 129% (HR, 2.29 [95% CI, 1.89-2.77]). There was no appreciable change in risk in those with stage 1 hypertension whose blood pressure returned to the normal-elevated range. Conclusions Stage 1 hypertension was associated with a significant increase in 10-year and lifetime cardiovascular disease risk. Progression to stage 2 hypertension was associated with a marked increase in lifetime risk. The current guidelines require revision to promote early detection and appropriate management of blood pressure.

Effects of intensive blood pressure lowering in patients with diabetes: A pooled analysis of the STEP and ACCORD-BP randomized trials.

AIM: To determine whether intensive systolic blood pressure (SBP) lowering can benefit hypertensive patients with diabetes. MATERIALS AND METHODS: We performed a pooled analysis of individual patient data from two randomized trials to compare intensive and standard SBP targets in hypertensive patients with diabetes (STEP diabetes subgroup and ACCORD-BP standard glycaemic group, n = 1627 and n = 2362, respectively). We defined a modified primary outcome as a composite of stroke, major coronary artery disease (myocardial infarction and unstable angina), heart failure, and cardiovascular death. The secondary outcomes were individual components of the primary outcome and death from any cause. A Cox proportional hazards regression model was used in the main analysis. We conducted one-stage mixed-effect models and two-stage analyses as sensitivity and supplementary analyses to verify the robustness of the findings. RESULTS: A total of 3989 patients were randomized to undergo intensive (n = 1984) or standard SBP treatment (n = 2005). After a median follow-up of 3.83 years, the primary outcome occurred in 193/1984 patients in the intensive group and in 247/2005 patients in the standard group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.64-0.93). The incidence rates for secondary outcomes were lower in the intensive group than in the standard group, but were not significantly different, except for stroke (intensive vs. standard: 32/1984 vs. 58/2005; HR 0.56, 95% CI 0.36-0.86). These results remained consistent in the additional sensitivity and supplementary analyses. CONCLUSIONS: An intensive SBP-lowering target of 110 to <130 mmHg reduces the cardiovascular outcomes compared with a standard SBP-lowering target of 130 to <150 mmHg. The findings of this study support the favourable effects of intensive SBP lowering in hypertensive patients with diabetes.

Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis.

OBJECTIVE: Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune-related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK. METHODS: To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes. RESULTS: A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK. CONCLUSION: This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome-metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Influence of baseline arterial stiffness on effects of intensive compared with standard blood pressure control: a post hoc analysis of the STEP trial.

BACKGROUND: The benefits and risks of intensive versus standard systolic blood pressure (SBP) treatment in older patients with arterial stiffness (AS) remains unclear. This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes. METHODS: In this post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, we involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity (baPWV). Patients were categorized by baseline AS status (AS, baPWV ≥ 1800 cm/s; non-AS, baPWV < 1800 cm/s). The primary outcome was a composite of cardiovascular events. The secondary outcomes were stroke, acute coronary syndrome (ACS), major cardiovascular events (MACE), and all-cause death. Cox regression was used to calculate hazard ratios for the outcomes. RESULTS: During a mean follow-up of 2.69 years, a total of 248 primary outcome events and 81 all-cause deaths occurred. The hazard ratios for the primary outcome were 0.76 (95% confidence interval (CI), 0.54-1.09) and 0.63 (95% CI, 0.43-0.92) in the AS and non-AS groups, respectively (P for interaction = 0.43), and that for stroke was 0.58 (95% CI, 0.33-1.02) and 0.48 (95% CI, 0.23-0.99) in the AS and non-AS groups, respectively (P for interaction = 0.68). Effects of intensive SBP treatment on safety outcomes and all-cause death were also similar in the two groups (P for interaction > 0.05 for all). CONCLUSIONS: In the STEP trial, the beneficial effects of intensive SBP treatment were similar among those in the AS group and the non-AS group at baseline. TRIAL REGISTRATION: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Association of stress hyperglycemia ratio and in-hospital mortality in patients with coronary artery disease: insights from a large cohort study.

