Hypertension Diagnostics, Therapy and Pharmacogenomics

Current Knowledge

Human hypertension has become a public health dilemma. The condition is one of the major public health burdens affecting approximately 1 billion people in the world. It is estimated that about 25% of the adults in the industrialized states are hypersentive. The disease epidemic has moved to developing countries too (Reddykys 1). Worse still, increase in the proportion of death due to hypertension is projected to rise from 25% in 1990 to above 40% by 2020. Hypertension increases the risks of several common cardiovascular diseases such as myocardial, infarction, stroke and related heart failure. Blood Pressure regulation mechanism is complex. The mechanism depends on integrated action of the renal, cardiovascular, endocrine and neural system. Hypertension is a subsequent to the malfunctioning of one or more the above systems (Lifton 676).

Renin- angiotensin system (RAS) is also a regulatory system. It is the key modulator for vascular tone, homeostasis such as salt water balance and Blood pressure levels. Some of the most common therapeutic drugs (angiotensin-converting enzyme inhibitors and the angiotensin type II) for lowering Bp levels act as inhibitors to RAS. Recent investigations have identified the primary components of RAS as the candidate gene for hypertension (International human genome sequencing consortium 1). For example, angiotensinogen have been identified as one of the genes having the primary role in the etiology of hypertension. Many other genes from other physiological pathways have been assessed through association studies with volunteers. Studies on β 2 androgenic receptor, guanine nucleotide binding protein (G protein), β polypeptide3 (GNB3) have revealed a positive association with hypertension. However, there is no reproducibility of the above association in genetic studies of hypertension (Goldstein and Cavalleri 1242).

Genomics revolution has brought new opportunities for improvements in the management of the hypertensive disorders in the world. The improvements are through understanding hypertension mechanism, and the mechanism that regulates blood pressure consequently, in the prevention and treatment of hypertension. During the past decade, two main approaches have been used to determine genetic causing agents for hypertension. These include candindate gene studies and genome wide screening (GWAS). The candidate gene approach uses a gene of known function to test for the association with hypertension while the genome wide screening involves analyzing polymorphic markers at various locations in the genome (Dominiczack and Collnell 1).

Complex disorders arise due to complex interaction between multiple genetic and environmental determinants (Lifton 680). Blood pressure and essential hypertension are examples of complex phenotypes. A range of genetic epidemiology approaches done with the aim to determine the genetic determinants of the phenotypes. However, the studies are constrained by small effect of sizes of each genetic variants detected and by the complexity of the phenotypes. More so, other constraints encountered are those of design, conduct, analysis and interpretation of the results. Lastly, the genetic epidemiology studies are of wide range of complex disorders (Ruthwell 948).

Early researchers have indicated the importance genes in determination of blood pressure and Hypertension. Further research works are currently proceeding simultaneously in areas such as the recurrence risks ratios, variance components heritability, Segregation analysis, and linkage analysis and linkage disequilibrium mapping association analysis to appraise existing evidence (Risch 856). In the characterization of phenotype of blood pressure, there are quandary as to whether the blood pressure should be considered as a quantitative trait or binary trait in the context of its genetic causation. The subject has been controversial since 1950s. Platt observation that bimodal blood pressure distribution in small size families was used to support that hypertension was a quantitative abnormality, thus was likely to behave in the Mendelian patterns of inheritance. This observation received controversial reaction form Pickering and other researchers whose observation that “the new idea that blood pressure was inherited as a graded character dawned and steadily became convincing, when tic became apparent that there was a quantitative relationship between the deviations from the norm of arterial pressures of our patients and those of their first-degree relative” (Dominiczack and Collnell 8).

Both Platt and Pickering were partially correct, it is evident today that hypertension represents the dichotomization of quantitative blood pressure, risk of hypertension is influenced by multiple genetic and environmental determinants, and that it is through their increased individual actions and interactions that have to elevate quantitative blood pressure. Familial aggregation of Hypertension is described in terms of correlation effect that ranges between 0.1 and 0.3. There have been attempts to locate and identify the hypertension causative genes. There are many genes whose usual effect is completely unknown. Therefore, researchers should attempt to localize regions of the genome to appear and should contain one or more genes that would be relevant (Dominiczack and Collnell 12).

