I'm gonna do a topic presentation in dyslipidemia so give me info and intro, pathophysiology, risk factors , clinical presentation, lab investigation, classification and diagnostic criteria, treatment and management ( pharmacological and non pharmacological ). From recent guidelines for dyslipidemia AHA 2026 and ESC 2025 guidelines compare it

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AHA 2026 dyslipidemia guidelines recommendations LDL targets

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ESC 2025 dyslipidemia guidelines lipid management cardiovascular risk

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dyslipidemia management guidelines lipid lowering

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https://heartcare.sydney/acc-aha-2026-dyslipidemia-guideline…

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https://pace-cme.org/news/focused-update-of-the-esceas-dysli…

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I now have all the data I need. Let me compile the comprehensive presentation.Here is your complete, presentation-ready guide on dyslipidemia, integrating textbook foundations with the most current guidelines.

DYSLIPIDEMIA - Complete Presentation Guide


1. INTRODUCTION & OVERVIEW

Dyslipidemia refers to any abnormality in plasma lipid concentrations - including elevated total cholesterol, LDL-C, triglycerides, or reduced HDL-C - that increases the risk of atherosclerotic cardiovascular disease (ASCVD). It is one of the most prevalent and modifiable cardiovascular risk factors globally, affecting approximately 1 in 4 adults in the United States alone.
Key epidemiological points:
  • Dyslipidemia is present in 38-53% of adults in high-income countries
  • Approximately 80% of cardiovascular disease events are preventable, and elevated LDL-C is a major driver
  • The 2026 ACC/AHA guideline replaces the 2018 blood cholesterol guidance and broadens scope beyond LDL to include Lp(a) and remnant particles
Why it matters: Every 1 mmol/L (39 mg/dL) reduction in LDL-C reduces major cardiovascular events by ~22%. The relationship between LDL and ASCVD risk is linear, causal, and lifelong.

2. PATHOPHYSIOLOGY

Lipoprotein Metabolism (Normal)

Lipoproteins are spherical complexes of lipid and protein that transport hydrophobic lipids through the aqueous bloodstream. Listed in decreasing order of atherogenicity:
Exogenous (dietary) pathway:
  • Dietary fats are absorbed and packaged as chylomicrons by the intestinal mucosa
  • Chylomicrons enter lymphatics → circulation → peripheral lipoprotein lipase (activated by apolipoprotein CII) hydrolyzes triglycerides → free fatty acids delivered to tissues
  • Chylomicron remnants are taken up by the liver
Endogenous pathway:
  • The liver secretes VLDL (triglyceride-rich) → lipoprotein lipase converts VLDL → IDL → LDL
  • LDL binds to LDL receptors on extrahepatic cells and liver → endocytosed (Figure A from Lippincott's Pharmacology)
  • HDL mediates reverse cholesterol transport: collects excess cholesterol from peripheral tissues → returns it to the liver for biliary excretion
Lipoprotein metabolism cycle showing chylomicrons, VLDL, IDL, LDL pathway and Fredrickson types
Figure: Normal plasma lipoprotein metabolism with Fredrickson type annotations - Lippincott's Illustrated Reviews: Pharmacology

Mechanisms of Dyslipidemia

MechanismConsequence
Increased hepatic VLDL productionElevated TG and LDL
Decreased LDL receptor activity (e.g., FH)LDL accumulation
Deficient lipoprotein lipase or apo CIIChylomicronemia (Type I)
Mutant apolipoprotein EIDL accumulation (Type III)
Insulin resistance / T2DMHigh TG, low HDL, small dense LDL
HypothyroidismReduced LDL receptor clearance

Atherogenesis

  • LDL-C penetrates the vascular endothelium and becomes oxidized (ox-LDL)
  • Macrophages take up ox-LDL via scavenger receptors → foam cells → fatty streak
  • Progressive inflammation → fibrous plaque → unstable plaque → rupture → ACS
  • Small dense LDL particles are especially atherogenic (penetrate endothelium more readily)
  • Lp(a) has pro-atherogenic and pro-thrombotic properties; levels are largely genetically determined

3. RISK FACTORS

Non-Modifiable

  • Genetics/Family history - familial hypercholesterolemia (FH), familial combined hyperlipidemia
  • Age - risk increases with age
  • Sex - men at higher risk earlier; post-menopausal women catch up
  • Ethnicity - South Asians have higher cardiovascular risk at lower LDL levels

Modifiable (Primary causes)

  • High saturated/trans fat diet - increases hepatic LDL production
  • Sedentary lifestyle - reduces HDL, impairs LPL activity
  • Obesity - insulin resistance, increased VLDL secretion, decreased HDL
  • Smoking - lowers HDL, promotes oxidation of LDL
  • Excessive alcohol - raises triglycerides

Secondary (Acquired) Causes - MUST BE RULED OUT

ConditionEffect on Lipids
Hypothyroidism↑ LDL (decreased LDL receptor expression)
Diabetes mellitus (T2DM)↑ TG, ↓ HDL, small dense LDL
Nephrotic syndrome↑ LDL, ↑ VLDL
Chronic kidney disease↑ TG, ↓ HDL
Cholestasis / biliary obstruction↑ Total cholesterol
Cushing's syndrome↑ LDL, ↑ TG
HIV/Antiretroviral therapy↑ TG, ↑ LDL (especially PIs and ritonavir)
MedicationsThiazides, beta-blockers, corticosteroids, oral estrogen
Harrison's Principles of Internal Medicine 22e, 2025

4. CLINICAL PRESENTATION

Most patients with dyslipidemia are asymptomatic - detected only by screening labs.

Physical Signs (usually in severe/familial cases)

SignAssociated Condition
Xanthomas (tendinous - Achilles, extensor tendons; tuberous over joints; eruptive in hypertriglyceridemia)Familial hypercholesterolemia, Type III, Type I/V
Xanthelasma (yellowish periorbital plaques)Hypercholesterolemia (not specific)
Corneal arcus (arcus senilis <45 years)FH in younger patients
Lipemia retinalis (creamy-white retinal vessels)Severe hypertriglyceridemia (>2000 mg/dL)
HepatosplenomegalyChylomicronemia syndrome
Eruptive xanthomasHypertriglyceridemia >1000 mg/dL

Complications (Clinical Presentations)

  • Acute pancreatitis - severe hypertriglyceridemia (TG >500-1000 mg/dL)
  • Premature coronary artery disease - angina, MI (especially FH)
  • Peripheral arterial disease - claudication
  • Ischemic stroke / TIA
  • Premature atherosclerosis in any vascular bed

5. LABORATORY INVESTIGATIONS

Standard Lipid Panel (Fasting or non-fasting)

TestNormalBorderlineHigh/Abnormal
Total cholesterol<200 mg/dL200-239≥240 mg/dL
LDL-C<100 mg/dL (optimal)130-159≥160 mg/dL
HDL-C≥60 mg/dL (protective)40-59<40 mg/dL (men), <50 (women)
Triglycerides<150 mg/dL150-199≥200 mg/dL (high), ≥500 (very high)
Non-HDL-C<130 mg/dL (optimal)≥160 mg/dL
LDL-C Calculation:
  • Friedewald equation (traditional): LDL = TC - HDL - (TG/5) - inaccurate when TG >400 or LDL <70
  • Martin/Hopkins or Sampson/NIH equations - now preferred by 2026 ACC/AHA guidelines (Class I recommendation) - more accurate across all ranges

Additional Tests (when indicated)

TestIndication
Apolipoprotein B (ApoB)Better reflects atherogenic particle number; especially useful when TG elevated, in metabolic syndrome, or to guide intensification after LDL-C goals achieved (2026 AHA: Class IIa)
Lipoprotein(a) [Lp(a)]Measured at least once in all adults (Class I - 2026 AHA); risk enhancer at ≥125 nmol/L (50 mg/dL)
hsCRPIf ≥2 mg/L on 2 occasions without identifiable cause → consider high-intensity statin (2026 AHA)
Coronary Artery Calcium (CAC)Risk reclassification when treatment decision uncertain; CAC >0 favors LLT initiation
TSHRule out hypothyroidism
Fasting glucose / HbA1cRule out diabetes
LFTs / CKBefore/during statin therapy
Renal function, urine proteinRule out CKD/nephrotic syndrome

6. CLASSIFICATION & DIAGNOSTIC CRITERIA

Fredrickson/WHO Classification (Phenotypic)

Fredrickson classification of familial hyperlipidemias showing Types I-V
Figure: Fredrickson Classification of Familial Hyperlipidemias - Lippincott's Illustrated Reviews: Pharmacology
TypeNameElevated LipoproteinLipid ChangeKey Feature
IFamilial hyperchylomicronemiaChylomicrons↑↑ TGLPL or apo CII deficiency; pancreatitis risk; no drug effective
IIAFamilial hypercholesterolemiaLDL↑↑ Chol, normal TGLDL receptor defect; accelerated CAD; xanthomas
IIBFamilial combined hyperlipidemiaLDL + VLDL↑ Chol + ↑ TGOverproduction of VLDL; most common familial type
IIIFamilial dysbetalipoproteinemiaIDL↑ Chol + ↑ TGApoE2/E2 mutation; xanthomas; vascular disease by middle age
IVFamilial hypertriglyceridemiaVLDL↑↑ TG, normal/↑ CholOverproduction/decreased removal of VLDL; obesity/DM
VFamilial mixed hypertriglyceridemiaVLDL + Chylomicrons↑↑ TG + ↑ CholPancreatitis risk; obesity/DM

