What is Atherosclerotic Cardiovascular Disease (ASCVD)?
Atherosclerotic cardiovascular disease (ASCVD) is a systemic condition caused by plaque buildup in arterial walls that manifests clinically as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, or peripheral arterial disease—all of atherosclerotic origin. 1
Clinical Definition and Scope
The American College of Cardiology/American Heart Association provides a comprehensive definition that includes all manifestations of atherosclerotic disease across multiple vascular beds 2:
- Coronary manifestations: Acute coronary syndromes, history of myocardial infarction, stable or unstable angina, and coronary revascularization procedures 1
- Cerebrovascular manifestations: Ischemic stroke and transient ischemic attack of atherosclerotic origin 2, 1
- Peripheral vascular manifestations: Peripheral artery disease and aortic aneurysm presumed to be atherosclerotic 1
A critical qualifier is that all manifestations must be of atherosclerotic origin, distinguishing ASCVD from other cardiovascular conditions like valvular disease or cardiomyopathy 1.
Pathophysiology and Disease Burden
ASCVD develops through the accumulation of atherogenic lipoproteins in arterial walls, leading to plaque formation over decades 3. This process:
- Represents the leading cause of morbidity and mortality worldwide 4
- Contributes to acute cardiovascular events including myocardial infarction, ischemic stroke, unstable angina, and cardiovascular death 3, 5
- Extends beyond acute events to impact dementia risk, chronic kidney disease, peripheral arterial disease with mobility impairment, and impaired sexual function 3
The relationship between elevated LDL-cholesterol and ASCVD risk is one of the most extensively validated associations in modern medicine, with elevated LDL-C being a necessary condition for atherogenesis 3.
Risk Assessment Framework
For primary prevention (patients without clinical ASCVD), the 10-year ASCVD risk is defined as the probability of nonfatal myocardial infarction, coronary heart disease death, or nonfatal and fatal stroke 2. This risk should be estimated using the Pooled Cohort Equations, which incorporate age, race, sex, cholesterol levels, blood pressure, diabetes status, and smoking 2.
For secondary prevention (patients with established clinical ASCVD), all individuals are automatically classified as high or very high risk regardless of their calculated 10-year risk score 2, 1.
Clinical Significance Across Vascular Beds
A common pitfall is excluding patients with peripheral or cerebrovascular manifestations from the ASCVD category 1. The guidelines emphasize that:
- A patient with peripheral artery disease has the same ASCVD designation as someone with prior myocardial infarction 1
- A patient with prior stroke requires the same intensive secondary prevention strategies as someone with coronary disease 1
- All patients with established ASCVD receive Class I recommendations for high-intensity statin therapy and aggressive risk factor modification 1, 6
Treatment Implications
The comprehensive ASCVD definition ensures that all patients with established atherosclerotic disease receive appropriate risk-reduction therapy regardless of which vascular bed initially manifested disease 1. This includes:
- High-intensity statin therapy for all patients ≤75 years with clinical ASCVD 6
- Moderate-intensity statins for patients >75 years or those with contraindications 6
- Blood pressure control with treatment thresholds based on ASCVD risk status 2
- Antiplatelet therapy and additional risk factor management 7
Special Populations
In young adults (typically defined as those presenting with coronary disease before age 40-50), ASCVD carries particular significance due to prolonged cardiovascular morbidity, recurrent major adverse cardiovascular events, and loss of quality-adjusted life years 8. Males are affected approximately twice as frequently as females in this age group 8.
Atherosclerotic coronary artery disease is the leading cause of sudden cardiac death and acute myocardial infarction in adult athletes over age 30-40 years 2. For many adults, sudden cardiac death or myocardial infarction is the first manifestation of ASCVD, as most acute events result from plaque disruption in lesions that were not previously flow-limiting 2.
Residual Risk Considerations
Even with excellent LDL-cholesterol control, adverse cardiovascular events remain a significant clinical problem 4. Emerging therapeutic targets beyond traditional LDL-lowering include: