Cardiovascular Disease & Cardiac Markers

Cardiovascular Disease

• Cardiovascular markers are used in the assessment and management of heart related conditions

Learning Objectives

• Cardiovascular disease should be accurately defined to ensure proper diagnosis and treatment
• Pre-analytical factors need to be considered to maintain accuracy of lab results for cardiac function
• Testing is used to assess cardiovascular disease risk and toxicity to cardioactive medications
• Cardiac function testing includes total CK, CK-MB, troponin I and T, LDH isoenzymes and homocysteine
• The predictive values of cardiac-related clinical laboratory tests are important for predicting heart disease

Introduction

• Elevated plasma lipids, especially cholesterol, are causally related to atherosclerosis
• Atherosclerosis is the cause of most cardiovascular diseases including coronary, cerebrovascular, and peripheral vascular diseases
• Cardiovascular disease is the leading cause of death in the US and UK for people under 60
• Managing hypercholesterolaemia and other risk factors reduces cardiovascular disease mortality
• Pre-analytical variability impacts the quality of lab results, including cardiac biomarkers
• Pre-analytical variables are important for accurate diagnosis
• Patient factors like gender, age, body mass, race, diet, medications, smoking, pregnancy, and exercise are pre-analytical variables
• Patient conditions, such as fasting status, exercise, and posture, influence lab diagnostics

Preanalytical Variability Factors

• Factors affecting lab testing accuracy for cardiac function include patient preparation, fasting status, exercise, and posture
• Blood drawing, misidentification, insufficient volume, hemolysis, contamination, and venous stasis also affect accuracy
• Blood collection devices, mixing, sample transportation and preparation, time, temperature, integrity, and centrifugation are additional variables to be aware of

Modifiable Risk Factors

• Smoking is a strong CVD risk factor
• Hypercholesterolaemia/apolipoprotein (raised ApoB/ApoA1) is a strong CVD risk factor
• Other modifiable risk factors include hypertension, diabetes mellitus and abdominal obesity
• Additionally, psychosocial factors, lack of fruits/vegetables, lack of exercise and alcohol consumption are modifiable risk factors
• Hyperfibrinogenaemia and high plasma homocysteine levels are also modifiable risk factors for myocardial infarction

Non-Modifiable Risk Factors

• Advanced age is a non-modifiable risk factor for CVD
• Genetics increase the risk of myocardial infarction if a first-degree relative had cardiovascular events before age 50
• Males tend to experience myocardial infarction earlier in life than females

Myocardial Infarction Biomarkers

• MI patients commonly have crushing central chest pain with ECG changes
• Plasma enzyme measurements aid in MI diagnosis
• The MB isoenzyme of creatine kinase (CK-MB) increases first, followed by total CK, AST, HBD, and LDH
• CK-MB was once the gold standard
• Myoglobin and troponins addressed specificity and sensitivity lacking in CK-MB

Cardiac Troponins

• Cardiac troponins (I and T) are proteins of myocardial cells expressed nearly exclusively in the heart
• Troponins are very specific and sensitive for myocardial damage and their levels help define myocardial infarction
• Troponins can increase in plasma in unstable angina
• A rising cardiac troponin pattern (cTn) above the 99th percentile URL with myocardial ischemia symptoms may indicate acute MI
• Serial cTn testing at 0, 3, and 6 hours provides insight into myocardial injury severity and progression

Hypertension Investigations

• Urine analysis is done for protein (renal disease) and glucose (diabetes, a cardiovascular risk factor)
• Plasma creatinine can reveal renal disease while plasma potassium level is tested for mineralocorticoid excess
• Plasma calcium is measured to check for hyperparathyroidism
• Assessing cholesterol and triglycerides aids in cardiovascular risk assessment
• Plasma renin and aldosterone tests for Conn's Syndrome
• Overnight dexamethasone suppression test is done to check for Cushing's Syndrome

Heart Failure

• Heart failure is the heart’s inability to meet the body's needs
• It's a clinical syndrome with different causes
• It can be a medical emergency (acute pulmonary oedema) or asymptomatic early on
• It is chronic and progressive, reducing life expectancy and quality of life
• Early non-specific symptoms can complicate diagnosis, but prognosis improves with treatment
• The heart secretes ANP and BNP, with ANP mainly from atria and BNP from ventricles
• Both increase in heart failure, but BNP is better for assessing ventricular function and prognosis
• BNP is synthesized as prohormone split into BNP and NT-proBNP after release from the muscle cell
• Normal values of either BNP or NT-proBNP virtually rule out heart failure and serve as a useful 'rule out' test

Heart Failure Investigations

• Full blood count reveals anaemia as a cause of "high output" heart failure
• Low plasma albumin indicates hypoalbuminaemia, a cause of oedema
• Plasma creatinine is tested to assess renal impairment
• Plasma potassium level can reveal diuretic induced hypokalaemia
• Thyroid function tests may be conducted to check for thyrotoxicosis
• Plasma ferritin can indicate haemochromatosis
• Serum and urine electrophoresis may be performed to look for myeloma-related amyloid

Imaging

• Imaging assesses myocardial perfusion, viability, thickness, thickening, and motion
• Imaging modalities include echocardiography, radionuclide imaging, and cardiac MRI
• Echocardiography detects regional wall motion abnormalities due to ischemia
• Cardiac MRI accurately assesses myocardial structure and function

Lipid Profile Studies

• Blood for lipid profile requires a 12-14 hour overnight fast to clear chylomicrons
• For two weeks before the test, the patient should maintain their regular diet
• Do not consume alcohol the evening before sampling due to its effect on triglyceride levels
• In patients with MI or stroke, blood should be drawn within 24 hours or after three months, due to disturbed lipoprotein metabolism

Cardiovascular Disease Management

• Statins are prescribed for cholesterol-lowering
• Target lipid concentrations should be below 5.0 mmol/L for total cholesterol or below 3.0 mmol/L for LDL-cholesterol; lower targets are set for high-risk patients
• Lifestyle changes such as improved diet, exercise, and smoking cessation should be combined with medication
• Beta-blockers reduce heart rate, blood pressure, and myocardial contractility to lower oxygen consumption
• ACE inhibitors relax veins/arteries to lower blood pressure
• Nitrates prevent or treat heart pain (angina), usually in the heart's arteries
• Nitrates dilate blood vessels to increase blood flow
• Aspirin, an NSAID, prevents platelet aggregation
• Aspirin's antithrombotic action inhibits cyclooxygenase (COX) which impairs thromboxane A2 (TXA2) synthesis, reducing platelet aggregation