04 — Risk Stratification

Table of Contents

1.0 Overview

Risk stratification is the central decision-making step in The Sandusky Dyslipidemia Model. It determines treatment intensity, the need for advanced testing, and follow-up frequency. This document describes the stepwise approach to risk assessment, integrating the AHA PREVENT equations, guideline-defined risk enhancers, and advanced tools.

See the Risk Stratification Flowchart for a visual representation of this process.

2.0 Step 1 — Identify Established ASCVD

Before calculating risk, determine whether the patient has established atherosclerotic cardiovascular disease (ASCVD):

Condition Qualifies as Established ASCVD
Prior myocardial infarction Yes
Acute coronary syndrome (history) Yes
Stable angina with obstructive CAD Yes
Coronary revascularization (PCI or CABG) Yes
Ischemic stroke Yes
Transient ischemic attack (TIA) with carotid stenosis Yes
Peripheral arterial disease (ABI < 0.9 or revascularization) Yes
Carotid endarterectomy or carotid stenting Yes

If established ASCVD is present: The patient is classified as very high risk and proceeds directly to aggressive treatment (see 05 — Treatment Pathways). PREVENT calculation is not required but may be performed for documentation.

3.0 Step 2 — AHA PREVENT Risk Calculation

For patients without established ASCVD, calculate 10-year and 30-year total cardiovascular disease (CVD) risk using the AHA Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations [1].

3.1 PREVENT Calculator Inputs

Input Required Source
Age (30–79 years) Yes Patient history
Sex Yes Patient history
Systolic blood pressure (mm Hg) Yes Clinic measurement
Total cholesterol (mg/dL) Yes Laboratory
HDL-C (mg/dL) Yes Laboratory
Current diabetes status Yes History or HbA1c ≥ 6.5%
Current smoking status Yes Patient history
eGFR (mL/min/1.73 m²) Yes Laboratory (CKD-EPI)
BMI (kg/m²) Yes Clinic measurement
Antihypertensive medication use Yes Medication review
Statin use Yes Medication review
HbA1c (%) Optional Laboratory (improves prediction in diabetics)
UACR (mg/g) Optional Laboratory (improves prediction)
Social Deprivation Index (SDI) Optional Geographic/zip code lookup

3.2 PREVENT Risk Categories

The 2026 ACC/AHA guidelines [2] define the following risk categories based on 10-year predicted ASCVD risk:

10-Year Risk Category Treatment Implications
< 5% Low Lifestyle modification; pharmacotherapy generally not indicated
5% to < 7.5% Borderline Consider risk enhancers; shared decision-making for statin therapy
7.5% to < 20% Intermediate Moderate-to-high intensity statin indicated; evaluate risk enhancers
≥ 20% High High-intensity statin; treat as high risk

The PREVENT equations produce total CVD risk (ASCVD + heart failure), not ASCVD risk alone. The PREVENT model also provides ASCVD-specific and HF-specific estimates. Use the total CVD risk for primary risk categorization per the 2026 guidelines [2]. An interactive calculator is available at Tools — PREVENT Calculator.

3.3 30-Year Risk

For patients aged 30–59 years with low 10-year risk, the 30-year risk estimate provides additional context regarding lifetime exposure to atherogenic lipoproteins. Elevated 30-year risk (≥ 39%) may support earlier initiation of lifestyle modification and consideration of pharmacotherapy [1].

4.0 Step 3 — Evaluate Risk Enhancers

For patients in the borderline (5–7.4%) or intermediate (7.5–19.9%) risk categories, risk enhancers are used to inform shared decision-making about statin initiation and to identify candidates for advanced testing.

