Deqin Geng

Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke: The CATIS Randomized Clinical Trial

IMPORTANCE Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain. OBJECTIVE To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS The China Antihypertensive Trial in Acute Ischemic Stroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013. INTERVENTIONS Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURES Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 14 days or hospital discharge. RESULTS Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (-12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (-7.2%) in the control group within 24 hours after randomization (difference, -5.5% [95% CI, -4.9 to -6.1%]; absolute difference, -9.1 mm Hg [95% CI, -10.2 to -8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, -9.3 mm Hg [95% CI, -10.1 to -8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93). CONCLUSION AND RELEVANCE Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01840072.

Serum matrix metalloproteinase-9 levels and prognosis of acute ischemic stroke

Objective: To examine the association between serum matrix metalloproteinases-9 (MMP-9) levels and prognosis of acute ischemic stroke. Methods: We measured serum MMP-9 levels in 3,186 participants (2,008 men and 1,178 women) from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular disease were collected at 3 months after stroke onset. Results: During 3 months of follow-up, 767 participants (24.6%) experienced major disability or died. Serum MMP-9 was significantly associated with an increased risk of death and major disability after adjustment for age, sex, time from onset to randomization, current smoking, alcohol drinking, admission NIH Stroke Scale score, diastolic blood pressure, plasma glucose, white blood cell counts, use of antihypertensive medications, and history of hypertension, coronary heart disease, and diabetes mellitus. For example, 1-SD (0.32 ng/mL) higher log–MMP-9 was associated with an odds ratio (95% confidence interval) of 1.16 (1.06–1.28) for the combined outcome of death and major disability, 1.12 (1.01–1.23) for major disability, and 1.29 (1.01–1.66) for death. The addition of serum MMP-9 to conventional risk factors improved risk prediction of the combined outcome of death or major disability (net reclassification index 9.1%, p = 0.033; integrated discrimination improvement 0.4%, p = 0.004). Conclusions: Higher serum MMP-9 levels in the acute phase of ischemic stroke were associated with increased risk of mortality and major disability, suggesting that serum MMP-9 could be an important prognostic factor for ischemic stroke.

Blood pressure reduction in acute ischemic stroke according to time to treatment: a subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke trial

Objective: The optimal time to initiate antihypertensive therapy among patients with acute ischemic stroke remains uncertain. We tested the effects of blood pressure reduction among patients with acute ischemic stroke according to time from onset to initiation of antihypertensive treatment. Methods: We randomly assigned 4071 acute ischemic stroke patients with elevated SBP to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. The primary outcome was a combination of death and major disability, and secondary outcomes included the modified Rankin score, recurrent stroke, vascular disease events, and all-cause mortality. Results: At 24 h after randomization, the differences in SBP reductions were 8.7, 9.5, and 9.6 mmHg between the antihypertensive treatment and control groups among patients receiving treatment within less than 12, 12–23, and 24–48 h after stroke onset, respectively (P < 0.001 in all subgroups). At day 14 or hospital discharge, the primary and secondary outcomes were not significantly different between the treatment and control groups in all subgroups. At the 3-month follow-up, death or major disability [odds ratio (OR) 0.73; 95% confidence interval (CI) 0.55–0.96; P = 0.03], recurrent stroke (OR 0.25; 95% CI 0.08–0.74; P = 0.01), and vascular events (OR 0.41; 95% CI 0.18–0.95; P = 0.04) were significantly reduced in the antihypertensive treatment group only among participants who received treatment between 24 and 48 h. Conclusion: Blood pressure reduction might reduce 3-month death and major disability and recurrent stroke among patients with acute ischemic stroke who receive antihypertensive treatment between 24 and 48 h after stroke onset. Trial registration: ClinicalTrials.gov Identifier: NCT01840072

Serum 25-hydroxyvitamin D deficiency predicts long-term poor prognosis among ischemic stroke patients without hyperglycaemia

