Page 849 - Cardiac Nursing

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C HAPTER 36 / Lipid Management and Cardiovascular Disease 825
Table 36-2 ■ GUIDELINES FOR INITIATION OF TLC AND/OR PHARMACOTHERAPIES—MODIFICATIONS BASED ON THE
UPDATE TO ATP III 3
Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy
†
1. High Risk* CHD or CHD Risk 100 mg/dL 100 mg/dL 100 mg/dL
‡
Equivalents (10-year risk 20%) optional goal 70 mg/dL 100 mg/dL: consider drug options
2. Moderately High Risk 130 mg/dL 130 mg/dL 130 mg/dL
10-year risk 10%–20% 100–129 mg/dL: consider drug options
3. Moderate Risk 130 mg/dL 130 mg/dL 160 mg/dL
10-year risk 10%
4. Lower Risk 160 mg/dL 160 mg/dL 190 mg/dL
0–1 risk factor 160–189 mg/dL: LDL lowering drug optional
*Risk factors include cigarette smoking, hypertension (BP 140/90 mm Hg or on antihypertensive medication), low HDL-C ( 40 mg/dL), family history of premature heart dis-
ease (CHD in first-degree male relative 55 years of age, or in a female relative 65 years of age), and age (men 45 years of age and women 55 years of age).
†
CHD includes history of MI, unstable angina, stable angina, coronary artery procedures (stenting, angioplasty, bypass surgery, or evidence of clinically significant myocardial
ischemia.
‡
CHD Risk Equivalents include manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease
(transient ischemic attach or stroke or carotid origin or 50% obstruction in carotid artery), diabetes, and 2
risk factors with 10-year risk for hard CHD 20%.
consequently, the most atherogenic lipoprotein. 21 Under normal
LIPID METABOLISM AND conditions, more than 93% of the cholesterol in the body is lo-
TRANSPORT cated in the cells, and only 7% circulates in the blood. Two
thirds of the blood cholesterol is carried by LDL. Increased cel-
The gut and liver are responsible for the production of the six lular uptake of cholesterol through the LDL receptor pathway
principal lipoproteins. Exogenous lipoproteins are formed in suppresses the cell’s own synthesis of cholesterol by inhibiting
the mucosa of the small intestine after digestion of dietary fats. the hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase
During the digestive process, hydrolyzed products of ingested enzyme. This enzyme determines the rate of cholesterol synthe-
fats enter epithelial cells of the small intestine, where they are sis. As cellular cholesterol levels increase, the activity of the LDL
converted into triglycerides and cholesterol esters. These prod- receptor is downregulated, and synthesis of new LDL receptors
26
ucts are then aggregated into the lipoprotein complexes known is inhibited. These feedback control mechanisms serve as the
as chylomicrons. Chylomicrons pass into small lymph vessels rationale for determining the treatment of elevated blood
and reach the circulatory system through the thoracic duct. In cholesterol.
the peripheral capillaries, chylomicrons are hydrolyzed by the Several metabolic and genetic disorders can be related to ele-
enzyme LPL, located on the capillary endothelium. Free fatty vated LDL cholesterol levels. Habitually high dietary intakes of
acids and glycerol then enter adipose tissue cells. A cholesterol- saturated fats and cholesterol beyond that needed for cell func-
rich chylomicron remnant (a second lipoprotein complex) is tions result in blood levels of LDL beyond normal and result in
released into the circulation when lipolysis is nearly complete.
Chylomicron remnants are cleared rapidly by the liver (Fig.
36-1). 23,24
In the liver, the endogenous lipoprotein cascade begins with
the production of very-low-density lipoproteins (VLDLs).
Triglycerides are resynthesized from chylomicrons and packaged EXOGENOUS PATHWAY
with specific apoproteins, apo B-100, apo C-I, apo C-II, and apo
E, to form VLDL. Once VLDL is released into the circulation, in- Exogenous pathway
termediate-density lipoproteins (IDLs) and VLDL remnants are
formed from VLDL lipolysis. This process takes place in the cap- Chylo-
illary endothelium and is mediated by LPL, the same enzyme re- micron
sponsible for the hydrolysis of chylomicrons. Apo C-II also acts as Gut
a cofactor in these processes. 25
LDL receptors in the liver recognize and bind with apo E on Lipoprotein lipase
the IDL particle and remove approximately half of the IDL from
the circulation. The remainder is converted by HL into smaller
cholesterol-rich lipoproteins known as LDL. Apo B-100 is the Chylomicron remnant receptor
y
C C Ch
C C
remaining protein left on the surface coat of LDL particles. The Ch llo-
LDL receptors on cells of the liver and other organs that require remnant
cholesterol for structural and metabolic functions bind with apo
B-100 and facilitate the removal of LDL from the blood. Figure ■ Figure 36-1 The exogenous metabolism of lipoproteins and the
36-2 illustrates the endogenous pathway. The LDL particle is transport of chylomicrons to the tissues and chylomicron remnants to
the major cholesterol-carrying lipoprotein in the blood and, the liver.