Effect of antihypertensive drug therapy on short‐term heart rate variability in newly diagnosed essential hypertension

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short‐term (5 min) heart rate variability (HRV) provides a non‐invasive probe of autonomic regulation of sino‐atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never‐treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (±SD) age 48 ± 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high‐frequency (HF) RR interval spectral power in the amlodipine + atenolol‐treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short‐term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol‐treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.     

高血压患者抗动脉粥样硬化治疗策略:降压联合降脂

高血压患者伴有高胆固醇血症时,其心血管疾病的发生危险将显著升高。同时治疗其高血压和高胆固醇血症可有更多获益,达到真正的抗动脉粥样硬化事件的作用,减少心脑血管疾病的发生。降胆固醇方案相同时,以氦氯地平为基础的降压方案的临床获益显著高于以阿替洛尔为基础的降压方案。并且,联合应用降雎及降胆固醇方案时,阿托伐他汀降胆固醇方案尽甲使用获益更多。     

Effect of rofecoxib on antihypertensive effects of candesartan in experimental models of hypertension

Given the high prevalence of hypertension, concomitant use of nonsteroidal anti-inflammatory drugs and antihypertensive medications is commonly encountered in clinical practice. The present study was designed to study the effect of indomethacin, nimesulide, and rofecoxib on blood pressure (BP) in normotensive and hypertensive rats and also to investigate the effect of rofecoxib on BP control in candesartan-treated hypertensive rats. Male Wistar rats weighing 150-200 g were divided into three groups: control, DOCA-hypertensive, and L-NAME-hypertensive rats. All the rats were given indomethacin (15 mg/kg body weight), nimesulide (20 mg/kg body weight), rofecoxib (10 mg/kg body weight), or vehicle orally and daily for 6 weeks. Hypertensive rats in separate groups were treated with either candesartan (1 mg/kg body weight) alone or a combination of candesartan (1 mg/kg body weight) and rofecoxib (10 mg/kg body weight) orally and daily for 6 weeks. BP measurements were performed using tail cuff method at baseline and 1-week intervals throughout the treatment period. All the three COX inhibitors resulted in increase in BP, but mean change in BP was the highest with rofecoxib. Rofecoxib-treated L-NAME-hypertensive rats exhibited a significant increase in mean arterial pressure at 6 weeks (168.3+/-5.7 mmHg) as compared with DOCA-hypertensive rats (128.818+/-7.2 mmHg). Administration of Rofecoxib L-NAME-hypertensive rats treated with candesartan resulted in a significant increase in BP. Systolic BP at 0 week (107.0+/-4.2 mmHg) rose to 141.6+/-2.0 mmHg at 6 weeks. Systolic BP at 2, 4, and 6 weeks was significantly higher as compared with (L-NAME+candesartan)- and (rofecoxib+candesartan)-treated group. In conclusion, concomitant use of rofecoxib resulted in poor BP control by candesartan in L-NAME-hypertensive rats.     

Combination antihypertensive therapy with valsartan and hydrochlorothiazide in Chinese patients with mild-to-moderate hypertension

ABSTRACT

Objectives: To compare the efficacy and safety of valsartan (VAL)/ HCTZ 80/12.5?mg with VAL 80?mg in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with VAL 80?mg alone.

Research design and methods: This was a multicenter, double-blind, double-dummy, randomized, active-controlled, parallel-group trial. Patients (1175) with mild-to-moderate essential hypertension (mean sitting diastolic blood pressure [MSDBP] ≥?95 and <?110?mmHg) from 26 centers in China received VAL 80?mg o.d. for 4?weeks, 864 patients whose MSDBP remained ≥?90 and <?110?mmHg were randomized (1:1) to receive VAL80/HCTZ12.5?mg (n?= 429) or VAL80?mg (n?= 435) for 8?weeks.

Main outcome measures: The efficacy variable was changed from baseline to endpoint in trough MSDBP. The secondary efficacy variables were changed in mean sitting systolic blood pressure (MSSBP), response rate, and control rate.

Results: Significant reductions in MSDBP and MSSBP from baseline to endpoint were observed in both groups. There were significantly greater reductions in MSDBP (8.4?mmHg vs. 6.2?mmHg) and MSSBP (10.2?mmHg vs. 6.7?mmHg), higher response (64.2% vs. 52.5%) and control rates (53.9% vs. 40.9%) in the VAL80/HCTZ12.5 group as compared with the VAL80 group at endpoint (?p?<?0.001). VAL80/HCTZ12.5 was equally effective in both age subgroups (≥?65 and <?65?years) and was well tolerated. There were no deaths and the two serious adverse events reported were unrelated to study medication.

