Clinician Tool

Cardiovascular Risk & Lipid Targets
Clinical Reference

Version 1.2  ·  May 2026
ESC/EAS 2019  ·  NICE NG238
2026 ACC/AHA Dyslipidemia Guideline  ·  Clinician Tool CT-augmented tiers
Published: mhaat.vercel.app/reference.html
Calculator: mhaat.vercel.app/score2-calculator.html
Nudge tool: mhaat.vercel.app/nudge.html
Developed by MedicalSpace Ltd for vat-trap.com and medical partnerships  ·  © MedicalSpace Ltd 2026
1 Lipid Targets by Risk Tier — Global Guideline Consensus

Lipid targets — ESC/EAS 2019 · NICE NG238 · 2026 ACC/AHA Dyslipidemia Guideline · Clinician Tool CT-augmented tiers

All three major guideline frameworks converge on the same core principle: the higher the cardiovascular risk, the more aggressive the lipid target. ESC/EAS, NICE and the 2026 ACC/AHA Multisociety Dyslipidemia Guideline (Blumenthal et al., JACC 2026) use slightly different risk-stratification language but their treatment targets align closely once converted to common units. LDL-C and non-HDL-C are shown in both mmol/L (SI / UK / Europe) and mg/dL (US conventional). ApoB is reported in g/L (ESC) or mg/dL (ACC/AHA) — both shown.

Global consensus — three guidelines, one principle
The 2026 ACC/AHA Multisociety Dyslipidemia Guideline (a major update on the 2018 cholesterol guideline) reaffirms LDL-C as the primary target with risk-stratified intensity, formally endorses numeric LDL-C and non-HDL-C treatment goals (a significant shift from the 2018 "% reduction only" approach), and aligns with ESC/EAS 2019 in supporting "lower is better". New in 2026: Lp(a) measurement at least once in all adults (COR 1) · ApoB on LLT (COR 2a) · the PREVENT-ASCVD calculator replaces the Pooled Cohort Equations for ages 30–79 with LDL 70–189 mg/dL (1.8–4.9 mmol/L) · CKM (cardiovascular-kidney-metabolic) syndrome formally introduced.

Three guideline frameworks — at a glance

ESC / EAS 2019
Europe — risk-stratified absolute targets
SCORE2-based tiers (Low / Moderate / High / Very high / Recurrent). LDL-C targets as absolute mmol/L thresholds plus ≥50% reduction at high/very-high tiers. ApoB and non-HDL-C targets formally defined for each tier. "Lower is better" endorsed.
NICE NG238 (UK)
UK — pragmatic % reduction goal
QRISK3 ≥10% triggers atorvastatin 20 mg primary prevention. Goal: >40% non-HDL-C reduction. Secondary prevention: LDL-C ≤2.0 mmol/L or non-HDL-C ≤2.6 mmol/L. ApoB not targeted. No risk-stratified subdivision of secondary prevention.
2026 ACC / AHA / MS
US — PREVENT-ASCVD + numeric goals
Four PREVENT-ASCVD risk groups: Low <3% · Borderline 3–<5% · Intermediate 5–<10% · High ≥10%. Borderline/Intermediate: LDL-C <100 mg/dL (2.6 mmol/L). High (≥10%): <70 mg/dL (1.8 mmol/L) + ≥50% ↓. Very-high-risk ASCVD: <55 mg/dL (1.4 mmol/L).

Unified risk-tier lipid targets — dual units

For patients without prior CTCA, a blended ESC / NICE / AHA approach is used — the three guidelines converge closely on the same numeric targets when converted to common units (LDL-C: 1 mmol/L ≈ 38.67 mg/dL). For any patient who has undergone CTCA ± FAI, CT findings may assign or upgrade to an Clinician Tool defined CT tier independently of calculated SCORE. The LDL-C:ApoB ratio (mmol/L ÷ g/L) is used as a clinically accessible surrogate for small dense LDL particle predominance.

Risk tier Who qualifies LDL-C target Non-HDL target ApoB target Guideline source LDL-C : ApoB ratio & particle pattern
No prior CTCA — blended ESC / NICE / AHA approach
Low / primary
ESC low · ACC/AHA low		 Primary prevention. ESC: SCORE2 <2.5–5% (age-banded). 2026 ACC/AHA: 10-yr ASCVD <3% (PREVENT-ASCVD). No major risk factors. Lifestyle therapy primary.
<3.0 mmol/L<116 mg/dL
<4.0 mmol/L<155 mg/dL
—
Not defined
 ESC ACC/AHA
ApoB not targeted. Ratio useful if atherogenic dyslipidaemia suspected.
>3.37 — Pattern A reassuring
2.59–3.37 — mixed A/B; discuss risk
Borderline / Moderate
ESC moderate · ACC/AHA borderline		 ESC: SCORE2 1%–5%; young diabetes w/o RFs; QRISK3 <10%. 2026 ACC/AHA borderline: 10-yr ASCVD 3% to <5% by PREVENT-ASCVD; consider risk-enhancers, CAC, reproductive risk markers in shared decision-making. hs-CRP ≥2 mg/L on 2 occasions → high-intensity statin (COR 2a).
<2.6 mmol/L<100 mg/dL
<3.4 mmol/L<130 mg/dL
<1.00 g/L<100 mg/dL
 ESC ACC/AHA
Expected ratio ≈2.6 at target LDL-C/ApoB.
>2.59 — Pattern A/B acceptable
<2.33 — Pattern B; intensify despite on-target LDL-C
Pattern B + waist:height >0.5 or high VATI → consider GLP-1 / VAT clinic referral
Intermediate
ESC high · ACC/AHA intermediate		 ESC: SCORE2 5–<10%; FH w/o RF; T2D >10 yrs or +RF; CKD eGFR 30–59. 2026 ACC/AHA intermediate: 10-yr ASCVD 5–<10% by PREVENT-ASCVD. Moderate-intensity statin, ≥30–49% reduction (goal LDL <100 mg/dL / 2.6 mmol/L); intensify with CAC ≥100, high-risk enhancers, or LDL-C >160 mg/dL (4.1 mmol/L).
<2.6 mmol/L<100 mg/dL
moderate-intensity statin · ≥30–49% ↓
<3.4 mmol/L<130 mg/dL
<1.00 g/L<100 mg/dL
 ESC ACC/AHA
Expected ratio ≈2.5 at target.
<2.33 — Pattern B; check ApoB. AHA risk-enhancer if ApoB ≥120 mg/dL (1.20 g/L).
High
ESC high / NICE secondary · ACC/AHA high		 ESC: SCORE2 ≥10%; FH + ASCVD/major RF; established CVD (NICE secondary). 2026 ACC/AHA high: 10-yr ASCVD ≥10% by PREVENT-ASCVD (primary prevention). High-intensity statin, ≥50% reduction. Add ezetimibe if not at LDL <70 mg/dL (1.8 mmol/L) goal. CAC 100–299 or ≥75th centile triggers this tier independently.
<1.8 mmol/L<70 mg/dL
high-intensity statin · ≥50% ↓
NICE: ≤2.0 mmol/L secondary
<2.6 mmol/L<100 mg/dL
<0.80 g/L<80 mg/dL
 ESC NICE ACC/AHA
Expected ratio ≈2.25 at target.
<2.33 — Pattern B expected at this LDL level; ApoB is primary driver. Consider PCSK9i/inclisiran if ApoB not at goal.
Very high
ESC very high · ACC/AHA non-VHR ASCVD		 Clinical ASCVD without very-high-risk criteria · eGFR <30 · FH + ASCVD or major RF · ESC SCORE2 ≥10% with imaging or established CVD. 2026 ACC/AHA secondary prevention (not VHR): high-intensity statin, ≥50% reduction. Initial goal LDL <70 mg/dL (1.8); add ezetimibe/PCSK9i/bempedoic to reach LDL <55 mg/dL (1.4) if not achieved. Severe hyperchol + ASCVD → goal <55 mg/dL (1.4) directly.
<1.4 mmol/L<55 mg/dL
+ ≥50% ↓
<2.2 mmol/L<85 mg/dL
<0.65 g/L<65 mg/dL
 ESC ACC/AHA
Expected ratio ≈2.15 at target.
<2.33 — severe Pattern B likely at these levels. ApoB is the dominant actionable target; ratio monitors particle normalisation.
Very-high-risk ASCVD
ESC extended · ACC/AHA VHR ASCVD		 ESC: recurrent vascular events despite therapy. 2026 ACC/AHA very-high-risk ASCVD: ≥2 major ASCVD events (ACS within 12 months · prior MI · ischaemic stroke · symptomatic PAD) OR 1 major event + multiple high-risk conditions (age >65 · prior revascularisation · current smoker · diabetes · HF · hypertension · LDL >100 mg/dL [2.6 mmol/L] despite max statin + ezetimibe). High-intensity statin + ezetimibe + PCSK9i/bempedoic to reach goal LDL <55 (1.4), non-HDL <85 (2.2).
<1.4 mmol/L<55 mg/dL
ACC/AHA 2026: COR 1
<1.0 mmol/L may be considered (ESC)
<2.2 mmol/L<85 mg/dL
<0.65 g/L<65 mg/dL
 ESC ACC/AHA
Expected ratio ≈2.15 at target.
Deep Pattern B territory. ApoB is sole primary marker; ratio confirms particle normalisation only.
CTCA-evaluated patients — CT-augmented Clinician Tool tiers (aligns with 2026 ACC/AHA CAC-guided LDL goals)
CT high risk
CTCA ± FAI positive
CTCA/FAI Tool		 Non-obstructive significant CAD on CTCA; FAI-Score 50th–74th centile with visible plaque; or ≥75th centile with non-proximal plaque; borderline FFR-CT. 2026 ACC/AHA CAC 100–299 AU or ≥75th centile (COR 1) → LDL <70 mg/dL (1.8 mmol/L) with high-intensity statin. Minimum: ESC very high risk / ACC/AHA secondary-prevention intensity.
<1.8 mmol/L<70 mg/dL
+ ≥50% ↓ · CAC 100–299 or ≥75th centile
<2.6 mmol/L<100 mg/dL
<0.80 g/L<80 mg/dL
 Tool ACC/AHA
Expected ratio ≈2.25 at target.
<2.33 with ApoB not at goal — escalate therapy. FAI elevation independently justifies intensification.
CT ultra-high risk
High-risk CT features
Ultra-high Tool		 Any of: FAI-Score ≥75th centile with zero plaque (pre-plaque inflammatory phenotype); FAI-Score ≥90th–95th centile regardless of plaque; vulnerable plaque (LRNC, spotty Ca²⁺, positive remodelling, napkin-ring sign); proximal LAD / LM involvement; multivessel disease; extensive plaque volume; stenosis ≥50%. 2026 ACC/AHA CAC 300–999 AU (COR 2a) → LDL <55 mg/dL (1.4 mmol/L) independently of stenosis grade. Equates to ACC/AHA very-high-risk ASCVD intensity.
<1.4 mmol/L<55 mg/dL
CAC 300–999 (COR 2a)
<1.0 (<40 mg/dL) may be considered
<2.2 mmol/L<85 mg/dL
<0.65 g/L<65 mg/dL
 Tool ACC/AHA
Expected ratio ≈2.15 at target.
Max statin + ezetimibe ± bempedoic acid. Initiate PCSK9i / inclisiran. ApoB is primary target. Serial ratio tracks particle-size improvement.
Persistent pattern B despite lipid Rx → VAT / GLP-1 clinic (see Section 4)

Unit conversions: LDL-C, non-HDL-C, TC, HDL-C — 1 mmol/L ≈ 38.67 mg/dL. Triglycerides — 1 mmol/L ≈ 88.5 mg/dL. ApoB — g/L × 100 = mg/dL (e.g. 0.80 g/L = 80 mg/dL). Lp(a) — nmol/L is the preferred unit globally; mg/dL conversion is isoform-dependent and discouraged for clinical decision thresholds.

