Longitudinal cardiovascular health measured by life's essential 8 metrics with incident diabetes: A 13-year prospective cohort study.

AIMS: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by 'Life's Essential 8' (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes. MATERIALS AND METHODS: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses. RESULTS: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH. CONCLUSIONS: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults.

Cumulative Serum Uric Acid Exposure and Its Time Course With the Risk of Incident Stroke.

BACKGROUND: Evidence on the longitudinal associations between serum uric acid (SUA) and stroke was limited and yielded inconsistent conclusions. We aimed to investigate the associations of cumulative SUA (cumSUA), incorporating the time course of cumSUA accumulation, with the risk of stroke. METHODS: The prospective cohort study enrolled 50 871 participants from Kailuan, China. CumSUA from 2006 to 2010 was derived by calculating the means of SUA values between consecutive examinations and multiplying by time intervals between visits. Time course of cumSUA accumulation was categorized as the slope of SUA versus time or by splitting the overall accumulation into an early (cumSUA06-08) and late accumulation (cumSUA08-10). Participants were classified by cumSUA quartiles, SUA slope (negative versus positive), and the combined median cumSUA (1105.21 µmol/L×year) with SUA slope, respectively. The associations with incident stroke between 2010 and 2019 were evaluated with competing risk model. RESULTS: During a median follow-up of 9.02 years, 2217 cases of incident stroke were identified. In the multivariable-adjusted model, a higher risk of stroke was observed in participants with the highest quartile versus the lowest quartile of cumSUA (subdistribution hazard ratio, 1.15 [95% CI, 1.01-1.31]), and those with a negative versus positive SUA slope (subdistribution hazard ratio, 1.09 [95% CI, 1.01-1.19]). Consistently, a later accumulation of SUA was not associated with the risk of stroke after adjustment for an early accumulation, indicating early accumulation may contribute more to the risk of stroke than later accumulation. When cumSUA was incorporated with its time course, those with changes in cumSUA suggesting early accumulation had elevated risk of stroke (subdistribution hazard ratio, 1.17 [95% CI, 1.03-1.33]). Similar results were observed for ischemic stroke. CONCLUSIONS: Incident stroke risk was associated with cumulative exposure to SUA and its accumulation time course. Early SUA accumulation resulted in a greater risk compared with later accumulation, underscoring the importance of early control of SUA to an optimal level.

Magnitude and time course of insulin resistance accumulation with the risk of cardiovascular disease: an 11-years cohort study.

BACKGROUND: The risk of cardiovascular disease (CVD) depended on the magnitude and exposure duration of insulin resistance (IR). This study aimed to investigate the associations of cumulative metabolic score for IR (cumMETS-IR) with incident CVD, and to further explore the modulated effects of time course of METS-IR accumulation. METHODS: We enrolled 47,270 participants without CVD and underwent three examinations during 2006-2010 from the Kailuan study. CumMETS-IR from 2006 to 2010 were calculated as the mean values of METS-IR between consecutive examinations multiplying by time intervals between visits. Time course of METS-IR accumulation was calculated as the slope of METS-IR versus time. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk were calculated with multivariable-adjusted Cox regressions. RESULTS: During a median follow-up of 10.99 years, we identified 3184 cases of incident CVD. The risk of incident CVD increased with increasing cumMETS-IR (HR, 1.77; 95% CI 1.58-1.98 for the Q4 versus Q1 group), exposure duration (HR, 1.60; 95% CI 1.45-1.77 for 6 years versus 0 years), and cumulative burden (HR, 1.49; 95% CI 1.37-1.61 for burden ≥ 0 versus < 0). A positive slope was associated with 14% higher risk of CVD (HR, 1.14; 95% CI 1.07-1.22). When combining cumMETS-IR and slope, those with cumMETS-IR ≥ median (142.78) and slope ≥ 0 had the highest risk of CVD (HR,1.38; 95% CI 1.25-1.53). CONCLUSIONS: The risk of CVD increased with elevated cumMETS-IR and an increasing trend over time, emphasizing the importance of maintaining optimal METS-IR levels across life span.

Association between cumulative atherogenic index of plasma exposure and risk of myocardial infarction in the general population.

