The Sandusky Dyslipidemia Model employs advanced diagnostic tools beyond standard lipid panels to identify patients at increased cardiovascular risk and to guide treatment intensification under a “lower is better” philosophy. This document consolidates the clinical protocols for each advanced tool.
Risk reclassification; de-risking when combined with ApoB
Carotid Duplex
Carotid stenosis and plaque
Standard indications; subclinical atherosclerosis
CCTA
Coronary anatomy and plaque characterization
Symptomatic patients with restricted eligibility
3.0 Apolipoprotein B (ApoB)
3.1 Pathophysiology
Each atherogenic lipoprotein particle (VLDL, IDL, LDL, Lp(a)) carries exactly one ApoB molecule. Therefore, ApoB directly quantifies the total number of atherogenic particles in circulation, regardless of the cholesterol content per particle [1]. When LDL particles are small and cholesterol-depleted (common in metabolic syndrome, diabetes, and hypertriglyceridemia), LDL-C underestimates true atherogenic burden while ApoB remains accurate [2].
3.2 Ordering Protocol
Scenario
Order ApoB?
All new patients at initial assessment
Recommended
LDL-C and non-HDL-C discordant (>10% difference in percentile ranking)
Yes
Metabolic syndrome or type 2 diabetes
Yes
Triglycerides 150–499 mg/dL
Yes
Patient at or near guideline LDL-C target
Yes — to assess for “lower is better” intensification
Risk enhancer if elevated; favors statin initiation
3.4 ApoB and De-Risking
ApoB below the risk-appropriate target in combination with CAC = 0 is the only combination that permits de-risking (deferring statin therapy). See 04 — Risk Stratification, Section 7.4.
4.0 Labcorp NMR LipoProfile
4.1 Platform and Specimen Requirements
Parameter
Details
Platform
Labcorp NMR LipoProfile (nuclear magnetic resonance spectroscopy)
Specimen
Serum or EDTA plasma
Fasting
Preferred (12 hours) for optimal triglyceride-related measurements; non-fasting acceptable for LDL-P
Total LDL particle concentration; correlates with ApoB; superior to LDL-C when discordant [3]
Small LDL-P
Varies
Proportion of small, dense LDL; marker of atherogenic dyslipidemia
LDL size (nm)
Pattern A: > 20.5 nm; Pattern B: ≤ 20.5 nm
Small dense LDL (Pattern B) associated with insulin resistance and higher ASCVD risk
HDL-P (large)
Varies
Research interest; no treatment target
LP-IR (Lipoprotein Insulin Resistance Index)
≤ 45 (lower = less insulin resistant)
Composite score; identifies insulin resistance independent of glucose metrics
VLDL-P
Varies
Triglyceride-rich lipoprotein burden
4.3 When to Order
Clinical Scenario
Rationale
Triglycerides 150–499 mg/dL
Characterize atherogenic dyslipidemia phenotype
Metabolic syndrome or type 2 diabetes
High prevalence of small dense LDL pattern
ApoB elevated but LDL-C concordant
NMR provides additional granularity
Persistent events despite LDL-C at target
Evaluate residual particle-mediated risk
Suspected insulin resistance without overt diabetes
LP-IR score assessment
4.4 Clinical Decision Framework
Elevated LDL-P with small dense predominance: Confirms atherogenic dyslipidemia → intensify LDL-lowering therapy; address metabolic drivers (insulin resistance, visceral adiposity)
Elevated LDL-P with normal LDL-C: LDL-C underestimates risk → treat based on LDL-P/ApoB
Normal LDL-P with elevated LDL-C: LDL-C overestimates risk → reassuring; may use ApoB to confirm
Elevated LP-IR: Insulin resistance marker → does not directly change lipid pharmacotherapy but supports aggressive metabolic risk management
5.0 Lipoprotein(a) [Lp(a)]
5.1 Pathophysiology
Lp(a) is a modified LDL particle with an additional apolipoprotein(a) covalently bound to the ApoB-100 molecule. It is >90% genetically determined by the LPA gene locus. Elevated Lp(a) contributes to ASCVD risk through three mechanisms: atherogenesis (LDL-like), thrombosis (structural homology with plasminogen), and inflammation (carries oxidized phospholipids) [4, 5].
5.2 Measurement Protocol
Parameter
Specification
Unit
nmol/L (preferred; isoform-insensitive)
Frequency
One-time measurement (genetically determined; does not change meaningfully over time)
Timing
Not affected by fasting status, statin therapy, or acute illness
Repeat testing
Only if initial result was borderline (75–124 nmol/L) and a different assay methodology is being used
5.3 Interpretation
Lp(a) Level
Risk Category
Clinical Action
< 75 nmol/L
Normal
No Lp(a)-specific action
75–124 nmol/L
Mildly elevated
Document as risk modifier; lower threshold for statin initiation in borderline/intermediate risk
≥ 125 nmol/L
Elevated
Risk enhancer per 2026 guidelines [6]; aggressive LDL-C lowering; screen first-degree relatives; counsel on inherited nature
De-risking possible only if ApoB also below target [9]
1–99
Mild atherosclerosis
Statin therapy favored; standard risk-appropriate treatment
100–299
Moderate atherosclerosis
High-intensity statin; additional agents as needed to meet targets
300–999
Extensive atherosclerosis
Per 2026 guidelines: LDL-C lowering therapy recommended with statin as first-line [6]
≥ 1000
Very extensive atherosclerosis
Treat as equivalent to high-risk category; aggressive multi-agent therapy
6.4 Age- and Sex-Based Percentiles
CAC scores should be interpreted relative to age- and sex-matched reference populations (MESA calculator) [10]. A score at or above the 75th percentile for age and sex indicates greater-than-expected atherosclerotic burden and should shift the patient toward more aggressive treatment regardless of the absolute score.
6.5 Repeat CAC Scoring
Routine repeat CAC scoring is not recommended. CAC progression on statin therapy does not indicate treatment failure (statins stabilize plaque and increase calcium density). Repeat CAC may be considered after 5+ years in borderline patients where the initial score was 0 and risk reassessment is clinically warranted [11].
7.0 Carotid Duplex Ultrasonography
7.1 Indications
This clinic orders carotid duplex ultrasonography for standard clinical indications only:
Indication
Details
Cervical bruit on auscultation
Screen for hemodynamically significant carotid stenosis
Prior ischemic stroke or TIA
Evaluate carotid stenosis as potential source
Known carotid stenosis
Surveillance for progression
Pre-operative assessment
Per surgical team request
7.2 Impact on Lipid Management
Finding
Lipid Management Impact
Normal / minimal plaque
No change to risk category based on carotid alone
Significant plaque (> 50% stenosis or heterogeneous plaque)
Reclassify to high-risk; high-intensity statin; aggressive LDL-C targets
> 70% stenosis or symptomatic
Manage as established ASCVD equivalent; surgical referral per guidelines
8.0 Coronary CT Angiography (CCTA)
8.1 Eligibility
CCTA is not a routine screening tool. It is reserved for symptomatic patients meeting strict eligibility criteria:
Criterion
Requirement
Symptoms
Present (chest pain, dyspnea, or anginal equivalent)
Pre-test probability
Low-to-intermediate for obstructive CAD
Cardiac rhythm
Sinus rhythm (no atrial fibrillation)
Body habitus
BMI ≤ 40 kg/m²
Prior coronary interventions
No prior stents (metal artifact)
8.2 Findings and Lipid Management Impact
Finding
Action
No coronary atherosclerosis
Reassuring; continue risk-appropriate management
Non-obstructive plaque (any location)
Initiate statin if not already on one; reclassify to at least intermediate risk
Non-obstructive plaque with high-risk features
Aggressive LDL-C lowering; close follow-up
Obstructive stenosis (≥ 50%)
Refer for functional testing or invasive angiography; treat lipids as established ASCVD
8.3 High-Risk Plaque Features on CCTA
Feature
Significance
Positive (outward) remodeling
Vulnerable plaque marker [12]
Low-attenuation plaque (< 30 HU)
Lipid-rich necrotic core
Napkin-ring sign
Thin fibrous cap overlying necrotic core
Spotty calcification
Active plaque inflammation
9.0 Integrated Decision Framework
The following table summarizes when each advanced tool adds value at different stages of the patient journey:
Clinical Stage
ApoB
NMR
Lp(a)
CAC
Carotid
CCTA
Initial assessment (all new patients)
Yes
Select
Yes (one-time)
Select
If indicated
No
Borderline/intermediate risk reclassification
Yes
If discordance
If not yet done
Yes
If indicated
No
On-treatment monitoring
Yes
Select
No (one-time)
No
No
No
Residual risk evaluation
Yes
Yes
Review prior
No
If indicated
No
Symptomatic evaluation
—
—
—
No
If indicated
If eligible
Legend: “Yes” = routinely recommended. “Select” = ordered in specific clinical scenarios (see individual sections). “If indicated” = standard clinical indications only. “No” = not appropriate at this stage.
10.0 Version History
Version
Date
Description
1.0.0
2026-03-30
Initial release
References
Sniderman AD, Thanassoulis G, Glavinovic T, et al. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA Cardiol. 2019;4(12):1287–1295.
Mora S, Buring JE, Ridker PM. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014;129(5):553–561.
Otvos JD, Mora S, Shalaurova I, et al. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 2011;5(2):105–113.
Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925–3946.
Tsimikas S, Fazio S, Ferdinand KC, et al. NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177–192.
2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia. J Am Coll Cardiol. 2026.
Raal FJ, Giugliano RP, Sabatine MS, et al. Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (OSLER-2). Lancet Diabetes Endocrinol. 2016;4(7):569–578.
Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827–832.
Blaha MJ, Cainzos-Achirica M, Greenland P, et al. Role of coronary artery calcium score of zero and other negative risk markers for cardiovascular disease. Circulation. 2019;140(16):e565–e579.
McClelland RL, Chung H, Detrano R, et al. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006;113(1):30–37.
Lehmann N, Erbel R, Mahabadi AA, et al. Value of progression of coronary artery calcification for risk prediction of coronary and cardiovascular events (Heinz Nixdorf Recall study). Circulation. 2018;137(7):665–672.
Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66(4):337–346.