LDL-C:ApoB ratio thresholds: Ratio = LDL-C (mmol/L) ÷ ApoB (g/L). >3.37 = Pattern A (large buoyant LDL); 2.59–3.37 = Pattern A/B mixed; 2.33–2.59 = Pattern B (small dense LDL); <2.33 = Severe Pattern B. At low absolute LDL-C levels (<1.8 mmol/L / <70 mg/dL) the ratio will typically fall in the Pattern B range as a mathematical consequence — ApoB and absolute particle number are the clinically actionable parameters at these levels.

ESC/EAS 2019: Risk-stratified LDL-C, non-HDL-C and ApoB targets per Mach et al., Eur Heart J 2020;41:111–188. ApoB targets are ESC-derived.

NICE NG238: Primary prevention — offer atorvastatin 20 mg at QRISK3 ≥10%; target >40% non-HDL reduction. Secondary prevention — LDL-C ≤2.0 mmol/L or non-HDL-C ≤2.6 mmol/L. NICE does not subdivide secondary prevention into ESC-style strata or provide ApoB targets.

2026 ACC/AHA Multisociety Dyslipidemia Guideline (Blumenthal RS et al., JACC 2026, doi:10.1016/j.jacc.2025.11.016 · co-published Circulation 2026). A major update on the 2018 cholesterol guideline. Key changes: (1) PREVENT-ASCVD equations replace Pooled Cohort Equations for ages 30–79 with LDL 70–189 mg/dL (1.8–4.9 mmol/L); (2) Risk groups: Low <3% · Borderline 3–<5% · Intermediate 5–<10% · High ≥10%; (3) Numeric LDL-C and non-HDL-C goals formally endorsed (a shift from 2018 % reduction only): borderline/intermediate goal LDL <100 mg/dL (2.6); high (≥10%) goal LDL <70 mg/dL (1.8); secondary prevention not VHR goal <70 mg/dL (1.8); very-high-risk ASCVD goal <55 mg/dL (1.4); (4) Lp(a) COR 1 — measure once in all adults; (5) ApoB COR 2a — measure on LLT particularly with ASCVD, CKM, T2D, or elevated TG; (6) hs-CRP ≥2 mg/L on 2 occasions in borderline → high-intensity statin (COR 2a); (7) CKM (cardiovascular-kidney-metabolic) syndrome formally introduced. CAC-guided goals: CAC = 0 in intermediate → defer + repeat in 3–7 years; CAC 1–99 (<75th centile) → moderate-intensity statin, LDL <100 mg/dL; CAC 100–299 or ≥75th centile → LDL <70 mg/dL (COR 1); CAC 300–999 → LDL <55 mg/dL (COR 2a).

CT-augmented tiers (Clinician Tool): FAI and high-risk CT morphological features escalate patients to higher-intensity targets independently of stenosis. Consistent with 2026 ACC/AHA endorsement of CAC ≥100 / ≥75th centile triggering high-intensity statin and CAC 300–999 triggering very-high-risk ASCVD-intensity LDL goals. sdLDL is not a formal treatment target in ESC/EAS 2019, NICE NG238 or 2026 ACC/AHA; LDL-C:ApoB ratio is used as a clinically accessible particle-size surrogate.

2 Risk Calculation — Global Tools (ESC · NICE · AHA)

SCORE / SCORE2 — what the ESC tool calculates

SCORE estimates the 10-year probability of dying from atherosclerotic CVD — fatal events only (MI, stroke, aortic rupture). It does not include non-fatal events. SCORE applies primarily to primary prevention patients without established high-risk conditions — see override table below.

Input variables

Input
Age
Input
Sex
Input
Smoking status
Input
Systolic BP (mmHg)
Input
Total cholesterol (or TC:HDL ratio)

In practice SCORE is read from ESC colour-coded risk charts — locate the age row, BP column and cholesterol column for smoker/non-smoker to read the % risk directly.

ESC/EAS 2019 risk categories

SCORE resultCategoryClinical meaningLipid target
<1% Low risk <1 in 100 chance of dying from CVD in next 10 years. Lifestyle advice first. LDL-C <3.0 mmol/L
1% to <5% Moderate risk 1–5 in 100 chance. Statin generally indicated if lifestyle insufficient. LDL-C <2.6 mmol/L
5% to <10% High risk 5–10 in 100 chance. Statin indicated. LDL-C <1.8 mmol/L + ≥50% reduction
≥10% Very high risk ≥10 in 100 chance. Intensive statin ± additional therapy. LDL-C <1.4 mmol/L + ≥50% reduction

Clinical overrides — SCORE not required

These conditions automatically assign a risk category. Go directly to the assigned tier — no chart lookup needed.

Condition
Detail
Assigned tier
Established ASCVD
Previous MI, ACS, PCI/CABG, stroke/TIA, PAD; or unequivocal ASCVD on imaging
Very high
Diabetes + organ damage
Microalbuminuria, retinopathy, neuropathy; or duration >10 yrs; or additional CV risk factors
Very high
Severe CKD
eGFR <30 mL/min/1.73m²
Very high
Familial hypercholesterolaemia + ASCVD or major RF
Familial hypercholesterolaemia with established CVD or another major risk factor
Very high
Familial hypercholesterolaemia (no other major RF)
Familial hypercholesterolaemia without other major risk factors
High
LDL-C >4.9 mmol/L
Markedly elevated LDL regardless of SCORE result
High (min)
BP ≥180/110 mmHg
Markedly elevated single risk factor
High (min)
CKD eGFR 30–59
Moderate CKD
High
Diabetes without complications
T2D >10 yrs or + another RF; T1D >35 yrs or duration >10 yrs
High
Young diabetes, no RFs
T1D <35 yrs, T2D <50 yrs, duration <10 yrs, no other risk factors
Moderate
Key principle: In a specialist cardiology clinic the majority of patients will fall into an automatic tier. SCORE is mainly relevant for cleaner primary prevention patients attending for health screening.

SCORE2 — updated 2021 framework

ESC 2021 updated to SCORE2, estimating fatal + non-fatal CVD events with age-stratified thresholds. The Clinician Tool lipid targets table is anchored to ESC/EAS 2019 (original SCORE). Digital tools (e.g. ESC CVD Risk app) now output SCORE2 values — thresholds differ by age band. UK uses the moderate-risk European region calibration.

Age 40–49
Low–mod <2.5%
High 2.5–<7.5%
Very high ≥7.5%
Age 50–69
Low–mod <5%
High 5–<10%
Very high ≥10%
Age ≥70 (SCORE2-OP)
Low–mod <7.5%
High 7.5–<15%
Very high ≥15%

QRISK3 — UK primary prevention in NHS practice

In the UK, QRISK3 is the primary prevention risk tool used in NHS general practice and recommended by NICE NG238. It is a separate system from ESC SCORE2 and is more widely used by UK GPs than ESC risk tools. The two systems are complementary but not directly equivalent — QRISK3 estimates total CV event risk (fatal + non-fatal) in a UK-calibrated population, while SCORE2 estimates fatal + non-fatal risk calibrated for European regions.

Feature
QRISK3 (NICE / NHS)
SCORE2 (ESC)
What it estimates
10-year risk of fatal or non-fatal CVD (MI, stroke)
10-year risk of fatal + non-fatal CVD; age-stratified thresholds
Population calibration
UK-specific (QResearch database, ~40 million patient-years). Includes ethnicity, deprivation.
European region-calibrated (low/moderate/high/very high risk countries). UK = low-risk region.
Key additional variables
Ethnicity, deprivation (Townsend), atrial fibrillation, rheumatoid arthritis, SLE, severe mental illness, HIV, erectile dysfunction, migraine, corticosteroid use, type 1 diabetes, CKD, BMI, family history of CVD, SBP variability
Age, sex, smoking, systolic BP, non-HDL cholesterol (SCORE2). Fewer variables — simpler to apply.
Treatment threshold (NICE)
Offer statin (atorvastatin 20 mg) at QRISK3 ≥10%. Discuss shared decision-making 7.5–10%.
No single NICE threshold — ESC uses age-banded SCORE2 thresholds (see above).
Where used
NHS GP practice. Embedded in SystmOne, EMIS, Vision. qrisk.org
ESC CVD Risk app, specialist cardiology, Clinician Tool risk calculator.
Lipid target alignment
NICE NG238: primary prevention target >40% non-HDL reduction. No risk-stratified LDL-C tiers.
ESC/EAS 2019: risk-stratified LDL-C, non-HDL and ApoB targets by SCORE tier.
Clinician Tool approach: Patients referred from primary care will usually have a QRISK3 score. In this tool this is used alongside SCORE2 to contextualise risk — both are informative. Where a QRISK3 score is ≥10% but SCORE2 places the patient in a lower tier (e.g. due to different variable weighting), clinical judgement applies. CTCA/FAI findings override both where available. Note that QRISK3 does not define ESC-style risk tiers (moderate/high/very high) or specify lipid targets beyond the NICE >40% non-HDL reduction goal.

PREVENT-ASCVD — US primary prevention (2026 ACC/AHA)

The 2026 ACC/AHA Multisociety Dyslipidemia Guideline formally adopts the PREVENT-ASCVD equations as the primary US risk calculator, replacing the Pooled Cohort Equations (PCE) for ages 30–79 with LDL-C 70–189 mg/dL (1.8–4.9 mmol/L). PREVENT estimates both 10-year and 30-year risk of total CVD (including heart failure), incorporates eGFR, BMI, HbA1c (if known) and an optional social-deprivation index, and is calibrated on a contemporary US population. Race is omitted as an input. Note: PCE remains valid for adults >75 or where PREVENT inputs are unavailable, but is no longer the preferred calculator.