4.1 Risk Enhancers per 2026 ACC/AHA Guidelines

# Risk Enhancer Notes
4.1.1 Family history of premature ASCVD Male first-degree relative < 55 years; female < 65 years
4.1.2 Persistently elevated LDL-C ≥ 160 mg/dL Despite lifestyle measures
4.1.3 Metabolic syndrome ≥ 3 of: waist circumference, elevated TG, low HDL-C, elevated BP, elevated fasting glucose
4.1.4 Chronic kidney disease eGFR 15–59 mL/min/1.73 m² (not on dialysis)
4.1.5 Chronic inflammatory conditions Rheumatoid arthritis, systemic lupus erythematosus, psoriasis, HIV
4.1.6 History of premature menopause < 40 years
4.1.7 Pregnancy-associated conditions Preeclampsia, pregnancy-associated hypertension
4.1.8 South Asian ancestry Well-established excess ASCVD risk [3]
4.1.9 Elevated lipoprotein(a) ≥ 125 nmol/L (see Section 6.0)
4.1.10 Elevated apolipoprotein B Discordant with LDL-C (see Section 5.0)
4.1.11 Ankle-brachial index < 0.9 Subclinical PAD
4.1.12 Elevated high-sensitivity troponin If available, persistently elevated

4.2 Clinical Action

  • ≥ 1 risk enhancer present: Favors statin initiation in borderline/intermediate risk patients. Consider advanced testing (CAC scoring, ApoB, Lp(a)) to further refine risk.
  • No risk enhancers: Shared decision-making regarding statin therapy based on patient preferences and calculated risk.

5.0 Apolipoprotein B (ApoB) Assessment

ApoB provides a direct count of atherogenic lipoprotein particles (one ApoB molecule per VLDL, IDL, LDL, and Lp(a) particle). It is the preferred measure of atherogenic burden when LDL-C may underestimate risk [4, 5].

5.1 When to Measure ApoB

Clinical Scenario Rationale
LDL-C and non-HDL-C are discordant ApoB resolves which metric better reflects true atherogenic burden
Triglycerides 150–499 mg/dL LDL-C calculation less accurate; ApoB is unaffected
Metabolic syndrome or type 2 diabetes High prevalence of LDL-C/particle number discordance (more small dense particles)
Patient at or near guideline LDL-C target ApoB used to identify residual risk and justify “lower is better” intensification
Obesity (BMI ≥ 30) Frequent discordance between LDL-C and ApoB
After initiation of lipid-lowering therapy ApoB may reveal inadequate particle lowering despite acceptable LDL-C

5.2 ApoB Thresholds

The following thresholds are used in this clinic, aligned with the 2026 ACC/AHA guidelines [2] and the European Atherosclerosis Society (EAS) consensus [5]:

Risk Category ApoB Target
Very high risk (established ASCVD) < 65 mg/dL
High risk (10-year risk ≥ 20%, DM with risk factors) < 80 mg/dL
Intermediate risk < 90 mg/dL
“Lower is better” intensification Lowest achievable with tolerated therapy

5.3 Clinical Action on ApoB Result

  • ApoB above target despite LDL-C at goal: This clinic treats this as evidence of residual atherogenic risk. Consider treatment intensification per the “lower is better” philosophy (see 05 — Treatment Pathways, Section 1.0).
  • ApoB below target with LDL-C above goal: Less common; reassuring. Continue current therapy; recheck.

6.0 Lipoprotein(a) Assessment

Lipoprotein(a) [Lp(a)] is a genetically determined, largely immutable risk factor for ASCVD and calcific aortic valve disease [6]. It is measured once per lifetime (repeat testing only if the initial result was borderline and a different assay is used).

6.1 Measurement

  • Preferred unit: nmol/L (mass-independent, isoform-insensitive)
  • Threshold for elevated risk: ≥ 125 nmol/L
  • When to measure: All new patients at The Sandusky Dyslipidemia Model clinic (one-time measurement)

6.2 Clinical Action on Elevated Lp(a)

Lp(a) Result Clinical Action
< 75 nmol/L Normal; no additional action attributable to Lp(a)
75–124 nmol/L Mildly elevated; document as risk modifier; no specific therapy but lower threshold for statin initiation
≥ 125 nmol/L Elevated risk. Counts as a risk enhancer per 2026 guidelines [2]. Drives more aggressive LDL-C lowering to offset Lp(a)-mediated risk. Counsel patient on inherited nature. Screen first-degree relatives.

6.3 Lp(a)-Targeted Therapies

Lp(a)-targeted pharmacotherapies (muvalaplin, lepodisiran, olpasiran) are not currently included in this clinic’s therapeutic plan. Phase 3 cardiovascular outcomes trials are ongoing. These agents may be incorporated in future versions as evidence matures and regulatory approvals are obtained [7].

6.4 Interim Management of Elevated Lp(a)

In the absence of specific Lp(a)-lowering agents, the approach is to aggressively reduce all modifiable atherogenic risk:

  • Maximize LDL-C lowering (statin + ezetimibe ± PCSK9i/inclisiran)
  • PCSK9 inhibitors reduce Lp(a) by approximately 20–30%, though this is not an FDA-approved indication [8]
  • Address all other modifiable ASCVD risk factors
  • Consider low-dose aspirin in higher-risk patients (shared decision-making)

7.0 Coronary Artery Calcium (CAC) Scoring

CAC scoring is available in-house and provides a direct measure of coronary atherosclerotic burden. It is the most powerful single predictor of ASCVD events in asymptomatic individuals [9, 10].

7.1 When to Order CAC

Clinical Scenario Rationale
Borderline risk (5–7.4%) with uncertainty about statin initiation CAC can reclassify risk upward or downward
Intermediate risk (7.5–19.9%) and patient hesitant about statin therapy CAC = 0 may support deferral; CAC > 0 supports initiation
Patient or provider uncertainty about therapy despite risk calculation CAC provides tangible, visual risk communication

7.2 When NOT to Order CAC

Scenario Rationale
Established ASCVD Already very high risk; CAC will not change management
Already committed to high-intensity statin Risk reclassification will not alter plan
Age < 40 or > 75 years Limited validation data at extremes of age
Prior coronary stenting or CABG Stents and surgical clips artifact the score

7.3 CAC Score Interpretation

CAC Score (Agatston Units) Interpretation Clinical Action
0 No detectable coronary calcium See Section 7.4 — De-Risking
1–99 Mild coronary atherosclerosis Statin therapy favored, especially if ≥ 75th percentile for age/sex
100–299 Moderate coronary atherosclerosis High-intensity statin recommended; consider treatment escalation
≥ 300 to 999 Extensive coronary atherosclerosis LDL-C lowering therapy recommended with consideration of statin as first line per 2026 ACC/AHA guidelines [2]
≥ 1000 Very extensive coronary atherosclerosis Aggressive multi-drug lipid-lowering; treat as equivalent to high-risk category

7.4 De-Risking: CAC = 0

A CAC score of 0 has strong negative predictive value for near-term ASCVD events [9]. However, in this clinic, de-risking (deferring statin initiation) is permitted only when BOTH conditions are met:

  1. CAC = 0 (Agatston score)
  2. ApoB is below the risk-appropriate target (i.e., “negative” — not elevated)

If CAC = 0 but ApoB is elevated, the patient retains an atherogenic particle burden that warrants treatment despite the absence of detectable calcification. Therapy should be initiated or continued.

De-risking with CAC = 0 does NOT apply to: patients with established ASCVD, LDL-C ≥ 190 mg/dL, familial hypercholesterolemia, or diabetes with additional risk factors. These patients require treatment regardless of CAC score.

8.0 Advanced Lipid Fractionation — Labcorp NMR LipoProfile

The Labcorp NMR LipoProfile provides nuclear magnetic resonance spectroscopy-based quantification of lipoprotein particles [11].

