Cerebrovascular Disease and Statins

Elevated low-density lipoprotein-cholesterol (LDL-C) is a causal factor for the development of atherosclerotic cardiovascular disease (ASCVD); accordingly, LDL-C lowering is associated with a decreased risk of progression of atherosclerotic plaques and development of complications. Currently, statins play a central role in any ASCVD management and prevention strategies, in relation to their lipid-lowering action and potentially to pleiotropic effects. After coronary artery disease, stroke is the most frequent cause of ASCVD mortality and the leading cause of acquired disability, a major public health problem. There is often a tendency to aggregate all types of stroke (atherothrombotic, cardioembolic, and haemorrhagic), which have, however, different causes and pathophysiology, what may lead to bias when interpreting the results of the studies. Survivors of a first atherothrombotic ischemic stroke are at high risk for coronary events, recurrent stroke, and vascular death. Although epidemiological studies show a weak relationship between cholesterol levels and cerebrovascular disease as a whole compared with other ASCVD types, statin intervention studies have demonstrated a decrease in the risk of stroke in patients with atherosclerosis of other territories and a decrease in all cardiovascular events in patients who have had a stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial demonstrated the benefit of high doses of atorvastatin in the secondary prevention of ischemic stroke. In this review, we discuss the evidence, use and recommendations of statins in the primary and secondary prevention of stroke, and their role in other scenarios such as the acute phase of ischemic stroke, cerebral hemorrhage, cardioembolic stroke, small vessel disease, and cognitive impairment.

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Causes and Secondary Prevention of Acute Ischemic Stroke in Adults

Hämostaseologie ◽

10.1055/s-0039-1700502 ◽

2019 ◽

Vol 40 (01) ◽

pp. 022-030 ◽

Cited By ~ 1

Author(s):

Märit Jensen ◽

Götz Thomalla

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Secondary Prevention ◽

Small Vessel Disease ◽

Recurrent Stroke ◽

Intravenous Thrombolysis ◽

Large Artery ◽

Symptomatic Carotid ◽

Symptomatic Carotid Stenosis ◽

Increased Risk

AbstractStroke still remains a major cause of death and disability worldwide. Ischemic stroke is the most common type of stroke. Causes of ischemic stroke can be classified into large-artery atherosclerosis, cardiogenic embolism, small-vessel disease, stroke of other determined etiology, and stroke of undetermined etiology. Stroke causes in adults are mainly attributable to classical cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, and smoking. In neuroimaging, stroke subtypes can be defined according to lesion localization and distribution (territorial infarct, lacunar infarct, hemodynamic infarct), which provide information as to the underlying etiology. Acute stroke management comprises rapid neurological assessment and rapid imaging to initiate effective reperfusion treatment with intravenous thrombolysis and mechanical thrombectomy. Stroke survivors are at increased risk of recurrent stroke. Therefore, diagnosis of the underlying cause and optimal secondary prevention is of importance. Pharmacologic secondary prevention includes antithrombotic therapy with antiplatelet drugs, oral anticoagulation, and treatment of vascular risk factors. Nonpharmacologic measures of secondary prevention comprise surgical or interventional revascularization of symptomatic carotid stenosis and interventional closure of patent foramen ovale.

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Evaluation on the compliance with secondary prevention and influence factors of ischemic stroke in Hainan province, China

Vascular ◽

10.1177/1708538113484022 ◽

2013 ◽

Vol 22 (3) ◽

pp. 181-187 ◽

Cited By ~ 5

Author(s):

Qingjie Su ◽

Kunxiong Yuan ◽

Faqing Long ◽

Zhongqin Wan ◽

Chaoyun Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Health Education ◽

Secondary Prevention ◽

Antiplatelet Therapy ◽

Influence Factors ◽

Significant Risk ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Logistic Regression Models ◽

Prevention Therapy

Survivors of ischemic stroke are still at a significant risk for recurrence. Numerous effective strategies for the secondary prevention of ischemic stroke have now been established; however, these guidelines are not widely known. In this retrospective, a multicenter study was conducted from January 2011 to February 2012 in 10 general hospitals, which included 1300 elderly patients who had previously been diagnosed with ischemic stroke and re-admitted to hospitals. Logistic regression models were fitted to determine the relationship between compliance with secondary prevention therapy and each variable of interest. The treatment rates of antihypertensive, antiplatelet and lipid-lowering therapy were only 56.3%, 48.9% and 19.6%, respectively. Multivariate analysis presented that cardiovascular risk factors would motivate patients with hypertension and hyperlipidemia to receive corresponding treatments. However, it is worth noting that they did not influence the use of antiplatelet therapy. In addition, high education, health education and insurance promote the use of secondary prevention in patients. In conclusion, the importance of antiplatelet therapy should not be ignored any more. Besides, health education will raise patients’ attention to ischemic stroke.

