The Health Thread

What is CHD?

Coronary Heart Disease (CHD) is a health condition that involves the constriction or obstruction of the coronary arteries, which are responsible for delivering oxygenated blood to the heart muscle. This constriction or obstruction is caused by the accumulation of fatty substances known as plaques on the inner lining of the arteries, a condition referred to as atherosclerosis. There are several types of plaques and some of the plaques are less likely to rupture because they have a thick fibrous cap with a small lipid core (LC) area . While unstable and vulnerable plaques have been characterized by several studies which indicate that they have a thin fibrous cap (< 65 µm) and its LC is substantial . If plaque ruptures in the carotid artery, it will either block the oxygenated blood from reaching the brain or bleed, which will lead the brain cells to die.[11] Over time, these plaques can limit the flow of blood to the heart, resulting in various symptoms such as angina (chest pain), breathlessness, and in severe instances, myocardial infarction (heart attack) [1].

CHD is a progressive disease that develops over several years, often due to a combination of factors, including genetic predisposition, lifestyle habits, and pre-existing health conditions. Risk factors for CHD encompass age, gender (men are generally at a higher risk, particularly before menopause), family history of heart disease, smoking, hypertension, hypercholesterolemia, diabetes, obesity, sedentary lifestyle, unhealthy diet, and chronic stress [2].

Why is CHD a Pandemic?CHD has escalated to pandemic levels due to a multitude of interconnected factors, ranging from lifestyle habits to global health disparities. Here’s an explanation of why CHD has attained pandemic status, supported by citations:

Global Prevalence: As individuals age, their arteries tend to stiffen and become more susceptible to damage, thereby increasing the risk of CHD [2].

Increasing Burden in Developing Countries: Low- and middle-income countries (LMICs) shoulder a significant burden of CHD, with over three-quarters of cardiovascular disease (CVD) deaths occurring in these regions [2]. Rapid urbanization, the adoption of unhealthy western lifestyles, and limited healthcare access contribute to the rising prevalence of CHD in LMICs.

Common Risk Factors: Shared risk factors such as tobacco use, unhealthy diet, physical inactivity, obesity, hypertension, and diabetes contribute to the global spread of CHD [3]. These risk factors are common across various populations and contribute to the worldwide proliferation of CHD.

Economic and Healthcare Systems Impact: CHD imposes a substantial economic burden on societies, encompassing direct medical costs, lost productivity, and social welfare losses. The World Heart Federation estimates the annual cost of CHD to be in the billions of dollars, with projections indicating a further increase in costs over time [4].

Health Inequities: Disparities in access to healthcare and preventive services exacerbate the impact of CHD, particularly in underserved communities and marginalized populations. Limited access to affordable healthcare, preventive interventions, and treatment modalities perpetuates the cycle of CHD burden in vulnerable populations [5].

Environmental and Social Determinants: Environmental factors such as air pollution, noise pollution ,inadequate urban planning, and exposure to toxins contribute to the development of CHD. Social determinants of health, including poverty, education level, and social support networks, also play a significant role in shaping CHD risk [6].

Globalization of Unhealthy Lifestyles: Globalization has facilitated the spread of unhealthy lifestyles characterized by sedentary behavior, poor dietary choices, and increased stress levels. These lifestyle factors contribute to the rising incidence of CHD worldwide, transcending geographical boundaries [7].

Current Status of CHD in Nepal

Coronary Heart Disease (CHD) in Nepal currently poses a significant public health challenge, underscored by increasing prevalence rates and associated risk factors. As per data from the World Health Organization (WHO), CHD contributes to a considerable portion of Nepal’s disease burden, accounting for approximately 12.26% of total deaths, with an age-adjusted death rate of 102.19 per 100,000 population [1].

Emerging epidemiological data suggests a worrying trend of rising CHD prevalence in Nepal. A study conducted in urban Kathmandu revealed a prevalence of 5.9%, indicating a significant burden of cardiovascular diseases in urban areas [2]. Moreover, recent findings indicate that the prevalence of smoking, hypertension, diabetes, and dyslipidemia among the population aged 40 to 80 years in rural Nepal was 27.8%, 34.4%, 6.9%, and 38.5%, respectively, highlighting the multifactorial nature of CHD risk factors in the Nepalese population [3].

Furthermore, the shift towards sedentary lifestyles, urbanization, and dietary changes exacerbates the prevalence of CHD. These factors, compounded by limited access to healthcare services, especially in rural regions, pose significant challenges to effective CHD management [4].

Addressing the Burden of CHD in Nepal

Addressing the burden of Coronary Heart Disease (CHD) in Nepal necessitates a comprehensive approach, drawing insights from strategies employed in both developed and developing nations. Here are some potential strategies for improvement, incorporating insights from global initiatives and interventions tailored for Nepal:

Health Education and Awareness Campaigns: The implementation of public health campaigns to raise awareness about CHD risk factors and promote healthy lifestyle choices is crucial. This strategy has proven effective in various contexts, including developed countries like the United States and Europe [1]. In Nepal, community-based health education programs can target both rural and urban populations, emphasizing the importance of quitting smoking, adopting healthy dietary habits, engaging in regular physical activity, and managing hypertension [2].

