Fawad Taj ( Department of Medicine, Aga Khan University, Karachi )
Ayeesha K. Kamal ( Department of Medicine, Aga Khan University, Karachi )
Madam, Stroke is the third leading cause of deathand the leading cause of permanent disability in the world.Most of these strokes occur in developing countries.1There is a paucity of epidemiological stroke data from Pakistan,however it is expected that stroke incidence in developing countries will increase despite worldwide decrease.Considering the relative contribution of the different races to the world's population, intracranial large-artery atherosclerosis may be one of the most important causes of ischaemic stroke worldwide.2 Asians are more prone to intracranial atherosclerosis.3Evidence continues to accumulate to suggest important role for inflammation in atherosclerosis,4specifically in stroke.Atherosclerosis is a dynamic, chronic, inflammatory condition due to a response to endothelial injury.5The inflammatory mechanisms at play include endothelialdys function, leukocyte migration, extra cellular matrix degradation, and platelet activation. This current paradigmhas lead to increased interest in inflammatory biomarkers,which may help elucidate pathophysiology and provide methods for quantitating inflammation.Cytokines and acute-phase reactants such ascytokines and CRP may be surrogate markers for basal inflammation that leads to atherosclerotic plaque. In humans, serum von-Willebrand Factor may reflectend othelial cell activation that is, along with endothelial cell-leukocyte interactions, necessary for initiation of inflammatory processes. Oxidative stress leading to modification of low-density lipoprotein (LDL) is a central paradigm of atherogenesis and plaque destabilization byLDL oxidation and foam cells formation. Plasma levels of Myeloperoxidase (MPO) may indicate the extent ofoxidative stress in atherosclerotic plaque. Matrix metalloproteinases (MMPs) are highly expressed inatherosclerotic plaques, with selective enrichment at the shoulder regions, may degrade fibrous cap and convertstable plaque to unstable plaque. Endothelial cells and Monocytes over express CD40 and CD40L, during platelet activation. This triggers an inflammatory response,particularly in advanced, rupture-prone plaques. Soluble CD40L binding to IIbß3 and/or CD40 may function in an autocrine loop to promote local platelet activation within developing aggregates. Unraveling the inflammatory biomarkers may enable clinicians to predict the risk of recurrent athero thrombosis,its clinical sequelae, and design optimal the rapeutic strategies.4Efforts must be made to understand locally relevant disease and sorting out robust clinical markers that have stability, reproducibility and ease of assay.Fawad Taj, Ayeesha K. Kamal Department of Medicine, Aga Khan University, Karachi
References
1.Bhattacharya S, Saha SP, Basu A, Das SK. A5 years prospective study ofincidence, morbidity and mortality profile of stroke in a rural community ofeastern India. J Indian Med Assoc 2005; 103:655-9.
2.Wong KS, Li H. Long-Term Mortality and Recurrent Stroke Risk AmongChinese Stroke Patients With Predominant Intracranial Atherosclerosis.Stroke 2003; 34:2361-6.
3.Moussouttas M, Aguilar L, Fuentes K, Anyanwu B, Manassarians H,Papamitsakis N, et al. Cerebrovascular disease among patients from theIndian subcontinent. Neurology 2006; 67:894-6.
4.Armstrong EJ, Morrow DA, Sabatine MS. Inflammatory biomarkers in acutecoronary syndromes: part II: acute-phase reactants and biomarkers ofendothelial cell activation. Circulation 2006; 113:e152-5.
5.Libby P, Theroux P. Pathophysiology of coronary artery disease. Circulation2005; 111:3481-8.
