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What's Inside (20 Slides)

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🫀 DYSLIPIDEMIA

Management & Treatment Guidelines

AHA / ACC 2026 · ESC / EAS 2025

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SLIDE 1 — What is Dyslipidemia?

⚠ CVD is the #1 cause of death globally. Dyslipidemia is a major modifiable risk factor.

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SLIDE 2 — Pathophysiology

• LDL particles enter the subendothelial space; quantity is driven by ApoB (one per particle)
• Oxidized LDL activates endothelium → monocyte recruitment → macrophage infiltration
• Macrophages engulf ox-LDL → foam cells → fatty streak (earliest plaque lesion)
• Fibrous cap forms → plaque vulnerability → rupture → ACS / stroke / PAD

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SLIDE 3 — Cardiovascular Risk Assessment

AHA 2026 — PREVENT-ASCVD Equations

• Replaces the 10-year Pooled Cohort Equations (PCE)
• Predicts 10-year AND 30-year ASCVD risk
• Variables: age, sex, race, BP, diabetes, smoking, kidney function, social deprivation, HbA1c, eGFR/uACR
• Better calibrated across diverse populations
• Used to guide initiation of pharmacotherapy in primary prevention

ESC 2025 — SCORE2 / SCORE2-OP

• SCORE2 for <70 years; SCORE2-OP for ≥70 years
• Estimates 10-year CV event risk (fatal + non-fatal)
• Region-calibrated (low / moderate / high / very high CV-risk countries)
• Risk modifiers refine the score: Lp(a), CAC, ABI, hsCRP, renal function
• Risk categories: Low → Moderate → High → Very High → Extreme (NEW)
• Replaces SCORE1 which only predicted CV mortality

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SLIDE 4 — Screening & Diagnosis

Fasting Lipid Panel

• Total cholesterol, LDL-C, HDL-C, triglycerides, non-HDL-C
• Non-fasting acceptable for most screening scenarios
• Repeat 4-12 weeks after therapy initiation, then every 6-12 months

Lipoprotein(a) — Lp(a)

• AHA 2026: Universal adult screening ≥1× in a lifetime (Class I)
• ESC 2025: Measure in adults with CV risk assessment
• ≥50 mg/dL (≥125 nmol/L) = significant risk modifier
• Largely genetic; minimally affected by lifestyle changes

ApoB — Apolipoprotein B

• Each atherogenic particle carries exactly one ApoB → reflects particle number more accurately than LDL-C
• AHA 2026: Selective measurement to refine risk (especially when LDL-C and non-HDL-C disagree)
• Goal for very high risk: ApoB < 65 mg/dL | High risk: < 80 mg/dL
• ESC 2025 also endorses ApoB as an alternative treatment target

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SLIDE 5 — AHA / ACC 2026: Key Updates

Published March 2026 in Circulation — Replaces the 2018 Blood Cholesterol Guideline

6 Major Changes

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SLIDE 6 — AHA 2026: LDL-C Treatment Goals by Risk

CAC Score → LDL-C Goal (Subclinical Atherosclerosis)

Very High Risk = ≥2 major ASCVD events OR 1 major event + ≥2 high-risk conditions (e.g., DM, CKD, HF, PAD, HTN, active smoking, age >65)

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SLIDE 7 — ESC / EAS 2025: Key Updates

Published August 29, 2025 — Focused update of the 2019 ESC/EAS Guidelines

6 Major Changes

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SLIDE 8 — ESC 2025: LDL-C Goals by Risk Category

Combination therapy can reduce LDL-C by up to 86%: High-intensity statin (↓55%) + Ezetimibe (additional ↓24%) + PCSK9 inhibitor (additional ↓60% on top of statin)

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SLIDE 9 — Lifestyle Modifications

🥗 Diet

• Mediterranean or DASH diet
• Reduce saturated fat <7% of calories; avoid trans fats entirely
• Increase soluble fiber (10-25 g/day)
• Plant sterols 2 g/day reduce LDL-C ~5-10%

🏃 Physical Activity

• ≥150 min/week moderate-intensity aerobic OR ≥75 min/week vigorous
• Resistance training 2×/week
• Reduces TG, raises HDL-C

⚖️ Weight Management

• 5-10% weight loss → LDL-C ↓5-8 mg/dL; significantly reduces TG
• Target BMI <25 kg/m²
• Bariatric surgery in refractory obesity

🚭 Smoking & Alcohol

• Smoking cessation → HDL-C ↑4-8 mg/dL; reduces ASCVD risk significantly
• Limit alcohol: ≤1 drink/day women, ≤2 men
• Heavy alcohol → severe hypertriglyceridemia

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SLIDE 10 — Pharmacotherapy

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SLIDE 11 — Treatment Algorithm

STEP 1 — Lifestyle Modifications
  Diet, exercise, weight loss, smoking cessation → ALL patients

      ↓ if LDL-C goal not met

STEP 2 — High-Intensity Statin
  Rosuvastatin 20-40 mg OR Atorvastatin 40-80 mg → ≥50% LDL-C reduction

      ↓ if LDL-C goal not met

STEP 3 — Add Ezetimibe
  10 mg/day add-on
  ESC 2025: Consider upfront statin + ezetimibe (fire-to-target)

      ↓ if LDL-C goal not met

STEP 4 — Add PCSK9 Inhibitor
  Evolocumab or alirocumab (SC injection)
  AHA 2026: No longer strictly sequential — choose by LDL-C gap needed

      ↓ if statin-intolerant

STEP 5 — Alternatives for Statin Intolerance
  Bempedoic acid ± ezetimibe
  Inclisiran as alternative to PCSK9 mAb
  Evinacumab for homozygous FH (HoFH)

Monitor lipid profile 4-12 weeks after therapy change, then every 6-12 months. Therapeutic inertia is a key barrier — intensify until goals are achieved.

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SLIDE 12 — Special Populations

Diabetes Mellitus (T2DM)

• High-intensity statin recommended even without clinical ASCVD
• LDL-C <70 mg/dL for high-risk DM; <55 for very high risk
• AHA 2026: PREVENT incorporates HbA1c in risk calculation
• GLP-1 agonists / SGLT2i reduce ASCVD events independently

Familial Hypercholesterolemia (FH)

• Universal childhood lipid screening: AHA 2026 ages 9-11; ESC 2025 ages 5-10
• Heterozygous FH: LDL-C >190 mg/dL despite lifestyle → high-intensity statin
• Homozygous FH: Evinacumab (anti-ANGPTL3) + LDL apheresis
• Cascade screening of all first-degree relatives recommended

Elderly (≥75 years)

• SCORE2-OP used in ESC 2025 for those ≥70 years
• Statins remain beneficial in secondary prevention regardless of age
• Primary prevention: individualize; risk of adverse effects increases with age
• Polypharmacy and drug interactions must be considered

HIV & Cardio-Oncology (ESC 2025 NEW)

• Statins recommended in HIV patients at CV risk
• Cancer therapy (anthracyclines, checkpoint inhibitors) → increased CV risk
• Rosuvastatin and pravastatin preferred (fewer drug interactions with ART)
• Monitor CYP3A4 interactions between ART and statins

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SLIDE 13 — AHA 2026 vs ESC 2025: Side-by-Side

★ Extreme Risk is unique to ESC 2025 — no equivalent category exists in AHA 2026

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SLIDE 14 — Hypertriglyceridemia

Classification

Common Causes

• Obesity and metabolic syndrome
• Type 2 diabetes / insulin resistance
• Hypothyroidism, Cushing syndrome
• Chronic kidney disease / nephrotic syndrome
• Excessive alcohol consumption
• Medications: thiazides, beta-blockers, isotretinoin, HIV ART, estrogens
• Familial hypertriglyceridemia (genetic)

Management

• Lifestyle: weight loss, reduce refined carbs, limit alcohol
• Treat secondary causes (glycemic control, thyroid)
• If TG ≥500 mg/dL → fibrates first (pancreatitis risk)
• Icosapentaenoic acid (EPA) 4 g/day — REDUCE-IT trial: ↓25% MACE
• AHA 2026: remnant particles highlighted as independent ASCVD risk
• Non-HDL-C is a better treatment target than TG directly

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SLIDE 15 — Lipoprotein(a): The Emerging Biomarker

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SLIDE 16 — Monitoring & Statin Safety

Follow-up Schedule

Statin Safety

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SLIDE 17 — 10 Take-Home Messages

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References

1. Blumenthal RS, Morris PB et al. 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia. Circulation. March 2026.
2. Mach F, Baigent C, Catapano AL et al. 2025 Focused Update of the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. August 2025.
3. Lloyd-Jones DM et al. PREVENT-ASCVD Equations. Circulation. 2024.
4. Nissen SE et al. Bempedoic acid and cardiovascular outcomes — CLEAR Outcomes. NEJM. 2023.
5. Ridker PM et al. Inclisiran — ORION-10 & ORION-11 trials. NEJM. 2020.
6. Bhatt DL et al. Cardiovascular risk reduction with icosapentaenoic acid — REDUCE-IT. NEJM. 2019.

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🩺 History Taking — Gout Patient

Complete Structured Checklist

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1. PRESENTING COMPLAINT (PC)

• Joint pain — which joint(s)?
• Swelling, redness, warmth
• Duration of current episode
• Onset: sudden vs gradual

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2. HISTORY OF PRESENTING COMPLAINT (HPC)

Pain Characterization (SOCRATES)

• Site: Which joint(s) — 1st MTP (podagra), ankle, knee, wrist, elbow, finger
• Onset: Sudden overnight onset? (classic gout pattern)
• Character: Burning, throbbing, crushing, aching
• Radiation: Spreading to other joints?
• Associated symptoms (see below)
• Timing: Constant or intermittent? Morning vs night?
• Exacerbating factors: Walking, touch, light pressure (even bedsheet intolerance?)
• Severity: Pain score 1-10; ability to weight-bear?

Attack Features

• How many hours from onset to peak severity?
• Hyperemia (intense redness) over joint?
• Desquamation (skin peeling) after attack?
• Can you bear weight on the joint?
• Any fever or systemic symptoms during attack?
• How long does each attack last untreated?
• Complete resolution between attacks?

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3. GOUT ATTACK HISTORY

• Age at first attack
• Total number of attacks
• Frequency of attacks (per year)
• Pattern — same joint each time or migrating?
• Any polyarticular attacks (multiple joints at once)?
• Longest pain-free interval between attacks
• Are attacks getting more frequent or severe over time?
• Any attacks at night specifically?
• Any spontaneous resolution?

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4. PRECIPITATING / TRIGGER FACTORS

Dietary Triggers (ask specifically)

• Red meat (beef, lamb, pork)
• Organ meats (liver, kidney, sweetbreads, brain)
• Seafood / shellfish (especially anchovies, sardines, mussels, scallops, shrimp)
• Alcohol — type and quantity:
  • Beer (highest purine content)
  • Spirits / whisky
  • Wine (lower risk but still ask)
• Sugary drinks / fructose-containing beverages (sodas, fruit juices)
• High-fructose corn syrup foods

Other Triggers

• Recent illness, infection, or surgery (physiological stress)
• Dehydration (recent fasting, poor fluid intake, hot weather)
• Recent initiation of diuretics
• Recent initiation of allopurinol or urate-lowering therapy (can trigger acute flare)
• Trauma to joint
• Excessive exercise
• Crash dieting / starvation
• Blood transfusion or chemotherapy (cell lysis → purine release)

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5. INTERVAL / INTERCRITICAL PERIOD

• Any joint symptoms between attacks?
• Joint stiffness between episodes?
• Full return to normal function?
• Duration of the pain-free intervals (becoming shorter?)