Modern Clinical Classification

  1. Primary (Genetic): Familial hypercholesterolemia (FH), familial combined hyperlipidemia, familial hypertriglyceridemia, Lp(a) excess
  2. Secondary (Acquired): Due to underlying disease or drug
  3. Mixed: Both genetic predisposition and secondary factors

Diagnostic Thresholds (Current Guidelines)

  • Hypercholesterolemia: Total cholesterol ≥240 mg/dL or LDL-C ≥160 mg/dL
  • Severe hypercholesterolemia / likely FH: LDL-C ≥190 mg/dL (adults)
  • Hypertriglyceridemia: TG ≥150 mg/dL (mild-moderate); TG ≥500 mg/dL (severe)
  • Low HDL-C: <40 mg/dL (men), <50 mg/dL (women)
  • Familial Hypercholesterolemia: Dutch Lipid Clinic Network score or Simon Broome criteria (clinical + genetic)

7. TREATMENT & MANAGEMENT

7A. Non-Pharmacological (Therapeutic Lifestyle Changes)

Diet:
  • Reduce saturated fat to <7% of total calories; eliminate trans fats entirely
  • Increase soluble fiber (oats, beans, psyllium) - reduces LDL by 5-10%
  • Plant stanols/sterols (2 g/day) - reduce LDL by ~10%
  • DASH or Mediterranean diet - strongly supported by both AHA 2026 and ESC 2025
  • Reduce dietary cholesterol and simple carbohydrates (for TG)
  • Omega-3 fatty acids (fish, supplements) - lower TG; icosapent ethyl (pure EPA) recommended by ESC 2025 for high-risk patients with TG ≥135 mg/dL
Physical Activity:
  • 150 min/week moderate-intensity aerobic exercise (brisk walking, cycling)
  • Resistance training 2x/week
  • Raises HDL by 5-10%, lowers TG
Weight Reduction:
  • Each 5-10 kg weight loss reduces LDL ~8%, TG ~20%, raises HDL ~2-5 mg/dL
  • In obesity: GLP-1 receptor agonists (semaglutide, liraglutide) reduce TG and may help LDL via weight loss
Smoking Cessation: Raises HDL, reduces oxidative modification of LDL
Alcohol Restriction: Essential for hypertriglyceridemia
Glycemic Control (in T2DM): SGLT-2 inhibitors and GLP-1 agonists reduce ASCVD risk beyond lipid effects

7B. Pharmacological Treatment

Drug Summary Table

Drug ClassPrimary EffectKey AgentsLDL ReductionNotes
StatinsInhibit HMG-CoA reductase → ↓ cholesterol synthesis → ↑ LDL receptor expressionRosuvastatin (high), Atorvastatin (high), Simvastatin, Pravastatin30-50% (moderate); 50-65% (high-intensity)First-line for all; pleiotropic effects (anti-inflammatory, plaque stabilization)
EzetimibeInhibits NPC1L1 → ↓ intestinal cholesterol absorptionEzetimibe 10 mg15-25% (additional on statin)Add-on when statin alone insufficient; IMPROVE-IT trial evidence
PCSK9 mAbsInhibit PCSK9 → ↑ LDL receptor recyclingEvolocumab, Alirocumab50-65% (additional)For very high risk; subcutaneous injection every 2-4 weeks
InclisiransiRNA → reduces PCSK9 synthesisInclisiran~50% (additional)Twice-yearly injection; 2026 AHA recommends as alternative to PCSK9 mAbs
Bempedoic AcidInhibits ACL (upstream of HMG-CoA reductase)Bempedoic acid 180 mg15-25%Statin-intolerant patients; oral; now Class I ESC 2025 for statin-intolerant patients
Bile acid sequestrantsBind bile acids → ↑ LDL receptorCholestyramine, Colesevelam15-30%Raise TG; constipation; limited use
FibratesPPAR-α agonist → ↓ VLDL production, ↑ LPLFenofibrate, GemfibrozilNeutral/slight ↓Primarily for TG ≥500; avoid with statins (myopathy risk with gemfibrozil)
Niacin (nicotinic acid)↓ VLDL, ↑ HDLExtended-release niacinVariableLimited CV benefit shown in trials (AIM-HIGH, HPS2-THRIVE); flushing
Omega-3 fatty acids↓ TG via ↓ VLDL secretionIcosapent ethyl (pure EPA), omega-3 combinationsTG ↓ 20-50%Icosapent ethyl has REDUCE-IT evidence for CV event reduction
LomitapideInhibits MTP → ↓ VLDL/chylomicron assemblyLomitapideLDL ↓ 40-50%Homozygous FH only
EvinacumabAnti-ANGPTL3 antibodyEvinacumab~50%New: ESC 2025 added Class IIa for HoFH
VolanesorsenASO targeting apo CIIIVolanesorsenTG ↓ 70-80%New: ESC 2025 Class IIa for familial chylomicronemia/severe hypertriglyceridemia
Sources: Lippincott's Illustrated Reviews Pharmacology; Harrison's Principles 22e; Goldman-Cecil Medicine; ESC 2025; ACC/AHA 2026

Statin Intensity Classification

IntensityLDL ReductionAgents
High≥50%Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg
Moderate30-49%Atorvastatin 10-20 mg, Rosuvastatin 5-10 mg, Simvastatin 20-40 mg, Pravastatin 40-80 mg
Low<30%Simvastatin 10 mg, Pravastatin 10-20 mg

8. ACC/AHA 2026 vs ESC/EAS 2025 GUIDELINE COMPARISON

This is a side-by-side comparison of the two most current major international guidelines.

Overview

FeatureACC/AHA 2026 (March 2026)ESC/EAS 2025 Focused Update (August 2025)
TypeFull replacement of 2018 guidelineFocused update of 2019 guideline
ScopeDyslipidemia (broader than 2018 blood cholesterol)Dyslipidemia (lipid modification for CV risk)
Risk ToolPREVENT-ASCVD equations (estimates 10-year risk; runs 40-50% lower than old PCE)SCORE2 (ages 40-69) / SCORE2-OP (≥70 years) - replaces old SCORE
FocusLifetime ASCVD risk; Lp(a) as universal markerAbsolute 10-year risk; risk modifiers

LDL-C Targets Comparison

Risk CategoryACC/AHA 2026 TargetESC/EAS 2025 Target
Very high risk (ASCVD + additional high-risk features)LDL-C <55 mg/dL (<1.4 mmol/L) + Non-HDL-C <85 mg/dL + ≥50% reductionLDL-C <55 mg/dL (<1.4 mmol/L) + ≥50% reduction
High risk (ASCVD not very high, or high primary prevention)LDL-C <70 mg/dL (<1.8 mmol/L) + ≥50% reductionLDL-C <70 mg/dL (<1.8 mmol/L) + ≥50% reduction
Intermediate riskLDL-C <100 mg/dL (<2.6 mmol/L) + 30-49% reductionLDL-C <100 mg/dL (<2.6 mmol/L)
Low riskLifestyle + consider statin if LDL ≥160 or 30-year risk ≥10%LDL-C <116 mg/dL (<3.0 mmol/L)
Severe hypercholesterolemia (LDL ≥190)Max statin + ezetimibe ± PCSK9i/bempedoic acid; aim LDL-C <100 or <70 mg/dL based on riskHigh-intensity statin; same targets by risk
Both guidelines converge on the same absolute LDL-C targets for high and very high-risk categories. The key difference is in risk estimation tools and scope.

Treatment Algorithm Comparison

StepACC/AHA 2026ESC/EAS 2025
1st lineLifestyle modificationsLifestyle modifications
2nd lineStatin (intensity based on risk category)Statin (high-intensity for high/very high risk)
3rd lineAdd ezetimibeAdd ezetimibe
4th lineAdd PCSK9 mAb or inclisiran or bempedoic acidAdd PCSK9 inhibitor; add bempedoic acid (Class I)
Statin-intolerantBempedoic acid, PCSK9i, ezetimibeBempedoic acid (Class I); PCSK9i
HoFHLomitapide, PCSK9i, LDL apheresisLomitapide; evinacumab (Class IIa - NEW)
Severe hypertriglyceridemiaFibrate, omega-3Icosapent ethyl (Class IIa); volanesorsen for familial chylomicronemia (Class IIa - NEW)