2026 ACC/AHA — PREVENT-ASCVD risk groups
Low <3%
Borderline 3% to <5%
Intermediate 5% to <10%
High ≥10%
Risk-enhancing factors (Table 13, 2026)
Premature ASCVD family hx (M<55, W<65) · Higher-risk ancestry (S Asian, Filipino) · High polygenic risk score · Chronic inflammatory disease (SLE, RA, advanced psoriasis) · Lp(a) ≥125 nmol/L or ≥50 mg/dL · hs-CRP ≥2 mg/L on >1 occasion · TG persistently ≥175 mg/dL (2 mmol/L) non-fasting or ≥150 mg/dL (1.7) fasting · CKM syndrome · LDL persistently 160–189 mg/dL (4.1–4.9), non-HDL 190–219 mg/dL, or ApoB ≥120 mg/dL (1.20 g/L) · Reproductive risk markers (premature menopause, preeclampsia, GDM, gestational HTN, preterm delivery)
CAC decision-modifier (COR 1 / 2a, 2026)
CAC = 0 Defer + repeat 3–7 yr (selected)
CAC 1–99 <75th centile Mod-intensity, LDL <100
CAC 100–299 or ≥75th % LDL <70 (COR 1)
CAC 300–999 LDL <55 (COR 2a)
Big-picture changes in 2026 ACC/AHA vs 2018
PREVENT replaces PCE (and the risk thresholds shift dramatically — 2018's 7.5%/20% become 2026's 5%/10%). Numeric LDL-C and non-HDL-C goals re-introduced after a decade of % reduction only — bringing ACC/AHA much closer to ESC/EAS philosophy. Lp(a) measurement at least once in every adult (COR 1). ApoB measurement on LLT (COR 2a), especially in ASCVD, T2D, CKM, or elevated TG. CAC = 0 + low-risk features can support deferring statin with reassessment in 3–7 years. CKM (cardiovascular-kidney-metabolic) syndrome formally introduced as a unifying construct. The very-high-risk ASCVD definition is retained but explicitly anchored to LDL <55 mg/dL (1.4 mmol/L) / non-HDL <85 mg/dL (2.2).

Three risk frameworks — side-by-side

Feature
SCORE2 (ESC)
QRISK3 (NICE/NHS)
PREVENT-ASCVD (2026 ACC/AHA)
What it estimates
10-yr fatal + non-fatal CVD (age-stratified thresholds)
10-yr fatal or non-fatal CVD (MI, stroke)
10- & 30-yr total CVD incl. HF (PREVENT-ASCVD subset = MI/stroke for treatment decisions)
Population calibration
European regions (low/mod/high/very-high). UK = low-risk region.
UK QResearch DB. Includes ethnicity, deprivation.
Contemporary US cohorts (NHANES + multiple US prospective cohorts). Calibrated to current incidence.
Key variables
Age, sex, smoking, SBP, non-HDL-C
+ Ethnicity, deprivation, CKD, T1DM/T2DM, AF, RA, SLE, BMI, FHx, SBP variability
Age, sex, smoking, SBP, BP-Rx, TC, HDL, T2DM, eGFR, BMI, HbA1c (optional), SDI (optional). Race omitted.
Statin threshold
Age-banded SCORE2 (see table)
QRISK3 ≥10%; SDM 7.5–10%
10-yr ASCVD ≥10% high → high-intensity, ≥50% ↓. Intermediate 5–<10% → moderate-intensity, ≥30–49% ↓. Borderline 3–<5% → SDM with risk-enhancers / CAC.
Where used
ESC CVD Risk app, EU specialist practice
UK NHS GP practice (SystmOne, EMIS, Vision)
ACC ASCVD Risk Estimator (PREVENT); AHA online PREVENT calculator
Lipid target alignment
Risk-stratified LDL-C, non-HDL-C, ApoB by SCORE2 tier
>40% non-HDL reduction; secondary prevention LDL ≤2.0 mmol/L
Numeric LDL/non-HDL goals: borderline/intermediate <100 mg/dL (2.6); high <70 (1.8) + ≥50% ↓; VHR ASCVD <55 (1.4); ApoB targets as alternative atherogenic marker.
All three frameworks — same direction of travel
Despite different inputs and population calibrations, all three calculators rank-order patients similarly and produce treatment recommendations that converge on the same lipid targets at each risk level. Where calculators disagree (e.g. a younger patient with strong family history scoring low on SCORE2 but having a CAC score above the 75th percentile), imaging-defined disease and risk-enhancing factors take precedence. The 2026 ACC/AHA Multisociety Dyslipidemia Guideline explicitly elevates CAC scoring to a primary decision-modifier (CAC = 0 supports deferring statin with reassessment in 3–7 years; CAC 100–299 or ≥75th centile triggers LDL goal <70 mg/dL [COR 1]; CAC 300–999 triggers LDL goal <55 mg/dL [COR 2a]) — paralleling and aligning with the Clinician Tool CT-augmented tier philosophy.
3 CTCA & FAI — CT Risk Classification

CT coronary angiography & fat attenuation index

CTCA images coronary anatomy, plaque burden, stenosis severity and plaque composition. FAI (fat attenuation index) quantifies pericoronary adipose tissue inflammation from the same scan — detecting active coronary inflammation before detectable stenosis or plaque. CT findings override SCORE-based tiers when present.

CAC score — Agatston score, centile interpretation & clinical tiers

The CAC (coronary artery calcium) Agatston score quantifies calcified plaque burden. Clinical interpretation requires both the absolute score and age/sex-specific centile — a score of 100 in a 45-year-old woman is far more significant than the same score in a 70-year-old man. The MESA (Multi-Ethnic Study of Atherosclerosis) centile reference is the most widely used. Centile lookup: mesa-nhlbi.org

Global alignment — CAC for primary-prevention decision-making (2026)
The 2026 ACC/AHA Multisociety Dyslipidemia Guideline and the ESC/EAS 2019 dyslipidaemia guideline both recommend CAC scoring as a primary decision-modifier in borderline or intermediate-risk patients. 2026 ACC/AHA CAC-specific LDL goals (a major change from 2018): CAC = 0 + no high-risk features → defer LLT and reassess in 3–7 years (selected). CAC 1–99 AU (<75th centile) → moderate-intensity statin, goal LDL <100 mg/dL (2.6 mmol/L) (COR 2a). CAC 100–299 AU or ≥75th centile → goal LDL <70 mg/dL (1.8 mmol/L) and non-HDL <100 mg/dL (2.6) (COR 1). CAC 300–999 AU → goal LDL <55 mg/dL (1.4 mmol/L) and non-HDL <85 mg/dL (2.2) (COR 2a) — equivalent to very-high-risk ASCVD intensity. The Clinician Tool CT-augmented tiers extend this concept by integrating FAI inflammation and CAD-RADS plaque morphology in CTCA-evaluated patients.
Agatston score Category Centile context (example: woman age 55) Clinical implication & Clinician Tool tier
0 Zero CAC 0 = 0th centile regardless of age/sex. Guarantor of very low near-term calcified plaque risk. Very low near-term event risk from calcified plaque. Does not exclude non-calcified (soft) plaque. May support shared decision-making to defer statin in low-risk primary prevention. If FAI elevated, CT tier may still apply.
1–99 Mild Score 50 in a 55-yr woman ≈ 50th–75th centile. Early atherosclerosis — above median for age/sex. Early atherosclerosis. Statin therapy generally appropriate. Intensify risk factor modification. No automatic Clinician Tool CT tier unless FAI or plaque features present.
100–399 Moderate Score 200 in a 55-yr woman ≈ 90th centile — markedly elevated for age/sex. Moderate–high plaque burden. High-intensity statin indicated. Functional assessment if symptomatic. ≥75th centile for age/sex → consider CT high risk tier regardless of absolute score.
≥400 Severe Score 400 in a 55-yr woman ≈ >95th centile — extreme for age/sex. Extensive calcified disease. Clinician Tool CT high risk tier minimum. Intensive lipid lowering. CTCA to assess for obstructive disease and non-calcified plaque burden.
≥1000 Very severe Score ≥1000 is above 99th centile in virtually all age/sex groups. Very extensive calcified burden. Clinician Tool CT ultra-high risk tier. CTCA mandatory. Cardiology review. Aggressive multifactorial treatment.

CAC centile reference — age/sex guide (MESA cohort)

Centiles are approximate and derived from MESA non-Hispanic white reference data. For clinical use always apply the full MESA calculator with patient ethnicity. Values shown are approximate 75th and 90th centile Agatston scores by age band and sex.

Age band Sex 50th centile 75th centile 90th centile Clinical note
45–49Woman0340Most women 45–49 have CAC=0. Any detectable CAC is above median; CAC ≥40 is high burden for this group.
45–49Man560200Men accumulate calcified plaque ~10 years earlier than women at equivalent burden.
50–54Woman01590Post-menopausal acceleration. CAC ≥90 = 90th centile — equivalent to CT high risk threshold.
50–54Man30120350CAC ≥350 = 90th centile; approaches Clinician Tool CT high risk tier.
55–59Woman040175Rapid post-menopausal increase. CAC ≥175 = 90th centile. Any CAC >0 now warrants statin.
55–59Man80250550High baseline burden by this age. Centile context essential — CAC 100 is below median for men 55–59.
60–64Woman10110340CAC ≥110 = 75th centile → CT high risk tier consideration regardless of absolute score.
60–64Man150420800CAC ≥400 (Clinician Tool CT high risk threshold) corresponds to ~75th centile in men this age.
65–69Woman30200500CAC ≥200 = 75th centile; ≥500 = 90th centile. High-intensity statin at minimum.
65–69Man2506001100Very high median burden. CTCA indicated in most. CAC alone insufficient — plaque morphology critical.

CAC-DRS — Coronary Artery Disease Reporting and Data System for CAC

CAC-DRS provides structured reporting of calcium scoring studies combining the Agatston score category (A0–A3) with a number of vessels involved (N0–N3). Two variants exist: CAC-DRS (AN) uses Agatston score + vessel number; CAC-DRS (VN) replaces the Agatston category with a volume score category (V0–V3). Both use the same N0–N3 vessel nomenclature.

Grade
CAC-DRS (AN) — Agatston category
Grade
CAC-DRS (VN) — Volume score category
A0
Agatston score = 0. No calcified plaque.
V0
Volume score = 0.
A1
Agatston 1–99. Mild calcification.
V1
Volume 1–99 mm³. Mild.
A2
Agatston 100–399. Moderate calcification.
V2
Volume 100–399 mm³. Moderate.
A3
Agatston ≥400. Severe calcification.
V3
Volume ≥400 mm³. Severe.
Vessel grade (N)
Definition — applies to both AN and VN variants
N0
No vessels involved (CAC = 0)
N1
1 vessel involved (LM, LAD, LCx, or RCA)
N2
2 vessels involved
N3
3 or more vessels involved (or LM + any vessel)

CAC-DRS is reported as a composite string: A[grade]/N[grade] (e.g. A3/N2) or V[grade]/N[grade] (e.g. V2/N2). Higher grades in either dimension indicate greater calcified plaque burden and broader vessel involvement.