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2014 Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack

International Journal of Stroke ◽

10.1177/1747493017694391 ◽

2017 ◽

Vol 12 (3) ◽

pp. 302-320 ◽

Cited By ~ 24

Author(s):

Yongjun Wang ◽

Ming Liu ◽

Chuanqiang Pu

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Transient Ischemic Attack ◽

Recurrent Stroke ◽

Stroke Recurrence ◽

Evidence Based ◽

Cerebrovascular Disorder ◽

Level Of Evidence ◽

Vascular Stenosis ◽

Ischemic Attack

Ischemic stroke and transient ischemic attack (TIA) are the most common cerebrovascular disorder and leading cause of death in China. The Effective secondary prevention is the vital strategy for reducing stroke recurrence. The aim of this guideline is to provide the most updated evidence-based recommendation to clinical physicians from the prior version. Control of risk factors, intervention for vascular stenosis/occlusion, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke are all recommended, and the prevention of recurrent stroke in a variety of uncommon causes and subtype provided as well. We modified the level of evidence and recommendation according to part of results from domestic RCT in order to facility the clinical practice.

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Abstract T MP57: Coexisting Cerebrovascular Disease and Risk of Occult Atrial Fibrillation in Patients With Embolic Stroke of Undetermined Source

Stroke ◽

10.1161/str.46.suppl_1.tmp57 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Esther Rojo ◽

María Sandín-Fuentes ◽

Ana I Calleja ◽

Gabriel Largaespada ◽

Elisa Cortijo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Secondary Prevention ◽

Cerebrovascular Disease ◽

Cox Regression ◽

Small Vessel Disease ◽

Brain Magnetic Resonance Imaging ◽

Embolic Stroke ◽

Small Vessel ◽

Large Artery ◽

Vessel Disease

Background and objective: Secondary prevention after embolic stroke of undetermined source (ESUS) remains a clinical problem. Presence of asymptomatic cerebral large-artery atherosclerosis or small vessel disease could be aprioristically taken as an indicator of a lower risk for an occult cardiac source of emboli, thus influencing our secondary prevention strategy. We aimed to study the relationship between presence and degree of coexisting cerebrovascular disease and the risk of occult paroxysmal atrial fibrillation (OPAF) in ESUS patients. Methods: Longitudinal prospective study in patients fulfilling ESUS criteria after complete neurovascular and cardiac diagnostic workup, who were implanted with a subcutaneous REVEAL-XT loop-recorder to detect OPAF and followed-up for≥ 6 months. At baseline, cerebral large-artery atherosclerosis was assessed with cervical and transcranial ultrasound. Brain magnetic resonance imaging was used to evaluate small vessel disease. Periventricular (PV) and subcortical (SC) white matter hiperintensities (WMH) were categorized using the Fazekas score. Results: We studied 136 ESUS patients from October 2010 to December 2013 (71 men, mean age 67), who were followed-up for a mean time of 594 days. OPAF was detected in 56 (41%) of them. No relationship was found between extracranial or intracranial atherosclerosis and OPAF. Kaplan-Meier curves and crude Cox-regression analyses found associations between OPAF risk and age, smoking, CHA2DS2VASC score, presence of lacunar infarctions, and presence and degree of PVWMH & SCWMH. A multivariable-adjusted Cox regression model identified grade 2-3 PVWMH (HR 3.6, [2.0-6.5], p<0.001) and age as independent predictors of OPAF. Conclusion: Coexisting small vessel disease, specifically in the form of periventricular WMH, is a predictor of OPAF in ESUS patients. Presence of large-artery atherosclerosis does not lower the risk for OPAF. Therefore, OPAF should be actively pursued in ESUS patients regardless the coexistence of asymptomatic cerebrovascular disease.

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Baseline D-Dimer Levels as a Risk Assessment Biomarker for Recurrent Stroke in Patients with Combined Atrial Fibrillation and Atherosclerosis

Journal of Clinical Medicine ◽

10.3390/jcm8091457 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1457 ◽

Cited By ~ 2

Author(s):

Kang-Ho Choi ◽

Woo-Keun Seo ◽

Man-Seok Park ◽

Joon-Tae Kim ◽

Jong-Won Chung ◽

...