Access to Healthcare Services:  Due to fragmented health care systems in many LMICs(Low and Middle Income Countries), many patients are unaware of the disease and disease symptoms resulting in the delay of the care-seeking behavior. People from remote areas and limited access to advanced technology are more prone to suffer. The limited ambulance services in these parts also play a major role in the delay.Apart from the delay in reaching the primary care centers or hospitals, the lack of specialists and inadequate medical facilities hinder the delivery of proper and timely care. [10]Enhancing access to healthcare services, especially in rural areas, is vital for effective CHD management. Telemedicine facilities and mobile clinics can help bridge the gap in healthcare access, as demonstrated in countries like India and Bangladesh [3]. In Nepal, initiatives to establish primary healthcare clinics in remote regions and promote telemedicine consultations can enhance CHD diagnosis, treatment, and follow-up care [4].

Risk Factor Modification:  Early identification of pre-diabetic and pre-hypertensive condition and applying appropriate dietary and behavioural measures will be crucial .Encouraging lifestyle modifications to reduce CHD risk factors is paramount. Developed countries have implemented policies to regulate the availability of unhealthy foods and promote smoke-free environments [5]. In Nepal, advocating for tobacco control measures, promoting healthy dietary patterns rich in fruits, vegetables, and whole grains, and facilitating access to affordable medications for hypertension and dyslipidemia can help mitigate CHD risk [6].

Policy Interventions: Implementing policies to regulate unhealthy behaviors and strengthen healthcare infrastructure is vital. Examples include taxation on tobacco products, legislation on trans-fat content in foods, and investments in healthcare workforce training and facility development [7]. In Nepal, aligning with the Multisectoral Action Plan for the Prevention and Control of Noncommunicable Diseases (2014–2020) and integrating CHD prevention strategies into primary healthcare systems can drive sustainable improvements [8].

Early Detection and Management: Enhancing screening programs for early detection of CHD risk factors and ensuring timely management of the condition are critical. Evidence-based treatment protocols and risk-based management approaches, as outlined in global initiatives like the HEARTS Technical Package, can guide healthcare providers in Nepal [9]. Strengthening data collection systems and integrating cardiovascular risk assessment tools into routine clinical practice are also essential steps.

By integrating these strategies into a comprehensive national CHD prevention and control program, Nepal can make significant strides in reducing the burden of CHD and improving cardiovascular health outcomes across diverse populations.

Glioblastoma (GBM), the most common primary malignant brain tumor, presents a daunting challenge in clinical management, with a meager 5-year survival rate of merely 5% [1]. Despite advancements in treatment modalities such as surgery, radiation, and chemotherapy, the prognosis remains dismal due to tumor heterogeneity and the intricate interplay between tumor cells and normal brain tissue, compounded by the impermeable blood-brain barrier.

Conventional therapies, including surgical resection, radiotherapy, and chemotherapy, have shown limited efficacy, resulting in high relapse rates and poor patient outcomes [2]. Therefore, there is an urgent need for innovative therapeutic approaches to combat GBM effectively.

Chimeric Antigen Receptor T (CAR-T) cell therapy, heralded for its success in hematological malignancies, has emerged as a promising avenue for solid tumors like GBM [3]. However, its application faces formidable challenges posed by the unique anatomical features of GBM, including the blood-brain barrier and the immunosuppressive tumor microenvironment, alongside tumor heterogeneity.

CAR-T therapy involves the extraction of T lymphocytes from the patient’s peripheral blood, genetic modification to express chimeric antigen receptors targeting specific tumor antigens, and reinfusion into the patient, thereby harnessing the immune system to target and destroy cancer cells [4].

The manufacturing process of CAR-T cells entails several meticulous steps, including T cell isolation, genetic engineering to introduce CAR genes, in vitro activation and expansion, and rigorous quality assessment before clinical administration [5].

While CAR-T therapies have demonstrated remarkable efficacy in hematologic malignancies, their application in solid tumors has been limited. The complexity of solid tumors, characterized by diverse cell populations, presents challenges in achieving sustained therapeutic responses [6].

Innovative strategies combining CAR-T therapy with bispecific antibodies, such as T-cell Engaging Antibody Molecules (TEAMs), hold promise in overcoming the hurdles posed by tumor heterogeneity [7]. These approaches aim to enhance the specificity and potency of CAR-T cells against solid tumors like GBM.

Recent clinical studies have reported encouraging outcomes with CAR-T therapy in GBM patients, demonstrating reduced tumor sizes and prolonged survival [8]. Notably, early-phase trials employing dual-target CAR-T cells, engineered to recognize multiple tumor-associated antigens, have shown promising results in shrinking tumors and extending patient survival [9].

Despite the progress, CAR-T cell therapy in GBM is not without limitations, with treatment-associated toxicities, including cytokine release syndrome and central nervous system complications, warranting careful monitoring and management [10].

In conclusion, the innovative field of CAR-T cell therapy is at the forefront of transforming the treatment paradigm for glioblastoma multiforme (GBM). The journey from preclinical studies to clinical trials has been fraught with challenges, yet these hurdles have been instrumental in uncovering and addressing the complexities of successful cancer treatment. The advent of CAR T cells equipped with multivalent receptors, combined with cutting-edge therapies, is tackling the problem of antigen escape [11]. Furthermore, the synergy of CAR T cell therapy with other treatments, such as immunotherapies, chemotherapies, or mechanical tumor ablation, is poised to foster a more inflammatory microenvironment conducive to better patient outcomes [11]. As research continues to refine these therapeutic strategies, there is a growing hope for significant advancements in the battle against this formidable disease.