BACKGROUND: Stress hyperglycemia is strongly associated with poor clinical outcomes in patients with acute coronary syndrome (ACS). Recently, the stress hyperglycemia ratio (SHR) has been proposed to represent relative hyperglycemia. Studies regarding the relationship between SHR and mortality in coronary artery disease (CAD) are limited. This study aimed to clarify the association between SHR and in-hospital mortality in patients with CAD. METHODS: A total of 19,929 patients with CAD who were hospitalized in Beijing Hospital were enrolled in this study. Patients with an estimated glomerular filtration rate < 30 ml/min, cancer, or missing blood glucose/HbA1c data were excluded; therefore, 8,196 patients were included in the final analysis. The patients were divided into three groups based on tertiles of SHR: T1 group (SHR < 0.725, n = 2,732), T2 group (0.725 ≤ SHR < 0.832, n = 2,730), and T3 group (SHR ≥ 0.832, n = 2,734). The primary endpoint was in-hospital mortality. RESULTS: The overall in-hospital mortality rate was 0.91% (n = 74). After adjusting for covariates, SHR was significantly associated with in-hospital mortality in patients with CAD [odds ratio (OR) = 17.038; 95% confidence interval (CI) = 9.668-30.027; P < 0.001], and the T3 group had a higher risk of in-hospital mortality (OR = 4.901; 95% CI = 2.583-9.297; P < 0.001) compared with T1 group. In the subgroup analysis, the T3 group had an increased risk of mortality among patients with pre-diabetes mellitus (pre-DM) (OR = 9.670; 95% CI = 1.886-49.571; P = 0.007) and diabetes mellitus (DM) (OR = 5.023; 95% CI = 2.371-10.640; P < 0.001) after adjustments for covariates. The relationship between SHR and in-hospital mortality among patients with ACS and chronic coronary syndrome was consistent with the main finding. SHR and in-hospital mortality exhibited a dose-response relationship, and the risk of in-hospital mortality increased when the SHR index was above 1.20. Moreover, the area under the curve of SHR for predicting in-hospital mortality in patients with CAD was 0.741. CONCLUSION: SHR is significantly associated with in-hospital mortality in patients with CAD. SHR may be an effective predictor of in-hospital mortality in patients with CAD, especially for those with pre-DM and DM.

Temporal Relationship Between Arterial Stiffness and Systolic Blood Pressure Under Intensive or Standard Control: A Post Hoc Analysis of the STEP Trial.

BACKGROUND: Whether or not the temporal relationship between arterial stiffness and systolic blood pressure (SBP) is affected by how strictly SBP is controlled (intensive, 110-<130 mm Hg; standard, 130-<150 mm Hg) has been unclear. METHODS: The temporal relationship between brachial-ankle pulse wave velocity (baPWV) and SBP was assessed using a cross-lagged panel model in the 5369 participants in the STEP trial (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) for whom baseline and follow-up baPWV data were complete. RESULTS: Patients with arterial stiffening (baPWV≥1800 cm/s) at baseline were significantly less likely to achieve their target SBP than those without arterial stiffening in the intensive and standard treatment groups (65.17% versus 76.91% and 97.33% versus 98.96%, respectively, both P<0.05). The standardized regression coefficient from baseline baPWV to follow-up SBP was 0.05 (95% CI, 0.02-0.08; P<0.001) and that from baseline SBP to follow-up baPWV was insignificant from zero (ß=-0.007 [95% CI, -0.03 to 0.02]; P=0.62) after adjustment for confounders. CONCLUSION: Arterial stiffening consistently preceded SBP in the intensive and standard groups, and it led to difficulty in reaching target SBP, particularly in the intensive treatment group. Besides, assignment to intensive treatment group was associated with an attenuation of the age-related increase in baPWV at 3-year follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03015311.

