Treatment and Clinical Management of Chronic Thromboembolic Pulmonary Hypertension:An Update of Literature Review

Chronic thromboembolic pulmonary hypertension(CTEPH)is a chronic,progressive,debilitating,and life-threa-tening complication of pulmonary embolism(PE).Recent technological advances have permitted various treat-ment options for the treatment of CTEPH,including surgery,angioplasty,and medical treatment,depending on the location and characteristics of lesions.Pulmonary endarterectomy(PEA)is the treatment of choice for CTEPH,as it offers excellent long-term outcomes and a high probability of recovery.Moreover,various medical and interventional therapies are currently being developed for patients with inoperable CTEPH.This review mainly summarizes the current treatment approaches of CTEPH,offering more options for specialist physicians to,thus,better manage chronic thromboembolic syndromes.

Development of pulmonary hypertension remains a major hurdle to corrective surgery in Down syndrome

Down syndrome is the most common chromosomal abnormality encountered in clinical practice with 50%of them having associated congenital heart disease(CHD).Shunt lesions account for around 75%of all CHDs in Down syndrome.Down syndrome patients,especially with large shunts are particularly predisposed to early development of severe pulmonary hypertension(PH)compared with shunt lesions in general population.This necessitates timely surgical correction which remains the only viable option to prevent long term morbidity and mortality.However,despite clear recommendations,there is wide gap between actual practice and fear of underlying PH which often leads to surgical refusals in Down syndrome even when the shunt is reversible.Another peculiarity is that Down syndrome patients can develop PH even after successful correction of shunt.It is not uncommon to come across Down syndrome patients with uncorrected shunts in adulthood with irreversible PH at which stage intracardiac repair is contraindicated and the only option available is a combined heartlung transplant.However,despite the guidelines laid by authorities,the rates of cardiac transplant in adult Down syndrome remain dismal largely attributable to the high prevalence of intellectual disability in them.The index case presents a real-world scenario highlighting the impact of severe PH on treatment strategies and discrimination driven by the fear of worse outcomes in these patients.

Intervention control of aerobic exercise in maintaining quality of life and pulmonary hypertension in hemodialysis patients

BACKGROUND Pulmonary hypertension is a serious complication in the treatment of maintenance hemodialysis patients,which seriously affects the quality of life of patients and threatens their life safety.Prevention,treatment and improvement of pulmonary hypertension are of great significance to improve the quality of life of patients.AIM To investigate the intervention and control of pedal-powered bicycle in maintaining quality of life and pulmonary hypertension in hemodialysis patients.METHODS 73 patients with maintenance hemadialysis combined with pulmonary arterial hypertension at a hemodialysis center in a certain hospital from May 2021 to May 2022 are selected.Patients are divided into two groups,37 cases in the control group(group C)and 36 cases in the intervention group(group I).Patients are divided into two groups,group C is treated with oral administration of betaglandin sodium combined with routine nursing care.Based on group C,group I conducts power cycling exercises.RESULTS After treatment,group I patients had higher muscle strength,36-Item Short Form Health Survey scores,and Kidney Disease Targets Areas scores;The 6-minute walk distance test index level was higher and the Borg score was lower;The group I had lower systolic blood pressure,greater vital capacity,higher positive emotion,lower systolic pulmonary artery pressure index level,higher arterial partial oxygen pressure level,lower pulmonary vascular resistance index level,and higher blood oxygen saturation level[158.91±11.89 vs 152.56±12.81,1795.01±603.18 vs 1907.20±574.15,24.00(22.00,29.00)vs 24.00(22.00,28.00),P<0.001].CONCLUSION Aerobic exercise combined with Western medicine treatment can effectively improve patients'pulmonary hypertension,alleviate their negative emotions,and enable them to achieve a higher level of quality of life.