Keyword(s):

Atrial Fibrillation ◽

Risk Assessment ◽

Ischemic Stroke ◽

Confidence Interval ◽

Secondary Prevention ◽

Primary Outcome ◽

Outcome Measure ◽

Recurrent Stroke ◽

Primary Outcome Measure ◽

D Dimer

Background: We investigated the effect of D-dimer levels and efficacy of different antithrombotic therapies according to the baseline D-dimer levels on recurrent stroke in patients with atrial fibrillation (AF)-related stroke and atherosclerosis. Methods: We enrolled 1441 patients with AF-related stroke and atherosclerosis in this nationwide multicenter study. The primary outcome measure was the occurrence of recurrent ischemic stroke over a 3-year period. Results: High D-dimer levels (≥2 μg/mL) were significantly associated with higher risk of recurrent ischemic stroke (adjusted hazard ratio (HR), 1.80; 95% confidence interval (CI), 1.13–2.84; p = 0.012). The risk of recurrent stroke was similar between the anticoagulant and the antiplatelet groups in all subjects (adjusted HR, 0.78; 95% CI, 0.46–1.32; p = 0.369). However, in patients with high D-dimer levels (≥2 μg/mL), risk of recurrent stroke was significantly lower in the anticoagulant group than in the antiplatelet group (adjusted HR, 0.40; 95% CI, 0.18–0.87; p = 0.022). Conclusion: Our findings suggested that baseline D-dimer levels could be used as a risk assessment biomarker of recurrent stroke in patients with AF-related stroke and atherosclerosis. High D-dimer levels would facilitate the identification of patients who are more likely to benefit from anticoagulants to ensure secondary prevention of stroke.

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Are recent statin recommendations to employ fixed doses and abandon targets effective for treatment of hypercholesterolaemia? Investigation based on number needed to treat

European Journal of Preventive Cardiology ◽

10.1177/2047487316667785 ◽

2016 ◽

Vol 24 (1) ◽

pp. 76-83 ◽

Cited By ~ 18

Author(s):

Handrean Soran ◽

Safwaan Adam ◽

Paul N Durrington

Keyword(s):

Secondary Prevention ◽

Moderate Intensity ◽

Fixed Dose ◽

Dose Titration ◽

Number Needed To Treat ◽

Atherosclerotic Cardiovascular Disease ◽

Cvd Risk ◽

Cholesterol Lowering ◽

Cholesterol Levels ◽

Lowering Therapy

Background Assessed by number needed to treat (NNT) to prevent one event, it was previously shown that for those at similar atherosclerotic cardiovascular disease (CVD) risk, the benefit accruing from treating people with higher cholesterol levels with statins is greater than for those with lower levels. Method By estimating NNT from both the absolute atherosclerotic cardiovascular risk and the pre-treatment low density lipoprotein cholesterol (LDL-C) concentration, recent recommendations for fixed dose high and moderate intensity statin treatment in the primary and secondary prevention of CVD were compared with cholesterol-lowering therapy aimed at a target LDL-C. Results We report that the USA and UK recommendations to employ a fixed dose of atorvastatin 20 mg daily for primary prevention will produce good results in people with low cholesterol levels, but are a disadvantage for those with higher levels who benefit more from a therapeutic target and statin dose titration and, where necessary, adjunctive cholesterol-lowering therapy to achieve this target. The higher dose of atorvastatin 80 mg daily with no target recommended for secondary prevention is generally more effective than aiming for a LDL-C goal except in people with particularly high cholesterol. Conclusion For optimum clinical effectiveness, initial LDL-C concentration must be considered in deciding whether a target will allow a greater decrease in LDL-C and thus a lower NNT than a fixed dose regimen. Individual variation in the LDL-C response to statins also makes post-treatment cholesterol measurement essential.

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Secondary prevention of stroke

10.1093/med/9780198737889.003.0010 ◽

2017 ◽

Author(s):

Hugh Markus ◽

Anthony Pereira ◽

Geoffrey Cloud

Keyword(s):

Secondary Prevention ◽

Recurrent Stroke ◽

Carotid Stenting ◽

Lipid Lowering ◽

Major Advance ◽

Endovascular Interventions ◽

Pharmacological Prevention ◽

Blood Pressure Treatment ◽

Lifestyle Measures ◽

Artery Disease

In the secondary prevention of stroke chapter the case is made for preventing recurrent stroke by targeted evidence-based intervention based on the aetiological cause of stroke. Lifestyle measures such as smoking cessation as well as pharmacological prevention strategies are discussed. Blood pressure treatment, lipid lowering, and antiplatelet therapy are all examined. Since the last edition there has been a major advance in the stroke prevention treatment of atrial fibrillation with the licensing of new anticoagulant agents and the evidence for their use is reviewed. Surgical and endovascular interventions for extracranial and intracranial stenosis are also outlined, including carotid endarterectomy, carotid stenting, extracranial-intracranial bypass, and intervention for vertebral artery disease.