Genetic linkage analysis is described by the probability for shorter haplotypes to be inherited by the next generation intact, without being subjected to recombination caused by cross over during meiosis. Therefore, if a genetic marker is passed down through the family such that it consistently accompanies hypertension, it would simply be indicated that the genetic marker correlates (is linked) to the gene associated to hypertension. There has been a success in locating genes of monogenic forms of hypertensions using the genetic linkage (Levy et al 483). However, there have been fewer successes with location of genes that underlie blood pressure and hypertension risks and complex traits. There are suggestive LOD scores that have been reported on every chromosome with very few replications in the independent population (Levy et al 483).

New ranges of strategies are being incorporated to investigate further the genetics of hypertension and blood pressure. Advances in genomics have provided exciting opportunities and challenges such that by 2020, there are likely to have substantial advances in the understanding of the etiology of the complex traits and consequently, treatment and prevention. The use of Mendelian randomization studies provides the possibility that the benefits of the developments could be realized by the entire populations (Risch 856).

Hypertension Diagnostics

Hypertension is defined as systolic blood pressure above 140mmHg or a diastolic pressure above 90mmHg. An average of two or more visits Blood pressure reading is sufficient to identify one as hypersensitive. This is because high elevations in blood pressures are known to be elevated, especially during an extreme stress or even acute illness. Untreated hypertension increases the risks of nonfatal and fatal coronary artery diseases, renal failure, congestive heart failure, stroke or worse still, mortality. However, mortality depends on the level of the hypertension, gender, age and other risk factors, including atherosclerosis, organ damaged or cardiovascular diseases (Norman and Weber 1).

Poor diagnostic techniques can result in either over diagnosis or under diagnosis of hypertension. “White coat” hypertension and pseudo hypertension can also cause misdiagnosis or potential abuse of antihypertensive therapy. Misdiagnosing can be avoided through repeated blood pressure’s measurement after every patients visit unless the BP elevation is clear or other indicative sign of hypertensive target on an organ prevails. The repeat measurement affirms that the hypertension is present and persistent (Norman and Weber 8).

The recommended step for proper Blood pressure measurement technique involves allowing the patient to sit down quietly on a chair with the back supported at heart level. Research findings shows that having patient standing or sitting unsupported raise blood pressure recordings by 5-10mmHg. The patient should be advised to avoid caffeine, exogenous use for androgenic stimulants or smoking within the last one hour. These stimulants are known to cause transient elevations in blood pressure (Norman and Weber 11). Cuff used should be of the appropriate size. The cuff should encircle at least 80% to the arm circumference. This prevents artificially elevated readings. Cuffs should be placed such that its antecubital space and that the bladder overlies the brachial artery pulse. While inflating the bladder, one should ensure that the subjects arm cuff is at the level with the heart (Norman and Weber 12). The bladder should be deflated at 2-3mmhg/sec. After two minutes, the reading should be retaken. Blood pressure devices should be regularly serviced and maintained. Recent technology has made professionals to rely on automated Oscillometric devices for blood pressure measurements. The advantage with these instruments is the consistency in their reading values compared to sphygmomanometers in that, they give less inter-observer variability and are less biased when determining the blood pressure values. However, they should be regularly confirmed for their accuracy. Every patient’s blood pressure recordings should be staged. Blood pressure measurements are classified (stage) into (Venkatesh and Gorelick 5).

  • Normal: SBP above 120 and DBP greater than 80
  • Pre-hypertension: SBP 120-139 and DBP 80-89
  • Stage 1 hypertension: SBP 140-159 or DBP 90-99
  • Stage 2 hypertension: SBP greater 160 or DBP above 100

More so, the physician should be able to differentiate between White coat hypertension and pseudo hypertension. White coat hypertension is the hypertension resulting when only during the doctor’s visits. All hypertension cases with no evidenced of organ damage should be combined with ambulatory monitoring to ensure persistence and consistence of hypersensitivity (Norman and Weber 12).