CAC-DRS report Variant Interpretation Clinician Tool clinical implication
A0/N0 CAC-DRS (AN) Agatston 0, no vessels. Equivalent to CAC = 0. Very low calcified plaque risk. Check FAI for pre-plaque inflammation. May support statin deferral in shared decision-making.
A1/N1 CAC-DRS (AN) Mild calcification, 1 vessel. Early disease in single vessel territory. Statin indicated. Intensify risk factor management. Centile context important — may represent CT high risk if above 75th centile for age/sex.
A3/N2 CAC-DRS (AN) Agatston ≥400 in 2 vessel territories. Extensive multivessel calcification. CT ultra-high risk tier — multivessel disease + severe Agatston. Intensive lipid therapy mandatory. CTCA to assess non-calcified burden, stenosis, and plaque morphology. Consider PCSK9i.
V2/N2 CAC-DRS (VN) Volume score 100–399 mm³, 2 vessel territories. Moderate volume, multivessel. CT high risk → ultra-high risk depending on centile. Multivessel involvement upgrades to Clinician Tool CT ultra-high tier. CTCA + FAI assessment indicated.
A2/N3 or A3/N3 CAC-DRS (AN) Moderate–severe calcification in ≥3 vessels or LM + vessel. Most extensive pattern. CT ultra-high risk tier. Highest calcified burden category. Urgent CTCA. Maximise all pharmacotherapy. Cardiology MDT.

CAD-RADS — Coronary Artery Disease Reporting & Data System (CTCA)

CAD-RADS 2.0 (2022) is the standardised reporting system for CTCA findings. It assigns a stenosis grade (0–5), a plaque burden descriptor (P0–P4), and optional modifiers including /HRP (high-risk plaque), /V, /N, /S, /G. A full CAD-RADS 2.0 report is structured as: CAD-RADS [stenosis]/P[burden]/[modifier] — e.g. CAD-RADS 2/P2/HRP or CAD-RADS 3/P3/V. Both the stenosis grade and plaque burden independently influence Clinician Tool tier assignment.

CAD-RADS grade Max stenosis Recommended action Clinician Tool tier / context
CAD-RADS 00% — no plaque, no stenosisNo further cardiac workup. Consider risk factor optimisation.No CT tier unless FAI elevated. Reassure patient with evidence-based discussion.
CAD-RADS 11–24% — minimal plaque, no stenosisPreventive therapy. No stress testing needed.Plaque present — statin indicated. CT tier depends on location, volume, and FAI.
CAD-RADS 225–49% — mild stenosisPreventive therapy. Functional testing optional if symptoms.CT high risk minimum. Intensive statin. FAI and plaque morphology determine if ultra-high.
CAD-RADS 3 50–69% — moderate stenosis Additional functional testing (FFR-CT, stress MRI, or nuclear) recommended. CT high → ultra-high risk. Obstructive disease — Clinician Tool CT ultra-high tier if FFR-CT ≤0.80. Intensify all therapy. Revascularisation assessment.
CAD-RADS 4A / 4B 4A: 70–99% severe; 4B: left main ≥50% or triple-vessel with FFR ≤0.80 Revascularisation strongly recommended. Cardiology MDT. CT ultra-high risk. LDL-C <1.0 mmol/L, ApoB <0.55 g/L. PCSK9i / inclisiran. Dual antiplatelet post-revascularisation.
CAD-RADS 5 Total occlusion (100%) Cardiology assessment for viability and revascularisation potential. CT ultra-high risk. Maximise all pharmacotherapy regardless of revascularisation decision.

Plaque burden descriptor — P0 to P4

The plaque burden descriptor is appended after the stenosis grade, separated by a slash (e.g. CAD-RADS 3/P2). It can be estimated from the CAC Agatston score, the Segment Involvement Score (SIS), or visual assessment on CTCA. P3 and P4 independently trigger the Clinician Tool CT ultra-high risk tier regardless of stenosis grade, reflecting the magnitude of atherosclerotic disease burden.

Grade Definition Agatston / SIS equivalent Clinician Tool tier & lipid target
P0 No plaque present. Optional to use — implied by CAD-RADS 0. Agatston 0 · SIS 0 No plaque — no CT tier from burden alone. FAI may still apply.
P1 Mild plaque burden. Agatston 1–100 · SIS ≤2 CT high risk minimum. Statin indicated. Further tier depends on stenosis, morphology, and FAI.
P2 Moderate plaque burden. Agatston 101–300 · SIS 3–4 CT high risk. High-intensity statin + ezetimibe. Consider PCSK9i if ApoB not at target. LDL-C <1.4 mmol/L, ApoB <0.65 g/L.
P3 Severe plaque burden. Agatston 301–999 · SIS 5–7 CT ultra-high risk. Extensive calcified burden — treat as highest tier regardless of stenosis grade. LDL-C <1.0 mmol/L, ApoB <0.55 g/L. Maximise statin + ezetimibe; initiate PCSK9i or inclisiran.
P4 Extensive plaque burden. Agatston >1000 · SIS ≥8 CT ultra-high risk. Most extensive plaque category. CTCA mandatory. Cardiology MDT. Maximise all pharmacotherapy. LDL-C <1.0 mmol/L, ApoB <0.55 g/L.

CAD-RADS modifiers

Modifier
Meaning
Clinician Tool significance
/HRP (High-Risk Plaque)
Plaque exhibits high-risk features: low attenuation, positive remodelling, spotty Ca²⁺, napkin-ring sign. Added after P grade — e.g. CAD-RADS 2/P2/HRP
CT ultra-high risk regardless of stenosis or P grade. Identical implication to the /V modifier — HRP and /V refer to the same high-risk plaque biology. Use whichever your reporting system generates.
/V (Vulnerable)
High-risk plaque features: LAP/LRNC, positive remodelling, spotty Ca²⁺, napkin-ring sign. Earlier CAD-RADS terminology — equivalent to HRP in CAD-RADS 2.0
Upgrades to CT ultra-high risk regardless of stenosis grade. CAD-RADS 2/V = CAD-RADS 2/P2/HRP in clinical implication.
/N (Non-diagnostic)
Segment(s) non-evaluable due to motion, calcium blooming, or other artefact
Document non-evaluable segments. Consider repeat with better HR control or alternative imaging.
/S (Stent)
Coronary stent present — evaluate in-stent segment
Prior PCI = established ASCVD → ESC very high risk minimum regardless of CAD-RADS grade.
/G (Graft)
Coronary bypass graft present
Prior CABG = established ASCVD → ESC very high risk minimum.
/E (Exception)
Exception (e.g. anomalous coronary anatomy)
Clinical significance case-dependent. Specialist review.
Worked example — CAD-RADS 3/P2/HRP: Moderate stenosis (50–69%) in proximal LAD, moderate plaque burden (Agatston ~200), with high-risk plaque features (positive remodelling + LAP). The stenosis grade (obstructive), P2 burden, and HRP modifier all independently support Clinician Tool CT ultra-high risk tier → LDL-C <1.0 mmol/L, ApoB <0.55 g/L. FFR-CT required. If FFR-CT ≤0.80, revascularisation discussion warranted.
Worked example — CAD-RADS 1/P3: Minimal stenosis (1–24%) but severe plaque burden (Agatston ~450, SIS 6). Despite low-grade stenosis, P3 alone assigns Clinician Tool CT ultra-high risk → LDL-C <1.0 mmol/L, ApoB <0.55 g/L. This illustrates the key principle: plaque burden is an independent risk driver from stenosis severity. Maximise statin + ezetimibe; initiate PCSK9i. CTCA follow-up in 2–3 years.
Worked example — A3/N2 (CAC-DRS AN): Agatston ≥400 in 2 vessel territories (e.g. LAD + RCA). No CTCA performed. Clinician Tool CT ultra-high risk tier on CAC alone — multivessel severe calcification. CTCA recommended to assess non-calcified plaque, stenosis severity, P grade, and FAI. Initiate high-intensity statin + ezetimibe pending CTCA. Reconsider PCSK9i at follow-up.

FAI-Score — CaRi-Heart centile-based interpretation

CaRi-Heart (Caristo Diagnostics) reports the FAI-Score as a population centile for each vessel (RCA, LAD, LCx), standardised against the Oxford ORFAN reference cohort. The highest vessel centile is used for clinical decision-making — not a simple average, and not raw HU values alone. Note that the LCx typically requires a higher centile threshold (≥95th) due to anatomical variance in pericoronary fat distribution. Plaque context matters: the mild–moderate band (50th–74th centile) should only trigger a tier upgrade when plaque is visible on CTCA. At ≥75th centile the inflammatory signal is strong enough to act on independently of plaque — including in patients with a normal CTCA — reflecting the recognised pre-plaque inflammatory phenotype.

Low
<50th centile
No significant coronary inflammation. Risk driven primarily by plaque burden and conventional risk factors.
No upgrade
Mild–moderate
50th–74th centile
Possible early inflammatory activity. Only upgrades tier if plaque is visible on CTCA. Zero-plaque: risk enhancer only — optimise risk factors, closer follow-up.
Upgrade if plaque present
High
≥75th centile
Active vascular inflammation. Independent risk signal — upgrades tier regardless of plaque burden, including normal CTCA (pre-plaque inflammatory phenotype).
CT high risk — always
Very high
≥90th–94th centile
Marked inflammation. Strong independent MACE predictor. Upgrades to ultra-high risk regardless of plaque.
CT ultra-high — always
Extreme
≥95th centile
Highest inflammatory phenotype. LCx threshold (requires ≥95th). Near-term event risk markedly elevated regardless of anatomy.
CT ultra-high — always

High-risk (vulnerable) plaque features on CTCA

Any single feature qualifies a lesion as high-risk, regardless of stenosis severity.

Low-attenuation plaque
LAP / LRNC — lipid-rich necrotic core
HU <30 within plaque. Large necrotic core = rupture-prone. Strongest independent predictor of acute events.
Spotty calcification
SC
Small punctate Ca²⁺ deposits within soft plaque. Associated with thin-cap fibroatheroma (TCFA) on IVUS.
Positive remodelling
PR — remodelling index >1.1
Vessel enlarges outward to accommodate plaque. Associated with active inflammation and instability.
Napkin-ring sign
NRS
Low-attenuation core with higher-attenuation rim — CT correlate of TCFA. High specificity; often under-reported.
Plaque ulceration
Surface discontinuity suggesting active lesion. Less common but high specificity for vulnerability when present.
High total plaque volume
Total atheroma burden
Extensive non-calcified or mixed plaque confers risk independent of stenosis grade.