Impact of diabetes mellitus on mortality in pulmonary hypertension:A systematic review and meta-analysis

BACKGROUND Pulmonary hypertension(PH)is a progressive disease characterized by endothelial dysfunction and vascular remodeling and is a leading cause of mortality worldwide.Although it is independently associated with multiple comorbidities,the impact of diabetes mellitus(DM)on mortality in patients with PH remains uncertain.To address this issue,we conducted a systematic review and meta-analysis to investigate the effect of DM on survival in patients with pulmonary hypertension.AIM To investigate the impact of diabetes mellitus on mortality in pulmonary hypertension patients.METHODS We conducted a comprehensive search of four major electronic bibliographic databases like PubMed,Google Scholar,Scopus,and Embase,and identified 106 relevant studies,out of 1561 articles,published since the year 2000 for full-text review.Fourteen retrospective and prospective cohort studies that compared survival between patients with DM and those without DM in the context of PH were deemed eligible for inclusion in our meta-analysis.The study was registered on PROSPERO with the identifier CRD42023390232.RESULTS A total of 116455 patients with PH were included in the meta-analysis,of whom 41228 suffered from DM and 75227 did not.The results of our meta-analysis indicate an elevated mortality rate among PH patients with diabetes mellitus in comparison to those without DM[odds ratio(OR)=1.40,95%CI:1.15–1.70,P=0.0006].The metaregression analysis unveiled a statistically significant negative association between mean age and effect size(coefficient=-0.036,P value=0.018).Conversely,a statistically significant positive association was detected between female proportion and effect size(coefficient=0.000,P value<0.001).CONCLUSION Our meta-analysis,which included approximately 116500 PH patients,revealed that the presence of diabetes mellitus was associated with increased odds of mortality when compared to non-diabetic patients.The metaregression analysis indicates that studies with older participants and lower proportions of females tend to exhibit smaller effect sizes.Clinically,these findings underscore the importance of incorporating diabetes status into the risk stratification of patients with PH with more aggressive monitoring and early intervention to improve prognosis potentially.

Effects of combined aerobic,resistance and inspiratory training in patients with pulmonary hypertension:A systematic review

BACKGROUND Pulmonary hypertension(PH)is a serious progressive disorder of the modern world,characterized by endothelial dysfunction and impaired vasoreactivity.Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity.Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities.However,data regarding the effects of combined exercise training programs in patients with PH still remains limited.AIM To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH.METHODS Our search included all available randomized controlled trials(RCTs)regarding combined aerobic,resistance and inspiratory training programs in patients with PH in 4 databases(Pubmed,PEDro,Embase,CINAHL)from 2012 to 2022.Five RCTs were included in the final analysis.Functional capacity,assessed by peak VO_(2)or 6-min walking test(6MWT),as well as quality of life,assessed by the SF-36 questionnaire,were set as the primary outcomes in our study.RESULTS Peak VO_(2)was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs.Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs(P<0.05).Quality of life was measured in 4 out of 5 RCTs.Although patients improved their quality of life in each group,however,only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls.CONCLUSION By this systematic review,we have demonstrated that combined aerobic,resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH.Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

Evolving paradigm of thrombolysis in pulmonary embolism:Comprehensive review of clinical manifestations,indications,recent advances and guideline

Thrombolytic therapy has been the mainstay for patients with pulmonary embolism(PE).Despite being linked to a higher risk of significant bleeding,clinical trials demonstrate that thrombolytic therapy should be used in patients with moderate to high-risk PE,in addition to hemodynamic instability symptoms.This prevents the progression of right heart failure and impending hemodynamic collapse.Diagnosing PE can be challenging due to the variety of presentations;therefore,guidelines and scoring systems have been established to guide physicians to correctly identify and manage the condition.Traditionally,systemic thrombolysis has been utilized to lyse the emboli in PE.However,newer techniques for thrombolysis have been developed,such as endovascular ultrasound-assisted catheter-directed thrombolysis for massive and intermediatehigh submassive risk groups.Additional newer techniques explored are the use of extracorporeal membrane oxygenation,direct aspiration,or fragmentation with aspiration.Because of the constantly changing therapeutic options and the scarcity of randomized controlled trials,choosing the best course of treatment for a given patient may be difficult.To help,the Pulmonary Embolism Reaction Team is a multidisciplinary,rapid response team that has been developed and is used at many institutions.Hence to bridge the knowledge gap,our review highlights various indications of thrombolysis in addition to the recent advances and management guidelines.

Role of pulmonary perfusion magnetic resonance imaging for the diagnosis of pulmonary hypertension:A review

Among five types of pulmonary hypertension,chronic thromboembolic pulmonary hypertension(CTEPH)is the only curable form,but prompt and accurate diagnosis can be challenging.Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH,however these are limited by radiation exposure,subjective qualitative bias,and lack of cardiac functional assessment.This review aims to assess the methodology,diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages,limitations and future research scope.

