Hyperlipidemia

Question 1

Pathophysiology of Hyperlipidemia

Answer 1

Atherosclerosis major cause of CAD
Lipoproteins: all contain triglycerides, phospholipids, & cholesterol
- Low-density lipoprotein (LDL)
- High-density lipoprotein (HDL)
- Very-low-density lipoprotein (VLDL)
- Triglycerides
Exogenous pathway: involves absorption of lipids via intestine
Endogenous pathway: lipids originate from liver

Question 2

Cholesterol Screening

Answer 2

All adults older than 20 years of age
Fasting lipid profile at least every 5 years
Lifestyle modification: balanced diet, weight loss, minimizing risk factors
- Hyperglycemia, smoking, high-fat diet

Childhood screening in those with risk factors: DM, obesity, family hx of familial hypercholesterolemia
- Emphasis on diet & exercise

Question 3

Lifestyle Modifications for Hyperlipidemia

Answer 3

Exercising 30 minutes/day
Dietary Therapy
- Reduced intake saturated fats not as strong
- Consuming plant sterols (2 g/day)
- Increased soluble fiber intake (10-25 g/day)
- Dietary fiber of 20-30 g/day
- Total calories to maintain or lose weight

Question 4

Drug Therapies for Dyslipidemia

Answer 4

HMG-CoA (3-hydroxy-3-methy-glutaryl-coenzyme A) reductase inhibitors
- Lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin

Fibrates: Fibric acid derivatives
- Gemfibrozil, micronized fenofibrate, clofibrate

Bile Acid Sequestrants
- Cholestyramine, colestipol, colesevelam

Ezetimibe (Zetia): most effective in combination with statin

Question 5

Vitamins and Supplements for Hyperlipidemia

Answer 5

Vitamins/antioxidants/herbs/natural products

• coenzyme Q10 is gaining evidence as good to take with statin
• Niacin (Vitamin B3) no longer FDA approved for treatment

Question 6

Rational Drug Selection for Hyperlipidemia

Answer 6

Lifestyle changes & no medication therapy for those with CV risk less than 7%
If cardiac risk fi greater than 7%, statin recommended
- Degree & number of risks determine if statins should be pushed aggressively or started at more moderate levels
Active liver disease is a contraindication for all anti-lipidemics except the bile acid sequestrants

Question 7

Statins- HMG-CoA Reductase Inhibitors: Pharmacodynamics

Answer 7

• Block synthesis of cholesterol in liver by competitively inhibiting HMG-CoA reductase activity
• Decrease levels of LDL by 25-65%
• Modest decreases in TG (10-40%) & very modest increases in HDL (5-17%) may occur with more potent statins
• Pregnancy: contraindicated (old category X)

Question 8

Fibrates- Fibric Acid Derivatives: MOA & Effects on lipids

Answer 8

MOA:

• inhibition of cholesterol synthesis
• decreased TG synthesis
• inhibition of lipolysis in adipose tissue
• decreased production of VLDL/increased clearance
• increased plasma & hepatic lipoprotein lipase (LPL) activity

Effects on lipids:
- Decreases TC, LDL, & TGs; increases HDL

Question 9

Bile Acid Sequestrants: Pharmacodynamics

Answer 9

• By promoting an increase in bile acid excretion, they enhance conversion of cholesterol to bile acids by the liver and increase uptake of LDL
• They bind with cholesterol in intestine and are not metabolized by liver
• They are excreted in bound form in feces
• They may be used in patients with active liver disease
• They lower TC, LDL, & TG and increase HDL

Question 10

Ezetimibe (Zetia): Pharmacodynamics

Answer 10

• Selectively inhibits the intestinal absorption of cholesterol & related phytosterols
• Has been shown to reduce TC, LDL, & TG while increasing HDL-C
• Most effective in combination with statin
• Not for children younger than 10 years

Question 11

Hyperlipidemia: Vitamins & Complementary, & Alternative Medicine

Answer 11

Vitamin E
- Consumption more than 100 IU/day for more than 2 years lowers rate of CHD progression
- Fat soluble; can accumulate; watch in patients with bleeding problems, ulcerative colitis
Beta carotene: increase physicians’ health study
Vitamin C: increased fibrinolytic activity, decreased platelet adhesiveness, decreased TC
Selenium: antioxidant, limited clinical evidence
- 100 mcg/day for CHD, watch toxicity
Folic acid: reduction in plasma homocysteine levels
Herbs: garlic, fish oils, oat bran, coenzyme Q10

Question 12

Hyperlipidemia- Children & Adolescents: Pharmacodynamics, Treatment

Answer 12

Genetic disorders of lipid metabolism
TC goal less than 170 mg/dL
Primary prevention best for lifestyle- associated hyperlipidemia
- Diet & exercise
Treatment
- Fiber, plant sterols, & omega-3 fatty acids
- Nicotinic acid
- Statins for familial hypercholesterolemia after puberty

Question 13

Hyperlipidemia- Patient Variables (middle-aged men, women, older adults, young adults)

Answer 13

Middle-aged men: Statins for high-risk patients; combination of statins & bile acid sequestrants

Women 45-75 years: statins if CHD risk; Hormone replacement therapy (HRT) not recommended for LDL lowering, esp. if combined w/ progestin

Older adults: statins first-line treatment; bile acid sequestrants may cause impaction if on fluid restrictions

Young Adults: maximization of lifestyle changes; pregnancy risk with many drugs

Question 14

Hyperlipidemia- Patient Variables (African Americans, Asian & Pacific Islanders, DM, Metabolic Syndrome)

Answer 14

African Americans: men- document creatine kinase (CK) before starting statin; treat HTN
Asian & Pacific Islanders: there is higher CHD risk at lower BMI, so early diagnosis is critical
Diabetes Mellitus: increased risk equal to CHD (treated as high risk); statins usually drug of choice; attention to TG as well
Metabolic Syndrome: increased risk of coronary disease; intensive lifestyle changes; statins drug of choice

Question 15

Hyperlipidemia: Monitoring

Answer 15

• 3 month dietary therapy trial
• Baseline liver function (no frequent checks unless issues), CK, lipid panel
  Rechecking of lipid panel at 6-8 weeks & after every dose adjustment
  —- Nicotinic acid check in 4-6 weeks
• Follow-up at 8-12 week intervals for 1 year after aggressive dosing changes

Question 16

Hyperlipidemia: Treatment Points

Answer 16

Focus is on LDL, especially for men, at first

HDL is NOT “protective” if LDL is high

TGs will reduce somewhat if LDL reduces, so treat LFL first of hypertriglyceridemia is present

Question 17

Triglycerides: Pharmacodynamics

Answer 17

Heavily linked to sugar intake & trans fatty acids

Dietary attention and fiber critical

Must use “high powered” omega-3 prescriptions for significant clinical outcomes

Question 18

Hyperlipidemia: Patient Education for All

Answer 18

Lifestyle changes stronger than medications 
Drug therapy
- dosing 
- drug interactions
- symptoms of toxicity
- monitoring frequency 
Adherence issues