Lipids Flashcards
Functions of Triglycerides
• Energy storage*
• Insulating and protecting organs
• Cellular membrane fluidity
• Fat soluble vitamin transport
Cholesterol is a component of: (5)
-Bile acids
-Progesterone
-Vitamin D
-Glucocorticoids
-Minerocorticoids
Function of cholesterol
Cell membrane fluidity
Sources of cholesterol
• De novo: endogenous (70-80%)-liver
• Diet
Cholesterol is eliminated through conversion by:
The liver to salts of bile acids
ApoB
Atherogenic: Chylomicrons, VLDL, IDL, LDL (“Bad”), Lp (A)
ApoA
Cardioprotective-HDL (“good”)
Main component of chylomicrons
Triglycerides
Chylomicrons are:
Exogenous: 12 hours to clear circulation
VLDL are the predominant carrier of:
Blood triglycerides
VLDLs are:
Endogenous*
IDLs are formed after:
Removal of some triglycerides from VLDL
LDLS are formed after:
Removal of triglycerides from IDL
LDLs carry:
Cholesterol to be deposited into tissues
Lp(a)
• LDL particle with additional lipoprotein attachment
• Highly heritable*, tend to be stable over time
Components of LDL
-45% cholesterol, 10% triglycerides, 20% phosphates, 25% protein
HDL is synthesized by:
Liver and small intestines
HDLs carry a higher percentage of:
Protein
(50% protein, 1-5% triglycerides, 15% cholesterol, 30% phospholipid)
Total Cholesterol: Desirable Level
125-200 mg/dL
LDLc Levels
<100: Optimal*
100-129: Near Optimal*
130-159: Borderline high*
160-189: high
>190: Very High
HDLc: Desirable Levels
• Men: >40 mg/dL
• Women: >46 mg/dL
HDLc tends to have an inverse relationship with:
Triglycerides
TC: HDL Ratio provides insight into balance between:
Atherogenic and cardioprotective lipoproteins
TC:HDL Radio: Average Risk
• 5:1 (males)
• 4.5:1 (females)
-3:1 (Ideal Ratio)
Non-HDL Cholesterol =
TC-HDLc
Non-HDL Cholesterol includes cholesterol carried by: (4)
VLDL, IDL, LDL, Lp(a)
Non-HDL Cholesterol: Desirable Level
LDL target + 30 mg/dL
Triglycerides: Desirable Level
Desirable: <150 mg/dL
HLP IIa: Description
Excessive LDL-c in circulation and excessive deposition in peripheral tissue
HLP IIa: Serum Cholesterol
500-1200mg/dL
HLP IIa: Signs/Symptoms
• Xanthelasmas
• Tendon and tuberous xanthomas*
• Arcus juvenilis
• Arterial bruit
• Claudication
• Accelerated atherosclerosis
HLPIIa: Lab Findings
**Serum cholesterol increased
• Homozygous – 500-1200 mg/dL
• Heterozygous – 250-500 mg/dL
• Triglycerides normal
• **Increased LDL (>190mg/dL)
HLP IV: Description
• Genetic problem causing decreased elimination of VLDL
HLP IV: Signs/Symptoms
-Obesity
-Lipemia retinalis
-Atherosclerosis
-Hepatosplenomegaly
-Possible pancreatitis* (esp if notable increase in triglycerides (>500))
HLP IV: Lab Findings
• **Increased triglycerides: 250-500mg/dL
• Normal cholesterol
• Normal LDL
• *Decreased HD
Hyperelphalipoproteinemia
• Elevated HDL cholesterol (80-100+)
Secondary Causes of Dyslipidemia
Diabetes Mellitus
Increased production of VLDL->Increased TGs/Decreased HDL
-Increased LDLc
-Increased TC
Hypothyroidism
-Increased LDL
-Increased TC
-Increased TGs
-Decreased HDLs
Chronic Liver Disease (2)
-Increased TGs
-Decreased HDL
Obstructive Liver Disease
-Cholelithiasis (gallstone-colicky pain)
-Increased LDL
-Increased TC: 400-500 (acute)/700-800 (chronic)
-Increased TGs
-Decreased HDL
Pregnancy
-Increased TGs (3rd trimester)
-Increased LDL
-Increased TC
-Decreased HDL
PCOS
-Increased TG
-Decreased HDL
-Increased LDL
-Increased TC
Certain Medications
-Oral contraceptives
-Corticosteroids
-Diuretics
• Lipid panel abnormalities tend to be _____ than those seen with genetic abnormalities
Milder
Ranges indicative of lifestyle factors
• Total cholesterol: 200-250
• LDLc: 100-190;
• Triglycerides: 150-250\
-HDL: Exercise, inverse of TGs
Causes of Hypocholesterolemia
-Chronic liver disease,
-Hyperthyroidism,
-Anemia
-MMMs (Malignancy, malnutrition, malabsorption)
Cardiac Risk Assessment: Pathophysiology
- Endothelial cell damage (HTN, smoking, hyperglycemia, increased homocystemia..)
