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Domain

Preventive Cardiology

Modules

ASCVD Risk & Primary Prevention

Pooled Cohort Equations, PREVENT (2023), and the role of CAC scoring.

Atherosclerosis: From Endothelial Injury to Plaque Rupture

Atherosclerosis begins with endothelial injury from risk factors such as hypertension, smoking, and hyperglycemia, which increases endothelial permeability to LDL particles that infiltrate and become trapped in the subendothelial space. Oxidized LDL triggers monocyte recruitment and differentiation into macrophages, which engulf lipid to become foam cells, the hallmark of the early fatty streak. Ongoing smooth muscle migration and collagen deposition form a fibrous cap over a lipid-rich necrotic core; rupture or erosion of this cap exposes thrombogenic material to flowing blood, precipitating the acute thrombosis that causes myocardial infarction or stroke. This is why risk assessment tools emphasize cumulative, modifiable exposures like LDL-C and blood pressure over the patient's lifetime rather than a single time point.

Risk Estimation

ASCVD Pooled Cohort Equations 10-year risk age 40–75. PREVENT (2023) extends to age 30–79, includes CKD and metabolic syndrome, removes race — more accurate.

Categories

LowBorderlineIntermediateHigh<5%5–7.5%7.5–20%≥20%10-year ASCVD risk (PREVENT) — statin decisions typically anchor at ≥7.5%Low <5%, borderline 5–7.5%, intermediate 7.5–20%, high ≥20%. Statin decisions typically at ≥7.5%.

Risk Enhancers

FHx premature ASCVD, LDL-C ≥160, metabolic syndrome, CKD, chronic inflammatory, premature menopause, high-risk ethnicity, Lp(a) ≥50 mg/dL, apoB ≥130, ABI <0.9, hs-CRP ≥2.0.

CAC Scoring

Strongest test for reclassifying borderline/intermediate risk. CAC = 0 in low-risk argues against statin. CAC ≥100 or ≥75th percentile favors statin.

Risk-Enhancing Factors and Coronary Calcium Scoring

For patients in the borderline or intermediate risk range, risk-enhancing factors — family history of premature ASCVD, chronic inflammatory disease, and elevated lipoprotein(a) among them — and coronary artery calcium scoring help decide whether to initiate statin therapy. A calcium score of zero can support deferring statin therapy in an otherwise intermediate-risk patient.
Clinical pearls
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A negative CAC score (CAC = 0) has a 10-year event rate of ~1% — powerful reassurance.
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Lp(a) is genetically determined and modifiable only with niacin, PCSK9 inhibitors (modest), and emerging antisense/siRNA therapies (olpasiran, pelacarsen, lepodisiran).
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Pooled Cohort Equations should be applied to adults aged 40–75 to estimate 10-year ASCVD risk before initiating statin therapy for primary prevention.
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Aspirin is no longer routinely recommended for primary prevention in adults over 70 or those at increased bleeding risk (Class III, no benefit).
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CAC scoring is most useful when the statin decision is otherwise uncertain — a borderline or intermediate calculated risk — rather than as a universal screening test.
Related guidelines