Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes.

BACKGROUND: Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. METHODS: A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography-mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. RESULTS: Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15-1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03-2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95-1.48]; cardioembolism, 1.54 [0.95-2.48]; others, 1.19 [0.98-1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91-3.01) and similarly found an increased risk of stroke recurrence. CONCLUSIONS: Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

Effect of Lipoprotein(a) on Stroke Recurrence Attenuates at Low LDL-C (Low-Density Lipoprotein) and Inflammation Levels.

BACKGROUND: Lp(a) (lipoprotein(a)) contributes to cardiovascular disease mainly through proatherogenic and proinflammatory effects. Here, we aimed to evaluate whether a residual stroke risk of Lp(a) would remain when the LDL-C (low-density lipoprotein cholesterol) and inflammatory levels are maintained low. METHODS: This prospective cohort study included 9899 patients with ischemic stroke or transient ischemic attack from the Third China National Stroke Registry who had measurements of plasma Lp(a) and were followed up for 1 year. Cutoffs were set at the 50 mg/dL for Lp(a). LDL-C was corrected for Lp(a)-derived cholesterol (LDL-Cc [LDL-C corrected]) and cutoffs were set at 55 and 70 mg/dL.The threshold values of IL-6 (interleukin 6) and hsCRP (high-sensitive C-reactive protein) were the median 2.65 ng/L and 2 mg/L. Multivariable-adjusted hazard ratio (HR) were calculated using Cox regression models for each category to investigate the associations of Lp(a) with stroke recurrence within 1 year. RESULTS: Among all patients, those with Lp(a) ≥50 mg/dL were at higher stroke recurrence risk than those with Lp(a) <50 mg/dL (11.5% versus 9.4%; adjusted HR, 1.20 [95% CI, 1.02-1.42]). However, the risk associated with elevated Lp(a) was attenuated in patients with LDL-Cc <55 mg/dL (high Lp(a) versus low Lp(a): 8.9% versus 9.0%; adjusted HR, 0.92 [95% CI, 0.65-1.30]) or IL-6 <2.65 ng/L (9.0% versus 7.8%; adjusted HR, 1.14 [95% CI, 0.87-1.49]). Notably, in the group with both low LDL-Cc and inflammation levels, the rate of patients with high Lp(a) did not significantly different from the rate of patients with low Lp(a; LDL-Cc <55 mg/dL and IL-6 <2.65 ng/L: 6.2% versus 7.1%; adjusted HR, 0.86 [95% CI, 0.46-1.62]; LDL-Cc <55 mg/dL and hsCRP <2 mg/L: 7.7% versus 7.6%; adjusted HR, 0.97 [95% CI, 0.57-1.66]). However, there was no interaction between the LDL-Cc, IL-6, hsCRP, and Lp(a) levels on stroke recurrence risk. CONCLUSIONS: Increased Lp(a) was significantly associated with stroke recurrence risk in patients with ischemic stroke/transient ischemic attack. However, at low LDL-Cc or IL-6 levels, the elevated Lp(a) -associated stroke recurrence risk was attenuated in a secondary prevention setting.

Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in CYP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity.

Background and Purpose- The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of CYP2C19 genotype and body mass index (BMI). Methods- CYP2C19 loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI <25 and ≥25 kg/m2, respectively. Primary outcome was defined as stroke recurrence at 3 months. Results- In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m2). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60-1.36), 0.87 (0.56-1.35), 0.65 (0.39-1.09), and 0.40 (0.22-0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with P=0.049 for interaction. Conclusions- Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in CYP2C19 LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between CYP2C19 genotype and efficacy of clopidogrel-aspirin therapy. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Association between Low-Density Lipoprotein Cholesterol Levels and Proximal Single Subcortical Infarction in Comparison with Distal Single Subcortical Infarction.

