Dyslipidemia-2

Dyslipidemia:

Pathophysiology, Diagnosis & Management

Dr. Eatimad Mahgoub Osheik

Assistant Professor

MD Internal Medicine

LEARNING OBJECTIVES

• Define dyslipidemia
• Understand lipid metabolism
• Interpret lipid profile
• Identify ASCVD risk
• Apply ACC/AHA guidelines
• Choose appropriate therapy

Background

• Lipids are organic water non soluble molecules
• Major types include
• Triglycerides serving as long term energy store
• Phospholipids is a key component of cell membrane
• Cholesterol is vital for building cells, producing hormones (like estrogen, testosterone, vitamin D), and making bile for digestion and brain development
• Cholesterol and triglycerides are carried in the bloodstream by spherical particles called lipoproteins.

A lipoprotein is a complex particle made of lipids like cholesterol , triglycerides and a protein that acts as the body’s transport system for these fats through the bloodstream to cells.

So what is Lipoprotein ?

Structure and Function

• Core: Contains fats like triglycerides and cholesterol.
• Outer Shell: Composed of phospholipids and special proteins called apolipoproteins (like ApoB for LDL, ApoA-I for HDL).
• Function : To carry fats to and from cells throughout the body.

Lipid Metabolism

• Lipoproteins
  • Chylomicrons
  • VLDL
  • IDL
  • LDL
  • HDL

Here’s a breakdown of major types, density, and size:

• Chylomicrons: Largest and least dense , transport dietary fats from the gut.
• VLDL (Very Low-Density Lipoprotein) Large , low density, carries triglycerides from the liver.
• IDL (Intermediate-Density Lipoprotein): Medium, intermediate density), derived from VLDL.
• LDL (Low-Density Lipoprotein): Smaller, delivers cholesterol to tissues,
• HDL (High-Density Lipoprotein): Smallest , removes cholesterol from tissues, “good” cholesterol.

Lipid Metabolism

INTRODUCTION

• Dyslipidemia = abnormal lipid levels in the blood

• consequence of abnormal Lipoprotein metabolism

• Major modifiable risk factor for ASCVD

• Strong association with:

  • Coronary artery disease
  • Stroke
  • Peripheral arterial disease

DYSLIPIDEMIA

Include

• ↑ Low Density Lipoprotein LDL
• ↓ High Density Lipoprotein HDL
• ↑ Triglycerides TG
• Mixed dyslipidemia

Classification of Hyperlipidemia

Primary Hyperlipidemia

secondly Hyperlipidemia

Primary hyperlipidemia

Single or multiple gene defect results in disturbance of LDL, HDL or/ and TG production or clearance

• Type I: Familial Chylomicronemia
• Type IIa: Familial Hypercholesterolemia
• Type IIb: Familial Combined Hyperlipidemia
• Type III: Dysbetalipoproteinemia
• Type IV: Hypertriglyceridemia
• Type V: Mixed Chylomicronemia–VLDL Elevation

DISEASE	LIPID PROFILE	ETIOLOGY
Type I Familial hyper-chylomicronemia	↑Chylomicrons	Deficiency in LPL or apoCII
Type IIA Familial hyper-cholesterolemia	↑LDL	Decreased or no functional LDL receptor expression
Type IIB Familial combined hyperlipidemia	↑ LDL ↑ VLDL	Overproduction of VLDL by liver
Type III Familial dysbeta-lipoproteinemia	↑ IDL	Abnormal apoE
Type IV Familial hyper-triglyceridemia	↑ VLDL	Overproduction and/or impaired catabolism of VLDL
Type V Familial mixed hyper-triglyceridemia	↑Chylomicrons ↑VLDL	Increased production or decreased clearance of VLDL & chylomicrons.