Factors that affect blood-pressure readings include Soft Korotkoff sounds (diastolic Blood pressure effect), pseudo hypertension, paretic arm, pain, anxiety, acute smoking, caffeine or drugs intake, talking and singing. These factors are said to increase the Blood pressure reading. Other factors include impaired hearing by the examiner or biased expectation. How cuffs are put in position may elevate blood pressure reading. Cuff’s that are too narrow or not centered, low positioned the elbow, short rest period, sitting back unsupported, arm unsupported also increase the Blood pressure reading. Noisy environment, leaky bulb valve, blocked manometer, cold hands or stethoscope and equipment setting also may over diagnose high Blood pressure reading (Venkatesh and Gorelick 10).

The following factors are known to decrease the Blood pressure reading, soft korotkoff sounds (systolic effect), recent feeding habits, missed auscultatory gap, High stroke volume, noisy environment, faulty aneroid, leaky bulb, examiner reading habits. Other factors include reading next to lowest 5 or 10mmHg expectation biased or biased hearing, resting for too long, elbow position too high, too rapid deflation of the bladder and excess bell pressure. However, the following conditions have no effect to pressure measurements. These include menstrual phase, chronic caffeine use, self inflation of cuff, thin shirt under stethoscope and room temperature (Norman and Weber 12).

Evaluation for the patients with hypertension is done mainly to identify known causes of high blood, assess the presence or absence of target organ damage, cardiovascular disease and the response of the therapy. More so, evaluation is done to identify the presence of other cardiovascular risk factors or contaminant disorders that could be of help in guidance for treatment. Evaluation information is obtained from records known from the patient’s medical history, physical examination, laboratory tests and other diagnostic procedures (Aschebrenner and Venable 501).

Medical history include identifying the duration since the subject was diagnosed with high blood pressure, other medical backgrounds such as coronary heart diseases, heart failure, cerbrovascular diseases, peripheral vascular disease, renal disease, cases related to diabetes, dyslipdermia and presence of comorboid conditions such as gout or sexual dysfunction. Family history is also very important. These are records such as the presence of High blood pressure in the family history, premature CHD, stroke, diabetes and renal failures. Other medical histories if importance includes incidences in loss of weight, smoking of tobacco, intake of saturate fat and caffeine. More so, other mischievous cases like self-medication, herbal remedies and intake of illicit drugs. Adverse reaction from hypertensive therapy and physiological and environment factors such as family, situation, employment status and other working conditions are also vey important during evaluation (Aschebrenner and Venable 499).

Physical examination includes two or more measurements of blood pressure using the above described procedures. The physical examination should be accompanied by other measurements, including the height, weight and age. Examination around the neck is done to check presence of carotid bruits, distended veins or enlarged thyroid gland. Examination in the lungs is done to check for rales or evident brachospasm. Abdomen should be examined for bruits, enlarged kidneys, masses and abnormal aortic pulsation and neurological assessment (Aschebrenner and Venable 505).

Laboratory diagnostic procedures include urinalysis, complete blood cell count, blood chemistry (K, Na, Cr and HDL) and 12 lead electrocardiograms. Other diagnostic procedures are optional. These include microbuminuria, blood calcium, uric acid, fasting triglycerides, LDL, TSH, and glcosylated hemoglobin (Norman and Weber 12).

Hypertension Pharmacogenomics

Over the last five decades, great progress has been made in understanding the molecular basis of drug response and in elucidating the genetic determinants of disease pathogenesis and drug reaction (Munroe 328). Pharmacogenomics is the field that aims to explicate further the inherited nature of inter-individual variation in drug disposition and effects. Its ultimate objective is provision of stronger scientific concepts to select the best drug therapy and dosages for each patient. The genetic insights are also aimed towards the discovery and development of new medication (Nebert 258). Individual patients vary in their response to different types of anti-hypersensitive drugs. The reason behind individual variation in responses to the hypertensive agents are inadequately researched on. However, researchers have identified variation in drug metabolism impacted by genetic variation.

The important role of pharmacogenomics is to attain the appropriate drug use for every individual. So far, pharmacogenomics studies of Adrogenic receptor (AR) has been focusing mainly on β-blocker therapy [1-3]. Adrogenic system has a critical role in hypertension.