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Statin-based therapy for primary and secondary prevention of ischemic stroke: A meta-analysis and critical overview

International Journal of Stroke ◽

10.1177/1747493019873594 ◽

2019 ◽

Vol 15 (4) ◽

pp. 377-384 ◽

Cited By ~ 1

Author(s):

Haralampos Milionis ◽

George Ntaios ◽

Eleni Korompoki ◽

Konstantinos Vemmos ◽

Patrik Michel

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Primary And Secondary Prevention ◽

Prevention Trials

Background and aims To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

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Residual Risk and Its Risk Factors for Ischemic Stroke with Adherence to Guideline-Based Secondary Stroke Prevention

Journal of Stroke ◽

10.5853/jos.2020.03391 ◽

2021 ◽

Vol 23 (1) ◽

pp. 51-60

Author(s):

Yuesong Pan ◽

Zixiao Li ◽

Jiejie Li ◽

Aoming Jin ◽

Jinxi Lin ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Secondary Prevention ◽

Acute Ischemic Stroke ◽

Stroke Prevention ◽

Recurrent Stroke ◽

Antihypertensive Agents ◽

Residual Risk ◽

Stroke Recurrence ◽

Secondary Stroke Prevention

Background and Purpose Despite administration of evidence-based therapies, residual risk of stroke recurrence persists. This study aimed to evaluate the residual risk of recurrent stroke in acute ischemic stroke or transient ischemic attack (TIA) with adherence to guideline-based secondary stroke prevention and identify the risk factors of the residual risk.Methods Patients with acute ischemic stroke or TIA within 7 hours were enrolled from 169 hospitals in Third China National Stroke Registry (CNSR-III) in China. Adherence to guideline-based secondary stroke prevention was defined as persistently receiving all of the five secondary prevention medications (antithrombotic, antidiabetic and antihypertensive agents, statin and anticoagulants) during hospitalization, at discharge, at 3, 6, and 12 months if eligible. The primary outcome was a new stroke at 12 months.Results Among 9,022 included patients (median age 63.0 years and 31.7% female), 3,146 (34.9%) were identified as adherence to guideline-based secondary prevention. Of all, 864 (9.6%) patients had recurrent stroke at 12 months, and the residual risk in patients with adherence to guidelinebased secondary prevention was 8.3%. Compared with those without adherence, patients with adherence to guideline-based secondary prevention had lower rate of recurrent stroke (hazard ratio, 0.85; 95% confidence interval, 0.74 to 0.99; P=0.04) at 12 months. Female, history of stroke, interleukin-6 ≥5.63 ng/L, and relevant intracranial artery stenosis were independent risk factors of the residual risk.Conclusions There was still a substantial residual risk of 12-month recurrent stroke even in patients with persistent adherence to guideline-based secondary stroke prevention. Future research should focus on efforts to reduce the residual risk.

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The Role of Lipid-Lowering Treatment in the Secondary Prevention of Ischemic Stroke

Diseases ◽

10.3390/diseases10010003 ◽

2021 ◽

Vol 10 (1) ◽

pp. 3

Author(s):

Alexandra Tsankof ◽

Konstantinos Tziomalos

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Pcsk9 Inhibitors ◽

Stroke Treatment ◽

Icosapent Ethyl ◽

History Of ◽

Coronary Events

Dyslipidemia is a major modifiable risk factor for ischemic stroke. Treatment with statins reduces the incidence of recurrent ischemic stroke and also reduces coronary events in patients with a history of ischemic stroke. Therefore, statins represent an important component of secondary prevention of ischemic stroke. In patients who do not achieve low-density lipoprotein cholesterol (LDL-C) targets despite treatment with the maximal tolerated dose of a potent statin, ezetimibe should be added to their lipid-lowering treatment and also appears to reduce the risk of cardiovascular events. Selected patients who do not achieve LDL-C targets despite statin/ezetimibe combination are candidates for receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Finally, it appears that adding icosapent ethyl might also reduce cardiovascular morbidity in patients who have achieved LDL-C targets but have persistently elevated triglyceride levels.

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