BACKGROUND: Atherogenic index of plasma (AIP) has been confirmed as a novel marker for myocardial infarction (MI), but few evidence on the long-term AIP and MI risk in general populations. We thus aimed to evaluate the relationships of cumulative exposure to AIP and its accumulation time course with the risk of MI. METHODS: A total of 54,440 participants were enrolled in the Kailuan study. Time-weighted cumulative AIP was calculated as the weighted sum of the mean AIP value for each time interval, then normalized by total exposure duration, the exposure duration was from 2006 to 2010. Duration of high AIP exposure was defined as the duration with high AIP and ranged from 0 to 6 years. The time course of AIP accumulation was categorized by the combination of time-weighted cumulative AIP < or ≥ median (- 0.12) and AIP slope. RESULTS: After 11.05 years of follow-up, 766 incident MI cases were documented. After adjustment for potential confounders, higher risk of MI was observed in participants with the highest time-weighted cumulative AIP quartile (HR, 1.89; 95% CI 1.47-2.43), the longest exposure duration of high AIP (HR, 1.52; 95% CI 1.18-1.95), and those with high time-weighted cumulative AIP and negative slope (HR, 1.42; 95% CI 1.13-1.79). CONCLUSIONS: Long-term cumulative exposure to AIP and the time course of AIP accumulation increased the risk of MI. High AIP earlier resulted in a greater risk increase than later in life with the same time-weighted cumulative AIP, emphasizing the importance of controlling atherogenic dyslipidemia early in life.

Cardiovascular health and life expectancy with and without cardiovascular disease in the middle-aged and elderly Chinese population.

BACKGROUND: High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women. METHODS: We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0-49 points], moderate [50-79 points] and high [80-100 points]) with Life's Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD. RESULTS: Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone. CONCLUSIONS: High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.

Baseline and longitudinal cardiovascular health using Life's Essential 8 metrics with the risk of incident hypertension.

OBJECTIVE: The quantification of cardiovascular health (CVH) was updated by the American Heart Association recently by using the "Life's Essential 8" (LE8) score. We aimed to investigate the associations of baseline and longitudinal CVH status measured by the new LE8 score (except for blood pressure) with the risk of hypertension. METHODS: A total of 52 990 participants with complete data on LE8 metrics and without hypertension were enrolled from the Kailuan study, Tangshan, China. The associations of incident hypertension with the overall baseline, time-updated, and time-varying CVH score (ranging 0 [lowest] to 100 [highest]), and each component of LE8, were assessed by Cox regressions. RESULTS: During a median follow-up of 10.73 years 28 380 cases of incident hypertension were identified. The risk of hypertension attenuated with increased CVH score (Ptrend < 0.0001), the hazard ratios (HRs) in high CVH versus low CVH group was 0.54 (95% confidence interval [CI], 0.51-0.57) for baseline CVH, 0.47 (95% CI, 0.45-0.50) for time-updated CVH, and 0.59 (95% CI, 0.55-0.63) for time-varying CVH. The predictive value of CVH in predicting hypertension improved by using LE8 than using Life's Simple 7 metrics. Among LE8 components, body mass index score was the strongest risk factor for hypertension. Subgroup analyses showed that the benefit of a higher CVH score on hypertension was more prominent in young adults and in women (Pinteraction < 0.05). CONCLUSIONS: A higher CVH score assessed by new LE8 is associated with a lower risk of subsequent hypertension, especially young adults and women.

Insulin resistance mediates obesity-related risk of cardiovascular disease: a prospective cohort study.

BACKGROUND: The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the insulin resistance seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity on cardiovascular disease (CVD) is mediated by insulin resistance. METHODS: A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. Insulin resistance was evaluated by the triglyceride-glucose (TyG) index, calculating as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Mediation analysis using a new 2-stage regression method for survival data proposed by Valeri and VanderWeele was to explore the mediating effects of the TyG index on the association between obesity and CVD. RESULTS: During a median follow-up of 13.01 years, we identified 7327 cases of CVD. Mediation analyses showed that 47.81% of the total association (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.12-1.24) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.07; 95% CI, 1.07-1.09), and the proportion mediated was 37.94% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 32.01, 35.02, and 31.06% for obesity, taken normal weight as reference. CONCLUSIONS: The association between obesity and CVD was mediated by TyG index, suggesting proper control of insulin resistance can be effective to reduce the effects of obesity on CVD.

