Antihypertensive drugs and glucose metabolism

Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

Risk Factors Affecting Ischemic Stroke: A Potential Side Effect of Antihypertensive Drugs

Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.

Synchronized separation of atorvastatin——an antihyperlipidemic drug with antihypertensive, antidiabetic, antithrombotic drugs by RP-LC for determination in combined formulations

A new rapid and sensitive high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of atorvastatin—an antihyperlipidemic drug along with most commonly prescribed drugs (antihyperlipidemic, antihypertensive, antidiabetic, antithrombotic) in bulk and marketed combined formulations. The chromatographic separation was carried out by gradient elution mode with acetonitrile as organic modifier and 0.1% triethylamine acetate (TEAA) buffer pH 5 at a flow rate of 1 mL/min and a diode array detector at wavelength 230 nm was employed for detection of the analytes. Calibration curves were linear in the range of 5-150 mg/mL for all the drugs with correlation coefficients of determination (r 2 values)Z0.999. Limits of detection (LODs) and Limits of quantification (LOQs) ranged from 0.1 to 0.27 mg/mL and 0.3 to 0.89 mg/mL respectively. Intra-day and inter-day precision was studied at three concentration levels (20, 60 and 100 mg/mL). The intra-day and inter-day RSD for all compounds was less than 2.0%. The accuracy for all compounds was found to be between 98% and 102%. Thus, the performance of the method described allows its use in quantification of atorvastatin along with 9 most commonly prescribed drugs available in market as atorvastatin combined dosage forms.

An Analysis of the Effects of Blood Pressure and Antihypertensive Drugs on Heart Disease

Background: The American College of Cardiology (ACC), American Heart Association (AHA) and other organizations announced a new hypertension guideline (2017 ACA/AHA Guideline) in November 2017. However, other organizations such as the European Society of Cardiology and European Society of Hypertension maintained their diagnostic thresholds. It is necessary to evaluate the effects of blood pressure (BP) and antihypertensive drugs on the probability of having heart disease (HD). Data and Methods: The effects of BP, antihypertensive drugs and other factors on the probability of undergoing HD treatment were analyzed. We used a dataset containing 83,287 medical check-up and treatment records obtained from 35,504 individuals in 5 fiscal years. The probit models were used in the study. Considering the possibility of endogeneity problems, different types of models were used. Results: We could not find evidence that a higher systolic BP increased the probability of undergoing HD treatment. However, diastolic BP increased the probability in most of the models. Taking antihypertensive drugs also increased the probability of undergoing HD treatment. Diabetes was another important risk factor. Conclusion: The results of this study did not support the new 2017 ACC/AHA Guideline. It is necessary to choose proper drugs and methods to reduce the risks of side effects. Limitations: The dataset was observatory, the data were obtained from just one medical society, and sample selection bias might exist.

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

Research on the World’s Most Valuable Antihypertensive Drugs Based on Patent Analysis

Objective To find out several patented technologies of antihypertensive drugs with the most market value through analysis,and provide a reference for the research and development of enterprises.Methods The most valuable patented technologies of antihypertensive drugs from 2009 to 2019 were analyzed to explore the patent layout and technical characteristics of the main patent applicants,and then the key directions of their research and development were gotten.Results and Conclusion Based on the method of patent analysis,five patents with the most market value are extracted to provide important technical support and market value reference for the research and development of generic drugs or new drugs.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.

Effect of Antihypertensive Drug Therapy on the Blood Pressure Control among Hypertensive Patients Attending Campus’ Teaching Hospital of Lome, Togo, West Africa

High blood pressure (HBP) is a health problem world—wide. In Togo, that affection constitutes a more and more pre-occupying cause of morbidity and mortality. This study is a prospective one which intended to identify the antihypertensive regimens prescribed and evaluate their effect on patients’ blood pressure (BP) control. Out of the 204 patients enrolled (mean: 55.01 ± 12.55 years;sex ratio: 1.3), 112/176 placed on antihypertensive therapy have controlled their BP (38.39% outpatients vs 61.61% inpatients). Related to the sex factor, we didn’t observe any significant difference in the BP control. Whereas, the mean median value of BP reduction of outpatients (30.00/15.00 mmHg) (p = 0.001) was half lower than that of inpatients (60.00/30.00 mmHg (p = 0.004)). Thirty five outpatients (81.40%) vs 64 inpatients (92.75%) were placed on combination therapy. The bitherapy was prescribed to 23 outpatients (53.49%) against 27 inpatients (39.13%) while the quadritherapy and more than 4 drugs combination were prescribed exclusively to inpatients (20.29%, n = 14). That quadritherapy induced a significant mean reduction of inpatients’ SBP compared to monotherapy (p = 0.043) and to bitherapy (p = 0.004). The favorite combinations were D + CCA, D + ACEI, D + CCA + ACEI and D + CCA + ACEI + CAAD of which the quadruple therapy showed a significant inpatients’ DBP control (p = 0.015) compared to D + CCA combination. The combinations including at least one diuretic induced a significant difference between outpatients (median value: 30.000/10.000 mmHg) (p < 0.001) and inpatients (median value: 60.000 mmHg/30 mmHg) (p < 0.001). The first-line molecules and fixe combinations prescribed in decreasing frequency were among others: hydrochlorothiazide + captopril, nicardipine, α methyldopa for outpatients;furosemide, nicardipine, captopril, α methyldopa, hydrochlorothiazide + captopril for inpatients. Diuretics, CCAs and ACEIs were the 3 favorite pharmacological groups for essential hypertension management in our African resource limited context. Combined to CAAD, they represented the best quadruple combination among inpatients having showed a significant difference in DBP control compared to D + CCA combination.

Association between serum homocysteine and arterial stiffness：role of anti-hypertensive drugs

To the Editor I read the article of Zhang, et al. with great interest. They investigated the association of homocysteine with arterial stiffness in Chinese community-based elderly persons. The carotid-femoral pulse wave velocity （PWV） was significantly higher in the high homocyteine group than in the normal one, however, there was no differences in carotid-radial PWV between the high homocyteine group and the normal one. Homocysteine levels were strongly associated with the carotidfemoral PWV even after adjustment for classical risk factors of cardiovascular disease. I congratulate the authors for this important study. However, I want to make minor criticism for this study from the methodological aspect.

Deprescribing antihypertensive treatment in nursing home patients and the effect on blood pressure

Background It is debatable whether treating multimorbid nursing home patients with antihypertensive drugs produces beneficial effects. Most cardiovascular guidelines promote treatment; few have advice on how to deprescribe when treatment may no longer be necessary. We investigated the effect of medication review on antihypertensive drug use and the association between cognition, blood pressure, and prescribing. Methods From August 2014 to December 2015, 765 patients from 72 units （clusters） in 32 Norwegian nursing homes were included in a 4-month, multicentre, cluster-randomized, controlled trial, with 9-month follow-up. Patients ≥ 65 years old with antihypertensive treatment （n = 295, 39%） were randomized to systematic medication review where the physician received support from peers （collegial mentoring） or were given care as usual （control condition）. Outcome measures were the number of antihypertensive drugs, systolic blood pressure, and pulse. We used hospitalizations and deaths as criteria to assess harm. Results At baseline, each patient used 9.2 ± 3.5 regular drugs, and 1.6 ± 0.7 antihypertensives. Mean blood pressure was 128/71 mmHg and 9% had a systolic pressure ≥ 160 mmHg. Between baseline and month four, antihypertensives were deprescribed to a significantly higher extent in the intervention group （n = 43, 32%） compared to control （n = 11, 10%）; Incidence Rate Ratio = 0.8, 95% CI = 0.7？0.9. In the intervention group, there was an immediate increase in systolic blood pressure when antihypertensives were reduced, from baseline 128 ± 19.5 mmHg to 143 ± 25.5 mmHg at month four. However, at month nine, the blood pressure had reverted to baseline values （mean 134 mmHg）. Deprescription did not affect pulse and systolic pressure. The number of hospitalizations was higher in control patients at month four （P = 0.031） and nine （P = 0.041）. Conclusion A systematic medication review supported by collegial mentoring significantly decreased the use of antihypertensive drugs in nursing home patients without an effect on the systolic blood pressure over time.

农村地区高血压患者服药情况及影响因素研究:基于家庭医生签约服务

背景高血压是心血管疾病主要的危险因素,降压用药不仅要考虑患者血压特征,也要考虑患者合并症情况。现阶段,基于家庭医生签约服务对高血压患者的服药状况及影响因素研究比较缺乏。目的调查安徽省界首市家庭医生签约服务的高血压患者服药现状,描述患者服药行为与患者特征之间的关联,探索患者用药调整的影响因素,并分析基层高血压患者用药的合理性。方法采用整群抽样的方法,于2021年7—8月从安徽省界首市随机抽取48个行政村,通过面对面调查法采用自制问卷收集患者特征和服药数据,参照《国家基层高血压防治管理指南2020版》将问卷中患者提到的降压药分为如下5类:A类为血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体阻滞剂(ARB),B类为β受体阻滞剂,C类为钙通道阻滞剂(CCB),D类为利尿剂,E类为单片复方制剂。通过科大讯飞智能语音血压计的后台获取患者上传的近1年血压数据,分析不同特征患者的服药行为。采用多因素Logistic回归分析探讨高血压患者用药调整的影响因素。本研究中联合用药是指服用复方制剂或2种以上降压药,用药调整是指患者过去服用其他降压药。结果本研究共纳入高血压患者3005例,其中男1291例(43.0%)、女1714例(57.0%),平均年龄为(65.5±9.8)岁,高血压服药率为79.1%,联合用药率为40.2%。2376例服用降压药的患者中,不同类型降压药服用率从高到低依次为(部分患者存在联合用药):E类(39.6%)、C类(35.1%)、D类(20.3%)、A类(20.1%)、B类(3.7%);服用最多的降压药为复方利血平(33.7%)。对于年均血压≥160/100mm Hg的患者,仍有12.2%和4.9%未服用降压药。患者联合用药以E类降压药为主。年均“舒张压≥100 mm Hg”且“患合并症”的患者,调整后A类和C类降压药的服用率增加相对较多,年均“收缩压≥160 mm Hg”且“未患合并症”的患者,调整后E类降压药的服用率增加相对较多。多因素Logistic回归结果显示,服药年数长(OR=1.042,95%CI=1.031~1.053,P<0.001)、初中以上文化程度(OR=1.488,95%CI=1.195~1.853,P<0.001)、合并高脂血症(OR=1.267,95%CI=1.052~1.525,P=0.013)、合并心血管疾病(OR=1.394,95%CI=1.166~1.667,P<0.001)、合并脑血管疾病(OR=1.258,95%CI=1.040~1.522,P=0.018)是患者用药调整的促进因素,高龄(OR=0.980,95%CI=0.971~0.990,P<0.001)是用药调整的抑制因素。结论界首市农村地区高血压患者的服药率较高,主要服用E类和C类降压药。服药年数长、初中以上文化程度、合并高脂血症、合并心脑血管疾病是患者用药调整的促进因素,高龄是用药调整的抑制因素。

Fabrication of core-shell PLGA/PLA-pNIPAM nanocomposites for improved entrapment and release kinetics of antihypertensive drugs