PURPOSE: Single subcortical infarction (SSI) in the middle cerebral artery (MCA) territory can be classified into proximal SSI (pSSI) and distal SSI (dSSI) based on the heterogeneous pathogenesis. It is hypothesized that pSSI is more relevant with atherosclerosis, as low-density lipoprotein cholesterol (LDL-C) is the major atherogenic lipoprotein, we conducted the present study to investigate the association between LDL-C levels and pSSI in comparison with dSSI. PATIENTS AND METHODS: This study is a subset of the Chinese Intracranial Atherosclerosis study. A total of 380 with SSI in the MCA territory classified as small artery occlusion stroke were enrolled in this study. 3.0-T magnetic resonance imaging (MRI) was performed to categorize the participants into two groups, pSSI (extending to the basal surface of MCA) and dSSI (not extending to the basal surface of MCA). RESULTS: Out of the 380 enrolled participants (273 men and 107 women), the proportion of pSSI and dSSI were 53.2% (202/380) versus 46.8% (178/380) based on MRI. The results of univariate and multivariate logistic regression were both at the borderline level of statistical significance. Further stratified analyses revealed that age is an interaction factor (P = 0.03), the association between LDL-C levels and the pSSI in participants aged over 65 had a significant positive relation (OR: 1.56; 95%CI: 1.14-2.12). CONCLUSION: LDL-C level is an independent risk factor for pSSI in patients aged over 65. Our result is in accordance with the hypothesis that pSSI is more relevant with atherosclerosis, thus appropriate treatment should be applied differently to pSSI and dSSI.

LDL-C Levels and Bleeding Risk in Patients Taking DAPT After Minor Ischemic Stroke or TIA.

Importance: Evidence on the bleeding risk associated with low-density lipoprotein cholesterol (LDL-C) levels in patients receiving dual antiplatelet therapy (DAPT) remains sparse. Objective: To investigate the association of LDL-C levels with bleeding risk in patients with minor ischemic stroke (MIS) or high-risk transient ischemic attack (HRTIA) receiving DAPT. Design, Setting, and Participants: This cohort study was an analysis of pooled data from 2 randomized, double-blind, placebo-controlled clinical trials in China of patients with MIS or HRTIA who were receiving DAPT: the CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) trial enrolled patients at 114 sites from October 2009 to July 2012, and the CHANCE-2 enrolled patients at 202 centers from September 2019 to March 2021. Both sets of patients were followed up for 90 days. Data analysis was performed from August 2022 to May 2023. Exposures: Baseline LDL-C levels and receipt of ticagrelor-aspirin and clopidogrel-aspirin DAPT. Main Outcomes and Measures: The primary outcome was any bleeding, and the secondary outcome was severe or moderate bleeding within 3 months after randomization. The association of LDL-C levels and all outcomes was assessed by using the Cox proportional hazard model. Hazard ratios (HRs) with 95% CIs were calculated on univariable (unadjusted) Cox regression models. Adjusted HRs (aHRs) and their 95% CIs were calculated on multivariable Cox regression models. Results: In total, 8996 patients with acute MIS or HRTIA who were receiving DAPT were included in the 2 trials, of whom 1066 without serum specimens and 490 patients with missing baseline LDL-C value were excluded. Finally, 7440 patients with DAPT (4486 in the clopidogrel-aspirin group and 2954 in the ticagrelor-aspirin group) were included in this study. The median (IQR) age was 64.32 (56.56-71.30) years, and 2479 patients (33.32%) were women. A total of 270 (3.63%) bleeding events were reported at 3 months, and LDL-C less than 70 mg/dL was associated with an increased risk of both any bleeding (aHR, 1.48; 95% CI, 1.03-2.12), and severe or moderate bleeding (aHR, 2.78; 95% CI, 1.18-6.53). The risk of any bleeding was increased at lower LDL-C levels in the ticagrelor-aspirin group (aHR, 1.71; 95% CI, 1.08-2.72). However, an increased risk of any bleeding was not observed in the clopidogrel-aspirin group (aHR, 1.30; 95% CI, 0.73-2.30). There was no significant association between LDL-C levels and the risk of severe or moderate bleeding in either the ticagrelor-aspirin or clopidogrel-aspirin group. Conclusions and Relevance: These findings suggest that low LDL-C levels are associated with an increased bleeding risk within 3 months among patients with MIS or HRTIA receiving DAPT, especially those taking ticagrelor-aspirin. Weighing the risks and benefits is crucial when simultaneously considering the selection of LDL-C target strategies and DAPT regimens among these patients.

Predicted resting metabolic rate and prognosis in patients with ischemic stroke.