Triglyceride-glucose index variability and incident cardiovascular disease: a prospective cohort study.

BACKGROUND: Recent studies have suggested that triglyceride-glucose (TyG) index is an independent predictor of cardiovascular disease (CVD). However, the impact of long-term visit-to-visit variability in TyG index on the risk of CVD is not known. We aimed to investigate the longitudinal association between baseline and mean TyG index as well as TyG index variability and incident CVD in a Chinese population. METHODS: We included 49,579 participants without previous history of CVD in the Kailuan study who underwent three health examinations (2006, 2008, and 2010) and were followed up for clinical events until 2019. TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. We measured TyG index variability as the SD of the residuals obtained from a linear regression on the three TyG index measurements for each individual. Multivariate-adjusted Cox models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) with incident CVD. RESULTS: During a median follow-up time of 9.0 years, 2404 developed CVD. The highest tertile (T3) of baseline and mean TyG index were each associated with higher CVD incidence as compared with the lowest tertile (T1): aHR, 1.25; 95% CI 1.11-1.42; and aHR 1.40; 95% CI 1.24-1.58, respectively. Tertile 3 of TyG index variability was associated with increased CVD incidence compared to T1 group (aHR, 1.12; 95% CI 1.01-1.24). Similar findings were observed in a series of sensitivity analyses. CONCLUSION: Higher TyG index level and greater TyGindex variability were each independently associated with a higher incidence of CVD.

Time course of the triglyceride glucose index accumulation with the risk of cardiovascular disease and all-cause mortality.

BACKGROUND: Future risk of cardiovascular disease (CVD) and mortality is associated with cumulative amount TyG index (cumTyG) exposure, while whether time course of TyG accumulation modulates the risk remains unclear. This study sought to examine the associations of cumTyG index accumulation time course with the risk of CVD and all-cause mortality. METHODS: We enrolled 51,734 participants free of CVD and underwent three examinations at year 2006, 2008, and 2010. CumTyG from baseline to the third examination was calculated. Time course of cumTyG accumulation was calculated as the slope of TyG versus time from 2006 to 2010, or as splinting the overall TyG index accumulation into early (cumTyG06 - 08) and late accumulation (cumTyG08 - 10). Participants were categorized by the combination of cumTyG < or ≥ median (34.44 × years) and a negative or positive TyG slope. RESULTS: During a median follow-up of 9.04 years, we identified 3,602 incident CVD cases and 3,165 deaths. The risk of CVD and all-cause mortality increased with decreased TyG slope, the corresponding adjusted hazard ratio (aHR) with 95% confidence interval (CI) was 1.11 (1.04-1.19) and 1.18 (1.10-1.26) for patients with a negative TyG slope, respectively. Consistently, a later accumulation of TyG index was not associated with the risk of CVD and all-cause mortality after adjustment for an early accumulation. When considering the combination of cumTyG index and time course, participants with a cumTyG ≥ median and a negative TyG slope had elevated risk of CVD (aHR, 1.37; 95% CI, 1.24-1.51) and all-cause mortality (aHR, 1.28; 95% CI, 1.15-1.43). Additionally, the association was more prominent in young adults. CONCLUSION: Early TyG index accumulation resulted in a greater risk of CVD and all-cause mortality than later TyG later accumulation with the same overall cumulative exposure, emphasizing the importance of optimal TyG index control earlier in life.

Triglyceride-glucose index and the risk of stroke and its subtypes in the general population: an 11-year follow-up.

BACKGROUND: Triglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort. METHODS: A total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006-2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression. RESULTS: During a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12-1.33, and adjusted HR 1.32, 95% CI 1.21-1.44, respectively, P for trend < 0.001). We also found a linear association between baseline TyG index with stroke. Similar results were found for ischemic stroke. However, no significant associations were observed between baseline TyG index and risk of intracranial hemorrhage. Parallel results were observed for the associations of updated cumulative average TyG index with outcomes. CONCLUSIONS: Elevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.

Current smoking is associated with extracranial carotid atherosclerotic stenosis but not with intracranial large artery disease.

