Risk Factors of Atherosclerosis

Risk Factors of Atherosclerosis and Mechanism

• Smoking: produces reactive oxygen species, leading to oxidative stress, damage to endothelial cells, and increased permeability, resulting in accumulation of lipoprotein in the subendothelial space
• Diabetes: glucose binds to blood lipids and proteins, forming Advanced Glycation End products (AGEs), which interact with and damage endothelial cells, leading to accumulation of lipoproteins in the subendothelial space
• Hypertension (HTN): shear mechanical stress on endothelial cells, decreasing nitric oxide production, leading to vasoconstriction and increased endothelial permeability
• Dyslipidemia (elevated LDL): increased LDL in the blood, leading to accumulation of lipoprotein in the subendothelial space

Formation of Atherosclerotic Plaque

• Excessive LDL deposition in the endothelium, leading to oxidation and formation of a soft, lipid-loaded core
• Platelet activation, growth factor release, and formation of a hard, fibrotic cap
• Types of atherosclerotic plaques: uncomplicated (slowly growing, asymptomatic), complicated (rupture, symptomatic), and unstable (rupture before occlusion)

Ischemic Heart Disease Syndromes

• Stable Ischemic Heart Disease (uncomplicated, stable plaque): chest pain, pressure, or tightness with activity, relieved with rest
• Acute Coronary Syndrome (complicated, unstable plaque): acute onset of chest pain or pressure at rest, due to rupture of atherosclerotic plaque with thrombosis
• Unstable Angina (reversible ischemia): acute onset of chest pain or pressure at rest, due to rupture of atherosclerotic plaque with thrombosis
• Acute Myocardial Infarction (irreversible infarction): acute onset of chest pain or pressure at rest, due to rupture of atherosclerotic plaque with 100% thrombosis

Diagnosis and Treatment

• Diagnosis of Stable Ischemic Heart Disease: normal ECG during rest, ST depression during stress test, and negative cardiac enzymes
• Diagnosis of Acute Coronary Syndrome: resting ECG (ST depression), negative cardiac enzymes, and anticoagulant and revascularization treatment
• Diagnosis of Acute Myocardial Infarction: resting ECG (ST depression or elevation), elevated cardiac enzymes, and treatment with anticoagulant and revascularization
• Treatment for Coronary Artery Syndrome: anticoagulant, revascularization, and aspirin to reduce platelet aggregation

Pathological Changes in Acute Myocardial Infarction

• Myocardial oxygen deprivation, leading to anaerobic metabolism, accumulation of lactate, and calcium influx into cells, causing cellular death (necrosis)
• Necrosis starts within 30 minutes, completes within 6-12 hours, and is recognized by macrophages within 3-7 days, leading to fibrosis and diminished heart function

Complications of Acute Myocardial Infarction

• Early complications: arrhythmias, cardiogenic shock, and acute rupture of cardiac structures
• Late complications: pericarditis, heart failure, and ventricular remodeling

Cardiac Output and Failure

• Cardiac Output: stroke volume x heart rate
• Stroke volume: end diastolic volume - end systolic volume
• Ejection fraction: stroke volume divided by end diastolic volume
• Stroke volume determinants: contractility, preload, and afterload
• Left Ventricular Systolic Heart Failure (HF with reduced EF): weak ventricular contraction, decreased stroke volume, and decreased cardiac output
• Left Ventricular Diastolic Heart Failure (HF with preserved EF): impaired ability to relax and accommodate volume, reduced end diastolic volume, and reduced stroke volume
• Causes of LV systolic HF: MI/ischemia, HTN, valvular disease, and rare diseases (myocarditis)
• Causes of LV diastolic HF: long-standing HTN, myocardial ischemia and infarction, and valvular disease

Compensatory Mechanisms

• Sympathetic nervous system activation: increases myocardial contractility, heart rate, and cardiac output
• Renin-angiotensin-aldosterone system (RAAS) activation: increases sodium and water retention, leading to increased preload and cardiac output
• Cardiac remodeling: mechanical stress on myocardium, leading to increased LV size, accommodation of increased end diastolic volume, and increased cardiac output

Diagnosis and Treatment of Heart Failure

• Diagnosis of LV systolic HF: echo (reduced LV contractility, reduced EF), chest x-ray (cardiomegaly, pulmonary congestion/edema), and treatment with beta blockers and ACE/ARBs
• Diagnosis of LV diastolic HF: echo (preserved EF, hypertrophy of wall), chest x-ray (pulmonary congestion/edema), and treatment with diuretics and SGLT2 inhibitors