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6. CHRONIC TOPHACEOUS GOUT

• Any lumps or nodules over joints, ears, tendons?
• Ask specifically about:
  • Ear pinnae (helix / antihelix)
  • Fingers / knuckles
  • Elbow (olecranon bursa)
  • Achilles tendon
  • First MTP joint
  • Forearm
• White chalky discharge from any lumps?
• Ulceration over lumps?
• Joint deformity?
• Functional limitation of any joint?

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7. URINARY / RENAL SYMPTOMS

• Kidney stones (uric acid nephrolithiasis) — ever passed a stone?
• Flank / loin pain (renal colic)
• Hematuria (blood in urine)
• Recurrent urinary tract infections
• Reduced urine output / foamy urine
• Known chronic kidney disease?
• Any prior renal ultrasound or CT for stones?

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8. PAST MEDICAL HISTORY (PMH)

• Hyperuricemia — known elevated serum uric acid? Previous readings?
• Hypertension — very strong association with gout
• Type 2 Diabetes Mellitus / Metabolic Syndrome
• Dyslipidemia (ask — links to metabolic syndrome)
• Obesity — weight history, BMI
• Chronic Kidney Disease — stage, GFR
• Cardiovascular disease — IHD, heart failure, stroke
• Psoriasis (associated with hyperuricemia)
• Haematological malignancy — leukemia, lymphoma, polycythemia (high cell turnover)
• Hypothyroidism (reduces uric acid excretion)
• Organ transplant (cyclosporine use → hyperuricemia)
• Previous joint disease — OA, RA, septic arthritis
• Renal transplant (especially — cyclosporine → gout very common)

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9. DRUG HISTORY (DH)

Drugs that RAISE Uric Acid (ask about each)

Current Gout Medications

• On allopurinol? Dose? How long?
• On febuxostat? Dose?
• On probenecid or benzbromarone?
• On colchicine (prophylaxis)?
• NSAIDs used during attacks? Which ones?
• Corticosteroids for acute attacks?

Other Current Medications

• ACE inhibitors / ARBs (losartan is uricosuric — beneficial)
• Metformin, SGLT2 inhibitors (mildly uricosuric)
• Statins
• Any over-the-counter medications / supplements?
• Vitamin C supplements (mildly lowers urate)

Allergies

• Drug allergies — especially allopurinol hypersensitivity (Stevens-Johnson syndrome risk, HLA-B*5801 association in Asian patients)
• NSAID allergy / intolerance

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10. FAMILY HISTORY (FH)

• Family history of gout (first-degree relatives)?
• Family history of kidney stones?
• Family history of hyperuricemia?
• Any rare inherited conditions:
  • Lesch-Nyhan syndrome (HGPRT deficiency — young males, severe hyperuricemia)
  • Kelley-Seegmiller syndrome
  • Familial juvenile hyperuricemic nephropathy (FJHN)
  • PRPP superactivity

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11. SOCIAL HISTORY (SH)

Alcohol

• Type, frequency, and quantity per week
• CAGE questionnaire if concerned
• Recent binge drinking before this attack?

Diet

• Red meat / organ meat consumption frequency
• Seafood frequency
• Soft drink / fizzy drink intake
• Dairy intake (dairy is protective — ask)
• Fluid / water intake per day (dehydration is a trigger)
• Coffee intake (mildly protective)
• Recent dietary changes / crash diet?

Occupation

• Type of work — manual labor (joint trauma)?
• Work schedule — night shifts (eating patterns, hydration)
• Occupational exposures (lead exposure → saturnine gout)

Lifestyle

• Smoking status
• BMI / weight history — recent weight gain?
• Exercise habits
• Recent travel or change in diet?

Social Circumstances

• Living situation, support at home
• Impact of gout on activities of daily living (ADLs)
• Ability to work / mobility during attacks
• Psychological impact — anxiety, depression?

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12. SYSTEMS REVIEW (SR)

Musculoskeletal

• Joint stiffness (morning stiffness duration?)
• Other joint involvement — asymmetric? Symmetric?
• Muscle weakness
• Bone pain

Renal

• Urine output, color, frothiness
• Flank pain, dysuria
• Known renal stones

Cardiovascular

• Chest pain, palpitations, shortness of breath
• Ankle swelling (CKD / heart failure)

Gastrointestinal

• Nausea, vomiting, diarrhea
• GI upset with NSAIDs or colchicine
• Peptic ulcer disease (relevant if considering NSAIDs)

Skin

• Rashes, tophi, ulceration
• Psoriatic plaques

Systemic

• Fever, chills (rule out septic arthritis)
• Fatigue, weight loss (haematological malignancy?)
• Night sweats

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13. FUNCTIONAL IMPACT

• Can the patient walk during an attack?
• Time off work due to gout?
• Sleep disturbance from pain?
• Ability to wear normal footwear?
• Impact on social life / activities?
• How is the patient coping emotionally?

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14. PATIENT'S IDEAS, CONCERNS & EXPECTATIONS (ICE)

• Ideas: What does the patient think is causing their symptoms?
• Concerns: What worries them most? (damage, disability, long-term medication)
• Expectations: What do they hope to achieve today? Pain relief? Diagnosis? Long-term prevention?
• Understanding of gout and uric acid?
• Previous advice given — has it been followed?
• Willingness to change diet / lifestyle?

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Quick Reference Summary Table

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🩺 Gout Patient — Clinical Interview Questions

Exact Questions for Diagnosis & Medical Record

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🔴 OPENING

"What brought you in today?" "Tell me about the pain you are having."

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1. PRESENTING JOINT PAIN

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2. ATTACK PATTERN & HISTORY

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3. TRIGGER FACTORS

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4. TOPHI (CHRONIC GOUT)

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5. KIDNEY / URINARY SYMPTOMS

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6. PAST MEDICAL HISTORY

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7. DRUG HISTORY

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8. FAMILY HISTORY

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9. SOCIAL HISTORY

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10. FUNCTIONAL IMPACT

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11. ICE — Ideas, Concerns & Expectations

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🔵 DIAGNOSTIC CHECKLIST — What to Document

DATE OF CONSULTATION:
PATIENT: Age / Sex / Ethnicity (HLA-B*5801 relevant in Asian patients)

PC:   Joint pain — [joint name], [duration]

HPC:
  - Site: _______________
  - Onset: Sudden / Gradual
  - Duration of current attack: ___ days
  - Severity: ___/10
  - Character: _______________
  - Hyperalgesia (bedsheet sign): Yes / No
  - Trigger identified: _______________
  - Number of previous attacks: ___
  - Attack frequency: ___/year
  - Complete resolution between attacks: Yes / No
  - Tophi present: Yes / No — Location: _______________
  - Renal stones: Yes / No

PMH:  HTN / DM / Dyslipidemia / CKD / CVD / Psoriasis / Malignancy / Transplant

DH:   [List all medications]
      Urate-raising drugs: Yes / No — _______________
      Current ULT: Yes / No — Drug/Dose: _______________
      Allergies: _______________

FH:   Gout / Renal stones / Kidney disease

SH:   Alcohol: ___ units/week (type: ___)
      Diet: High purine? ___
      Smoking: ___
      Occupation: ___
      Lead exposure: Yes / No

FUNCTIONAL STATUS: _______________

ICE:  _______________

SYSTEMS REVIEW: _______________

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🟡 KEY DIAGNOSTIC POINTERS FROM HISTORY

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🫀 DYSLIPIDEMIA

A Complete Topic Presentation

Based on AHA / ACC 2026 Guidelines

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PART 1 — INTRODUCTION

Definition

• Elevated LDL-C (low-density lipoprotein cholesterol)
• Elevated non-HDL-C
• Elevated triglycerides (TG)
• Elevated lipoprotein(a) [Lp(a)]
• Low HDL-C (high-density lipoprotein cholesterol)

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Why It Matters — AHA 2026 Context

The guideline is retitled from "Blood Cholesterol" to "Management of Dyslipidemia" — reflecting that ASCVD risk extends beyond LDL-C to include triglyceride-rich remnants and Lp(a).

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Lipoprotein Structure — Brief Review

AHA 2026 key principle: Every atherogenic particle carries exactly one ApoB molecule. ApoB is therefore a more accurate measure of atherogenic particle number than LDL-C alone.

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PART 2 — EPIDEMIOLOGY

Global Burden

• Cardiovascular disease (CVD) is the #1 cause of death globally, accounting for ~18 million deaths per year (WHO, 2024)
• Dyslipidemia is present in approximately 50% of adults worldwide
• Elevated LDL-C is estimated to cause 4.4 million deaths annually
• Only one-third of individuals with dyslipidemia are aware of their condition
• Only one-fifth of those aware are adequately treated

United States (AHA 2026 Data)

• ~94 million U.S. adults (age ≥20) have total cholesterol ≥200 mg/dL
• ~28% of U.S. adults have LDL-C ≥130 mg/dL
• ~25% of U.S. adults have low HDL-C (<40 mg/dL men, <50 mg/dL women)
• ~25% have hypertriglyceridemia (TG ≥150 mg/dL)
• ~20% of the population has elevated Lp(a) ≥50 mg/dL
• Hypertriglyceridemia affects ~1 in 4 American adults
• Despite statin availability, only ~55% of very-high-risk patients achieve LDL-C goals

Demographic Patterns

Pediatric Epidemiology

• AHA 2026 recommends universal lipid screening for children ages 9–11 years
• Familial hypercholesterolemia (FH) affects ~1 in 250 persons worldwide
• FH is one of the most common genetic disorders but remains >90% undiagnosed
• Childhood hypercholesterolemia accelerates atherosclerosis beginning in the first decade of life (Bogalusa Heart Study)

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PART 3 — PATHOPHYSIOLOGY

Overview of Normal Lipid Metabolism

Exogenous Pathway (Dietary Lipids)

1. Dietary fat absorbed in gut → packaged into chylomicrons (contain ApoB-48)
2. Chylomicrons enter lymphatics → circulation → deliver TG to muscles and adipose tissue via lipoprotein lipase (LPL)
3. Chylomicron remnants taken up by liver via ApoE receptor

Endogenous Pathway (Hepatic Lipids)

1. Liver synthesizes TG and cholesterol → packaged into VLDL (contain ApoB-100)
2. LPL in peripheral tissues hydrolyzes VLDL TG → VLDL becomes IDL, then LDL
3. LDL delivers cholesterol to peripheral tissues via LDL receptor (LDLR)
4. LDLR expression is regulated by intracellular cholesterol and PCSK9 (which degrades LDLR)

Reverse Cholesterol Transport

1. HDL (ApoA-I) picks up excess cholesterol from peripheral tissues
2. LCAT esterifies cholesterol → HDL matures
3. Cholesterol transferred back to liver via SR-B1 receptor or exchanged to LDL/VLDL via CETP

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Atherogenesis — Step by Step

Step 1 — LDL Entry

• LDL particles (especially small, dense LDL) cross endothelium into subendothelial space (intima)
• Entry is driven by particle number (ApoB) and endothelial dysfunction (HTN, smoking, hyperglycemia, shear stress)

