What are the risk factors for Atherosclerotic Cardiovascular Disease (ASCVD)?

Risk Factors for Atherosclerotic Cardiovascular Disease (ASCVD)

ASCVD risk factors are categorized into traditional modifiable factors, non-modifiable factors, and risk-enhancing factors that should guide clinical decision-making for preventive interventions. 1

Traditional Risk Factors

Non-Modifiable Risk Factors

• Family history of premature ASCVD (males age <55 years; females age <65 years) 1
• Age as an independent risk determinant 1
• Sex (male sex confers higher baseline risk) 1
• High-risk race/ethnicity (particularly South Asian ancestry) 1

Major Modifiable Risk Factors

• Hypertension (systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg) 1
• Dyslipidemia including elevated LDL-C, low HDL-C (<40 mg/dL in men; <50 mg/dL in women), and elevated triglycerides 1
• Diabetes mellitus (both type 1 and type 2) 1
• Cigarette smoking (current smoking confers hazard ratio of 2.12 for ASCVD events even with zero coronary calcium) 2
• Physical inactivity and sedentary behavior 1
• Obesity (particularly increased waist circumference by ethnically appropriate cutpoints) 1
• Poor diet quality 1

Risk-Enhancing Factors for Intermediate-Risk Patients

Lipid and Metabolic Markers

• Primary hypercholesterolemia (LDL-C 160-189 mg/dL; non-HDL-C 190-219 mg/dL) 1
• Persistently elevated triglycerides (≥175 mg/dL, nonfasting, measured on 3 occasions) 1
• Metabolic syndrome (requires 3 of 5 criteria: increased waist circumference, elevated triglycerides >150 mg/dL, elevated blood pressure, elevated glucose, low HDL-C) 1
• Elevated apolipoprotein B (≥130 mg/dL, particularly when triglycerides ≥200 mg/dL) 1
• Elevated lipoprotein(a) (≥50 mg/dL or ≥125 nmol/L, especially with family history of premature ASCVD) 1

Kidney Disease

• Chronic kidney disease (eGFR 15-59 mL/min/1.73 m² with or without albuminuria, not on dialysis) 1
• Albuminuria (≥30 μg albumin/mg creatinine) 1

Inflammatory and Autoimmune Conditions

• Chronic inflammatory conditions including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease 1
• HIV/AIDS 1
• Elevated high-sensitivity C-reactive protein (≥2.0 mg/L) 1

Women-Specific Risk Factors

• Adverse pregnancy outcomes including preeclampsia 1
• Premature menopause (before age 40 years) 1
• Polycystic ovarian syndrome 1
• History of cardiotoxic chemotherapy or chest wall radiation 1

Additional Clinical Markers

• Ankle-brachial index <0.9 1

Social Determinants and Psychosocial Factors

• Race/ethnicity, education level, income, and residential zip code affect access to healthy diet and exercise facilities 1
• Depression, anxiety, loneliness, and perceived stress independently contribute to ASCVD risk 1
• Short sleep duration (<6 hours) and poor sleep quality are associated with hypertension 1
• Socioeconomic disadvantage and residence in inner-city or rural environments with limited healthcare access 1

Critical Clinical Considerations

Among patients with zero coronary artery calcium, current cigarette smoking (HR 2.12), diabetes (HR 1.68), and hypertension (HR 1.57) remain independently associated with incident ASCVD over 16-year follow-up, indicating these factors warrant aggressive management regardless of calcium score. 2

High systolic blood pressure is the primary contributor to ischemic heart disease and ischemic stroke burden, while high fasting plasma glucose and high BMI are becoming the most rapidly increasing contributors to ASCVD burden globally. 3

The ACC/AHA ASCVD Risk Estimator Plus calculator incorporates diabetes as a risk factor but does not account for diabetes duration or presence of complications such as albuminuria, retinopathy, or neuropathy, which independently increase risk. 1