Treatment Of Essential Hypertension Research Articles

52. Sympathetic and cardiovascular reactivity during mental stress in patients with essential hypertension

Essential hypertension (EH) has been associated with abnormal sympathetic outflow particularly during mental stress. However data were unclear because of associated pharmacological drugs often taken by patients. The aim of this study is to ascertain abnormalities of sympathetic during mental stress in patients with untreated EH. We studied 7 untreated patients with established criteria for EH, and 10 sex and age matched healthy subjects. Patients with EH underwent an extensive laboratory screening excluding secondary causes of hypertension. Subjects underwent sitting microneurographic recording of muscle sympathetic activity (MSNA) from peroneal nerve, heart rate (HR) and blood pressure (BP) during resting state and mental stress (3-min of paced auditory serial arithmetic test -PASAT) and a cold test (two minutes immersion of a hand in ice water). The pharmacological treatment for EH was usually started after the microneurographby evaluation. As expected EH patients showed increased resting BP compared to controls but MSNA was not significantly increased although showed a tendency toward the increase. During mental stress BP was increased compared to controls but HR and MSNA did not show a significant difference. Sympathetic and cardiovascular parameters did not differ during cold test. Our data confirmed the higher BP reactivity in EH patients but this was not due to increased MSNA. However these data are preliminary and a larger cohort of patients must be recruited before drawing a definite conclusion.

Effects of traditional Chinese patent medicine on essential hypertension: a systematic review.

Traditional Chinese patent medicine (TCPM) is widely used for essential hypertension (EH) in China. However, there is no critically appraised evidence, such as systematic reviews or meta-analyses, regarding the potential benefits and disadvantages of TCPM to justify their clinical use and recommendation. The aim of this review was to systematically evaluate and meta-analyze the effects of TCPM for EH.Seven databases, the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Chinese Biomedical Literature Database, and the Wanfang Database, were searched from their inception to August 2014 for relevant studies that compared one TCPM plus antihypertensive drugs versus antihypertensive drugs alone. The methodological quality of the included trials was assessed using the Cochrane risk-of-bias tool. The primary outcome measures were mortality or progression to severe complications and adverse events. The secondary outcome measures were blood pressure (BP) and quality of life (QOL).Seventy-three trials, which included 8138 patients, on 17 TCPMs were included. In general, the methodological quality was low. Two trials evaluated the effects of TCPMs on mortality and the progression to severe complications after treatment, and no significant difference was identified compared with antihypertensive drugs alone. No severe adverse events were reported. Thirteen TCPMs used in complementary therapy significantly decreased systolic BP by 3.94 to 13.50 mmHg and diastolic BP by 2.28 to 11.25 mmHg. QOL was significantly improved by TCPM plus antihypertensive drugs compared with antihypertensive drugs alone.This systematic review provided the first classification of clinical evidence for the effectiveness of TCPM for EH. The usage of TCPMs for EH was supported by evidence of class level III. As a result of the methodological drawbacks of the included studies, more rigorously designed randomized controlled trials that focus on mortality and cardiovascular events during long-term follow-up are warranted before TCPM can be recommended for hypertensive patients. Two TCPMs, Song ling xue mai kang capsules and Yang xue qing nao granules, should be prioritized for further research.

Pathogenesis of essential hypertension: Development of a 4-dimensional model

Essential hypertension (EH) is regarded as a multifactorial and poly- genic disease, and its underlying mecha- nism is very complex. A new model of EH pathogenesis was developed in the pres- ent work. This model is suitable for the study, diagnosis, treatment, and preven- tion of EH. It incorporates not only genetic and environmental factors, but also com- pensatory and time factors as the third and fourth types of factors that contribute to the development of EH. Compensatory factors are defined here as specific blood pressure (BP) regulators, the ability of the body to regulate BP, and the process of BP regulation. Time factors include the age of the patient and the duration of EH in that patient. Over time, genetic, environmental, compensatory, and time factors are dy- namic. In this way, the development of EH is influenced by the interactions between these four factors. Herein, a 4-dimension- al (4-D) model of EH pathogenesis is de- scribed, including primary approaches and technical considerations. The 4-D model will be useful in understanding the pathogenesis, diagnosis, treatment, and prevention of EH.

Tianma Gouteng Yin as Adjunctive Treatment for Essential Hypertension: A Systematic Review of Randomized Controlled Trials

Background. Tianma Gouteng Yin (TGY) is widely used for essential hypertension (EH) as adjunctive treatment. Many randomized clinical trials (RCTs) of TGY for EH have been published. However, it has not been evaluated to justify their clinical use and recommendation based on TCM zheng classification. Objectives. To assess the current clinical evidence of TGY as adjunctive treatment for EH with liver yang hyperactivity syndrome (LYHS) and liver-kidney yin deficiency syndrome (LKYDS). Search Strategy. 7 electronic databases were searched until November 20, 2012. Inclusion Criteria. RCTs testing TGY combined with antihypertensive drugs versus antihypertensive drugs were included. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 22 RCTs were included. Methodological quality was generally low. Except diuretics treatment group, blood pressure was improved in the other 5 subgroups; zheng was improved in angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and “CCB + ACEI” treatment groups. The safety of TGY is still uncertain. Conclusions. No confirmed conclusion about the effectiveness and safety of TGY as adjunctive treatment for EH with LYHS and LKYDS could be made. More rigorous trials are needed to confirm the results.

