Source of Health
2026 ACC/AHA Clinical Visual Guide

Inside the
Artery
How Lipids Damage,
How We Heal

An interactive visual tool for patients and practitioners built on the 2026 ACC/AHA Dyslipidemia Guidelines. Real-time plaque modeling, particle biology, CKM pathways, and live therapy simulation.

Published March 13, 2026
Source JACC + Circulation
Authors Blumenthal, Morris et al.
Replaces 2018 Cholesterol Guideline
Module 01

The Particles That Build or Break the Artery

Not all lipoproteins are equal. Size, density, apolipoprotein cargo, and oxidation potential determine whether they traffic cholesterol safely — or embed it into vessel walls over decades.

LDL — Low Density Lipoprotein

22–25 nm  ·  ApoB-100  ·  PRIMARY ATHEROGENIC AGENT

ApoB-100 belt ~22–25 nm
ApolipoproteinApoB-100
AtherogenicityHIGH — primary driver
Intimal penetrationYes — size-dependent
2026 target<55 / <70 / <100 mg/dL
Most dangerous formsdLDL (small-dense)

HDL — High Density Lipoprotein

8–12 nm  ·  ApoA-I  ·  REVERSE CHOLESTEROL TRANSPORT

ApoA-I (×2) ~8–12 nm
ApolipoproteinApoA-I
FunctionReverse cholesterol transport
Anti-inflammatoryYes — when functional
Target levelsMen >40 / Women >50 mg/dL
CKM caveatDysfunctional in T2D/CKD

Lp(a) — Lipoprotein Little-a

20–70 nm  ·  ApoB-100 + Apo(a)  ·  CLASS 1 TEST ONCE

Apo(a) kringles S–S disulfide bond
Unique featureApo(a) kringle domains
Heritability80–90% genetic
Risk threshold≥50 mg/dL (≥125 nmol/L)
2026 Class 1 recTest ONCE per lifetime
Mimics plasminogenPro-thrombotic effect

VLDL & TG-Rich Remnants

30–80 nm  ·  ApoB-100 + ApoC-III  ·  NEW 2026 FOCUS

TG TG TG ApoC-III IDL remnant TG-rich → atherogenic remnants
TG threshold≥150 mg/dL = elevated
ApoC-III roleInhibits lipoprotein lipase
Remnant penetrationIntimal access confirmed
2026 treatmentFenofibrate / Icosapent ethyl
FCS (TG≥1000)ApoC-III inhibitors

ASCVD Pathology Cascade — From Particle to Event

🔬

LDL Retention

ApoB-100 binds proteoglycans in intimal matrix. Penetration size-dependent.

Oxidation

Retained LDL oxidized by ROS → oxLDL triggers immune cascade.

🫧

Foam Cells

Macrophages engulf oxLDL via scavenger receptors → fatty streak formation.

🧱

Fibrous Cap

SMC proliferation forms fibrous cap over necrotic lipid core → vulnerable plaque.

💥

Rupture → ACS

Cap ruptures, thrombus forms → acute coronary syndrome or stroke.

Coronary Artery — Progressive Stenosis

Cross-sectional views at increasing cumulative LDL-C exposure. Stenosis % reflects combined particle burden, not a single time point.

Module 02

Live Plaque Calculator

Adjust risk parameters and watch the coronary artery respond in real time — both in longitudinal cross-section and transverse view. Up to 80 years of cumulative exposure modeled.

Risk Parameters

LDL-C (mg/dL)130
40100160220280
HDL-C (mg/dL)50
20406080100
Triglycerides (mg/dL)150
50150300450600
Systolic BP (mmHg)130
90120150175200
hs-CRP (mg/L)1.5
02.557.510
Lp(a) (mg/dL)25
050100150200
Age (years)45
2035506580
Years of Exposure20
120406080
Lifestyle Modifiers

Live Arterial Cross-Section

CORONARY ARTERY · ANIMATED · REAL-TIME PLAQUE RESPONSE
Moderate
Longitudinal View
Transverse Cross-Section
Stenosis
Lumen reduction
10-yr ASCVD
PREVENT-aligned
Non-HDL
mg/dL total burden