BACKGROUND: Accumulating evidence has shown that cigarette smoking is an important risk factor for ischemic stroke. However, it is not clear about the potential mechanisms through which cigarette smoking affects stroke risk. In the study, we aimed to investigate the relationship between cigarette smoking and the occurrence of extracranial (ECAS) and intracranial atherosclerotic stenosis (ICAS). METHODS: We analyzed patients enrolled in the Chinese intracranial atherosclerosis (CICAS), which was a prospective, multicenter, hospital-based cohort study. Smoking status was classified into never, former and current smoking. For those patients with current smoking, data on time duration (year) and extent (the number of cigarette smoked per day) was recorded and pack year of smoking was calculated. ICAS was evaluated with 3-dimentional time-of-flight MRA and ECAS was evaluated with cervical ultrasonography or contrast-enhanced MRA. Multivariable Logistic regression was performed to identify the association between smoking status and the occurrence of ECAS and ICAS. RESULTS: A total of 2656 patients (92.7%) of acute ischemic stroke and 208 (7.3%) of transient ischemic attack were analyzed. The mean age was 61.9 ± 11.2 and 67.8% were male. There were 141 (4.9%) patients had only ECAS, 1074 (37.5%) had only ICAS, and 261 (9.1%) had both ECAS and ICAS. Current smoking was significantly associated with the occurrence of ECAS (adjusted OR = 1.47, 95% CI = 1.09-1.99, P < 0.01). In addition, with 1 year of smoking increment, the risk of ECAS increased by 1.1% (adjusted OR = 1.011; 95% CI = 1.003-1.019; P = 0.005); with one cigarette smoked per day increment, the risk of ECAS increased by 1.0% (adjusted OR = 1.010; 95% CI = 1.001-1.020; P = 0.03); and with one pack year of smoking increment, the risk of ECAS increased by 0.7% (adjusted OR = 1.007; 95% CI = 1.002-1.012; P < 0.01). However, no significant association was found between smoking status and the occurrence of ICAS. CONCLUSION: A dose-response relationship was identified between cigarette smoking and the occurrence of ECAS, but not ICAS. Further studies on molecular mechanisms were warranted.

Association between 5,10-Methylenetetrahydrofolate Reductase C677T Gene Polymorphism and Risk of Ischemic Stroke: A Meta-analysis.

BACKGROUND: Hyperhomocysteinemia, a condition that is strongly determined by dietary intake of B vitamins, has been suggested to be an independent risk factor for ischemic stroke (IS). To test this hypothesis, we performed a meta-analysis to investigate the associations between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which plays a critical role in modulating plasma homocysteine concentrations, and IS risk. MATERIALS AND METHODS: We searched case-control studies on the association between MTHFR C677T genetic polymorphism and susceptibility to IS through PubMed, Embase, and Medline databases from January 2000 up to October 2014. The random-effects model was employed because moderate heterogeneity across studies was observed, as assessed by I(2) statistic. Publication bias was estimated using funnel plot and Egger's regression test. RESULTS: A total of 22 case-control studies were included in the current meta-analysis. Significant associations between MTHFR C677T genetic polymorphism and IS were found under the dominant model (pooled odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.24-1.57), the recessive model (pooled OR = 1.37, 95% CI: 1.16-1.61), and the allele model (pooled OR = 1.29, 95% CI: 1.18-1.42). CONCLUSIONS: The meta-analysis suggests that MTHFR C677T genetic polymorphism is significantly associated with susceptibility to IS, which provides evidence supporting hyperhomocysteinemia as a risk factor for stroke.

Risk score to predict hospital-acquired pneumonia after spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: We aimed to develop a risk score (intracerebral hemorrhage-associated pneumonia score, ICH-APS) for predicting hospital-acquired stroke-associated pneumonia (SAP) after ICH. METHODS: The ICH-APS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Variables routinely collected at presentation were used for predicting SAP after ICH. For testing the added value of hematoma volume measure, we separately developed 2 models with (ICH-APS-B) and without (ICH-APS-A) hematoma volume included. Multivariable logistic regression was performed to identify independent predictors. The area under the receiver operating characteristic curve (AUROC), Hosmer-Lemeshow goodness-of-fit test, and integrated discrimination index were used to assess model discrimination, calibration, and reclassification, respectively. RESULTS: The SAP was 16.4% and 17.7% in the overall derivation (n=2998) and validation (n=2000) cohorts, respectively. A 23-point ICH-APS-A was developed based on a set of predictors and showed good discrimination in the overall derivation (AUROC, 0.75; 95% confidence interval, 0.72-0.77) and validation (AUROC, 0.76; 95% confidence interval, 0.71-0.79) cohorts. The ICH-APS-A was more sensitive for patients with length of stay >48 hours (AUROC, 0.78; 95% confidence interval, 0.75-0.81) than those with length of stay <48 hours (AUROC, 0.64; 95% confidence interval, 0.55-0.73). The ICH-APS-A was well calibrated (Hosmer-Lemeshow test) in the derivation (P=0.20) and validation (P=0.66) cohorts. Similarly, a 26-point ICH-APS-B was established. The ICH-APS-A and ICH-APS-B were not significantly different in discrimination and reclassification for SAP after ICH. CONCLUSION: The ICH-APSs are valid risk scores for predicting SAP after ICH, especially for patients with length of stay >48 hours.

Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.

BACKGROUND: Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). METHODS: The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. RESULTS: A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P < 0.001). When compared to 8 existing models, the DFS-AIS showed significantly better discrimination for good functional outcome and mortality at discharge, 3-month, 6-month, and 1-year after AIS (all P < 0.0001). CONCLUSION: The DFS-AIS is a valid risk model to predict functional outcome at discharge, 3-month, 6-month, and 1-year after AIS.

Risk score to predict gastrointestinal bleeding after acute ischemic stroke.

BACKGROUND: Gastrointestinal bleeding (GIB) is a common and often serious complication after stroke. Although several risk factors for post-stroke GIB have been identified, no reliable or validated scoring system is currently available to predict GIB after acute stroke in routine clinical practice or clinical trials. In the present study, we aimed to develop and validate a risk model (acute ischemic stroke associated gastrointestinal bleeding score, the AIS-GIB score) to predict in-hospital GIB after acute ischemic stroke. METHODS: The AIS-GIB score was developed from data in the China National Stroke Registry (CNSR). Eligible patients in the CNSR were randomly divided into derivation (60%) and internal validation (40%) cohorts. External validation was performed using data from the prospective Chinese Intracranial Atherosclerosis Study (CICAS). Independent predictors of in-hospital GIB were obtained using multivariable logistic regression in the derivation cohort, and ß-coefficients were used to generate point scoring system for the AIS-GIB. The area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively. RESULTS: A total of 8,820, 5,882, and 2,938 patients were enrolled in the derivation, internal validation and external validation cohorts. The overall in-hospital GIB after AIS was 2.6%, 2.3%, and 1.5% in the derivation, internal, and external validation cohort, respectively. An 18-point AIS-GIB score was developed from the set of independent predictors of GIB including age, gender, history of hypertension, hepatic cirrhosis, peptic ulcer or previous GIB, pre-stroke dependence, admission National Institutes of Health stroke scale score, Glasgow Coma Scale score and stroke subtype (Oxfordshire). The AIS-GIB score showed good discrimination in the derivation (0.79; 95% CI, 0.764-0.825), internal (0.78; 95% CI, 0.74-0.82) and external (0.76; 95% CI, 0.71-0.82) validation cohorts. The AIS-GIB score was well calibrated in the derivation (P = 0.42), internal (P = 0.45) and external (P = 0.86) validation cohorts. CONCLUSION: The AIS-GIB score is a valid clinical grading scale to predict in-hospital GIB after AIS. Further studies on the effect of the AIS-GIB score on reducing GIB and improving outcome after AIS are warranted.

Temporal relationship between arterial stiffness and blood pressure variability and joint effect on cardiovascular disease.

