PBC403 Cardiovascular Disorders Lecture 8 PDF

PMC 403 Cardiovascular Disorders Lecture 8 Outline How the heart works? Cardiovascular Disorders Myocardial Infarction Heart failure Thromboembolic disease Cardiovascular risk factors Metabolism of plasma lipoproteins Investigatio...

PMC 403 Cardiovascular Disorders Lecture 8 Outline How the heart works? Cardiovascular Disorders Myocardial Infarction Heart failure Thromboembolic disease Cardiovascular risk factors Metabolism of plasma lipoproteins Investigation of lipid abnormalities Cardiovascular Disorders (CVD) Key facts Cardiovascular diseases (CVDs) are the leading cause of death globally. An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke. Over three quarters of CVD deaths take place in low- and middle- income countries. Out of the 17 million premature deaths (under the age of 70) due to noncommunicable diseases in 2019, 38% were caused by CVDs. Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol. It is important to detect cardiovascular disease as early as possible so that management with counselling and medicines can begin. A beating heart https://www.youtube.com/watch?v=CWFyxn0qDEU Heart disease types include: Narrowing of your heart’s blood vessels because of fatty deposits (coronary artery disease). Abnormal heart rhythms (arrhythmias). Heart valve diseases. Abnormal heart muscle (cardiomyopathy). Heart squeezing and relaxation difficulties (heart failure). Heart issues you have at birth (congenital heart disease). Issues with the fluid-filled sac surrounding your heart (pericardium). Classification of CVDs PAD: Peripheral arterial disease HFrEF: heart failure with reduced ejection fraction VT: ventricular tachycardia AF: atrial fibrillation CMD: coronary microvascular dysfunction MD: coronary microvascular dysfunction Tests to diagnose various types of heart disease include: Electrocardiogram (EKG or ECG). Ambulatory monitors. Echocardiogram (Echo). Cardiac computerized tomography (CT). Heart magnetic resonance imaging (MRI). Blood tests. Stress test. Cardiac catheterization. Myocardial Infarction What is myocardial infarction? Myocardial infarction (MI), colloquially known as "heart attack," is caused by decreased or complete cessation of blood flow to a portion of the myocardium. Myocardial infarction may be "silent," and go undetected, or it could be a catastrophic event leading to hemodynamic deterioration and sudden death. Myocardial infarction happens when one or more areas of the heart muscle don't get enough oxygen. This happens when blood flow to the heart muscle is blocked. What is myocardial infarction? The blockage is caused by a buildup of plaque in the arteries (atherosclerosis). Plaque is made up of deposits, cholesterol, and other substances. When a plaque breaks (ruptures), a blood clot quickly forms. The blood clot is the actual cause of the heart attack. If the blood and oxygen supply is cut off, muscle cells of the heart begin to suffer damage and start to die. Irreversible damage begins within 30 minutes of blockage. The result is heart muscle affected by the lack of oxygen no longer works as it should. Diagnosis According to the WHO, the diagnosis of myocardial infarction is confirmed when patient has at least two of the following: History of chest pain Acute myocardial infarction ECG abnormality Rise in biochemical markers However, in addition there should be one of the following: Symptoms of ischaemia ECG changes of new ischaemia Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Acute myocardial infarction Biochemical tests in myocardial infarction and ischaemia After MI, a number of intracellular proteins are released from the damaged cells, e.g. Troponin I & Troponin T Creatine kinase CK-MB Aspartate aminotransferase (AST) Lactate dehydrogenase (LDH) Myoglobin Ischaemia-modified albumin Severity of MI with increasing concentration of troponin Troponin complex is only present in striated muscle fibres. It regulates calcium- mediated interactions of myosin and actin. It has equimolar quantities of troponin T, troponin I and troponin C. Troponin Complex Troponin T binds tropomyosin. Troponin I is an inhibitory protein. Troponin C is responsible for binding calcium. In the human heart, the cardiac-specific tropinin T and troponin I are largely insoluble but 3-5% exist as soluble cytoplasmic pool. After cardiac myocyte necrosis, the soluble fraction reaches the circulation and the insoluble fraction accounts for the prolonged plateau of troponin release. In normal condition, there is no troponin T or troponin I in the blood, but they may also be elevated in renal failure, severe heart failure and acute pulmonary embolism. Myoglobin It is a sensitive index of myocardial damage. It rises rapidly after onset of infarction. BUT it is not specific, as