Clinical Biochemistry: Diagnostic and Treatment Methods for Atherosclerosis
Clinical biochemistry plays an essential role in health care. Its importance has been highly acknowledged by the UK National Health Service as one of the largest and most important clinical science that needs constant training and specialization. A clinical biochemist is essentially an advisor for the interpretation of biochemical tests through the understanding of laboratory limitations and the constant evaluation of clinical values, which is critical to diagnostic services. While clinical biochemistry paves the way for efficient health care, it also progressively contributes to research and the development of technologies through laboratory investigation.
Globally, cardiovascular diseases (CVD) are with the highest morbidity and mortality rates, at which individuals at risk demonstrate abnormal blood pressure, glucose, and lipid levels among other indicators. These indicators are then evaluated in clinical biochemistry laboratories for diagnosis and prognosis, so to provide effective medical care (World Health Organization, n.d.). Different risk factors, including hypertension, diabetes, smoking, obesity, and genetics, accompany different types of cardiovascular diseases but are essentially caused by damaged blood vessels that result to restricted blood flow. Atherosclerosis, for instance, is the leading cause of many cardiovascular diseases such as heart attacks and strokes, which are characterized by the buildup of lipids and other substances, called plaques or atheroma, in the walls of the arteries. These plaques cause hardening and narrowing of arteries that can potentially rupture and form blood clots which can then impede blood flow and oxygen supply to vital organs in the body such as the heart and brain.
In this context, clinical biochemistry proves to be essential beyond the monitoring of cholesterol, glucose, and blood pressure levels as biochemical tests are deemed critical to the determination and evaluation of enzyme and protein biomarkers. These markers, among other indicators, are critical to the decision-making process as to what tests and treatment steps are necessary for diagnosis and prognosis. However, cardiovascular diseases are one of the most complicated diseases to investigate in the clinical biochemistry laboratory due to the lack of accurate and prompt identification and treatment of risk factors. While risk scores are very high, the need to accelerate the methods for the analysis of biomarkers continues to be an urgent requirement for the improvement of prevention and treatment techniques. Atherosclerosis, in particular, is a chronic disease that is often left undetected until serious complications arise. It does not show symptoms at the early stages, which makes it life-threatening as it can potentially lead to many severe cardiovascular diseases if left untreated. It is an extremely complex and multifactorial biochemical process that is difficult to diagnose in a preventive approach with conventional testing methods. Hence, the challenge essentially lies in developing technologies for the early identification of the disease.
This review aims to highlight atherosclerosis and the challenge it provides to clinical biochemistry. By understanding the empirical knowledge surrounding the disease, the furtherance of diagnostic methods for cardiovascular diseases will be better realized - so to ensure higher regard for the urgent need to develop more advanced and comprehensive techniques. The biochemistry of and the development of diagnostic tools and predictive models for the risk assessment of atherosclerosis will be studied in detail, as well as the clinical interventions necessary to stop the progression of the chronic disease and to alleviate the conditions that accompany it.
Atherosclerosis is a chronic inflammatory disease that is characterized by the buildup of lipids and other substances in the artery wall - referred to as plaques or atheroma. These plaques harden and narrow the arteries, which can potentially rupture and form blood clots that can impede blood flow and oxygen supply to vital organs such as the heart and brain. Atherosclerosis is a progressive condition but does not show symptoms at the early stages and is often left undetected until serious complications arise that are then difficult to intervene, making preventive action critical especially since there is currently no treatment available for the disease. However, lifestyle changes may still help the condition from worsening, and additional treatments can be made available to alleviate the complications and reduce the risk of developing life-threatening cardiovascular diseases such as heart attacks and strokes.
The development of atherosclerotic plaques involves the trapping of foam cells or cholesterol-engorged macrophages that form fatty streak lesions in the subendothelial matrix of the arteries. These fatty streaks lesions are clinically insignificant but are principal precursors to the advancement of lesions, which are characterized by the accumulation of lipid-rich necrotic debris and smooth muscle cells that will then become calcified and large plaques which can restrict blood flow. However, the most critical clinical complications arise from the rupture or erosion of the plaques, which triggers blood clots or the formation of a thrombus that can result to myocardial infarction of stroke.
Epidemiological studies how that there are numerous risk factors for atherosclerosis that with significant genetic references and of substantial environmental sources. The genetic risk factors involve multiple genes but are primarily centered on the relative abundance of different plasma lipoproteins, which at high levels are a prerequisite for many cardiovascular diseases. The environmental factors, on the other hand, are primarily driven by lifestyle with which a high-fat diet, smoking, low antioxidant levels, lack of exercise, and infectious agents are some of the most frequent drivers of cardiovascular diseases. However, these are rather inconclusive due to the complex interaction between genetic and environmental risk factors, which provides a challenge to clinical investigation.