🔬 ApoB — True Atherogenic Particle Count

Beyond LDL-C
Estimated ApoB
mg/dL
Particle Burden
vs LDL-C
ApoB Target
mg/dL goal
Calculating concordance…

Overall ASCVD Risk

Low <3%Borderline 3–5%Intermediate 5–10%High ≥10%

🌱 Lifestyle Modification — LDL-C Reduction Potential

Mediterranean diet
−8%
Aerobic exercise
−5%
10% body weight loss
−15%
Quit smoking
+HDL
All combined
~50%↓

⚕ Sex Hormones & Lipid Modulation

Estradiol, progesterone, testosterone, and thyroid hormone (T3) each have measurable, directional effects on lipid metabolism. Toggle your patient's profile to see adjusted risk and lipid outputs. Note: These effects represent physiologic mechanisms supported by evidence — not yet incorporated into 2026 ACC/AHA guidelines.

Total Testosterone (ng/dL) 500
503006009001100
Free T3 (pg/mL) 3.2
1.5 (low)2.53.55.06.0 (high)
Status:
Estradiol E2 (pg/mL) 80
5 (post)50150280400
Free T3 (pg/mL) 3.2
1.5 (hypo)2.53.55.06.0
Progesterone (ng/mL) 1.0
0.1151525
Female Testosterone (ng/dL) 35
53070110150
LDL-C Effect
HDL-C Effect
TG Effect
Lp(a) Effect
ApoB Effect
CV Risk Adj.
Module 03

Hard vs Soft Plaque — The Critical Distinction

Not all plaque is equal. Soft (lipid-rich, vulnerable) plaque carries dramatically higher rupture risk than calcified (hard) plaque. The Cleery CTA platform revolutionizes our ability to distinguish them non-invasively.

⚠ Soft / Vulnerable

Lipid-Rich Necrotic Core

High risk of rupture · Thin fibrous cap · Active inflammation

Cap thickness<65 μm (vulnerable)
Lipid coreLarge, necrotic (>40% volume)
HU on CTA<30 HU (lipid) / 30–130 HU (fibrous)
Rupture riskHIGH — acute MI source
Macrophage contentDense — active inflammation
Response to statinsCap thickens, stabilizes
✓ Hard / Calcified

Calcified Stable Plaque

Lower rupture risk · Dense fibrous cap · Healed/scarred lesion

Cap thickness>200 μm (stable)
Calcified coreDense hydroxyapatite
HU on CTA>130 HU (calcified)
Rupture riskLOW — but causes stenosis
Macrophage contentMinimal — quiescent
CAC scoringQuantified by Agatston score

Cleery Coronary CTA — Advanced Plaque Characterization

Coronary CT Angiography with AI-enhanced plaque analysis can non-invasively characterize plaque composition, identify vulnerable lesions, and guide treatment intensity — capabilities that standard CAC scoring alone cannot provide.

🔍

Plaque Tissue Characterization

Distinguishes low-attenuation (lipid-rich), fibrous, and calcified plaque components using Hounsfield unit analysis. Soft plaque HU <30 signals highest vulnerability.

High-Risk Plaque Features (HRPF)

Identifies positive remodeling index >1.1, pericoronary fat attenuation, napkin-ring sign, and spotty calcification — each independently predicts ACS events.

📊

CCTA-Derived FFR (CT-FFR)

Computational fluid dynamics applied to CTA data estimates fractional flow reserve non-invasively — identifies hemodynamically significant lesions without catheterization.

🎯

Total Plaque Volume

Quantifies total atherosclerotic burden (TAB) — non-calcified, mixed, and calcified segments. Serial imaging tracks regression with aggressive LLT. ORION-3/FOURIER extension data.

🧬

Pericoronary Fat Inflammation

Fat attenuation index (FAI) quantifies perivascular inflammation — elevated FAI predicts cardiac events independent of traditional risk factors and plaque burden.

