Page 129 - Cardiac Nursing

0/0
0/0
6/2
3
3
3
1
1
0:4
6/2
009
009
xd
09
7-1
7-1
p
p
09
q
q
xd
10.
10.
q
A
p
p
05
05
A
ara
ara
ara
p
t
t
e 1
M
M
M
0:4
0 A
0 A
g
g
e 1
Pa
Pa
g
0-c
K34
K34
04_
04_
0-c
LWB
LWBK340-c04_ pp097-110.qxd 30/06/2009 10:40 AM Page 105 Aptara
LWB
C HAPTER 4 / Genetics 105
evidence, knowledge of genetic susceptibility to CAD has value in
DIAGNOSIS AND RISK providing risk information and can guide decision making re-
ASSESSMENT: APPLICATION garding lifestyle modification and participation in disease preven-
OF GENETIC SUSCEPTIBILITY tion and management strategies.
Early detection strategies for CAD are generally not recom-
INFORMATION IN THE mended for the general population, because many lack adequate
PREVENTION OF CORONARY sensitivity and specificity whereas others are too invasive and costly.
ARTERY DISEASE However, use of early detection strategies such as electron beam com-
puted tomography may ultimately prove to be more cost-effective
CAD is a heterogeneous disorder; logically, no universal path of pre- for genetically susceptible persons at high risk. There is consistent
vention exists for all patients. 152 In the future, knowledge of a pa- evidence that coronary calcification correlates highly with the pres-
tient’s genetic risk factors will identify important biologic differences ence and degree of obstructive and nonobstructive plaque, 167,168
that could improve disease prevention and management through tar- nonfatal infarction, and need for subsequent coronary revasculariza-
geted interventions. Failure to recognize these differences may deny tion in asymptomatic individuals 169–171 and patients undergoing
appropriate access to care for those patients who may benefit from coronary angiography. 172 Once CAD is identified in high-risk indi-
alternative prevention and management strategies. viduals with a genetic susceptibility, more aggressive risk factor mod-
Cardiovascular disease is heterogeneous in manifestation, and ification, for example, pharmacological intervention and procedures
the most appropriate therapy will depend on the particular sub- such as angioplasty or revascularization, can be considered.
type of disease. Therefore, one application of screening may be to Genetic susceptibility to disease can be assessed by direct
distinguish different forms of the disease so that pharmacological DNA-based testing, direct measurement of biochemical traits,
intervention can be more effectively targeted. Classification is al- physical and pathologic characteristics, and personal and family
ready used clinically because patients are grouped according to the history collection. Physical examination findings can be instru-
variety of risk factors they display, but genetic testing will greatly mental in identifying a genetic risk for CAD (e.g., tendon xan-
expand the subdivisions of the disease. thomas and xanthelasma seen in hereditary lipid disorders). How-
Because heart disease and stroke are diseases of adulthood, ever, many hereditary syndromes are rare and account for only a
knowledge of susceptibility to disease could be available years be- small percentage of cardiovascular disease. 173 Conversely, DNA
fore clinical disease develops, permitting earlier intervention. Test- markers associated with common forms of disease are generally
ing for elevated LDL cholesterol and decreased HDL cholesterol prevalent and of low magnitude, and thus in isolation are not
levels and blood pressure have long been advocated as a way of highly predictive of CAD risk. 174 Moreover, modeling the cumu-
identifying individuals at increased risk, and other factors have lative risk of the multiple low-magnitude genetic risk factors is
emerged more recently as risk indicators (see Table 4-1). Once the still evolving and their application to clinical risk assessment is
genes contributing to common forms of the disease have been currently premature. Therefore, the systematic collection of fam-
identified, along with their underlying genetic lesions, genetic ily history information currently appears to be the most appropri-
tests will add greatly to our ability to assess risk. ate screening approach for identification of individuals with a ge-
Cholesterol lowering is a central tenet of primary and second- netic susceptibility to CAD (see Tables 4-1 and 4-2).
ary prevention of CAD. 153–160 However, despite effective lipid In addition to identifying individuals with increased cardiovascu-
lowering, CAD will develop in a substantial proportion of indi- lar risk, the family history can identify qualitative characteristics of
viduals, or those with CAD will have progression of their dis- CAD risk, which are important when planning disease prevention
ease. 161 Moreover, elevated plasma cholesterol level is not a sensi- and management strategies. 175 Familial aggregation of CAD, dys-
tive predictor of individuals with the greatest genetic susceptibility lipidemia, hypertension, stroke, and type 2 diabetes suggests insulin
to CAD. 162 Elevated levels of lipoprotein(a) [Lp(a)], a proinflam- resistance (commonly referred to as the metabolic syndrome). 176 Al-
matory subpopulation of LDL particles modified by the tered hemostasis may be suspected in a family that features multiple
apolipoprotein(a) protein, are not currently detected with routine affected relatives with early onset of CAD and stroke or other throm-
cholesterol screening, and only 3% of patients with hyper-Lp(a) boembolic events. Recognition of these qualitative features may have
had elevated LDL cholesterol values. Epidemiological studies have important implications for recommending appropriate diagnostic
shown that plasma HDL cholesterol is inversely related to CAD tests as well as individualized surveillance and prevention strategies.
and that there is an inverse relationship between HDL cholesterol Family history reports of CAD, diabetes, and hypertension are
and triglyceride levels. 163 Also, hypertriglyceridemia is an inde- generally accurate, with sensitivity of a case report for CAD rang-
pendent risk factor for CAD. 20 Fibrates reduce death from CAD ing from 67% to 85%. 177–179 Specificity values for family history
and nonfatal myocardial infarction in secondary prevention of reports of these conditions approach 90%. 177 A positive family
CAD in men with low levels of HDL cholesterol. During fibrate history can generally be used with a high degree of confidence for
treatment, HDL cholesterol levels predicted the magnitude of re- the identification of individuals who may be at increased risk for
duction in risk for CAD events. Supplementation with the cofac- CAD. Nonetheless, when possible, verification of family history
tors involved in homocysteine metabolism, vitamins B 6 , B 12 , and by review of medical records and death certificates is preferable,
folate, is effective in reducing homocysteine levels, particularly if although not always feasible. Studies of family history validity
there is a vitamin deficiency, 164–166 although the long-term effect indicate some underreporting of disease in relatives; thus, a negative
of cofactor supplementation on reducing cardiovascular events is report should not be used as an indicator of a minimum or
still undergoing study. However, data are lacking regarding the ef- decreased disease risk (less than the general population risk).
ficacy of these agents on reducing cardiovascular events in indi- An important goal of genetic evaluation for CAD is the devel-
viduals who have modified novel genetic risk factors contributing opment of individualized preventive strategies based on genetic
to unfavorable homocysteine and Lp(a) levels. Despite this lack of risk assessment and the personal medical history and lifestyle.