Key Feature Comparison

FeatureACC/AHA 2026ESC/EAS 2025
Lp(a) testingClass I - measure at least once in ALL adults; risk enhancer at ≥125 nmol/L (≥250 nmol/L = ≥2x risk)Risk enhancer at Lp(a) >50 mg/dL (>105 nmol/L); emphasize in FH and high-risk patients
ApoB measurementClass IIa - in adults on LLT with ASCVD/CKM/T2DM/elevated TG to guide intensificationUsed as alternative to LDL-C
LDL calculationMartin/Hopkins or Sampson/NIH preferred (Class I) over FriedewaldDirect LDL or Friedewald acceptable
CAC scoringClass I: CAC >0 → initiate LLT; CAC 0 → defer and repeat in 3-7 yearsConsider as risk modifier
Children screeningUniversal lipid screening at age 9-11 (new)Selective
ACS - timingInitiate LLT earlyStart combination/intensified therapy at index ACS hospitalization (stronger emphasis)
HIV patientsAddress dyslipidemia per risk categoryStatins recommended for HIV patients ≥40 years
Cancer patientsAddress ASCVD riskStatins for cancer patients at CV risk
Dietary supplementsNot recommended to replace drug therapyExplicitly not recommended for LDL reduction
PREVENT risk toolYes (replaces PCE)Not used; uses SCORE2/SCORE2-OP
Non-HDL-CEmphasized alongside LDL-C as a co-targetNon-HDL-C as primary indicator (replaces total cholesterol)

Where They Differ Most

  1. Risk Calculators: AHA uses PREVENT (which gives lower risk estimates than old PCE, potentially treating fewer people); ESC uses SCORE2/SCORE2-OP (which estimates both fatal and non-fatal events, broader age range 40-89)
  2. Lp(a) Universality: AHA 2026 makes Lp(a) testing a Class I recommendation for all adults - more proactive than ESC 2025's emphasis on high-risk populations
  3. Pediatric Screening: AHA 2026 recommends universal cholesterol screening for all children aged 9-11 - ESC does not take this position
  4. Bempedoic Acid Status: ESC 2025 gives bempedoic acid a Class I recommendation for statin-intolerant patients (strong recommendation); AHA 2026 includes it as an option but without the same Class I force for statin intolerance
  5. Novel Agents for HoFH: ESC 2025 adds evinacumab (anti-ANGPTL3) as Class IIa; AHA 2026 acknowledges lomitapide and PCSK9i with LDL apheresis
  6. Volanesorsen: ESC 2025 adds volanesorsen (Class IIa) for familial chylomicronemia syndrome - not specifically highlighted in AHA 2026

Where They Agree

  • Same absolute LDL-C targets for high and very high-risk patients (<70 and <55 mg/dL)
  • Statins remain first-line for all lipid-lowering pharmacotherapy
  • Add-on therapy with ezetimibe → PCSK9 inhibitors is the stepwise approach for both
  • Lifestyle modification is foundational for all risk categories
  • No role for dietary supplements or vitamins in LDL reduction
  • Early intervention post-ACS with intensive LLT
  • Icosapent ethyl for elevated TG in high/very high-risk patients on statins
  • Individualized treatment based on cardiovascular risk assessment

QUICK SUMMARY TABLE FOR PRESENTATION

DomainKey Points
DefinitionAbnormal lipid levels (↑ LDL, TG; ↓ HDL); major modifiable ASCVD risk
PathophysiologyDisrupted lipoprotein metabolism → LDL accumulation → endothelial penetration → foam cell → atherosclerosis
Risk factorsNon-modifiable: age, sex, genetics; Modifiable: diet, obesity, smoking, DM; Secondary: hypothyroidism, CKD, medications
Clinical signsUsually silent; xanthomas, xanthelasma, corneal arcus, lipemia retinalis in severe cases
ComplicationsCAD, stroke, PAD, pancreatitis (hypertriglyceridemia)
LabsLipid panel (TC, LDL, HDL, TG); Lp(a) once in lifetime; ApoB, CAC in selected patients
ClassificationFredrickson Types I-V; Primary vs Secondary; by lipid fraction elevated
Non-pharm RxDASH/Mediterranean diet, exercise, weight loss, smoking cessation, alcohol restriction
Pharm RxStatins (1st line) → Ezetimibe → PCSK9i/Inclisiran/Bempedoic acid
AHA 2026 keyPREVENT tool, LDL targets reinstated, universal Lp(a), Martin/Hopkins equation, CAC scoring, pediatric screening
ESC 2025 keySCORE2/SCORE2-OP, bempedoic acid Class I for statin-intolerant, evinacumab for HoFH, volanesorsen for chylomicronemia, earlier ACS intervention

Sources:
  • Lippincott's Illustrated Reviews: Pharmacology (textbook figures and drug mechanisms)
  • Harrison's Principles of Internal Medicine, 22e (2025)
  • Goldman-Cecil Medicine, International Edition
  • Braunwald's Heart Disease, 2-Vol Set
  • ACC/AHA 2026 Guideline on the Management of Dyslipidemia (published March 13, 2026 in JACC and Circulation)
  • ESC/EAS 2025 Focused Update of the 2019 Dyslipidemia Guidelines (published at ESC Congress 2025, Madrid; Eur Heart J / Atherosclerosis)
  • Burnett et al. (2025) Network Meta-Analysis of non-statin LLTs [PMID: 40358978]Here is everything you need for your dyslipidemia presentation, organized and complete. Let me give you a quick orientation of what's covered:

What's in this guide:
  1. Introduction - epidemiology, global burden, why LDL matters
  2. Pathophysiology - complete lipoprotein metabolism cycle with diagrams (exogenous/endogenous pathways, atherogenesis mechanism)
  3. Risk Factors - non-modifiable, modifiable, and a full secondary causes table (hypothyroidism, CKD, HIV/ART, drugs, etc.)
  4. Clinical Presentation - signs (xanthomas, xanthelasma, corneal arcus, lipemia retinalis) + complications (ACS, pancreatitis, PAD)
  5. Lab Investigations - standard lipid panel with thresholds + advanced testing (Lp(a), ApoB, CAC, hsCRP)
  6. Classification - full Fredrickson Types I-V with the diagram from Lippincott's, plus modern primary/secondary classification
  7. Treatment - non-pharmacological (diet, exercise, lifestyle) + complete drug table (statins through evinacumab/volanesorsen)
  8. AHA 2026 vs ESC 2025 comparison - side-by-side across risk tools, LDL targets, treatment algorithms, novel agents, and where they agree vs differ
Key guideline highlights to emphasize in your presentation:
  • AHA 2026: LDL targets are back after the 2018 guidelines abandoned them; PREVENT tool replaces PCE; universal Lp(a) for all adults; pediatric screening at age 9-11
  • ESC 2025: Transitions from SCORE → SCORE2/SCORE2-OP; bempedoic acid gets Class I for statin-intolerant patients; adds evinacumab for HoFH and volanesorsen for familial chylomicronemia; stronger push to start LLT during ACS hospitalization
  • Both agree: same LDL targets (<55, <70, <100 by risk tier), statins are first-line, stepwise add-on therapy

Make it short to for fast and detailed presentation to doc

Here is the condensed, high-yield version - every section tight and presentation-ready for a medical audience.

DYSLIPIDEMIA - High-Yield Presentation Summary


1. INTRO & OVERVIEW

  • Abnormal plasma lipids: ↑ LDL-C, ↑ TG, ↓ HDL-C, or ↑ total cholesterol
  • Affects 1 in 4 adults worldwide; major modifiable ASCVD risk factor
  • Every 1 mmol/L ↓ LDL-C = ~22% ↓ major CV events (causal, linear, lifelong relationship)
  • 2026 ACC/AHA guideline replaces 2018; ESC/EAS 2025 is a focused update of 2019

2. PATHOPHYSIOLOGY

Two pathways → both lead to LDL accumulation:
PathwayKey Steps
ExogenousDietary fat → intestine → chylomicrons → LPL hydrolysis → remnants → liver
EndogenousLiver → VLDL → IDL → LDL → LDL receptor uptake by tissues
ReversePeripheral cholesterol → HDL → liver → bile excretion
Atherogenesis sequence: LDL enters endothelium → oxidized (ox-LDL) → macrophage uptake → foam cells → fatty streak → fibrous plaque → rupture → ACS
Key molecular drivers:
  • ↓ LDL receptor activity (FH) → LDL accumulates
  • Insulin resistance → ↑ VLDL, ↓ HDL, small dense LDL (most atherogenic)
  • PCSK9 degrades LDL receptors → ↑ circulating LDL
  • Lp(a) - pro-atherogenic + pro-thrombotic; genetically determined

3. RISK FACTORS

CategoryExamples
Non-modifiableAge, male sex, family history / FH, ethnicity (South Asians)
ModifiableHigh saturated/trans fat diet, obesity, sedentary lifestyle, smoking, excess alcohol
Secondary causesHypothyroidism (↑ LDL), T2DM (↑ TG, ↓ HDL), nephrotic syndrome (↑ LDL), CKD (↑ TG), cholestasis (↑ TC), HIV/ART - especially PIs (↑ TG, ↑ LDL), drugs: thiazides, beta-blockers, corticosteroids
Always rule out secondary causes before labeling primary dyslipidemia

4. CLINICAL PRESENTATION

Mostly asymptomatic - found on screening
Physical signs (severe/familial cases):
SignCondition
Tendinous / tuberous xanthomasFH, Type IIA/III
Eruptive xanthomasTG >500-1000 mg/dL (Types I, IV, V)
XanthelasmaHypercholesterolemia
Corneal arcus (<45 yrs)FH
Lipemia retinalisSevere hypertriglyceridemia (>2000 mg/dL)
HepatosplenomegalyChylomicronemia
Complications:
  • Premature CAD / MI, Stroke, PAD
  • Acute pancreatitis (TG >500-1000 mg/dL)