it rises after any form of muscle damage. A negative result can rule out MI. A positive result needs confirmation. Ischaemia-modified albumin It is a new early and sensitive marker. BUT it is not specific, so not widely used. Free radicals released during an ischemia/reperfusion process can rapidly attack albumin and modify it in a site-specific manner, reducing its ability to bind transition metals, particularly cobalt cations CK-MB (creatine kinase-myocardial band) It is more sensitive and specific than total CK. Preferable plasma CK-MB is measured together with CK. Heart Failure Heart failure means that the heart is unable to pump blood around the body properly. It usually happens because the heart has become too weak or stiff. It's sometimes called congestive heart failure, although this name is not widely used now. Heart failure does not mean the heart has stopped working. Common symptoms of heart failure trouble breathing, an irregular heartbeat, swollen legs, neck veins that stick out, and sounds from fluid built up in lungs BNP (B-Natriuretic Peptide) Without heart failure, normal BNP levels are less than 100 picograms per milliliter (pg/mL). BNP levels over 100 pg/mL may be a sign of heart failure. For NT-proBNP (N-terminal prohormone of brain natriuretic peptide), normal levels are less than 125 pg/mL for people under 75 years old and less than 450 pg/mL for people over age 75. Thromboembolic Disease A thromboembolism is a circulating blood clot that gets stuck and causes an obstruction or move to travel in the blood (an embolus). Both deep vein thrombosis (DVT, a venous thrombus most commonly occurs in the deep veins of the legs or pelvis) and pulmonary embolism are included under the umbrella term of venous thromboembolic diseases because both have the potential to obstruct blood flow in veins. A thrombosis is a blood clot. A thromboembolism is a circulating blood clot that gets stuck and causes an obstruction. Diagnosis D-dimer test measures levels of a substance that is released when blood clots dissolve. D-dimer is the degradation product of crosslinked (by factor XIII) fibrin. It reflects ongoing activation of the hemostatic system. High levels of the substance may be an indication of blood clotting. Blood tests can also measure oxygen levels in your blood and screen for inherited clotting disorders. Imaging Vascular ultrasound MR venography Figure 1. Generation of D-dimers. D-dimer molecules are generated through the degradation of crosslinked fibrin during fibrinolysis. D-dimer generation requires the activity of three enzymes: thrombin, activated factor XIII (factor XIIIa), and plasmin. First step is thrombin-mediated conversion of soluble fibrinogen to fibrin monomers. The fibrinogen molecules consist of a central E domain linked by coiled-coil regions to 2 peripheral D domains. To form fibrin monomers, thrombin cleaves short peptides (fibrinopeptides) from the N-terminal domain of the alpha- and beta-chains to expose “knobs” in the E domains (not shown). Second step is spontaneous polymerization end to end in a half-staggered, overlapping manner to form double-stranded fibrin protofibrils (the exposed knobs in the E domains insert into pre-existing “holes” in the D domains). Because the monomers and protofibrils are associated noncovalently, the fibrin network is unstable. Third step is factor XIIIa-mediated cross-linking of the D domains of adjacent fibrin monomers. Fourth step is plasmin-mediated degradation of of the fibrin network into soluble fragments, including DD(E) and DD. The presence of D-dimer molecules is suggestive of intravascular coagulation because it can only be generated after thrombin formation and subsequent degradation of cross- linked fibrin. D-dimer is the degradation product of crosslinked (by factor XIII) fibrin. It reflects ongoing activation of the hemostatic system. Cardiovascular Risk Factors Risk factors for heart disease include: High cholesterol. High blood pressure. Tobacco product use. Inactive lifestyle. Heart disease in your biological family. Type 2 diabetes. Having a BMI (body mass index) higher than 25 (having overweight). Eating unhealthy foods. Substance use disorder. The major lipids present in the plasma are fatty acids, triglycerides, cholesterol and phospholipids. Other lipid-soluble substances, present in much smaller amounts, include fat-soluble vitamins and steroid hormones. Elevated plasma concentrations of lipids, particularly cholesterol, are causally related to the pathogenesis of atherosclerosis, the process responsible for the majority of cardiovascular disease (coronary, cerebrovascular and peripheral vascular disease). Effective management of hypercholesterolaemia and other risk factors is of proven benefit in reducing cardiovascular disease mortality.