When to suspect primary hyperlipidemia

• Early onset hyperlipidemia (childhood or young adulthood)
• Strong family history of premature cardiovascular disease
• Very high lipid levels
  • LDL-C ≥ 190 mg/dL
  • Triglycerides ≥ 500 mg/dL
• Poor response to diet and lifestyle changes
• No secondary cause
• Characteristic signs: tendon xanthomas, xanthelasma, corneal arcus at young age

Clinical signs of primary hyperlipidemia

Secondary (acquired) hyperlipidemia

• Endocrine causes diabetes mellitus; hypothyroidism; obesity
• Renal disease—nephrotic syndrome; chronic renal failure
• Hepatic dysfunction; cholestasis
• Medications—thiazide diuretics; β-blockers; oral estrogens; steroids
• Lifestyle factors—excessive alcohol intake; high fat and carbohydrate diets; smoking;

Lipid Profile Interpretation

Normal Values

Total Cholesterol < 200 mg/dL

LDL < 100 mg/dL

HDL. > 40 (men), > 50 (women)

Triglycerides < 150 mg/dl

ASCVD Risk Factors

Nonmodifiable

• Age (men ≥ 45 y; women ≥ 55 y)
• Male sex
• Family history of premature ASCVD
• Race/ethnicity

Modifiable

• Dyslipidemia
• Hypertension
• Diabetes mellitus
• Smoking
• Obesity/metabolic syndrome

ASCVD (KEY CONCEPT)

ASCVD includes

• Coronary artery disease
• Cerebrovascular disease ;Stroke / TIA
• Peripheral arterial disease

ACC/AHA focuses on ASCVD risk, not LDL alone

Lipid-Lowering Therapies Summary Table

Class	Examples	Primary Effect	Use Case	Common Side Effects
Statins	Atorvastatin, Rosuvastatin	↓ LDL, ↓ TG, ↑ HDL	First-line for high CV risk	Muscle pain, liver enzyme elevation
Ezetimibe	Ezetimibe	↓ LDL	Add-on to statins or statin-intolerant	GI upset, rare liver effects
PCSK9 Inhibitors	Evolocumab, Alirocumab	↓↓↓ LDL	High-risk, familial hypercholesterolemia	Injection site reactions
Bempedoic Acid	Bempedoic acid	↓ LDL	Statin-intolerant patients	Hyperuricemia, tendon rupture
Fibrates	Fenofibrate, Gemfibrozil	↓ TG, ↑ HDL	Severe hypertriglyceridemia	Myopathy (esp. with statins), GI upset
Omega-3 Fatty Acids	Icosapent ethyl (Rx fish oil)	↓ TG	High triglycerides, CV risk reduction	GI upset, bleeding risk
Niacin	Niacin	↓ LDL, ↓ TG, ↑ HDL	Rarely used now due to side effects	Flushing, liver toxicity

Statins:

Mechanism of Action:

• Inhibit Hydroxy Methyl Glutaryl -CoA reductase → ↓ cholesterol synthesis in liver

• Liver compensates by ↑ LDL receptor expression → ↑ LDL clearance from blood

• Result: ↓ LDL (primary), modest ↓ TG, slight ↑ HDL

• Side Effects & Management:

  • Muscle pain/myopathy → check CK, reduce dose, switch statin, or try alternate-day dosing.
  • rhabdomyolysis (rare) → stop statin, hospitalize, hydrate.
  • Elevated liver enzymes → monitor AST/ALT, stop or reduce dose if > 3 × ULN.
  • GI upset → take with food ,at night
  • Drug interactions

STATIN INTENSITY

High-Intensity (↓ LDL ≥50%)

• Atorvastatin 40–80 mg
• Rosuvastatin 20–40 mg

Moderate-Intensity (↓ LDL 30–49%)

• Atorvastatin 10–20 mg
• Rosuvastatin 5–10 mg
• Simvastatin 20–40 mg

Management according to ACC/AHA

Initial Evaluation (All Patients)

A. Fasting or Non-fasting Lipid Panel

• Total cholesterol
• LDL-C
• HDL-C
• Triglycerides

B. Identify Secondary Causes,. Review Medications

C. Assess ASCVD Risk

• Use Pooled Cohort Equations (age 40–75)
• 10-year ASCVD risk categories:
  • Low: <5%
  • Borderline: 5–7.4%
  • Intermediate: 7.5–19.9%
  • High: ≥20%

Lifestyle Measures(All Patients)

• Heart-healthy diet (Mediterranean/DASH; Dietary Approaches to Stop Hypertension )
• Weight reduction
• Physical activity (≥ 150 min/week)
• Smoking cessation
• Limit alcohol

STATIN BENEFIT GROUPS (ACC/AHA)

Statins recommended for 4 major groups

1. Clinical ASCVD
2. LDL ≥ 190 mg/dL
3. Diabetes (age 40–75)
4. High ASCVD risk (≥7.5%)

Clinical ASCVD

Includes:

• Prior MI, stroke/TIA
• PAD
• Coronary or arterial revascularization

Management

• High-intensity statin
  • Atorvastatin 40–80 mg
  • Rosuvastatin 20–40 mg

Goal

• ≥ 50% LDL-C reduction
• LDL-C < 70 mg/dL (practical target)

If LDL ≥ 70 despite max statin

• Add ezetimibe
• If still ≥ 70 → PCSK9 inhibitor

Severe Hypercholesterolemia

LDL-C ≥ 190 mg/dL (age 20–75)

Management

• High-intensity statin (no risk calculation needed)

If LDL ≥ 100

• Add ezetimibe
• Consider PCSK9 inhibitor (esp. familial hypercholesterolemia)

Diabetes Mellitus (Age 40–75, LDL ≥70)

Management

• Moderate-intensity statin (minimum)
• High-intensity statin if:
  • Age 50–75
  • Multiple ASCVD risk factors

Primary Prevention (No ASCVD, No DM, LDL 70–189)

Based on 10-yr ASCVD Risk

• Borderline (5–7.4%):
  • → Consider statin if risk enhancers present
• Intermediate (7.5–19.9%):
  • → Moderate-intensity statin
• High (≥ 20%):
  • → High-intensity statin

. Risk-Enhancing Factors (Help Decide Statin Use)

• Family history of premature ASCVD
• LDL ≥ 160 mg/dL
• Metabolic syndrome
• CKD
• Chronic inflammatory diseases
• South Asian ethnicity
• Elevated TG ≥ 175 mg/dL
• hs-CRP ≥ 2 mg/L
• Lp(a), ApoB elevation

Hypertriglyceridemia

• TG <5.6 mmol/L (150–499 mg/dL)
  • Statins first-line for ASCVD risk reduction
  • Consider icosapent ethyl (EPA) in high-risk patients on statins
  • Fibrates not routine
• TG ≥5.6 mmol/L (≥500 mg/dL)
  • Goal: prevent pancreatitis
  • Fibrate first-line
  • Add omega-3 fatty acids
  • Statin if ASCVD risk present
• TG ≥11.3 mmol/L (≥1000 mg/dL)
  • Very high pancreatitis risk
  • Very low-fat diet, strict glucose control
  • Hospitalize if symptomatic

General Management Flowchart

ACC/AHA-Based Statin Decision

Hypertriglyceridemia Management

Triglycerides Level

<150 mg/dL → Normal

150–499 mg/dL → Lifestyle + Statin (if ASCVD risk)

≥500 mg/dL → Fibrate ± Omega-3

Prevent Acute Pancreatitis

Scenario 1

Patient: 62-year-old male, history of MI 2 years ago

Lipid profile:

• Total cholesterol: 220 mg/dL
• LDL-C: 150 mg/dL
• HDL-C: 35 mg/dL
• TG: 150 mg/dL

Scenario 2

Patient: 35-year-old female, no ASCVD, family history of premature CAD

Lipid profile:

• Total cholesterol: 330 mg/dL
• LDL-C: 250 mg/dL
• HDL-C: 40 mg/dL
• TG: 150 mg/dL

Scenario 3

Patient: 50-year-old male, type 2 diabetes, no ASCVD

Lipid profile:

• Total cholesterol: 210 mg/dL
• LDL-C: 130 mg/dL
• HDL-C: 38 mg/dL
• TG: 180 mg/dL

Scenario 4

Patient: 45-year-old female, no ASCVD, non-diabetic, borderline 10-year ASCVD risk 7%

Lipid profile:

• Total cholesterol: 210 mg/dL
• LDL-C: 140 mg/dL
• HDL-C: 50 mg/dL
• TG: 150 mg/dL

Scenario 5

Patient: 40-year-old male, presents for routine check-up,
BMI 32

Lipid profile:

• Total cholesterol: 250 mg/dL
• LDL-C: 120 mg/dL
• HDL-C: 35 mg/dL
• TG: 800 mg/dL

Summary

• Dyslipidemia is a major, modifiable cause of ASCVD
• LDL-C is the primary treatment target
• Statins are first-line therapy
• Lifestyle modification is essential for everyone
• Risk stratification guides therapy
• Add non-statins when needed
• Triglycerides matter /pancreatitis risk
• Treat secondary causes first

THANK YOU