Step 2 — Oxidative Modification

• LDL trapped in intima is oxidized → oxidized LDL (ox-LDL)
• ox-LDL activates endothelial cells → expression of ICAM-1, VCAM-1, MCP-1
• Monocytes recruited from blood → enter intima → differentiate into macrophages

Step 3 — Foam Cell Formation

• Macrophages express scavenger receptors (SR-A, CD36) — these are not downregulated by intracellular cholesterol
• Macrophages engulf ox-LDL uncontrolled → become foam cells
• Foam cells accumulate → fatty streak (earliest visible atherosclerotic lesion, present even in children)

Step 4 — Plaque Development

• Smooth muscle cells (SMC) migrate from media → intima → secrete collagen → form fibrous cap
• Necrotic core develops: foam cells die → release cholesterol crystals, proteases, cytokines
• Vulnerable plaque = large necrotic core + thin fibrous cap + active inflammation

Step 5 — Plaque Rupture → ASCVD Event

• Metalloproteinases (MMPs) degrade fibrous cap → plaque rupture
• Subendothelial collagen exposed → platelet aggregation + thrombus formation
• Results: ACS (STEMI/NSTEMI), ischemic stroke, TIA, PAD

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Role of Key Lipid Particles in Atherogenesis

LDL-C

• Each LDL particle carries one ApoB → more particles = more intimal entry
• Causal relationship confirmed by Mendelian randomization studies
• Every 1 mmol/L (38.7 mg/dL) reduction in LDL-C → ~22% reduction in MACE

VLDL / Remnant Particles

• AHA 2026 highlights triglyceride-rich remnant particles as independent atherogenic particles
• Remnants are small enough to penetrate endothelium
• Non-HDL-C includes all atherogenic particles (LDL + VLDL + IDL + Lp(a))
• Non-HDL-C = Total cholesterol − HDL-C

Lp(a)

• Lp(a) = LDL + apo(a) linked by disulfide bond
• Pro-atherogenic: enters intima like LDL; promotes foam cell formation
• Pro-thrombotic: apo(a) inhibits fibrinolysis (structural homology with plasminogen)
• Independently increases risk of MI, stroke, aortic stenosis, PAD
• Levels are >90% genetically determined — not modifiable by diet

HDL

• Reverse cholesterol transport: removes cholesterol from vessel wall → liver
• Also has anti-inflammatory, antioxidant, antithrombotic properties
• Low HDL-C (<40 mg/dL men, <50 mg/dL women) = independent CV risk factor
• HDL raising drugs (niacin, CETP inhibitors) have not reduced CV events in trials → HDL function more important than level

PCSK9 — Mechanism Critical for Treatment

• PCSK9 = proprotein convertase subtilisin/kexin type 9
• Synthesized in liver → binds LDLR → targets it for lysosomal degradation
• Loss-of-function PCSK9 mutations → very low LDL-C + protection from ASCVD
• Gain-of-function mutations → very high LDL-C (familial hypercholesterolemia phenotype)
• PCSK9 inhibitors (evolocumab, alirocumab) block this → more LDLR on hepatocyte surface → ↓LDL-C 50–65%

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PART 4 — CLINICAL FEATURES

Most Patients Are Asymptomatic

1. Physical signs of lipid deposition
2. Manifestations of ASCVD complications

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Physical Signs of Lipid Deposition

Xanthomas

Corneal Arcus (Arcus Senilis)

• White/grey ring around corneal periphery
• Normal in elderly >60 years
• In patients <45 years = suggests significant hypercholesterolemia / FH

Lipemia Retinalis

• Cream-colored retinal vessels on fundoscopy
• Occurs with TG >2000 mg/dL
• Indicates severe hypertriglyceridemia

Hepatosplenomegaly

• Seen in severe hypertriglyceridemia
• Organ enlargement from lipid-laden reticuloendothelial cells

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ASCVD Manifestations (Complications)

Coronary Artery Disease (CAD)

• Stable angina: exertional chest tightness, pressure, radiation to arm/jaw
• Acute coronary syndrome (ACS): rest pain, diaphoresis, dyspnea, nausea
• Silent MI: especially in diabetics

Cerebrovascular Disease

• Transient ischemic attack (TIA): transient focal neuro deficits
• Ischemic stroke: sudden weakness, speech difficulty, vision loss
• Carotid bruits on auscultation

Peripheral Arterial Disease (PAD)

• Intermittent claudication: calf pain on walking, relieved by rest
• Rest pain, non-healing ulcers, gangrene (severe)
• Absent peripheral pulses, decreased ankle-brachial index (ABI)

Acute Pancreatitis (Hypertriglyceridemia Specific)

• Severe abdominal pain, nausea, vomiting
• Occurs when TG ≥500 mg/dL (risk rises sharply at ≥1000 mg/dL)
• Eruptive xanthomas may precede pancreatitis

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Symptoms by Lipid Type Summary

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PART 5 — LABORATORY INVESTIGATIONS

Standard Lipid Panel

AHA 2026: Non-fasting lipid testing is adequate for most clinical scenarios. Fasting is required if TG >400 mg/dL or for accurate LDL-C calculation (Friedewald equation requires fasting).

LDL-C Calculation

LDL-C = Total Cholesterol − HDL-C − (TG ÷ 5)

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Extended Lipid Testing — AHA 2026 Additions

Lipoprotein(a) — Lp(a)

• AHA 2026: Class I — Measure at least once in all adults
• Units: mg/dL or nmol/L (nmol/L preferred — avoids particle size variation)
• Risk thresholds:
  • ≥75 nmol/L (≈30 mg/dL) = risk modifier
  • ≥125 nmol/L (≈50 mg/dL) = high risk — reclassify upward
• Cannot be meaningfully reduced by lifestyle — genetic determination
• Repeat only if clinical decision-making requires

Apolipoprotein B (ApoB)

• AHA 2026: Selective use to improve risk assessment and guide treatment
• One ApoB per atherogenic particle → better reflects particle burden than LDL-C
• Especially useful when:
  • LDL-C and non-HDL-C are discordant
  • Hypertriglyceridemia (LDL-C underestimated)
  • Metabolic syndrome / diabetes (small dense LDL)
• Treatment goals (AHA 2026):

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Additional Investigations for Risk Assessment

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Coronary Artery Calcium (CAC) Scoring

CAC = 0 in a patient age ≥40 has very high negative predictive value for near-term ASCVD — can safely defer statin therapy with lifestyle only. Incidental CAC found on non-cardiac CT should also trigger lipid-lowering therapy consideration.

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Risk Calculation — PREVENT-ASCVD

• Age, sex, race
• Systolic BP (treated vs untreated)
• Total cholesterol, HDL-C
• Diabetes (yes/no) + HbA1c
• Smoking status
• eGFR + uACR (renal function — NEW)
• Zip code-level social deprivation index (NEW)

• 10-year ASCVD risk
• 30-year ASCVD risk (new — enables earlier intervention discussion)

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PART 6 — DIAGNOSTIC CRITERIA & CLASSIFICATION

AHA 2026 Classification of Dyslipidemia

By Lipid Parameter

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Fredrickson / WHO Classification (Phenotypic)

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Primary vs Secondary Dyslipidemia

Primary (Genetic) Causes

Secondary Causes

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Familial Hypercholesterolemia — Diagnostic Criteria

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PART 7 — RISK FACTORS

Non-Modifiable Risk Factors

Modifiable Risk Factors

Lifestyle

Medical Comorbidities

Drug-Induced Dyslipidemia

Risk Enhancers (AHA 2026 — Reclassify Risk Upward)

• LDL-C ≥160 mg/dL (primary prevention)
• Lp(a) ≥125 nmol/L
• ApoB ≥130 mg/dL
• hsCRP ≥2.0 mg/L
• ABI <0.9 (PAD)
• Chronic inflammatory conditions (RA, psoriasis, SLE)
• HIV infection
• Premature menopause (<40 years)
• Preeclampsia history
• South Asian ancestry
• Social deprivation / low SES

---

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PART 8 — TREATMENT & MANAGEMENT

AHA 2026 Treatment Framework

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AHA 2026 LDL-C Treatment Goals

In ALL patients on pharmacotherapy: Also target ≥50% LDL-C reduction from pre-treatment baseline.

Very High Risk = ≥2 major ASCVD events OR 1 major ASCVD event + ≥2 high-risk conditions (diabetes, CKD, heart failure, PAD, HTN, active smoking, age >65, prior PCI/CABG)

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A. NON-PHARMACOLOGICAL MANAGEMENT

1. Dietary Modifications

Dietary Pattern

Foods to Reduce / Avoid

• Red meat, processed meat, organ meats
• Full-fat dairy (butter, cheese, cream)
• Tropical oils (coconut oil, palm oil)
• Fried foods, fast food, pastries
• Sugar-sweetened beverages, fructose (↑ TG)
• Excess alcohol (especially for hypertriglyceridemia)

Foods to Increase

• Oily fish (salmon, mackerel, sardines) — omega-3
• Nuts (walnuts, almonds)
• Legumes, whole grains
• Fruits and vegetables (soluble fiber)
• Soy protein
• Low-fat dairy (mildly lowers LDL-C)
• Coffee (filtered — not unfiltered which raises LDL-C)

Dietary Supplements — AHA 2026 Position

Class 3 (No Benefit): Fish oil, red yeast rice, plant sterols are NOT recommended as routine ASCVD risk-reduction strategies. Evidence is limited and inconsistent.

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2. Physical Activity

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3. Weight Management

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4. Smoking Cessation

• Smoking cessation → ↑ HDL-C 4-8 mg/dL within months
• Reduces oxidative stress → less ox-LDL formation
• Endothelial function improves within weeks
• Significant reduction in ASCVD risk

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5. Alcohol Reduction

• Limiting alcohol reduces hypertriglyceridemia significantly
• For TG ≥500 mg/dL → abstinence from alcohol is mandatory
• No protective "safe" alcohol level for ASCVD in AHA 2026

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B. PHARMACOLOGICAL MANAGEMENT

Drug Class 1 — Statins (HMG-CoA Reductase Inhibitors)

Mechanism:

• Inhibit HMG-CoA reductase → ↓ intracellular cholesterol synthesis
• ↑ LDLR expression on hepatocytes → ↑ LDL clearance from plasma
• Pleiotropic effects: anti-inflammatory, plaque-stabilizing, endothelial-protective

Statin Intensity Classification (AHA 2026):

AHA 2026 Statin Recommendations:

• Very high risk → High-intensity statin (mandatory first step)
• Secondary prevention → high-intensity statin regardless of baseline LDL-C
• Primary prevention PREVENT ≥7.5% + risk enhancers → moderate-to-high intensity statin
• Diabetes (any) → statin therapy recommended

Side Effects:

Statin benefit ALWAYS outweighs risk in high-risk patients. Do not discontinue without specialist review.