PURPOSE: Resting metabolic rate (RMR) could represent metabolic health status. This study aims to examine the association of the predicted RMR with 1-year poor functional outcome and all-cause mortality in patients with ischemic stroke as a proxy of metabolic profile. METHODS: A total of 15,166 patients with ischemic stroke or transient ischemic attack (TIA) from the Third China National Stroke Registry (CNSR-III) were enrolled in this study. The Harris-Benedict equation based on sex, age, weight, and height was used to predict RMR. The primary endpoints were poor functional outcome defined as ≥3 modified Rankin Scale (mRS) score and all-cause mortality within 1 year. The association between predicted RMR and prognosis was assessed by multivariable regression analysis. Besides that, subgroup analysis of age, sex, and body mass index (BMI) with predicted RMR was also performed. RESULTS: 12.85% (1657) individuals had poor functional outcome and 2.87% (380) died of whatever causes within 1 year. An inverse association was found between predicted RMR with poor functional outcome and all-cause mortality. Compared to the lowest quartile, the highest quartile was significantly associated with lower risk of poor functional outcome (adjusted odds ratio [OR], 0.43 [95% confidence interval (CI) 0.33-0.56]) and all-cause mortality (adjusted hazard ratio [HR], 0.44 [95% CI 0.28-0.71]). No significant interaction was between predicted RMR and specified subgroup. CONCLUSIONS: Predicted RMR by the Harris-Benedict equation seems to be an independent protective predictor of poor functional outcome and all-cause mortality after ischemic stroke as a metabolic proxy.

Time-variant associations of ambulatory pulse rate with short-term neurologic functional outcomes following acute ischemic stroke.

This study aims to assess the associations of functional outcomes following acute ischemic stroke (IS) with ambulatory pulse rate (PR) and characterize the time-variant properties of the associations. The prospective cohort consisted of 1831 patients who had ambulatory blood pressure (BP) and PR monitoring following acute IS, and neurologic status evaluated at discharge and 3-month follow-up. The neurologic disability was defined as modified Rankin Scale ≥3. Logistic regression and generalized penalized functional regression models were used to examine the associations of ambulatory BP and PR with neurologic disability. Adjusting for covariates, the neurologic disability at discharge and 3-month was associated with high average 24-h, daytime, and nocturnal PR (odds ratio, OR = 1.20-1.34; p < 0.05 for all), high standard derivation of nocturnal PR (OR = 1.19 and 1.32; p < 0.05 for both), and low nocturnal PR decline (OR = 0.76 and 0.76; p < 0.05 for both). The OR functions of ambulatory PR on neurologic disability were "W-shaped" from 0 a.m. to 12 p.m., with ORs >1 in the wee hours and at noon, and ORs <1 before dawn and at night. The ambulatory BP profiles were not associated with neurologic disability at discharge or 3-month. The ambulatory PR is associated with the risk of short-term neurologic disability of stroke patients, with four different phases in a 24-h cycle. Ambulatory PR monitoring, especially nocturnal PR monitoring, has significant clinical implications for the prevention of short-term neurologic disability in stroke inpatients.

Acute-phase heart rate trajectories and functional outcomes in acute ischemic stroke.

The heart rate (HR) trajectory is a dynamic metric that shows how HR changes over time. Previous studies have demonstrated that elevated HR is associated with stroke events. However, little research has been done on the influence of shifting HR throughout the acute period on clinical outcomes. This study aims to investigate the effect of HR trajectories on functional outcomes in patients with acute ischemic stroke (AIS). A total of 981 AIS patients were included in the study. A latent mixture model was used to assess HR trends over the first 7 days following disease onset. The patients were divided into four groups based on different HR trajectories: markedly decreasing in 48 h (T1), mildly decreasing in 48 h (T2), sustained moderate in 7 days (T3), and sustained high in 7 days (T4). Poor outcome was defined as a modified Rankin Scale (mRS) score of ≥3 in 3 months. Logistic regression was used to analyze the correlation between different HR trajectories and outcomes. The incidence of poor outcomes was 9.02%, 10.80%, 11.79%, 16.36% in T1 (n = 133), T2 (n = 352), T3 (n = 441), and T4 (n = 55) groups, respectively. Compared with T1 group, T4 group was significantly associated with a higher risk of poor outcome at 3 months (odds ratio = 3.00, 95% confidence interval = 1.06-8.54, p value = .0392). This suggests that in AIS patients, a sustained high HR trajectory is linked to a greater likelihood of poor functional outcome than a markedly decreasing HR trajectory. HR trajectories demonstrate the utility of repeated HR measurements for outcome assessment.

Residual Risk of Trimethylamine-N-Oxide and Choline for Stroke Recurrence in Patients With Intensive Secondary Therapy.

