Factors associated with intensification of antihypertensive drug therapy in patients with poorly controlled hypertension

Objective To assess antihypertensive management of older patients with poor blood pressure(BP)control.Methods Physicians,voluntary participating in the study,included six consecutive hypertensive patients during routine visits.Hypertension had to have been previously recognized and averaged office BP was>140 and/or>90 mmHg in spite of>6 weeks of antihypertensive therapy.The physicians completed a questionnaire on patients'history of cardiovascular(CV)risk factors,comorbidities,home BP monitoring,anthropometric data and the pharmacotherapy.Results Mean age of the 6462 patients was 61 years,7%were>80 years,51%were female.Mean士SD office BP values were 158士13/92土10 mmHg.The most commonly prescribed antihypertensive drugs were:diuretics(67%),ACE inhibitors(64%),calcium channel blockers(58%)and卩-blockers(54%),and their use increased with age.On monotherapy or dual therapy,43%of the patients and 40%had their latest treatment modification within six months.Home BP monitoring was a factor that accelerated the modification of the therapy.Older patients had to have less chance on faster modification of antihypertensive therapy in spite of presence of diabetes and higher systolic BP.Conclusions Our study suggests that a large number of outpatients with poor BP control receive suboptimal antihypertensive therapy,especially in primary care.In older patients,higher BP values in the office settings are more frequently accepted by physicians even in case of higher CV risk.Regular home BP monitoring hastens the decision to intensify of antihypertensive treatment.

The number of antihypertensive agents simply reflects the grade and the risk of atherosclerosis in patients with type 2 diabetes mellitus

Aims: The associations between the number of antihypertensive agents being taken by type 2 diabetic patients and 1) the grade of atherosclerosis according to non-invasive surrogate markers for atherosclerosis and 2) the other risk factor for atherosclerosis, were cross-sectionally investigated. Methods: The association between the blood pressure control and the clinical characteristics was evaluated in 1359 patients with type 2 diabetes mellitus. Results: The number of antihypertensive agents was 1.5 ± 1.4 (2.0 ± 1.2 among the 990 patients with hypertension). The proportion of patients taking no antihypertensive agents was 29%, 22% were taking one, 29% were taking two and 21% of the patients were taking three or more antihypertensive agents. The value of the ankle-brachial pressure index significantly decreased with the increase in the number of antihypertensive agents even if the blood pressure was corrected to the target value. The values of brachial-ankle pulse wave velocity and carotid intima-media thickness were also increased. The prevalence of risk factors for atherosclerosis, such as obesity, hyperlipidemia, chronic kidney disease, hyperuricemia and anemia was significantly elevated with the number of agents. Conclusions: The number of antihypertensive agents simply reflects the grade and risk of atherosclerosis in patients with type 2 diabetes mellitus.

Non-interventional management of resistant hypertension

Hypertension is one of the most popular fields of re-search in modern medicine due to its high prevalence and its major impact on cardiovascular risk and con-sequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the "uncontrollable" part of arterial hy-pertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. As-pects like the exact prevalence and prognosis are yet tobe clarified. In an effort to manage patients with resis-tant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hyper-tension and provide practical recommendations for cli-nicians dealing with such patients.

A Systematic Review of Factors Influencing Medication Adherence to Hypertension Treatment in Developing Countries

Background: Coronary heart disease (CHD), a complication of hypertension, is one of the most important and common causes of morbidity, hospitalisation, and mortality among hypertensive population. In recent decades, increased urbanisation and changes to lifestyle, diet and physical activity in developing countries have led to a major increase in the population incidence of chronic diseases including CHD. Poor medication adherence is one of the leading causes of failure to achieve hypertension control. The objective of this systematic review is to describe the prevalence of non-adherence to anti-hypertensive medications among hypertensive population in developing countries and identify factors associated with it. Methods: A literature search was conducted using the following scholarly electronic databases: Proquest, PubMed, JSTOR and Science Direct. The online search engine, Google Scholar was also used to search for and identify relevant papers. Peer-reviewed full-text articles published in English on hypertensive adults in developing countries that measured adherence to antihypertensive medications and their associations with different factors were eligible for inclusion. The review followed the PRISMA reporting and analytical guidelines for systematic reviews. Results: In all, 42 studies conducted across 19 developing countries were selected for the review. The mean prevalence of medication non-adherence (MNA) among the select hypertensive population was 47.34%. Very few studies were conducted in community settings and except for one, no study examined gender differences in MNA factors. The analysis revealed a range of factors that can influence MNA including low household income and socioeconomic status;knowledge and beliefs of hypertension and its management;avoiding side effects of medications;cost of medication;use of herbal preparations;absence of symptoms;irregular follow-up;and dissatisfaction with the treatment and health services provided. There was a general lack of consideration of role of health system in health care delivery, self-efficacy, cultural barriers, perceived individual risk of hypertension complications. There was also a lack of gender-specific research which is necessary at community settings given the social and economic vulnerabilities faced by women in developing countries that may affect adherence to antihypertensive medications. Conclusions: Future research in developing countries should consider individual risk perceptions, cultural barriers, gender and the role of local health system in health care delivery when assessing MNA among hypertensive population at community settings.

Hypertension in the elderly:Are we all on the same wavelength?

Hypertension is of frequent occurrence in the elderly population.Isolated systolic hypertension(ISH) accounts for the majority of cases of hypertension in the elderly.ISH is associated with a 2-4-fold increase in the risk of myocardial infarction,left ventricular hypertrophy,renal dysfunction,stroke,and cardiovascular mortality.There have been many studies to determine the optimal treatment for hypertension in the elderly. Why,when and how to treat hypertension in the elderly was the scope of the majority of these trials.Despite countless efforts many aspects remain obscure.While a number of novel drugs are being developed,the issue of whether all antihypertensive drugs bestow parallel benefits or whether some agents offer a therapeutic advantage beyond blood pressure control remains of crucial importance.Furthermore,the response of theelderly to different antihypertensive agents also differs from that of younger patients and may explain some of the disparities in outcomes of trials conducted in elderly patients with hypertension.

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.

Effects of Magnetic Needle Acupuncture on Blood Pressure and Plasma ET-1 Level in the Patient of Hypertension

Endothelin-1 (ET-1) is ever known as a bio-peptidewith the strongest vasoconstrictive action and withwide biological effects.

Hypertension in the elderly： insights from recent research

高血压在全世界是死亡和病态的一个领先的原因并且，高血压的流行与 aging.Hypertension 正在增加在老与钠敏感的增加的出现率被联系，孤立的收缩高血压，并且“上衣 effect'.Arterial 僵硬和 endothelial 机能障碍也与 age.These 因素增加的白色应该在选择这治疗的主要目的是阻止控制 tr 的 stroke.The fmdings 的 antihypertensive therapy.The

Impact of hepatitis C oral therapy in portal hypertension

Chronic hepatitis C is a leading cause of morbidity and mortality, mainly related to fibrosis/cirrhosis and portal hypertension. Direct antiviral agents are highly effective and safe and can now cure > 90% of the patients. Sustained viral response(SVR) after interferon-based regimens has been associated with improvement in liver function, fibrosis and portal hypertension in a significant proportion of patients, although a point of no return seems to exist from which viral elimination is no longer capable of preventing portal hypertension progression and liver decompensation. Indeed, although SVR is associated with improvement of hepatic venous pressure gradients and therefore a decreased risk of de novo esophageal varices, several studies show that viral clearance does not eliminate the risk of variceal progression, liver decompensation and death in patients with pre-established portal hypertension. Although evidence about the effects of direct antiviral agents(DAAs) on clinically significant outcomes is still scarce and with short follow-up, DAAs can decrease the burden of the disease if patients are timely treated before significant fibrosis and portal hypertension develops. Studies with longer follow-up are waited to establish the real magnitude of hepatitis C treatment on portal hypertension. Future studies should also focus on predictors of portal hypertension resolution since it can influence management and avoid unnecessary

HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

Bioactive molecules from terrestrial and seafood resources in hypertension treatment:focus on molecular mechanisms and targeted therapies

Hypertension(HTN),a complex cardiovascular disease(CVD),significantly impacts global health,prompting a growing interest in complementary and alternative therapeutic approaches.This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN,with an emphasis on the molecular mechanisms of action found in substances found in plants,herbs,and seafood.Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies.Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure(BP)-regulating effects of these natural substances better.Polyphenols,flavonoids,alkaloids,and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone,reducing oxidative stress(OS),reducing inflammation,and improving endothelial function.The article explains the vasodilatory,diuretic,and renin-angiotensin-aldosterone system(RAAS)modifying properties of vital plants such as garlic and olive leaf.Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs,providing diverse strategies to combat HTN due to their biological actions.The review also discusses the functions of calcium channel blockers originating from natural sources,angiotensin-converting enzyme(ACE)inhibitors,and nitric oxide(NO)donors.Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN.Omega-3 fatty acids,peptides,and minerals obtained from seafood sources have anti-inflammatory,vasodilatory,and antioxidant properties that improve vascular health and control BP.Overall,we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats

Objective:To investigate the effect of epigallocatechin-3-gallate(EGCG)on endothelial dysfunction in spontaneously hypertensive rats(SHR).Methods:Wistar-Kyoto(WKY)rats and SHR were divided into four groups;WKY control,SHR control and SHR treated with EGCG(50 mg/kg/day)or losartan(10 mg/kg/day).The treatment was given daily for 4 weeks by oral gavage and the blood pressure was monitored by tail-cuff method every 3 days.Acetylcholineinduced endothelium-dependent relaxations were assessed in isolated phenylephrine-precontracted aortic rings at the end of treatment.The vascular levels of reactive oxygen species,nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate were also measured.Moreover,the expression of angiotensinⅡtype 1(AT_(1))receptor protein was determined.Results:The systolic blood pressure was significantly decreased in SHR treated with EGCG.The impaired endothelium-dependent relaxation was significantly improved in aortic ring isolated from the EGCG-treated SHR group.EGCG also significantly increased the levels of nitric oxide,tetrahydrobiopterin,and cyclic guanosine monophosphate,while decreasing the level of reactive oxygen species and the protein expression of AT_(1)receptor in SHR.Conclusions:EGCG attenuates endothelial dysfunction in SHR by decreasing oxidative stress and increasing vascular nitric oxide bioavailability,which may be modulated partly by inhibition of vascular AT_(1)receptors.An increase in endothelium-dependent relaxation may contribute to a decrease in blood pressure in hypertensive animals.

Antihypertensive prescribing patterns in non-dialysis dependent chronic kidney disease:Findings from the Salford Kidney Study

BACKGROUND Hypertension is commonly observed in patients living with chronic kidney disease(CKD).Finding an optimal treatment regime remains challenging due to the complex bidirectional cause-and-effect relationship between hypertension and CKD.There remains variability in antihypertensive treatment practices.AIM To analyze data from the Salford Kidney Study database in relation to antihypertensive prescribing patterns amongst CKD patients.METHODS The Salford Kidney Study is an ongoing prospective study that has been recruiting CKD patients since 2002.All patients are followed up annually,and their medical records including the list of medications are updated until they reach study endpoints[starting on renal replacement therapy or reaching estimated glomerular filtration rate(eGFR)expressed as mL/min/1.73 m2≤10 mL/min/1.73 m2,or the last follow-up date,or data lock on December 31,2021,or death].Data on antihypertensive prescription practices in correspondence to baseline eGFR,urine albumin-creatinine ratio,primary CKD aetiology,and cardiovascular disease were evaluated.Associations between patients who were prescribed three or more antihypertensive agents and their clinical outcomes were studied by Cox regression analysis.Kaplan-Meier analysis demonstrated differences in survival probabilities.RESULTS Three thousand two hundred and thirty non-dialysis-dependent CKD patients with data collected between October 2002 and December 2019 were included.The median age was 65 years.A greater proportion of patients were taking three or more antihypertensive agents with advancing CKD stages(53%of eGFR≤15 mL/min/1.73 m2 vs 26%of eGFR≥60 mL/min/1.73 m2,P<0.001).An increased number of patients receiving more classes of antihypertensive agents was observed as the urine albumin-creatinine ratio category increased(category A3:62%vs category A1:40%,P<0.001),with the upward trends particularly noticeable in the number of individuals prescribed renin angiotensin system blockers.The prescription of three or more antihypertensive agents was associated with all-cause mortality,independent of blood pressure control(hazard ratio:1.15;95%confidence interval:1.04-1.27,P=0.006).Kaplan-Meier analysis illustrated significant differences in survival outcomes between patients with three or more and those with less than three antihypertensive agents prescribed(log-rank,P<0.001).CONCLUSION Antihypertensive prescribing patterns in the Salford Kidney Study based on CKD stage were consistent with expectations from the current United Kingdom National Institute of Health and Care Excellence guideline algorithm.Outcomes were poorer in patients with poor blood pressure control despite being on multiple antihypertensive agents.Continued research is required to bridge remaining variations in hypertension treatment practices worldwide.