5. LAB INVESTIGATIONS

Standard Lipid Panel:
ParameterOptimalHigh-Risk Target
LDL-C<100 mg/dL<55-70 mg/dL (see risk category)
HDL-C≥60 mg/dL (protective); <40 (men) / <50 (women) = low
TG<150 mg/dL<150
Non-HDL-C<130 mg/dL<85 (very high risk)
Total cholesterol<200 mg/dL
LDL calculation: Martin/Hopkins or Sampson/NIH equations preferred (2026 AHA Class I) - more accurate than Friedewald especially at low LDL or high TG
Advanced testing:
TestWhen / Why
Lp(a)Once in all adults (AHA 2026 Class I); risk enhancer ≥125 nmol/L
ApoBBetter atherogenic particle count; guides intensification in TG, DM, metabolic syndrome
CAC scoreReclassifies risk when treatment decision uncertain
hsCRP≥2 mg/L → consider high-intensity statin
TSH, glucose/HbA1c, renal function, urine proteinRule out secondary causes

6. CLASSIFICATION

Fredrickson/WHO (Phenotypic)

TypeDisorderElevatedLDLTGCHD RiskKey Feature
IFamilial hyperchylomicronemiaChylomicronsN↑↑↑NoneLPL/apo CII deficiency; pancreatitis; no drug works
IIAFamilial hypercholesterolemiaLDL↑↑N↑↑↑LDL receptor defect; xanthomas; early MI
IIBFamilial combinedLDL + VLDL↑↑↑↑Most common familial type; ↑ VLDL production
IIIDysbetalipoproteinemiaIDL↑↑↑↑ApoE2 mutation; palmar xanthomas
IVFamilial hypertriglyceridemiaVLDLN/↑↑↑↑Common; obesity/DM
VMixed hypertriglyceridemiaVLDL + CMN/↓↑↑↑↑Pancreatitis risk; obesity/DM

Clinical Classification

  • Primary: Genetic (FH, familial combined hyperlipidemia, Lp(a) excess)
  • Secondary: Acquired (hypothyroidism, DM, CKD, drugs)
  • Mixed: Both

FH Diagnostic Criteria

  • LDL-C ≥190 mg/dL in adult + family history or tendon xanthomas
  • Dutch Lipid Clinic Network Score or Simon Broome criteria (clinical + genetic)

7. TREATMENT & MANAGEMENT

Non-Pharmacological

InterventionEffect
Reduce saturated fat (<7% cal), eliminate trans fat↓ LDL 8-10%
Soluble fiber (oats, psyllium)↓ LDL 5-10%
Plant sterols/stanols (2 g/day)↓ LDL ~10%
Mediterranean / DASH diet↓ LDL + CV events
Exercise (150 min/week moderate aerobic)↑ HDL 5-10%, ↓ TG
Weight loss (5-10 kg)↓ LDL ~8%, ↓ TG ~20%
Smoking cessation↑ HDL, ↓ ox-LDL
Alcohol restrictionEssential for hypertriglyceridemia

Pharmacological - Step-Up Approach

Step 1: STATIN (intensity based on risk)
         ↓ (goal not achieved)
Step 2: + EZETIMIBE
         ↓ (goal not achieved)
Step 3: + PCSK9 inhibitor (evolocumab/alirocumab)
            OR inclisiran (siRNA, twice-yearly injection)
            OR bempedoic acid (statin-intolerant)
Drug Table:
DrugMechanismLDL ↓Use
Statins (atorva, rosuva)↓ HMG-CoA reductase → ↑ LDL receptors30-65%1st line ALL
Ezetimibe↓ NPC1L1 intestinal absorption+15-25%Add-on
PCSK9 mAbs (evolocumab, alirocumab)Prevent LDL receptor degradation+50-65%Very high risk
InclisiransiRNA ↓ PCSK9 production+50%Twice-yearly; alternative to PCSK9 mAb
Bempedoic acid↓ ACL (upstream of HMG-CoA)+15-25%Statin-intolerant
Bile acid sequestrants↑ LDL receptor via bile acid depletion15-30%Limited (↑ TG)
FibratesPPAR-α → ↓ VLDL, ↑ LPLTG ↓ 30-50%TG ≥500 mg/dL
Icosapent ethyl (pure EPA)↓ VLDL secretionTG ↓ 20-40%High-risk + TG ≥150; REDUCE-IT trial
EvinacumabAnti-ANGPTL3 → ↓ LDL independent of LDL-RLDL ↓ ~50%HoFH (NEW - ESC 2025)
VolanesorsenASO ↓ apo CIII → ↓ TGTG ↓ 70-80%Familial chylomicronemia (NEW - ESC 2025)
Lomitapide↓ MTP → ↓ VLDL/chylomicron assemblyLDL ↓ 40-50%HoFH only

8. GUIDELINE COMPARISON: ACC/AHA 2026 vs ESC/EAS 2025

At a Glance

ACC/AHA 2026ESC/EAS 2025
PublishedMarch 13, 2026August 2025 (ESC Congress, Madrid)
TypeFull new guideline (replaces 2018)Focused update (of 2019)
Risk toolPREVENT-ASCVD (10-year; ages 30-79)SCORE2 (40-69) / SCORE2-OP (≥70)
Risk categoriesLow <3%, Borderline 3-<5%, Intermediate 5-<10%, High ≥10%Low, Moderate, High, Very High

LDL-C Targets (BOTH AGREE)

Risk TierTarget
Very High (ASCVD + high-risk features)<55 mg/dL + ≥50% reduction
High (ASCVD / high-risk primary)<70 mg/dL + ≥50% reduction
Intermediate<100 mg/dL
Low/BorderlineLifestyle; consider statin

Key Differences

FeatureAHA 2026ESC 2025
Lp(a)Class I: measure in ALL adults (≥125 nmol/L = risk enhancer; ≥250 nmol/L = ≥2x risk)Measure in FH / high-risk; >50 mg/dL = risk factor
Bempedoic acidOption for statin-intolerant (Class IIa context)Class I for statin-intolerant (stronger)
EvinacumabAcknowledged for HoFHNEW Class IIa for HoFH
VolanesorsenNot specifically highlightedNEW Class IIa for familial chylomicronemia
Pediatric screeningUniversal at age 9-11 (new)Selective
LDL formulaMartin/Hopkins preferred (Class I)Friedewald acceptable
ApoBClass IIa to guide intensificationAlternative to LDL-C
CAC scoringClass I: CAC >0 → start LLT; CAC 0 → deferRisk modifier
ACSEarly LLT initiationStrong emphasis: start at index hospitalization
HIV patientsTreat per risk categoryStatins recommended ≥40 yrs (new)
Dietary supplementsNot recommendedExplicitly not recommended

Where They Fully Agree

  • Same LDL-C absolute targets (<55 / <70 / <100 mg/dL)
  • Statins = first-line universally
  • Add ezetimibe → then PCSK9i/inclisiran stepwise
  • Lifestyle change is foundational
  • Icosapent ethyl for high-risk + elevated TG
  • No supplements/vitamins for LDL reduction

Bottom line for your presentation:
AHA 2026 = broader scope (universal Lp(a), pediatric screening, lifetime risk, PREVENT tool, LDL targets reinstated)
ESC 2025 = deeper refinement (SCORE2 tool, stronger push for bempedoic acid, novel agents for rare conditions, ACS timing)
Both arrive at the same treatment targets - the difference is in how you stratify risk and which drugs get the strongest endorsement

Give me topic presentation for dyslipidemia from AHA 2026 guidelines

Asking for Preferences

What format do you want for the presentation? · How detailed should the slides be?

Reading File
Searching the Web

ACC AHA 2026 dyslipidemia guideline full recommendations PREVENT risk tool LDL targets treatment algorithm

Reading File
Reading Web Page

https://reference.medscape.com/cc2/p10/guideline-acc-aha-dys…

Reading File
Now I have everything I need. Let me build the full PPTX presentation.
Running Command

ls /home/daytona/workspace/ 2>/dev/null && mkdir -p /home/daytona/workspace/dyslipidemia-aha2026

Writing File

~/dyslipidemia-aha2026/build.js

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pres.layout = "LAYOUT_16x9";
pres.title = "Dyslipidemia – ACC/AHA 2026 Guideline";
pres.author = "Medical Presentation";