Individual’s genetic variation impact on drug response is infinitesimal. The variation is associated generally with the heterogeneity mechanism of essential hypertension. Several genes have been linked with essential hypertension (Risch 856). In RAS, the genes identified include polymorphisms in the angiotensinogen gene, the ACE gene and the angiotensin II subtype 1receptor gene. However, there is weak evidence that the above genetic variants play any role in inducing responses to drugs that antagonizes or inhibit RAS. However, Angiotensinogen and ACE genes polymorphisms induce plasma levels of their protein products. A probable elucidation for this incidence is that under normal circumstances, the changes are insufficient to influence the activity of RAS (Munroe 328).

Recently, a new observation involving Adducin gene was reported. Adducin is an alpha beta heterodimeric protein present in the renal tubule. Its function is to regulate ion transport by controlling changes in the actins cytoskeleton (Bray 698). GLY-460- Trp polymorphism present in the Adducin gene have been associated with hypertension. The Trp-460 allele shows increase in proximal tubular re-absorption. A study in Italy on two hypertensive cohorts, individuals possessing Trp-460 variant lowered their blood pressure by 70% with thiazide diuretic treatment than those carrying Gly -460 allele (Padmanabhan, Paul and Dominczak 13).

However, the findings are yet to be established, and when confirmed; it will be of great significance especially in determining individuals who are likely to respond positively to diuretic treatment. Another likely case is the mutation in the beta sub unit (T594M) that has been found to be common in hypersensitive African-American individuals in London. The T594M variant has shown increased sodium retention through increased channel activity. The subjects are likely to show positive response to diuretic agent too (Bray 698).

What is important for current researchers is to avoid confining themselves to the genes associated or linked with hypertension and broaden their search to other genes. The ability to attain drug responses is practicable and easily replicated. Therefore, focus should be directed towards candidate genes and especially to the variants that influence on the activity of the product gene (Binder 184). An assessment was done by O’Shaughnessy and colleagues to determine if beta 1 androreceptor gene indicated that G389R had influence in Blood pressure response to beta-blockade in hypertensive individuals. Although polymorphism is not usually associated with hypertension, O’Shaughnessy et al vitro studies indicated that polymorphism affects G-protein coupling of the receptor consequently, AMP production followed by the activation with the R389. However, their 147 cohort study findings showed no evidence of G389R variant to the clinical blood pressure reaction to 1 month of beta 1 receptor blockade treatment (Padmanabhan, Paul and Dominczak 13)

The future of hypertension pharmakogenomics lies on how well the following factors will be devoted to. First, the focus should be shifted to functional genetic variants and haplotypes to establish accurately gene variation at a locus. This is practicable especially with the advanced technology of chip based genotyping. More so, more precise research methods and design should be put into place. For example, studies should include 24-ambulatory blood pressure recording (Padmanabhan, Paul and Dominczak 13). More so, cooperation from the pharmaceutical industries should be encouraged. For example, clinical evaluation of anti-hypertensive drugs to determine drug efficacy can be incorporated with the study to determine who will respond better to the agents. Such studies together with participation of DNA bank would be progression in identifying genetic determinants responsible for the various responses to anti-hypertensive agent. More so, clinical research works like that of O’Shaughnessy et al with accurate monitored subsequent blood pressure responses with introduction or addition of anti-hypersensitive drugs would yield substantial information to facilitate progression in the identification of the genetic factors (Padmanabhan, Paul and Dominczak 13).

Identifying patients characteristics associated with blood pressure response to the therapy is important because it will increase control rates and improve the trial and error approach used by clinicians to select drug therapy for hypertension. Some of the factors that can be used for predictive purposes include age, obesity, and excessive dietary, presence of other disorders such as kidney failures, gender and the measurement of the rennin angiotensin-aldosterone system (RAAS). Researchers have showed that these combined effects to account for interindividual variation inn systolic and diastolic pressure and to response of anti hypertensive drugs such as thiazdine diuretics. Therefore, pharmacogenomics will play a great role in facilitating the identification of the respond drug responders and non responders especially those susceptible to the adverse effects (Chapman et al. 1047).

Hypertension Therapies

Hypertension treatment requires patient’s involvement and commitment to modifying their behavior for it to be successful. This might require total transformation from their usual lifestyle modification such as smoking cessation, reduction of salt intake, alcohol intake moderation and most importantly, involvement of multidrug treatment. Sometimes, there are cases of poor adherence to medication therapies. Such behavior can increase health care expenditures. Large comparative studies have been done on anti hypertensive agents. Anti hypertensive drugs lower blood pressure by acting on specific targets in the blood pressure regulation system. Ideally the agent chosen for administration should have rapid and short duration of action with minimal neurological reaction e.g. sedation or elevated intracranial pressure. The drug (β {1-3]) has been in use for cardiovascular diseases such as hypertension, ischemic heart disease, and chronic heart failure (Brewster et al. 627).