CTCA vessel findings — risk tiers

CT ultra-high risk Proximal / left main involvement & multivessel disease
Vessels at risk
Left main (LM); proximal LAD; proximal LCx; proximal RCA
Why it matters
Large myocardial territory at risk. Even non-obstructive plaque here escalates risk substantially.
Multivessel disease
Plaque in ≥2 major epicardial vessels — independent MACE predictor regardless of individual stenosis grade.
Stenosis ≥50%
Haemodynamically significant. FFR-CT ≤0.80 confirms ischaemia. Revascularisation discussion warranted.
Target: LDL-C <1.0 mmol/L (<40 mg/dL) · ApoB <0.55 g/L (<55 mg/dL) · Non-HDL <1.8 mmol/L (<70 mg/dL). Maximise statin + ezetimibe; initiate PCSK9i or inclisiran. Cardiology MDT review. Aligns with 2026 ACC/AHA very-high-risk ASCVD intensity (LDL <55 mg/dL / 1.4 mmol/L formally; <40 mg/dL may be considered).
CT high risk Non-proximal plaque / non-obstructive CAD
Vessels
Mid or distal segments; non-dominant RCA; OM branches
Plaque type
Significant non-calcified or mixed plaque without high-risk morphological features
Stenosis
<50% non-obstructive. Clinically significant plaque burden present.
FAI-Score
≥75th centile (upgrades regardless of plaque); or 50th–74th centile with visible plaque present
Target: LDL-C <1.4 mmol/L (<55 mg/dL) · ApoB <0.65 g/L (<65 mg/dL) · Non-HDL <2.2 mmol/L (<85 mg/dL). Intensify statin; add ezetimibe if not at target. Consider PCSK9i if ApoB persists above goal. Aligns with 2026 ACC/AHA CAC 300–999 → LDL <55 mg/dL (COR 2a) and VHR ASCVD intensity.

Clinician Tool CT risk upgrade — quick reference

Any single criterion is sufficient to assign the tier. The "plaque required?" column indicates whether visible coronary plaque on CTCA is needed for the FAI finding to trigger a tier upgrade.

Finding
Threshold / definition
Plaque required?
Clinician Tool tier
FAI-Score ≥95th centile
Highest vessel (RCA, LAD, or LCx ≥95th); extreme inflammatory phenotype
No
Ultra-high
FAI-Score ≥90th–94th centile
Very high inflammation; strong independent MACE predictor
No
Ultra-high
FAI-Score ≥75th–89th centile
High inflammation; pre-plaque phenotype recognised — acts independently
No
CT high risk
FAI-Score 50th–74th centile
Mild–moderate inflammation; risk enhancer only if zero plaque
Yes
CT high risk
FAI-Score 50th–74th + zero plaque
No tier upgrade. Optimise risk factors; repeat imaging 2–3 years; closer follow-up.
—
No upgrade
P4 plaque burden (CAD-RADS 2.0)
Agatston >1000 or SIS ≥8 — extensive plaque burden
—
Ultra-high
P3 plaque burden (CAD-RADS 2.0)
Agatston 301–999 or SIS 5–7 — severe plaque burden regardless of stenosis grade
—
Ultra-high
HRP modifier / /V modifier (CAD-RADS 2.0)
High-risk plaque features — low attenuation, positive remodelling, spotty Ca²⁺, NRS. E.g. CAD-RADS 2/P2/HRP
—
Ultra-high
Vulnerable plaque (any feature)
LAP/LRNC, spotty Ca²⁺, positive remodelling, napkin-ring sign (pre-CAD-RADS 2.0 nomenclature)
—
Ultra-high
Proximal or LM plaque
LM, proximal LAD, proximal LCx, proximal RCA
—
Ultra-high
Multivessel disease
Plaque in ≥2 major epicardial vessels
—
Ultra-high
Obstructive CAD
Stenosis ≥50% or FFR-CT ≤0.80
—
Ultra-high
P2 plaque burden (CAD-RADS 2.0)
Agatston 101–300 or SIS 3–4 — moderate plaque burden
—
CT high risk
Non-obstructive non-proximal plaque / P1
Significant burden without high-risk features; or Agatston 1–100 / SIS ≤2
—
CT high risk
CAC ≥400 (no CTCA)
Extensive calcified burden; CTCA not done or non-diagnostic
—
CT high risk (min)
CT tiers override SCORE-based categories. FAI-Score ≥75th centile upgrades to CT high risk minimum regardless of whether plaque is visible. P3 or P4 plaque burden (CAD-RADS 2.0) assigns CT ultra-high risk independently of stenosis grade — a CAD-RADS 1/P3 carries the same lipid target as a CAD-RADS 4A. HRP and /V modifiers similarly escalate to CT ultra-high regardless of stenosis or P grade. LDL-C <1.0 mmol/L, ApoB <0.55 g/L applies to all CT ultra-high tier patients.

CAD-RADS 2.0 plaque burden (P) descriptor: Cury RC et al. CAD-RADS 2.0 — 2022 Coronary Artery Disease-Reporting and Data System. JACC Cardiovasc Imaging 2022;15:1974–2001. Plaque burden graded P0–P4 using Agatston score, Segment Involvement Score (SIS), or visual estimation. Reported as CAD-RADS [stenosis]/P[grade]/[modifier] — e.g. CAD-RADS 2/P2/HRP. P3 (Agatston 301–999 / SIS 5–7) and P4 (Agatston >1000 / SIS ≥8) assign Clinician Tool CT ultra-high risk regardless of stenosis grade.

FAI-Score methodology: CaRi-Heart (Caristo Diagnostics) reports FAI as a population centile standardised against the Oxford ORFAN reference cohort (Antoniades C et al., ORFAN; Oikonomou EK et al., CRISP-CT, Eur Heart J 2019;40:2472–2483). The highest vessel centile drives clinical decision-making. LCx characteristically requires a higher threshold (≥95th centile) due to anatomical variation in pericoronary adipose distribution. Raw HU values alone should not be used for risk stratification — always use the reported centile.

Four clinical phenotypes (CaRi-Heart framework): (1) Low/no plaque + high FAI (≥75th centile) — biologically active pre-plaque inflammatory phenotype; often missed on standard reporting; treat as CT high risk regardless of anatomy. (2) High plaque + low FAI — stable/burnt-out disease; risk driven by plaque burden; standard secondary prevention. (3) High plaque + high FAI — highest risk phenotype; structural + biological risk combined. (4) Zero plaque + mild–moderate FAI (50th–74th centile) — risk enhancer only; no automatic tier upgrade; optimise risk factors, consider repeat imaging at 2–3 years, particularly in younger patients, diabetics, and strong FHx.

Vulnerable plaque nomenclature: Per SCCT guidelines and Libby P et al. JACC 2019. Napkin-ring sign: Maurovich-Horvat P et al. JACC Cardiovasc Imaging 2008. HRP modifier in CAD-RADS 2.0 is equivalent to the /V (vulnerable) modifier used in earlier reporting.

Note: Total plaque volume quantification (e.g. Cleerly, HeartFlow AI platforms) may allow future addition of a volumetric plaque threshold for the ultra-high tier. To be defined when platform data become available.

4 Visceral Adiposity & GLP-1 Therapy — Metabolic Risk Modification

VAT, sdLDL pattern B & GLP-1 receptor agonists

Visceral adipose tissue (VAT) is a direct driver of atherogenic dyslipidaemia — specifically small dense LDL (pattern B), elevated ApoB, low HDL-C, and hypertriglyceridaemia — through hepatic free fatty acid flux and adipokine-mediated insulin resistance. In patients at high or ultra-high cardiovascular risk, a low LDL-C:ApoB ratio (pattern B / severe pattern B) with elevated waist-to-height ratio or high VATI on CT body composition should prompt consideration of GLP-1 receptor agonist therapy as a targeted metabolic intervention, over and above conventional lipid lowering.

Screening thresholds — visceral adiposity

Waist-to-height ratio
>0.5
Widely available, no equipment needed. Sensitive for central adiposity. Threshold applies across sexes and ethnicities.
CT VAT index (VATI)
High / elevated
Quantified from CT body composition (L3 level). available within this tool. Most accurate measure of visceral adipose tissue burden. Specific thresholds sex-dependent.
LDL-C:ApoB ratio
<2.33 (severe pattern B)
<2.59 (pattern B)
Metabolic / atherogenic dyslipidaemia phenotype. Pattern B in the absence of high absolute LDL-C suggests VAT-driven sdLDL excess as the predominant residual risk mechanism.
BMI (NHS/NICE criterion)
≥27 kg/m²
(≥25 for South Asian)
NICE threshold for semaglutide eligibility in established CVD. NHS rollout criterion where CT VAT assessment is not available.
ApoB excess vs LDL-C
ApoB at goal;
LDL-C above target
Discordance where ApoB is proportionally higher than LDL-C suggests sdLDL particle predominance — a metabolic rather than pure cholesterol problem. GLP-1 agonists preferentially reduce this discordance.
Triglycerides
≥1.7 mmol/L
(≥150 mg/dL)
Non-fasting TG ≥1.7 mmol/L (150 mg/dL) is a marker of atherogenic dyslipidaemia and VAT-driven metabolic syndrome. Supports pattern B diagnosis when LDL-C:ApoB ratio is borderline. 2026 ACC/AHA Table 13 risk-enhancing factor: persistently TG ≥175 mg/dL (2 mmol/L) non-fasting or ≥150 mg/dL (1.7 mmol/L) fasting. CKM syndrome (cardiovascular-kidney-metabolic — formally introduced in the 2026 guideline) is also listed as a risk-enhancing factor and aligns conceptually with the Clinician Tool VAT-driven phenotype.

Why VAT drives pattern B — mechanistic pathway

VAT → hepatic FFA flux
Visceral fat lipolysis delivers free fatty acids directly to the liver via the portal circulation, stimulating hepatic VLDL overproduction — the upstream driver of sdLDL generation.
VLDL overproduction → sdLDL
Elevated VLDL triggers CETP-mediated exchange with LDL particles, producing triglyceride-enriched, cholesterol-depleted LDL that is subsequently remodelled to small dense particles by hepatic lipase.
sdLDL — enhanced atherogenicity
Smaller particles penetrate the arterial wall more readily, have lower LDL-receptor affinity (prolonged circulation), and are more susceptible to oxidation — all amplifying atherogenic signal per particle.
Insulin resistance amplification
VAT-driven adipokine dysregulation (↓ adiponectin, ↑ TNF-α, ↑ IL-6) promotes hepatic insulin resistance, further increasing VLDL secretion and impairing ApoB clearance — a self-reinforcing cycle.