“Treat-Repair-Treat”:Management of Left Main Coronary Compression by a Pulmonary Artery Aneurysm in a Patient with Atrial Septal Defect and Significant Pulmonary Hypertension

Left main coronary compression syndrome(LMCS)may complicate pulmonary artery aneurysms(PAA),usually developed in the context of pulmonary arterial hypertension(PAH).We report the case of a 51-year-old female patient with an atrial septal defect(unsuitable for device closure)complicated by a PAA generating a 90%left main stenosis.The significant PAH held us back from immediate surgery.After specific dual PAH-targeted therapy(sildenafil and bosentan),the atrial septal defect could be closed with a unidirectional valved patch;the PAAinduced LMCS was treated by reductive arterioplasty.The postoperative course was uneventful.Follow-up showed clinical improvement,but PAH treatment was still needed.After three months,coronary angiography showed only an insignificant residual left main stenosis,proving that reductive pulmonary arterioplasty was effective in treating LMCS.Any PAA requires further evaluation for LMCS,a dangerous but treatable complication.The“treat-repair-treat”strategy and shunt-closure with a unidirectional valved patch can both improve surgical prospects of LMCS with shunt-related PAH.

Bosentan Is Associated with a Reduction in Right Ventricular Systolic Pressure N-Terminal Pro-Hormone B-Type Natriuretic Peptide Levels in Young Patients with Pulmonary Hypertension

Pulmonary hypertension is a rare and potentially fatal disease in children if left untreated. Emerging therapies, including Bosentan, a dual endothelin receptor antagonist, have shown significant benefits in the adult pulmonary hypertension population;however, few studies have assessed the efficacy and safety of endothelin receptor antagonists in infants and young children. Our study was a single-center retrospective analysis of patients less than two years of age with a confirmed diagnosis of pulmonary hypertension and initiated on Bosentan therapy between 2017 and 2020. Twelve cases met eligibility criteria. Demographic data, laboratory data, echocardiographic, and cardiac catheterization data were analyzed. With treatment, there was a statistically significant decrease in mean right ventricular systolic pressure estimated by the tricuspid regurgitation jet (79 ± 23 mmHg reduced to 52 ± 25 mmHg;p < 0.001) N-terminal pro-hormone B-type natriuretic peptide levels (21,071 reduced to 2,037;p < 0.001). Additionally, improvement and eventual normalization of right ventricular function and septal geometry was seen within the first four months of therapy. Patients who underwent cardiac catheterization after therapy initiation (n = 4) demonstrated hemodynamic improvements;however, only the decrease in diastolic pulmonary artery pressure was statistically significant (p = 0.018). No significant differences in hemoglobin, platelet count, or liver function tests were observed between groups. In conclusion, these data suggest that Bosentan may be an effective and relatively safe treatment option for children less than two years of age with pulmonary hypertension. Further long-term randomized control studies are necessary to validate the potential clinical benefit of utilizing this drug therapy in young children.

Twin pregnancy with sudden heart failure and pulmonary hypertension after atrial septal defect repair: A case report

BACKGROUND Pulmonary arterial hypertension(PAH)in pregnancy is one of the major obstetric complications and is considered a contraindication to pregnancy as it is classified as a class IV risk in the revised risk classification of pregnancy by the World Health Organisation.Pregnancy,with its adaptive and expectant mechanical and hormonal changes,negatively affects the cardiopulmonary circulation in pregnant women.Do patients with repaired simple congenital heart disease(CHD)develop other pulmonary and cardiac complications during pregnancy?Can pregnant women with sudden pulmonary hypertension be treated and managed in time?In this paper,we present a case of a 39-year-old woman who underwent cesarean section at 33 wk'gestation and developed PAH secondary to repaired simple CHD.Our research began by a PubMed search for"pulmonary hypertension"and"pregnancy"and"CHD"case reports.Three cases were selected to review PAH in pregnancy after correction of CHD defects.These studies were reviewed,coupled with our own clinical experience.CASE SUMMARY Herein,a case involving a woman who underwent atrial septal defect repair at the age of 34,became pregnant five years later,and had a sudden onset of PAH and right heart failure secondary to symptoms of acute peripheral edema in the third trimester of her pregnancy.As a result,the patient underwent a cesarean section and gave birth to healthy twins.Within three days after cesarean delivery,her cardiac function deteriorated as the pulmonary artery pressure increased.Effec-tive postpartum management,including diuresis,significant oxygen uptake,vasodilators,capacity and anticoagulants management,led to improvements in cardiac function and oxygenation.The patient was discharged from hospital with a stable recovery and transferred to local hospitals for further PAH treatment.CONCLUSION This case served as a reminder to obstetricians of the importance of pregnancy after repair of CHD.It is crucial for patients with CHD to receive early correction.It suggests doctors should not ignore edema of twin pregnancy.Also,it provides a reference for the further standardization of antenatal,in-trapartum and postpartum management for patients with CHD worldwide.

