Despite progress in recent years in the prevention, detection, and treatment of
high blood pressure (BP),
hypertension remains an important public health challenge.
Hypertension affects approximately 1 billion individuals worldwide. High BP is associated with an increased risk of mortality and morbidity from
stroke,
coronary heart disease,
congestive heart failure, and
end-stage renal disease; it also has a negative impact on the quality of life.
Hypertension cannot be eliminated because there are no
vaccines to prevent the development of
hypertension, but, its incidence can be decreased by reducing the risk factors for its development, which include
obesity, high dietary intake of fat and
sodium and low intake of
potassium, physical inactivity, smoking, and excessive alcohol intake. For established
hypertension, efforts are to be directed to control BP by lifestyle modification (LSM). However, if BP cannot be adequately controlled with LSM, then
pharmacotherapy can be instituted along with LSM. Normalization of BP reduces cardiovascular risk (for cardiovascular death,
myocardial infarction, and
cardiac arrest), provides renoprotection (prevention of the onset or slowing of
proteinuria and progression of renal dysfunction to
end-stage renal disease in patients with
hypertension,
diabetes mellitus types 1 and 2, and
chronic renal disease), and decreases the risk of cerebrovascular events (
stroke and cognition impairment), as has been amply demonstrated by a large number of randomized clinical trials. In spite of the availability of more than 75
antihypertensive agents in 9 classes, BP control in the general population is at best inadequate. Therefore,
antihypertensive therapy in the future or near future should be directed toward improving BP control in treated hypertensive patients with the available drugs by using the right combinations at optimum doses, individually tailored gene-polymorphism directed
therapy, or development of new modalities such as gene therapy and
vaccines. Several studies have shown that BP can be reduced by lifestyle/behavior modification. Although, the reductions appear to be trivial, even small reductions in systolic BP (for example, 3-5 mm Hg) produce dramatic reduction in
adverse cardiac events and
stroke. On the basis of the results of clinical and clinical/observational studies, it has been recommended that more emphasis be placed on lifestyle/behavior modification (
obesity, high dietary intake of fat and
sodium, physical inactivity, smoking, excessive alcohol intake, low
dietary potassium intake) to control BP and also to improve the efficacy of pharmacologic treatment of high BP. New classes of
antihypertensive drugs and new compounds in the established
drug classes are likely to widen the armamentarium available to combat
hypertension. These include the
aldosterone receptor blockers,
vasodilator beta-blockers,
renin inhibitors,
endothelin receptor antagonists, and dual
endopeptidase inhibitors. The use of fixed-dose
combination drug therapy is likely to increase. There is a conceptual possibility that gene therapy may yield long-lasting
antihypertensive effects by influencing the genes associated with
hypertension. But, the treatment of human
essential hypertension requires sustained over-expression of genes. Some of the challenging tasks for successful gene therapy that need to be mastered include identification of target genes, ideal gene transfer vector, precise delivery of genes into the required site (target), efficient transfer of genes into the cells of the target, and prompt assessment of gene expression over time. Targeting the RAS by antisense gene therapy appears to be a viable strategy for the long-term control of
hypertension. Several problems that are encountered in the delivery of gene therapy include 1) low efficiency for gene transfer into vascular cells; 2) a lack of selectivity; 3) problem in determining how to prolong and control transgene expression or antisense inhibition; and 4) difficulty in minimizing the adverse effects of viral or nonviral vectors. In spite of the hurdles that face gene therapy administration in humans, studies in animals indicate that gene therapy may be feasible in treating human
hypertension, albeit not in the near future.
DNA testing for genetic polymorphism and determining the genotype of a patient may predict response to a certain class of
antihypertensive agent and thus optimize
therapy in individual patients. In this regard, there are some studies that report the effectiveness of
antihypertensive therapy based upon the genotype of selected patients. Treatment of human
hypertension with
vaccines is feasible but is not likely to be available in the near future.