Kamalesh Chakravarty

High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta‐analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database ‘PubMed’, ‘EMBASE’, and ‘Google Scholar’ as well as from many trial databases. The following search terms were used: ‘Statin therapy’ AND ‘Cardiovascular Disease’, AND ‘Dose’ AND ‘Intracerebral hemorrhage’, AND ‘Randomized Controlled Trials’ AND ‘High Dose Statin’. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed‐effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random‐effect model was used. Beggs funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high‐dose statin and 31,105 subjects receiving placebo were analyzed in our meta‐analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16–2.01; P = 0.002). There was no difference in all‐cause mortality between the two groups (RR = 0.95; 95% CI: 0.86–1.06; P = 0.36). No publication bias was observed through Beggs funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Genetic association between inflammatory genes (IL-1α, CD14, LGALS2, PSMA6) and risk of ischemic stroke: A meta-analysis

Background Sequence variations in genes involved in inflammatory system are known to contribute to the risk of cerebrovascular diseases (CVD) including stroke. Very few number of studies have been published in the context of the association between Interleukin-1α(IL-1α), CD14 cell surface glycoprotein (CD14), Galectin-2-encoding gene (LGALS2)and proteasome subunit type 6 (PSMA6) gene polymorphisms with susceptibility to ischemic stroke (IS). Objective The present meta-analysis aimed to provide a comprehensive account of the association between IL-1α (-C889T and -C511T), CD14 (-C159T), LGALS2 (-C3279T) and PSMA6 (-C8G) gene polymorphisms and susceptibility to IS. Methods A literature search for eligible genetic studies published before August 31, 2015 was conducted in the PubMed, Medline, EMBASE, OVID, and Google Scholar databases. Fixed or random effects models were used to estimate the Pooled Odds ratio (OR) and 95% confidence interval (CI) using RevMan 5.3 software. Results Total 21 studies were included in our meta-analysis. No significant association was observed between IL-1α (-C889T) [OR = 1.18, 95% CI: 0.67–2.08, P = 0.58], IL-1α (-C511T) [OR = 0.95, 95% CI: 0.66–1.37, P = 0.77], LGALS2(-C2379T) [OR = 0.29, 95% CI: 0.02–4.26, P = 0.37] and CD14 (-C260T) [OR = 0.93, 95% CI: 0.77–1.11, P = 0. 42] gene polymorphisms and risk of IS. However, protective level of association was observed between PSMA6 (-C8G) gene polymorphism and susceptibility to IS under the recessive model [OR = 0.25, 95% CI: 0.08–0.72, P = 0.01]. Conclusion Our meta-analysis shows that IL-1α (-C889T and -C511T), CD14 (-C159T), LGALS2 (-C3279T) and gene polymorphisms are not significantly associated with the risk of IS while PSMA6 (-C8G) gene polymorphism may play a protective role with the susceptibility of IS. Further prospective large epidemiological studies are needed to confirm these findings in different populations.

Role of Interleukin-10 (-1082A/G) gene polymorphism with the risk of ischemic stroke: a meta-analysis.

The role of anti-inflammatory Interleukin-10 (IL-10) cytokine gene polymorphism with the risk of ischemic stroke (IS) remains controversial. The aim of present meta-analysis was to investigate the association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS. A literature search for candidate gene association studies published before 29 February 2016 was conducted in the PubMed, EMBASE, Google Scholar, and TRIP database. The following search terms were used: ‘Interleukin-10’ or ‘IL-10’ and ‘Ischemic stroke’ or ‘IS’ and ‘Cerebral Infarction’ or ‘CI’ and ‘genetic polymorphism’ or ‘single nucleotide polymorphisms’ or ‘SNP’. Fixed or random effects models were used to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Begg’s funnel plot was used to assess the potential for publication bias. In our meta-analysis, five case-control studies involving 1209 IS cases and 1139 controls were included. Overall, there was no significant association between IL-10 (-1082 A/G) [rs1800896] and risk of IS under dominant [AA + AG vs. GG], recessive [AA vs. AG + GG], and allelic [G vs.A] models. However, based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, we observed significant association of IL-10 (-1082 A/G) gene polymorphism with the risk of IS for Large Vessel Disease (LVD), Small Vessel Disease (SVD), and other (others due to determined and undetermined etiology) subtypes of IS. This is the first meta-analysis to conclude that IL-10-1082A/G gene polymorphism is associated with the risk of LVD, SVD, and other subtypes of IS. Further well-designed large sample size studies based on TOAST classification are needed to validate these findings.

Association between Endothelial nitric oxide synthase G894T gene polymorphism and risk of ischemic stroke in North Indian population: a case-control study.

Background and purpose: Stroke is a multi-factorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between Endothelial Nitric Oxide Synthase G894T (rs1799983) gene polymorphism and susceptibility to ischemic stroke (IS) in North Indian population. Methods: In this present case-control study, genotyping was performed by using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) method for 250 IS patients and 250 age and sex matched controls. PCR results were confirmed by DNA sequencing. Frequency distribution of genotypes and alleles were compared between cases and controls using conditional logistic regression. Results: Hypertension, Diabetes, Dyslipidemia, Low Socioeconomic Status and Family History of Stroke were found to be independent risk factors for IS. Mean age of cases and controls were 52.83 ± 12.59 and 50.97 ± 12.70 years. Multivariate logistic regression analysis showed a significant association between eNOS G894T (rs1799983) polymorphism and risk of IS [OR = 1.57; 95%CI 1.05–2.37; p = 0.028] under dominant model. Based on Trial of Org 10172 in Acute Stroke Treatment classification, an independent association of large vessel disease (LVD) was observed with the risk of IS under the dominant [OR = 2.09; 95% CI 1.17–3.75; p = 0.01] and recessive [4.09 95% CI 1.06–15.68; p = 0.04] models. All the observed genotype frequencies were in accordance with the Hardy–Weinberg equilibrium (HWE) in both cases and controls. Conclusion: The findings of the present study suggest that polymorphism in G894T position of eNOS gene might be a risk factor for IS mainly for LVD stroke subtype in North Indian population. Further large prospective studies are required to confirm these findings.

Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review

Bone marrow mononuclear cell (BM‐MNC) therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review of published studies using BM‐MNC therapy in patients with ischaemic stroke (IS). Literature was searched using MEDLINE, PubMed, EMBASE, Trip Database, Cochrane library and clinicaltrial.gov to identify studies on BM‐MNC therapy in IS till June, 2016. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta‐analysis. We included non‐randomized open‐label, single‐arm and non‐randomized comparative studies or randomized controlled trials (RCTs) if BM‐MNCs were used to treat patients with IS in any phase after the index stroke. One randomized trial, two non‐randomized comparative trials and four single‐arm open‐label trials (total seven studies) involving 227 subjects (137 patients and 90 controls) were included in the systematic review and meta‐analysis. The pooled proportion for favourable clinical outcome (modified Rankin Scale score ≤2) in six studies involving 122 subjects was 29% (95% CI 0.16–0.43) who were exposed to BM‐MNCs and pooled proportion for favourable clinical outcome of 69 subjects (taken from two trials) who did not receive BM‐MNCs was 20% (95% CI 0.12–0.32). The pooled difference in the safety outcomes was not significant between both the groups. Our systematic review suggests that BM‐MNC therapy is safe up to 1 year post‐intervention and is feasible; however, its efficacy in the case of IS patients is debatable. Well‐designed randomized controlled trials are required to provide more information on the efficacy of BM‐MNC transplantation in patients with IS.

Genetics of ischemic stroke: An Indian scenario.

Stroke, a heterogeneous multifactorial disorder, is known to be a major cause of death and adult disability within both the developed and developing countries. Approximately 85% of stroke cases are ischemic, whereas the remaining 15% are hemorrhagic. It is caused by multiple genetic factors, environmental factors, and interactions among these factors. Several candidate genes have been found to be associated with ischemic stroke. The most extensively studied genes include those involved in hemostasis, inflammation, nitric oxide production, homocysteine and lipid metabolism, and rennin-angiotensin-aldosterone system. Combined linkage/association studies have demonstrated that genes encoding phosphodiesterase 4D (PDE4D) and arachidonate 5-lipoxygenase-activating protein (ALOX5AP) confer risk for stroke. Even though there is substantial evidence for the genetic basis of stroke as provided by the epidemiological data from twin- and family-based studies, the contribution of genetic factors identified till now is either not enough or very less to explain the entire spectrum of encountered phenomena associated with ischemic stroke. Till date, no genome-wide association studies (GWAS) have been carried out in India. We aim to extensively review the studies on candidate genes that may have potential applications in the early diagnosis, prevention, and treatment of ischemic stroke in the Indian population. This article further emphasizes the role of GWAS in ischemic stroke and the need for an extensive GWAS in the Indian population.

Is Prevalence of Hypertension Increasing in First-Ever Stroke Patients?: A Hospital-Based Cross-Sectional Study

Background: Stroke is a devastating and disabling cerebrovascular disease with some amount of residual deficit leading to economic loss. Recent Indian studies have shown a stroke prevalence rate of 471.58/100,000 populations. Hypertension has been known to be the main risk factor for causing stroke. Purpose: To investigate the prevalence of hypertension in first-ever stroke patients and its comparison with the previous stroke registry. Methods: The study was a hospital-based cross-sectional study. Consecutive patients, who were admitted in the Neurology ward of All India Institute of Medical Sciences (AIIMS), New Delhi, India, were recruited for the study from the period July 2012 to January 2014. The stroke units consisted of a computerized record containing the details of all the admitted patients. Results: A total of 260 patients were recruited in which 194 (74.6%) were ischemic and 66 (25.4%) were hemorrhagic stroke patients. Hypertension was present in 169 (65%) patients. When compared with the previous stroke registry of 2,628 patients, hypertension was recorded in 1,503 (57.2%) patients. Conclusion: Our data show that there is an increase in the proportion of hypertension among first-ever stroke patients reported in AIIMS in the years 2012–2014 as compared to that reported in during the period 1998–2011.

Nominations for B. K. Bachhawat Memorial Life Time Achievement Award & KT Shetty Memorial Oration of Indian Academy of Neurosciences

Singh, Dean, Indian Academy of Neurosciences and Director, Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi – 110 054, E-Mail director@dipas.drdo.in and a copy of the same to Dr. Vinay K. Khanna, Secretary HQ and Principal Scientist, CSIR – Indian Institute of Toxicology Research, MG Marg, Lucknow – 226 001, E-Mail vkkhanna1@gmail. com positively by July 31, 2016. Nominations received after the last date will be considered next year. Nominations for B. K. Bachhawat Memorial Life Time Achievement Award and KT Shetty Memorial Oration for 2016 and 2017 are invited. The nominee must be a Fellow/Life Member of the Indian Academy of Neurosciences. He/She should have at least 10 years standing in the area of Neurosciences. The contributions in Neuroscience in India will be judged by i. Research publications ii. Awards iii. Contributions to growth of Neuroscience in India. Nominations alongwith complete Bio-data and supporting documents should be sent to Dr. Shashi Bala Published online: July 7, 2016

Contents Vol. 3, 2015

48 The Pulse of Asia May 22–23, 2015, Shanghai, China Guest Editor: Wang, J.-G. (Shanghai)