Renal function in primary hypertension

Studies of kidney cross-transplantation in the Milan hypertensive strain of rats (MHS) and in its control strain (MNS) have demonstrated that the kidney has a causal role in the development of hypertension in this animal model. The same result was obtained in two other strains of rats with genetic hypertension. Patients receiving a kidney from a donor with hypertensive parents require more antihypertensive therapy than recipients of a kidney from a donor with a normotensive family. When MHS rats and a subset of patients with primary hypertension were compared with their appropriate controls, similar changes in kidney function and Na–K–Cl cotransport were observed. Offspring of hypertensive parents exhibit altered kidney function compared with their controls. Na–K–Cl co-transport in MHS rats is genetically determined and genetically associated with hypertension. In MHS rats the increase in Na–K–Cl co-transport seems to be linked to a cytoskeletal protein, adducin. In conclusion, a consistent sequence of events from a protein abnormality to cell and renal dysfunction may be proposed as being responsible for hypertension.     

Influence of PRKCH gene polymorphism on antihypertensive response to amlodipine and telmisartan

This study aimed to evaluate the effect of PRKCH rs2230500 genetic polymorphism on efficacy of amlodipine and telmisartan for patients with hypertension. A total of 136 essential hypertension (EH) patients were treated with amlodipine (70 patients) or telmisartan (66 patients), respectively. Genetic polymorphism was genotyped by Sanger sequencing. Both baseline and post-treatment blood pressure (BP) and heart rate were measured to evaluate the influence of genetic polymorphism on the antihypertensive response. No significant difference in the absolute decrease in diastolic blood pressure (DBP),systolic blood pressure (SBP), and mean arterial pressure (MAP) was observed among PRKCH rs2230500 genotypes after 4-week amlodipine or telmisartan therapy (p > 0.05). However, when compared with carriers or GG genotype, the antihypertensive effect of PRKCH rs2230500 GA/AA carriers was superior in telmisartan treatment group. PRKCH rs2230500 gene polymorphism is significantly related to the efficiency in telmisartan therapy (p = 0.02). The PRKCH rs2230500 may influence the antihypertensive efficacy of telmisartan in Chinese EH patients, and further studies are needed to confirm these findings.     

Effects of guanethidine and methyldopa on a standardized test for renin responsiveness.

A standardized test for renin responsiveness, employing the dual stimulus of upright posture and the loop diuretic furosemide, was applied to 19 hypertensive patients in the untreated state and during therapy with the antihypertensive agents guanethidine and methyldopa. During therapy with guanethidine, 6 of 10 patients with "low-renin essential hypertension" experienced elevations of plasma renin activity to levles ordinarily diagnostic of "normal-renin" hypertension (P less than 0.05), whereas methyldopa had no significant effect on plasma renin activity in either "low-renin" or "normal-renin" patients. It is suggested that methyldopa has a negligible influence on renin responsiveness when stimulated under the above conditions and that it may be used during assessment of plasma renin activity in hypertensive patients whose blood pressure is too severely elevated for temporary withdrawal of therapy.     

Effects of antihypertensive drugs and gene variants in the renin-angiotensin system.

Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient's blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ABP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion I allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the antihypertensive therapy, the determination of genotype might be of help in the management of essential hypertension.     

Gene markers and antihypertensive therapy

Increasingly, detailed characterization of human molecular genetic variation will facilitate the use of genetic information in preventing, diagnosing, and treating common diseases. One promising application is the identification of genetic variants influencing responses to drugs used to lower blood pressure (BP) and prevent target-organ complications of hypertension. This update on gene markers to guide antihypertensive therapy highlights polymorphisms recently reported to predict interindividual differences in response to antihypertensive medications. However, single-site variation in most genes makes only a small contribution to differences in BP response, and, after all known genetic and environmental predictors have been considered, most variation in responses still remains unexplained. Advancing beyond our current "trial-and-error" approach to selecting drug therapy in individual patients will undoubtedly require whole-genome approaches to discover additional, novel genetic pathways influencing drug response. In addition, larger samples will be required to more fully characterize genetic variation within candidate genes and to consider the joint effects of gene-gene and gene-environment interactions. Eventually, knowledge of genetic variants that influence BP responses may allow more individualized tailoring of therapy to optimally reduce BP and target-organ damage.     

