Risk Factors for Atherosclerotic Cardiovascular Disease (ASCVD)
The major risk factors for ASCVD include tobacco smoking, hypertension, dyslipidemia (high LDL cholesterol, low HDL cholesterol), diabetes mellitus, and advancing age, which together explain 75-90% of cardiovascular events. 1
Traditional Risk Factors
Traditional risk factors can be categorized into several groups:
Constitutional (Non-modifiable) Risk Factors
- Age (increasing risk with advancing age)
- Sex (males at higher risk; females' risk increases after menopause)
- Family history of premature ASCVD (males <55 years; females <65 years)
- Race/ethnicity (e.g., South Asian ancestry carries higher risk)
Behavioral/Lifestyle Risk Factors
- Tobacco use/smoking (most potent modifiable risk factor)
- Physical inactivity
- Poor nutrition/unhealthy diet
- Obesity/overweight
Physiological Risk Factors
- Hypertension (blood pressure ≥130/80 mmHg or treated)
- Dyslipidemia:
- Elevated LDL cholesterol (≥160 mg/dL)
- Low HDL cholesterol (<40 mg/dL in men; <50 mg/dL in women)
- Elevated triglycerides (≥175 mg/dL, nonfasting)
- Diabetes mellitus (types 1 and 2)
- Metabolic syndrome
Medical Conditions
- Chronic kidney disease (eGFR 15-59 mL/min/1.73 m²)
- Chronic inflammatory conditions (psoriasis, rheumatoid arthritis, lupus, HIV/AIDS)
Risk-Enhancing Factors
Beyond traditional risk factors, several additional factors can enhance ASCVD risk assessment 1:
Female-Specific Risk Enhancers
- Premature menopause (before age 40)
- Pregnancy-associated conditions (e.g., preeclampsia)
- Polycystic ovarian syndrome
Biomarkers
- Elevated high-sensitivity C-reactive protein (≥2.0 mg/L)
- Elevated lipoprotein(a) (≥50 mg/dL or ≥125 nmol/L)
- Elevated apolipoprotein B (≥130 mg/dL)
- Ankle-brachial index <0.9
Social Determinants of Health
- Socioeconomic status
- Education level
- Income
- Geographic location/zip code
Psychological Factors
- Depression
- Anxiety
- Perceived stress
- Loneliness
Risk Factor Interactions and Importance
Risk factors often cluster and interact synergistically. Multiple risk factors substantially increase ASCVD risk compared to single risk factors 1. For example:
- Smoking carries a higher risk for CHD in persons with elevated cholesterol levels
- Diabetes combined with other risk factors significantly increases risk
Risk Assessment Approach
The ACC/AHA guidelines recommend using the Pooled Cohort Risk Equations to estimate 10-year ASCVD risk in adults 40-79 years of age 1. These equations incorporate:
- Age
- Sex
- Race
- Total cholesterol
- HDL cholesterol
- Systolic blood pressure
- Treatment for hypertension
- Diabetes
- Current smoking status
Clinical Implications
Risk Stratification: Patients can be categorized into low, intermediate, high, and very high risk groups based on their risk factor profile.
Preventive Strategies: The intensity of preventive interventions should match the level of ASCVD risk.
Risk Reassessment: Measuring and updating ASCVD risk factors every 4-6 years improves both short-term and long-term risk prediction 1.
Residual Risk: Even with statin therapy, significant residual ASCVD risk remains, particularly in those with multiple risk factors 2.
Common Pitfalls in Risk Assessment
- Underestimating risk in women: Women have unique risk factors that should be considered in assessment.
- Focusing only on LDL cholesterol: Multiple risk factors beyond lipids contribute significantly to ASCVD risk.
- Neglecting subclinical disease: Measures like coronary artery calcium can identify high-risk individuals who appear to have low risk by traditional factors.
- Overlooking emerging risk factors: Inflammatory markers and other novel biomarkers may provide additional risk information in intermediate-risk patients.
Remember that while individual risk factors are important, the total risk profile and the presence of multiple risk factors provide the most accurate assessment of ASCVD risk.