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CHAPTER
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L L L L Lipid Management and Cardiovascular Disease
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Kathleen A. Berra / Joan M. Fair
Cardiovascular diisease (CVD) is hthe leading cause of death for
Thiis u date highlighteedd he iimportance off lipid-lowe iring ther-
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Ca rd io va sc ul ar d is se ( CV D) i le ad g f or Th pd h gh th e p o li pi d ng he r-
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American women and men and is responsible for 35.2% of all ap apyy iin hhigh-risk annd moderately high-risk patients too acchieve a
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de d athhs. Approximately one in every fiive AAmeriicans di ded from 30% tto 40% reduction inn LLDL cholesteroll level, even if baseliine
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CVDD in 20055. The death rates varyy by gender, age, ethnicityy, and
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CV in 2 00 T he d ea th r at es v ar by g en de r, a ge , et hn ic it a nd le levels weree low or “nnormal” by current guidelines. An LDL goal
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socioeconomic status. Importantly, the overall death rates from of 100 mg/dL iss now con ideredd aa reasonable optionn ffor pa-
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CVD ddeclliin ded by 24 7%% ffrom 1994 to 2004 likkelly as a resullt of f tients designated at high risk. For those considered to be at very
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improved risk factor surveillance and management. Elevated high risk an LDL goal of 70 mg/dL is proposed. The LDL goal
serum cholesterol and, particularly, elevated low-density lipopro- of 70 mg/dL is suggested on the basis of the known elevated
tein (LDL) cholesterol levels are significant modifiable risk fac- risk for heart attack and stroke in this group. This important
tors associated with the development and progression of CVD. ATP III update significantly expands both the numbers of per-
More than 106 million Americans have a blood cholesterol sons needing treatment and redefines LDL treatment goals.
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higher than the desirable level of 200 mg/dL. Furthermore, Therapeutic Lifestyle Change (TLC) remains the cornerstone of
more than 37 million Americans have a blood cholesterol more treatment for all adults with elevated risk. TLC includes heart
than 240 mg/dL, a level at which current treatment guidelines healthy nutrition, weight control, and regular physical activity.
recommend the initiation of dietary or pharmacologic inter- Initiation of pharmacologic therapies is based on risk classifica-
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ventions. 1–3 The good news is that, in the United States, age- tion. See Table 36-2 for LDL goals and cut points for initiation
adjusted prevalence of high LDL cholesterol level in adults of TLC and pharmacological therapies. Cardiovascular nurses
dropped from 26.6% in 1984 to 25.3% in 2004. This was asso- need to understand the pathophysiology of dyslipidemia and
ciated with an increased awareness of the relationship between should actively participate in the identification and management
high LDL cholesterol and CVD (39.2% vs. 63%) and an in- of lipid disorders. 19
creased use of pharmacological therapies to reduce high blood
cholesterol (11.7% to 40.8%). The end result has been a decrease
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in overall death and disability from CVD. This information
demonstrates that both the incidence of high blood cholesterol BLOOD LIPIDS: STRUCTURE
and the benefits of treatment are substantial. AND FUNCTIONS
There is a large body of evidence, including animal stud-
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ies, observational studies, and numerous clinical trials, that The complex relationships between genetic and metabolic mech-
consistently point to a relationship between high blood lipids anisms and the molecular interactions within the cell wall help ex-
and CVD. A very recent example of this compelling relation- plain the association between lipid abnormalities and CVD. The
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ship is the INTERHEART Study. The INTERHEART study major lipid particles, cholesterol and triglycerides, both have im-
using data from 52 countries, showed that 90% of population- portant functions in the body. Cholesterol is an essential compo-
attributable risk is strongly associated with nine easily meas- nent of cell membranes, functioning to provide stability while
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ured risk factors. Two thirds (or 66%) of the population- permitting membrane transport; it is a precursor to adrenal
attributable risks are accounted for by abnormal lipids (using steroids, sex hormones, and bile and bile acids. Triglycerides are
the apo B/apo A-I ratio as a marker for abnormal lipids—a sur- the major source of energy for the body. Both cholesterol and
rogate for LDL measure) and by current smoking. This associ- triglycerides are insoluble molecules and must be transported in
ation holds true for both men and women, across different ge- the circulation as lipoproteins.
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ographic regions, and ethnic groups. Table 36-1 summarizes Lipoproteins are complexes of nonpolar lipid cores (triglyc-
the results of large randomized lipid-lowering primary and erides and cholesterol esters) surrounded by a surface coat of po-
secondary prevention trials. 2,7–15 Meta-analyses of the choles- lar lipids (phospholipids and free cholesterol) and specific proteins
terol-lowering clinical trials estimated that a 10-mg/dL reduc- called apoproteins. Total cholesterol, for example, is composed of
tion in total cholesterol results in a 22% reduction in CVD in- 18 different lipid and lipoprotein particles. 20 Lipoproteins can be
cidence after 2 years of intervention, and a 25% reduction classified according to their density, their migration on an elec-
after 5 years. 3,16 There is some evidence that cholesterol low- trophoretic field, or their lipid and apoprotein composition. 21
ering begun at an early age (e.g., age 40 years) may provide During the 1980s, significant advances were made in deter-
greater risk reduction than if started at a later age (e.g., age 70 mining the function of the apoproteins, the lipid processing en-
years). 17 However, recent clinical trials including persons zymes, and lipoprotein receptors. Apoproteins function as more
older than 65 years show benefit for CVD risk reduction in than transport vehicles; they have variant properties that acti-
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The Adult Treatment Panel III (ATP III) Guidelines were up- or removal of lipoproteins from the circulation. 22 The func-
dated in 2004 in response to these important clinical trials. 3 tions of nine apoproteins in the lipid metabolic cascade have
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