- LDL deposition in tunica intima
- WBCs enter, release free radicals*
- LDL oxidized*
- Positive feedback loop
- Lipid plaque formed from dead WBCs and smooth mucles that engulfed LDL
- Lipid plaques become fibrous*
- Inflammation>plaque instability>plaque rupture*
Major Risk Factors
• Smoking
• High blood pressure
• High LDL cholesterol
• Low HDL cholesterol
• Diabetes
• Age: Male (45+)/Female (55+/menopause)
• Premature family history of cardiovascular disease (1st degree): Male (<55)/Female (<65)
Risk Enhancing Factors
-Based on 10 year risk profile
• Obesity
• Sedentary
• Diet
• Alcohol
• Stress and psychosocial factors
• Elevated triglycerides
• Metabolic syndrome
Risk Enhancing Factors: Other Abnormalities
• Lp(a)
• Hyperhomocystinemia
• Prothrombotic factors (fibrinogen)*
• hsCRP (inflammation)
-Sleep apnea
Cluster of metabolic abnormalities->increased risk for:
• Type 2 DM
• Cardiovascular disease
• Stroke
• Fatty liver
• Certain cancers
Metabolic Abnormalities
• Intra-abdominal obesity
• Dyslipidemia
• Hypertension
• Insulin resistance (w/ or w/o insulin impaired glucose tolerance)
• Proinflammatory state
• Prothrombotic state
Metabolic Syndrome: Epidemiology
• Predominant age: >60 years old
• Male = female
• >1/3 US affected
In order to be diagnosed with metabolic syndrome, we need 3+ of the following:
Abdominal obesity
•Waist circumference:
• >40 inches men
• >35 inches women
• TGs >150 mg/dL
Low HDL cholesterol
• Men: <40 mg/dL
• Women: <50 mg/dL
• BP >130/85 mm Hg
• Fasting glucose ≥100 mg/dL but <126 mg/dL (prediabetes)
Metabolic Syndrome: Management
• Primary therapeutic goal is to prevent or reduce obesity
• Aggressive lifestyle modification (diet and exercise) considered first line therapy
• Treat lipid and non-lipid risk factors if they persist despite lifestyle changes
Metabolic Syndrome: Prognosis
-Increased risk of: Type 2 DM (5x), CAD (3x), Acute myocardial infarct (3x), All-cause mortality (1.5x)
A risk assessment primarily includes:
History, physical exam, lipoprotein panel, additional lab testing
A lipoprotein panel primarily assesses:
Cardiac risk
Most risk assessment still focuses on:
LDL-c, Total Cholesterol, HDL-c
CRP measures levels from:
10 mg/L to 10,000 mg/L (general inflammation)
Hs-CRO measures levels from
0-10 mg/L (cardio CS/inflammation-endothelial damage
Hs-CRP: Levels
-Normal: <0.3mg/L
-Low: <1mg/L
-Average: 1-3mg/L
-High>3mg/L
-General Inflammation: >10mg/L
Lipoprotein particle size
Small/dense (more athrogenic), large/pillowy (less athro.
AHA Guidelines: Dietary pattens
Mediterranean, DASH, low glycemic index/load, plant-based
AHA guidelines: Activity
Activity: About 150 minutes of moderate to vigorous exercise per week (3-4 40-minute sessions)
AHA guidelines: Other factors
• Maintaining healthy body weight
• Smoking cessation
• Limiting alcohol use
• Sleep
Lipid Panel: What factors must we determine if abnormalities are due to primary causes or secondary
• Biliary obstruction
• Hypothyroidism
• Chronic kidney disease
• Pancreatic disease (diabetes mellitus, chronic pancreatitis)
• Pregnancy
• Certain medications
Statin use Guidelines
- LDL-c >190 (21+ years of age)
- LDL-c 70-189 in adults 40-75 with diabetes
- LDL-c 70-189 in adults 40-75 with moderate risk
Neutraceuticals
• Red yeast rice: LDL, TC
• Plant sterols and stanols: LDL
• EPA/DHA: Triglycerides
• CoQ10
-Niacin
Statin induced myopathy: Symptoms
• Fatigue, muscle pain/tenderness, weakness, tendon pain, nocturnal muscle cramping
• Proximal, generalized, worse with exercise (bilateral)
Lower CRP by:
Exercise, alcohol
Lower homocysteine
Exercise, B6, folate, B12
Risk Assessment: Follow-Up and Monitoring
• Discuss other risk factors: Lp(a), homocysteine, HsCRP
• Rule out pathology as secondary cause: Diabetes, hypothyroid, pregnancy, Ckd, meds
• Recommend dietary lifestyle changes for 6 months
• Retest lipid panel at 6-8 weeks, 3 months, and 6 months
• If pharmaceutical intervention is decided upon:
• Liver enzymes and CPK should be measure before initiation and after several months
