Definition of Premature Atherosclerotic Disease
Premature atherosclerotic disease is defined as coronary artery disease occurring before age 55 years in men and before age 65 years in women, particularly when affecting first-degree relatives. 1, 2
Standard Age Thresholds
The American College of Cardiology and American Heart Association have established clear age cutoffs that define premature disease:
- Men: Disease onset before age 55 years constitutes premature coronary heart disease 1, 2
- Women: Disease onset before age 65 years constitutes premature coronary heart disease 1, 2
These thresholds apply specifically when evaluating family history as a cardiovascular risk factor and when determining which patients require more aggressive screening and prevention strategies. 3
Clinical Significance and Risk Implications
The presence of premature atherosclerotic disease in a first-degree relative dramatically elevates an individual's cardiovascular risk:
- Risk increases by 1.5- to 2.0-fold independent of other traditional risk factors 1, 2
- Approximately 75% of patients with premature coronary heart disease have a positive family history, demonstrating the strong hereditary component 1, 2
- The Canadian Cardiovascular Society recommends doubling a person's estimated risk when they have a family history of premature atherosclerotic cardiovascular disease 2
The risk amplification is even greater when:
- The affected relative developed disease at a younger age 1, 2
- Multiple relatives are affected 1, 2
- The genealogical proximity is closer (first-degree vs. second-degree relatives) 1, 2
Pediatric Context and High-Risk Conditions
In pediatric populations, premature atherosclerotic disease takes on additional meaning. The American Heart Association has stratified certain childhood conditions into risk tiers based on evidence of manifest coronary artery disease occurring at age 30 years or younger: 3
Tier I (High Risk) - Manifest disease by age 30:
- Homozygous familial hypercholesterolemia 3
- Type 1 diabetes mellitus 3
- Chronic kidney disease/end-stage renal disease 3
- Post-heart transplantation 3
- Kawasaki disease with current coronary aneurysms 3
Tier II (Moderate Risk) - Accelerated atherosclerosis:
- Heterozygous familial hypercholesterolemia 3
- Type 2 diabetes mellitus 3
- Kawasaki disease with regressed coronary aneurysms 3
- Chronic inflammatory disease 3
Screening and Management Implications
When premature atherosclerotic disease is identified in a family or individual, specific actions are mandated:
- Screen all first-degree relatives of patients who developed coronary heart disease before age 55 (men) or 65 (women) 1
- Begin lipid screening at age 20 rather than age 40 in adults with a family history of premature cardiovascular disease 2
- Measure blood pressure annually from age 3 in children with a family history of early cardiovascular disease 2
- Recognize that multifactorial cardiovascular risk will be higher than estimated from standard risk calculators in these individuals 1
- Consider coronary artery calcium scoring for patients with a family history of premature coronary artery disease and a low global coronary artery disease risk score 2
Special Considerations
The presence of any detectable coronary artery calcium in patients under age 50 years is associated with 5-fold increased coronary events and 3-fold increased cardiovascular events, representing a distinct high-risk phenotype. 1
For peripheral artery disease specifically, premature disease is characterized by diagnosis before age 50 years, and these patients tend to have an aggressive vascular disease process with high burden of cardiovascular risk factors. 4