Conclusion: In Chinese patients with mild-to-moderate essential hypertension not adequately controlled by VAL 80?mg alone, VAL80/HCTZ12.5?mg combination was well tolerated and showed additional BP reduction. The limitations of this study were the inability to include an HCTZ arm as a control group and the short trial duration.

Trial registration: NCT00250562.     

河南汉族人群抗高血压药物相关基因多态性与高血压发病及降压效果的关联研究

目的:研究抗高血压药物相关基因多态性在河南汉族人群中的频率分布,并探讨其与高血压发病的相关性,同时评价抗高血压药物基因检测的临床应用价值.方法:选取2019年1-12月郑州市中心医院确诊的526例原发性高血压患者作为高血压组,同时选取100例健康体检者作为对照组.应用PCR-荧光探针法对5类抗高血压药物相关的7个基因多...     

老年高血压的积极治疗与平稳降压

高血压是导致老年人心脑血管疾病发病率和病死率升高的主要危险因素之一。与年轻患者相比,老年高血压的发病机制、临床表现和预后等具有一定的特殊性,是一种特殊类型的高血压。治疗中应重视老年高血压的病理生理特点及特殊机制,实施个体化治疗。本文结合近年来国内外老年高血压的循证医学证据及诊治的新进展,综述有关临床治疗现状。     

Impact of increased heart rate on clinical outcomes in hypertension: implications for antihypertensive drug therapy

Thirty-eight studies have been published to date on the association between elevated heart rate and mortality. After adjustment for other risk factors, only two studies for all-cause mortality and four studies for cardiovascular mortality reported an absence of association between heart rate and mortality in male populations. This relationship has been found to be generally weaker among females. Most of these studies investigated samples of general populations. The four studies performed in hypertensive men found a positive association between heart rate and all-cause mortality (hazard ratios ranging from 1.9 to 2.0) or cardiovascular mortality (hazard ratios ranging from 1.3 to 1.7). In spite of this evidence, elevated heart rate remains a neglected cardiovascular risk factor in both genders. The pathogenetic mechanisms connecting high heart rate, hypertension, atherosclerosis and cardiovascular events have also been explicated in many studies. Elevated heart rate is due to an increased sympathetic and decreased parasympathetic tone. This altered balance of the autonomic nervous system tone could explain the increase in events with the increased heart rate. However, it has also been proved that blood flow changes associated with high heart rate favour both the formation of the atherosclerotic lesion and the occurrence of the cardiovascular event. Reduction of heart rate in hypertensive patients with increased heart rate could be an additional goal of antihypertensive therapy. Several trials retrospectively showed the beneficial effect of cardiac-slowing drugs, such as beta-adrenoceptor antagonists (beta-blockers) and non-dihydropyridine calcium channel antagonists, on mortality, notably in patients with coronary heart disease, but no published data are available in patients with hypertension free of coronary heart disease. Other antihypertensive drugs that have been shown to reduce the heart rate are centrally acting drugs and angiotensin II receptor antagonists, but their bradycardic effect is rather weak. The f-channel antagonist ivabradine is a selective heart rate-lowering agent with no effect on blood pressure. Although it has not been proven in existing trials, it would seem reasonable to recommend antihypertensive agents that decrease the heart rate in hypertensive patients with a heart rate higher than 80-85 beats per minute. Since the fast heart rate per se causes cardiovascular damage, all drugs that lower the heart rate have the potential of further reducing cardiovascular events in patients with elevated heart rate. Unfortunately, lowering of the heart rate is not a clinically recognised goal. Prospective trials investigating whether treatment of high heart rate can prevent cardiovascular events, notably in hypertensive patients, are warranted.     