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Drug Class 2 — Ezetimibe

• Mechanism: Inhibits NPC1L1 transporter in intestinal brush border → ↓ cholesterol absorption
• LDL-C reduction: 18–24% (additional, on top of statin)
• Dose: 10 mg/day
• Key trial: IMPROVE-IT (simvastatin + ezetimibe vs simvastatin alone → ↓ MACE 6.4%)
• AHA 2026: Add ezetimibe if LDL-C goal not achieved on maximally tolerated statin
• Side effects: Generally well tolerated; mild GI upset, rare myopathy

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Drug Class 3 — PCSK9 Inhibitors (Monoclonal Antibodies)

• Mechanism: Monoclonal antibody binds PCSK9 → prevents LDLR degradation → more LDLR → ↓ LDL-C 50–65%
• Key trials: FOURIER (evolocumab, ↓ MACE 15%), ODYSSEY OUTCOMES (alirocumab, ↓ MACE 15%)
• Also reduces Lp(a) by ~20–25%
• AHA 2026: For very high risk not at LDL-C goal; no longer strictly sequential — choose based on LDL-C gap needed
• Side effects: Injection site reactions; generally very well tolerated; safety data to LDL-C as low as 30 mg/dL with no safety concerns

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Drug Class 4 — Bempedoic Acid

• Mechanism: Inhibits ATP-citrate lyase (ACL) — upstream of HMG-CoA reductase; activated only in liver (not muscle → less myopathy)
• LDL-C reduction: ~18% (alone); ~28% with ezetimibe (combination tablet available)
• Dose: 180 mg/day oral
• Key trial: CLEAR Outcomes (2023) — bempedoic acid in statin-intolerant patients → ↓ MACE 13%
• AHA 2026: Recommended for statin-intolerant patients requiring LDL-C lowering
• Side effects: Gout (↑ uric acid — avoid in active gout), tendon rupture (rare), GI upset

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Drug Class 5 — Inclisiran (siRNA PCSK9 Inhibitor)

• Mechanism: Small interfering RNA (siRNA) → silences PCSK9 mRNA in hepatocytes → ↓ PCSK9 production → ↑ LDLR → ↓ LDL-C ~50%
• Dose: 284 mg SC at 0, 3 months, then every 6 months
• Advantage over mAbs: Less frequent dosing → better adherence
• Key trials: ORION-10, ORION-11 → consistent ~50% LDL-C reduction
• AHA 2026: Second-line if PCSK9 mAb not tolerated or accessible
• Side effects: Injection site reactions; generally well tolerated

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Drug Class 6 — Fibrates

• Mechanism: PPAR-α agonists → ↑ LPL activity → ↓ VLDL → ↓ TG; ↑ HDL-C
• TG reduction: 30–50%; HDL-C: ↑10–20%; LDL-C: variable
• Agents: Fenofibrate, gemfibrozil, bezafibrate
• Indication: TG ≥500 mg/dL (pancreatitis prevention); adjunct for combined dyslipidemia
• Caution: Gemfibrozil + statin → ↑ myopathy risk (pharmacokinetic interaction) — prefer fenofibrate with statins
• AHA 2026: Not recommended for primary ASCVD risk reduction alone; used for TG management

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Drug Class 7 — Omega-3 Fatty Acids (EPA)

AHA 2026: Icosapentaenoic acid (EPA only) 4 g/day recommended for ASCVD risk reduction in patients on statin with TG 135–499 mg/dL. Mixed EPA+DHA formulations do NOT have the same benefit.

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Drug Class 8 — Evinacumab (for Homozygous FH only)

• Mechanism: Monoclonal antibody against ANGPTL3 → ↑ LPL + EL activity → ↓ LDL-C even in LDLR-null patients
• LDL-C reduction: ~47% in HoFH (LDL-C independent of LDLR expression — works even when no functional receptors)
• AHA 2026: Approved add-on for HoFH patients not at goal despite max therapy
• Dose: 15 mg/kg IV every 4 weeks

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Drug Class 9 — Pelacarsen (Lp(a) Targeting — Pipeline)

• Mechanism: Antisense oligonucleotide → inhibits hepatic apo(a) synthesis → ↓ Lp(a) by ~80%
• Status: Phase 3 LPA-HPIV trial (Lp(a) HORIZON trial) results anticipated — AHA 2026 acknowledges as emerging therapy
• AHA 2026: Not yet a guideline-endorsed treatment target for Lp(a) — but notes Lp(a) will likely become a pharmacological target in near future

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Treatment Algorithm Summary

ESTABLISH RISK CATEGORY (using PREVENT-ASCVD equations + CAC if needed)
                    ↓
ALL PATIENTS → LIFESTYLE MODIFICATIONS (diet, exercise, weight, smoking)
                    ↓
If pharmacotherapy indicated:
                    ↓
STEP 1 → High-intensity statin (rosuvastatin 20-40 mg OR atorvastatin 40-80 mg)
         Target: ≥50% LDL-C reduction
                    ↓
         Recheck lipid panel in 4-12 weeks
                    ↓
STEP 2 → If LDL-C goal not met: ADD EZETIMIBE 10 mg/day
                    ↓
         Recheck lipid panel in 4-12 weeks
                    ↓
STEP 3 → If LDL-C goal still not met (very/high risk):
         ADD PCSK9 INHIBITOR (evolocumab or alirocumab)
         [AHA 2026: No longer mandatory to wait — can add earlier based on LDL-C gap]
                    ↓
IF STATIN INTOLERANT → Replace statin with:
         Bempedoic acid ± ezetimibe
         OR inclisiran
         OR PCSK9 inhibitor alone
                    ↓
SPECIAL:
  - HoFH → Add evinacumab + consider LDL apheresis
  - TG ≥500 → Fibrate first; EPA (4g/day) if TG 135-499 on statin
  - Elevated Lp(a) → PCSK9 inhibitor (↓ 20-25%); pelacarsen (investigational)

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Monitoring After Therapy

Both AHA 2026 guidelines identify therapeutic inertia (failure to intensify treatment despite uncontrolled lipids) as a major barrier to achieving LDL-C goals.

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Special Population Management Summary

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SUMMARY TABLE — AHA 2026 Key Numbers

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References: Blumenthal RS, Morris PB et al. 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia. Circulation. March 2026. JACC Guideline-at-a-Glance. Volume 87, Number 19. 2026.

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DYSLIPIDEMIA

AHA / ACC 2026 Guidelines — Topic Presentation

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1. INTRODUCTION

• Dyslipidemia = abnormal levels of lipoproteins (↑LDL, ↑TG, ↓HDL, ↑Lp(a))
• Leading modifiable risk factor for ASCVD
• AHA 2026 replaces 2018 guideline — broader scope beyond LDL-C alone
• Key shift: from treating a number → treating lifetime cardiovascular risk

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2. EPIDEMIOLOGY

• CVD = #1 cause of death globally (~18 million deaths/year)
• ~94 million U.S. adults have TC ≥200 mg/dL
• ~28% have LDL-C ≥130 mg/dL
• ~20% have elevated Lp(a) ≥50 mg/dL
• Only 55% of very-high-risk patients reach LDL-C goals
• FH affects 1 in 250 — >90% undiagnosed

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3. PATHOPHYSIOLOGY

↑ LDL-C (ApoB)
      ↓
Enters subendothelial space
      ↓
Oxidized → LDL (ox-LDL)
      ↓
Macrophage engulfs → Foam cells → Fatty streak
      ↓
Fibrous cap + Necrotic core → Plaque
      ↓
Rupture → Thrombus → ACS / Stroke / PAD

• LDL-C — primary atherogenic driver
• Remnant particles — now highlighted in AHA 2026
• Lp(a) — pro-atherogenic + pro-thrombotic; genetic
• ApoB — one per atherogenic particle; best reflects particle burden

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4. CLINICAL FEATURES

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5. LAB INVESTIGATIONS

• Lp(a) — once in all adults (Class I)
• ApoB — selective use; goal <65–90 mg/dL by risk
• CAC score — expands primary prevention decisions
• PREVENT-ASCVD — 10 + 30-year risk (replaces PCE)
• Supporting: HbA1c, eGFR, uACR, hsCRP, LFTs, CK

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6. DIAGNOSTIC CRITERIA & CLASSIFICATION

• Primary — genetic: FH, familial combined hyperlipidemia, elevated Lp(a)
• Secondary — DM, hypothyroidism, CKD, obesity, alcohol, drugs (thiazides, steroids, cyclosporin)

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7. RISK FACTORS

• Age (M ≥45 / F ≥55), male sex, family history, genetics, ethnicity

• Unhealthy diet, physical inactivity, obesity, smoking, alcohol excess
• DM, hypertension, metabolic syndrome, CKD

• Thiazides, beta-blockers, corticosteroids, cyclosporin, HIV ART

• Lp(a) ≥125 nmol/L, hsCRP ≥2 mg/L, ABI <0.9, chronic inflammation (RA, SLE), preeclampsia history, South Asian ancestry, social deprivation

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8. TREATMENT & MANAGEMENT

LDL-C Goals (AHA 2026)

All patients on therapy: also achieve ≥50% LDL-C reduction

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A. NON-PHARMACOLOGICAL

❌ AHA 2026 Class 3: Fish oil, red yeast rice, plant sterol supplements — NOT recommended as ASCVD prevention

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B. PHARMACOLOGICAL

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Treatment Algorithm

ALL PATIENTS
    → Lifestyle modification first

PHARMACOTHERAPY:

STEP 1 → High-intensity statin
STEP 2 → + Ezetimibe (if goal not met)
STEP 3 → + PCSK9 inhibitor (if still not at goal)

STATIN INTOLERANT → Bempedoic acid ± ezetimibe / Inclisiran

SPECIAL:
• TG ≥500 → Fibrate first
• TG 135-499 on statin → EPA 4 g/day
• HoFH → Evinacumab + LDL apheresis

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KEY NUMBERS TO REMEMBER

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Source: AHA/ACC 2026 Guideline on the Management of Dyslipidemia — Circulation, March 2026

⚠ Important Note: The ADA (American Diabetes Association) does not publish a standalone dyslipidemia guideline. The ADA 2026 Standards of Care in Diabetes covers dyslipidemia specifically in the context of diabetes management. The dedicated dyslipidemia guideline is the ACC/AHA 2026 (which the ADA co-authored and endorsed as a writing partner society). What follows covers both — the ADA 2026 dyslipidemia recommendations for diabetic patients + the shared diagnostic criteria.

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DYSLIPIDEMIA — Diagnostic Criteria

ADA 2026 Standards of Care + ACC/AHA 2026 (Co-authored by ADA)

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1. WHAT IS DYSLIPIDEMIA? (ADA Definition)

ADA 2026 notes: Non-HDL-C is more predictive of persistent dyslipidemia and atherosclerosis in diabetic patients than LDL-C, total cholesterol, or HDL-C alone — because it captures the full atherogenic burden (LDL + VLDL + IDL + Lp(a)).

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2. DIAGNOSTIC / CLASSIFICATION CRITERIA

Standard Lipid Panel Diagnostic Thresholds

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3. ADA 2026 — RISK-BASED CLASSIFICATION IN DIABETES

Tier 1 — Extreme / Very High Risk

• Established ASCVD (prior MI, stroke, ACS, coronary revascularization, PAD)
• DM + multiple major ASCVD risk factors (age ≥55M/≥65F, HTN, smoking, CKD, albuminuria, LDL-C ≥100)
• DM + target organ damage (retinopathy, neuropathy, eGFR <60, uACR >30)

Tier 2 — High Risk

• DM, age 40–75 years, without established ASCVD
• Duration of diabetes ≥10 years (T2DM) or ≥20 years (T1DM)

Tier 3 — Moderate Risk

• DM, age 40–75 years, short duration, no major risk factors

ADA 2026 states: LDL-lowering pharmacotherapy is recommended for ALL adults aged 40–75 with diabetes, regardless of baseline LDL-C level.

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4. SCREENING CRITERIA (ADA 2026)

Adults with Diabetes

Children & Adolescents with Diabetes

Non-HDL-C is the preferred screening marker in children — more predictive than LDL-C for persistent dyslipidemia and atherosclerosis.