Polylactic acid (PLA)and poly(lactic-co-glycolic)acid (PLGA)are two commonly applied biodegrad- able polymers for the preparation of nanocomposites used in drug-delivery systems.However,these polymers lack desirable attributes such as resistance to aggregation during long-term storage due to lyophilisation.To improve their efficacy,in this work,PLA and PLGA were encapsulated within a shell of poly(N-isopropylacrylamide)(pNIPAM)using a single emulsion technique followed by an aqueous free radical precipitation polymerisation process,yielding core-shell PLA/PLGA-pNIPAM nanocomposites. The nanocomposites were cbaracterised using zeta potential,dynamic light scattering,and transmission electron microscopy analyses and were further applied as a delivery system for ramipril,an antihypertensive drug.The drug-loaded PLGA-pNIPAM core-shell nanoparticles exhibited a higher drug content (91%)and entrapment efficiency (78%)than their PLA counterparts.An in vitro release study of the formulations at pH 7.3in phosphate-buffered saline indicated that PLGA was more efficient than PLA with a sustained release of 86% of ramipril from the polymer matrix within 24h.Furthermore,to determine the release kinetics,the data were fitted to Korsmeyer-Peppas and Higuchi models;the release of ramipril from the polymer matrix followed zero-order rate kinetics and an anomalous (non-Fickian)diffusion mechanism.

Antihypertensive drugs in pregnancy

Chronic hypertension complicates 3%-5% of pregnancies and gestational hypertension occurs in 6% of pregnancies.Preeclampsia complicates 25% of the pregnancies with chronic hypertension,and approximately 15%-45% of the patients with gestational hypertension will develop preeclampsia,a dangerous condition that harms the maternal and fetal safety.Antihypertensive medication is used to treat severe hypertension to prevent serious maternal and fetal complications,but there is no consensus on when and how to treat mild-to-moderate hypertension in pregnancy.This article reviews the usage,effect and safety of first,second and third line antihypertensive drugs for mild-to-moderate hypertension in pregnancy.

Analysis of Drug Use in Outpatients with Hypertension Based on Real-World Study

Objective To explore the situation and trend of drug use in the treatment of hypertension in outpatient department of a hospital,and to provide reference for clinical rational drug use.Methods The data of 833 outpatients with hypertension in a hospital from July to December in 2020 were retrospectively analyzed.Results and Conclusion Among the 833 cases,calcium channel blocker(CCB)was the most frequently used drug(38.54%),followed by angiotensin receptor blocker(ARB)(13.81%),β-receptor blockers(β-RB)(10.44%),angiotensin-converting enzyme inhibitor(ACEI)(5.52%),and diuretics(0.72%).The combination rate was 37.09%(including single-pill combination,SPC).The highest rate was the combination of two drugs(28.21%),followed by the combination of three drugs(8.64%)and four drugs(1.20%).The DDDs and DDC of SPC were the highest among the six kinds of drugs.The use of antihypertensive drugs in outpatient department of the hospital is in line with the medication guidelines,but a small number of drugs are used irrationally,which needs further supervision and management.

降压药物肾脏相关不良事件风险分析

目的为临床合理、安全使用降压药物提供参考。方法利用OpenVigil 2.1平台提取美国食品和药物管理局不良事件报告系统(FAERS)2016年1月至2023年12月降压药物肾脏相关不良事件(ADE)报告。采用监管活动医学词典(MedDRA 27.0)的首选语描述ADE,采用报告比值比法和比例报告比值比法挖掘相关信号。结果共纳入10494例报告。其中,低钾血症、肾功能异常、痛风性关节炎、痛风性结晶沉积和尿酸性肾损害分别有8159,1727,446,109,53例,阳性信号数量分别有66,43,27,8,6个;男性患者在除尿酸性肾脏损害外的ADE类别中均多于女性;主要年龄以≥41岁居多;美国是报告各类ADE最多的国家。共42种降压药物显示出肾功能异常阳性信号,涉及利尿剂、α受体拮抗剂、β受体拮抗剂、钙通道阻滞剂、血管紧张素转化酶抑制剂、血管紧张素Ⅱ受体拮抗剂、肾素抑制剂和复方制剂。共8种降压药物显示出痛风性关节炎、痛风性结晶沉积阳性信号,涉及利尿剂、α受体拮抗剂、β受体拮抗剂、血管紧张素转换酶抑制剂、血管扩张剂。共18种药物具有≥3个ADR信号,其不良转归结局基本相似。结论多种降压药物均可导致肾脏相关ADE;降压治疗过程中,需严密监测肾功能异常、低钾血症、痛风性关节炎、痛风性结晶沉积和尿酸性肾损害发生风险,尤其关注产生多种ADE的降压药物。