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// ─── SLIDE 2: WHY A NEW GUIDELINE? ───────────────────────────────────────────
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// ─── SLIDE 3: SECTION DIVIDER – PATHOPHYSIOLOGY ──────────────────────────────
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// ─── SLIDE 4: LIPOPROTEIN METABOLISM & ATHEROGENESIS ─────────────────────────
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    { lp: "IDL", origin: "VLDL catabolism", carries: "Chol + TG", fate: "Liver / → LDL" },
    { lp: "LDL", origin: "IDL catabolism", carries: "Cholesterol", fate: "LDL-R uptake (liver & tissues)" },
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// ─── SLIDE 5: SECTION – CLASSIFICATION ───────────────────────────────────────
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// ─── SLIDE 6: FREDRICKSON CLASSIFICATION ─────────────────────────────────────
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    { type:"III", disorder:"Dysbetalipoproteinemia",            lp:"IDL (remnants)",ldl:"↑",  tg:"↑",   chd:"↑↑",   feat:"ApoE2/E2 mutation; palmar xanthomas; vascular disease by mid-life",       color:"FDEBD0" },
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    { type:"V",   disorder:"Mixed Hypertriglyceridemia",        lp:"VLDL + Chylos",ldl:"N/↓", tg:"↑↑↑", chd:"↑",   feat:"Genetic + secondary; pancreatitis risk; obesity/DM; severe HTG",         color:"FDEBD0" },
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// ─── SLIDE 7: SECTION – RISK ASSESSMENT ──────────────────────────────────────
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// ─── SLIDE 8: PREVENT RISK TOOL & CATEGORIES ─────────────────────────────────
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    { text: "• Estimates 10-year & 30-year ASCVD risk\n", options: {} },
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    { label:"BORDERLINE",   val:"3–<5%", color:C.gold,   action:"Consider moderate-intensity statin; aim 30–49% LDL-C reduction" },
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    "LDL-C ≥160 mg/dL or non-HDL-C ≥190 mg/dL (persistent)",
    "Lp(a) ≥125 nmol/L (≥50 mg/dL)",
    "hsCRP ≥2 mg/L (on 2 occasions, no identifiable cause)",
    "ABI <0.9 (subclinical PAD)",
    "Metabolic syndrome (3+ criteria)",
    "Chronic kidney disease (eGFR 15–59)",
    "Chronic inflammatory conditions (RA, psoriasis, HIV)",
    "Premature menopause (<40 yrs) / history of pre-eclampsia",
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  });
  s.addShape(pres.ShapeType.rect, { x: 5.1, y: 4.95, w: 4.9, h: 0.38, fill: { color: C.teal } });
  s.addText("CAC — Class I: CAC >0 → initiate LLT (esp. ≥100 AU or ≥75th %ile) | CAC=0 → defer, repeat in 3–7 yrs | Incidental CT finding → act", {
    x: 5.15, y: 4.95, w: 4.75, h: 0.38, fontSize: 8, color: C.white, valign: "middle", margin: 2,
  });
  footer(s, 5);
}

// ─── SLIDE 9: SECTION – CLINICAL PRESENTATION & LABS ─────────────────────────
{
  const s = pres.addSlide();
  sectionDivider(s, 4, "Clinical Presentation & Lab Investigations", "Signs, symptoms, screening, and biomarker testing");
}

// ─── SLIDE 10: CLINICAL FEATURES & INVESTIGATIONS ────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "Clinical Presentation & Laboratory Investigations", "Most patients are ASYMPTOMATIC — detected by screening");

  // Left: Physical signs
  s.addShape(pres.ShapeType.roundRect, { x: 0.28, y: 1.08, w: 4.55, h: 2.9, fill: { color: C.white }, line: { color: C.navy, width: 1 }, rectRadius: 0.1 });
  s.addShape(pres.ShapeType.rect, { x: 0.28, y: 1.08, w: 4.55, h: 0.3, fill: { color: C.navy } });
  s.addText("Physical Signs (Severe / Familial)", { x: 0.3, y: 1.08, w: 4.5, h: 0.3, fontSize: 10, bold: true, color: C.white, valign: "middle", margin: 4 });

  const signs = [
    { sign: "Tendinous xanthomas", assoc: "FH (Type IIA) — Achilles, extensor tendons", color: C.red },
    { sign: "Eruptive xanthomas", assoc: "Hypertriglyceridemia >500–1000 mg/dL (Types I, IV, V)", color: C.orange },
    { sign: "Tuberous xanthomas", assoc: "Type IIA/III — over elbows, knees", color: C.orange },
    { sign: "Xanthelasma", assoc: "Periorbital yellow plaques — not specific", color: C.gold },
    { sign: "Corneal arcus <45 yrs", assoc: "Suspect FH in young patients", color: C.teal },
    { sign: "Lipemia retinalis", assoc: "TG >2000 mg/dL — creamy retinal vessels", color: C.navy },
    { sign: "Hepatosplenomegaly", assoc: "Chylomicronemia syndrome (Type I/V)", color: C.gray },
  ];
  signs.forEach((sg, i) => {
    const y = 1.42 + i * 0.36;
    s.addShape(pres.ShapeType.roundRect, { x: 0.35, y: y + 0.04, w: 1.55, h: 0.26, fill: { color: sg.color }, rectRadius: 0.05 });
    s.addText(sg.sign, { x: 0.35, y: y + 0.04, w: 1.55, h: 0.26, fontSize: 7.5, bold: true, color: C.white, align: "center", valign: "middle", margin: 2 });
    s.addText(sg.assoc, { x: 1.95, y: y + 0.02, w: 2.8, h: 0.3, fontSize: 8, color: C.gray, valign: "middle", margin: 2 });
  });

  // Complications
  s.addShape(pres.ShapeType.roundRect, { x: 0.28, y: 4.08, w: 4.55, h: 0.85, fill: { color: C.red }, rectRadius: 0.1 });
  s.addText("COMPLICATIONS:", { x: 0.38, y: 4.1, w: 4.3, h: 0.22, fontSize: 9, bold: true, color: C.white, margin: 2 });
  s.addText("Premature CAD/MI  •  Ischemic Stroke  •  PAD / Claudication\nAcute Pancreatitis (TG >500–1000 mg/dL)  •  HF (IHD-related)", {
    x: 0.38, y: 4.3, w: 4.3, h: 0.57, fontSize: 8.5, color: C.white, margin: 2,
  });

  // Right: Lab investigations
  s.addShape(pres.ShapeType.roundRect, { x: 5.0, y: 1.08, w: 4.72, h: 3.85, fill: { color: C.white }, line: { color: C.teal, width: 1 }, rectRadius: 0.1 });
  s.addShape(pres.ShapeType.rect, { x: 5.0, y: 1.08, w: 4.72, h: 0.3, fill: { color: C.teal } });
  s.addText("Laboratory Investigations", { x: 5.05, y: 1.08, w: 4.6, h: 0.3, fontSize: 10, bold: true, color: C.white, valign: "middle", margin: 4 });

  const labs = [
    { test:"Standard Lipid Panel", detail:"TC, LDL-C, HDL-C, TG, non-HDL-C\nFasting not required unless known hypertriglyceridemia\nScreen adults from age 19; children at age 9–11 (universal)" },
    { test:"LDL-C Calculation", detail:"Martin/Hopkins or Sampson/NIH (AHA 2026 Class I)\nPreferred over Friedewald — accurate at low LDL & high TG" },
    { test:"Lp(a)", detail:"Measure once in ALL adults (Class I)\n≥125 nmol/L = risk enhancer; ≥250 nmol/L = ≥2× ASCVD risk" },
    { test:"ApoB (Class IIa)", detail:"Use in ASCVD, T2DM, elevated TG, or LDL-C/ApoB discordance\nVery high-risk goal: ApoB <55 mg/dL" },
    { test:"hsCRP", detail:"If ≥2 mg/L on 2 occasions (no cause) → consider high-intensity statin\nTip for borderline/intermediate risk patients" },
    { test:"Secondary cause workup", detail:"TSH (hypothyroidism) · HbA1c/glucose (T2DM)\nCreatinine/eGFR + urine protein (CKD/nephrotic) · LFTs · LFTs for statin monitoring" },
  ];

  labs.forEach((lab, i) => {
    const y = 1.43 + i * 0.58;
    s.addShape(pres.ShapeType.roundRect, { x: 5.08, y: y, w: 1.45, h: 0.4, fill: { color: C.navy }, rectRadius: 0.06 });
    s.addText(lab.test, { x: 5.08, y: y, w: 1.45, h: 0.4, fontSize: 7.5, bold: true, color: C.white, align: "center", valign: "middle", margin: 3 });
    s.addText(lab.detail, { x: 6.58, y: y - 0.04, w: 3.07, h: 0.58, fontSize: 8, color: C.gray, valign: "middle", margin: 2 });
  });

  footer(s, 6);
}

// ─── SLIDE 11: LIPID TARGETS TABLE ───────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "AHA 2026 — LDL-C & Non-HDL-C Treatment Targets", "Risk-based goals restored — return of numeric targets");

  const tRows = [
    { risk:"VERY HIGH RISK", detail:"Clinical ASCVD + ≥2 major events OR 1 major event + ≥2 high-risk conditions", ldl:"< 55 mg/dL\n(1.4 mmol/L)", nhdl:"< 85 mg/dL\n(2.2 mmol/L)", red:C.red, reduction:"≥50% from baseline" },
    { risk:"HIGH RISK", detail:"Clinical ASCVD not very high risk; OR High primary prevention (ASCVD risk ≥10%)", ldl:"< 70 mg/dL\n(1.8 mmol/L)", nhdl:"< 100 mg/dL\n(2.6 mmol/L)", red:C.orange, reduction:"≥50% from baseline" },
    { risk:"INTERMEDIATE RISK", detail:"Primary prevention 5–<10% ASCVD risk; OR Diabetes without other risk factors", ldl:"< 100 mg/dL\n(2.6 mmol/L)", nhdl:"< 130 mg/dL\n(3.4 mmol/L)", red:C.gold, reduction:"30–49% reduction" },
    { risk:"BORDERLINE RISK", detail:"Primary prevention 3–<5% ASCVD risk; use risk enhancers to decide on therapy", ldl:"< 100 mg/dL\n(2.6 mmol/L)", nhdl:"< 130 mg/dL\n(3.4 mmol/L)", red:C.green, reduction:"30–49% reduction" },
    { risk:"LOW RISK", detail:"ASCVD risk <3%; young adults (30–59 yrs); counsel on lifestyle; consider statin if LDL 160–189 or 30-yr risk ≥10%", ldl:"Lifestyle first;\nStatin if LDL\n160–189", nhdl:"Consider statin\nif 30-yr risk ≥10%", red:C.teal, reduction:"Lifestyle ± 30–49%" },
    { risk:"LDL ≥190 mg/dL\n(Severe Hypercholest.)", detail:"Regardless of ASCVD risk — likely FH; screen family; treat aggressively", ldl:"< 100 mg/dL\n(+risk factors: <70)", nhdl:"< 130 mg/dL\n(+risk: <100)", red:C.navy, reduction:"Max statin + add-on" },
  ];