Although arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and blood pressure (BP) significantly correlated, the relationship between baPWV and BP variation (BPV) was unclear. This study aimed to examine the temporal relationship between brachial-ankle pulse wave velocity (baPWV) and systolic blood pressure variation (SBPV) and their joint effect on the development of cardiovascular disease (CVD). This study included 6632 participants with repeated assessments of baPWV and BP during 2006 to 2018. The baseline and follow-up SBPV was calculated as absolute SBP difference divided by mean SBP over sequential visits, using data between 2006-2010 and 2014-2018, respectively. Cross-lagged analysis was used to assess the temporal relation between baPWV and SBPV, and logistic analysis was used to assess the joint effect of baPWV and SBPV on CVD. After adjustment for confounder, the path coefficient from baseline baPWV to follow-up SBPV (ß1 = 0.040; P = 0.0012) was significantly had greater than the path from baseline SBPV to follow-up baPWV (ß2 = 0.009; P = 0.3830), with P = 0.0232 for the difference between ß1 and ß2. This unidirectional relationship from baseline baPWV to follow-up SBPV was consistent in patients without hypertension, with isolated systolic, high systolic and diastolic, uncontrolled and controlled hypertension. In addition, participants with high levels of baseline baPWV and follow-up SBPV had greater risk of CVD (odds ratio, 5.82; 95% confidence interval, 2.50-12.60) than those with low-low levels. The findings suggested that arterial stiffness appeared to precede the increase in SBPV and their joint effect is predictive of the development of CVD.

Roles of general and central adiposity in cardiometabolic multimorbidity: revisiting the obesity paradox using a multistate model.

OBJECTIVE: The objective of this study was to evaluate the associations of general and central obesity with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM), and death. METHODS: A total of 86,169 participants who were CMD-free were included from the Kailuan cohort and categorized into four groups by quartiles of BMI, waist to hip ratio (WHR), weight-adjusted waist index, and waist to height ratio. We defined FCMD as the first onset of diabetes, stroke, or myocardial infarction and CMM as co-occurrence of at least two CMDs. Multistate models were used to estimate hazard ratios and 95% CI. RESULTS: A total of 18,461 participants developed FCMD, of whom 1476 progressed to CMM, and 10,009 died during follow-ups. Both general and central adiposity indices increased the risk of transition from baseline to FCMD and from FCMD to CMM. However, compared with the first quartile, the hazard ratio (95% CI) of the fourth quartile of BMI was 0.86 (95% CI: 0.80-0.91) for transition from health to death and 0.66 (95% CI: 0.59-0.74) from FCMD to death, whereas the corresponding estimates of WHR were 1.22 (95% CI: 1.14-1.31) and 1.16 (95% CI: 1.02-1.32), respectively. CONCLUSIONS: Central adiposity indices such as WHR were associated with an increased risk of CMD and mortality, showing no evidence for the obesity paradox and thereby supporting a shift of public focus from BMI only to both general obesity and adiposity distribution.

Interrelationship among common medical complications after acute stroke: pneumonia plays an important role.

BACKGROUND AND PURPOSE: Medical complications are common among patients with stroke. However, little is known about the potential interrelationship among them. In the present study, we aimed to investigate the association between common in-hospital medical complications after acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH). METHODS: We analyzed patients enrolled in the China National Stroke Registry from 2007 to 2008. The occurrence of 11 common stroke-associated medical complications during acute hospitalization was prospectively registered. Multivariable analysis using generalized estimation equation was performed to assess association between medical complications in AIS and ICH cohort, respectively. RESULTS: A total of 14 702 patients with AIS and 5221 patients with ICH were enrolled. The median age was 65 years (interquartile range, 55-74 years), and 38.1% were female. The median length of hospital stay was 14 days (interquartile range, 10-20 days) for AIS and 18 days (interquartile range, 11-26 days) for ICH. Pneumonia was the most common medical complication after AIS (11.4%) and ICH (16.8%). In the AIS cohort, after adjusting for potential confounders, pneumonia was significantly associated with development of gastrointestinal bleeding (adjusted odds ratio [OR], 8.35; 95% confidence interval [CI], 6.27-11.1; P<0.001), decubitus ulcer (adjusted OR, 5.31; 95% CI, 3.39-8.31; P<0.001), deep vein thrombosis (adjusted OR, 4.27; 95% CI, 2.41-7.59; P<0.001), epileptic seizure (adjusted OR, 3.96; 95% CI, 2.67-5.88; P<0.001), urinary tract infection (adjusted OR, 3.34; 95% CI, 2.73-4.10; P<0.001), atrial fibrillation/flutter (adjusted OR, 3.17; 95% CI, 2.58-3.90; P<0.001), and recurrent stroke (adjusted OR, 2.65; 95% CI, 2.07-3.40; P<0.001). Similar significant association between pneumonia and development of several nonpneumonia medical complications was verified in ICH cohort as well. CONCLUSIONS: Pneumonia is closely associated with the development of several nonpneumonia medical complications after AIS and ICH.