集采政策对医疗机构心血管药品采购的影响研究

目的:分析药品集采政策对不同等级医疗机构心血管药品采购的影响,为药品集采政策的调整与优化提供参考。方法:分析心血管药品在各级医疗机构的采购量变化情况,采用Mann-Kendall(M-K)趋势性检验判断心血管药品采购量的长期变化趋势。结果:药品集采政策实施后,心血管药品中选产品采购量大幅增长;各级医疗机构集采品种采购量增幅随采购周期的延长而降低;试点地区基层医疗机构中选产品采购量显著增长,联盟地区仅基层医疗机构非中选产品采购量显著下降,基层医疗机构可替代品种采购量呈下降趋势。结论:药品集采政策效应可能存在滞后性,且随采购周期的延长而逐渐弱化,可替代品种的采购量增长值得进一步关注。

中国肾脏移植受者高血压临床诊疗指南

为了进一步规范中国肾脏移植术后高血压的诊断和治疗,中华医学会器官移植学分会组织肾脏移植专家和心血管病专家,在《中国实体器官移植术后高血压诊疗规范(2019版)》的基础上,结合我国器官移植后高血压的临床现状,并参考近年国内外高血压最新诊治指南,从流行病学、诊断和治疗等方面,制定《中国肾脏移植受者高血压临床诊疗指南》,为中国肾脏移植领域医务工作者在术后高血压诊治方面提供理论借鉴和参考,以期更好地控制肾脏移植术后成人高血压,改善不良结局,提高生命质量。

2023美国心脏协会癌症治疗相关高血压科学声明解读

2023年1月,美国心脏协会(AHA)发布癌症治疗相关高血压科学声明,对其发病机制和临床管理进行综述。现代抗癌治疗多以心血管毒性为代价,其中高血压是最常见的副作用之一,尤其是血管内皮生长因子抑制剂、酪氨酸激酶抑制剂和蛋白酶体抑制剂。癌症治疗相关高血压通常是剂量限制性,并且在中断或停止治疗后通常是可逆的。高血压的确切分子机制尚不清楚,近期研究表明,一氧化氮减少、内皮素-1增加、氧化应激、内皮功能障碍、交感神经外流增加和微血管稀疏具有重要作用。结合国际心脏肿瘤学会(IC-OS)的建议,该文对癌症治疗相关高血压的诊断及管理进行解读,目前尚无针对癌症治疗相关高血压患者的降压药物循证证据,故遵循普通人群高血压指南,并且需要多学科合作优化管理,以确保癌症治疗的最佳治疗效果,同时最大限度地减少心血管毒性。

不同降压药物治疗原发性高血压患者血压变异的研究进展

血压变异性是心、脑血管疾病及肾脏损伤的独立危险因素,并在其发生、发展及严重程度方面较平均动脉压具有更高的预测价值,同时也是评价降压药物疗效的重要指标之一。所以早期判断高血压患者的血压变异情况并对其进行积极干预,防止心脑血管事件的进一步发展已成为高血压管理过程中的重要环节。本文将从血压变异性的定义及分类、控制血压变异性的意义以及常见降压药物的疗效观察这几个方面展开综述。

围手术期高血压的管理与控制

围手术期未得到控制的高血压可能影响患者手术中血流动力学稳定性,进而影响患者预后,增加其他并发症出现和死亡的风险。对于接受手术的高血压患者,都需要权衡利弊选择合适的降压药物来降低围手术期不良事件的发生率。目前我国对围手术期血压的管理尚无统一定论,该文从非心脏手术、心脏手术、妊娠、嗜铬细胞瘤4个手术类型系统梳理围手术期血压的控制目标与药物使用方案,为高血压患者的围手术期管理提供参考。