  // Header
  s.addShape(pres.ShapeType.rect, { x: 0.28, y: 1.08, w: 9.44, h: 0.3, fill: { color: C.navy } });
  ["Risk Category","Clinical Scenario","LDL-C Target","Non-HDL-C","% Reduction"].forEach((h, i) => {
    const xA = [0.3, 1.8, 5.8, 7.3, 8.6];
    const wA = [1.45, 3.95, 1.45, 1.25, 1.1];
    s.addText(h, { x: xA[i], y: 1.08, w: wA[i], h: 0.3, fontSize: 8.5, bold: true, color: C.white, valign: "middle", margin: 2 });
  });

  tRows.forEach((r, i) => {
    const y = 1.38 + i * 0.68;
    const bg = i % 2 === 0 ? C.white : "EBF5FB";
    s.addShape(pres.ShapeType.rect, { x: 0.28, y, w: 9.44, h: 0.68, fill: { color: bg } });
    // Risk badge
    s.addShape(pres.ShapeType.roundRect, { x: 0.32, y: y + 0.1, w: 1.4, h: 0.48, fill: { color: r.red }, rectRadius: 0.07 });
    s.addText(r.risk, { x: 0.32, y: y + 0.1, w: 1.4, h: 0.48, fontSize: 7.5, bold: true, color: C.white, align: "center", valign: "middle", margin: 3 });
    s.addText(r.detail, { x: 1.8, y, w: 3.95, h: 0.68, fontSize: 8, color: C.gray, valign: "middle", margin: 3 });
    s.addText(r.ldl, { x: 5.8, y, w: 1.4, h: 0.68, fontSize: 9, bold: true, color: r.red, align: "center", valign: "middle", margin: 2 });
    s.addText(r.nhdl, { x: 7.3, y, w: 1.25, h: 0.68, fontSize: 8.5, color: C.navy, align: "center", valign: "middle", margin: 2 });
    s.addText(r.reduction, { x: 8.6, y, w: 1.1, h: 0.68, fontSize: 8, color: C.teal, align: "center", valign: "middle", margin: 2 });
  });
  footer(s, 7);
}

// ─── SLIDE 12: SECTION – TREATMENT ───────────────────────────────────────────
{
  const s = pres.addSlide();
  sectionDivider(s, 5, "Treatment & Management", "Non-pharmacological + Pharmacological — AHA 2026 Algorithm");
}

// ─── SLIDE 13: NON-PHARMACOLOGICAL ───────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "Non-Pharmacological Management", "Therapeutic lifestyle change — foundational for ALL risk categories");

  const pillars = [
    { title:"DIET",       color:C.teal,   icon:"🥗",
      items:["Reduce saturated fat <7% total calories; eliminate trans fats entirely","↑ Soluble fiber: oats, beans, psyllium → LDL ↓ 5–10%","Plant stanols/sterols 2 g/day → LDL ↓ ~10%","Mediterranean or DASH diet — strongest CV evidence base","Omega-3 fatty acids (fish) — lower TG; icosapent ethyl for high-risk","Reduce simple carbohydrates/alcohol in hypertriglyceridemia"] },
    { title:"EXERCISE",   color:C.navy,   icon:"🏃",
      items:["≥150 min/week moderate-intensity aerobic (brisk walk, cycling)","Resistance training ≥2×/week","Raises HDL-C by 5–10 mg/dL; lowers TG 20–30%","Reduces insulin resistance (improves small dense LDL pattern)","Start low, go slow — any increase in activity is beneficial"] },
    { title:"WEIGHT",     color:C.green,  icon:"⚖️",
      items:["Each 5–10 kg weight loss: LDL ↓ ~8%, TG ↓ ~20%, HDL ↑ 2–5 mg/dL","GLP-1 receptor agonists (semaglutide): additional TG benefit via weight loss","BMI and waist circumference are included in PREVENT equations","Target BMI <25; waist <102 cm (M), <88 cm (F)"] },
    { title:"LIFESTYLE",  color:C.red,    icon:"🚭",
      items:["Smoking cessation: ↑ HDL, ↓ oxidative modification of LDL","Alcohol restriction: essential for HTG — even moderate intake raises TG","Optimal glycemic control in T2DM: SGLT-2i + GLP-1a reduce ASCVD risk beyond glucose","Stress reduction and sleep optimization improve metabolic profile"] },
  ];

  pillars.forEach((p, i) => {
    const col = i % 2;
    const row = Math.floor(i / 2);
    const x = 0.28 + col * 4.8;
    const y = 1.08 + row * 2.2;
    s.addShape(pres.ShapeType.roundRect, { x, y, w: 4.6, h: 2.1, fill: { color: C.white }, line: { color: p.color, width: 1.5 }, rectRadius: 0.1 });
    s.addShape(pres.ShapeType.rect, { x, y, w: 4.6, h: 0.34, fill: { color: p.color } });
    s.addText(`${p.title}`, { x: x + 0.1, y, w: 4.4, h: 0.34, fontSize: 11, bold: true, color: C.white, valign: "middle", margin: 4 });
    s.addText(p.items.map(it => `• ${it}`).join("\n"), {
      x: x + 0.12, y: y + 0.37, w: 4.35, h: 1.68, fontSize: 8.5, color: C.gray, valign: "top", margin: 4,
    });
  });
  footer(s, 8);
}

// ─── SLIDE 14: PHARMACOLOGICAL – DRUG TABLE ───────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "Pharmacological Treatment — Drug Classes (AHA 2026)", "Five new FDA-approved therapies incorporated into the 2026 guideline");

  const drugs = [
    { cls:"Statins",          mech:"HMG-CoA reductase inhibition → ↑ LDL receptors",   agents:"Rosuvastatin, Atorvastatin (high); Simvastatin, Pravastatin (mod/low)", ldl:"30–65%",    role:"FIRST-LINE ALL patients",   color:C.navy },
    { cls:"Ezetimibe",        mech:"↓ NPC1L1 intestinal cholesterol absorption",         agents:"Ezetimibe 10 mg daily",                                                 ldl:"+15–25%",   role:"Add-on step 2",             color:C.teal },
    { cls:"PCSK9 mAbs",       mech:"Prevent PCSK9-mediated LDL receptor degradation",    agents:"Evolocumab 140 mg Q2W; Alirocumab 75–150 mg Q2W",                       ldl:"+50–65%",   role:"Very high / high risk; add-on step 3", color:C.red },
    { cls:"Inclisiran",       mech:"siRNA → ↓ hepatic PCSK9 synthesis",                 agents:"Inclisiran 284 mg SC — Day 1, Day 90, then Q6M",                        ldl:"+~50%",     role:"Alternative to PCSK9 mAb (AHA 2026)", color:C.orange },
    { cls:"Bempedoic Acid",   mech:"↓ ATP-citrate lyase (upstream HMG-CoA) → ↓ chol",  agents:"Bempedoic acid 180 mg daily (oral)",                                    ldl:"+15–25%",   role:"Statin-intolerant; add-on option",   color:C.green },
    { cls:"Bile Acid Seques.", mech:"Bind bile acids → ↑ LDL receptor upregulation",   agents:"Cholestyramine 4–24 g; Colesevelam 3.75 g",                             ldl:"15–30%",    role:"Limited use; ↑ TG, GI SE",          color:C.gray },
    { cls:"Fibrates",         mech:"PPAR-α agonist → ↓ VLDL secretion, ↑ LPL activity",agents:"Fenofibrate 145 mg; avoid gemfibrozil with statin (myopathy)",           ldl:"TG↓30–50%", role:"TG ≥500 mg/dL; pancreatitis prevention", color:C.teal },
    { cls:"Icosapent ethyl",  mech:"Pure EPA → ↓ VLDL secretion + anti-inflammatory",  agents:"Icosapent ethyl 4 g/day (2 g BID with meals)",                          ldl:"TG↓20–40%", role:"High/very high risk + TG ≥150; REDUCE-IT trial", color:C.navy },
    { cls:"Evinacumab",       mech:"Anti-ANGPTL3 mAb → ↓ LDL independent of LDL-R",   agents:"Evinacumab 15 mg/kg IV monthly",                                        ldl:"+~50%",     role:"Homozygous FH only (AHA 2026 COR 2b)", color:C.red },
    { cls:"Lomitapide",       mech:"↓ MTP → ↓ VLDL/chylomicron assembly",             agents:"Lomitapide 5–60 mg daily (titrate); LFT monitoring",                    ldl:"40–50%",    role:"Homozygous FH only",                color:C.orange },
  ];