8.1 Key Parameters Reported

Parameter Clinical Utility
LDL particle number (LDL-P) Total concentration of LDL particles; correlates with ApoB; superior to LDL-C for risk prediction when discordant [12]
Small LDL-P Proportion of small, dense LDL particles; marker of atherogenic dyslipidemia
LDL particle size Small dense LDL pattern associated with higher risk
HDL-P (large and small) Research interest; no established treatment targets
VLDL-P Reflects triglyceride-rich lipoprotein burden
LP-IR (Lipoprotein Insulin Resistance Index) Composite index of insulin resistance derived from lipoprotein subclass patterns

8.2 When to Order NMR LipoProfile

Clinical Scenario Rationale
Triglycerides 150–499 mg/dL with suspected atherogenic dyslipidemia Characterize particle phenotype
Metabolic syndrome or type 2 diabetes High prevalence of small dense LDL-predominant pattern
ApoB elevated but LDL-C appears concordant NMR provides additional granularity (particle number and size)
Persistent ASCVD events despite LDL-C at target Evaluate residual particle-mediated risk

8.3 Interpretation Guidance

NMR results should be interpreted in the context of the full lipid profile, ApoB, and clinical risk assessment. In general:

  • Elevated LDL-P (> 1000 nmol/L in low-risk, > 700 nmol/L in high-risk): Supports treatment intensification, analogous to elevated ApoB
  • Small dense LDL-predominant pattern: Characteristic of insulin-resistant states; treat underlying metabolic dysfunction and intensify LDL-lowering therapy
  • LP-IR score: Useful for identifying insulin resistance; does not directly alter lipid pharmacotherapy decisions

9.0 Carotid Duplex Ultrasonography

9.1 Standard Indications

Carotid duplex ultrasonography is ordered for the following standard clinical indications:

Indication Notes
Carotid bruit on auscultation Screen for hemodynamically significant stenosis
History of TIA or ischemic stroke Evaluate for carotid stenosis as source
Pre-surgical assessment Per surgical team request
Known carotid stenosis surveillance Monitoring for progression

9.2 Findings That Alter Lipid Management

  • Carotid stenosis ≥ 50% or significant carotid plaque: Reclassifies patient to high-risk category regardless of calculated PREVENT score. High-intensity statin and aggressive LDL-C lowering indicated.

10.0 Coronary CT Angiography (CCTA)

10.1 Eligibility Criteria

CCTA is available for patients meeting all of the following:

Criterion Requirement
Symptoms Symptomatic (chest pain, dyspnea, or equivalent)
Pre-test probability Low-to-intermediate probability of obstructive CAD
Rhythm Not in atrial fibrillation
Body habitus BMI ≤ 40 kg/m²
Prior interventions No prior coronary stents

10.2 CCTA Findings That Alter Management

Finding Clinical Action
Non-obstructive plaque (any) Reclassify to at least intermediate risk; initiate statin therapy if not already on one
Obstructive stenosis ≥ 50% Refer for functional testing or invasive angiography; treat as established ASCVD for lipid management
High-risk plaque features (positive remodeling, low-attenuation, napkin-ring sign) Aggressive lipid-lowering therapy

11.0 Integrated Risk Assessment Algorithm

After completing the steps above, the provider assigns a final integrated risk category:

Final Risk Category Criteria LDL-C Target ApoB Target
Low PREVENT < 5%, no enhancers, CAC = 0 + ApoB below target < 130 mg/dL < 100 mg/dL
Borderline PREVENT 5–7.4%, no enhancers < 130 mg/dL < 100 mg/dL
Intermediate PREVENT 7.5–19.9% or borderline with risk enhancers < 100 mg/dL < 90 mg/dL
High PREVENT ≥ 20%, DM with risk factors, LDL-C ≥ 190 mg/dL, CAC ≥ 300 < 70 mg/dL < 80 mg/dL
Very High Established ASCVD, recurrent events, multivessel CAD < 55 mg/dL < 65 mg/dL

Per the “lower is better” philosophy of this clinic, these targets represent minimum thresholds. If a patient tolerates therapy and ApoB remains above target despite LDL-C at goal, treatment intensification is warranted.

12.0 Version History

Version Date Description
1.0.0 2026-03-30 Initial release

References

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  2. 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia. J Am Coll Cardiol. 2026.
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© 2026 The Sandusky Dyslipidemia Model. For clinical decision support only. Not a substitute for clinical judgment.