Essential hypertension

Essential hypertension (EH) is characterized by chronic elevation of blood pressure (BP) due to an unknown etiology. It affects nearly 95% of hypertensive patients [1]. Genetic causes account for about half of EH (see below). In the US, more than 65 million adults have EH [2]. Since EH is usually asymptomatic and requires lifelong treatment; as a result, only 70% of these people become aware that they have elevated BP, only 59% are being treated, and only 34% have well controlled BP [2]. Sustained high BP due to undiagnosed, untreated or suboptimally treated hypertension leads to target organ damage. Epidemiological data indicate that EH is a major modifiable risk factor for coronary heart disease, stroke, congestive heart failure and renal failure [2]. Since its pathogenesis is left unclear, treatment of EH remains largely empiric, with physicians selecting one or several different kinds of antihypertensive medicines until BP is adequately controlled. Because of the high prevalence of EH, the inability to make treatment specifically directed at the underlying etiology, and the need for lifelong treatment and follow-up, the care of patients with EH has become one of the largest expenses in the American health care budget. In the past several decades, a wide variety of physiological studies have established that many signaling pathways affect short-term BP regulation [3]. These include the renin-angiotensin II(AII)-aldosterone system, sympathetic nerve-adrenergic receptor system, a series of genes participating in control of renal salt handling [4], endothelin (ET) and its A receptor (ETA) signaling in vascular smooth muscle (VSM) cells, pathways which all result in vasoconstriction, and factors produced by vessel endothelial cells that cause vasodilation (e.g. nitric oxide) (Figure 1). While the effect of these systems has been established for short-term BP regulation, determining which of these pathways contributes to EH as primary alterations or secondary responses has proven difficult. However, study of monogenic forms of EH has consistently shown that genetic hypertension originally derives from variations of genes involved in renal salt handling [3, 4]. Activation of any one of these pathways leads to resistance arterial remodeling and increased vascular tone, resulting in high BP. Once elevated vascular tone is established, it cannot be returned to the original normal point, even though available anti-hypertensive drugs alone or in combination can effectively and temporarily reverse the vascular tone to normal. The critical issue to be elucidated in the next decade is what common downstream gene activation in these signaling pathways triggers irreversible vascular remodeling, to cause a new set point for vascular tone. If a target gene responsible for the final common pathway converging from these different signaling systems is identified, a novel antihypertensive medicine against this gene activity could permanently alter vascular remodeling and reverse elevated vascular tone to normal. Such a therapy could replace lifelong treatment, which not only brings about a huge expense in health care, but also can cause lack of adherence and compliance to the medical regimen, leading to inadequate blood pressure control. Figure 1 This diagram depicts those different causal factors with ageing trigger vessel remodeling and permanently increased vascular tone leading to EH through unknown BP signaling molecules. ET: endothelin, ETA: ET receptor A, NO: nitric oxide Another important issue is what factors cause EH. With advances from molecular biology, it is well accepted that EH is an age-dependent, complex common trait resulting from the interaction of environmental, epigenetic and genetic determinants (Figure 1). However, the pathogenesis of EH is largely not understood despite intense efforts.

DNA Methylation and Essential Hypertension: A Review*

Essential hypertension (EH) is a complex disease caused by interaction of genetic and environmental factors. Increasing evidences suggest that hypomethylation of certain genes is involved in pathogenesis of EH. Alteration in methylation status affects expression of genes encoding 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2), endothelin converting enzyme-1 (ECE-1) and angiotensin Ⅱ receptor type 1b (AT1b) and hence results in hyperactivation of renin-angiotensin-aldosterone system and reduced renal sodium retention. Genomic hypomethylation can be induced by homocystine (Hcy). Study of metabolizing enzyme and receptor gene methylation regulation and its relation to antihypertensive effects will help understand the pathogenesis of EH and provide evidence for improving clinical treatment of EH.

Management of hypertension in chronic heart failure

Chronic heart failure (CHF) is associated with frequent hospitalizations and high mortality. It affects more than 5 million individuals in the USA, and another 660,000 new cases are diagnosed each year; overall, heart failure (HF) now accounts for 7% of all deaths from cardiovascular disease. Hypertension (HTN) increases the risk of development of HF and it precedes it in 75% of cases. HF patients are nearly evenly divided between those with reduced left ventricular (LV) function or systolic dysfunction and those with preserved LV systolic function or diastolic dysfunction. The management of HTN in patients with CHF is challenging. Drugs such as β-blockers, angiotensin-converting enzyme inhibitiors, angiotensin receptor blockers, aldosterone receptor blockers, hydralazine and nitrates, which have shown mortality benefit in CHF and exert antihypertensive effects, should be used as first-line agents to control HTN in CHF. In addition, antihypertensive drugs such as α-receptor blockers that can increase mortality in HF should be avoided. The dihydropyridine group of calcium channel blockers are good antihypertensive medications with a neutral effect on mortality in patients with CHF. These may be used in CHF patients with refractory HTN. In patients with HF with reduced ejection fraction, HTN is treated differently in comparison to patients with HF with normal ejection fraction. This article reviews the treatment of essential HTN in patients at risk for developing HF, in the presence of HF and the latest developments in treatment that might benefit both HTN and HF management.