Association between the triglyceride-glucose index and severity of coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index, which is a reliable surrogate marker of insulin resistance (IR), has been associated with cardiovascular diseases. However, evidence of the impact of the TyG index on the severity of coronary artery disease (CAD) is limited. This study investigated the relationship between the TyG index and CAD severity of individuals with different glucose metabolic statuses. METHODS: This study enrolled 2792 participants with CAD in China between January 1, 2018 and December 31, 2021. All participants were divided into groups according to the tertiles of the TyG index as follows: T1 group, TyG index < 6.87; T2 group, TyG index ≥ 6.87 to < 7.38; and T3 group, TyG index ≥ 7.38. The glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus (pre-DM), and diabetes mellitus according to the standards of the American Diabetes Association. CAD severity was determined by the number of stenotic vessels (single-vessel CAD versus multi-vessel CAD). RESULTS: We observed a significant relationship between the TyG index and incidence of multi-vessel CAD. After adjusting for sex, age, body mass index, smoking habits, alcohol consumption, hypertension, estimated glomerular filtration rate, antiplatelet drug use, antilipidemic drug use, and antihypertensive drug use in the logistic regression model, the TyG index was still an independent risk factor for multi-vessel CAD. Additionally, the highest tertile of the TyG group (T3 group) was correlated with a 1.496-fold risk of multi-vessel CAD compared with the lowest tertile of the TyG group (T1 group) (odds ratio [OR], 1.496; 95% confidence interval [CI], 1.183-1.893; P < 0.001) in the multivariable logistic regression model. Furthermore, a dose-response relationship was observed between the TyG index and CAD severity (non-linear P = 0.314). In the subgroup analysis of different glucose metabolic statuses, the T3 group (OR, 1.541; 95% CI 1.013-2.344; P = 0.043) were associated with a significantly higher risk of multi-vessel CAD in individuals with pre-DM. CONCLUSIONS: An increased TyG index was associated with a higher risk of multi-vessel CAD. Our study indicated that TyG as an estimation index for evaluating IR could be a valuable predictor of CAD severity, especially for individuals with pre-DM.

Neutrophil to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular outcomes in subjects with pre-diabetes: a large cohort study from China.

BACKGROUND: This study aimed to examine whether the neutrophil to high-density lipoprotein cholesterol ratio (NHR) can predict cardiovascular outcomes in normoglycemic individuals with elevated fasting glucose levels. METHODS: A total of 130,801 participants with normal blood glucose levels were enrolled in the Kailuan study. Participants were categorized according to NHR quartiles and further divided into normal glucose regulation (NGR) and pre-diabetes (pre-DM) subgroups. The follow-up endpoint was major adverse cardiovascular events (CVE), including stroke and myocardial infarction. RESULTS: Over a median of 12.53 (8.95-13.08) years of follow-up, subjects with NHR levels in the highest quartile experienced more CVE than those with NHR levels in the lowest quartile. Multivariate Cox analyses showed that continuous changes in NHR (hazard ratio, 1.21; 95% confidence interval [CI], 1.15-1.28) and the highest quartile of NHR (hazard ratio, 1.30; 95% CI, 1.21-1.39) were independent predictors of CVE (all P < 0.001). Furthermore, when participants were categorized by both NHR quartile and glucose metabolism status, the NHR level in the highest quartile plus pre-DM group was associated with a 1.60-fold (95% CI, 1.38-1.86; P < 0.001] higher risk of CVE than that in the lowest quartile plus normoglycemic group. Significantly, the addition of NHR only, presence of pre-DM only, or combination of NHR and pre-DM to the prediction algorithm, including traditional risk factors, improved the C-statistic by 0.19, 0.05, and 0.23 (all P < 0.001). CONCLUSIONS: Elevated NHR or fasting blood glucose level were independently associated with a higher risk of CVE among normoglycemic individuals. Moreover, pre-DM participants with high NHR levels tended to have worse prognosis, suggesting that NHR could provide greater risk stratification value than traditional risk factors for subjects with pre-DM.

Severity of Nonalcoholic Fatty Liver Disease is Associated With Cardiovascular Outcomes in Patients With Prehypertension or Hypertension: A Community-Based Cohort Study.

