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Review Article
Moyamoya disease: insights into the clinical implications of the RNF213 gene
Taedong Ok
Cardiovasc Prev Pharmacother. 2024;6(4):109-115.   Published online October 31, 2024
DOI: https://doi.org/10.36011/cpp.2024.6.e14
  • 348 View
  • 8 Download
Abstract PDF
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid arteries and the formation of compensatory collateral vessels, which appear as a “puff of smoke” on cerebral angiography. It is a significant cause of stroke in East Asia, with an incidence of 0.5 to 1.5 cases per 100,000 people annually. The etiology of MMD remains unclear; however, the identification of the RNF213 gene, particularly the R4810K variant, as a major susceptibility factor among the East Asian population, has provided crucial insights into the disease's pathophysiology and clinical manifestations. MMD typically presents with transient ischemic attacks, ischemic and hemorrhagic strokes, seizures, headaches, and cognitive deficits. Diagnostic criteria have evolved to emphasize advanced imaging techniques. Pathological features include fibrocellular intimal thickening, irregular undulation of the elastic lamina, and the formation of moyamoya vessels. The mutation in the RNF213 gene impairs the degradation of proteins involved in vessel development, leading to abnormal angiogenesis. Genotype-phenotype studies indicate that the RNF213 variant is associated with an earlier onset, transient ischemic attacks, infarctions, and involvement of the posterior cerebral artery, although its effects vary between regions. Additionally, the homozygous RNF213 variant consistently correlates with an earlier age of onset and a higher risk of cerebral infarction. However, further research is necessary to fully understand its long-term impacts and its relationship with revascularization outcomes. Ongoing research is crucial to fully comprehend the pathophysiology and genetics of MMD, improve prognostic predictions, and develop novel therapies.
Original Articles
Variation in blood viscosity based on the potential cause of stroke of undetermined etiology
Jinyoung Oh, Youngchan Jung, Jin Kim, Sun Ki Min, Sang Won Han, Jong Sam Baik
Cardiovasc Prev Pharmacother. 2023;5(4):144-150.   Published online October 25, 2023
DOI: https://doi.org/10.36011/cpp.2023.5.e14
  • 1,553 View
  • 27 Download
  • 3 Citations
Abstract PDF
Background
This study investigated potential differences in blood viscosity (BV) among patients with stroke of undetermined etiology, negative evaluation (SUDn), specifically those with potential atherothrombosis (SUDn-AT) and those with possible embolism (SUDn-E).
Methods
This single-center study employed a retrospective observational design. The participants were patients over 20 years old with the SUDn stroke subtype who were admitted within 5 days of symptom onset. These patients were categorized as SUDn-AT or SUDn-E. Patients in the SUDn-AT group had nonsignificant stenosis (<50%) of a major brain artery relevant to their symptoms and exhibited one or more signs of systemic atherosclerosis, including atherosclerosis of at least one major brain artery other than those clinically relevant, coronary artery disease, and/or peripheral artery disease. For the SUDn-E group, the SUDn criteria from the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification system were strictly applied.
Results
The final analysis included 153 patients, with 104 (68%) classified as SUDn-E and the remaining 32% as SUDn-AT. Patients in the SUDn-AT group had a higher systolic BV (P=0.012) and diastolic BV (P=0.020) than those in the SUDn-E group. Multivariable logistic regression analysis revealed that age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03–1.13; P=0.003), systolic BV (OR, 3.11; 95% CI, 1.41–6.85; P=0.005), and diastolic BV (OR, 1.08; 95% CI, 1.02–1.14; P=0.009) were associated with SUDn-AT.
Conclusions
Within the TOAST system, two SUDn entities may be distinguishable, with potentially different underlying etiologies: atherothrombosis and embolic stroke of undetermined source.