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5. DIAGNOSTIC LABS REQUIRED (ADA 2026)

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6. PREDIABETES — ADA 2026 CRITERIA LINK TO DYSLIPIDEMIA

• ↑ Triglycerides
• ↓ HDL-C
• Hypertension
• Abdominal / visceral obesity

Presence of prediabetes with any of these lipid findings should prompt comprehensive CV risk factor screening immediately — not waiting for T2DM diagnosis.

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7. LIPID TARGETS SUMMARY TABLE (ADA 2026)

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8. WHEN TO DIAGNOSE DYSLIPIDEMIA IN A DIABETIC PATIENT

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QUICK REFERENCE CARD

ADA 2026 — Dyslipidemia in Diabetes

SCREEN:  At diagnosis → annually (adults)
         At diagnosis → every 3 years if normal (children T1DM)

DIAGNOSE: Any lipid abnormality on standard panel
          Non-HDL-C preferred marker in DM

CLASSIFY BY RISK:
  Established ASCVD    → Very High Risk → LDL-C < 55
  DM age 40-75         → High Risk      → LDL-C < 70
  DM young, no RF      → Moderate Risk  → LDL-C < 100

TREAT: ALL adults 40-75 with DM → statin therapy
       regardless of baseline LDL-C level

MONITOR: Recheck 4-12 weeks after therapy → then annually

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Sources: ADA. Standards of Care in Diabetes — 2026. Diabetes Care. Jan 2026; 49(Suppl.1). Blumenthal RS et al. 2026 ACC/AHA/Multisociety Guideline on the Management of Dyslipidemia (ADA co-authored). Circulation. March 2026.

DYSLIPIDEMIA — Follow-Up

Post-Presentation Topic Slide

AHA 2026 / ADA 2026 Guidelines

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1. FOLLOW-UP SCHEDULE

After Starting or Changing Therapy

ADA 2026: Obtain lipid profile at initiation of statin → 4–12 weeks after → annually thereafter.

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2. WHAT TO CHECK AT EVERY FOLLOW-UP VISIT

Lipid Parameters

Safety Labs

Clinical Assessment

• Blood pressure — measure every visit
• Weight / BMI — calculate at every visit
• Waist circumference — assess for metabolic syndrome
• Symptoms of ASCVD — angina, claudication, TIA
• Adherence to medications — ask directly
• Adherence to lifestyle changes — diet, exercise, smoking
• Drug side effects — myalgia, fatigue, GI symptoms

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3. TREATMENT RESPONSE ASSESSMENT

Is the Patient at Goal?

Step 1 — Check % LDL-C reduction from baseline
         Target: ≥50% reduction on therapy

Step 2 — Check absolute LDL-C goal
         Very high risk   → < 55 mg/dL
         High risk        → < 70 mg/dL
         Intermediate     → < 100 mg/dL

Step 3 — Check non-HDL-C goal
         Very high risk   → < 85 mg/dL
         High risk        → < 100 mg/dL

Step 4 — Check ApoB if discordance suspected

BOTH percentage reduction AND absolute goal must be met.

If Goal NOT Met — Escalate Therapy

AHA 2026: Therapeutic inertia = failure to intensify therapy despite uncontrolled lipids — this is a major documented barrier to achieving goals. Do not accept subtherapeutic responses.

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4. MONITORING SPECIFIC DRUG SIDE EFFECTS

Statins

Ezetimibe

• Generally well tolerated
• Rare: GI upset, headache, arthralgias
• No routine lab monitoring required

PCSK9 Inhibitors

• Injection site reactions — ask at follow-up
• Safe at very low LDL-C (no safety signal down to LDL-C ~20 mg/dL)
• No routine lab monitoring required beyond lipid panel

Bempedoic Acid

• Uric acid — check at each visit (raises uric acid → can precipitate gout)
• Tendon rupture (rare) — ask about tendon pain
• Avoid in patients with active gout

Fibrates

• LFTs, CK, renal function — especially if combined with statin
• Gemfibrozil + statin = avoid (↑ myopathy risk)
• Fenofibrate + statin = safer combination

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5. LIFESTYLE FOLLOW-UP (Ask Every Visit)

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6. WHEN TO REFER TO LIPID SPECIALIST

• LDL-C ≥190 mg/dL (suspected Familial Hypercholesterolemia)
• Homozygous FH (HoFH) — any patient
• Not at LDL-C goal despite maximum tolerated statin + ezetimibe + PCSK9i
• Statin intolerance — multiple statins failed
• Severe hypertriglyceridemia (TG ≥1000 mg/dL)
• Complex drug interactions
• Pregnancy with severe dyslipidemia
• Pediatric patients with LDL-C ≥190 mg/dL or known FH

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7. SPECIAL POPULATIONS — FOLLOW-UP NOTES

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8. PATIENT EDUCATION AT FOLLOW-UP

• ✅ "Lower LDL-C for longer = less lifetime risk"
• ✅ Statins are safe long-term — do not stop without doctor advice
• ✅ Lifestyle changes work alongside medication — not instead of it
• ✅ Missing doses reduces protection significantly
• ✅ Lp(a) cannot be lowered by diet — it needs medication if very high
• ❌ Supplements (fish oil, red yeast rice) are not recommended by AHA 2026

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FOLLOW-UP SUMMARY CARD

VISIT CHECKLIST — DYSLIPIDEMIA FOLLOW-UP

□ Lipid panel — LDL-C, non-HDL-C, TG, HDL-C
□ % LDL-C reduction from baseline — did we hit ≥50%?
□ Absolute goal met? (<55 / <70 / <100 depending on risk)
□ Ask about myalgia / muscle symptoms
□ Ask about medication adherence
□ HbA1c + glucose (statin DM risk + DM patients)
□ BP, weight, BMI
□ Lifestyle review — diet, exercise, smoking, alcohol
□ eGFR / CK — if indicated
□ Escalate therapy if goal NOT met
□ Refer to lipid specialist if needed
□ Educate patient — reinforce lower is better, longer is better

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Sources: AHA/ACC 2026 Guideline on Dyslipidemia · ADA 2026 Standards of Care in Diabetes

DYSLIPIDEMIA — Follow-Up

AHA 2026 / ADA 2026

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FOLLOW-UP SCHEDULE

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GOALS TO CHECK AT EACH VISIT

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WHAT TO ASSESS

• ✅ Medication adherence
• ✅ Myalgia / muscle symptoms (CK only if symptomatic)
• ✅ Weight, BP, waist circumference
• ✅ Lifestyle — diet, exercise, smoking, alcohol
• ✅ HbA1c + fasting glucose annually (statin → new DM risk)
• ✅ eGFR — drug dose adjustment if CKD

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IF GOAL NOT MET — ESCALATE

Statin alone        → Add Ezetimibe
Statin + Ezetimibe  → Add PCSK9 inhibitor
Statin intolerant   → Bempedoic acid ± Ezetimibe
Still not at goal   → Refer to Lipid Specialist

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REFER TO LIPID SPECIALIST IF

• LDL-C ≥190 mg/dL (suspect FH)
• Not at goal despite statin + ezetimibe + PCSK9i
• Statin intolerance (multiple statins failed)
• TG ≥1000 mg/dL
• Homozygous FH

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KEY MESSAGE TO PATIENT

"Lower LDL-C + longer duration = less lifetime CV risk" Do not stop statins without medical advice. Lifestyle changes work with medication, not instead of it.

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AHA 2026 · ADA 2026 Standards of Care

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✅ Confirmed from AHA 2026 Guidelines

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⚠️ What Was Added from ADA 2026

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Bottom Line

The core follow-up framework — 4–12 weeks recheck, 6–12 month monitoring, ≥50% reduction target, absolute LDL-C goals, escalation steps, and specialist referral criteria — are all directly from AHA 2026.

The ADA 2026 adds diabetes-specific monitoring on top of that (HbA1c, eGFR, annual glucose) since ADA co-authored the AHA 2026 dyslipidemia guideline.

Lab Investigations in Dyslipidemia

Priority Order + CAC & Fredrickson Explained Simply

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PART 1 — LAB INVESTIGATIONS IN ORDER OF PRIORITY

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🥇 FIRST & MOST IMPORTANT — Do This Always

Fasting Lipid Panel

This is the single most important test. Do this first in every patient.

Fasting 9–12 hours before the test AHA 2026: Non-fasting is acceptable UNLESS TG is very high or you suspect hypertriglyceridemia

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🥈 SECOND PRIORITY — Do Next

Lp(a) — Lipoprotein(a)

• AHA 2026: Class I — measure at least ONCE in every adult
• It is genetic — one test in a lifetime is enough
• Normal: <75 nmol/L
• High risk: ≥125 nmol/L

ApoB — Apolipoprotein B

• Selective use — not everyone needs it
• Order it when:
  • TG is very high (LDL-C becomes unreliable)
  • Patient has diabetes
  • LDL-C looks normal but risk seems high
• Normal: <90 mg/dL (general); <65 mg/dL (very high risk)

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🥉 THIRD PRIORITY — Supporting Tests

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SIMPLE PRIORITY SUMMARY

STEP 1 — ALWAYS FIRST
  → Fasting Lipid Panel
     (TC + LDL-C + HDL-C + TG + Non-HDL-C)

STEP 2 — ALWAYS DO ONCE
  → Lp(a) — every adult, once in lifetime

STEP 3 — IF NEEDED
  → ApoB — if TG high, DM, or discordant results

STEP 4 — SUPPORTING
  → HbA1c, eGFR, uACR, TSH, LFTs, CK, hsCRP

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PART 2 — CAC SCORE EXPLAINED SIMPLY

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What is CAC?

CAC = Coronary Artery Calcium Score

🫀 Your coronary arteries (the pipes that supply blood to your heart) can slowly collect calcium deposits as part of plaque build-up. The more calcium = the more plaque = the higher your heart attack risk.

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CAC Score — What the Numbers Mean

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Simple Analogy for CAC

Imagine your heart arteries are water pipes. CAC is like an X-ray of the pipes looking for rust/mineral buildup inside.

• CAC = 0 → Pipes are clean → No urgent action
• CAC = 500 → Significant rust forming → Time to treat aggressively
• CAC = 1000+ → Pipes badly clogged → Maximum treatment needed

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When Does AHA 2026 Use CAC?

Patient has borderline risk on PREVENT score
          ↓
Unclear if statin is needed?
          ↓
Order CAC scan
          ↓
CAC = 0   → Hold statin, lifestyle only
CAC > 100 → Start statin
CAC ≥1000 → Treat as very high risk

Key point: CAC = 0 is very reassuring — it can safely delay starting medication and avoid unnecessary treatment.

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PART 3 — FREDRICKSON CLASSIFICATION EXPLAINED SIMPLY

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What is Fredrickson Classification?

It is a system that classifies dyslipidemia by which lipoprotein (fat particle) is elevated in the blood. Think of it as giving each type of dyslipidemia a type number (I–V).