Chronic thromboembolic pulmonary hypertension is associated with a loss of total lung volume on computed tomography

BACKGROUND Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension(CTEPH),approximately 20%-29%of patients exhibit a restrictive pattern on pulmonary function testing.AIM To quantify longitudinal changes in lung volume and cardiac cross-sectional area(CSA)in patients with CTEPH.METHODS In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019,we evaluated 15 patients with CTEPH who had chest computed tomography(CT)performed at baseline and after at least 6 mo of therapy.We matched the CTEPH cohort with 45 control patients by age,sex,and observation period.CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test.RESULTS Total,right lung,and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline(total,P=0.004;right lung,P=0.003;right lower lobe;P=0.01).In the CTEPH group,the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group(total,P=0.01;right lung,P=0.007;right lower lobe,P=0.01;CSA,P=0.0002).There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort.CONCLUSION After at least 6 mo of treatment,CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling.

Research progress in the etiology of pulmonary hypertension

Pulmonary hypertension(PH)is a progressive disorder affecting the pulmonary circulation,characterized by a grim prognosis that often culminates in right heart failure and mortality.Pulmonary vascular remodeling stands out as the predominant feature in the pathogenesis and pathological alterations of PH.Whereas,the pathogenic factors of PH are intricate,involving multiple interacting elements,and the mechanism behind pulmonary vascular remodeling remains not entirely comprehended.In this context,inflammation,chemokines,and gut microbiota may make a intricate and interrelated difference during the process of pulmonary vascular remodeling.

Intensified, optimized and standardized management of Chinese patients with hypertension: Comments on “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”

The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiated and organized by the Chinese Hypertension League.Based on the “2010 Chinese Guidelines for the Management of Hypertension” and recent evidence from domestic and international research in the field of hypertension,considering national conditions and the current situation of hypertension management in China,and reference to the latest European and American hypertension guidelines,the 2018 Guidelines make comprehensive and in-depth elaborations and recommendations of the diagnosis and assessment of hypertension,strategies and goals of prevention and treatment of hypertension and pathway of intervention,etc.The 2018 Guidelines not only provide Chinese medical personnel with guidance and reference for the clinical practice and population management of hypertension,but also serve as the latest textbook on updating concepts and knowledge in the field of hypertension.

Does High Systolic Blood Pressure Truly Increase Medical Expenditure?—An Empirical Analysis of the New 2017 ACC/AHA Hypertension Guideline

Background: High blood pressure (BP) or hypertension is considered one of the top global disease burden risk factors. In November 2017, the ACC/AHA and other organizations announced a new hypertension guideline of 130/80 mmHg. Data and Methods: We evaluate the effects of BP on increases in medical expenditures using transformation tobit models and a dataset containing 175,123 medical checkups and 6,312,125 receipts from 88,211 individuals in three health insurance societies. The sample period was April 2013 to March 2016. We first created a database of combined checkup results and medical expenditures. The power transformation tobit model was then used to remove the effects of other variables, and we investigated the relation between medical expenditures and BP, especially systolic BP (SBP). Results: We observed negative effects of SBP on medical expenditures. The results raise uncertainty about the reliability of the new guideline, at least for SBP. Although the simple correlation coefficient of medical expenditures and SBP was positive, the sign of the SBP estimate became negative when a variable representing obesity was included. In terms of other medical checkup items, while LDL is considered the “bad” cholesterol, it reduced medical expenditures. Conclusion: Our results did not support the new 2017 ACC/AHA guideline for SBP. A wide and careful range of reviews not only for heart diseases but also for other disease types will be absolutely necessary. New studies to verify the guideline should also be conducted. Limitations: The dataset was observatory, the sample period only 3 years, and we could not complete a time-series analysis of individuals.