浙江景宁人群中α-内收蛋白基因Gly460Trp多态性与外周及中心动脉血压的关系

目的探讨在中国畲族人群中α-内收蛋白基因Gly460Trp多态性与外周及中心动脉血压的关系。方法在浙江省景宁县随机选择6个村,以核心家系为单位募集人群样本,运用水银柱血压计听诊法连续测量坐位非优势臂血压5次,取平均值用做统计分析。运用标准化问卷收集饮酒、吸烟、高血压用药史。采用SphygmoCor动脉脉搏波分析仪测量中心动脉血压。采集静脉血,分离DNA,以限制性酶切长度多态性方法检测α-内收蛋白基因的基因型。使用方差分析、广义估计方程(generalizedestimatingequations,GEE)进行关联分析。结果442例受检者中包括230例(52·0%)女性,116例(26·2%)高血压患者,其中49例(11·1%)服用抗高血压药物。α-内收蛋白GlyGly、GlyTrp、TrpTrp三个基因型的频率分别为21·3%、54·5%和24·2%。α-内收蛋白Gly460Trp多态性与肱动脉收缩压、舒张压及脉压无显著性关联,但在调整性别、年龄、年龄2、体重指数、有无吸烟、饮酒、抗高血压药物治疗等协变量前后,该多态性与中心动脉收缩压及中心脉压均有显著相关性(P<0·02)。GlyGly、GlyTrp、TrpTrp三个基因型的中心动脉收缩压分别为(122·5±3·5)mmHg、(114·1±1·5)mmHg、(109·1±1·8)mmHg(P=0·01)。相应的中心脉压值分别为(39·4±1·3)mmHg、(36·4±1·0)mmHg、(32·9±0·9)mmHg(P=0·002)。结论在浙江景宁畲族人群中,α-内收蛋白基因Gly460Trp多态性与中心动脉的收缩压及脉压有显著相关性,Trp等位基因可能对中心动脉血压增高有保护作用。     

Progression of kidney disease in type 2 diabetes – beyond blood pressure control: an observational study

Background

Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies.

Methods

The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used.

Results

No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P =.08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype.

Conclusion

The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with increased risk for hypertension.     

Implementing ABPM into Clinical Practice

Purpose of Review

To review the data supporting the use of ambulatory blood pressure monitoring (ABPM), and to provide practical guidance for practitioners who are establishing an ambulatory monitoring service.

Recent Findings

ABPM results more accurately reflect the risk of cardiovascular events than do office measurements of blood pressure. Moreover, many patients with high blood pressure in the office have normal blood pressure on ABPM—a pattern known as white coat hypertension—and have a prognosis similar to individuals who are normotensive in both settings. For these reasons, ABPM is recommended by the US Preventive Services Task Force to confirm the diagnosis of hypertension in patients with high office blood pressure before medical therapy is initiated. Similarly, the 2017 ACC/AHA High Blood Pressure Clinical Practice Guideline advocates the use of out-of-office blood pressure measurements to confirm hypertension and evaluate the efficacy of blood pressure-lowering medications. In addition to white coat hypertension, blood pressure phenotypes that are associated with increased cardiovascular risk and that can be recognized by ABPM include masked hypertension—characterized by normal office blood pressure but high values on ABPM—and high nocturnal blood pressure. In this review, best practices for starting a clinical ABPM service, performing an ABPM monitoring session, and interpreting and reporting ABPM data are described.

Summary

ABPM is a valuable adjunct to careful office blood pressure measurement in diagnosing hypertension and in guiding antihypertensive therapy. Following recommended best practices can facilitate implementation of ABPM into clinical practice.

     

内收蛋白与高血压

综述了内收蛋白的生物学研究进展及其遗传学改变与原发性高血压发生之间的关系 ,主要内容有 :内收蛋白的生化结构、组织分布、生物学功能及其调节 ;内收蛋白基因多态性与高血压大鼠动物模型和人类原发性高血压发病之间的关系 ,以及内收蛋白基因改变引起高血压的可能机制。     

Daily sodium intake influences the relationship between angiotensin‐converting enzyme gene insertion/deletion polymorphism and hypertension in older adults