💊

Treatment Response Monitoring

Serial CCTA demonstrates statin-induced plaque stabilization: cap thickening, lipid core reduction, calcification progression. PCSK9 inhibitor data shows plaque regression at LDL <55 mg/dL.

Clinical Implication: A patient with CAC score of 0 may still harbor non-calcified soft plaque detectable only on CCTA. Conversely, high CAC (≥400) indicates substantial calcified burden with lower acute rupture risk than equivalent soft plaque — but significant stenosis risk. The 2026 guidelines selectively recommend CAC for risk reclassification; CCTA provides the full picture when CAC results are borderline or discordant with clinical risk.

Hounsfield Unit Spectrum — CTA Tissue Density Reference

Plaque component identification on coronary CTA is based on tissue attenuation (HU). Understanding this spectrum is essential for interpreting Cleery and CCTA reports.

Lipid Core
−100 to 30 HU
Fibrous Tissue
30–130 HU
Mixed Plaque
130–350 HU
Calcified
>350 HU
Lumen (contrast)
350–600 HU
Pericoronary Fat
−30 to −190 HU
Module 04

Lipid-Lowering Therapy Simulator

Toggle therapies and adjust doses to see cumulative LDL-C reduction, non-HDL impact, and residual ASCVD risk. Based on 2026 ACC/AHA guideline pharmacotherapy evidence.

Therapy Configuration

Baseline LDL-C 160 mg/dL
100160220280
Statin Therapy Cornerstone
Low-intensity (pravastatin 10–20mg)
Moderate-intensity (atorva 10–20mg)
High-intensity (atorva 40–80mg / rosuva 20–40mg)
Ezetimibe Add-on · Generic
Ezetimibe 10mg daily (−18–22% add'l)
Bempedoic Acid New 2026
Bempedoic acid 180mg (−17–28%)
Bempedoic + ezetimibe combo pill
PCSK9 Inhibitors High Potency
Evolocumab (Repatha) 140mg Q2W
Alirocumab (Praluent) 75–150mg Q2W
Inclisiran (siRNA, 2× yearly)
TG-Lowering Agents When TG ≥150
Fenofibrate (−30–50% TG, +5–15% HDL)
Icosapent ethyl / Vascepa (−25% TG, CVOT)
Volanesorsen / ApoC-III inhibitor (FCS)
Baseline 10-yr ASCVD Risk 18%
3%10%20%30%40%

LDL-C Reduction & Target Achievement

Baseline LDL
160
mg/dL
On-Treatment LDL
80
mg/dL
% Reduction
50%
from baseline
Very High Risk
<55
mg/dL goal
High Risk
<70
mg/dL goal
Borderline Risk
<100
mg/dL goal
Active Therapy Regimen
1

Lifestyle + Statin

Foundation of all LLT

2

+ Ezetimibe

Generic, well-tolerated

3

+ Bempedoic Acid

Statin-intolerant option

4

+ PCSK9 Inhibitor

Very-high-risk / residual LDL

5

TG-Lowering Agent

When TG ≥150 mg/dL

Estimated MACE Risk Reduction

UNTREATED 10-yr Risk
18%
major adverse cardiac events
ON-TREATMENT Risk
major adverse cardiac events
— based on 2026 guideline RRR evidence. Each 38.7 mg/dL LDL-C reduction ≈ 22% relative risk reduction (CTT meta-analysis).
Mechanism of Action

Why These Therapies Work

Each agent in the simulator acts on a specific step of hepatic lipoprotein handling. This figure maps the full pathway: LDL receptor uptake and recycling, the PCSK9 degradation axis (where PCSK9 inhibitors act), de novo synthesis (suppressed by statins), and the VLDL to IDL to LDL cascade with HDL reverse transport. Sex hormone effects are included to show how estradiol and testosterone shift the lipid picture across systems.

