DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION III
MODULATION OF CARDIOVASCULAR FUNCTION
Table 31–7
Secondary Causes of Dyslipidemia
DISORDER
MAJOR LIPID EFFECT
Diabetes mellitus Triglycerides > cholesterol;
low HDL-C
Nephrotic syndrome Triglycerides usually >
cholesterol
Alcohol use
Triglycerides > cholesterol
Contraceptive use Triglycerides > cholesterol
Estrogen use
Triglycerides > cholesterol
Glucocorticoid excess Triglycerides > cholesterol
Hypothyroidism Cholesterol > triglycerides
Obstructive liver Cholesterol > triglycerides
disease
HDL-C, high-density-lipoprotein cholesterol.
aggressive lipid-lowering therapy has beneficial effects
beyond those obtained by simply decreasing lipid deposition
in the arterial wall. Aggressive lipid lowering
results only in very small increases in lumen diameter
but promptly decreases acute coronary events (Cannon
et al., 2004). Lesions causing <60% occlusion are
responsible for more than two-thirds of the acute
events. Aggressive lipid-lowering therapy may prevent
acute events through positive effects on the arterial
wall; it corrects endothelial dysfunction, corrects
abnormal vascular reactivity (spasm), and increases
plaque stability.
Atherosclerotic lesions containing a large lipid
core, large numbers of macrophages, and a poorly
formed fibrous cap are prone to plaque rupture and acute
thrombosis. Aggressive lipid lowering appears to alter
plaque architecture, resulting in less lipid, fewer
macrophages, and a larger collagen and smooth muscle
cell–rich fibrous cap. Stabilization of plaque susceptibility
to thrombosis appears to be a direct result of LDL-C
lowering or an indirect result of changes in cholesterol
and lipoprotein metabolism or arterial wall biology (see
“Potential Cardioprotective Effects Other Than LDL
Lowering,”later in the chapter).
Whom and When to Treat?
Large-scale trials with statins have provided new
insights into which patients with dyslipidemia should
be treated and when treatment should be initiated.
Gender. Both men and women with or without a prior
vascular disease event benefit from lipid-lowering
therapy (Heart Protection Study Collaborative Group,
2002; Ridker et al., 2008). Statins, rather than hormonereplacement
therapy, now are the recommended firstline
drug therapy for lowering lipids and preventing
CHD events in postmenopausal women. This recommendation
reflects the increased CHD morbidity in
older women with established CHD who were treated
with hormone-replacement therapy (see Chapter 40).
Age. Age >45 years in men and >55 years in women is
considered to be a CHD risk factor. The statin trials have
shown that patients >65 years of age benefit from
therapy as much as do younger patients. In fact, in those
>70 years, the reduction of absolute mortality is stunning
compared with individuals 55 years of age (Afilalo
et al., 2008; Diamond and Kaul, 2008). Old age per se
is not a reason to refrain from initiating drug therapy in
an otherwise healthy person.
Cerebrovascular Disease Patients. In most observational
studies, plasma cholesterol levels correlate positively
with the risk of ischemic stroke. In clinical trials,
statins reduced stroke and transient ischemic attacks in
patients with and without CHD (Amarenco and
Labreuche, 2009).
Peripheral Vascular Disease Patients. Statins prevent CHD
events and may improve walking distance in patients
with peripheral vascular disease (Aung et al., 2007).
Hypertensive Patients and Smokers. The relative risk
reduction for coronary events in statin trials of hypertensive
patients is similar to that in subjects without
hypertension (Franz et al., 2008). Relative risk is
reduced more in smokers in statin clinical trials than in
nonsmokers (Cheung et al., 2004).
Type 2 Diabetes Mellitus. Patients with type 2 diabetes benefit
very significantly from aggressive lipid lowering (see
“Treatment of Type 2 Diabetes Patients,” later in the
chapter) (Cholesterol Treatment Trialists’ Collaborators,
2008; Heart Protection Study Collaborative Group, 2003).
Post–Myocardial Infarction or Revascularization Patients.
As soon as CHD is diagnosed, it is essential to begin
lipid-lowering therapy (NCEP guidelines: LDL-C goal
<70 mg/dL for very high-risk patients) (Grundy et al.,
2004b). Compliance with drug therapy is greatly
enhanced if treatment is initiated in the hospital. Statin
therapy administered prior to angioplasty reduces the
requirement for procedures related to myocardial
infarction risk and the need for repeat revascularization
(Ebrahimi et al., 2008; Zhang et al. 2010). Statin therapy
also improves the long-term outcome after bypass
surgery.