Coronary Artery Disease: Understanding Pathophysiology, Risk Factors, and Modern Management Approaches

Coronary artery disease (CAD) remains the leading cause of mortality worldwide, responsible for approximately one-third of all deaths in individuals over age 35. This complex cardiovascular condition develops through a progressive process of atherosclerotic plaque formation in the coronary arteries, potentially leading to myocardial ischemia, infarction, heart failure, and sudden cardiac death. Despite its prevalence and severity, significant advances in understanding CAD pathophysiology, risk stratification, and treatment options have dramatically improved outcomes over recent decades. This comprehensive guide explores the fundamental aspects of coronary artery disease, from its underlying mechanisms and risk factors to contemporary diagnostic and management strategies, providing evidence-based insights for healthcare professionals and patients navigating this common but serious cardiovascular condition.

Pathophysiology and Disease Progression

Atherosclerosis Development

The foundation of coronary disease:

• Endothelial dysfunction:
• Initial trigger in atherosclerosis
• Reduced nitric oxide bioavailability
• Increased endothelial permeability
• Enhanced adhesion molecule expression

• Proinflammatory state development

• Lipid accumulation:

• LDL cholesterol infiltration into intima
• Oxidative modification of LDL
• Foam cell formation
• Extracellular lipid accumulation

• Lipid core development

• Zánětlivé procesy:

• Monocyte recruitment and adhesion
• Macrophage transformation
• Cytokine and chemokine release
• T-cell activation
• Chronic inflammatory response

Plaque Progression and Vulnerability

From stable to unstable disease:

• Plaque composition:
• Fibrous cap formation
• Smooth muscle cell proliferation
• Extracellular matrix production
• Neovascularization

• Intraplaque hemorrhage

• Vulnerable plaque characteristics:

• Thin fibrous cap (<65 μm)
• Large lipid-rich necrotic core
• Increased macrophage infiltration
• Reduced smooth muscle cell content

• Positive remodeling

• Plaque rupture mechanisms:

• Mechanical stress factors
• Matrix metalloproteinase activity
• Inflammatory cell-mediated degradation
• Endothelial erosion
• Calcified nodule formation

Clinical Manifestations

From asymptomatic to acute syndromes:

• Stable coronary artery disease:
• Effort-induced angina pectoris
• Flow-limiting stenosis
• Predictable symptom pattern
• Exercise intolerance

• Stable plaque morphology

• Acute coronary syndromes:

• Unstable angina
• Non-ST-elevation myocardial infarction
• ST-elevation myocardial infarction
• Sudden cardiac death

• Plaque rupture or erosion

• Ischemic cardiomyopathy:

• Progressive ventricular dysfunction
• Hibernating myocardium
• Ventricular remodeling
• Vývoj srdečního selhání
• Arrhythmia substrate formation

Risk Factors and Prevention

Traditional Risk Factors

Well-established contributors:

• Non-modifiable factors:
• Age (increasing risk with advancing age)
• Male sex (earlier onset than females)
• Family history (genetic predisposition)
• Genetic polymorphisms

• Ethnicity-related risks

• Modifiable lifestyle factors:

• Tobacco use (active and passive)
• Physical inactivity
• Poor dietary patterns
• Obesity (particularly central adiposity)

• Psychosocial stress

• Medical conditions:

• Hypertension
• Dyslipidemia
• Diabetes mellitus
• Metabolic syndrome
• Chronické onemocnění ledvin

Emerging Risk Factors

Newer considerations in risk assessment:

• Zánětlivé markery:
• Vysoce citlivý C-reaktivní protein
• Interleukiny
• Tumor nekrotizující faktor alfa
• Myeloperoxidáza

• Fosfolipáza A2 asociovaná s lipoproteiny

• Thrombotic factors:

• Fibrinogen
• Plasminogen activator inhibitor-1
• D-dimer
• von Willebrand factor

• Platelet reactivity

• Other biomarkers:

• Homocysteine
• Lipoprotein(a)
• Small dense LDL particles
• Apolipoprotein B/A1 ratio
• Natriuretic peptides

Primary Prevention Strategies

Preventing initial disease development:

• Lifestyle modifications:
• Mediterranean or DASH dietary patterns
• Regular physical activity (150+ minutes/week)
• Odvykání kouření
• Weight management

• Stress reduction techniques

• Risk factor management:

• Blood pressure control (<130/80 mmHg)
• Lipid management (LDL-C targets based on risk)
• Diabetes control (HbA1c <7%)
• Metabolic syndrome management

• Aspirin in selected high-risk individuals

• Preventive pharmacotherapy:

• Statins for appropriate risk categories
• Antihypertensive therapy
• Diabetes medications with CV benefits
• Emerging preventive agents
• Risk-based approach to therapy

Diagnosis and Risk Stratification

Klinické hodnocení

Initial assessment approach:

• History taking:
• Chest pain characteristics
• Associated symptoms
• Risk factor assessment
• Functional limitation evaluation