Background Trimethylamine N-oxide (TMAO) contributes to cardiovascular disease through its prothrombotic, proatherothrombotic, and proinflammatory effects. We aimed to evaluate whether residual risk of recurrent stroke of TMAO and its precursor choline remain among patients who received dual-antiplatelet therapy and intensive lipid-lowering therapy and with a low inflammation level (high-sensitivity C-reactive protein <2 mg/L on admission). Methods and Results Patients with ischemic stroke or transient ischemic attack were enrolled from the CNSR-III (Third China National Stroke Registry) in China. Plasma TMAO and choline concentrations at baseline were measured in 9793 participants using liquid chromatography-mass spectrometry. The primary outcome was a new stroke within 1 year. Multivariable-adjusted hazard ratios were calculated using Cox regression models to investigate the associations of TMAO and choline with stroke recurrence. Among all patients, elevated TMAO and choline levels were associated with an increased risk of recurrent stroke (adjusted hazard ratios, 1.28 [95% CI, 1.12-1.45]; and 1.50 [95% CI, 1.32-1.71], respectively). Moreover, elevated TMAO and choline levels were associated with an increased risk of recurrent stroke among patients who received dual-antiplatelet therapy (1.65 [95% CI, 1.28-2.13]; and 1.70 [95% CI, 1.32-2.19], respectively), intensive lipid-lowering therapy (1.49 [95% CI, 1.15-1.94]; and 1.49 [95% CI, 1.15-1.92], respectively), with high-sensitivity C-reactive protein <2 mg/L (1.39 [95% CI, 1.14-1.69]; and 1.88 [95% CI, 1.53-2.30], respectively), and concurrently received dual-antiplatelet therapy, intensive lipid-lowering therapy and with high-sensitivity C-reactive protein <2 mg/L (3.57 [95% CI, 1.73-7.38]; and 2.19 [95% CI, 1.16-4.16], respectively). Conclusions TMAO and choline were risk factors for recurrent stroke independent of dual-antiplatelet therapy, intensive lipid-lowering therapy at discharge, and low inflammation on admission.

Effects of individual and integrated cumulative burden of blood pressure, glucose, low-density lipoprotein cholesterol, and C-reactive protein on cardiovascular risk.

AIM: This study aimed to demonstrate the impact of cumulative burden of cardiovascular risk factors (CVRFs) on risk of cardiovascular events (CVEs). METHODS AND RESULTS: A total of 34 959 participants were enrolled who participated in the four surveys during 2006-2013. Cumulative CVRF burden was calculated as number of years (2006-2013) multiplied by the values of CVRFs including systolic blood pressure, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), and high-sensitive C-reactive protein (hs-CRP). The primary outcome was defined as the CVE during 2012-2017, including ischaemic stroke, myocardial infarction, and all-cause mortality. During 4.62 (±0.71) years follow-up on average, there were 2118 (6.06%) CVE, including 847 (2.42%) ischaemic stroke, 221 (0.63%) myocardial infarction, and 1185 (3.39%) all-cause mortality. Higher cumulative burden of individual CVRF was significantly associated with increased risk of outcomes, except for LDL-C for all-cause mortality, FBG for myocardial infarction, and hs-CRP for ischaemic stroke. In Cox proportional hazards model, compared with the group, of the lower quartile of integrated cumulative burden, the hazard ratio (95% confidence intervals) of the upper quartile was 2.45 (2.03-2.94) for CVE, 3.65 (2.68-4.96) for ischaemic stroke, 4.51 (2.19-9.27) for myocardial infarction, and 1.73 (1.36-2.21) for all-cause mortality. CONCLUSION: We demonstrated the correlation between cumulative burden of CVRFs and cardiovascular risk, except for cumulative burden of hs-CRP and ischaemic stroke. Thus, our study suggests the necessity to extend the observation duration of CVRFs in order to elucidate the life-course cumulative effect.

The role of urinary albumin-to-creatinine ratio as a biomarker to predict stroke: A meta-analysis and systemic review.