An observational study of the medical events associated with clinician-initiated changes in treatment for essential hypertension.

We report a retrospective longitudinal observational study of co-morbidities and medical events associated with initiations and changes in antihypertensive therapy in 475 hypertensive patients of a large general practice. The median follow-up time was 7.0 years for males and 7.2 years for females. The data showed a low frequency of appropriate lifestyle recommendations (<30%), a gender-bias in lifestyle recommendations against women and that more than half of all patients' blood pressure (BP) was uncontrolled when last seen. Nearly half of all patients had co-morbidities relevant to essential hypertension (EHT) at first treatment for EHT and more than 11% of patients had more than one such co-morbidity. Whilst there was an increase in usage of ACE inhibitors and calcium channel blockers (CCB) as first treatment for EHT, there was also evidence that the existence of relevant co-morbidities rationally accounted for the majority of that increase. There were 5176 medical events relevant to EHT associated with change of drug or dosage treatment of EHT and the study provided evidence that the occurrence of such relevant medical events can rationally account for the majority of changes to EHT treatment. The study suggests that whilst general practitioners may fail to promote lifestyle changes to their patients with EHT, there is evidence that, when examined in sufficient detail, general practitioners' decisions to initiate changes in antihypertensive therapy are in keeping with the evidence base.

Effects of prolonged L-arginine administration on blood pressure in patients with essential hypertension (EH).

L-arginine (L-Arg) was administered intravenously through 4 consecutive days to 20 males (40-63 years old) with essential hypertension (EH). Significant decrease (p < 0.02) of systolic blood pressure (SBP) was observed only during the first day of the therapy and tachyphylaxis against L-Arg was noticed. The reduction of diastolic blood pressure (DBP) was more marked (p < 0.001). Significant changes in cGMP plasma level and the nitrite/nitrate urine concentration were not observed. L-Arg caused a significant activation of fibrinolysis (p < 0.005). The decrease of platelet activity, measured by the ADP-induced aggregation, after L-Arg administration was not statistically significant. Therefore, L-Arg may play only a secondary role in the treatment of EH.

Angiotensin II receptor blockade: an innovative approach to cardiovascular pharmacotherapy.

Through the multiple actions of angiotensin II (AII), the renin-angiotensin system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by binding to specific membrane-bound receptors, which are coupled to one of several signal transduction pathways. These AII receptors exhibit heterogeneity, represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major cardiovascular action of the RAS. This receptor has been cloned from multiple species, disclosing features consistent with a transmembrane, G-protein-linked receptor. Further AII receptor heterogeneity is evident by the cloning of isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor is the most direct site to inhibit the actions of the RAS. Many AII receptor antagonists, including peptide analogs of AII and antibodies directed against AII, possess unfavorable properties that have limited their clinical utility. The discovery and further development of imidazole compounds with AII antagonist properties and favorable characteristics, however, has promise for clinical utility. The leader in this field is a selective AT1 receptor antagonist losartan (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an effective antagonist of many AII-induced actions and an effective antihypertensive agent in many animal models of hypertension (HTN). Losartan also demonstrated secondary benefits in preventing stroke, treating congestive heart failure (CHF), and delaying the progression of renal disease in animal models. Clinical studies confirm the AII antagonist action of losartan and suggest that losartan will be effective in the treatment of essential HTN. AII antagonism is likely to provide useful treatment in essential HTN and CHF, conditions in which the RAS is known to play a major role. The utility of AII antagonism may extend beyond that of HTN and CHF, as suggested by the potential usefulness of angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of many other diseases. The key advantage AII antagonists provide over ACE inhibitors is that they may avoid unwanted side effects, related to bradykinin potentiation with the latter drugs. The AII antagonists will help determine the role of the RAS in physiologic regulation and in the pathophysiology of various disease states.

Magnesium and hypertension.

Essential hypertension (EHT) is one of the most common risk factors for cerebrovascular and cardiovascular disease (CVD), which in turn are among the most common causes of death and disability in developed countries. Drug treatment of EHT has proven effective in lessening the risk of CVD, but has attendant risk of side effects, some of which are of risk to the CV system. Thus, increasing attention is being paid to non-drug treatment of EHT, which includes changing the daily intake of such electrolytes as sodium (Na), potassium (K), calcium (Ca), and magnesium (Mg). Decreasing Na intake to control blood pressure (BP) is well established. On the basis of epidemiologic and experimental studies, increasing K and/or Mg intakes, and increasing of decreasing Ca intakes, have each been proposed to have beneficial effects of BP. Presented here is a review of the background data supporting the rationale for adding Mg to the anti-hypertensive regimen. There is evidence that Mg can exert a favorable effect in EHT, particularly when used in combination with K during diuretic therapy.