Subharmonic aided pressure estimation in portal hypertension:A noninvasive ultrasound-based technique to assess portal pressure gradient

Portal hypertension(PH)is a clinical syndrome,characterized by elevated pressure gradient between portal vein and inferior vena cava.These elevated pressures gradient due to increased vascular resistance and/or increased volume of blood flowing through the portal vein circulation,results in blood outflow difficulty from portal vein to hepatic veins and inferior vena cava.

安罗替尼致高血压文献病例分析

目的探讨安罗替尼相关高血压的临床特点。方法检索中国知网、万方、PubMed、Web of Science数据库(截至2023年7月31日),收集安罗替尼相关高血压文献病例报告类文献,提取患者基本情况、安罗替尼用药情况、高血压情况、干预措施和转归等,进行描述性统计分析。结果纳入分析的文献为16篇,患者18例,男性8例,女性10例;年龄27~76岁,平均58岁;非小细胞肺癌13例,结缔组织和软组织恶性肿瘤2例,肝内胆管癌1例,卵巢癌1例,子宫癌1例。联用其他抗肿瘤药物4例;安罗替尼初始剂量均为12 mg/d。发生的高血压分级为1级3例(17%),2级4例(22%),3级9例(50%),4级2例(11%)。除8例患者从服用安罗替尼至发生高血压的时间不详外,其余10例患者从服用安罗替尼至发生高血压的时间在7 d~6个月内,中位时间36(30,42)d,其中7例(39%)发生在服用安罗替尼2个月内。18例患者中出现不同程度乏力6例(33%),头痛6例(33%),头晕5例(28%),呕吐3例(17%),视物模糊2例(11%),恶心1例(6%),抽搐1例(6%)。13例伴其他不良反应,其中手足综合征7例(39%),蛋白尿3例(17%),高脂血症3例(17%),可逆性后部白质脑病综合征2例(11%),癫痫1例(6%),便血1例(6%),皮疹1例(6%)。1~2级患者安罗替尼未调整(6例)或减量治疗(1例)后耐受良好;3~4级患者中,8例停用安罗替尼且接受降压药治疗,2例减量治疗,1例未调整,随访血压控制平稳。结论安罗替尼相关高血压多发生在用药2个月内,往往伴其他不良反应,3级以上高血压常见,但大多数患者经对症处理、停药或减量后转归良好。

重视夜间高血压的管理--《夜间高血压管理中国专家共识》述评

夜间高血压是心血管疾病重要的危险因素之一,与心血管事件和心血管死亡风险关系密切。单纯夜间高血压是隐蔽性高血压的主要类型,漏诊率极高。未控制的夜间高血压是高血压管理中的短板,是患者血压控制率低下的主要原因之一。改善夜间高血压管理状况有助于实现高质量降压策略的基本要求。本文就《夜间高血压管理中国专家共识》(2023版)做一解析和述评,以供临床参考与借鉴。

高龄高血压患者在我国专家推荐降压标准下的血压控制现状调查

目的分析我国高龄高血压住院患者在降压标准150/90 mm Hg(1 mm Hg=0.133 kPa)下的降压达标率、用药及并发症分布情况。方法选择解放军空军特色医学中心所有科室年龄≥80岁且被诊断为高血压的409例住院患者为研究对象,将409例患者分为强化降压组(106例,收缩压<130 mm Hg)、标准降压组(155例,收缩压130~149 mm Hg)和降压未达标组(148例,收缩压≥150 mm Hg),分析各组患者血压控制现状。结果以150/90 mm Hg为降压标准时,强化降压组占25.9%,标准降压组占37.9%,降压未达标组占36.2%,降压未达标组年龄>90岁比例显著低于强化降压组和标准降压组(4.1%vs 7.5%、12.3%,P<0.05)。标准降压组一联用药比例显著高于强化降压组(46.5%vs 32.1%),强化降压组二联用药比例显著高于标准降压组(35.8%vs 22.6%),差异有统计学意义(P<0.05)。强化降压组并发心脏损害和脑血管损害比例显著高于标准降压组(43.4%vs 21.9%,26.4%vs 14.8%),合并视网膜病变比例显著低于标准降压组(11.3%vs 23.9%),差异有统计学意义(P<0.05)。结论对于高龄高血压患者,以150/90 mm Hg为启动降压标准更具有科学性、实用性,强化降压反而增加了高龄高血压患者心脑血管损害。