At present, there are multiple types of tests available for the diagnosis of atherosclerosis. Analyte testing, such as serological (blood) testing, is the most practical diagnostic method when symptoms start to arise. It checks the levels of cholesterol, sugar, proteins, and other indicators in the blood, which provide basic data for the evaluation of risk factors for atherosclerosis. Certain biochemical markers, such as C-reactive protein, can also use to predict the likelihood of ischemic events. In addition, extravascular imaging, such as Computed Tomography scans, Echocardiography, electrocardiograms, and Chest X-rays among others, can also be used in combination with other testing types to further the accuracy of diagnosis depending on the presence of symptoms or severity of the condition. Furthermore, invasive methods such as catheterization can also be used for a more advanced and reliable diagnosis, however, it is rather expensive and with significant risk. Ultimately, the type of tests necessary for a comprehensive diagnosis is critical to intervention but is rather a difficult decision-making process. In this context, Point of Care Testing (POCT) is an effective tool in clinical care which enables for prompt diagnosis and treatment decisions so to promote a guideline-recommended initiation of methods. Clinical biochemistry plays a huge role in this system of care delivery as it is central to the decision-making and employment of the tests and interventions necessary. POCT is evidence-based, which makes it feasible and practical in both preventive and primary care. Hence, it is critical that while clinical research aims to overcome the limitations of existing diagnostic and treatment methods, POCT is also improved to provide reliable and effective health care.
The primary symptom for diagnosis includes ischemia, which is characterized by the restriction of blood supply, and thus, the shortage of oxygen to tissues for cellular metabolism. Basic diagnostic methods include physical examination, history assessment, fasting lipid profiling, plasma glucose, and glycosylated hemoglobin level testing, and C-reactive protein measurement, which could be highly predictive indicators of cardiovascular conditions.
The extent and location of the occlusion, especially with patients that have documented disease, are determined through both invasive and noninvasive tests to evaluate the risk for atherosclerosis. Noninvasive tests which include imaging techniques such as 3D Vascular Ultrasonography, Computed Tomography Angiography, Magnetic Resonance Angiography, Immunoscintigraphy, and Positron Emission Tomography, are used to assess vulnerable plaque morphology and characteristics. Invasive techniques on the other hand are primarily catheter-based, which include Intravascular Ultrasonography to produce ultrasound images of the arterial lumen and wall, Angioscopy to directly visualize the arterial surface, Plaque Thermography to detect temperature changes in actively inflamed plaques, Optical Coherence Tomography to produce infrared images of the arterial surface, and Elastography to detect lipid-rich plaques. These techniques render real-time and more accurate results, however, they come with a high cost and significant risk.
Technically, the tests for asymptomatic patients with risk factors for atherosclerosis are referred to as screening. Typical guidelines recommend lipid profile screening for men that are 40 years old and over, women that are post-menopausal andor 50 years old and over, patients with type 2 diabetes, metabolic syndrome, hypertension, or chronic inflammatory conditions, or individuals with a history of familial hypercholesterolemia.
Predictive models through pooled cohort risk assessment can also be employed using risk calculators, such as the American Heart Association (AHA) Risk Calculator and Systemic Coronary Risk Estimation (SCORE), which are primarily based on sex, age, race, cholesterol levels, systolic blood pressure, blood sugar levels, and smoking habits. In addition, a lipoprotein(a) measurement can be used for patients at intermediate risk to improve risk evaluation. Furthermore, Computed Tomography (CT) imaging for coronary artery calcium can be employed to refine risk estimates and for the recommendation of statin therapy in selected patients, provided that strong evidence of significant risks is identified.
Although there are no available direct treatments that can reverse atherosclerosis, proactive alterations of the risk factors may help with the significant slowing and induced regression of existing plaques, which should reduce the risk of life-threatening conditions such as heart attacks and strokes. Lifestyle changes, drugs, statin therapy, and possibly invasive procedures for severe cases are the treatments currently available for diagnosed patients.
Lifestyle Changes
Diet
Dietary changes include limited alcohol intake, a substantial decrease in saturated fat and processed carbohydrates, and increased consumption of fiber-rich carbohydrates. These adjustments to a healthier diet are a prerequisite for lipid control and weight reduction, which should be done in consistently substantial amounts to be effective. Fat intake should be limited to 20 g a day, with no highly atherogenic transfats and not over 2 g of saturated fat. Caloric deficiency due to the substantial decrease in fat should be compensated by increased consumption of proteins and fiber-rich carbohydrates rather than processed carbohydrates to increase plasma triglyceride and high-density lipoprotein (HDL) levels, as well as to decrease refined sugar intake, especially in individuals at risk of diabetes. Fiber intake of 5-10 g soluble fiber daily is recommended to decrease low-density lipoprotein (LDL) levels by about 5%, resulting to decreased total cholesterol, glucose, and insulin. Alcohol is limited at about 30 mL of ethanol 5 to 6 times a week to protect against coronary atherosclerosis as alcohol increases HDL at moderate doses. Dietary supplements that contain vitamins, phytochemicals, and minerals, such as fish oil supplements, can also be consumed. While some may have minor effects on blood pressure or cholesterol, these healthy foods may have adverse interactions with existing drugs.