  const headers = ["Drug Class","Mechanism","Key Agents","LDL↓","Role / Indication"];
  const hX =     [0.28, 1.8, 4.05, 6.95, 7.6];
  const hW =     [1.48, 2.2, 2.85, 0.6, 2.15];

  s.addShape(pres.ShapeType.rect, { x: 0.25, y: 1.08, w: 9.5, h: 0.27, fill: { color: C.navy } });
  headers.forEach((h, i) => {
    s.addText(h, { x: hX[i], y: 1.08, w: hW[i], h: 0.27, fontSize: 8, bold: true, color: C.white, valign: "middle", margin: 2 });
  });

  drugs.forEach((d, i) => {
    const y = 1.35 + i * 0.43;
    const bg = i % 2 === 0 ? C.white : "EBF5FB";
    s.addShape(pres.ShapeType.rect, { x: 0.25, y, w: 9.5, h: 0.43, fill: { color: bg } });
    s.addShape(pres.ShapeType.roundRect, { x: 0.3, y: y + 0.06, w: 1.4, h: 0.3, fill: { color: d.color }, rectRadius: 0.05 });
    s.addText(d.cls, { x: 0.3, y: y + 0.06, w: 1.4, h: 0.3, fontSize: 7.5, bold: true, color: C.white, align: "center", valign: "middle", margin: 2 });
    s.addText(d.mech, { x: 1.82, y, w: 2.18, h: 0.43, fontSize: 7.5, color: C.gray, valign: "middle", margin: 2 });
    s.addText(d.agents, { x: 4.07, y, w: 2.82, h: 0.43, fontSize: 7.5, color: C.navy, valign: "middle", margin: 2 });
    s.addText(d.ldl, { x: 6.97, y, w: 0.58, h: 0.43, fontSize: 8, bold: true, color: d.color, align: "center", valign: "middle", margin: 2 });
    s.addText(d.role, { x: 7.62, y, w: 2.1, h: 0.43, fontSize: 7.5, color: C.gray, valign: "middle", margin: 2 });
  });
  footer(s, 9);
}

// ─── SLIDE 15: TREATMENT ALGORITHM ───────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "AHA 2026 — Stepwise Treatment Algorithm", "Risk-stratified lipid-lowering therapy (LLT) approach");

  // Step-up boxes left column
  const steps = [
    { n:"Step 1", label:"Therapeutic Lifestyle Change", color:C.green,
      text:"ALL patients — diet, exercise, weight loss, smoking cessation\nFoundation regardless of pharmacotherapy" },
    { n:"Step 2", label:"Statin (1st-line pharmacotherapy)", color:C.navy,
      text:"High-intensity: Atorva 40–80 mg or Rosuva 20–40 mg → ≥50% LDL↓\nModerate-intensity: Atorva 10–20 mg, Rosuva 5–10 mg → 30–49% LDL↓" },
    { n:"Step 3", label:"Add Ezetimibe 10 mg", color:C.teal,
      text:"If LDL-C goal not achieved on maximally tolerated statin\nAdds 15–25% further LDL-C reduction" },
    { n:"Step 4", label:"Add Non-statin LLT", color:C.red,
      text:"PCSK9 mAb (evolocumab/alirocumab) OR inclisiran (Q6M injection)\nOR bempedoic acid (statin-intolerant)\nOR combination, guided by how far from goal" },
  ];

  steps.forEach((st, i) => {
    const y = 1.08 + i * 1.08;
    s.addShape(pres.ShapeType.roundRect, { x: 0.28, y, w: 0.6, h: 0.85, fill: { color: st.color }, rectRadius: 0.08 });
    s.addText(st.n, { x: 0.28, y, w: 0.6, h: 0.85, fontSize: 9, bold: true, color: C.white, align: "center", valign: "middle", margin: 2 });
    s.addShape(pres.ShapeType.roundRect, { x: 0.95, y, w: 5.6, h: 0.85, fill: { color: C.white }, line: { color: st.color, width: 1.5 }, rectRadius: 0.08 });
    s.addText(st.label, { x: 1.05, y: y + 0.04, w: 5.4, h: 0.25, fontSize: 10, bold: true, color: st.color, margin: 4 });
    s.addText(st.text, { x: 1.05, y: y + 0.3, w: 5.4, h: 0.52, fontSize: 8.5, color: C.gray, margin: 4 });
    if (i < 3) {
      s.addShape(pres.ShapeType.rect, { x: 0.54, y: y + 0.85, w: 0.12, h: 0.23, fill: { color: C.lgray } });
    }
  });

  // Right column: special scenarios
  const scenarios = [
    { title:"Statin Intolerant", color:C.orange, text:"Bempedoic acid (oral) — Class I in ESC, option in AHA\nEzetimibe + PCSK9 mAb\nInclisiran as PCSK9 mAb alternative" },
    { title:"Post-ACS (very high risk)", color:C.red, text:"Initiate high-intensity statin during hospitalization\nAdd ezetimibe ± PCSK9 mAb if LDL >55 mg/dL at discharge\nDo NOT wait for outpatient follow-up" },
    { title:"Familial Hypercholesterolemia", color:C.navy, text:"HeFH: Max statin + ezetimibe + PCSK9 mAb\nHoFH: Add evinacumab or lomitapide; consider LDL apheresis if LDL ≥100 on max therapy\nTarget LDL <70 (HeFH) or <100 mg/dL (HoFH)" },
    { title:"Hypertriglyceridemia", color:C.teal, text:"TG 150–499: lifestyle, address secondary causes; icosapent ethyl if high-risk\nTG ≥500: fibrate (fenofibrate) ± omega-3 to prevent pancreatitis\nTG ≥1000: hospitalize; very low fat diet; insulin if DM" },
  ];

  scenarios.forEach((sc, i) => {
    const y = 1.08 + i * 1.08;
    s.addShape(pres.ShapeType.roundRect, { x: 6.75, y, w: 3.1, h: 1.0, fill: { color: C.white }, line: { color: sc.color, width: 1.5 }, rectRadius: 0.1 });
    s.addShape(pres.ShapeType.rect, { x: 6.75, y, w: 3.1, h: 0.3, fill: { color: sc.color } });
    s.addText(sc.title, { x: 6.8, y, w: 3.0, h: 0.3, fontSize: 9, bold: true, color: C.white, valign: "middle", margin: 4 });
    s.addText(sc.text, { x: 6.8, y: y + 0.33, w: 3.0, h: 0.63, fontSize: 7.5, color: C.gray, valign: "top", margin: 3 });
  });

  footer(s, 10);
}

// ─── SLIDE 16: STATIN INTENSITY ───────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "Statin Intensity Classification & Side Effects", "Intensity guided by absolute ASCVD risk — not lipid level alone");

  // Three intensity columns
  const intensities = [
    { label:"HIGH INTENSITY", target:"≥50% LDL-C reduction",  color:C.red,
      drugs:["Atorvastatin 40 mg → ~49% LDL↓","Atorvastatin 80 mg → ~60% LDL↓","Rosuvastatin 20 mg → ~52% LDL↓","Rosuvastatin 40 mg → ~55% LDL↓"],
      use:"Clinical ASCVD (all)\nHigh primary prevention (≥10%)\nLDL-C ≥190 mg/dL" },
    { label:"MODERATE INTENSITY", target:"30–49% LDL-C reduction", color:C.orange,
      drugs:["Atorvastatin 10 mg → ~37% LDL↓","Rosuvastatin 5–10 mg → ~38% LDL↓","Simvastatin 20–40 mg → ~35% LDL↓","Pravastatin 40–80 mg → ~34% LDL↓","Fluvastatin 40–80 mg → ~25% LDL↓"],
      use:"Intermediate primary prevention (5–<10%)\nBorderline risk with enhancers\nDiabetes (varies by risk)" },
    { label:"LOW INTENSITY", target:"<30% LDL-C reduction", color:C.green,
      drugs:["Simvastatin 10 mg","Pravastatin 10–20 mg","Lovastatin 20 mg"],
      use:"Statin-intolerant patients on partial therapy\nRarely first-choice — use moderate instead if tolerated" },
  ];

  intensities.forEach((inten, i) => {
    const x = 0.28 + i * 3.2;
    s.addShape(pres.ShapeType.roundRect, { x, y: 1.08, w: 3.1, h: 3.2, fill: { color: C.white }, line: { color: inten.color, width: 2 }, rectRadius: 0.12 });
    s.addShape(pres.ShapeType.rect, { x, y: 1.08, w: 3.1, h: 0.52, fill: { color: inten.color } });
    s.addText(inten.label, { x: x + 0.08, y: 1.08, w: 2.94, h: 0.3, fontSize: 10, bold: true, color: C.white, align: "center", margin: 4 });
    s.addText(`Target: ${inten.target}`, { x: x + 0.08, y: 1.36, w: 2.94, h: 0.24, fontSize: 8.5, color: C.white, align: "center", margin: 2 });
    s.addText("Drugs:", { x: x + 0.1, y: 1.64, w: 2.9, h: 0.22, fontSize: 8.5, bold: true, color: inten.color, margin: 2 });
    s.addText(inten.drugs.map(d => `• ${d}`).join("\n"), { x: x + 0.1, y: 1.84, w: 2.9, h: 1.2, fontSize: 8.5, color: C.gray, valign: "top", margin: 2 });
    s.addShape(pres.ShapeType.rect, { x: x + 0.1, y: 3.0, w: 2.9, h: 0.02, fill: { color: C.lgray } });
    s.addText("Use for:", { x: x + 0.1, y: 3.06, w: 2.9, h: 0.2, fontSize: 8.5, bold: true, color: inten.color, margin: 2 });
    s.addText(inten.use, { x: x + 0.1, y: 3.25, w: 2.9, h: 0.8, fontSize: 8.5, color: C.gray, valign: "top", margin: 2 });
  });