Incretin-based therapy — cardiovascular and metabolic evidence

GLP-1 receptor agonists and dual GIP/GLP-1 agonists have demonstrated cardiovascular event reduction beyond weight loss alone. The SELECT trial (semaglutide 2.4 mg, n=17,604) showed 20% RRR in MACE in patients with established CVD and BMI ≥27 without diabetes. Tirzepatide (Mounjaro) — a dual GIP/GLP-1 receptor agonist — produces superior weight loss and VAT reduction compared to GLP-1 monotherapy, with emerging CV outcome data and substantially better gastrointestinal tolerability.

Trial
Agent / dose
Population
Key outcome
SELECT (2023)
Semaglutide 2.4 mg sc weekly
Established CVD, BMI ≥27, no T2DM
−20% MACE
SUSTAIN-6 (2016)
Semaglutide 0.5/1.0 mg sc weekly
T2DM + high CV risk
−26% MACE
SURMOUNT-MMO (ongoing)
Tirzepatide 10/15 mg sc weekly
Established CVD or HF, BMI ≥27, no T2DM
CV outcomes awaited
SURMOUNT-1 (2022)
Tirzepatide 5/10/15 mg sc weekly
Obesity, no T2DM
−20.9% body weight (15 mg)
SURPASS-CVOT (2024)
Tirzepatide vs dulaglutide
T2DM + high CV risk
Non-inferior; superior metabolic

Both agents reduce atherogenic dyslipidaemia (↓ TG, ↓ sdLDL, modest ↓ ApoB), visceral fat mass, blood pressure, and systemic inflammation (↓ hsCRP). Tirzepatide additionally activates GIP receptors, producing greater VAT reduction, lean mass preservation, and superior tolerability profile compared to GLP-1 monotherapy.

Clinician Tool prescribing approach — tirzepatide as preferred agent

Aspect
Detail
Status / rationale
First-line agent in this tool
Tirzepatide (Mounjaro) — dual GIP/GLP-1 agonist. Preferred over semaglutide (Wegovy) for most patients due to superior tolerability, greater VAT reduction, and better lean mass preservation.
Tool preference Off-label for CV indication
Off-label use
Tirzepatide is licensed for T2DM (Mounjaro) and obesity (Mounjaro for weight management). Its use for cardiovascular risk reduction in non-diabetic CHD patients is off-label pending SURMOUNT-MMO outcomes and NICE guidance. Prescribe with appropriate consent and documentation.
Informed consent required
Microdose titration protocol
Clinician Tool uses a slow microdose escalation algorithm to improve GI tolerability — starting below the licensed 2.5 mg initiation dose and titrating at extended intervals based on individual tolerance. Reduces nausea/vomiting dropout significantly.
Clinician Tool protocol
Semaglutide (Wegovy)
Reserved for patients where tirzepatide is not tolerated, contraindicated, or where NICE-pathway semaglutide eligibility applies and access is via NHS route.
Second-line in this tool
Monitoring
Serial weight, waist:height ratio, CT VATI (where available), LDL-C:ApoB ratio, TG, ApoB. Muscle mass assessment (DEXA or CT SMI) where available. Heart rate monitoring (GLP-1 mediated HR ↑ ~2–4 bpm).
Standard

NICE guidance & NHS eligibility — semaglutide 2.4 mg (Wegovy)

Criterion
Detail
Status
NICE recommendation
Semaglutide 2.4 mg weekly as add-on to standard care for overweight patients with established CVD to reduce recurrent CV events
Final draft / imminent — May 2026 expected
BMI threshold
BMI ≥27 kg/m² (general); ≥25 kg/m² for South Asian, Chinese, other high-risk ethnicities
NICE criterion
CVD requirement
Established ASCVD — prior MI, stroke/TIA, PAD, or revascularisation
NICE criterion
NHS rollout
Planned 2026. Not yet universally available. Access via specialist weight management services or cardiology in early rollout phase.
In progress
Clinician Tool VAT clinic
CT body composition VATI available in this tool. Enables metabolic phenotyping beyond BMI — identifying high-VAT patients who meet biological eligibility even at lower BMI.
Clinician Tool capability

Clinician Tool lifestyle programme — mandatory adjunct to incretin therapy

Incretin therapy in this tool is prescribed as part of a structured metabolic programme, not as standalone pharmacotherapy. Patients are required to engage with dietary and exercise components as a condition of the programme. The rationale is preservation of skeletal muscle mass — the principal risk with rapid weight loss on incretin therapy — and optimisation of metabolic phenotype change beyond what pharmacotherapy alone achieves.

High-protein diet
Target ≥1.6 g protein/kg body weight/day (ideally 1.8–2.2 g/kg in those doing resistance training). Distributes protein across meals (≥30 g per meal) to maximise muscle protein synthesis. Prioritises leucine-rich sources. Supports satiety alongside GLP-1/GIP effect, reducing catabolic pressure during caloric deficit.
Low-carbohydrate approach
Reduces hepatic VLDL secretion directly via reduced insulin stimulation — complementary to GLP-1 mechanism. Lowers TG, raises HDL-C, and improves LDL-C:ApoB ratio by reducing VLDL-driven sdLDL generation. Target: moderate low-carb (<100g/day) rather than strict keto, to permit adequate protein intake and long-term adherence.
Resistance training
Mandatory 2–3 sessions/week minimum. Counters incretin-associated lean mass loss — trials show 25–40% of weight lost on GLP-1/GIP is lean mass without resistance training. Skeletal muscle is the primary site of insulin-stimulated glucose disposal; preserving muscle mass improves insulin sensitivity and further reduces atherogenic dyslipidaemia independent of fat loss.
Why skeletal muscle matters
Mechanism
Monitored by
Insulin-stimulated glucose disposal
Skeletal muscle accounts for ~80% of postprandial glucose uptake. Muscle loss worsens insulin resistance and perpetuates VAT-driven sdLDL cycle even as total weight falls.
HOMA-IR, fasting glucose, HbA1c trend
Resting metabolic rate preservation
Lean mass loss reduces basal metabolic rate, increasing risk of weight regain on dose reduction or cessation. Resistance training preserves RMR and long-term programme durability.
Body composition (DEXA / CT SMI)
ApoB and particle clearance
Muscle GLUT4 upregulation with resistance training enhances hepatic LDL-receptor expression, improving ApoB clearance independently of statin therapy — directly complementing lipid-lowering targets.
Serial ApoB, LDL-C:ApoB ratio
Cardiovascular fitness
Progressive resistance training improves cardiac output, autonomic balance, and endothelial function in CHD patients. Monitoring required — cardiac rehab-level supervision recommended for post-MI patients initiating programme.
6-min walk, HR recovery, CPET where indicated
Programme adherence requirement: Engagement with the dietary and resistance training programme is a condition of incretin prescribing in this tool. Patients are counselled that pharmacotherapy addresses the metabolic driver of VAT accumulation, while diet and resistance training protect lean mass, optimise the lipid phenotype change, and preserve the metabolic benefits during and after dose titration. Serial LDL-C:ApoB ratio and TG are used as objective metabolic response markers alongside weight and waist:height ratio.

GLP-1 therapy should be considered in parallel with, not instead of, intensive lipid lowering. It addresses the residual inflammatory–metabolic risk axis that persists after LDL-C and ApoB are at target.

Clinical phenotype Identifying features GLP-1 consideration Lipid target interaction
Priority — residual metabolic risk Established ASCVD or CT high/ultra-high; LDL-C at target; ApoB persisting above goal; LDL-C:ApoB <2.33 (severe pattern B); waist:height >0.5 or high VATI Strong indication. Tirzepatide (Mounjaro) preferred in this tool — superior VAT reduction and tolerability via microdose protocol. Semaglutide 2.4 mg if NICE-pathway NHS access. Programme engagement mandatory. Pattern B likely to improve with VAT reduction. Serial LDL-C:ApoB ratio monitors response alongside weight and TG.
Post-MI, controlled LDL, overweight SELECT trial phenotype — established CVD, BMI ≥27, no or well-controlled diabetes. LDL-C on target. Ongoing event risk. NICE-eligible (semaglutide, imminent). Tirzepatide preferred in this tool off-label for superior metabolic effect. 20% MACE reduction (SELECT). Microdose protocol + mandatory lifestyle programme. Offer when NHS semaglutide pathway available as alternative. GLP-1 reduces TG and sdLDL burden independently. Continue maximal lipid-lowering therapy.
CT high/ultra-high, no prior event FAI-positive or vulnerable plaque; high VATI on CT; waist:height >0.5; pattern B dyslipidaemia Consider via Clinician Tool VAT clinic. Not yet NICE-mandated for primary prevention, but metabolic phenotype supports early intervention. Address both axes: escalate lipid therapy to CT tier targets and initiate GLP-1 / metabolic programme.
T2DM + high CV risk Established CVD or high-risk CT; T2DM; atherogenic dyslipidaemia; BMI ≥27 Dual benefit — CV event reduction + glycaemic control. LEADER / SUSTAIN-6 data. Often first-line GLP-1 choice in T2DM with CVD. Insulin resistance drives both pattern B and residual ApoB excess. GLP-1 addresses both mechanistically.
Low BMI, high VATI "Normal weight obesity" — BMI <27 but elevated VATI on CT body composition. Metabolically obese phenotype. Clinician Tool VAT clinic pathway. Outside NICE BMI criterion but CT-confirmed visceral adiposity is the biological target. Clinician Tool clinical judgement. VATI-guided, not BMI-guided. LDL-C:ApoB ratio and TG used to confirm metabolic phenotype.
Clinician Tool VAT & GLP-1 clinic: Clinician Tool operates a dedicated VAT-reduction and incretin therapy clinic for CHD patients with high BMI or elevated VATI. Tirzepatide (Mounjaro) is the preferred agent, used off-label for cardiovascular risk reduction via a slow microdose titration protocol to optimise tolerability. Semaglutide (Wegovy) is available where NHS pathway access applies or tirzepatide is not tolerated. All patients are enrolled in a structured programme combining high-protein low-carbohydrate diet and progressive resistance training — mandatory, not optional — to preserve skeletal muscle mass and maximise metabolic phenotype improvement. CT body composition (L3 VATI) enables phenotyping beyond BMI. NHS semaglutide rollout for established CVD (BMI ≥27) expected 2026 pending NICE final publication.

SELECT trial: Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023;389:2221–2232. 17,604 patients, established CVD, BMI ≥27, no diabetes. Primary endpoint 3-point MACE: HR 0.80 (95% CI 0.72–0.90).