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The 5 Fredrickson Types — Made Simple

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🔴 TYPE I — "Too Many Chylomicrons"

• What's high: Chylomicrons (dietary fat particles)
• Blood test: TG very very high (>1000 mg/dL); LDL normal
• Cause: Missing enzyme called LPL (lipoprotein lipase) — genetic, very rare
• Risk: Pancreatitis (not usually heart disease)
• Sign: Creamy/milky blood when drawn; eruptive xanthomas
• Memory tip: "Type I = I ate too much fat and can't clear it"

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🔴 TYPE IIa — "Too Much LDL" ← MOST COMMON

• What's high: LDL-C only
• TG: Normal
• Cause: Familial Hypercholesterolemia (FH) — genetic defect in LDL receptor
• Risk: High heart disease risk — early heart attacks
• Sign: Tendon xanthomas, corneal arcus, xanthelasma
• Memory tip: "Type IIa = II bad = LDL only going up"

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🔴 TYPE IIb — "LDL + TG Both High"

• What's high: LDL-C + VLDL (both elevated)
• Blood test: ↑ LDL-C + ↑ TG
• Cause: Familial Combined Hyperlipidemia — most common genetic dyslipidemia overall
• Risk: High heart disease risk
• Memory tip: "Type IIb = II things are bad = LDL AND TG both up"

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🟡 TYPE III — "Remnant Particles" (Rare)

• What's high: IDL / Remnant particles
• Blood test: TC and TG both equally elevated
• Cause: ApoE2/E2 genotype — remnants cannot be cleared properly
• Risk: Early heart disease AND PAD (legs)
• Sign: Palmar xanthomas (yellow deposits in palm creases) — pathognomonic
• Memory tip: "Type III = 3 things wrong = TC + TG + palm xanthomas"

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🟡 TYPE IV — "Too Much VLDL / High TG"

• What's high: VLDL
• Blood test: ↑ TG; LDL normal or low; HDL low
• Cause: Familial hypertriglyceridemia; also caused by DM, obesity, alcohol
• Risk: Moderate heart disease risk; pancreatitis if TG very high
• Memory tip: "Type IV = 4 = FOUR triglycerides going up"

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🔴 TYPE V — "Everything High" (Severe)

• What's high: VLDL + Chylomicrons
• Blood test: Very high TG (>1000 mg/dL)
• Cause: Combined genetic + secondary causes (DM, alcohol, obesity)
• Risk: High pancreatitis risk
• Sign: Eruptive xanthomas, lipemia retinalis (cream-colored retinal vessels)
• Memory tip: "Type V = Very bad TG = pancreatitis danger"

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FREDRICKSON QUICK TABLE

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Simple Memory Trick for Fredrickson

I    → I can't clear dietary fat (chylomicrons)
IIa  → II bad = LDL alone (FH pattern)
IIb  → II bad things = LDL + TG (combined)
III  → Three problems = TC + TG + palm xanthomas
IV   → Four = TG going up (VLDL only)
V    → Very severe = TG extreme + pancreatitis

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Which Types Are Most Clinically Important?

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Based on AHA 2026 Guidelines · ADA 2026 Standards of Care · Fredrickson WHO Classification

Acute Pancreatitis Due to Hypertriglyceridemia

Treatment & Management

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FIRST — CONFIRM THE DIAGNOSIS

⚠️ Note: In severe HTG, amylase/lipase can be falsely normal due to interference from lipemia — TG level is the key diagnostic clue.

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IMMEDIATE MANAGEMENT (Emergency)

Step 1 — Admit to Hospital (ICU if severe)

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Step 2 — Aggressive IV Fluid Resuscitation ⭐ Most Important

• Ringer's Lactate preferred over normal saline
• Rate: 250–500 mL/hour in first 12–24 hours
• Goal: urine output ≥0.5 mL/kg/hour
• Reassess every 6 hours — avoid over-resuscitation

This is the #1 treatment — adequate fluids prevent pancreatic necrosis.

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Step 3 — Nil by Mouth (NPO) / Bowel Rest

• Stop all oral intake initially
• Early enteral feeding (nasogastric/nasojejunal tube) preferred over TPN
• Start enteral feed within 24–48 hours if tolerated
• Avoid TPN unless enteral feeding is not possible
• No fat in feeds initially — reduces TG stimulation

⚠️ Avoid IV lipid emulsions (TPN with lipids) — will worsen hypertriglyceridemia.

---

Step 4 — Pain Management

---

Step 5 — Rapidly Lower Triglycerides

🔴 Target: Bring TG below 500 mg/dL as fast as possible

---

Option A — Insulin Infusion ⭐ First-line

• Regular insulin IV infusion at 0.1–0.2 units/kg/hour
• Activates lipoprotein lipase (LPL) → breaks down TG rapidly
• Monitor blood glucose every 1–2 hours
• Dextrose infusion alongside to prevent hypoglycemia
• Works even in non-diabetic patients

---

Option B — Heparin

• Unfractionated heparin IV bolus then infusion
• Releases endothelial LPL → ↓ TG
• Often used with insulin for additive effect
• Note: Short-term effect only — LPL stores deplete with prolonged use

---

Option C — Plasmapheresis / Plasma Exchange

• Used when TG >1000–2000 mg/dL and not responding to insulin
• Physically removes TG-rich lipoproteins from blood
• Rapidly reduces TG within hours
• Available in tertiary centers
• Consider early in severe or refractory cases

---

Option D — Fibrates (After Acute Phase)

• Not used during the acute attack (oral route not possible)
• Start fenofibrate once patient is stable and eating
• Long-term TG management to prevent recurrence

---

Step 6 — Treat Underlying Triggers

---

Step 7 — Antibiotics

• Not routinely given
• Only if infected pancreatic necrosis suspected:
  • Fever persisting >7 days
  • CT showing necrosis + gas
  • Positive blood cultures
• Drug of choice: Imipenem or Meropenem (penetrates pancreatic tissue)

---

Step 8 — Monitoring in Hospital

---

AFTER STABILIZATION — LONG-TERM PREVENTION

---

SUMMARY ALGORITHM

HTG-Acute Pancreatitis (TG ≥500 mg/dL)
              ↓
ADMIT → IV Fluids (Ringer's Lactate) — MOST URGENT
              ↓
NPO → Early enteral feeding (NO IV lipids)
              ↓
Pain control — IV opioids
              ↓
Rapidly ↓ TG:
  TG 500–1000  → Insulin infusion ± Heparin
  TG >1000     → Insulin + Heparin + consider Plasmapheresis
              ↓
Treat trigger (DM, alcohol, drugs, thyroid)
              ↓
Monitor: TG q12-24h, glucose q1-2h, vitals hourly
              ↓
Once stable + eating → Start Fenofibrate
              ↓
Long-term: Low fat diet, no alcohol, fibrate, follow-up TG

---

Based on ACG Clinical Guidelines · AHA 2026 · ADA 2026 Standards of Care

Standard Lipid Panel — Units of Measurement

---

The Two Main Unit Systems

---

Conversion Formula

mg/dL → mmol/L: Divide by 38.67 (for cholesterol) Divide by 88.57 (for triglycerides)

mmol/L → mg/dL: Multiply by 38.67 (for cholesterol) Multiply by 88.57 (for triglycerides)

---

Full Conversion Table — All Lipid Parameters

Total Cholesterol

---

LDL-C (Primary Target)

---

HDL-C (Protective)

---

Triglycerides

---

Non-HDL-C

---

Key Clinical Values at a Glance (Both Units)

---

Lp(a) — Special Units

Lp(a) has two different units and this causes confusion:

⚠️ nmol/L is preferred because Lp(a) particle size varies — mg/dL can be misleading depending on particle size. Always note which unit the lab uses.

---

ApoB Units

---

Quick Conversion Cheat Sheet

CHOLESTEROL (TC, LDL, HDL, Non-HDL):
  mg/dL ÷ 38.67 = mmol/L
  mmol/L × 38.67 = mg/dL

TRIGLYCERIDES:
  mg/dL ÷ 88.57 = mmol/L
  mmol/L × 88.57 = mg/dL

EXAMPLES:
  LDL 70 mg/dL  = 70 ÷ 38.67 = 1.81 mmol/L
  LDL 55 mg/dL  = 55 ÷ 38.67 = 1.42 mmol/L
  TG 500 mg/dL  = 500 ÷ 88.57 = 5.65 mmol/L
  TC 200 mg/dL  = 200 ÷ 38.67 = 5.17 mmol/L

---

Conversion factors: Cholesterol molecular weight = 386.7 g/mol · Triglyceride average molecular weight = 885.7 g/mol

TC/HDL-C Ratio Explained

---

What Is It?

TC/HDL-C Ratio = Total Cholesterol ÷ HDL-C

---

It Has NO Units

TC/HDL-C ratio = just a plain number — no mg/dL, no mmol/L

---

Simple Example

---

What the Numbers Mean

---

Why Is <5 the Cutoff?

• 5.0 is the average ratio for the general adult population
• Being below 5 means your good cholesterol (HDL) is doing its job well relative to your total cholesterol
• Being above 5 means there is more "bad" cholesterol burden relative to the protective HDL

Think of it like a balance scale:

• HDL = good weight on one side
• TC = total burden on the other side
• Ratio <5 = scale is balanced or tipped toward protection
• Ratio >5 = too much burden, not enough protection

---

Quick Calculation

Formula:
  TC/HDL-C Ratio = Total Cholesterol ÷ HDL-C

Example:
  TC = 210 mg/dL
  HDL = 42 mg/dL
  Ratio = 210 ÷ 42 = 5.0 → borderline, monitor

  TC = 190 mg/dL
  HDL = 55 mg/dL
  Ratio = 190 ÷ 55 = 3.45 → excellent

---

Important Note

The TC/HDL-C ratio is a screening/risk assessment tool — it does NOT replace LDL-C as the primary treatment target in AHA 2026. It is useful when you want a quick overall picture of lipid balance, especially in populations or when only TC and HDL-C are available.

Why We Measure Creatine Kinase (CK) in Dyslipidemia

---

What is CK?

Creatine Kinase (CK) is an enzyme found inside muscle cells. When muscle cells are damaged or broken down, CK leaks out into the bloodstream. So a high CK = muscle damage.

---

Why It Matters in Dyslipidemia — One Main Reason

Statins can cause muscle damage as a side effect. CK tells us how bad the muscle damage is.

---

The Statin-Muscle Problem

---

Why We Check CK — Step by Step

Before Starting Statin (Baseline)

• We check CK before starting the statin
• This gives us a reference point
• If CK is already high before starting → investigate why first (thyroid, vigorous exercise, muscle disease)

During Treatment (Only if Symptomatic)

• Do NOT check CK routinely in every follow-up — AHA 2026 says check only if patient complains of muscle symptoms
• If patient says: "My muscles ache, I feel weak" → check CK immediately

---

What to Do Based on CK Result

---

Rhabdomyolysis — Why It Is Dangerous

When massive muscle breakdown occurs: Muscle releases myoglobin → enters kidney tubules → blocks them → Acute Kidney Injury (AKI)

• Severe muscle pain and weakness
• Dark brown / cola-colored urine ← key sign
• Decreased urine output
• CK extremely high (thousands of U/L)

This is a medical emergency — IV fluids must be given urgently to flush the kidneys.

---

Other Reasons CK Can Be High (Not Statin-Related)

---

Simple Summary

WHY WE CHECK CK IN DYSLIPIDEMIA:

Before statin  → Get baseline level
               → If already high, investigate first

During statin  → Only check IF patient has muscle symptoms
               (NOT routine)

CK normal      → Muscle is fine → continue statin
CK >10× ULN   → Stop statin immediately
CK >40× ULN   → Emergency — rhabdomyolysis → admit + IV fluids

Goal = Catch muscle damage EARLY
       before kidneys are affected

---

Normal CK Values (Reference)

Values may vary slightly between laboratories — always compare to your lab's reference range.