N-carbamylglutamate restores nitric oxide synthesis and attenuates high altitudeinduced pulmonary hypertension in Holstein heifers ascended to high altitude

Background: High-altitude pulmonary hypertension(HAPH) is a life-threating condition for animals in high altitude,and disturbance of endothelial nitric oxide(NO) synthesis contributes to its pathogenesis. N-carbamylglutamate(NCG), which enhances arginine synthesis, promotes endogenous synthesis of NO. In this study, we determined the effects of NCG on alleviating HAPH in Holstein heifers that ascended to Tibet(Lhasa, 3,658 m).Methods: Exp. 1, 2,000 Holstein heifers were transported from low elevation(1,027 m) to Lhasa. After being exposed to hypoxia for 1 yr, Holstein heifers were assigned to a healthy group(Control, n = 6) with mean pulmonary hypertension(mPAP) < 41 mmHg, and an HAPH affected group(HAPH, n = 6) with mPAP > 49 mmHg.Lung tissues were collected to evaluate histopathological changes and the expression of endothelial nitric oxide synthase(eNOS). Exp. 2, ten healthy heifers and 10 HAPH affected heifers were supplemented with NCG(20 g/d per heifer) for 4 wk. Physiological parameters were determined and blood samples were collected on d-1 and d 28 of the feeding trial.Results: Expression of e NOS in small pulmonary arteriole intima was higher in the healthy than HAPH group(P = 0.006), whereas HAPH group had significantly thicker media and adventitia than healthy group(all P < 0.05). The mRNA of eNOS and protein level of eNOS were higher in the lungs of heifers in the healthy group than in the HAPH group(both P < 0.001), whereas endothelin-1 protein levels were higher in HAPH group than in the healthy group(P = 0.025). NCG supplementation decreased mPAP and ammonia(both P = 0.001), whereas it increased the expression of eNOS, arginine, and plasma NO(all P < 0.05).Conclusions: The expression of eNOS was decreased in Holstein heifers with HAPH. NCG supplementation decreased m PAP through the restoration of eNOS and endogenous NO synthesis.

New guidelines for the diagnosis and management of pulmonary embolism:Key changes

Pulmonary embolism(PE)is an important public health problem.In August2019,the European Society of Cardiology in collaboration with the European Respiratory Society released new guidelines for the diagnosis and management of PE.We discuss the basic changes between these recent guidelines and the previous guidelines that were published in 2014.Regarding diagnosis,the new guidelines propose the use of an age-adjusted cut-off level of D-dimers instead of a fixed cut-off value.A D-dimer test adapted to clinical possibility should also be considered instead of fixed cut-off level of D-dimer.Detailed recommendations for the diagnosis of PE during pregnancy are also provided.Regarding risk stratification,assessment of PE-related early mortality risk is recommended.Moreover,the importance of right ventricular dysfunction is emphasized in lowrisk patients.For further risk stratification of the severity of PE in patients without hemodynamic instability,use of validated scores that combine clinical,imaging and laboratory PE-related prognostic factors might also be considered.Regarding treatment,the possibility of early discharge is mentioned in patients without severe comorbidities,who are not of high risk for sudden death and in whom proper medical management at home and proper medical follow up can be ensured.The new guidelines also suggest that pro-brain natriuretic peptide levels,right ventricular function and the presence of thrombus in the right heart could be useful for guiding the decision of early discharge.Overall,these new guidelines introduce several key changes and knowledge and adherence to them will improve the outcome of patients with PE.