妊娠期高血压疾病降压治疗的安全性探讨

目的对降压治疗妊娠期高血压疾病的安全性及有效性进行探讨。方法对2010年5月～2011年11月在本院就诊的100例妊娠期高血压患者的病例资料进行回顾性分析。通过随机方式将100例患者分为试验组和对照组,试验组患者40例,对照组患者60例。对照组接受传统常规降压药物进行治疗,试验组则通过静脉滴注和口服肼苯哒嗪及利血平等药物进行降压治疗。并对两组患者产后出血以及凝血功能情况进行及时的观察和记录。结果试验组40例患者经治疗后在产后出血以及凝血功能等方面均好于对照组,证明其治疗的安全性和有效性要好于传统方法。结论治疗妊娠期高血压疾病采用肼苯哒嗪、利血平等药物治疗效果较好,安全性高,值得应用。     

Effect of long-term eprosartan versus enalapril antihypertensive therapy on left ventricular mass and coronary flow reserve in stage I-II hypertension. Eprosartan Study Group

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. This paper reports the results of 27 asymptomatic patients who were recruited into a single centre substudy of the multicentre trial and randomised to receive either eprosartan (200-300 mg b.i.d.) or enalapril (5-20 mg o.d.). Blood pressure (BP) reduction, left ventricular (LV) mass regression and change in coronary flow reserve (CFR) after 6 months' treatment with either eprosartan or enalapril were compared. At the end of the study, eprosartan and enalapril were found to have caused similar reductions in BP. There was an increase in CFR in the eprosartan group to 1.6 +/- 0.3 and a decrease in CFR in the enalapril group to 1.3 +/- 0.3. Neither value was significantly different from baseline although the difference between the two groups was significant (p = 0.05). By study endpoint, there was a significant reduction in LV mass in the enalapril group (p = 0.05), but not the eprosartan (p = ns) group. Further investigation of the effects of angiotensin receptor blockers on CFR and LV mass regression appear warranted.     

Effect of food intake on plasma levels and antihypertensive response during maintenance therapy with endralazine

Summary A sensitive HPLC assay has been used to determine the effect of food on plasma endralazine levels in 8 patients with essential hypertension. Subjects were investigated whilst on maintenance therapy with endralazine combined with a fixed antihypertensive baseline treatment for at least 4 weeks, samples being collected after the usual oral morning dose of endralazine (5 mg and 10 mg), on two occasions at least 7 days apart. Endralazine was administered with the concomitant therapy in randomised order once 90 min before and once immediately after a standard breakfast. Acetylator status did not affect its pharmacokinetics in the postprandial study after a 5 mg dose, the peak endralazine concentration averaged 57.5% lower and the AUC had fallen significantly by 49.9%, whereas after 10 mg the postprandial peak level and the AUC were 82.9% and 64.7%, lower. In the 5 mg study the mean arterial blood pressure was decreased by 30 mm Hg in the fasting subjects and by 21 mm Hg in the post-prandial group. For the 10 mg dose the corresponding values were 35 and 24 mm Hg. The blood pressure lowering effect was only weakly correlated with the food — related reduction in the plasma endralazine levels. The results suggest that endralazine has a similar kinetic interaction with food as that found for hydralazine.     

Effect of systemic autonomic inhibition on the hemodynamic response to antihypertensive therapy with timolol

To evaluate the role of systemic autonomic tone in the hemodynamic response to beta-inhibitors, the hemodynamic effects of long-term timolol therapy were studied in hypertensive patients under two sets of conditions: at rest and after pharmacologic systemic autonomic inhibition (SAI). Hemodynamic studies were performed in every subject at the end of a 4-week placebo period and again at the end of a 9-week treatment period. The antihypertensive effect of timolol was associated with decreased cardiac output and unchanged peripheral resistance at rest and with unchanged cardiac output and decreased peripheral resistance after SAI. The hemodynamic response to SAI during the two studies was also markedly different. The findings provide evidence of increased alpha-adrenergic component of systemic autonomic tone during long-term therapy with timolol.     

The effects of antihypertensive therapy on haemostatic parameters

There is extensive trial-based evidence showing that antihypertensive drugs reduce the risk of vascular events (e.g. stroke and myocardial infarction) as well as target organ damage (e.g. left ventricular hypertrophy and microalbuminuria). However, some of these benefits appear to be, at least partially, independent of the extent of blood pressure (BP) lowering. It is also evident that in certain clinical situations some antihypertensive drugs are more effective than others. In this review we discuss the effects of antihypertensive drugs on the endothelium, platelets, fibrinolysis and coagulation. These properties may account for the observed BP-independent actions. Antihypertensive drugs exert multiple effects on the vascular endothelium. These include effects on nitric oxide (NO) and angiotensin II-mediated actions. Many BP lowering drugs can inhibit platelet activity, although the relevance of this property is unknown, especially if patients are also taking platelet inhibitors (e.g. aspirin). Antihypertensive drugs also influence fibrinolysis and coagulation. These effects may be mediated by a variety of mechanisms, including altering insulin sensitivity. The haemostatic actions of antihypertensive drugs deserve greater recognition and further investigation.     