Citations

Citations to this article as recorded by  
  • Association of Cerebral Artery Stenosis with Blood Viscosity in Patients with Transient Ischemic Attack
    Young Chan Jung, Sang Won Han, Joong Hyun Park
    Journal of Neurosonology and Neuroimaging.2024; 16(1): 8.     CrossRef
  • A Comprehensive Study of Risk Factors, Etiology, and Infarction Patterns in Cerebrovascular Accidents at a Tertiary Care Hospital in India
    Raju Hansini Reddy, Pradnya Diggikar, Mayank Mundada, Arun Oommen, Tushar Pancholi, Bhavya Yammanuru, Sree Vidya Yekkaluru, Advit Sangwan
    Cureus.2024;[Epub]     CrossRef
  • The Effect of Organic Vegetable Mixed Juice on Blood Circulation and Intestine Flora: Randomized, Double-Blinded, Placebo-Controlled Clinical Trial
    Yun-Ha Lee, Jae-Ho Lee, Soo-Min Jeon, Il-Kyu Park, Hyun-Bin Jang, Soo-A Kim, Soo-Dong Park, Jae-Jung Shim, Seong-Soo Hong, Jae-Hwan Lee
    Diseases.2024; 12(9): 223.     CrossRef
Fabry disease screening in young patients with acute ischemic stroke in Korea
Yunjung Choi, Taedong Ok, Kyung-Yul Lee
Cardiovasc Prev Pharmacother. 2023;5(2):54-60.   Published online April 24, 2023
DOI: https://doi.org/10.36011/cpp.2023.5.e5
  • 1,820 View
  • 46 Download
Abstract PDF
Background
Fabry disease is an X-linked lysosomal storage disorder that results from a mutation in the α-galactosidase A (GLA) gene. It shows multiple organ involvement, including cerebrovascular disease. Since Fabry disease has a prevalence of approximately 4% in young patients with cryptogenic stroke, screening for this condition is recommended for young stroke patients. This study aimed to investigate the prevalence of Fabry disease in young acute ischemic stroke patients in Korea, the distribution of GLA gene mutations, and the subtypes of ischemic stroke.
Methods
This study included 211 young patients with acute ischemic stroke or transient ischemic attack. To screen for Fabry disease, α-galactosidase A (α-Gal A) enzyme activity was measured and DNA sequencing analysis of the GLA gene was performed.
Results
None of the patients exhibited low α-Gal A enzyme activity or had a pathogenic GLA mutation, but 18 nonpathogenic GLA gene variants were detected, including c.-10C>T in 16 patients, c.-33C>T in one patient, and c.196G>C in one patient. The mean α-Gal A enzyme activity in 14 male patients with the c.-10C>T variant was 5.17±1.19, which was significantly lower than that of male patients with the normal genotype (7.47±3.48, P<0.05). The distribution of stroke subtypes in patients with GLA gene polymorphisms was not significantly different from that in patients with a normal genotype.
Conclusions
This study demonstrates that Fabry disease is rare in young patients with ischemic stroke or transient ischemic attack in Korea, and we suggest that routine screening for Fabry disease may not be necessary for ischemic stroke patients.
Indirect comparison of nonvitamin K oral anticoagulants and left atrial appendage occlusion
Sung-Hwan Kim, So-Yoon Park, Seung-Sik Hwang
Cardiovasc Prev Pharmacother. 2022;4(1):18-25.   Published online January 18, 2022
DOI: https://doi.org/10.36011/cpp.2022.4.e1
  • 4,101 View
  • 51 Download
Abstract PDFSupplementary Material
Background
Anticoagulation is important in atrial fibrillation (AF) patients to reduce the occurrence of thrombotic events. We evaluated the efficacy and safety of percutaneous left atrial appendage occlusion (LAAO) as an alternative to systemic anticoagulation through an indirect comparative analysis.
Methods
An indirect comparative analysis of nonvitamin K oral anticoagulants (NOACs) and LAAO was conducted. Comparisons were made using data from four landmark randomized clinical trials (RE-LY, ROCKET-AF, ARISTOTLE, and PROTECT AF). Using warfarin as the common comparator, an indirect comparison was performed using data from each trial, and the relative risk was calculated between NOACs and LAAO.
Results
NOACs and LAAO showed similar results for the reduction of stroke and systemic embolism, with a non-statistically significant trend favoring NOACs (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.37–1.46 for dabigatran; HR, 0.99; 95% CI, 0.50–1.92 for rivaroxaban; HR, 0.89; 95% CI, 0.45–1.74 for apixaban). Significantly fewer major bleeding and procedure-related complications were found in patients treated with apixaban compared with LAAO (HR, 0.45; 95% CI, 0.26–0.75). Cardiovascular death occurred more frequently in patients administered NOACs than in patients with LAAO (HR, 2.28; 95% CI, 1.03–5.10 for dabigatran; HR, 2.41; 95% CI, 1.09–5.42 for rivaroxaban; HR, 2.40; 95% CI, 1.10–5.36 for apixaban).
Conclusions
The rate of all-cause death was similar between NOACs and LAAO. Compared with LAAO, NOACs led to a nonsignificant numerical decrease in stroke and embolism in AF patients. Significantly fewer safety events occurred in patients treated with apixaban. LAAO significantly reduced cardiovascular death.
Review Articles
Antiplatelet Therapy for Secondary Stroke Prevention in Patients with Ischemic Stroke or Transient Ischemic Attack
Kyung-Yul Lee
Cardiovasc Prev Pharmacother. 2021;3(4):86-94.   Published online October 31, 2021
