Cholesterol Levels and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis
Hou et al performed a meta-analysis to investigate the potential association between different categories of cholesterol and risk of cerebral hemorrhage. They included prospective studies published between 1980 and 2013 that reported on an association between cholesterol (total serum cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol) and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage). Twenty-three studies including American, European, and Asian populations were selected for the final meta-analysis involving 1 430 141 participants with 7960 (5.6%) ICH or subarachnoid hemorrhage events. Using the random effects model summary, relative risks and 95% confidence intervals (CIs) for high versus low levels of cholesterol were calculated. Dose–response analyses were performed to estimate the relative risks and 95% CIs per 1 mmol/L increment of cholesterol concentration. Comparing high versus low levels, an inverse relationship between cholesterol levels and risk of ICH/subarachnoid hemorrhage risk was noted: 0.69 (95% CI, 0.59–0.81) for total cholesterol and 0.98 (95% CI, 0.80–1.19) for low-density lipoprotein cholesterol. In dose–response analyses, the relative risk of hemorrhagic stroke per 1 mmol/L increment of total serum cholesterol was 0.85 (95% CI, 0.80–0.91) and for low-density lipoprotein cholesterol when excluding 1 study (95% CI, 0.86–0.996). No significant association between high-density lipoprotein cholesterol and hemorrhagic stroke was noted. Only when analyzed separately, the risk of ICH or subarachnoid hemorrhage significantly increased per 1 mmol/L high-density lipoprotein cholesterol increment. The authors caution that publication bias was detected in studies of total serum cholesterol, which might overestimate the inverse relationship because harmful associations might have been more frequently published. Several included studies reported on hemorrhagic stroke precluding distinction between hemorrhage subtypes, and the use of statins was not described. Although these results do not help guide the treatment of individual patients, this meta-analysis provides further evidence for the presumed, but poorly understood, link between cholesterol levels and risk for ICH on a large public-health scale. See p 1833.
Diabetes Mellitus, Admission Glucose, and Outcomes After Stroke Thrombolysis: A Registry and Systematic Review
Poststroke hyperglycemia is common and associated with poor clinical outcome and death. Desilles et al evaluated the potential association between diabetes mellitus history or admission glucose level (AGL) on outcome in acute ischemic stroke patients treated by intravenous and intraarterial therapy included in their prospective clinical registry (n=709; Bichat University Hospital). The primary study outcome was the percentage of patients who achieved a 90-day modified Rankin Scale score of 0 to 2. Secondary outcomes included 90-day modified Rankin Scale score of 0 to 1, early neurological improvement, any recanalization, complete recanalization, 90-day mortality, hemorrhagic complications, and symptomatic intracerebral hemorrhage. Early recanalization status was assessed in a subset of patients undergoing endovascular therapy (n=240). Within their registry, history of diabetes mellitus was not associated with the primary or secondary outcomes. Conversely, AGL was associated with all outcomes, except with early neurological improvement. There was no significant difference in recanalization rates between the diabetes mellitus subgroups. Subsequently, the authors investigated the potential association between diabetes mellitus, AGL, and outcome by performing a systematic review of previous observational studies (including their registry data). This meta-analysis indicated that the incidence of good outcome was significantly lower in patients with history of diabetes mellitus compared with those without. Symptomatic intracranial hemorrhage was not significantly associated with history of diabetes mellitus. Patients with good outcome had a significantly lower AGL than patients without good outcome, and patients without symptomatic intracranial hemorrhage had a significantly lower AGL than patients with symptomatic intracranial hemorrhage. Together, these data highlight that history of diabetes mellitus and higher AGL contribute to various measures of worse outcome but that the underlying pathophysiology of this association may likely be different. See p 1915.
Effects of Candesartan in Acute Stroke on Cognitive Function and Quality of Life: Results From SCAST
Hypertension is detected in >60% of patients with acute ischemic stroke. The Scandinavian Candesartan Acute Stroke Trial (SCAST) studied whether the angiotensin receptor blocker Candesartan improved 6-month outcome compared with placebo. Although treated patients had significantly lower blood pressure values during the first week, there was no beneficial impact on outcome, and this trial was stopped early because of slow recruitment. Now, Hornslien et al examined whether Candesartan given in the acute phase of stroke may prevent cognitive impairment and low quality of life as suggested by previous studies. Cognitive function at 6 months was assessed by the Mini Mental State Examination (MMSE), and quality of life was measured by the EuroQol instrument (EQ-5D) and a summary visual analog scale (EQ-VAS) score. Of the 2 029 patients included in the trial, data on MMSE scores, EQ-5D indices, and EQ-VAS scores were available in 1644 (81%), 1734 (85%), and 1697 (84%) patients, respectively. Ordinal regression analysis showed a small, nonsignificant difference between the distribution of MMSE scores in the 2 groups disfavoring Candesartan (odds ratio, 1.11; 95% confidence interval, 0.91–1.34). Multivariable linear regression analysis showed a significant difference between EQ-5D disfavoring Candesartan, which was also noted when the 5 individual EQ-5D domains were tested separately. Finally, there was no difference between the mean EQ-VAS scores of treated versus untreated patients. This study was not powered to reliably detect differences in these outcomes, and the follow-up period was relatively short. Nevertheless, considering that Candesartan did not reduce the risk for recurrent stroke in SCAST, these results seem consistent with the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), which did not show a clear effect on either dementia or cognitive decline in the absence of recurrent stroke. This highlights that antidementive effects of antihypertensives, such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are likely linked to their ability to reduce the risk for further strokes. See p 2022.
- © 2013 American Heart Association, Inc.