• Previous cardiovascular events

• Physical examination:

• Vital signs assessment
• Cardiovascular examination
• Signs of heart failure
• Vascular examination

• Comorbidity evaluation

• Initial testing:

• Electrocardiogram
• Basic laboratory assessment
• Chest radiography
• Risk score calculation
• Determination of pre-test probability

Non-invasive Testing

Functional and anatomical assessment:

• Exercise stress testing:
• Treadmill or bicycle ergometry
• ECG monitoring during exertion
• Hemodynamic response assessment
• Functional capacity evaluation

• Duke treadmill score risk stratification

• Stress imaging modalities:

• Stress echocardiography
• Nuclear perfusion imaging
• Stress cardiac MRI
• PET perfusion imaging

• Comparative advantages of each

• Anatomical assessment:

• Coronary calcium scoring
• Coronary CT angiography
• CT-derived fractional flow reserve
• Plaque characterization
• Radiation considerations

Invasive Assessment

Definitive evaluation:

• Coronary angiography:
• Indications and timing
• Access site considerations
• Lesion characterization
• SYNTAX score assessment

• Limitations of luminography

• Intravascular imaging:

• Intravascular ultrasound (IVUS)
• Optical coherence tomography (OCT)
• Plaque composition assessment
• Stent optimization

• Vulnerable plaque identification

• Physiological assessment:

• Fractional flow reserve (FFR)
• Instantaneous wave-free ratio (iFR)
• Coronary flow reserve
• Microvascular function testing
• Hyperemic stenosis resistance

Medical Management

Antiplatelet Therapy

Foundation of pharmacological treatment:

• Aspirin:
• Mechanism of action
• Dosing considerations
• Duration of therapy
• Posouzení rizik a přínosů

• Resistance phenomenon

• P2Y12 inhibitors:

• Clopidogrel characteristics
• Prasugrel advantages and limitations
• Ticagrelor features
• Genetic considerations

• Duration based on clinical scenario

• Dual antiplatelet therapy:

• Indications for combination therapy
• Duration considerations
• Nástroje pro stratifikaci rizika
• Hodnocení rizika krvácení
• De-escalation strategies

Lipid-Lowering Therapy

Critical for plaque stabilization:

• Statins:
• High-intensity vs. moderate-intensity
• Pleiotropic effects
• LDL-C targets by risk category
• Management of intolerance

• Monitoring and follow-up

• Non-statin therapies:

• Ezetimibe mechanism and indications
• PCSK9 inhibitors
• Bempedoic acid
• Inclisiran

• Kombinované přístupy

• Advanced lipid management:

• Lipoprotein(a) considerations
• Triglyceride-rich lipoproteins
• HDL functionality
• Remnant cholesterol
• Emerging targets

Anti-ischemic Therapies

Symptom control and myocardial protection:

• Beta-blockers:
• Mechanism of action
• Agent selection
• Dosing strategies
• Kontraindikace

• Benefits beyond symptom control

• Calcium channel blockers:

• Dihydropyridine vs. non-dihydropyridine
• Indications and contraindications
• Combination with beta-blockers
• Side effect management

• Zvláštní skupiny obyvatel

• Nitrates:

• Short-acting formulations
• Long-acting preparations
• Tolerance development
• Combination strategies

• Hemodynamic considerations

• Novel anti-anginal agents:

• Ranolazine
• Ivabradine
• Nicorandil
• Trimetazidine
• Emerging therapies

Risk Factor Modification

Comprehensive approach:

• Hypertension management:
• Target blood pressure
• First-line agents
• Combination strategies
• Resistant hypertension approach

• Monitoring and follow-up

• Diabetes management:

• Glycemic targets
• Agents with cardiovascular benefits
• SGLT2 inhibitors
• GLP-1 receptor agonists

• Comprehensive approach

• Lifestyle interventions:

• Cardiac rehabilitation programs
• Structured exercise prescription
• Nutritional counseling
• Smoking cessation strategies
• Psychosocial support

Revascularization Strategies

Percutaneous Coronary Intervention

Catheter-based approaches:

• Stent platforms:
• Bare metal stents
• Drug-eluting stent generations
• Bioresorbable scaffolds
• Polymer technologies

• Drug selection and elution kinetics

• Complex PCI techniques:

• Chronic total occlusion approaches
• Bifurcation strategies
• Left main intervention
• Calcified lesion modification

• High-risk PCI support

• Adjunctive technologies:

• Intravascular imaging guidance
• Physiologic assessment
• Embolic protection
• Mechanical circulatory support
• Specialized devices

Coronary Artery Bypass Grafting

Surgical revascularization:

• Conduit selection:
• Internal mammary arteries
• Radial artery
• Saphenous vein
• Alternative conduits

• Harvesting techniques

• Surgical approaches:

• On-pump vs. off-pump
• Minimally invasive techniques
• Robotic-assisted surgery
• Hybrid revascularization

• Total arterial revascularization

• Special considerations:

• Diabetes-specific approaches
• Renal dysfunction
• Advanced age
• Previous cardiac surgery
• Concomitant valve disease

Revascularization Decision-Making

Individualized approach:

• Heart team concept:
• Multidisciplinary assessment
• Shared decision-making
• Patient preference incorporation
• Risk-benefit analysis

• Úvahy o kvalitě života

• Pokyny založené na důkazech:

• Left main disease
• Multivessel disease
• Proximal LAD involvement
• Diabetes considerations

• Heart failure influence

• Risk assessment tools:

• STS score
• EuroSCORE II
• SYNTAX score
• Clinical SYNTAX score
• SYNTAX score II

Special Populations and Considerations

Women with Coronary Artery Disease

Gender-specific aspects:

• Unique features:
• Atypical presentation patterns
• Microvascular dysfunction prevalence
• Non-obstructive CAD
• Spontaneous coronary artery dissection

• Stress-induced cardiomyopathy

• Diagnostic challenges:

• Lower specificity of standard testing
• Interpretation modifications
• Additional testing considerations
• Radiation concerns

• Emerging female-specific approaches

• Treatment considerations:

• Medication response differences
• Bleeding risk with antithrombotics
• Revascularization outcomes
• Cardiac rehabilitation participation
• Psychosocial support needs

Elderly Patients

Úvahy související s věkem:

• Presentation differences:
• Atypical symptoms
• Reduced exercise tolerance
• Komorbidita způsobuje zmatky
• Frailty assessment importance

• Cognitive considerations

• Diagnostic approach:

• Modified testing protocols
• Pharmacologic stress preference
• Comorbidity impact on testing
• Risk-benefit of invasive assessment

• Goals of care discussions

• Treatment adaptations:

• Medication dosing adjustments
• Polypharmacy considerations
• Revascularization risk-benefit
• Quality of life emphasis
• Individualized goal setting

Diabetes and CAD

Challenging comorbidity:

• Disease interactions:
• Accelerated atherosclerosis
• Diffuse disease pattern
• Mikrovaskulární dysfunkce
• Impaired collateralization

• Silent ischemia prevalence

• Diagnostic considerations:

• Higher pre-test probability
• Testing modality selection
• Screening approaches
• Silent ischemia detection

• Comprehensive risk assessment

• Management specifics:

• Glycemic targets
• Preferred antidiabetic agents
• Revascularization strategy preference
• Secondary prevention intensity
• Multidisciplinary care importance

Emerging Concepts and Future Directions

Precision Medicine Approaches

Individualized care:

• Genetic risk assessment:
• Skóre polygenních rizik
• Pharmacogenomics
• Genetic determinants of plaque vulnerability
• Family screening approaches

• Integration into clinical practice

• Advanced biomarkers:

• Proteomics
• Metabolomics
• MicroRNA profiles
• Circulating cell-free DNA

• Multi-marker risk scores

• Imaging-guided therapy:

• Plaque characterization
• Molecular imaging
• Artificial intelligence applications
• Personalized intervention planning
• Treatment response prediction

Novel Therapeutic Targets

Beyond traditional approaches:

• Inflammation modulation:
• IL-1β inhibition (canakinumab)
• Colchicine
• Methotrexate evaluation
• NLRP3 inflammasome targeting

• Resolution pathway enhancement

• Lipid metabolism targets:

• ANGPTL3 inhibition
• Triglyceride reduction strategies
• Lipoprotein(a) lowering
• Reverse cholesterol transport enhancement

• HDL functionality improvement

• Cellular therapies:

• Stem cell applications
• Exosome delivery
• Gene therapy approaches
• Regenerative strategies
• Tissue engineering

Zřeknutí se lékařské odpovědnosti

Důležité upozornění: This information is provided for educational purposes only and does not constitute medical advice. Coronary artery disease is a serious medical condition that requires proper evaluation and management by qualified healthcare professionals. The diagnostic and treatment approaches discussed should only be implemented under appropriate medical supervision. Individual treatment decisions should be based on patient-specific factors, current clinical guidelines, and physician judgment. If you are experiencing symptoms such as chest pain, shortness of breath, or other concerning symptoms, seek immediate medical attention. This article is not a substitute for professional medical advice, diagnosis, or treatment.

Závěr

Coronary artery disease remains a leading cause of morbidity and mortality worldwide, but significant advances in understanding its pathophysiology, risk stratification, and management have dramatically improved outcomes. A comprehensive approach incorporating precise diagnosis, aggressive risk factor modification, evidence-based pharmacotherapy, and appropriate revascularization when indicated offers the best opportunity for improved quality and quantity of life. The evolution toward more personalized approaches based on individual risk profiles, disease characteristics, and treatment response promises to further enhance outcomes in the future. As research continues to uncover new therapeutic targets and refine existing strategies, the management of coronary artery disease will continue to advance, offering hope for further reductions in the global burden of this common but serious cardiovascular condition.