Tirzepatide (Mounjaro): Dual GIP/GLP-1 receptor agonist. SURMOUNT-1: Jastreboff AM et al. N Engl J Med 2022;387:205–216 — 20.9% mean weight loss at 15 mg vs 2.5% placebo. SURMOUNT-MMO: ongoing CV outcomes trial (NCT05556512), results awaited. Used off-label in this tool for cardiovascular risk reduction in non-diabetic CHD patients — prescribe with documented informed consent and clear clinical rationale.

Microdose titration: Clinician Tool slow-escalation protocol initiates tirzepatide below the licensed 2.5 mg starting dose with extended dose-escalation intervals based on individual GI tolerance. Rationale: incretin-related nausea/vomiting is dose-rate dependent; slow titration substantially reduces early dropout without compromising eventual therapeutic dose attainment.

Resistance training and lean mass: Muscle mass loss on GLP-1/GIP therapy: Wilding JPH et al. Diabetes Obes Metab 2023. Skeletal muscle and insulin sensitivity: DeFronzo RA, Tripathy D. Diabetes Care 2009;32(Suppl 2):S157–163. Resistance training and LDL-receptor upregulation: Mann S et al. J Strength Cond Res 2014.

NICE guidance: Semaglutide 2.4 mg (Wegovy) for overweight adults with established CVD — final draft expected May 2026. NHS England rollout planned 2026. Subject to local commissioning. Tirzepatide for CV indication not yet in NICE guidance.

VAT and sdLDL: Despres JP, Lemieux I. Nature 2006;444:881–887. Austin MA et al. JAMA 1988;260:1917–1921.

LDL-C:ApoB ratio as pattern B surrogate: Ratio = LDL-C (mmol/L) ÷ ApoB (g/L). <2.33 = severe pattern B; should prompt metabolic phenotyping and consideration of Clinician Tool VAT/incretin clinic referral in eligible patients.

5 Integrated CV Risk Nudge Framework

Beyond SCORE2 — integrating imaging, biology, VAT & resilience

SCORE2 and QRISK3 estimate statistical probability of a cardiovascular event. They do not directly measure actual disease burden, genetic susceptibility, cumulative metabolic exposure, or individual biological trajectory. The Clinician Tool Integrated CV Risk Nudge Framework provides a structured, additive modifier system that sits above the baseline SCORE2 result to produce a final clinical phenotype classification. The interactive calculator is available at mhaat.vercel.app/nudge.html.

Core conceptual model: Risk calculators estimate probability · Imaging shows actual disease · Biology predicts trajectory · This framework integrates all three. "Use SCORE2 for probability, imaging for reality, and modifiers for trajectory."

Step 1 — Baseline risk

Calculate ESC SCORE2 (or QRISK3 where GP-referred) and assign the baseline category: Low / Moderate / High / Very high. This is the starting point only — not the final risk classification.

Step 2 — Nudge modifiers

Apply upward and downward modifiers from the four domains below. The total nudge score is added to the baseline to determine the final phenotype.

Points Modifier category Specific modifier Rationale & notes
+2 Major upward
Any one may justify high-risk phenotype		 CAC ≥100 or ≥75th centile for age/sex Established calcified plaque burden above age/sex median — strong independent MACE predictor
+2 Obstructive CAD on CTCA (stenosis ≥50% or FFR-CT ≤0.80) Haemodynamically significant disease — treat as very high risk minimum
+2 High-risk plaque features (LRNC, positive remodelling, spotty Ca²⁺, napkin-ring sign) Vulnerable plaque — independent MACE predictor regardless of stenosis grade
+2 Lp(a) high — ≥125 nmol/L (ESC risk-enhancing threshold) Strong independent atherogenic and thrombotic risk. Genetic, LDL-independent mechanism. Lifelong elevated risk even with normal SCORE2. nmol/L measurement only (isoform-independent).
+1 (moderate) Lp(a) intermediate — 75–124 nmol/L Moderate risk-enhancing signal. Warrants monitoring, lifestyle attention, and consideration of statin if other risk factors present. Re-measure if borderline.
+2 Familial hypercholesterolaemia (Dutch Lipid Clinic Score ≥6 or genetic confirmation) Lifelong LDL-C exposure; markedly elevated lifetime risk even with normal SCORE2
+2 Premature family history of CHD (1st-degree: men <55, women <65) Powerful independent risk signal reflecting heritable susceptibility via epigenetic, polygenic, and shared environmental mechanisms. Upgrades from moderate to major — premature CHD in a 1st-degree relative carries risk magnitude equivalent to established genetic risk factors.
+2 Diabetes with target organ damage (microalbuminuria, retinopathy, neuropathy, or CKD ≥3) ESC automatic very high risk; combined metabolic and vascular disease burden
+1 Moderate upward
Stackable; 2–3 ≈ 1 major		 CAC 1–99 (any detectable calcified plaque) Early atherosclerosis present — patient is not low risk regardless of SCORE2
+1 Non-obstructive plaque on CTCA (stenosis <50%) Atherosclerosis confirmed — plaque burden and morphology drive further risk stratification
+1 Elevated FAI-Score (CaRi-Heart ≥50th centile on any vessel) Coronary inflammation signal — independent MACE predictor above plaque burden
+1 Early menopause (<45 years) Loss of oestrogen-mediated vascular protection — accelerates atherosclerosis trajectory
+1 CKD stage ≥3 (eGFR <60) — if not already a major modifier Independent cardiovascular risk factor via multiple mechanisms
+1 Elevated ApoB or non-HDL above target for assigned risk tier Residual atherogenic particle burden — primary actionable lipid target
+1 Persistent elevated TG (>2.3 mmol/L) or low HDL (<1.0 M / <1.2 F mmol/L) Atherogenic dyslipidaemia — often VAT-driven; supports metabolic risk axis
+1 Biological signal
Interpret carefully		 Very high HDL-C — men ≥2.5 mmol/L · women ≥3.0 mmol/L U-shaped risk curve: very high HDL may reflect dysfunctional HDL biology. Never protective. Trigger review: alcohol, liver disease, hyperthyroidism, medications, genetic cause. Does not offset imaging disease, LDL burden, or genetic risk.
+1 VAT / metabolic load
Cap total VAT at +2		 High current VAT — waist:height >0.5 or elevated VATI on CT body composition Active visceral adiposity driving atherogenic dyslipidaemia, insulin resistance, and inflammation
+1 VAT-years moderate — 5–10 years of elevated visceral adiposity Cumulative metabolic exposure — analogous to pack-years concept for smoking
+2 VAT-years high — >10–15 years of elevated visceral adiposity High cumulative metabolic burden. VAT total capped at +2 (current VAT + VAT-years combined).
−1 Downward modifiers
Short-term risk only — apply cautiously		 CAC = 0 Very low calcified plaque burden. Does not exclude soft plaque. Cannot be applied if other plaque evidence present.
−1 Normal CTCA — no plaque, no stenosis (CAD-RADS 0) No anatomical atherosclerotic disease. Strong short-term reassurance. Does not erase lifetime or genetic risk.
−1 Favourable metabolic profile — normal weight, insulin-sensitive, low TG, HDL in normal range Reduced metabolic risk burden. Does not offset genetic or imaging-confirmed risk.
−1 High lifetime fitness — high aerobic capacity (VO2max), consistent vigorous exercise history Resilience modifier — reduces event risk but does not negate plaque, high CAC, Lp(a), or FH.
−1 FAI-Score <50th centile on all vessels (CaRi-Heart report) No significant pericoronary inflammation. Reduces likelihood of active inflammatory plaque biology. Apply only when full CaRi-Heart report available; does not override anatomical plaque burden on CTCA or CAC.

Step 3 — Calculate nudge score

Total score = (+2 × major modifiers) + (+1 × moderate modifiers) + (VAT contribution, capped at +2) + (biological signals) − (downward modifiers)

Nudge scoreInterpretationAction
≥ +2High-risk phenotypeTreat as high risk regardless of baseline SCORE2. Initiate or intensify statin ± ezetimibe. Consider PCSK9i if genetic accelerators present. Refer to Clinician Tool VAT clinic if metabolic load significant.
+1Intermediate+Consider escalation from baseline tier. Intensify lifestyle. Repeat imaging if currently negative. Discuss shared decision-making re statin intensification.
0Neutral — follow SCORE2Apply SCORE2-guided lipid targets. Address modifiable risk factors. Routine reassessment.
≤ −1Lower short-term riskConsider cautious de-escalation in low-risk primary prevention only. Maintain statin if Lp(a), FH, or strong family history present — short-term reassurance does not erase lifetime risk.

Step 4 — Override rules (always apply first)

Override rule
Trigger
Classification
1. Any imaging disease
CAC >0 or any plaque on CTCA
Not low risk — downward modifiers for clean imaging cannot apply
2. Major imaging burden
CAC ≥100 / obstructive CAD / high-risk plaque
Force high-risk phenotype — regardless of nudge score or baseline
3. Lifetime risk persists
High LDL burden, Lp(a), FH, or strong family history with clean imaging
Imaging-negative · high lifetime risk — maintain moderate statin minimum; repeat CAC 3–5 yrs
4. Fitness cannot override biology
High fitness present alongside plaque, CAC, Lp(a), or FH
Fitness is a resilience modifier only — does not negate imaging-confirmed disease or genetic risk
5. Very high HDL never protective
HDL ≥2.5 (M) or ≥3.0 (F) mmol/L alongside imaging disease or genetic risk
Never offsets imaging burden, LDL, or FH. Review for secondary cause (alcohol, liver, thyroid, medications, genetics).
6. Stacking rule
2–3 moderate modifiers present simultaneously
2–3 moderate = 1 major equivalent. Multiple small signals constitute meaningful cumulative risk.

Step 5 — Final phenotype classification

Phenotype
Qualifiers (add as applicable)
Lipid target (SI / US)
Low current risk
Only if no imaging disease and no major modifiers
LDL-C <3.0 mmol/L (<116 mg/dL) — ESC low / 2026 ACC/AHA low (<3%)
Intermediate risk
Metabolic-driven risk · Imaging-negative but elevated biological risk
LDL-C <2.6 mmol/L (<100 mg/dL) — ESC moderate / 2026 ACC/AHA borderline 3–<5% or intermediate 5–<10%
High-risk phenotype
Imaging-defined disease · High lifetime risk · Imaging-negative but high lifetime risk · Metabolic-driven
LDL-C <1.8 mmol/L (<70 mg/dL) + ≥50% ↓ (ESC high / 2026 ACC/AHA high ≥10% / secondary prevention not VHR) or <1.4 mmol/L (<55 mg/dL) if CT tier or CAC ≥300 AU
Very high / CT ultra-high
Obstructive CAD · Major imaging burden + genetic accelerator · CT ultra-high tier
LDL-C <1.4 mmol/L (<55 mg/dL) very high · <1.0 mmol/L (<40 mg/dL) CT ultra-high / recurrent — aligns with 2026 ACC/AHA very-high-risk ASCVD (goal <55 mg/dL formally; lower may be considered)
Online nudge calculator: The interactive version of this framework — with live scoring, override logic, qualifier assignment, and PNG download — is available at mhaat.vercel.app/nudge.html. Use alongside the SCORE2 + CAC + CAD-RADS calculator at mhaat.vercel.app/score2-calculator.html.