Who Needs CK Testing?

Simple & Clear Guide — AHA 2026

---

SHORT ANSWER

No — we do NOT check CK in every patient. CK is only checked in specific situations.

---

WHEN TO CHECK CK — 3 Situations

---

Situation 1 — BEFORE Starting Statin

(Baseline — Selected Patients Only)

Healthy young/middle-aged patient with no risk factors starting a statin → NO baseline CK needed

---

Situation 2 — DURING Statin Therapy

(Only If Patient Has Muscle Symptoms)

Do NOT routinely check CK at every follow-up visit. Only check if patient complains of:

• Muscle pain, aching, soreness
• Muscle weakness
• Muscle cramps
• Dark urine (emergency — check immediately)
• Unexplained fatigue affecting daily activities

No symptoms = No CK check needed

---

Situation 3 — EMERGENCY

(Any time rhabdomyolysis is suspected)

• Severe muscle pain + weakness
• Cola/dark brown urine
• Muscle swelling
• Acute kidney injury signs (↓ urine output, creatinine rising)

---

SIMPLE DECISION CHART

STARTING A STATIN?
        ↓
Does patient have any risk factor for myopathy?
(muscle disease, hypothyroid, CKD, drug interactions,
 elderly, previous statin myalgia, family Hx)
        ↓
   YES → Check baseline CK first
   NO  → Start statin directly, no CK needed

─────────────────────────────────────

PATIENT ALREADY ON STATIN?
        ↓
Any muscle symptoms? (pain, weakness, dark urine)
        ↓
   YES → Check CK now
   NO  → Do NOT check CK routinely

─────────────────────────────────────

CK RESULT?
        ↓
Normal + symptoms    → Reassure, continue statin
>3× ULN, no symptoms → Monitor, recheck in 4–6 weeks
>10× ULN             → STOP statin
>40× ULN             → EMERGENCY — admit, IV fluids

---

SUMMARY TABLE — Who Gets CK?

---

Key Point to Remember

AHA 2026 is clear:

• CK before statin → only in high-risk patients
• CK during statin → only if muscle symptoms develop
• Routine CK monitoring in asymptomatic patients = not recommended

---

PART 1 — How Lp(a) Risk Thresholds Work

---

What Is Lp(a) Doing in the Body?

Lp(a) is like a double-threat particle:

• Acts like LDL → enters artery wall → causes plaque
• Also blocks clot breakdown → promotes thrombosis

---

The Two Units — This Is Where Confusion Happens

⚠️ These two units do not convert simply because Lp(a) particles vary in size. The same mg/dL value can mean different particle numbers in different people. That is why nmol/L is preferred.

---

How the Risk Thresholds Work

AHA 2026 — Two Thresholds

Normal          Risk Modifier         High Risk
─────────────────────────────────────────────────
    <75 nmol/L │ 75–124 nmol/L │ ≥125 nmol/L
    (<30 mg/dL)│(30–49 mg/dL)  │ (≥50 mg/dL)
               │               │
            Watch & monitor   ACTION needed

---

Threshold 1 — ≥75 nmol/L (≈30 mg/dL)

= Risk Modifier

Patient's ASCVD risk gets reclassified upward

• If a patient was borderline risk on PREVENT-ASCVD → now pushed to intermediate or high risk
• Clinician should intensify lifestyle changes
• May start statin earlier than originally planned
• Does not yet mean aggressive drug treatment specifically for Lp(a)

---

Threshold 2 — ≥125 nmol/L (≈50 mg/dL)

= High Risk — Action Needed

This level carries independent ASCVD risk regardless of LDL-C

---

Why Does Lp(a) RECLASSIFY Risk Rather Than Have Its Own Treatment Target?

Because currently there is no approved drug that specifically targets Lp(a) with proven CV outcome benefit yet.

High Lp(a) found
      ↓
Cannot directly treat Lp(a) yet
      ↓
Instead → treat everything else MORE aggressively
  → Lower LDL-C harder (PCSK9i helps Lp(a) too ~20%)
  → Control BP, DM, smoking more strictly
  → Reclassify risk upward → lower LDL-C targets
      ↓
FUTURE: Pelacarsen (antisense oligo) → ↓Lp(a) 80%
        Phase 3 trial results awaited
        Will likely create specific Lp(a) targets

---

Simple Analogy

Think of Lp(a) like a criminal record:

• No record (low Lp(a)) → normal risk assessment
• Minor record (≥75 nmol/L) → watch more carefully, be cautious
• Serious record (≥125 nmol/L) → treat as high risk even if other factors look okay

You cannot erase the record (genetic) — but you can reduce the damage it causes by controlling everything else harder.

---

Summary

Test once in a lifetime — Lp(a) barely changes, so one measurement is enough.

---

---

PART 2 — CAC Scoring: How It Is Done & When to Order It

---

What Is a CAC Scan?

A CAC scan = Coronary Artery Calcium CT scan It is a special low-dose CT scan of the chest that counts calcium deposits inside the coronary arteries. No injection. No contrast dye. Takes about 10 minutes.

---

How It Is Done — Step by Step

Before the Scan

• Patient lies on CT table
• No injection, no contrast, no preparation needed
• Patient asked to hold breath for 10 seconds during scan
• ECG leads placed on chest to synchronize scan with heartbeat (cardiac gating)

During the Scan

• Low-dose CT X-ray takes images of the heart
• Scanner captures multiple thin slices of the coronary arteries
• Total scan time: ~10 minutes
• Radiation dose: very low (~1 mSv — similar to a mammogram)

After the Scan

• Computer software analyzes the images
• Calculates the Agatston Score (the standard CAC scoring system)
• Score is based on:
  • Area of calcium deposit
  • Density (brightness) of calcium
• Final result = a single CAC score number

---

What Is the Agatston Score?

Named after cardiologist Arthur Agatston. It multiplies the area × density of each calcium deposit in each coronary artery and adds them all up.

---

What Does the Score Mean?

---

The 75th Percentile — What Does That Mean?

Your CAC score is also compared to other people of your same age, sex, and race. If your score is in the top 25% (≥75th percentile) even if the number seems low — it still means higher risk than expected for your age.

• A 45-year-old man with CAC = 50
• Average for his age group = 10
• His CAC is ≥75th percentile → treat as higher risk → LDL-C goal <70 mg/dL

---

When To Order a CAC Scan — AHA 2026

ORDER CAC when:

Primary prevention patient (no heart disease yet)
+
PREVENT-ASCVD risk is BORDERLINE or UNCERTAIN
+
Doctor and patient are UNSURE whether to start a statin
        ↓
CAC helps make the decision

Specific Situations to Order CAC:

---

When NOT to Order CAC

---

AHA 2026 Age Recommendations for CAC

Below these ages, CAC = 0 is expected and not informative.

---

Simple Summary

CAC SCAN — SIMPLE OVERVIEW

What:   Low-dose CT scan of heart arteries
        No injection. No contrast. 10 minutes.

Measures: Calcium in coronary arteries = Agatston Score

When:   Primary prevention + UNCERTAIN if statin needed

Result:
  CAC = 0      → Clean arteries → Hold statin → Lifestyle only
  CAC 1-99     → Early disease → Consider statin → LDL <100
  CAC 100-999  → Definite disease → Start statin → LDL <70
  CAC ≥1000    → Severe disease → Aggressive → LDL <55

Goal:   Make the RIGHT decision —
        Not over-treating low-risk patients
        Not under-treating high-risk patients

---

Based on AHA/ACC 2026 Guideline on the Management of Dyslipidemia

Indications for CAC Scoring

AHA 2026 Guidelines

---

MAIN PRINCIPLE

CAC is ordered when the treatment decision is uncertain — it helps the doctor decide whether to start, defer, or intensify lipid-lowering therapy.

---

✅ INDICATIONS — When to Order CAC

1. Borderline PREVENT-ASCVD Risk

• 10-year risk 5% to <7.5%
• Not clearly low, not clearly high
• CAC clarifies whether statin is needed or can be deferred

2. Intermediate PREVENT-ASCVD Risk — Patient Hesitant

• 10-year risk 7.5% to <20%
• Patient reluctant or hesitant to start statin
• CAC = 0 → can safely defer and reassure
• CAC high → motivates patient to accept treatment

3. Family History of Premature ASCVD

• First-degree relative with heart disease:
  • Father / brother <55 years
  • Mother / sister <65 years
• Patient themselves has borderline risk
• CAC helps identify if early subclinical disease is already present

4. Diabetes — Primary Prevention

• Type 2 DM, age 40–75, no established ASCVD
• When deciding how aggressively to treat
• High CAC → treat to <70 or <55 mg/dL target

5. Incidental Calcium Found on Another CT

• Calcium spotted on chest CT, abdominal CT, or any non-cardiac imaging
• Should always trigger formal CAC scoring and lipid management review

6. Risk Enhancers Present but Decision Still Unclear

• Patient has risk enhancers (Lp(a) ≥125, hsCRP ≥2, ABI <0.9) but PREVENT risk is borderline
• CAC provides the final deciding factor

7. Patient Wants to Understand Their Personal Risk

• Patient prefers to see their own imaging evidence
• Shared decision-making — CAC result helps patient understand and engage in treatment

---

❌ CONTRAINDICATIONS — When NOT to Order CAC

---

INDICATIONS SUMMARY TABLE

---

One-Line Rule to Remember

"Order CAC only when the treatment decision is genuinely uncertain in a primary prevention patient." If you already know the patient needs a statin — just start it. If you already know they are low risk — just watch. CAC is for the grey zone in between.

---

AHA/ACC 2026 Guideline on the Management of Dyslipidemia

Fredrickson Classification — Who Needs It & When

Indications & Clinical Use

---

FIRST — What Is Fredrickson Used For?

Fredrickson is NOT a routine classification used in every dyslipidemia patient. It is used specifically to identify the TYPE of lipoprotein abnormality when:

• The lipid pattern is unusual or severe
• A genetic cause is suspected
• Standard treatment is not working
• A specific treatment decision depends on which particle is elevated

---

WHO NEEDS FREDRICKSON CLASSIFICATION?