天麻钩藤饮联合硫酸镁、拉贝洛尔对妊娠期高血压患者的降压效果及血液流变学的影响评价

【目的】观察天麻钩藤饮联合硫酸镁、拉贝洛尔对妊娠期高血压患者的降压效果及血液流变学的影响。【方法】将90例妊娠期高血压肝阳偏亢型患者随机分为联合组和对照组,每组各45例。对照组给予硫酸镁联合拉贝洛尔治疗,联合组在对照组的基础上加用天麻钩藤饮治疗,疗程为5 d。观察2组患者治疗前后收缩压、舒张压、尿蛋白水平及血液流变学指标的变化情况,比较2组患者的不良妊娠结局、不良反应及满意度情况,并以Logistic回归分析法探讨妊娠期高血压患者不良妊娠结局的影响因素。【结果】(1)降压效果方面,治疗后,2组患者的收缩压、舒张压和尿蛋白水平均较治疗前明显降低(P<0.05),且联合组的降低程度均明显优于对照组(P<0.01)。(2)血液流变学方面,治疗后,2组患者的血浆黏度、全血黏度和红细胞比容均较治疗前明显降低(P<0.05),且联合组的降低程度均明显优于对照组(P<0.05或P<0.01)。(3)不良妊娠结局方面,联合组的不良妊娠结局总发生率为11.11%(5/45),明显低于对照组的33.33%(15/45),差异有统计学意义(P<0.05)。(4)满意度方面,联合组的满意度为97.78%(44/45),明显高于对照组的84.44%(38/45),差异有统计学意义(P<0.05)。(5)不良反应方面,联合组的不良反应总发生率为13.33%(6/45),对照组为8.89%(4/45),组间比较,差异无统计学意义(P>0.05)。(6)影响因素方面,经Logistic回归分析,未使用天麻钩藤饮联合拉贝洛尔、硫酸镁治疗及降压效果不佳均是妊娠期高血压患者不良妊娠结局的独立危险因素(均OR>1,P<0.05)。【结论】天麻钩藤饮联合拉贝洛尔、硫酸镁中西医结合治疗妊娠期高血压患者的降压效果确切,能有效改善血液流变学指标以及不良妊娠结局,提升患者的满意度。

Management of Hypertension in Pregnancy

Hypertension in pregnancy is currently defined as a systolic blood pressure(BP)of 140 mmHg or more,or a diastolic BP of 90 mmHg or more.This level of BP warrants antihypertensive therapy.Treating to a target BP of 135/85 mmHg halves the risk of severe hypertension that is itself associated with adverse maternal and perinatal outcomes,similar in magnitude to preeclampsia.While based on the results of the Control of Hypertension in Pregnancy Study(CHIPS)trial,this finding is consistent with all antihypertensive trials to date.Also,in the CHIPS trial,“tight”BP control also halved the risk of progression to thrombocytopenia and elevated liver enzymes for the mother,without adverse effects for the fetus or newborn.This was true regardless of the gestational age at which BP control was instituted.While methyldopa,labetalol,and nifedipine are the most commonly-recommended oral antihypertensives,it is not clear that one antihypertensive agent has advantages over the others for treatment of non-severe hypertension in pregnancy.No antihypertensives,including renin-angiotensin-aldosterone system(RAAS)inhibitors,have been shown to be teratogenic,although there may be an increase in malformations associated with the underlying condition of chronic hypertension.Atenolol and RAAS inhibitors should not be used once pregnancy is diagnosed,based on fetotoxicity.At present,BP treatment targets used in clinic are the same as those used at home as the differences are quite variable among hypertensive women.For treatment of acute severe hypertension,the most commonly-recommended antihypertensives are oral nifedipine,IV labetalol,and IV hydralazine,although oral agents have also been shown to be effective in the majority of women;while concerns raised about IV hydralazine-induced maternal hypotension and its consequences have not been confirmed,this medication may be an inferior antihypertensive to oral nifedipine.While treatment recommendations are based on evidence,women should be engaged in decision-making,as their values may alter target BP and antihypertensive choice.Future work will clarify the optimal target BP based on home BP measurements;whether BP targets should be lowered further if the definition of hypertension is based on a lower BP;which,if any,antihypertensive medication for non-severe hypertension is better with regards to maternal and perinatal outcomes;and whether factors beyond BP level(such as variability,race,and other physiological variables)should inform antihypertensive therapy in pregnancy.