494
Choice of Drugs for Hypertension
Over 100 medications are available for treatment of HPN in several categories:
diuretics, α-blockers, β-blockers, aldosterone antagonists, angiotensin-converting
enzyme (ACE) inhibitors, angiotensin II receptor antagonists, CNS active agents and
calcium channel blockers. Each of these categories contains several distinct drugs,
which vary in their effi cacy and liability to produce adverse reactions in different
patient populations. β-adrenergic antagonists are generally recommended as fi rst-
line therapy, along with thiazide diuretics, for the treatment of HPN. However, as
many as 60 % of hypertensive patients do not achieve adequate lowering of BP from
monotherapy with β-blockers. It is plausible that genetic variation in the β-adrenergic-
receptor genes accounts for some of the observed variability in BP response.
Antihypertensive monotherapy does not address the multifactorial nature of HPN
as a disease with many pathways. An approach to increase chances of effi cacy is to
use fi xed combination of drugs with different modes of action as initial therapy in the
treatment of HPN. The additive or synergistic effect of combination therapy may
lower blood pressure in patients who tend to have less than full response to one com-
ponent only. This is still an approximate method and may increase the adverse effects
of drug interactions unless the combination is selected individually for each patient.
Correction of Causes and Risk Factors of Hypertension
A number of causes and risk factors of HPN have been identifi ed and these should
be corrected. Low-salt diet for salt-sensitive HPN and management of stress by
relaxation and meditation are well known and should be incorporated in personal-
ized life style modifi cation advice. A mendelian randomization study has shown
that low plasma 25-hydroxyvitamin D (25OHD) concentration is one cause of HPN
and this is partially due to genetic variants associated with low endogenous produc-
tion of 25(OH)D, raising the possibility of preventing or reducing HPN with vita-
min D supplementation (Vimaleswaran et al. 2014 ). This fi nding warrants further
investigation in an independent, similarly powered study.
Genes and Hypertension
Recently there is increasing interest in genes related to hypertension. Genetic fac-
tors account for 40–50 % of a person’s susceptibility to hypertension. HPN is more
prevalent and contributes to more severe manifestations of cardiovascular disease in
African Americans than in any other US ethnic group. Previous searches of the
genome found limited evidence of genes that determine HPN. So far, most gene
discovery studies have involved people of European descent. A landmark study
involving nearly 30,000 African-Americans has discovered four novel gene varia-
tions associated with blood pressure, which are also associated with blood pressure
across other populations (Franceschini et al. 2013 ). Although it is unknown how the
genes regulate blood pressure, the fi ndings contribute to better understanding of
14 Personalized Management of Cardiovascular Disorders