What are the risk factors for coronary artery disease?

Risk Factors for Coronary Artery Disease

The major risk factors for coronary artery disease are tobacco smoking, elevated LDL cholesterol, hypertension, diabetes mellitus, low HDL cholesterol, and advancing age, with additional contributions from obesity, physical inactivity, atherogenic diet, family history, and psychosocial stress. 1, 2

Major Risk Factors (Direct Causal)

These factors directly cause coronary artery disease and independently predict cardiovascular events:

• Tobacco smoking is a powerful risk factor with risk increasing proportionally to the number of cigarettes smoked daily, and cessation reduces cardiovascular risk significantly within 3-4 years 1, 3
• Elevated LDL cholesterol shows a strong, independent, continuous, and graded positive association with coronary events, with levels ≥130 mg/dL contributing a population attributable fraction of 17% 1, 4, 3
• Hypertension (systolic blood pressure ≥130 mm Hg) carries a population attributable fraction of 28% and independently predicts coronary disease morbidity and mortality 1, 4, 3
• Diabetes mellitus significantly increases coronary artery disease risk and is considered a coronary heart disease risk equivalent, requiring equally intensive risk factor intervention as those with established disease 1, 2
• Low HDL cholesterol independently predicts cardiovascular disease incidence and is considered a major risk factor despite not being a direct cause 1, 2
• Advancing age independently predicts cardiovascular disease by reflecting the cumulative accumulation of atherosclerosis over time 1, 2

Underlying Risk Factors

These factors affect risk both through major risk factors and through independent mechanisms:

• Obesity and overweight contribute through multiple mechanisms including effects on blood pressure, lipid metabolism, and glucose tolerance, with central obesity conferring particularly high risk as part of metabolic syndrome 1, 2, 3
• Physical inactivity is a significant modifiable risk factor, with even modest activity (30 minutes at least 5 days per week) documented to reduce cardiovascular event risk 2
• Atherogenic diet high in saturated fats and low in fruits and vegetables increases risk through effects on lipid profiles and endothelial function 1, 2
• Family history of premature coronary artery disease (male first-degree relatives <55 years, female <65 years) confers a 1.5-1.7 fold increased risk independent of other risk factors, with sibling history showing stronger association than parental history 1, 5
• Socioeconomic and psychosocial stress independently contribute to coronary artery disease risk through mechanisms beyond traditional risk factors 1, 2

Emerging Risk Factors

These factors correlate with coronary artery disease risk but are not routinely included in risk prediction equations:

• Left ventricular hypertrophy significantly increases risk of sudden cardiac death with a hazard ratio of 1.45 for each 50 g/m² increment in left ventricular mass 2, 6
• Elevated heart rate has been reported as a specific predictor of sudden cardiac death in multiple studies 2
• Inflammatory markers such as high-sensitivity C-reactive protein may provide additional prognostic information, though routine measurement is not currently recommended 1, 2
• Thrombotic factors including elevated fibrinogen, factor VII, von Willebrand factor, t-PA, and PAI-1 are associated with increased coronary risk 1, 3
• Hyperhomocysteinemia is independently associated with increased risk of coronary artery disease, though clinical benefit of treatment remains under evaluation 3

Multiple Risk Factor Interaction

A critical principle is that persons with multiple major risk factors are at significantly higher risk than those with a single risk factor, and absolute risk increases exponentially with the number of risk factors present. 1, 2, 5

• Ten-year risk should be calculated for all patients with 2 or more major risk factors using validated prediction equations (Framingham, SCORE2, or Pooled Cohort Equations) to assess need for primary prevention strategies 1, 7
• Patients with coronary heart disease risk equivalents (atherosclerosis in other vascular beds, diabetes mellitus, chronic kidney disease, or 10-year risk >20%) should receive equally intensive risk factor intervention as those with clinically apparent disease 1
• The presence of peripheral atherosclerotic disease places a person in a high-risk category for coronary events 2

Age-Specific Considerations

Risk assessment and intervention priorities vary by age:

• Childhood and young adulthood: Fatty streaks are present in coronary arteries in 50% of children and 85% of young adults, with fibrous plaques increasing from 8% prevalence in childhood to 69% in young adulthood 5
• Premature coronary artery disease (males <45 years, females <55 years): Dyslipidemia (particularly abnormal total cholesterol/HDL ratio and elevated LDL cholesterol) and smoking are of particular importance 8
• Older adults: Prognostic performance of risk models decreases with age (C indices: 0.75 for ages 45-54, declining to 0.62 for ages 75-84), but absolute risk reductions from treatment increase substantially 4

Clinical Pitfalls to Avoid

• Do not wait until patients develop multiple risk factors before initiating prevention—this approach contributes to the high prevalence of coronary artery disease 1
• Do not dismiss single elevated risk factors as low priority—even single risk factors, if severe and sustained, can lead to premature coronary artery disease 1
• Do not assume available risk prediction equations apply equally to all populations—differences in underlying risk factors create variability in absolute risk estimates across populations 1
• Do not overlook the importance of calculating specific 10-year risk numbers, as these serve as powerful educational interventions to motivate lifestyle changes 1