Drug therapy is recommended to every patient diagnosed with hypertension whether stage 1 or 2. Therapy is also recommended in pre-hypertension of patients who have compelling conditions such as diabetes type 1 with proteinuria, heart failure, isolated systolic hypertension especially in older adults. Therapy has shown efficacy in decreasing blood pressure. Drugs used include diuretics, beta blockers, calcium channel, ACE inhibitors and angiotensin 11 receptor blockers. All hypertension that cannot be controlled by the first line therapy requires combination therapies. This may involve use of rennin inhibitors, alpha 2 stimulators, alpha beta blockers and direct vasodilators and adjunctive treatment such as lipid lowering agents.

Some of the intravenously administered drugs include labetalol, hydralazine, esmolol, nicardipine, nitroglycerine, nitroprusside, enalapril, Urapidil and fenoldopam. Blockade β adrogenic system has been removed from the first line therapy due to its relative in effectiveness for primary prevention. The therapy has been identified with broad adverse effects such as impairment of glucose and lipid metabolism thus less effective in prevention of cardiovascular diseases compared to other anti-hypertensive drugs. Thiazide diuretic is used to treat patients with uncomplicated hypertension. The medication can be supplemented with other drugs from other classes.

Hypertension that occurs in conditions where there is existence of complicated physiologic conditions usually cause adverse reaction to drug therapy. For such cases, single agent therapy is given with combination with other therapy. Monotherapy is only effective when the blood pressure is slightly elevated. Combination therapy is meant for stage 2 hypertension. The exactly combination of drugs used to treat hypertension vary according to the hypersensitive co morbidities (Brewster et al. 627).

Drug dosage should be started low and then titrated up to what is seen as effective. Ideal drug should have therapeutic effect within 24 hours with a dose taken once daily. If the target blood pressure is not attained, then a second dose may be considered. This helps in achieving therapeutic response and reduces the risk of adverse effects. Diuretics lower blood pressure effectively, there are concerns that it lowers glomerular filtration rate to less than 40mL/min. Diuretics should be avoided when serum creatinine levels are greater than 2.3mg/Dl. Recommendations should be 25mg/day since the agents are affordable. However, it shows significant side effects on patients with hyperuricemia (Aschebrenner and Venable 499). The importance of rennin system suppression in the antihypertensive efficacy of beta adrenergic receptor blockade is supported by the direct relationship of anti-hypersensitive efficacy. The lack of response of rennin level with pre-treatment with beta blockade implies that there is other non rennin mechanism present in the metabolic pathway (Brewster et al. 627).

The primary objective for drug therapy is to prevent, effectively control hypertension and reduce morbidity and mortality by the least intrusive means possible. The main focus of the treatment is to achieve the targeted systolic pressure. This prevents other conditions such as stroke, heart failure and renal failure. Blood pressure can be controlled by primary prevention including lifestyle medication and pharmacological treatment. Lifestyle modification includes dietry management such as Sodium restriction. Sodium causes contraction and may be the cause of low Blood pressure. Other ways include Caloric restriction, reduction of cholesterol and saturated fat intake. Diet of high fruits and physical exercise is also important among hypertensive individuals (Aschebrenner and Venable 499).

The prevailing Ethnic differences to beta blockers and ACE inhibitors agents suggest that there are different pathways involved in hypertension causation. It is shown that African-American respond more favorably to diuretics or calcium channel blockers while Americans respond to other drug classes. It is evident that African-American responds better in to diuretics and calcium blockers while Americans respond better to ACE Inhibitors and beta blockers. Therefore, there exist different metabolic pathways in these two individuals. Personalized therapy is targeted towards achieving specific pathway based on ethnicity. However, the overlap possibility between the two ethnic groups is not clear (Munroe 328).