抗焦虑治疗对降压效果的影响

目的:观察高血压伴有焦虑的患者中,抗焦虑治疗对药物效果的影响.方法:117例高血压患者根据焦虑自评量表(SAS)分为无焦虑组72例,伴有焦虑45例中再随机分为焦虑组22例.3组患者均给予依那普利5mg,每日2次,抗焦虑组同时加服抗焦虑药物治疗.4周后比较3组降压效果.结果:无焦虑组及抗焦虑组的收缩压(SBP)、舒张压(DBP)均有明显下降,而焦虑组下降较小,与前两组比较差异有显著性(P＜0.01).降压有效率,无焦虑组与抗焦虑组差异无显著性,分别为80.5%与81.8%.而焦虑组为52.17%,与前两组比较差异有显著性(P＜0.05).结论:焦虑情绪明显影响着降压药物的治疗效果,消除焦虑可明显提高药物的降压作用.提示高血压伴有焦虑的患者给予抗焦虑治疗是必要的.     

Recent advances in antihypertensive therapy

There are multiple different approaches that have been adopted in the past to cure hypertension. Hypertension is a multifactorial disease frequently associated with other cardiovascular problems. None of the antihypertensive drugs available can cure all cases of hypertension. This situation causes a unique scenario in this area of therapeutic research: less recent approaches, which make use of drugs acting on the adrenergic system, diuretics, calcium antagonists, nitro-vasodilators and so on, have not yet been abandoned, while new compounds are still being developed today. Newly acquired and more detailed knowledge of the renin-angiotensin system, of the role of the endothelium and ionic channels in the homeostasis of blood pressure has opened up new lines of study. There are also a number of experimental compounds targeted for other action mechanisms (phosphodiesterase inhibitors, neuropeptide Y antagonists, ouabain-like factor antagonists), that could also represent innovative approaches to hypertension therapy. Some hints regarding the current developments in the well established and innovative categories of antihypertensives will be given in this review.     

高血压表观遗传药理学研究进展

伴随着遗传药理学的发展,人们逐渐认识到基因多态性不能完全解释降压药物疗效的个体差异。在分子水平上,高血压药物相关代谢酶、受体、转运体都受到基因表达调控的影响,并在降压疗效差异中起着重要的作用。因此,从表观遗传学的角度研究遗传因素与降压药物之间的关系,将有助于更好地解释临床上药物反应产生的个体差异。本文综述总结了DNA甲基化、组蛋白修饰和microRNAS等表观遗传调控方式对高血压相关药物编码基因的影响。     

吴茱萸次碱对高血压大鼠血压的影响及作用机制

目的观察吴茱萸次碱对高血压模型大鼠血压的影响,并初步探讨其作用机制。方法分别采用自发性高血压大鼠(SHR)及两肾一夹(2K1C)高血压大鼠模型,设正常对照组、模型组、卡托普利阳性组及吴茱萸次碱低、中、高剂量组(10,20,40 mg/kg),每日灌胃给药1次,给药4周,每周测定1次血压,末次给药后,腹主动脉取血,分别测定血浆血栓素(TXB2)、6-酮-前列腺-F1α(6-Keto-PGF1α)、肾素活性(PRA)、心房钠肽(ANP)水平。结果在两个模型中吴茱萸次碱均有较好的降压作用,并能使SHR大鼠血浆TXB2水平降低,6-Keto-PGF1α水平升高;使2K1C大鼠血浆PRA、ANP水平升高。结论吴茱萸次碱能明显降低SHR及2K1C大鼠血压,其降压效果可能通过调节PGI2和TXA2水平,改善血管内皮功能及增加舒血管物质ANP水平实现的。     

关于高血压特殊人群降压药物选择的调查研究

高血压是一种临床常见的慢性心血管疾病,严重威胁患者身体健康。对于高血压的临床药物选择,众多医生见仁见智。为了解临床医生在高血压防治药物选择上的具体情况,特做此调研,旨在规范临床用药,提高用药合理性,造福患者。