What are the risk factors for coronary artery disease (CAD)?

Risk Factors for Coronary Artery Disease

The major risk factors for coronary artery disease are divided into traditional modifiable factors (smoking, hypertension, dyslipidemia, diabetes mellitus) and non-modifiable factors (age, sex, family history), with global risk assessment tools like the Framingham Risk Score recommended to quantify cumulative risk. 1

Traditional Modifiable Risk Factors

Lipid Abnormalities

• Elevated LDL cholesterol is a primary driver of atherosclerotic plaque formation through endothelial dysfunction, lipid accumulation, and inflammatory cell infiltration in the arterial wall 1, 2
• Low HDL cholesterol independently increases CAD risk and frequently clusters with other metabolic abnormalities 3
• Hypertriglyceridemia, particularly triglyceride-rich lipoproteins, associates strongly with prothrombotic factors including fibrinogen and PAI-1 3

Hypertension

• Elevated blood pressure is a robust independent predictor of future coronary events when incorporated into multivariable risk models 1
• Patients with hypertension have significantly higher mortality rates and acute heart failure risk in acute coronary syndromes 1

Diabetes Mellitus

• Diabetes requiring medication is classified as a high-risk enhancer for extended antithrombotic therapy decisions 1
• Diabetic patients demonstrate greater extent of underlying CAD, more severe left ventricular dysfunction, and significantly higher mortality in both STEMI and NSTE-ACS presentations 1
• The combination of diabetes with multiple other risk factors creates a CAD risk equivalent to established coronary disease 4

Cigarette Smoking

• Current smoking is one of the classic risk factors with robust prognostic data from prospective epidemiological studies 1
• Smoking status must be documented at regular intervals as part of comprehensive risk assessment 4
• Paradoxically, current smokers may present with acute coronary syndromes at younger ages with less severe underlying CAD due to thrombosis on less advanced plaques 1

Non-Modifiable Risk Factors

Age and Sex

• Age is the strongest independent prognostic risk factor, with risk increasing most steeply beyond 70 years 1
• Age ≥60 years identifies patients at high risk for significant CAD requiring coronary imaging before liver transplantation 1
• Male sex increases likelihood of obstructive CAD compared to women with similar clinical presentations 1
• Women more frequently have non-obstructive disease, coronary vasospasm, and microvascular dysfunction, with up to 37% showing non-obstructive CAD on angiography despite positive biomarkers 2

Family History

• Family history of premature CAD (first-degree relatives with CAD in men <55 years, women <65 years) is associated with increased coronary artery calcium scores and 30-day cardiac event risk 1
• Sibling history of premature CAD demonstrates stronger association than parental history 1

High-Risk Enhancers and Emerging Factors

Chronic Kidney Disease

• CKD with eGFR 15-59 mL/min/1.73 m² is classified as both a high-risk enhancer for extended antithrombotic therapy and a CAD risk equivalent requiring intensive risk factor modification 1, 4

Polyvascular Disease

• Presence of extracardiac vascular disease (carotid, aortic, or peripheral arterial disease) is a major risk factor for poor outcomes in acute coronary syndromes 1
• Polyvascular disease (CAD plus peripheral arterial disease) qualifies as high thrombotic risk 1

Inflammatory Conditions

• Chronic systemic inflammatory diseases (HIV, viral hepatitis, systemic lupus erythematosus, chronic arthritis) associate with overall poor outcomes in young adults with CAD 1
• Concomitant systemic inflammatory disease is classified as a high-risk enhancer for extended antithrombotic therapy 1

Obesity and Metabolic Factors

• BMI >30 kg/m² identifies high-risk patients for CAD, particularly in liver transplant candidates 1
• Visceral obesity clusters with peripheral insulin resistance, increased hepatic apolipoprotein B production, and hypertension in patients with premature CAD 3
• Target weight management includes BMI 18.5-24.9 kg/m², waist circumference <40 inches (102 cm) for men, <35 inches (89 cm) for women 4

Additional Risk Factors

• MASH (metabolic dysfunction-associated steatohepatitis) as transplant indication increases CAD risk 1
• Left ventricular hypertrophy identifies high-risk patients requiring coronary imaging 1
• Premature CAD (age <45 years) or accelerated CAD (new lesion within 2-year timeframe) qualifies as high thrombotic risk 1
• History of recurrent MI is classified as both high and moderate thrombotic risk enhancer 1

Risk Assessment Strategy

Global Risk Scoring

• The Framingham Risk Score or equivalent global risk instruments must be obtained for all asymptomatic adults without clinical CHD history to combine individual risk factors into a single quantitative estimate 1
• Patients are stratified as high risk (≥20% 10-year hard CHD events), intermediate risk (6-20%), or low risk (<6%) 1
• The Risk Factor-weighted Clinical Likelihood model is recommended for estimating pre-test likelihood of obstructive epicardial CAD 1

Risk Factor Clustering

• Patients with ≥2 major risk factors require formal 10-year CHD risk calculation to determine treatment intensity 4
• Multiple risk factors frequently cluster together, including lipoprotein abnormalities, hypertension, visceral obesity, and insulin resistance 3
• The number of controlled risk factors inversely correlates with CAD risk—those with no targets achieved have four times greater risk than those with two targets achieved 5

Clinical Pitfalls

• Traditional risk factors (hypertension, hypercholesterolemia, smoking) are only weakly predictive of acute ischemia likelihood in symptomatic patients and should not solely determine admission decisions, though they strongly predict outcomes once ACS is established 1
• Prior aspirin use at ACS presentation paradoxically associates with increased cardiovascular event risk, likely reflecting more multivessel CAD and later presentation 1
• The "obesity paradox" (lower short-term mortality in overweight/obese ACS patients) reflects younger presentation age and more aggressive management, not protective effects of obesity 1
• Clinicians frequently misestimate risk without quantitative instruments, either overestimating or underestimating actual cardiovascular event probability 1