A novel risk score to predict 1-year functional outcome after intracerebral hemorrhage and comparison with existing scores.

INTRODUCTION: Spontaneous intracerebral hemorrhage (ICH) is one of leading causes of mortality and morbidity worldwide. Several predictive models have been developed for ICH; however, none of them have been consistently used in routine clinical practice or clinical research. In the study, we aimed to develop and validate a risk score for predicting 1-year functional outcome after ICH (ICH Functional Outcome Score, ICH-FOS). Furthermore, we compared discrimination of the ICH-FOS and 8 existing ICH scores with regard to 30-day, 3-month, 6-month, and 1-year functional outcome and mortality after ICH. METHODS: The ICH-FOS was developed based on the China National Stroke Registry, in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1 year after ICH. Multivariable logistic regression was performed to determine independent predictors, and ß-coefficients were used to generate scoring system of the ICH-FOS. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. RESULTS: The overall 1-year poor functional outcome (mRS ≥ 3) was 46.7% and 44.9% in the derivation (n = 1,953) and validation (n = 1,302) cohorts, respectively. A 16-point ICH-FOS was developed from the set of independent predictors of 1-year poor functional outcome after ICH including age (P < 0.001), admission National Institutes of Health Stroke Scale score (P < 0.001), Glasgow Coma Scale score (P < 0.001), blood glucose (P = 0.002), ICH location (P < 0.001), hematoma volume (P < 0.001), and intraventricular extension (P < 0.001). The ICH-FOS showed good discrimination (AUROC) in the derivation (0.836, 95% CI: 0.819-0.854) and validation (0.830, 95% CI: 0.808-0.852) cohorts. The ICH-FOS was well calibrated (Hosmer-Lemeshow test) in the derivation (P = 0.42) and validation (P = 0.39) cohort. When compared to 8 prior ICH scores, the ICH-FOS showed significantly better discrimination with regard to 1-year functional outcome and mortality after ICH (all P < 0.0001). Meanwhile, the ICH-FOS also demonstrated either comparable or significantly better discrimination for poor functional outcome and mortality at 30-day, 3-month, and 6-month after ICH. CONCLUSION: The ICH-FOS is a valid clinical grading scale for 1-year functional outcome after ICH. Further validation of the ICH-FOS in different populations is needed.

[The impact of in-hospital pneumonia on the risk of in-hospital and long-term mortality in patients with acute ischemic stroke].

OBJECTIVE: To observe the short-term and long-term impacts of in-hospital pneumonia on outcomes of patients hospitalized with acute ischemic stroke. METHODS: All consecutive patients older than 18 years with acute ischemic stroke were prospectively recruited to this study, including 132 clinical centers in 32 provinces and 4 municipalities (including Hong Kong region) in China from September 2007 to August 2008. Case report form was designed. Data of pneumonia and survival outcomes at baseline; discharge; 3, 6 and 12 months after admission were recorded. Multivariable logistic regression was used for statistical correlation analysis. RESULTS: A total of 1373 (11.88%) patients from 11 560 acute ischemic stroke patients were notified with in-hospital pneumonia. The case fatality rate was 14.4% (1664 patients) within 12 months after stroke onset. The fatality rate in patients with pneumonia was higher than that of patients without pneumonia.In-hospital pneumonia was an independent risk factor for death at discharge (adjusted OR = 5.916; 95%CI 4.470-7.831), at 3 months (adjusted OR = 3.641; 95%CI 3.035-4.367), 6 months (adjusted OR = 3.445; 95%CI 2.905-4.086), and 12 months (adjusted OR = 3.543; 95%CI 3.016-4.161) after onset. CONCLUSION: In-hospital pneumonia is an adverse factor for the short-term and long-term survival of acute ischemic patients in China.