Albuminuria excretion rate, calculated as urinary albumin-to-creatinine ratio (UACR), is used clinically to evaluate albuminuria. There are different attitudes to whether high UACR predicts higher risk of stroke. The aim of this study was to evaluate the relationship between UACR and stroke. Two investigators independently searched MEDLINE, EMBASE, Cochrane Controlled Trials Register Database, Scopus and Google Scholar from January 1966 through June 2021 were screened. In addition, a manual search was conducted using the bibliographies of original papers and review articles on this topic. Two blinded reviewers abstracted the data independently to a predefined form. Among the 10,939 initially identified studies, 7 studies with 159,302 subjects were finally included. It is demonstrated that UACR predicted an increased risk of stroke using cutoff value of either 0.43 (HR, 2.39; 95% CI: 1.24 - 4.61; P <0.01), 10 mg/g (HR, 1.60; 95% CI: 1.30 - 1.97; P < 0.01) or 30 mg/g (HR, 1.84; 95% CI: 1.49 - 2.28; P < 0.01). The overall analysis confirmed that high UACR was associated with an increased rate of stroke (HR, 1.81; 95% CI: 1.52 - 2.17; P < 0.01). Furthermore, High UACR predicted higher risk of stroke in local inhabitants (HR, 1.67; 95% CI: 1.17 - 2.37; P = 0.04), adults (HR, 2.21; 95% CI: 2.07 - 2.36; P < 0.01) or elderly adults (HR, 1.96; 95% CI: 1.56 - 2.46; P < 0.01). Whereas, high UACR was unable to predict stroke in patients with either T2DM (HR, 2.25; 95% CI: 0.55 - 9.17; P = 0.26) or hypertension (HR, 0.95; 95% CI: 0.28 - 3.22; P = 0.93). Another subgroup analysis revealed that high UACR was associated with increased risk of ischemic stroke (HR, 1.60; 95% CI: 1.43 - 1.80; P < 0.01), as well as hemorrhagic stroke (HR, 1.76; 95% CI: 1.22 - 1.45; P < 0.01). In conclusion, UACR is associated with an increased risk of hemorrhagic and ischemic stroke. UACR may be used as an indicator to predict stroke in non-diabetic and non-hypertensive subjects.

Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.

Background Trimethyllysine, a trimethylamine N-oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Methods and Results Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR-III (Third China National Stroke Registry) and 1-year follow-up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03-2.86) and all-cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40-2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N-oxide. Both estimated glomerular filtration rate and hs-CRP (high-sensitivity C-reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Conclusions Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.

Effect of Low Diastolic Blood Pressure to Cardiovascular Risk in Patients With Ischemic Stroke or Transient Ischemic Attacks Under Different Systolic Blood Pressure Levels.

Background: In the context of recently updated strategies of pressure management, there is a paucity of evidence on the effect of diastolic blood pressure (DBP) level on adverse events among stroke patients. This study aimed to examine the effect of low DBP (<60 mmHg) under different levels of systolic blood pressure (SBP) on the risk of composite events and stroke recurrence among patients with ischemic stroke (IS) or transient ischemic attack (TIA). Material and Methods: This study was conducted in 2,325 patients with IS or TIA. DBP values were categorized into <60, 60-70, 70-80 (reference), 80-90, and ≥90 mmHg in the main sample and were further categorized as <60 and ≥60 mmHg (reference) when patients were stratified according to SBP levels (<140, <130, and <120 mmHg). The outcomes were defined as recurrent stroke and cumulative composite events (defined as the combination of nonfatal myocardial infarction, nonfatal congestive heart failure, and death) at 1 year. Results: During 1 year of follow-up, a total of 95 composite events and 138 stroke recurrences were identified. The patients with low DBP showed a significantly higher risk of composite events [hazard ratio (HR) = 4.86, 95% confidence interval (CI) = 2.54-8.52], especially the elderly patients (≥60 years); however, this result was not observed for stroke recurrence (HR = 0.90, 95% CI = 0.46-1.74). With the reduction of the SBP levels, the proportion of patients with low DBP increased (6.87, 12.67, and 34.46%), and the risk for composite events persisted. Conclusions: Along with the new target levels of SBP suggested by updated criteria, there is a trend for DBP to be reduced to a harmfully low level, which was associated with an increased risk of composite events among patients with IS or TIA.

Different contribution of SBP and DBP variability to vascular events in patients with stroke.

