Characteristics of Subjects with Very Low Serum Low-Density Lipoprotein Cholesterol and the Risk for Intracerebral Hemorrhage

Lee, Jae-Geun; Koh, Sung Joo; Yoo, Jeong Rae; Yu, Jung Re; Lee, Sang Ah; Koh, Gwanpyo; Lee, Daeho

doi:10.3904/kjim.2012.27.3.317

Cited by 14 publications

(10 citation statements)

References 34 publications

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“…12 In a meta-analysis of 31 randomized controlled trials (patients without recent stroke), 9 statin therapy was not associated with an increased risk of ICH, but statin use was associated with a decreased risk of all types of stroke and decreased all-cause mortality. In another very large observational study, 24 incidence of ICH was not associated with either statin use or lowdensity lipoprotein level. One large observational study 25 re-ported that statin use was associated with an increased risk of symptomatic ICH in patients receiving thrombolytic treatment for acute ischemic stroke, despite also being associated with improved poststroke outcomes.…”

Section: Discussionmentioning

confidence: 89%

Effect of Statin Use During Hospitalization for Intracerebral Hemorrhage on Mortality and Discharge Disposition

et al. 2014

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IMPORTANCE Statin use during hospitalization is associated with improved survival and a better discharge disposition among patients with ischemic stroke. It is unclear whether inpatient statin use has a similar effect among patients with intracerebral hemorrhage (ICH). OBJECTIVE To determine whether inpatient statin use in ICH is associated with improved outcomes and whether the cessation of statin use is associated with worsened outcomes. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 3481 patients with ICH admitted to any of 20 hospitals in a large integrated health care delivery system over a 10-year period. Detailed electronic medical and pharmacy records were analyzed to explore the association between inpatient statin use and outcomes. MAIN OUTCOMES AND MEASURES The primary outcome measures were survival to 30 days after ICH and discharge to home or inpatient rehabilitation facility. We used multivariable logistic regression, controlling for demographics, comorbidities, initial severity, and code status. In addition, we used instrumental variable modeling to control for confounding by unmeasured covariates at the individual patient level. RESULTS Among patients hospitalized for ICH, inpatient statin users were more likely than nonusers to be alive 30 days after ICH (odds ratio [OR], 4.25 [95% CI, 3.46-5.23]; P < .001) and were more likely than nonusers to be discharged to their home or an acute rehabilitation facility (OR, 2.57 [95% CI, 2.16-3.06]; P < .001). Patients whose statin therapy was discontinued were less likely than statin users to survive to 30 days (OR, 0.16 [95% CI, 0.12-0.21]; P < .001) and were less likely than statin users to be discharged to their home or an acute rehabilitation facility (OR, 0.26 [95% CI, 0.20-0.35]; P < .001). Instrumental variable models of local treatment environment (to control for confounding by unmeasured covariates) confirmed that a higher probability of statin therapy was associated with a higher probability of 30-day survival (with an increase in probability of 0.15 [95% CI, 0.04-0.25]; P = .01) and a better chance of being discharged to home or an acute rehabilitation facility (with an increase in probability of 0.13 [95% CI, 0.02-0.24]; P = .02). CONCLUSIONS AND RELEVANCE Inpatient statin use is associated with improved outcomes after ICH, and the cessation of statin use is associated with worsened outcomes after ICH. Given the association between statin cessation and substantially worsened outcomes, the risk-benefit balance of discontinuing statin therapy in the acute setting of ICH should be carefully considered.

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Section: Discussionmentioning

confidence: 89%

Effect of Statin Use During Hospitalization for Intracerebral Hemorrhage on Mortality and Discharge Disposition

et al. 2014

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“…It is reasonable to note, however, that no mechanism for vessel damage or loss of vessel structural integrity due to low cholesterol has been experimentally well established, and this remains a poorly understood relationship. Focusing on patients with very low LDL cholesterol levels, no association between low levels of LDL-cholesterol related to statins and risk of ICH could be found [30]. Similarly, LDL levels at baseline and during treatment were not related to hemorrhage risk in the SPARCL trial [7].…”

Section: Potential Effects Of Statins On Risk Of Intracerebral Hemorrmentioning

confidence: 93%

Statins in Intracerebral Hemorrhage

Lauer

Greenberg

Gurol

2015

Curr Atheroscler Rep

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While statins play an indisputable role in primary and secondary prevention of ischemic cardiovascular and cerebrovascular disease, a concern exists regarding a possible association between low lipoprotein levels and statin use on the risk of intracerebral hemorrhage (ICH). While these data may incline physicians to discontinue statins after ICH, an increasing amount of preclinical and clinical evidence suggests that statins might have a beneficial effect on outcome and recovery in this context that goes beyond lipid lowering effects. Different etiologies of ICH and the related risk of recurrence should also be taken into account when deciding about statin use/avoidance in patients with high risk of ICH. The problem is compounded by paucity of data from randomized controlled trials and well-designed prospective observational studies. This review will discuss the existing evidence on potential interactions between statins and risk of ICH as well as outcomes in order to provide practical recommendations for clinical decision-making.

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“…Our observations also suggest that absolute levels of serum lipid measurements may not be biologically relevant for stroke risk associations. 35 This may be of relevance in informing designs of future prospective clinical trials for lipid biomarkers or lipid-lowering agents in stroke. Given our study limitations, these findings should be considered hypothesis-generating at present, and future studies are needed to replicate these results in prospective cohorts, probe for potential mediation effects between TC and LDL, and further characterize changes in serum lipid trends as a potential biomarker of impending acute cerebral injury.…”

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confidence: 99%

Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage

et al. 2016

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Objective: We aimed to describe the temporal variation in circulating lipid levels among patients with intracerebral hemorrhage (ICH) and investigate their association with ICH risk.Methods: This was a single-center, retrospective, longitudinal, case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a hospital-based clinical data registry. Piecewise linear mixed-effect random coefficient models were used to determine the significance of changes in serum lipid trends on ICH risk.Results: Two hundred twelve ICH cases and 301 control individuals were analyzed. Overall trends in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels differed between ICH cases and non-ICH controls (p 5 0.00001 and p 5 0.0092, respectively). Patients with ICH experience accelerated decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 and 24 months pre-ICH (TC: 229.25 mg/dL, p 5 0.001; LDL: 221.48 mg/dL, p 5 0.0038), which was not observed in non-ICH controls. Subgroup analysis confirmed that this phenomenon cannot be attributed to statin or alcohol exposure. Serum triglycerides and high-density lipoprotein trends did not differ between groups.Conclusions: Longitudinal lipid levels differ between ICH cases and non-ICH controls, most notably for a decline in serum TC and LDL levels within 6 months preceding primary ICH, independent of statin or alcohol use. These changes in serum TC and LDL trends suggest a biological pathway that precipitates ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury. Growing evidence supports a paradoxical role of dyslipidemia in cerebrovascular disease.

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Characteristics of Subjects with Very Low Serum Low-Density Lipoprotein Cholesterol and the Risk for Intracerebral Hemorrhage

Cited by 14 publications

References 34 publications

Effect of Statin Use During Hospitalization for Intracerebral Hemorrhage on Mortality and Discharge Disposition

Effect of Statin Use During Hospitalization for Intracerebral Hemorrhage on Mortality and Discharge Disposition

Statins in Intracerebral Hemorrhage

Subacute decline in serum lipids precedes the occurrence of primary intracerebral hemorrhage

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