Smoking Habits
Smoking induces oxidative stress, vascular inflammation and dysfunction, platelet coagulation, and impairment of lipid profile. It been proven to pose adverse effects on cardiovascular health, and thus, should be stopped altogether to reduce the damage and prevent the worsening of cardiovascular diseases like atherosclerosis. The NHS Smokefree helpline can be contacted for advice and treatments about how to stop smoking.
Physical Activity
Regular physical activity promotes a healthy weight, which both prevents and helps treat atherosclerosis. It has been proven to lower cholesterol levels, reduce insulin resistance and glucose intolerance, lower blood pressure, increase triglyceride concentrations, and decrease HDL levels. Evidence demonstrates a linear relationship between physical activity and risk, however, the intensity, duration, frequency, and types of exercise should still be advised a physician, especially for patients who have had ischemic events.
Drugs
Oral antiplatelet drugs, such as aspirin and clopidogrel, are essential in counteracting platelet activation and thrombosis from plaque rupture. In combination with antithrombotic drugs, the recommended dose of aspirin is 81 mg daily for the secondary prevention of coronary atherosclerosis with a very high risk to minimize the risk of bleeding. Clopidogrel can be used as a substitute when ischemic events recur in patients taking aspirin and those who are aspirin-intolerant, or in combination with aspirin to increase effectivity. However, resistance to clopidogrel can also occur, and in that case, newer and more effective drugs such as prasugrel and ticagrelor can be used. Other drugs can also be used for targeted potentiality. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers reduce the risk of atherosclerosis by inhibiting the contributions of angiotensin to endothelial inflammation and dysfunction. Ezetimibe lowers LDL levels by blocking cholesterol uptake via the inhibition of the Niemann-Pick C1-like 1 protein and can be added to statin therapy to reduce cardiovascular events. Proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitors lower LDL cholesterol by improving the clearance of plasma LDL on the liver, which will be most useful in patients with familial hypercholesterolemia, who are statin-intolerant or require lipid-lowering. Rivaroxaban at 2.5 mg dose twice daily is recommended in patients with a stable atherosclerotic vascular disease whose take 100 mg aspirin dosage daily to decrease the risk of cardiovascular events, however, it is with a high risk of major bleeding.
Statin Therapy
Statin therapy is recommended as preventive therapy for patients with clinical atherosclerotic cardiovascular disease, LDL cholesterol level of 190 mgdL and over, or individuals aged 40-70 years old with 70-189 mgdL LDL cholesterol who are diabetic or scored 7.5% and over in the estimated 10-year risk of arteriosclerotic cardiovascular disease. Statins lower LDL cholesterol, which also induces the enhancement of nitric oxide production, stabilization and regression of atherosclerotic plaques, and reduction of lipid accumulation in the arterial walls. Statin therapy is employed in high, moderate, or low intensity in diagnosed patients with risk scores of 7.5%, 5-7.5%, and individuals who cannot tolerate intense treatments, respectively. Depending on the intensity, the response to statin therapy is measured in the decrease of LDL cholesterol levels.
In urgent or worsening cases of severe atherosclerosis, patients can opt to undergo invasive procedures such as coronary angioplasty and carotid endarterectomy to bypass narrowed or blocked blood vessels which will be connected to a healthy blood vessel in order to redirect blood flow. Although bypass surgeries come with high risk and cost, the efficacy after a successful procedure is significantly high with considerable survival or life expectancy.
The limitations in the diagnosis and treatment of atherosclerosis stem from the challenges in clinical research surrounding the disease. While the accumulation of plaque in the arteries that restricts blood flow seems to an uncomplicated process, the multifactorial process proves to be rather complex. Despite the efforts in understanding the development of the disease, the biological processes behind it are still not fully comprehended. The understanding surrounding the causes of fibrous cap thinning and plaque rupture is still incomplete, while the mechanisms leading to thrombosis on unruptured plaques are still unknown. While the assessment of risk factor predictive models render significant predictive power, they are rather inconclusive especially because symptoms do not appear until the disease has already progressed and is often only learned through a clinical event. By the time that the disease is diagnosed, treatment cannot reverse the disease and is only be limited to stopping it from worsening and reducing the risk of cardiovascular events, or in some cases, surgical redirection of blood flow from damaged blood vessels.
The development of diagnostic and treatment methods for atherosclerosis continues to be a challenge in clinical biochemistry. While the proactive approach is directed at prevention or the reduction of the risk factors, predictive tools are struggling with accuracy. Hence, it is critical that the intervention and diagnostic methods are advanced with urgency, considering the asymptomatic but life-threatening nature of the disease. Ultimately, it is imperative that research is geared at overcoming the limitations in clinical biochemistry by gaining a deeper understanding of the mechanisms surrounding the disease, which will pave the way for the progressive furtherance of preventive, diagnostic, and treatment methods.