VAT-years concept: Analogous to pack-years in smoking risk quantification. Cumulative duration of elevated visceral adiposity produces metabolic risk through persistent hepatic FFA flux, chronic low-grade inflammation, and progressive insulin resistance — independent of current BMI or weight. Estimating VAT-years requires a clinical history of weight trajectory and abdominal adiposity duration.

Very high HDL-C: The U-shaped relationship between HDL-C and cardiovascular risk is well documented at very high HDL levels. Possible mechanisms include dysfunctional HDL particles (pro-inflammatory, impaired reverse cholesterol transport), secondary causes (alcohol excess, CETP deficiency, liver disease, hyperthyroidism), and genetic variants (e.g. SCARB1 mutations). Reference: Madsen CM et al. Eur Heart J 2017;38:2478–2486; Bowe B et al. Eur Heart J 2016;37:1304–1311.

Lp(a) thresholds (ESC, nmol/L only): Low <75 nmol/L (0 points) · Intermediate 75–124 nmol/L (+1 moderate modifier) · High ≥125 nmol/L (+2 major modifier, ESC risk-enhancing threshold). Measurement must be in nmol/L — isoform-independent assay. Conversion from mg/dL is imprecise and should not be used for threshold decisions. Reference: Kronenberg F et al. Eur Heart J 2022;43:3925–3946; ESC/EAS Lipid Guidelines 2019 (Mach F et al.).

Framework status: The Clinician Tool Integrated CV Risk Nudge Framework is an Clinician Tool clinical practice resource (v1.2, May 2026). It is not a validated clinical risk score and is intended to structure clinical reasoning alongside guideline-based tools (SCORE2, QRISK3, PREVENT-ASCVD, ESC/EAS 2019, NICE NG238, 2026 ACC/AHA Multisociety Dyslipidemia Guideline), not to replace them.

Ref Key References & Guideline Sources

References

This document draws on the following primary guideline sources, landmark trials, and methodological papers. Where Clinician Tool clinical protocols extend beyond current formal guideline recommendations, this is noted explicitly throughout the document.

Lipid targets — primary guidelines

Source
Reference
Accessed / version
ESC/EAS 2019 Dyslipidaemia Guidelines
Mach F et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2020;41:111–188. doi:10.1093/eurheartj/ehz455
Current version. Primary source for all ESC risk-stratified LDL-C, non-HDL-C and ApoB targets.
2026 ACC/AHA Multisociety Dyslipidemia Guideline
Blumenthal RS, Morris PB, Cho L, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2026 (co-published Circulation 2026). doi:10.1016/j.jacc.2025.11.016
Major update on 2018 ACC/AHA guideline. PREVENT-ASCVD replaces PCE for ages 30–79 (LDL 1.8–4.9 mmol/L). New risk groups: Low <3% · Borderline 3–<5% · Intermediate 5–<10% · High ≥10%. Numeric LDL/non-HDL goals formally endorsed. Lp(a) COR 1, ApoB COR 2a, hs-CRP-driven escalation, CKM syndrome, and CAC-specific LDL goals (≥100 → <70 mg/dL; ≥300 → <55 mg/dL).
AHA PREVENT equations
Khan SS et al. Development and Validation of the American Heart Association's PREVENT Equations. Circulation 2024;149:430–449. doi:10.1161/CIRCULATIONAHA.123.067626
Contemporary US-population calculator. Estimates 10- and 30-year risk of total CVD (incl. HF). Adopted as primary US risk tool in 2026 ACC/AHA Dyslipidemia Guideline. Adds eGFR, BMI, HbA1c, social deprivation; race omitted.
2018 AHA/ACC Cholesterol Guideline (superseded by 2026)
Grundy SM et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation 2019;139:e1082–e1143. doi:10.1161/CIR.0000000000000625
Foundational reference; introduced the very-high-risk ASCVD category and CAC-guided shared decision-making framework. Now superseded by the 2026 Blumenthal et al. update (above).
NICE NG238 — Cardiovascular disease: risk assessment and reduction
NICE guideline NG238 (2023). Cardiovascular disease: risk assessment and reduction, including lipid modification. nice.org.uk/guidance/ng238
Current version. Primary source for NICE primary/secondary prevention targets and QRISK3 thresholds.
SCORE2 — ESC 2021
SCORE2 working group & ESC Cardiovascular risk collaboration. SCORE2 risk scores and national calibrations for estimating 10-year cardiovascular risk in 45 European countries. Eur Heart J 2021;42:2439–2454. doi:10.1093/eurheartj/ehab309
Basis for SCORE2 calculator. UK uses low-risk region calibration.
SCORE2-OP — ESC 2021
SCORE2-OP working group. SCORE2-OP risk scores for estimating 10-year cardiovascular risk in patients ≥70 years. Eur Heart J 2021;42:2455–2467. doi:10.1093/eurheartj/ehab312
Applies to patients aged ≥70 years.
ApoB as primary treatment target
Sniderman AD et al. The Causal Exposure to ApoB-Containing Lipoproteins Is Determined by Both the Rate of Their Entry into the Plasma and Their Fractional Catabolic Rate. Eur Heart J 2022. Also: Thanassoulis G. Apolipoprotein B in preventive cardiology. Curr Opin Cardiol 2021.
Supports use of ApoB as primary marker for atherogenic particle burden.

Coronary CT angiography & FAI

Source
Reference
Relevance
CRISP-CT trial
Oikonomou EK et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (CRISP CT). Eur Heart J 2019;40:2472–2483. doi:10.1093/eurheartj/ehz235
Validation of FAI-Score as independent predictor of cardiac mortality. Key evidence base for CT risk tiers.
ORFAN study
Antoniades C et al. Detecting human coronary inflammation by imaging perivascular fat (ORFAN). Sci Transl Med 2019;11. doi:10.1126/scitranslmed.aav4294
Oxford methodology for FAI centile standardisation. Basis for CaRi-Heart centile thresholds.
CaRi-Heart / Caristo Diagnostics
Commandeur F et al. Deep learning–based quantification of epicardial adipose tissue volume and attenuation predicts major adverse cardiovascular events. Circ Cardiovasc Imaging 2023. See also: caristodx.com
Commercial platform used in this tool for FAI centile reporting. LCx threshold ≥95th centile per platform guidance.
Vulnerable plaque — SCCT guidelines
Cury RC et al. CAD-RADS 2.0 — 2022 Coronary Artery Disease-Reporting and Data System. JACC Cardiovasc Imaging 2022;15:1974–2001. Libby P et al. Atherosclerosis. Nat Rev Dis Primers 2019;5:56.
Basis for high-risk plaque feature definitions (LAP/LRNC, spotty Ca²⁺, positive remodelling, napkin-ring sign).
Napkin-ring sign
Maurovich-Horvat P et al. The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc Imaging 2008;1:440–6.
High specificity for thin-cap fibroatheroma. Often under-reported in routine CT reporting.

GLP-1 / incretin therapy — cardiovascular outcome trials

Trial
Reference
Key finding
SELECT (2023)
Lincoff AM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023;389:2221–2232. doi:10.1056/NEJMoa2307563
20% RRR in MACE. Established CVD, BMI ≥27, no T2DM. Primary evidence base for NICE semaglutide guidance.
SUSTAIN-6 (2016)
Marso SP et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016;375:1834–1844. doi:10.1056/NEJMoa1607141
26% RRR in MACE in T2DM + high CV risk.
SURMOUNT-1 (2022)
Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205–216. doi:10.1056/NEJMoa2206038
20.9% body weight reduction at 15 mg vs 2.5% placebo. Basis for tirzepatide as preferred agent in this tool.
SURMOUNT-MMO (ongoing)
ClinicalTrials.gov NCT05556512. Tirzepatide 10/15 mg weekly vs placebo. Established CVD or HF, BMI ≥27, no T2DM. CV outcomes primary endpoint.
Awaited. Will provide definitive CV outcome data for tirzepatide in non-diabetic CHD patients.

NICE guidance — semaglutide for CVD

Source
Reference
Status
NICE — semaglutide 2.4 mg for CVD risk reduction
NICE technology appraisal (expected 2026). Semaglutide 2.4 mg (Wegovy) as add-on therapy to reduce recurrent CV events in adults with established CVD and BMI ≥27. nice.org.uk/guidance/indevelopment/gid-ta11270
Final draft expected May 2026. NHS England rollout planned 2026. Subject to local commissioning.
NICE — obesity management (NG238 / TA875)
NICE TA875 (2023). Semaglutide for managing overweight and obesity. nice.org.uk/guidance/ta875
Current obesity indication. Separate from the CVD risk-reduction indication.

Disclaimer: This document represents Clinician Tool clinical guidance based on the ESC/EAS 2019, NICE NG238 (2023), and the newly-published 2026 ACC/AHA Multisociety Dyslipidemia Guideline (Blumenthal RS et al., JACC 2026; doi:10.1016/j.jacc.2025.11.016 · co-published Circulation). It is intended for use by clinicians at Clinician Tool and does not constitute standalone national or international clinical guidance. Where Clinician Tool protocols extend beyond formal ESC, NICE or ACC/AHA recommendations (e.g. CT-augmented risk tiers, tirzepatide off-label use), this is clearly indicated. Guidelines are updated periodically — users should verify current versions at escardio.org/Guidelines, nice.org.uk and acc.org / professional.heart.org.

For US users: All lipid targets in this document are presented in dual units — mmol/L (SI / UK / Europe) alongside mg/dL (US conventional). The 2026 ACC/AHA Dyslipidemia Guideline (Blumenthal et al.) has converged with ESC/EAS philosophy: numeric LDL-C / non-HDL-C goals are now formally endorsed, PREVENT-ASCVD replaces PCE as the recommended calculator (ages 30–79), and CAC-specific LDL goals link imaging directly to treatment intensity. The three frameworks (ESC/EAS, NICE, ACC/AHA) now align more closely than at any prior point.

Online resources: This reference document: mhaat.vercel.app/reference.html  ·  Clinician Tool risk calculator: mhaat.vercel.app/score2-calculator.html  ·  Integrated CV Risk Nudge Tool: mhaat.vercel.app/nudge.html

Developed by MedicalSpace Ltd for vat-trap.com and medical partnerships  ·  © MedicalSpace Ltd 2026. All rights reserved.  ·  Clinician Tool · Version 1.2 · May 2026