Hypertension and the Societal Impacts

Hypertension is one of the major causes of deaths in the world. It is estimated that about 7 million people die annually due to hypertensive related cases. World health organization record indicates that hypertension causes one in every eight deaths in the world. This makes it third leading killer and a major cause of disability in the world. It is estimated that for individuals at the age of 55years have a 90% risk for developing the condition. Research studies shows that African –American individuals have greater cases of morbidity and mortality rate than white women due to hypertension (Adeyemo et al. 1).

The rate of hypertension in African –American individuals is about two to three times than that of American individuals. Thus, hypertension prevalence is high among African –American individuals. Other risk factors include family history, cigarette, sedentary lifestyle and obesity. There is emerging hypothesis suggesting that an excess case of hypertension of African American women is due to psychological and environmental factors. The studies have little contribution that would facilitate in understanding the association between racism and hypertension. Therefore, key factors underlying the elevated rates of hypertension among African –American individuals are not well understood. However, there are assumptions that they are linked to the psychological factors than the genetic factors and the access to care (Goodman 1702).

Socio economic factor also plays a major role but do not fully account for racial differences in the blood pressure. The socio economic positions are generally weak (Pickering 277). Hypertension prevalence in African –American individuals is high irrespective of Social Economic Position and gender (Mensah et al. 1241). An early studies in Detroit results indicated that both African –American individuals and Americans who resided in low stress areas categorized by the level of economic deprivation, crime and marital instability had low blood pressures than those in high stress areas. The association recorded was higher for African –American individuals than for Americans. Other studies in US and Europe have confirmed that neighborhood and housing characteristics are associated with blood pressures (Aslanyan, Weir, Leess, Reid and McInnes 2628). More so, specific stressors in residential environments like noise from industries or airports, overcrowding, violence, cold indoor temperatures have been positively associated with high blood pressure. Other factors include economic deprivation, physical activities and access to nutritious foods (Diez 589).

Socio-economic and racial enthnic disparities in health are the biggest challenge facing US health research and policy. Reasons behind these disparities are yet to be identified. U.S. and many other nations view the social contexts as additional potential determinants of health and factors contributing to health disparities. Spatial location and segregation may expose affected groups to sources of chronic stress and social support in their residential environments. This could in turn generate disparities in blood pressure levels. Segregation may influence the kind and level of quality care for diagnosed individuals, and in treating of hypertension (Diez 589).

Other factors include knowledge, beliefs and attitude towards hypertension. Research indicates that those who are older and are of lower socioeconomic status or education background have non-clinically based beliefs about hypertension. Some even have denial that they have hypertension. Low socio-economic status is often coupled with lack of health insurance. This makes it difficult for such population has the ability to attain proper medical care and might end up being diagnosed at later stage, hence being unable to keep disease under control (Pickering 277).

The economic burden is felt at two levels. First, the effects felt by the macroeconomic policies and opportunities for prevention in the population. Second, the overall cost found in maintaining interventions in terms of effectiveness and health gains for the population at large. The economic burden is especially felt by the poor. Their prevalence rate is said to be six times more, making them more vulnerable. The medication cost is estimated to be US$100 a month (Goodman 1742).

The total cost to health service is also very high. For example, US, hypertension cost takes approximately 2% of the gross domestic product, Canada US$12 billion/year. Mores so, uncontrolled hypertension leads to loss in productivity. The lost productivity through lost work days for the individuals suffering or to the care giver is estimated to be about $1,046.7 in US

According to America Heart association, the condition has led to direct and indirect estimated cost of $475 billion in 2009.The world health organization estimates at least 21 million years are wasted due to hypertension and CVD each year. It is undisputable that economic growth depends on health, stock of labor, quality of labor and the physical capital. Therefore, bad health will reduce the rate of return on investments and in the education sector. The impact is also felt in nation’s competitiveness. The cost of hypertension treatment is even felt more in the developing countries. For example, South Africa, 2% of their gross domestic product is spent on treatment of the hypertension (Wilson, Lier and Sica 326).

