Aspirin Prophylaxis for the Prevention of Thrombosis: Expectations and Limitations

Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events. In spite of its extensive use as an antiplatelet drug for the prevention of vascular thrombosis, there is considerable concern about the degree of protection it offers, to patients under aspirin therapy. In this paper, we explain the phenomenon of aspirin resistance, discuss the limitations of aspirin therapy, and suggest methods to monitor “at-risk” individuals. Ability to monitor and determine at risk patients will provide opportunities for the clinicians to customize antiplatelet therapies

Biomedical Research and Healthcare: Opportunities, Expectations, and Limitations

The last fifty years have been the “golden era” of biomedical research and innovation. Major discoveries in genetics, genomics and various fields of “Omics”, together with the technology revolution, has created unlimited opportunities for the development, and improvements in the way the healthcare is delivered. Not a single day goes by, without an announcement of a new sensor, new app, or a new and novel technology, that can be integrated with the wealth of knowledge in biomedical research and applications. To the extent, one of the largest insurance provider, John Hancock announced, that they no longer offer policies, that do not include digital tracking. They will sell only “interactive” policies that collect health data through wearable devices, such as smart watch. The breakthroughs in biomedicine, and advances in technologies, have been miraculous. This is especially true in the USA, which is the envy of other nations, when it comes to innovations in research and technology. The fact that all of these innovations are “news makers” creates great expectations from the care receivers. Having said that, patients, clinicians, and healthcare providers feel at times a letdown, or question the slow pace of advance, escalating cost, sometimes dubious clinical values and inappropriate exploitations. Policy makers and economists are debating, about the cost-effectiveness and the return on the investment in biomedical research, as it relates to improvements in health care. Researchers worldwide are debating about the availability of “Precision Medicine” and “Personalized Medicine.” Despite the developments in biomedical research and emerging technologies, which have raised our expectations and created infinite opportunities, there seems to be some limitations in their applications. In this mini review, we will briefly discuss some of the developments in biomedical research and innovation. We will also express our views on the opportunities available and explain limitations

Acute Vascular Events: Cellular and Molecular Mechanisms

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An estimated 17.9 million individuals died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke. Cardiometabolic risks, such as hypertension, excess weight, obesity, type 2 diabetes, and vascular diseases, contribute significantly to the progression of coronary artery disease. Known sequelae of events that lead to these cardiometabolic diseases include oxidative stress, inflammation, development of dysfunction of vascular adipose tissue, altered blood pressure and blood lipids, altered glucose metabolism, hardening of the arteries, endothelial dysfunction, development of atherosclerotic plaques, and activation of platelet and coagulation pathways. The Framingham Heart Study Group has developed a Risk Score that estimates the risk of developing heart disease in a 10-year period. This group of experts has developed mathematical functions for predicting clinical coronary disease events. These prediction capabilities are derived by assigning weights to major CVD risk factors such as sex, age, blood pressure, total cholesterol, low-density lipoprotein, high-density lipoprotein cholesterol, smoking behavior, and diabetes status. Currently, there is a growing interest in the use of artificial intelligence and machine learning applications. AI-based mimetic pattern-based algorithms seem to be better than the conventional Framingham Risk Score, in predicting clinical events related to CVDs. However, there are limitations to these applications as they do not have access to data on the specific factors that trigger acute vascular events, such as heart attack and stroke. This overview briefly discusses some salient cellular and molecular mechanisms involved in precipitating thrombotic conditions. Further improvements in emerging technologies will provide greater opportunities for patient selection and treatment options. Several clinical studies have demonstrated that most CVDs can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical activity, and harmful use of alcohol. Early detection and better management of the modifiable risks seem to be the only way to reduce, reverse, or prevent these diseases