DOI: https://doi.org/10.36011/cpp.2021.3.e10
  • 9,987 View
  • 379 Download
Abstract PDF
The risk of stroke recurrence is highest in the acute phase after transient ischemic attack (TIA) or ischemic stroke. Therefore, patients with TIA or ischemic stroke should be treated with antiplatelet medication for stroke prevention. The short-term use of dual antiplatelet therapy between 21 and 90 days may be considered in those with acute minor stroke or TIA and highrisk of recurrence. However, the long-term use of dual antiplatelet therapy is not recommended due to the risk of bleeding. The current stroke guideline does not specify the administration of an antiplatelet for the secondary prevention of ischemic stroke. However, as clinical studies progress, antiplatelet therapy may become a personalized treatment in the future.
Dose Selection of Non-Vitamin K Antagonist Oral Anticoagulants in Korean Patients with Non-Valvular Atrial Fibrillation
So-Ryoung Lee, Young Keun On
Cardiovasc Prev Pharmacother. 2020;2(1):1-10.   Published online January 31, 2020
DOI: https://doi.org/10.36011/cpp.2020.2.e5
  • 4,114 View
  • 63 Download
Abstract PDF
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. In the Asian population, patients with AF have been shown to have increased risks of ischemic stroke and all-cause death compared to patients without AF by 3.34- and 2.61-fold, respectively. AF guidelines recommend oral anticoagulation (OAC) therapy in AF patients with a CHA2DS2-VASc score of ≥1 for men and ≥2 for women with non-valvular AF. After the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) as a treatment for AF, their use has become widespread. Compared to warfarin, NOACs showed comparable efficacy for the prevention of thromboembolic events and superior safety in terms of bleeding complications, especially intracranial hemorrhage. Physicians should keep in mind considerations for optimal OAC therapy to achieve the best outcome. Furthermore, appropriate dose selection in order to achieve the best clinical outcome is an important issue in clinical practice. All NOACs do not have the same rules for dose reduction, and dose reduction of NOACs is primarily recommended according to the dose reduction criteria investigated in pivotal randomized control trials. In this review, we focus on the optimal dose of NOAC and summarize current guidelines and evidence for appropriate dosing of NOACs.
Original Article
CYP2C19 Polymorphisms and Smoking Status Affects Responsiveness to the Platelet P2Y12 Receptor Antagonist Clopidogrel
Sang Won Han, Yong-Jae Kim, Woo-Keun Seo, Sungwook Yu, Hyo Suk Nam, Sung Sang Yoon, Seo Hyun Kim, Jong Yun Lee, Jun Hong Lee, Yang-Ha Hwang, Jun Lee, Kyung-A Lee, Kyung-Yul Lee
Cardiovasc Prev Pharmacother. 2019;1(2):63-70.   Published online October 31, 2019
DOI: https://doi.org/10.36011/cpp.2019.1.e8
  • 25,436 View
  • 15 Download
  • 1 Citations
Abstract PDF
Background
The “comparison of triflusal and clopidogrel effects in secondary prevention of stroke based on cytochrome P450 2C19 (CYP2C19) genotyping (MAESTRO)” study was a prospective, multicenter, randomized, open-label, and blind genotype trial. We performed a subgroup analysis of the MAESTRO study to explore the relationship between VerifyNow P2Y12 assay with regard to CYP2C19 polymorphisms and smoking status in patients with non-cardiogenic ischemic stroke who underwent clopidogrel treatment.
Methods
For the study, patients treated with clopidogrel and who underwent VerifyNow P2Y12 assay was selected from the MAESTRO study.
Results
Of the 393 patients in 18 hospitals, 256 (65%) patients in 12 hospitals were entered for this subgroup analysis. P2Y12 reaction unit (PRU) was significantly lower and percent inhibition (% INH) was higher in the current smoking group than in the nonsmoking group (p<0.001). The same results were also observed in the good genotype group when compared with the poor genotype group (p<0.001). Among the groups, significant lower PRU and higher % INH was demonstrated in current smoking with good genotype group. However, there was no difference in PRU and % INH between current smoking with poor genotype group and nonsmoking with good genotype group, suggesting that clopidogrel activity was concurrently related to CYP2C19 polymorphisms and smoking status.
Conclusions
Regarding secondary stroke prevention, patients who were current smokers and had a poor genotype for clopidogrel metabolism may benefit from clopidogrel treatment similar to that in patients who were nonsmokers and had a good genotype.

Citations

Citations to this article as recorded by  
  • Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the smoker’s paradox
    Frank A. Plakogiannis, Jakob Weidmann, Blake Fraser, Justin Kwong, Diana Asi, Pratham Kumar, Madeleine Baldock, Jasmine Naamo, Ruhani Baluja, Rachelle Catanzariti, Stewart Yeung, Lisa Pont, Kylie Williams, Gabriele De Rubis, Kamal Dua, Nadeem Irfan Bukhar
    Pathology - Research and Practice.2024; 257: 155290.     CrossRef

CPP : Cardiovascular Prevention and Pharmacotherapy
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