These societal impacts associated with hypertension can be addressed potential using population based and personal based interventions. Personal based interventions include lifestyle modification, dietary, pharmacological and surgical interventions. Lifestyle and dietary interventions involves weight loss, feeding on diet rich in potassium and low in sodium, more fruits and lower fat products getting physically involved and moderate alcohol consumption. Such transformation lowers blood pressure effectively. More so, those diagnosed with hypertension should adhere to medications. This helps them to lower risk associated with the condition such as stroke and heart failure. Such interventions lowers costs incurred during screening, purchase of drugs, time consumed during clinic visits (Moss 321). For example, International Drug price indicator Guide indicated the annual cost of 40mg Lovastatin have ranged from US$14 in Barbados to US$217 in Costa Rica. The annual personal cost on medication in a year was US$1000 in a year by 2002. However, the drugs are becoming increasingly affordable today. For community based interventions can be done through educative programs. Lastly, more research on ideal hypertension therapy combination for every individual should be done. This should be done principally on cost, tolerability and ability to lower risk factors levels (Management sciences for health 4).

Future Opportunities in Hypertension

Hypertension is known to be the leading factor for cardiovascular morbidity and mortality as well as the renal failure. For example, Hypertension condition has affected about 24% of US population. As already described above, the regulation of blood pressure is a complex system involving multiple genes. However, some of the pathways of blood pressure regulation have been described in humans and other experimental models. Identifying genes that are responsible for blood pressure in populations have been a major challenge. Recent investigations are hypothesizing on the free association of scans and the genome (genome wide association studies, GWAS) to identify new loci for hypertension susceptibility and Blood pressure distribution. There are several collaboration studies on blood pressure traits going on with expectations to publish the next genetics findings that might provide new insights biology of blood pressure regulation; and provide more suggestions on therapy to reduce negative drug response and population risks (Franceschini, Reiner and Heiss 2010).

Studies done on genome wide association studies have flooded the literature. This has informed us regarding the identified causative genetic risk factors for hypertension and cardiovascular diseases. More so, the slow moving tide of the classical candidate gene approach progress in the attempt to clarify the interaction between gene function and pathogenesis of hypertension. From the studies, it is evident that genetic factors have role in blood pressure and hypertension (Bray 658).

To start with the normal distribution of blood pressure in the population shows that there are multiple environmental and genetic factors, hence a polygenic aetiology. Thus, it can be hypothesized that minor variations in the genes contributes to the common hypertension. More so, studies from twins and family aggregation studies have confirmed the presence of heritable component. It has also been identified that almost 30% of variation in blood pressure is due to genetic factors. Offspring’s from two hypertensive parents are likely to have hypertension (Padmanabhan et al. 219).

The most measures used are the determination of heritability which can be defined as the fraction of variation in disease susceptibility due to genetic factors. Sibling’s recurrent risk is defined as the risk of a disease for a sibling of an infected individual in comparison to other members of the general population. Following the derath of positive results from GWAS of hypertension and blood pressure, there are advancement and achievements in the recent studies. This is viewed as optimism guidance for progression of genomics work. The key question is what way do researchers in genomics follow? To start with, they should increase the likelihood of detecting genetic effects through recruitment of hyper controls and subjects with severe hypertension. This will ensure that there is a high fidelity in phenotyping and in all overall study design. This is especially when comparing results from cases and controls of extremities. The effort will facilitate in reduction of miscalculations and biased (Eischer et al. 450)

Most of the unexplained variation in blood pressure may be due to rare variants that are undetectable through traditional GWAS case control study design. However, intensively genotyped samples are now available from the 1000 Genomes Project. This project is run by an international consortium and their aim is to describe over 90% genetic variation to 1%MAF. The consortium has sequenced genomes of more than 1000 individuals. The resource is meant to facilitate study of low frequency variants and aid fine mapping of regions of interest. More so, the next generation is lucky due to the progression of deep sequencing technology which will be able to increase the chances of rare variants detection. All this is carried out with the aim to improve hypertension diagnosis and treatment (Welcome Trust Case Consortium 679).

The future of hypertension pharmakogenomics is great only if focus is shifted to functional genetic variants and haplotypes to establish accurately gene variation at a locus. The method can be done through chip based genotyping. Cooperation by the pharmaceutical industries will help substantially. For example, clinical evaluation of anti-hypertensive drugs to determine drug efficacy can be done simultaneously with cohort study to determine who will respond better to the agents. Such studies help in identifying genetic determinants responsible for the various responses to anti-hypertensive agent. More so, clinical research works like that of O’Shaughnessy et al coupled by accurate monitored subsequent blood pressure response for any introduction or addition of anti-hypersensitive drugs will yield substantial information to facilitate progression in the identification of the genetic factors (Padmanabhan et al. 13).