Background: It is unclear whether more severe non-alcoholic fatty liver disease (NAFLD) combined with prehypertension or hypertension is associated with a higher risk of cardiovascular events (CVEs). To evaluate the relationship between the severity of NAFLD and CVEs among patients with prehypertension or hypertension. Methods: In this prospective community-based Kailuan cohort, participants without cardiovascular disease and alcohol abuse, or other liver diseases were enrolled. NAFLD was diagnosed by abdominal ultrasonography. Prehypertension was defined as systolic blood pressure (BP) of 120-139 mmHg or diastolic BP of 80-89 mmHg. Participants with NAFLD were divided into mild, moderate, and severe subgroups. Follow-up for CVEs including myocardial infarction, hemorrhagic stroke, and ischemic stroke. The Cox proportional hazards model was used to estimate hazard ratios and 95% CIs of CVEs according to the severity of NAFLD and hypertensive statutes. The C-statistic was used to evaluate the efficiency of models. Results: A total of 71926 participants (mean [SD] age, 51.83 [12.72] years, 53794 [74.79%] men, and 18132 [25.21%] women) were enrolled in this study, 6,045 CVEs occurred during a median of 13.02 (0.65) years of follow-up. Compared with participants without NAFLD, the hazard ratios of CVEs for patients with mild, moderate, and severe NAFLD were 1.143 (95% CI 1.071-1.221, P < 0.001), 1.218 (95% CI 1.071-1.221, P < 0.001), and 1.367 (95% CI 1.172-1.595, P < 0.001), respectively. Moreover, participants with prehypertension plus moderate/severe NAFLD and those with hypertension plus moderate/severe NAFLD had 1.558-fold (95% CI 1.293-1.877, P < 0.001) and 2.357-fold (95% CI 2.063-2.691, P < 0.001) higher risks of CVEs, respectively, compared with those with normal BP and no NAFLD. Adding a combination of NAFLD and BP status to the crude Cox model increased the C-statistic by 0.0130 (0.0115-0.0158, P < 0.001). Conclusions: Our findings indicated that the increased cardiovascular risk with elevated BP is largely driven by the coexistence of moderate/severe NAFLD, suggesting that the severity of NAFLD may help further stratify patients with prehypertension and hypertension.

Non-alcoholic Fatty Liver Disease Is Associated With Cardiovascular Outcomes in Subjects With Prediabetes and Diabetes: A Prospective Community-Based Cohort Study.

Background: There have been no studies of the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular events (CVEs) in patients with pre-diabetes (pre-DM), and diabetes mellitus (DM). We performed a community-based cohort study to evaluate the relationship between NAFLD and CVEs in patients with glucose metabolism disorder. Methods: We enrolled 71,852 participants from the Kailuan study who had not experienced CVEs, after excluding alcohol abuse and other liver diseases. NAFLD was assessed using abdominal ultrasonography. Besides, participants were categorized by glucose metabolism status [normal glucose regulation (NGR), pre-DM, and DM]. All subjects were followed up for the occurrence of CVEs. Results: During a median of 13.01 (0.64) years of follow-up, 6,037 CVEs occurred. NAFLD was present in 22,525 (31.3%), and compared with participants without NAFLD, those with NAFLD had a 12.3% [95% confidence interval (CI) 1.059-1.191, P < 0.001] higher risk of CVEs, after adjustment for potential confounders. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.104 (95% CI 1.035-1.179, P < 0.001), 1.149 (95% CI 1.055-1.251, P < 0.001), and 1.235 (95% CI 1.059-1.441, P < 0.001), respectively. Moreover, participants with pre-DM plus NAFLD and participants with DM plus NAFLD had 1.267-fold (95% CI 1.151-1.395, P < 0.001) and 1.829-fold (95% CI 1.666-2.008, P < 0.001) higher risks of CVEs, respectively, compared with those with NGR and no NAFLD. The addition of the combination of NAFLD and glucose metabolism status to the crude Cox model increased the C-statistic by 0.0066 (0.0053-0.0080, P < 0.001). Conclusions: NAFLD is associated with higher risks of CVEs. Moreover, NAFLD is an independent predictor of CVEs in patients with pre-DM and DM, suggesting that NAFLD may provide greater risk predictive value for patients with glucose metabolism disorder.

Roles of long noncoding RNAs in aging and aging complications.

Aging is a universal and time dependent complex biological process, characterized by a progressive physiological dysfunction and an increased vulnerability to death. Though the physiological process of aging is still not fully understood, several cellular and molecular mechanisms have been identified. Long noncoding RNAs is a class of regulatory ncRNAs with transcript lengths >200 nucleotides. Discovery of this vast pool of regulators in mammalian genome supplies a new dimension to study and explore the aging process. In this review, we discuss the contribution of lncRNAs in aging and aging complications, and raise interest of serving lncRNAs as biomarkers and potential therapeutic targets to prolong health and ameliorate age-associated diseases. We hope understanding the roles of these high specificity and low conservation regulators in generating age-associated phenotypes might benefit human lifespan.