Inhibition of Expression of Hypoxia-inducible Factor-1α mRNA by Nitric Oxide in Hypoxic Pulmonary Hypertension Rats

In order to study the effect of nitric oxide (NO) on the expression of hypoxia inducible factor 1 alpha (HIF 1α) mRNA in hypoxic pulmonary hypertension (HPH) rats, 30 healthy male Wistar rats were randomly divided into normoxic control group, chronic hypoxic group and hypoxia plus L argine (L Arg) group. The animal model of HPH was developed. The mean pulmonary arterial pressure (mPAP) was measured by inserting a microcatheter into the pulmonary artery. The HIF 1α mRNA expression levels were detected by in situ hybridization (ISH) and semiquantitative RT PCR. It was found that after 14 days hypoxia, the mPAP in normoxic control group (17.6±2 7 mmHg,1 mmHg=0 133 kPa) was significantly lower than that in chronic hypoxic group(35.8±6.1 mmHg, t =0.2918, P <0.05) and mPAP in chronic hypoxic group was higher than that in hypoxia plus L argine group(24.4±3.8 mmHg, t =0.2563, P <0.05). ISH showed that the expression of HIF 1α mRNA in the intraacinar pulmonary arteriolae (IAPA) in normoxic control group (0.1076±0.0205) was markedly weaker than that in chronic hypoxic group (0.3317±0.0683, t =3.125, P <0.05) and that in chronic hypoxic group was stronger than that in hypoxia plus L argine group (0.1928±0.0381, t =2.844, P <0.05). RT PCR showed that the content of HIF 1α mRNA in chronic hypoxic group (2.5395±0.6449) was 2.16 times and 1.75 times higher than that in normoxic control group (1.1781±0.3628) and hypoxia plus L argine group (1.4511±0.3981), respectively. It is concluded that NO can reduce the mPAP by the inhibition of the expression of HIF 1α mRNA, which may be one of the mechanisms through which NO affects the pathogenesis of HPH.

Analysis of Cardiovascular Risk Factors in Newly Defined Stage 1 Hypertension among Chinese on the Basis of the 2017 ACC/AHA Hypertension Guidelines

In 2017,American College of Cardiology(ACC)/American Heart Association(AHA)et al.jointly released the latest guidelines for adult hypertension,exactly including prevention,diagnosis,assess and treatment,in which blood pressure levels greater than 130/80 mm Hg were defined as hypertension[1].Based on these modified guidelines,the morbidity of hypertension in US increased from 32%to 46%.

Nice new hypertension guidelines

The National Institute for Clinical Excellence in the United Kingdom published a new set of guidelines on the management of primary hypertension in August 2011, reflecting some important changes in the diagnosis and treatment of hypertension. Ambulatory blood pressure measurement is now the new gold standard for diagnosis. Home blood pressure monitoring is a useful alternative for the diagnosis and monitoring of hypertension. Calcium channel blockers(CCB) and blockers of the renin-angiotensin system have surpassed diuretics and β-blockers as first line options. Patients younger than 55 should receive an angiotensin-converting enzyme inhibitor, or an angiotensin receptor blocker if the former is not tolerated. Older patients should be started on a CCB. A thiazide diuretic can be added to these two groups for better blood pressure control, but. chorthalidone and indapamide are the preferred diuretics as they showed favorable outcomes in large clinical trials. Treatment with these three drug classes should be sufficient in the majority of patients, but if triple therapy is still insufficient, referral to a hypertension specialist is recommended. Additional diuretic therapy, spironolactone, or an α or β blocker can be used as the fourth line treatment.

Reduction of diastolic blood pressure: Should hypertension guidelines include a lower threshold target?

Reduction of diastolic blood pressure to less than 60-80 mm Hg does not improve mortality and may lead to adversecardiovascular events in high risk patient populations. Despite a growing body of evidence supporting the J-curve phenomenon, no major society guidelines on hypertension include a lower threshold target for diastolic blood pressure. Many major society guidelines for hypertension have been updated in the last 5 years. Some guidelines include goals specific to age and co-morbid conditions. The Sixth Joint Task Force of the European Society of Cardiology and the Canadian Hypertension Education Program are the only guidelines to date that have recommended a lower threshold target, with the Canadian guidelines recommending a caution against diastolic blood pressure less than or equal to 60 mm Hg in patients with coronary artery disease. While systolic blood pressure has been proven to be the overriding risk factor in hypertensive patients over the age of 50 years, diastolic blood pressure is an important predictor of mortality in younger adults. Post hoc data analysis of previous clinical trials regarding safe lower diastolic blood pressure threshold remains inconsistent. Randomized clinical trials designed to determine the appropriate diastolic blood pressure targets among different age groups and populations with different comorbidities are warranted. Hypertension guideline goals should be based on an individual's age, level of risk, and certain co-morbid conditions, especially coronary artery disease, stroke, chronic kidney disease, and diabetes.