The angiotensin‐converting enzyme insertion/deletion (I/D) gene polymorphism has been widely reported as being associated with hypertension; however, most studies do not consider environmental/behavioral factors. This study aimed to investigate the relationship among angiotensin‐converting enzyme insertion/deletion gene polymorphism, environmental/behavioral factors, and hypertension in community‐dwelling elderly individuals. All community‐dwelling older adults from Aiquara, Bahia, Brazil, were invited to take part in this study. After exclusions, 234 elderly participants were submitted to a data collection, which included sociodemographics, lifestyle and health status questionnaires, clinical assessment, and blood withdrawal. From the blood samples, the gene polymorphism was identified through polymerase chain reaction and patients grouped as II or D allele carriers (ID and DD genotypes). Hypertension was defined by self‐report of the condition and confirmed by antihypertensive drug treatment. Chi‐square test was used to identify differences in the proportions distributed between groups of each dependent variable (ie, genotype, diagnosis of hypertension, and blood pressure state from medicated patients with hypertension). The prevalence of hypertension was 59.3% and was associated with diabetes mellitus and obesity, but not with angiotensin‐converting enzyme insertion/deletion gene polymorphism. However, carriers of the II genotype, a salt‐sensitivity genotype, exhibited a significantly greater estimated sodium intake. In addition, among medicated elderly patients with hypertension, II genotype carriers exhibited poor blood pressure control, despite similar antihypertensive drug treatment in D allele carriers, while exhibiting a greater estimated sodium intake. Our results provide new evidence regarding the interaction of genetic and environmental/behavioral factors in the genesis of hypertension among elderly patients, as well as in blood pressure control in medicated elderly patients with hypertension.     

The Burden of Uncontrolled Hypertension: Morbidity and Mortality Associated With Disease Progression

Even small elevations above optimal blood pressure values (<120/80 mm Hg) increase the likelihood of developing hypertension (blood pressure 140/90 mm Hg) and incurring target organ damage. Until recently, the main emphasis in hypertension treatment had been lowering diastolic blood pressure; however, in the past decade, the important contributions of systolic hypertension, increased pulse pressure, and a blunted reduction in nocturnal blood pressure have been described. Primary hypertension arises from complex, interrelated pathologies. Among the contributors are genetic, environmental, metabolic, vascular, and endothelial factors. Signs of target organ damage herald a poorer prognosis and may present in the heart, blood vessels, kidneys, brain, or eyes. Later consequences include cardiac, cerebrovascular, vascular, and renal morbidities and death. The goal in treating hypertension is to prevent cardiovascular and renal complications. Thus, hypertensive patients with high-normal blood pressure values may benefit from intensive lifestyle interventions to further reduce blood pressure. This is particularly true in patients with additional cardiovascular risk factors. Because of the complex nature of hypertension, it is not surprising that single antihypertensive agents normalize blood pressure for less than a majority of hypertensive patients. Using combination antihypertensive therapy consisting of agents from two or more different antihypertensive drug classes not only increases the likelihood of achieving the target blood pressure goal, but also offers the potential for greater protection against target organ damage by targeting separate pathologic mechanisms.     

Stress,Genes, and Hypertension. Contribution of the ISIAH Rat Strain Study

Purpose of Review

Acute psychoemotional stress is one of the causes of a sharp increase in blood pressure. However, the question if the stress may promote the hypertensive disease development is still open. This review aims, firstly, to show that the genetically determined enhanced responsiveness to stress is linked to sustained hypertension development and, secondly, to characterize the main physiological mechanisms and genetic factors implicated in the pathogenesis of stress-sensitive hypertension.

Recent Findings

Recent findings helped to characterize the main neuroendocrine mechanisms and the specificity of the genetic background contributing to the stress-sensitive hypertension development in the ISIAH rats.

Summary

The ISIAH rat strain, which is an original model of the stress-sensitive arterial hypertension, can be considered as “living” proof that the genetic predisposition to increased stress-reactivity can lead to the development of persistent stress-dependent arterial hypertension. The ISIAH rat strain is characterized by the genetically determined enhanced response of the neuroendocrine and renal regulatory systems to stress and is a suitable model that allows one to explore the genetic and physiological mechanisms involved in stress-sensitive hypertension development. There are common genetic loci (QTLs) associated with both basal and stress-induced blood pressure (BP) levels as well as QTLs associated with BP and other traits, which may be related to hypertension development in ISIAH rats. Multiple genes differentially expressed in the target organs/tissues of hypertensive ISIAH and normotensive control rats are associated with many biological processes and metabolic pathways involved in stress response and arterial hypertension. The genotype of ISIAH rats is characterized by numerous specific and common SNPs as compared with other models of hypertensive rats. The results of the studies are valuable for the search for genetic markers specific for stress-induced arterial hypertension, as well as for the selection of new molecular targets that may be potentially useful for prevention and/or therapy of hypertensive disease.

