Stroke is the second leading cause of death and the leading cause of serious, long-term disability worldwide.¹ Clinical trials have documented that lowering blood pressure reduces the risk of stroke in hypertensive^2,3 and normotensive patients with a history of stroke or transient ischemic attack.^4-6 Although the benefit of lowering blood pressure for primary and secondary prevention of stroke has been established, the effect of immediate antihypertensive treatment in patients with acute ischemic stroke and elevated blood pressure is uncertain.^7,8 Elevated blood pressure is common during acute ischemic stroke. In the US National Hospital Ambulatory Medical Care Survey, 76.5% of patients with acute ischemic stroke had systolic blood pressures of 140 mm Hg or greater on arrival at the emergency department.⁹ Observational studies have reported that a decrease in blood pressure within the first 48 hours after symptom onset was associated with poorer, better, or no difference in adverse clinical outcomes among patients with acute ischemic stroke.^10-12 There are no published clinical trials with sufficient statistical power to address the question of whether lowering blood pressure reduces adverse clinical outcomes among patients with acute ischemic stroke.

Background: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations. Methods: A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations. Results: During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index’s association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio’s association with CVD, respectively. Conclusions: Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension.

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.

Background: Conflicting findings of the association between serum uric acid ( UA ) and stroke have been reported in both men and women, and it is unclear whether this association was different between men and women. We preformed this meta‐analysis to assess the sex‐specific effect of serum UA on the risk of stroke and its subtypes. Methods and Results: Prospective studies that reported sex‐specific association of UA levels with stroke or reported in a certain sex were included. Dose‐response relationships were assessed by the generalized least squares trend estimation, and summary effect estimates were evaluated with random‐effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Altogether, 13 prospective studies were identified in this study. The summary of relative risks (95% CIs) of stroke for a 1‐mg/dL increase in serum UA levels were 1.10 (1.05–1.14) for men and 1.11 (1.09–1.13) for women. There is no significant difference in the effect of UA on future stroke risk between men and women ( P _interaction =0.736). Subgroup analyses showed that the significant associations persisted in most stratifications, and sensitivity analyses according to various inclusion criteria yielded similar results. A nonlinear relationship was observed in men ( P _{non‐linearity} <0.001), with risk increasing significantly from a UA of 6 mg/dL and more steeply at higher UA levels. Conclusions: Elevated serum UA levels were significantly associated with modestly increased risk of stroke in both men and women and have similar adverse effects on development of stroke in both sexes.