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stroke when treated with diuretics compared with other antihypertensive therapies.
With regard to BP response, interactions were also found between genetic polymor-
phisms for eNOS and diuretics and the ACE gene and angiotensin II type 1 receptor
antagonists. Although there are controversies to settle and diffi culties to overcome,
pharmacogenetics may yield successful strategies to optimize drug therapy. Several
candidate genes are currently under investigation for their potential to modify
response to antihypertensive drugs. Findings from previous studies require confor-
mation in other studies to be able to make defi nitive conclusions about current posi-
tive drug-gene interactions. It is also important that research groups collaborate
more in order to facilitate the conduct of a metaanalysis for conclusive results. With
the development of effi cient methods for analyzing massive amounts of data, phar-
macogenetic studies may eventually lead to the optimization of antihypertensive
drug therapy based on genetic profi les of patients.
Pharmacogenetic-guided therapy has clinical potential for management of HPN,
but there are few controlled studies on this topic. A clinical trial on individuals with
uncomplicated HPN aims to identify the genetic determinants of the antihyperten-
sive and adverse metabolic responses to a thiazide diuretic (hydrochlorothiazide), a
β-blocker (atenolol), and their combination (Johnson et al. 2009 ). This will be
accomplished through candidate gene and genome-wide association approaches.
Current antihypertensive therapy is discontinued, and HPN is confi rmed, along with
collection of other baseline data. Subjects are then randomized to either hydrochlo-
rothiazide or atenolol, with one dose titration step, followed by assessment of
response to therapy after at least 6 weeks on the target dose. Those with blood pres-
sure >120/70 mmHg have the second drug added, with similar dose titration and
response assessment procedures. Data collected include home, offi ce, and 24 h
ambulatory blood pressure. Biological samples collected in the fasting state include
plasma, serum, DNA, and urine. This trial will add substantially to our understand-
ing of the genetic determinants of antihypertensive and adverse metabolic responses
to two commonly used antihypertensive drug classes.
Scheme for Management of Hypertension by Personalized Approach
Despite the many therapeutic options for HPN, only 27 % of the patients achieve
adequate control of BP. Therefore, there is an opportunity to improve the manage-
ment of HPN by a personalized approach as shown in Fig. 14.1.
Pharmacogenetics of Lipid-Lowering Therapies
Cardiovascular disease is associated with nonmodifi able risk factors such as age,
gender, and genetic background, and with modifi able risk factors such as lipid con-
centrations. Lowering serum lipid levels has been demonstrated to slow the pro-
gression of, or even induce regression in, atherosclerosis. However, like any other
14 Personalized Management of Cardiovascular Disorders