MECHANISM OF ACTION HEPATIC LIPOPROTEIN METABOLISM LDL LDL DEGRADATION LDL-RECEPTOR RECYCLING LYSOSOME PCSK9 increases LDL-R / LDL lysosomal degradation NUCLEUS Increased PCSK9 release PCSK9 INHIBITOR Blocks LDL-R mediated degradation, increasing LDL uptake GLUCAGON BIOFLAVONOIDS STATINS Decreased hepatic cholesterol production INSULIN Increases hepatic cholesterol production Triglycerides Apo B Cholesterol DE NOVO SYNTHESIS VLDL Apo E CII IDL Cholesterol / triglyceride distribution LDL Apo B HDL Apo A1 LCAT CETP PERIPHERAL TISSUE ABSORPTION T3 stimulates LDL-RME E2 Testosterone SEX HORMONE MODULATION OF LIPID METABOLISM Estradiol ↑ hepatic LDL-receptor expression → ↑ LDL clearance; ↑ ApoA1 / HDL. Transdermal is triglyceride-neutral; oral modestly ↑ TG (first-pass). Testosterone modestly ↓ HDL / ApoA1, ↓ triglycerides, may ↓ Lp(a); net LDL ≈ neutral.

Hormone effects vary by route and dose; transdermal estradiol is triglyceride-neutral, and the testosterone HDL effect is greater with oral or supraphysiologic dosing. Sources: Walsh et al., NEJM 1991; hormone-lipid literature; physiologic-dose data.

Module 05

CKM Syndrome & Lifetime Trajectory

Cardiovascular-Kidney-Metabolic syndrome is one interconnected biological system. See how early lifestyle intervention redirects the risk curve — from age 5 to age 80.

CKM Interconnection Network

Hover nodes to reveal bidirectional biological pathways. Particles flow continuously along active edges.

CKM Syndrome — The 5 Stages

🌱
Stage 0

Ideal Health

Primordial prevention window. Screen lipids 9–11.

Stage 1

Excess Adiposity

Insulin resistance, VLDL overproduction begins.

🌀
Stage 2

Metabolic Risk

T2D, CKD 3–4, HTN — no CVD event yet.

❤️‍🔥
Stage 3

Subclinical CVD

CAC positive, subclinical atherosclerosis on imaging.

🚨
Stage 4

Clinical Events

MI, stroke, HFpEF with CKM drivers ongoing.

Lifetime ASCVD Risk Trajectory — Age 5 to 80

Toggle intervention pathways to see how risk curves diverge. Earlier interventions create the greatest lifetime benefit through compounding protection.

No Intervention
Average American diet, sedentary. LDL drifts up with age.
Diet Change at 30
Mediterranean pattern. LDL −8%, TG −20%.
Exercise + Diet at 20
Early aerobic + diet. HDL↑, inflammation↓.
Statin Started at 40
High-intensity statin, 50% LDL reduction.
Childhood Optimization
Screening 9–11, early lifestyle. Lifelong low LDL.
Full Protocol
Childhood + lifelong lifestyle + statin at 40.
🫀

Obesity → Dyslipidemia

Visceral fat drives VLDL overproduction. Every 10 lb excess ≈ +5 mg/dL TG, −2 mg/dL HDL. Directly worsens plaque in Module 2 calculator.

🫘

CKD → Uremic Dyslipidemia

GFR decline impairs TG clearance, raises Lp(a), creates dysfunctional HDL. Standard LDL-C underestimates CKD vascular risk — ApoB needed.

🍭

Insulin Resistance → sdLDL

T2D shifts LDL particle profile to small-dense — more oxidizable, more atherogenic per particle, poorly captured by LDL-C alone.

🔥

Inflammation Amplifies All

IL-6, TNF-α from adipose tissue increase hepatic VLDL synthesis, reduce HDL function, and directly destabilize fibrous plaque caps.

🧬

Gut Microbiome → TMAO

Gut dysbiosis produces TMAO — an atherogenic metabolite amplified by red meat intake. Mediterranean diet directly reduces TMAO production.

🌙

Sleep → Metabolic Health

Poor sleep (Life's Essential 8) disrupts cortisol/insulin rhythms, elevates TG and CRP. Sleep deprivation accelerates all CKM pathways.