Antiplatelet therapies: An overview

The role of blood components including platelets, in initiating inflammation, endothelial dysfunction, atherosclerosis, thrombus formation, thrombus growth, and acute vascular ischemic events, is well established. Given this recognized role played by platelets, there is a considerable interest in understanding the physiology and function of platelets, as well as in the development of novel platelet function-inhibitory drugs. The generation of the second messengers, calcium mobilization, shape change, adhesion, aggregation, contraction, release of granule contents, thrombus development, thrombus growth, and formation of hemostatic plug at the injured vessel surfaces, in brief, constitute platelet activation. Some of the known compounds that inhibit platelet activation include inhibitors of arachidonic metabolism (cyclooxygenase-1 inhibitors; aspirin, ibuprofen, etc.), adenosine diphosphate receptor antagonists (P2Y 12 inhibitors), adenylyl and guanylyl cyclase stimulators, calcium antagonists, and GP11b/111a receptor antagonists. Since platelets have multiple mechanisms of achieving in vivo activation, it is difficult to design a novel drug that offers total protection for developing acute ischemic vascular events, without compromising coagulation mechanisms. Given this complexity, any aggressive antiplatelet therapy results in increased bleeding episodes. Having said that, we feel that there is a great window of opportunity for developing novel antiplatelet therapies. There is also scope for the development of fixed-dose combinations for the primary and secondary management of chronic diseases such as hypertension, heart disease, and type-2 diabetes

Contributions of the South Asian Society on Atherosclerosis and Thrombosis and the Indian Society for Atherosclerosis Research, to our understanding of Atherosclerosis and Thrombosis

South Asians (Indians, Bangladeshis, Pakistanis and Sri Lankans) have very high incidence of cardiometabolic diseases, such as hypertension, central abdominal obesity, metabolic syndrome, type-2 diabetes, ischemic heart disease and stroke. To create awareness, develop educational and a prevention program, a professional society was started at the University of Minnesota in 1993. This society (South Asian Society on Atherosclerosis Thrombosis) organized international conferences in India every other year, on the topic of "Atherosclerosis and Thrombosis" and published several monographs on this subject. During the same period, another sister society, Indian Society of Atherosclerosis Research (ISAR) was started in India, which organized conferences on topics related to basic research and clinical aspects of atherosclerosis. Together, these professional societies have contributed significantly to our understanding of chronic cardiometabolic diseases. SASAT is currently located at the Division of Clinical and Preventive Cardiology, Medanta, The MediCity, New Delhi, India and is affiliated with the professional journal; Journal of Clinical and Preventive Cardiology. For information on ISAR, readers are urged to visit their web site: www. isar.co.in

Diabetes and cardiovascular disease in South Asians: A global perspective

South Asians (Indians, Pakistanis, Bangladeshis, and Sri Lankans), have very high incidence of metabolic diseases, such as hypertension, abdominal obesity, metabolic syndrome, type-2 diabetes, and vascular disease. To create awareness, develop educational and preventive strategies, we started a professional society, South Asian Society on Atherosclerosis and Thrombosis (SASAT) in 1993, at the University of Minnesota. Since that time, we have organized fifteen international conferences in India and published several monographs on this topic. In our conferences, we have discussed all aspects of epidemiology, risk factors, and excess burden of these diseases in this ethnic group in India and abroad. In general, South Asians seem to have excess incidence of diabetes and coronary artery disease, no matter which country they live. There are speculations about the reasons for this excess; however, no definite risk factor or a cluster of risks have been attributed to be responsible for this excess disease burden. National health programs in various countries, such as the UK, and Canada, with large number of South Asian Immigrants, have developed ethnic-specific preventive measures. The World Health Organization has issued special guidelines about the BMI cutoff, for this ethnic group. During the tenure of the President William Clinton, recognizing the important role the South Asian community has played in the USA, he recommended some studies related to their health. Again in 2009, President Barack Obama signed an executive order, calling for strategies to improve the health of Asian Americans. In a recent issue of the Journal of Circulation, the American Heart Association has published a scientific statement about the atherosclerotic disease in the South Asians living in the USA. The Vice chair of one of the councils, Dr Latha Palaniappan also has published a companion report called, “Call to Action”: A science advisory from the AHA. In this overview, we will discuss briefly the work of SASAT, and present our views with a global perspective

Risk assessment, risk management, and prevention of acute vascular events

South Asians have a very high incidence of cardiometabolic diseases such as hypertension, central abdominal obesity, metabolic syndrome, type 2 diabetes, heart disease, and stroke. In spite of the fact that common risk factors associated with these clinical conditions are known, we do not have point-of-care assays, to monitor the disease of the vessels, and the efficacy of antiplatelet therapy. We have a window of opportunity to develop three-dimensional ultrasound methodologies, to monitor the subclinical atherosclerosis, altered flow velocities of regional vascular beds, as well as plaque progression and regression in the major vessels. We also have opportunities to develop state-of-the-art methodologies for monitoring the efficacy or otherwise of antiplatelet therapies. In this overview, we share our views and strategies for the development of affordable medical technologies in India, for monitoring vessel wall pathology as well as for better management of antiplatelet therapies