BACKGROUND: High blood pressure variability (BPV) is a novel risk factor for cardiovascular disease. However, the heterogeneity of systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV) for different vascular events remains unclear. This study aims to investigate whether SBPV or DBPV has different contribution to vascular events in patients with acute ischaemic stroke (IS) or transient ischaemic attack (TIA). METHODS: Data from the BOSS (blood pressure and clinical outcome in TIA or IS) study were examined for vascular events at 3-month and 1-year follow-up. BPV was defined as the SD and coefficient of variation (CV) of day-to-day measurements within 3 months after IS/TIA. Vascular events include cardiovascular events (myocardial infarction, unstable angina, cardiac death and congestive heart failure) and cerebrovascular events (ischaemic or haemorrhagic stroke). Logistic regression model was used to test the associations between BPV and vascular events. RESULTS: Of 2325 patients with IS or TIA, 103 (4.43 %) experienced a recurrent stroke and 64 (2.75 %) had cardiovascular events within 3 months. Day-to-day SBPV was only associated with stroke recurrence (BPVSD: OR, 1.72, 95% CI 1.09 to 2.71; BPVCV: 1.86, 95% CI 1.19 to 2.92), but not cardiovascular events (BPVSD: 1.67, 95% CI 0.94 to 2.94; BPVCV: 1.51, 95% CI 0.86 to 2.64). However, DBPV seems to be related to both stroke (BPVSD: 1.60, 95% CI 1.02 to 2.49; BPVCV: 1.53, 95% CI 0.99 to 2.37) and cardiovascular events (BPVSD: 2.48, 95% CI 1.37 to 4.48; BPVCV: 1.92, 95% CI 1.09 to 3.36). Similar results were found at 1 year. CONCLUSIONS: For patients with IS/TIA, stroke recurrence was associated with both SBPV and DBPV; however, cardiovascular events seem to be only related to DBPV.

Uric Acid Contributes to Obesity-Paradox of the Outcome of Ischemic Stroke.

Background: The mechanism of obesity paradox in stroke is not clear. This study aimed to investigate whether uric acid (UA) contributes to obesity-stroke outcome paradox. Material and Methods: The study cohort consisted of 1,984 IS patients recruited in the ACROSS-China study. Serum UA and BMI were measured at admission. Low and high BMI groups were defined by the threshold of 24, and low and high UA by the age- and sex-specific median. Poor outcomes were defined as modified Rankin scale score ≥3 in 1 year after onset. Results: UA was significantly and positively correlated with BMI. Lower levels of UA and BMI were significantly associated with higher risk of poor outcomes. Incidence of the poor outcome was 34.5, 29.4, 27.7, and 23.5% in the BMI/UA groups of low/low, high/low, low/high and high/high, respectively, with p = 0.001 for trend. The association between low UA and poor outcome was significant in lower BMI groups (odds ratio = 1.36, p = 0.006 in quartile 1 and 1.28, p = 0.021 in quartile 2), but the odds ratios were not significant in the BMI quartile 3 and 4 groups, with p = 0.038 for trend. The adverse effect of lower UA was significant in males, but not in females, with p = 0.006 for sex difference. Conclusions: These findings suggest that low UA and low BMI have a joint effect on poor outcomes in IS patients. Across BMI categories, uric acid is differentially associated with functional outcome after stroke. This effect of low UA in the low BMI groups may be one of the mechanisms underlying the obesity-stroke paradox of the outcome in IS patients.

Acute-phase blood pressure trajectories and clinical outcomes in ischemic stroke.

High blood pressure (BP) is frequent in acute ischemic stroke (IS). However, the impact of BP change patterns during acute phase on clinical outcomes is not conclusive. This study aims to investigate the association between the acute-phase BP trajectories and clinical outcomes in IS patients with high admission BP. The cohort consisted of 316 IS patients with admission systolic BP (SBP) ≥160 mm Hg. SBP trajectories during the first 7 days after onset were characterized using a random effects model. The patients were classified into three groups based on the SBP trajectory curve parameters: sustained high SBP (T1), moderate decrease (T2), and rapid decrease in SBP (T3). Poor outcomes were defined as modified Rankin scale score ≥3 in 3 months after onset. The relationship between SBP trajectory groups and the outcome was examined in multivariable logistic regression models. The decreasing trend was greater in the favorable than in the poor outcome group (P = 0.028 for difference in linear slopes). The incidence of poor outcomes was 25.9%, 13.5%, and 9.8% in T1 (n = 54), T2 (n = 170), and T3 (n = 92) groups, respectively. Compared with T1 group, the decrease in SBP in T2 and T3 groups was significantly associated with lower risk of the poor outcome (odds ratio = 0.25, 95% confidence interval = 0.10-0.67, P = 0.006). These findings suggest that a decrease in BP in the acute phase is predictive of favorable outcomes in IS patients. BP trajectories have a greater power to detect the association than individual BP values at one time-point.