Adeyemo et al. “A genome wide association study of hypertension and blood pressure in African American.” PlosGenet 5.7 (2009): 1. Print.

Aschebrenner, Diane and Venable, Samantha. Drug therapy in nursing. New York, NY: Lippincott Williams and Wilkins, 2008. Print.

Aslanyan, Stella., Weir, Christopher., Lees, Kkennedy., Reid, John and McInnes, Gordon. “Effect of area based deprivation on the severity subtype and outcome of ischemic stroke.” Stroke 34.11 (2003): 2623-2628. Print.

Binder, Alexander. “A review of genetics essential hypertension.” Curr Opin Cardiol 22.3 (2007): 176-184. Print.

Bray, Molly. “Association and linkage analysis of the alpha adducing gene and blood pressure.” Am J hypertension 13.6 (2000): 698-703. Print.

Brewster et al. “Sytematic review.antihypertensive drug therapy in black patients.” Annals Internal Medicine 141.8 (2004): 614-627. Print.

Chapman et al. “Predictors of antihypertensive response to a standard dose of hydrochlorothiazide for essential hypertension.” Official Journal of the International Society of Nephrology 61.3 (2002), 1047-1055. Print.

Diez, Rave. “Residential environments and cardiovascular risk.” Journal of urban health 80.4 (2010): 569-589. Print.

Franceschini, Noran., Reiner, Alexander and Heiss, Gerrdo. “Recent findings in the genetics of blood pressure and hypertension traits.” American Journal of Hypertension 1.1 (2010): 1. Print.

Goldstein, David and Cavalleri, Gianpiero. “Understanding human diversity.” Nature 1.1 (2005): 1241-1242. Print.

Goodman, Alan. “Why genes don’t count (for racial differences in health).” AMJ Public Health 1.1 (2000): 1699-1702. Print.

International Human Genome Sequencing Consortium. “Initial sequencing and analysis of human genome.” Nature 409 (2001): 860-921. Print.

Levy et al. “Evidence for gene influencing blood pressure on chromosome. 17. Genome scan linkage results for longitudinal blood pressure phenotypes from the Framingham heart study.” Hypertension 36.4 (2000): 477-483. Print.

Lifton, Richard. “Molecular genetics of human blood pressure variation science.” Science 272.5262 (1996): 676-680. Print.

Mensah et al. “State of disparities in cardiovascular health in the US.” Circulation 111.10 (2001):1233-1241. Print.

Moss, Nan. “What are the underlying sources of racial differences in health?” Annals of Epidemiol 7 (1997): 320-321. Print.

Munroe, Caulfield. “Genetics of hypertension.” Curr Opin GENET Dev 10 (2000): 325-329. Print.

Nebert, Walter. “Pharmacogenetics and pharcogenomics: Why is this relevant to the clinical geneticists?” Clinic Genet 56 (1999): 247-258. Print.

Norman, Kaplan and Weber, Michael. Hypertension essentials. New York, NY: Jones and Bartlett learning Sudbury, 2009. Print.

Padmanabhan et al. “Genetic factors in hypertension.” Arch. Med.Sci 9.5 (2009): S212-S219. Print.

Padmanabhan, Sandosh., Paul, Laura and Anna, Dominzak. “The pharmarcogenomics of anti hypertensive therapy.” Pharmaceuticals, 3 (2000): 1779-1791. Print.

Pickering, Tom. “Cardiovascular pathways: socioeconomic status and stress effects on hypertension and cardiovascular function.” Annals of the New York academy of sciences 896 (1992): 262-277. Print.

Reddy, Kranthikumar. “Cardiovascular disease in non- western countries.” NEnglJ med (2004): 1. Print.

Ruthwell, Peter. “Limitation of the usual blood pressure of variability, instability and episodic hypertension.” Lancet 375 (2010): 938-948. Print.

Venkatesh, Aiyagari and Gorelick, Philip. Hypertension and stroke. Pathophysiology and management. New York, NY: Springer, 2010. Print.

Find out your order's cost