BACKGROUND It is unclear whether 25-hydroxyvitamin D [25(OH)D] has a protective effect on long-term prognosis of ischemic stroke and whether it is affected by blood glucose levels. We aim to examine the effect of serum vitamin D especially its deficiency on 1-year poor outcome of ischemic stroke patients in total patients and by blood glucose subgroups. METHODS A total of 3041 ischemic patients from China Antihypertensive Trial in Acute Ischemic Stroke were included. The serum concentrations of 25(OH)D were measured at baseline. All subjects were followed up for death and vascular events at 1year after acute ischemic stroke. RESULTS Among total ischemic stroke patients and those with hyperglycemia, 25(OH)D deficiency was not associated with the risk of vascular events and death. In the normoglycemic subgroup, 25(OH)D deficiency subjects had a significantly higher risk of poor prognosis compared with those with 25(OH)D≥20ng/ml. The hazard ratio (95% confidence interval) was 1.58(1.04-2.41) in the multivariable adjusted model (P for linear trend=0.02). CONCLUSION Serum 25(OH)D deficiency may be merely an independent risk factor of 1-year poor prognosis in ischemic stroke patients without hyperglycemia. Future studies about improving long-term prognosis of ischemic stroke by vitamin D supplementation could be first applied to these patients.

Antiphosphatidylserine Antibodies and Clinical Outcomes in Patients With Acute Ischemic Stroke

Background and Purpose— Antiphosphatidylserine antibodies (aPS) have been associated with the risk of ischemic stroke. However, it remains unclear whether aPS will influence clinical outcomes in patients with acute ischemic stroke. Methods— A total of 3013 patients with acute ischemic stroke recruited from 26 hospitals across China from August 2009 to May 2013 were included in the study The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes included death, major disability, recurrent stroke, and vascular events. Results— Composite outcome of death and major disability rates were 29.1% versus 23.9% in aPS-positive and aPS-negative groups. Compared with aPS-negative, adjusted odds ratios or hazard ratios (95% confidence interval) associated with aPS-positive were 1.35 (1.07–1.71), 1.63 (0.99–2.69), and 1.25 (0.98–1.59) for composite outcome of death or major disability, death, and major disability, respectively. For 1 interquartile range increase of aPS, the adjusted odds ratios or hazard ratios were 1.10 (1.01–1.20), 1.19 (1.05–1.35), and 1.05 (0.96–1.14), respectively. Adding aPS status to a model containing conventional risk factors improved risk prediction for composite outcome of death or major disability (net reclassification improvement index=11.3%, P=0.006; integrated discrimination improvement=0.2%, P=0.04). There was no significant association between aPS and risks of recurrent stroke and vascular events. Conclusions— We found that positive aPS increased risks of death or major disability at 3 months after an acute ischemic stroke, suggesting that aPS might be a prognostic marker for ischemic stroke.

Serum Galectin-3 and Poor Outcomes Among Patients With Acute Ischemic Stroke

Background and Purpose— Elevated galectin-3 has been associated with atherosclerosis and poor outcomes in patients with heart failure. However, it remains unclear whether galectin-3 has any effect on the poor outcomes of ischemic stroke. The aim of the present study was to examine the association between galectin-3 with poor outcomes among patients with acute ischemic stroke. Methods— Serum galectin-3 was measured in 3082 patients with acute ischemic stroke. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after stroke. Results— Compared with the lowest quartile of galectin-3, multivariate adjusted odds ratios (95% confidence intervals) for the highest quartile of galectin-3 were 1.55 (1.15–2.09) for composite outcome, 2.10 (0.89–4.95) for death, and 1.43 (1.05–1.93) for major disability. The addition of galectin-3 to the conventional risk factors significantly improved prediction of the combined outcome of death or major disability in patients with ischemic stroke (net reclassification index, 18.9%; P<0.001; integrated discrimination improvement, 0.4%; P=0.001). Conclusions— Higher levels of serum galectin-3 were independently associated with increased risk of death or major disability after stroke onset, suggesting that galectin-3 may have prognostic value in poor outcomes of ischemic stroke.

