4.5: Disorders of Systemic Arterial Blood Flow

What is the leading cause of death in the United States?

Cardiovascular disease (CVD)

What is hyperlipidemia?

An excess of lipids in the blood

What types of molecules are considered lipids?

Triglycerides, phospholipids, and cholesterol

What is hypercholesterolemia?

Elevated levels of blood cholesterol

What is hyperlipidemia a major risk factor for?

Atherosclerosis, heart attack, and stroke

Why do lipids require stabilization in the blood?

They are insoluble in plasma

What stabilizes lipids in the blood?

Phospholipids and proteins

What are the proteins in lipoproteins called?

Apoproteins

What are lipid transport particles called?

Lipoproteins

What are the functions of transported lipids?

Energy utilization, lipid deposition, steroid hormone production, and bile acid formation

What are the five types of lipoproteins?

Chylomicrons, VLDL, IDL, LDL, HDL

What can genetic defects in apoproteins lead to?

Hyperlipidemia and accelerated atherosclerosis

Where are lipoproteins synthesized?

Small intestine and liver

Which lipoprotein is the largest?

Chylomicrons

What do chylomicrons primarily carry?

Triglycerides

What else do chylomicrons carry?

Small amounts of phospholipids, cholesterol, and apoprotein B

Which lipoprotein carries triglycerides?

VLDL

Which lipoprotein primarily carries cholesterol?

LDL

Which lipoprotein is considered “bad cholesterol”?

LDL

How is LDL removed from circulation?

LDL receptors and macrophages

What percentage of LDL is removed by LDL receptors?

Approximately 70%

What happens if LDL receptor availability is low?

Macrophage activity increases

What happens when macrophages take up LDL in arterial walls?

Cholesterol accumulation and atherosclerosis

Which lipoprotein is considered “good cholesterol”?

HDL

What is the function of HDL?

Carry cholesterol from tissues to the liver for excretion

What is the relationship between HDL and atherosclerosis?

Higher HDL is associated with lower risk

What increases HDL levels?

Exercise and certain lipid medications

What decreases HDL levels?

Smoking and metabolic syndrome

What can cause elevated serum cholesterol levels?

Any type of lipoprotein

What factors can raise blood lipid levels?

Nutrition, genetics, medications, comorbid conditions, and metabolic disease

Is hyperlipidemia usually caused by one factor?

No, it is usually multifactorial

What is primary hypercholesterolemia?

Elevated cholesterol independent of other health problems

What is secondary hypercholesterolemia?

Elevated cholesterol associated with other health problems and behaviors

What causes many types of primary hypercholesterolemia?

Faulty genetics

What genetic issues can lead to primary hypercholesterolemia?

Defective apoprotein synthesis, lack of receptors, defective receptors, or defective cholesterol handling

What is familial hypercholesterolemia?

An autosomal dominant disorder caused by defective LDL receptors

What is the LDL level range in heterozygous familial hypercholesterolemia?

250 to 500 mg/dL

What is the LDL level range in homozygous familial hypercholesterolemia?

Up to 1000 mg/dL

What are xanthomas?

Cholesterol deposits in tissues

Where can xanthomas appear?

Skin, cornea, and tendons

What condition is associated with xanthomas?

Atherosclerosis

What are common causes of secondary hypercholesterolemia?

Obesity and diabetes mellitus

How does a high-calorie diet affect lipids?

Increases VLDL production and triglycerides

What happens to VLDL in high-calorie diets?

Increased conversion to LDL

What is the effect of reduced LDL receptors?

Decreased LDL removal from circulation

What lipid pattern is seen in diabetes mellitus and metabolic syndrome?

High triglycerides, low HDL, and low to moderate LDL increase

What other conditions can cause elevated lipids?

Hypothyroidism, nephrotic syndrome, and obstructive liver disease

What medications can increase lipid levels?

Beta-blockers, estrogens, and protease inhibitors

What organization provides guidelines for cholesterol levels?