The Use of Microblog "Weibo" by Chinese Patent Medicine Companies in China.

BACKGROUND: In order to introduce regulatory measures to regulate social media use by the Chinese patent medicine (CPM) companies, it needs better understanding of CPM companies' promotional activities using social media. Thus, this study aimed to analyze the nature of the information conveyed to the public by the CPM companies through microblog (Weibo) in China. METHODS: The content of 17 CPM Weibo accounts was analyzed. These accounts were established by 13 CPM companies, each of which had more than 10,000 followers, over 1000 posts and updated posts in 2016. RESULTS: Of the 40,798 original posts identified in the 17 Weibo accounts, 98.39% (n = 40,142) were classified into 6 main themes: (1) social living (36%); (2) health science (26%); (3) health maintenance (14%); (4) direct product promotion (11%); (5) corporate branding (7%); and (6) medical and industrial information (6%). Among the posts directly related to product promotion, more than half (n = 2550) focused on customer interactions followed by product efficacy (n = 945). Among the posts about corporate branding, about half of them (n = 1,443) focused on company image. CONCLUSIONS: Weibo is being used by CPM companies widely for strategic product promotion. With one of the key strategies being overt marketing driven by covert marketing, a large amount of health-related information is disseminated through this platform. Regulatory policies to ensure the credibility of information disseminated in the social media used by the CPM companies for promotion purposes are warranted to help protect the public's interests.

Phytochemicals, pharmacology, clinical application, patents, and products of Amomi fructus.

Amomi fructus (A. fructus) (Sharen) is a well-known traditional Chinese medicine widely used to treat gastrointestinal diseases. It has high medical and economic values, which have been confirmed both in vitro and in vivo studies. This review highlights the phytochemicals, pharmacology, clinical application, patents, and products of A. fructus. More than 100 phytochemicals have been isolated and identified from A. fructus, mainly including volatile oils, saponins, flavonoids, organic acids, inorganic ingredients, and polysaccharides. The main pharmacology of gastrointestinal protection, anti-inflammatory activity, analgesic activity, antidiarrheal activity, antibacterial activity, anti-microbial activity and hypoglycemic activity have been confirmed. The main clinical applications include functional digestion disorder, gastritis, helicobacter pylori infection in children and treatment of mastitis. There are 23 patents and 405 different drug products of A. fructus.

[Bioassay for enrich-blood bioactivity of Agelicae Sinensis Radix].

Danggui, Agelicae Sinensis Radix, is a widely used Chinese herb to enrich blood, but its quality cannot be effectively assessed by the known chemical markers such as ferulic acid, ligustilide, polysaccharides, etc. A new bioassay was therefore developed to quantify the Enrich-Blood Bioactivity (EBB) for the quality assessment of Danggui raw materials. Danggui sample was first extracted with ethanol and water, respectively. Then the ethanolic extract and water extract were mixed as a test sample to quantify the amount of EBB by mice experiment. The blood deficiency mode in mice was developed by intraperitoneal injecting cyclophospharmide and phenylhdrazine hydrochloride. The quantity of red blood cell was chosen as EBB marker. Cyclosporine A was chosen as a control substance. EBB in analytes was quantified by the amount reaction of parallel line analysis (3, 3') method. The results indicated that the reliability test for quantifying EBB was passed through and the measured value was valid. The analytes showed the significant EBB (P < 0.05). The correlation coefficient was 0.9984 (n=5) between the amount of cyclosporine A (0.035-0.56 g x kg(-1)) and the increased number of red blood cell. The relative standard deviation (RSY) on the amount of EBB was estimated to be 6.15% (n = 6) by six replicated tests, and the confidence limit rate was 26.68% (n = 6). Five Danggui samples, which were collected from different cultivation areas with various morphological characters, showed the variety of EBB in the range of 21.95-44.16 U x g(-1). It is concluded that the developed method is accurate to quantify the EBB of Danggui raw materials, and is therefore suitable to assess its quality.