Serum 25-hydroxyvitamin D deficiency predicts poor outcome amongst acute ischaemic stroke patients with low high density lipoprotein cholesterol

Current observational studies indicate that a lower vitamin D level is associated with a higher risk of poor ischaemic stroke prognosis. Whether this association is affected by lipid levels is unclear. Our aim was to examine the effect of serum vitamin D especially its deficiency on the global outcome of ischaemic stroke stratified by individual lipid component level.

Sex-specific Association Between Uric Acid and Outcomes After Acute Ischemic Stroke: A Prospective Study from CATIS Trial

The relationship between serum uric acid (UA) and outcomes after acute ischemic stroke remains debatable in human studies, and the sex effect on this association has yet to be explored. Here, we investigated these associations in a prospective study from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline UA levels were measured in 3284 acute ischemic stroke patients. Primary outcome was defined as a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months. UA levels were significantly higher in men than women (310.6 ± 96.1 vs 257.5 ± 89.9 μmol/L, P < 0.001). The association between serum UA and the primary outcome was appreciably modified by sex (P-interaction = 0.007). After multivariate adjustment, a high serum UA was associated with a decreased risk of primary outcome in men [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44–0.91; P-trend = 0.01] but not in women (OR, 1.29; 95% CI, 0.83–2.01; P-trend = 0.15), when two extreme quartiles were compared. Subgroup and sensitivity analyses further confirmed these sex-specific findings. Our study indicated that there was a sex-specific association between serum UA and prognosis of acute ischemic stroke. Elevated serum UA was positively associated with better prognosis in men, but not in women.

Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke

Background and Purpose— Serum hepatocyte growth factor (HGF) is positively associated with poor prognosis of heart failure and myocardial infarction, and it can also predict the risk of ischemic stroke in population. The goal of this study was to investigate the association between serum HGF and prognosis of ischemic stroke. Methods— A total of 3027 acute ischemic stroke patients were included in this post hoc analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months. Results— After multivariate adjustment, elevated HGF levels were associated with an increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval, 1.10–2.03; Ptrend=0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed HGF was associated with 14% (95% confidence interval, 2%–27%) increased risk of primary outcome. Adding HGF quartiles to a model containing conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 17.50%, P<0.001; integrated discrimination index: 0.23%, P=0.022). The association between serum HGF and primary outcome could be modified by heparin pre-treatment (Pinteraction=0.001), and a positive linear dose–response relationship between HGF and primary outcome was observed in patients without heparin pre-treatment (Plinearity<0.001) but not in those with heparin pre-treatment. Conclusions— Serum HGF levels were higher in the more severe stroke at baseline, and elevated HGF levels were probably associated with 3-month poor prognosis independently of stroke severity among ischemic stroke patients, especially in those without heparin pre-treatment. Further studies from other samples of ischemic stroke patients are needed to validate our findings.

Prognostic Value of White Blood Cell in Acute Ischemic Stroke Patients

BACKGROUND AND AIMS It is unclear whether white blood cell on admission has a prognosis value on ischemic stroke and whether its function is affected by other inflammation factors. We hypothesized that elevated white blood cell is associated with stroke severity and 3-month mortality after acute ischemic stroke. METHODS A total of 3891 acute ischemic stroke subjects from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) were included in this analysis. Participants were divided into four groups according to quartiles of white blood cell on admission (cutoff points for the quintiles: 5.60×109/L,6.83×109/L,8.50×109/L). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months. Secondary outcomes were major disability, death, and vascular events, respectively. RESULTS After adjustment for major conventional risk factors, elevated white blood cell on admission was associated with poor primary and secondary outcomes after acute ischemic stroke. Compared with the lowest quartile, the ORs (95% CIs) for the highest quartile were 1.79 (1.37-2.91) and 1.62 (1.21-3.55) for primary outcome in model 1 and model 2. In addition, there was a linear association between white blood cell and primary outcome at 3-months (P for linear trend = 0.001). CONCLUSION This analysis indicated that elevated white blood cell on admission is associated with 3-months poor prognosis in ischemic stroke patients independently of other inflammation factors. The results emphasize the need for further research on the application of anti-inflammatory therapy.