     

Management of hypertension in elderly long-term care residents

OBJECTIVE:

To determine the adequacy of hypertension management in institutionalized elderly patients.

METHODS:

Retrospective chart review of all patients with a physician-documented diagnosis of hypertension at 15 long-term care facilities in Edmonton, Alberta.

RESULTS:

Of 2063 long-term care residents, 733 (36%) were diagnosed with hypertension (mean age 84 years), and 566 (77%) of this cohort were receiving antihypertensive medication. The most frequently prescribed antihypertensive drugs were angiotensin-converting enzyme inhibitors (341 patients [60%]). Of the long-term residents prescribed antihypertensive therapy, 274 (48%) were on one medication, 203 (36%) were on two and 89 (16%) received three or more agents. Blood pressure readings were taken every 14 days on average (interquartile range two to 31 days). Overall, 467 (64%) of these residents with a diagnosis of hypertension achieved target blood pressure.

CONCLUSION:

Hypertension treatment and control rates are better in elderly patients who are institutionalized than those reported in studies of patients who reside in the community. Determining the reasons for this discrepancy will be important for the design of strategies to improve hypertension control rates in the community.     

Hypertension in Pediatric Dialysis Patients: Etiology,Evaluation, and Management

Purpose of Review

Review epidemiology, pathophysiology, and management of hypertension in the pediatric dialysis population.

Recent Findings

Interdialytic blood pressure measurement, especially with ambulatory blood pressure monitoring, is the gold standard to assess for hypertension. Tools to assess dry weight aid in achievement of euvolemia, the primary therapy for management of hypertension. Persistent hypertension should be treated with antihypertensive medications and potentially with native nephrectomies.

Summary

Cardiovascular disease continues to be the primary cause of morbidity and mortality in the dialysis population with hypertension as an important modifiable factor. Achievement on dry weight and limiting both aggressiveness of interdialytic weight gain and ultrafiltration rate underlie the best approach. Tools to assess volume status beyond clinical assessment have shown promise in achieving euvolemia. When hypertension persists despite achievement of euvolemia, antihypertensive medications may be required and in some cases native nephrectomies. Future studies in children are needed to determine the best antihypertensive class and ideal rate of ultrafiltration on hemodialysis towards achievement of normotension and reduction of cardiovascular risk.

     

Hypertension in the elderly: can we improve results of therapy?

Awareness of and therapy for hypertension in the United States have been increasing in older patients. Despite this improvement, hypertension continues to be poorly controlled in this patient population. The control rate, defined as systolic blood pressure less than 140 mm Hg and diastolic blood pressure less than 90 mm Hg, is surprisingly low for older patients, despite abundant data documenting the reduction of cardiovascular events by treating both systolic-diastolic and isolated systolic hypertension. Comorbid diseases and physiological alterations in the elderly, including reduced myocardial contractility, renal function, total body water, baroreceptor responsiveness, and cognitive function, must be considered, but in general these have not limited the effectiveness of antihypertensive drug therapy.     

Hypertension and SNP genotyping in antihypertensive treatment

Hypertension is prevalent, affecting approx 20–25% of the adult population in the Western world. Primary hypertension is a multifactorial, complex disorder where many genes and genetic variants are assumed to interact with environmental factors in order to produce the specific blood pressure level for a given individual. Family and twin studies show that between 30 and 60% of blood pressure variation is determined by genetic factors. Monogenic disorders of hypertension are rare and do not explain blood pressure variability in the population at large. Obvious candidate genes for the study of hypertension are those that encode components of a blood pressure regulating system targeted by an antihypertensive drug, or those that are involved in counterregulatory systems. In this review, we give a brief pathophysiological blackgroud to hypertension and the rational behind utilizing SNP genotyping in the study of hypertension and the antihypertensive response to treatment. We also discuss some of the novel results of pharmacodynamic studies in antihypertensive treatment, an area in its infancy.     

Perceived symptoms amongst hypertensive patients in routine clinical practice – a population-based study

Kjellgren KI, Ahlner J, Dahlöf B, Gill H, Hedner T, Säljö R (Faculty of Health Sciences, Linköping; Sahlgrenska University Hospital, Göteborg; and Linköping University, Linköping, Sweden). Perceived symptoms amongst hypertensive patients in routine clinical practice – a population-based study. J Intern Med 1998; 244 : 325–332.

Objectives

.To compare perceived symptoms between patients undergoing antihypertensive therapy and hypertensive patients without drug treatment, and to assess reasons for change of antihypertensive medication in routine clinical practice.