  // Side effects box
  s.addShape(pres.ShapeType.roundRect, { x: 0.28, y: 4.38, w: 9.44, h: 0.95, fill: { color: C.white }, line: { color: C.red, width: 1 }, rectRadius: 0.1 });
  s.addShape(pres.ShapeType.rect, { x: 0.28, y: 4.38, w: 9.44, h: 0.28, fill: { color: C.red } });
  s.addText("⚠  Statin Safety & Side Effects", { x: 0.35, y: 4.38, w: 9.3, h: 0.28, fontSize: 9, bold: true, color: C.white, valign: "middle", margin: 4 });
  s.addText(
    "• Myopathy / Myalgia (most common) — check CK if symptomatic; switch statin or reduce dose\n" +
    "• Rhabdomyolysis (rare) — CK >10× ULN; discontinue immediately | Hepatotoxicity (rare) — monitor LFTs at baseline\n" +
    "• New-onset T2DM (~10% risk over 4 yrs on high-intensity; benefits outweigh risk in high-risk patients)\n" +
    "• Drug interactions: Avoid simvastatin >20 mg with strong CYP3A4 inhibitors (clarithromycin, itraconazole); gemfibrozil + statin → myopathy risk",
    { x: 0.35, y: 4.66, w: 9.3, h: 0.63, fontSize: 8, color: C.gray, valign: "top", margin: 2 }
  );
  footer(s, 11);
}

// ─── SLIDE 17: SECTION – SPECIAL POPULATIONS ──────────────────────────────────
{
  const s = pres.addSlide();
  sectionDivider(s, 6, "Special Populations", "Diabetes · CKD · Elderly · Pregnancy · HIV · FH · Children");
}

// ─── SLIDE 18: SPECIAL POPULATIONS ────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.ice } });
  titleBar(s, "Management in Special Populations", "AHA 2026 guidance for specific clinical groups");

  const pops = [
    { title:"Type 2 Diabetes", color:C.orange,
      text:"Most T2DM have at least moderate CV risk → statin therapy indicated\nT2DM age 40–75 at high risk: high-intensity statin → LDL-C <70 mg/dL\nAdd SGLT-2i or GLP-1RA for additional ASCVD + renal protection\nPattern: ↑ TG, ↓ HDL, small dense LDL — address all components" },
    { title:"Chronic Kidney Disease", color:C.teal,
      text:"CKD stage 3–5 (not on dialysis): moderate or high-intensity statin\nOn dialysis: initiate new statin not beneficial; continue if already on\nNephrotic syndrome → severe secondary hyperlipidemia — treat underlying\nAvoid high-dose simvastatin (myopathy risk in CKD)" },
    { title:"Elderly (≥75 years)", color:C.navy,
      text:"Continue statin if already on therapy with established ASCVD\nPrimary prevention in >75 yrs: individualize — discuss risk/benefit, polypharmacy, frailty\nRisk of statin side effects higher in elderly (myopathy, DDI)\nCAC, functional status, life expectancy guide decisions" },
    { title:"Pregnancy", color:C.red,
      text:"Statins CONTRAINDICATED in pregnancy (teratogenic — Category X)\nDiscontinue 1–3 months before planned conception\nBile acid sequestrants (colesevelam) safest option if needed\nHypertriglyceridemia in pregnancy: very low fat diet; omega-3; fenofibrate if TG >1000 (pancreatitis risk)" },
    { title:"HIV / Chronic Inflammation", color:C.green,
      text:"HIV: dyslipidemia from both disease + ART (PIs raise TG/LDL most)\nUse pravastatin or rosuvastatin (less CYP3A4 interaction with PIs)\nAvoid simvastatin/lovastatin with PI boosted regimens\nRA, psoriasis, SLE: CV risk enhancers → lower threshold for statin" },
    { title:"Children & Adolescents", color:C.gold,
      text:"Universal lipid screening at age 9–11 yrs (AHA 2026 — NEW Class I)\nFH: LDL-C ≥160 mg/dL in child → screen family; statin if ≥8–10 yrs\nLifestyle foundation: diet + exercise first for 3–6 months\nLDL ≥190 mg/dL in adolescent + family hx → consider statin referral" },
  ];

  pops.forEach((p, i) => {
    const col = i % 2;
    const row = Math.floor(i / 3);
    // 3 per column, 2 columns
    const colIdx = Math.floor(i / 3);
    const rowIdx = i % 3;
    const x = 0.25 + colIdx * 5.0;
    const y = 1.08 + rowIdx * 1.47;
    s.addShape(pres.ShapeType.roundRect, { x, y, w: 4.7, h: 1.38, fill: { color: C.white }, line: { color: p.color, width: 1.5 }, rectRadius: 0.1 });
    s.addShape(pres.ShapeType.rect, { x, y, w: 4.7, h: 0.28, fill: { color: p.color } });
    s.addText(p.title, { x: x + 0.08, y, w: 4.54, h: 0.28, fontSize: 10, bold: true, color: C.white, valign: "middle", margin: 4 });
    s.addText(p.text, { x: x + 0.08, y: y + 0.3, w: 4.54, h: 1.05, fontSize: 8.5, color: C.gray, valign: "top", margin: 3 });
  });
  footer(s, 12);
}

// ─── SLIDE 19: KEY TAKEAWAYS ─────────────────────────────────────────────────
{
  const s = pres.addSlide();
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 10, h: 5.625, fill: { color: C.navy } });
  s.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 0.22, h: 5.625, fill: { color: C.red } });
  s.addShape(pres.ShapeType.rect, { x: 0, y: 1.85, w: 10, h: 0.06, fill: { color: C.teal } });

  s.addText("KEY TAKEAWAYS", { x: 0.4, y: 0.18, w: 9, h: 0.6, fontSize: 28, bold: true, color: C.white, charSpacing: 4, margin: 0 });
  s.addText("ACC / AHA 2026 Dyslipidemia Guideline — 10 Points Every Clinician Must Know", {
    x: 0.4, y: 0.78, w: 9, h: 0.38, fontSize: 12, color: C.gold, italic: true, margin: 0,
  });

  const takeaways = [
    { n:"1", text:"LDL-C targets are back: <55 (very high), <70 (high), <100 (intermediate) mg/dL" },
    { n:"2", text:"Use PREVENT (not PCE) — estimates 10-yr ASCVD risk for ages 30–79; runs 40–50% lower than old PCE" },
    { n:"3", text:"Measure Lp(a) at least once in ALL adults (Class I) — ≥125 nmol/L = risk enhancer; act on it" },
    { n:"4", text:"CAC >0 → initiate LLT (Class I); CAC = 0 + no high-risk conditions → defer, repeat in 3–7 yrs" },
    { n:"5", text:"Statin = first-line always; high-intensity for high/very high risk; titrate to goal" },
    { n:"6", text:"Step up: Statin → + Ezetimibe → + PCSK9 mAb / Inclisiran / Bempedoic acid" },
    { n:"7", text:"Inclisiran (siRNA): twice-yearly injection — equivalent to PCSK9 mAb; now formally recommended" },
    { n:"8", text:"Icosapent ethyl (pure EPA 4 g/day) for high/very high risk patients with TG ≥150 mg/dL on statin" },
    { n:"9", text:"Universal pediatric lipid screening at age 9–11 — screen family if child has LDL ≥160" },
    { n:"10", text:"New ApoB targets: <55 mg/dL (very high risk) — use when LDL-C and ApoB are discordant" },
  ];

  takeaways.forEach((t, i) => {
    const col = Math.floor(i / 5);
    const row = i % 5;
    const x = 0.38 + col * 4.9;
    const y = 2.02 + row * 0.68;
    s.addShape(pres.ShapeType.ellipse, { x, y: y + 0.06, w: 0.38, h: 0.38, fill: { color: C.red } });
    s.addText(t.n, { x, y: y + 0.06, w: 0.38, h: 0.38, fontSize: 10, bold: true, color: C.white, align: "center", valign: "middle", margin: 0 });
    s.addText(t.text, { x: x + 0.46, y, w: 4.3, h: 0.52, fontSize: 9.5, color: C.white, valign: "middle", margin: 0 });
  });
}

// ─── SAVE ─────────────────────────────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/dyslipidemia-aha2026/Dyslipidemia_AHA2026.pptx" })
  .then(() => console.log("DONE: Dyslipidemia_AHA2026.pptx saved"))
  .catch(e => { console.error("ERROR:", e); process.exit(1); });
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