National Cholesterol Education Program (NCEP)

How often should adults get a fasting lipoprotein profile?

Every 5 years starting at age 20

What is considered optimal LDL cholesterol?

Less than 100 mg/dL

What LDL level is considered near optimal?

100 to 129 mg/dL

What LDL level is considered borderline high?

130 to 159 mg/dL

What LDL level is considered high?

160 to 189 mg/dL

What LDL level is considered very high?

Greater than or equal to 190 mg/dL

What total cholesterol level is desirable?

Less than 200 mg/dL

What total cholesterol level is borderline high?

200 to 239 mg/dL

What total cholesterol level is high?

Greater than or equal to 240 mg/dL

What HDL level is considered low?

Less than 40 mg/dL

What HDL level is considered high?

Greater than or equal to 60 mg/dL

What triglyceride level is normal?

Less than 150 mg/dL

What triglyceride level is borderline high?

150 to 199 mg/dL

What triglyceride level is high?

200 to 499 mg/dL

What is the primary target of cholesterol-lowering therapy?

Reducing LDL cholesterol

What are risk factors for coronary heart disease?

Smoking, hypertension, family history, age, and low HDL

What ages increase CHD risk?

Men ≥45 years and women ≥55 years

What HDL level increases CHD risk?

Less than 40 mg/dL

What is the first step in treating hyperlipidemia?

Lifestyle and dietary changes

What are therapeutic lifestyle changes?

Physical activity, weight reduction, and smoking cessation

What dietary changes help treat hyperlipidemia?

Reduce calories, saturated fat, trans fat, and cholesterol

What is the recommended saturated fat intake?

Less than 7% of daily intake

What is the recommended trans fat intake?

Less than 1% of daily intake

What is the recommended cholesterol intake?

Less than 300 mg/day

What foods should be increased in the diet?

Fruits, vegetables, and fish

What should be reduced in the diet?

Sugar, alcohol, and salt

When is drug therapy started for hyperlipidemia?

After 3 months if lifestyle changes fail

When is drug therapy started immediately?

In high-risk patients such as those with diabetes

What are the five classes of hyperlipidemia drugs?

Statins, bile acid resins, cholesterol absorption inhibitors, niacin, and fibrates

What are HMG CoA reductase inhibitors also called?

Statins

What do statins do?

Reduce hepatic cholesterol synthesis

Are statins first-line therapy?

Yes

What effects do statins have on lipids?

Lower LDL and triglycerides and increase HDL

What do bile acid-binding resins do?

Bind bile acids, increase LDL receptor production, increased removal of cholesterol from blood

When are bile acid-binding resins used?

When further LDL reduction is needed

What effect do bile acid-binding resins have on HDL?

Increase HDL by 3 to 5 percent

What is niacin also known as?

Vitamin B3

What does niacin do to lipids?

Decreases VLDL, IDL, LDL and increases HDL

What are common side effects of niacin?

Flushing and headache

What do fibrates do?

Decrease VLDL synthesis and increase triglyceride clearance

What effect do fibrates have on triglycerides?

Decrease triglycerides by 20 to 50%

What is atherosclerosis?

Hardening of the arteries

What type of lesions form in atherosclerosis?

Fibrofatty lesions

Where do atherosclerotic lesions form?

In the lining of large and medium-sized arteries

Which vessels are commonly affected by atherosclerosis?

Aorta, coronary arteries, and vessels supplying the brain

What major diseases are associated with atherosclerosis?

Ischemic heart disease, stroke, and peripheral vascular disease

When do symptoms of atherosclerosis typically appear?

20 to 40 years after development

What is the major risk factor for atherosclerosis?

Hypercholesterolemia

What are modifiable risk factors for atherosclerosis?

Smoking, obesity, visceral fat, hypertension, and diabetes mellitus

Why does smoking increase atherosclerosis risk?

Endothelial damage

How much does hypertension increase CAD risk?

Two-fold