---

✅ Patient 1 — Very High Triglycerides (TG ≥500 mg/dL)

• Type I → fibrates do NOT work well → dietary fat restriction is primary treatment
• Type IV → fibrates + lifestyle + treat underlying cause (DM, obesity)
• Type V → pancreatitis risk → emergency TG lowering needed

---

✅ Patient 2 — Suspected Familial Hypercholesterolemia

• LDL-C ≥190 mg/dL in adult
• LDL-C ≥160 mg/dL in child
• Tendon xanthomas
• Corneal arcus <45 years
• Family history of early heart attacks

• Pure LDL elevation + normal TG = Type IIa
• Confirms genetic LDL receptor defect pattern
• Guides need for PCSK9 inhibitor + family cascade screening

---

✅ Patient 3 — Combined High LDL + High TG

• Patient has both ↑ LDL-C AND ↑ TG together
• Family history of mixed hyperlipidemia
• Multiple family members with different lipid abnormalities

• Most common genetic dyslipidemia
• Needs both LDL-C AND TG treatment
• Statin + fibrate or statin + omega-3 combination

---

✅ Patient 4 — Palmar Xanthomas or Unusual Xanthomas

• Yellow deposits in the palm creases (palmar xanthomas) — pathognomonic
• Tuberous xanthomas over elbows/knees
• Both TC and TG elevated equally
• Early PAD + premature CAD together

• Very specific treatment → fibrates are first-line (not statins alone)
• ApoE genotyping confirms diagnosis
• Responds dramatically to fibrate therapy

---

✅ Patient 5 — Young Patient with Early Heart Attack

• MI or stroke <55 years (men) / <65 years (women)
• Strong family history of premature ASCVD
• LDL-C very high despite lifestyle

• Changes treatment aggressiveness
• Family members need cascade screening
• May need PCSK9 inhibitor from diagnosis

---

✅ Patient 6 — Acute Pancreatitis with Unknown Cause

• Recurrent pancreatitis with no gallstones, no alcohol
• Very high TG found during pancreatitis workup
• Young patient with pancreatitis

• Type I → genetic LPL deficiency → ultra-low fat diet
• Type V → combined → fibrates + lifestyle

• If Type I → fibrates do NOT help → diet is the only treatment
• Prevents future attacks with correct management

---

✅ Patient 7 — Statin Not Working as Expected

• On maximum statin dose but LDL-C still very high
• Suspecting underlying genetic cause

• Type IIa (FH) → needs PCSK9 inhibitor added
• Type IIb → needs TG management added

---

INDICATIONS SUMMARY TABLE

---

When You Do NOT Need Fredrickson

---

How to Apply It Clinically — Simple Steps

STEP 1 — Look at the lipid panel
  Which is elevated?
  LDL only? TG only? Both? Equally?

STEP 2 — Look at the patient
  Xanthomas? Young MI? Family history? Pancreatitis?

STEP 3 — Match to Fredrickson Type

STEP 4 — Decide treatment based on type
  Type IIa  → Statin + PCSK9i
  Type IIb  → Statin + fibrate or omega-3
  Type III  → Fibrate first
  Type IV   → Fibrate + lifestyle
  Type I/V  → Ultra-low fat diet ± fibrate

---

One-Line Rule

Use Fredrickson when the lipid pattern is unusual, severe, or genetic — not in routine everyday dyslipidemia management.

---

Based on WHO/Fredrickson Classification · AHA 2026 · Clinical Lipidology Practice

• 🔁 Redo the same content — repeat Fredrickson indications differently?
• ✂️ Make it shorter — give a crisp version?
• 🔄 Different format — table only, bullet points only?
• 📋 Different angle — clinical cases / exam-style?

---

Fredrickson Classification

Complete & Simple

---

What Is It?

A system that classifies dyslipidemia by which lipoprotein particle is elevated. Gives each pattern a Type number (I to V).

---

THE 5 TYPES

---

TYPE I

---

TYPE IIa ⭐ Most Important

---

TYPE IIb ⭐ Very Common

---

TYPE III

---

TYPE IV ⭐ Most Common Overall

---

TYPE V

---

QUICK COMPARISON TABLE

---

MEMORY TRICK

I    → I can't clear fat from food (chylomicrons)
IIa  → 2 letters, 1 problem = LDL only (FH)
IIb  → 2 letters, 2 problems = LDL + TG (combined)
III  → 3 = TC + TG + palmar xanthomas (triad)
IV   → 4 = TG goes up (VLDL, most common)
V    → Very bad = Everything high = pancreatitis

---

CLINICAL SIGNIFICANCE — Which Types Matter Most?

---

Fredrickson-Levy-Lees WHO Classification · AHA 2026

Fruits & Vegetables for Dyslipidemia

What to Eat & Why

---

WHY FRUITS & VEGETABLES HELP

They work through 3 main mechanisms:

• Soluble fiber → binds cholesterol in gut → prevents absorption → ↓ LDL-C
• Plant sterols/stanols → block cholesterol absorption in intestine
• Antioxidants → prevent LDL oxidation → slow atherogenesis

---

🍎 FRUITS

---

⭐ Best Fruits for Dyslipidemia

Apples & Pears

• Rich in pectin (soluble fiber)
• Pectin directly binds LDL cholesterol in gut
• Effect: ↓ LDL-C ~5%
• Eat with skin — fiber is in the skin

Berries (Blueberries, Strawberries, Raspberries)

• High in polyphenols + antioxidants
• Reduce LDL oxidation
• Raise HDL-C slightly
• Anti-inflammatory — slows plaque progression
• Low sugar — safe for diabetics too

Avocado 🥑

• Rich in monounsaturated fat (MUFA)
• Replaces saturated fat → ↓ LDL-C
• ↑ HDL-C
• Contains beta-sitosterol (plant sterol)
• Effect: ↓ LDL-C 13–17% when eaten daily

Citrus Fruits (Orange, Grapefruit, Lemon)

• Contain hesperidin + pectin
• ↓ LDL-C, ↓ TG
• Grapefruit: caution — interacts with statins (CYP3A4 inhibitor)
  • Avoid large amounts of grapefruit if on atorvastatin/simvastatin
  • Safe in small amounts; rosuvastatin not affected

Grapes

• Contain resveratrol + flavonoids
• Anti-inflammatory, antioxidant
• ↑ HDL-C modestly
• Red/purple grapes preferred over green

Pomegranate

• High in punicalagins (potent antioxidants)
• Reduces LDL oxidation
• May reduce arterial plaque progression

Kiwi

• Rich in vitamin C + fiber
• ↓ TG, ↑ HDL-C
• Anti-platelet effect — reduces clotting risk

Mango, Papaya

• Rich in soluble fiber + carotenoids
• Moderate glycemic index — eat in moderation
• Good antioxidant support

---

⚠️ Fruits to Limit

Rule: Eat whole fruit — not juice. Juice removes fiber and concentrates sugar.

---

🥦 VEGETABLES

---

⭐ Best Vegetables for Dyslipidemia

Leafy Greens (Spinach, Kale, Swiss Chard)

• Highest in lutein + antioxidants
• Reduce LDL oxidation
• Contain plant sterols — block cholesterol absorption
• Kale: high in fiber + vitamin K — helps arterial health
• Eat daily if possible

Broccoli & Cauliflower

• Rich in soluble fiber + sulforaphane
• ↓ LDL-C
• Anti-inflammatory
• Contains plant sterols

Okra (Ladies Fingers) 🌿

• One of the best vegetables for cholesterol
• Very high in soluble fiber (mucilage/pectin)
• Directly binds bile acids → removes cholesterol from body
• Effect: ↓ LDL-C significantly
• Particularly recommended in South Asian populations

Eggplant (Brinjal)

• Contains chlorogenic acid + fiber
• ↓ LDL-C
• Low calorie — good for weight management

Garlic 🧄

• Contains allicin
• ↓ LDL-C 5–10%
• ↓ TG
• Anti-platelet, anti-inflammatory
• Best eaten raw or lightly cooked
• 1–2 cloves daily

Onions

• Contain quercetin (flavonoid)
• ↓ LDL-C, anti-inflammatory
• Red onion more potent than white

Tomatoes

• Rich in lycopene
• ↓ LDL-C oxidation
• ↓ LDL-C ~10% with regular intake
• Cooked tomatoes (sauce, paste) have MORE lycopene than raw

Carrots

• High in pectin + beta-carotene
• ↓ LDL-C
• Antioxidant — reduces oxidized LDL

Sweet Potato

• High in soluble fiber + potassium
• ↓ LDL-C, ↓ TG
• Better than regular potato (lower glycemic index)

Beans & Legumes (Lentils, Chickpeas, Kidney Beans)

• Very high in soluble fiber
• ↓ LDL-C 5–8% per serving
• Also reduce TG
• Excellent protein source — replace red meat

Corn / Oats (Grain Vegetables)

• Beta-glucan in oats = most studied soluble fiber
• ↓ LDL-C 5–10%
• FDA-approved health claim for oats and heart disease

---

SOLUBLE FIBER — The Key Mechanism

How soluble fiber lowers LDL-C:

Soluble fiber eaten
      ↓
Forms gel in intestine
      ↓
Binds bile acids (made from cholesterol)
      ↓
Bile acids excreted in stool instead of reabsorbed
      ↓
Liver needs more cholesterol to make new bile acids
      ↓
Liver upregulates LDL receptors
      ↓
More LDL pulled from blood → ↓ LDL-C

---

BEST FOODS BY LIPID EFFECT

---

DAILY DIET RECOMMENDATION

BREAKFAST
  → Oats with berries + apple slices

LUNCH
  → Large leafy green salad (spinach/kale)
    + tomatoes + carrots + olive oil dressing
    + lentils or chickpeas

DINNER
  → Broccoli / okra / eggplant as side dish
    + garlic in cooking
    + avocado

SNACK
  → Handful of berries or an apple (with skin)
    NOT fruit juice

---

WHAT TO AVOID

---

SIMPLE RULE TO REMEMBER

"Eat whole, eat colorful, eat fiber-rich"

• Every color of vegetable = different antioxidant
• Whole fruit > juice always
• More fiber = more LDL pulled out of the body
• Aim for 5–9 servings of fruits and vegetables per day

---

Based on AHA 2026 Dietary Guidelines · Mediterranean Diet Evidence · Portfolio Diet Studies

Pharmacological Treatment — Dyslipidemia

Indications & Contraindications for All Drugs

---

DRUG 1 — STATINS

(Atorvastatin, Rosuvastatin, Simvastatin, Pravastatin)

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

DRUG-SPECIFIC NOTES

---

DRUG 2 — EZETIMIBE

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

---

DRUG 3 — PCSK9 INHIBITORS

(Evolocumab, Alirocumab)

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

NOTES

• Very safe overall — no myopathy, no hepatotoxicity
• Safety confirmed to LDL-C as low as 20–30 mg/dL
• Main side effect: injection site reactions (mild)
• No routine lab monitoring required beyond lipid panel
• AHA 2026: No longer strictly sequential — add based on LDL-C gap needed

---

DRUG 4 — BEMPEDOIC ACID

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

NOTES

• Works only in liver (not muscle) → much less myopathy than statins
• Available as combination tablet: bempedoic acid + ezetimibe
• Raises uric acid — ask about gout history before prescribing

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DRUG 5 — INCLISIRAN (siRNA)

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

NOTES

• Dosing: SC injection at 0, 3 months → then every 6 months
• Very good for adherence — less frequent than PCSK9 mAbs
• Main side effect: injection site reactions
• No drug-drug interactions (RNA interference — not CYP metabolized)

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DRUG 6 — FIBRATES

(Fenofibrate, Gemfibrozil, Bezafibrate)

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

FIBRATE COMPARISON

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DRUG 7 — OMEGA-3 FATTY ACIDS (EPA)

(Icosapentaenoic acid — Vascepa/Omacor)

✅ INDICATIONS

⚠️ AHA 2026: Only icosapentaenoic acid (EPA alone / Vascepa 4g) has proven CV benefit. Mixed EPA+DHA formulations (Lovaza) do NOT have the same CV outcome evidence.

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

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DRUG 8 — EVINACUMAB

(For Homozygous FH only)

✅ INDICATIONS

❌ CONTRAINDICATIONS

⚠️ USE WITH CAUTION

• Infusion reactions — premedicate with antihistamine
• Liver function monitoring recommended
• IV administration only (15 mg/kg every 4 weeks)

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COMPLETE CONTRAINDICATION SUMMARY TABLE

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INDICATION BY CLINICAL SCENARIO

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Based on AHA/ACC 2026 Guideline on the Management of Dyslipidemia · ADA 2026 · ESC/EAS 2025