Page 125 - Cardiac Nursing

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C HAPTER 4 / Genetics 101
ways. An individual can inherit genetic diseases, caused by abnor- Stroke
mal groups of genes passed down from one generation to the next.
Such heritable disorders are classified into three general classes. The Studies also have indicated a genetic predisposition to ischemic
first class is single gene mutations of large effect, which can be and hemorrhagic stroke. Although single gene disorders explain a
readily identified given detailed family history review coupled with small fraction of strokes, the genetic contribution to stroke most
appropriate genetic testing (e.g., familial hypercholesterolemia). likely will be multifactorial and complex. Recent family studies,
This class of genetic disorders is commonly referred to as including the Framingham Heart Study, have highlighted a signif-
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mendelian disorders, named after the founder of the modern prin- icant genetic component to stroke. Twin and family studies pro-
4
ciples of genetics, Gregor Mendel. The more common class of vide evidence that genetic factors contribute to the risk of stroke
heritable disorders is those of multifactorial inheritance, caused by and that their role may be at least as important in stroke as in coro-
the complex interplay of several genes and environmental factors nary heart disease. Genetic variation of cystathionine -synthase or
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(e.g., diabetes, hypertension, and atherosclerosis). The last class is methylenetetrahydrofolate reductase result in markedly elevated
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chromosomal aberrations, abnormalities of either chromosomal plasma homocysteine levels and homocystinuria. Homocysteine
structure or number. Such gross alterations to the genome can re- is a sulfur-containing amino acid derivative formed during me-
sult from a cellular “accident” or from a parent who carries a chro- thionine metabolism. Homocystinemia increases the risk of coro-
mosomal aberration (e.g., trisomy 21 or Down syndrome). nary artery disease (CAD), peripheral artery disease, stroke, and
Altered gene function can manifest at the molecular level in venous thrombosis, and it is a risk factor for premature vascular
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several ways. Genetic alterations can result in enzyme defects, disease. The angiotensin-1-converting enzyme gene harbors a
which result in the synthesis of a defective enzyme with reduced polymorphism, which in some but not all studies is a risk factor
activity or reduce quantity. This can lead to substrate accumula- for myocardial infarction. Similar studies in stroke patients also
tion, a metabolic block with a decreased amount of end product, show inconsistent results, but most of these studies have been un-
or the failure to inactivate a tissue-damaging substrate. Another derpowered to detect a small contribution to stroke risk from the
mechanism of disease is malfunctions in receptors and transport ACE gene. Recent meta-analysis suggests that the polymorphism,
systems. For example, in familial hypercholesterolemia, a reduced acting recessively, is a modest but independent risk factor for is-
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function of LDL receptor leads to an inability to transport LDL chemic stroke onset.
into the cell, which causes elevated levels of plasma cholesterol The apolipoprotein E (apoE) 4 allele is associated with in-
and accelerates atherosclerosis. 5 creased risk of coronary heart disease and is also a major genetic
As the science of genetics has matured, research has shifted fo- susceptibility locus for Alzheimer disease. This polymorphism is
cus from rare, single gene disorders to common, multifactorial also associated with ischemic stroke and poorer outcomes after
chronic diseases. Chronic disease affects more than 90 million stroke. Carriers of the rare 4 are more frequent among patients
Americans, accounting for 70% of all deaths and 60% of the na- with ischemic cerebrovascular disease compared with control sub-
tion’s medical costs. As research progresses, genetics offers the op- jects. A recent meta-analysis provides evidence for a role for the
portunity to target health promotion and disease prevention pro- apoE genotype in the pathogenesis of some cases of ischemic cere-
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grams better and the possibility to conserve health care program brovascular disease.
resources. However, the contribution of genetics to chronic dis-
ease is complex, reflecting the interaction of many genes with the Atherosclerosis
environment and with one another. 6
Atherosclerosis is a progressive disease characterized by the accu-
mulation of lipids and fibrous elements in the large arteries (see
OVERVIEW: HEART DISEASE Chapter 5). The early lesions of atherosclerosis consist of suben-
dothelial accumulations of cholesterol-engorged macrophages
called foam cells. Lesions are usually found in the aorta in the first
Cardiovascular Disease
decade of life, the coronary arteries in the second decade, and the
According to the Centers for Disease Control and Prevention, car- cerebral arteries in the third or fourth decade. Because of differ-
diovascular disease, principally heart disease and stroke, is the ences in blood flow dynamics, there are preferred sites of lesion
leading cause of death among men and women in all racial and formation within the arteries. Plaques can become increasingly
ethnic groups. Cardiovascular disease affects approximately complex, involving calcification, ulceration, and hemorrhage
58 million Americans and costs the nation $274 billion each year, from small vessels within the lesion. Although advanced lesions
including health expenditures and lost productivity. Research has may encroach and block blood flow, the critical clinical complica-
begun to uncover a number of potential genetic susceptibility tion is an acute occlusion caused by thrombus formation, result-
genes for heart disease and stroke and their risk factors (e.g., obe- ing in angina, myocardial infarction, or stroke.
sity and high blood pressure). 7
Heart disease has become a major focus of genetic research. In Sudden Cardiac Death
the past decade, the number of publications on genetic contribu-
tions to heart disease has risen exponentially. Genetic mutations Although CAD accounts for the majority of sudden death cases in
have been associated with various risk factors for heart disease, in- cardiac arrest, a small proportion ( 5%) is attributable to sudden
cluding lipid metabolism and transport, hypertension, and ele- arrhythmia death syndrome. A prolonged Q-T interval is a com-
vated plasma homocysteine levels. It is believed that while tradi- mon thread among the various phenotypes associated with this phe-
tional risk factors including environmental influences explain nomenon. A number of drugs are known to cause QT prolonga-
approximately 50% of the cases of cardiovascular disease, genetics tion, as well as disorders of potassium, calcium, and magnesium
may help explain the remaining disease burden. homeostasis, myocarditis, and endocrine and nutritional disorders.