Design

.Population-based multicentre study. Consecutive patients from a randomized sample of centres were given a standardized questionnaire to assess symptoms as well as opinions about their antihypertensive drugs.

Setting

.Fifty-five Swedish primary health care centres and 11 clinics of internal medicine.

Patients

.One thousand and thirteen hypertensive patients on their individually prescribed antihypertensive medication and 135 without antihypertensive therapy.

Main outcome measures

.Prevalence and perception of symptoms with and without antihypertensive drug therapy, changes of medication and reasons for this.

Results

.Amongst the group of patients on antihypertensive medication, 57% spontaneously reported having had symptoms of high blood pressure before they started their drug therapy. Amongst the patients without antihypertensive drugs, 52% reported having such symptoms. When answering direct questions about different symptoms related to current drug treatment or increased blood pressure, patients with and without medication reported symptoms to a similar extent: 80 and 85%, respectively. A majority of patients (64%) had changed their medication during the course of treatment (range 0–61 years). The mean number of changes was 2.4 times over 12 years. The most common reported cause for changing drug treatment was side-effects (42%).

Conclusions

.The study shows that patients in general perceive symptoms from hypertension. Antihypertensive medication decreases the frequency and intensity of symptoms that might be related to high blood pressure but adds other symptoms linked to the medication. Changes in medication were mostly related to side-effects. The follow-up should pay attention to patients' experience of treatment. A sign of a well-managed hypertension population would be a decrease of symptoms over time.

     

Characteristics of hypertensive Canadians not receiving drug therapy

BACKGROUND:

Many Canadians known to have hypertension remain untreated. To aid in the development of specific programs to improve hypertension management, the present report characterizes Canadians who indicated that they had hypertension but were not taking antihypertensive drug therapy.

METHODS:

The 2005 Canadian Community Health Survey (cycle 3.1) was used to estimate the proportion of Canadians 20 years of age and older who reported having high blood pressure or ever being diagnosed with high blood pressure. Sociodemographic characteristics, reported health, lifestyle factors and health care resource use of those who reported taking or not taking high blood pressure medication in the previous month were described and compared.

RESULTS:

Over one-half of hypertensive respondents 20 to 39 years of age reported no antihypertensive treatment compared with 17% and 5% among those 40 to 59 years and 60 years of age and older, respectively. In most age groups, several factors were associated with the absence of pharmacotherapy (eg, male sex, fewer health care professional consultations, perceived excellent health status and most markers of lower cardiovascular risk, with the exception of daily smoking). The proportion of young hypertensive Canadians not receiving pharmacotherapy remained consistent, regardless of the presence of cardiovascular risk factors.

CONCLUSIONS:

Many hypertensive Canadians, particularly those who are younger than 60 years of age, are not taking antihypertensive drug therapy despite having one or more cardiovascular risks. The increased risk of no drug therapy among smokers warrants special attention.     

Use of gene markers to guide antihypertensive therapy

Sequencing of the human genome has elevated the potential for genetic information to aid in the prevention, diagnosis, and treatment of common chronic diseases. One beneficial application of genetic information is the identification of variants that influence response to pharmaceutical agents used to lower blood pressure and prevent target organ complications of hypertension. Knowledge of genetic variants that influence blood pressure response to antihypertensive drugs may allow more individualized tailoring of antihypertensive drug therapy, and provide greater insight into the molecular mechanisms regulating blood pressure levels and causing hypertension.     

Therapierefrakt?re Hypertonie

Sympathetic overexpression can be found in a majority of hypertensive patients. Resistant arterial hypertension requires a targeted diagnostic procedure in order to exclude secondary causes of hypertension which can be treated specifically with established therapies. If secondary reasons are not identified, the antihypertensive medication is already optimal and lifestyle changes have been realized, but still the goal of antihypertensive therapy cannot be achieved, alternative invasive therapy strategies such as renal sympathetic denervation and baroreflex activation have been developed to achieve blood pressure control. These therapies are restricted to specialized centers which treat well-defined patients with therapy-resistant hypertension. Little long-term data concerning safety and efficacy are available for the two strategies. However, they should preferably be used as an ultima-ratio and add-on pathway to conservative procedures when established medication fails to achieve blood pressure control. To date, the effectiveness of the interventional antihypertensive therapies has only been shown on patients with systolic blood pressure over 160?mmHg and a mean oral medication of five drugs.