Pharmacoepidemiologic study of association between apparent treatment resistant hypertension, cardiovascular disease and interaction effect by sex and age

BACKGROUND A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension(aTRH)and risk of cardiovascular disease(CVD).AIM To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association.METHODS We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT).ALLHAT recruited participants(n=25516)from 625 primary care settings throughout the United States,Canada,Puerto Rico,and United States Virgin Islands,aged 55 and older with hypertension and at least one additional risk factor for heart disease.aTRH was assessed from the year 2 visit.CVD event was defined as one of the following from the year 2 follow-up visit:Fatal or non-fatal myocardial infarction,coronary revascularization,angina,stroke,heart failure,or peripheral artery disease.Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk.Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction.RESULTS Of the total study participants(n=25516),5030 experienced a CVD event during a mean of 4.7 years follow-up.aTRH was associated with a 30%increase in risk of CVD compared to non-aTRH[hazards ratio(HR)=1.3,95%CI:1.19-1.42].Sex and age modified this relationship on both multiplicative and additive scales independently.Stratified by sex,aTRH was associated with a 64%increase in risk of CVD(HR=1.64,95%CI:1.43–1.88)in women,and a 13%increase in risk of CVD(HR=1.13,95%CI:1.01–1.27)in men.Stratified by age,aTRH had a stronger impact on the risk of CVD in participants aged<65(HR=1.53,95%CI:1.32–1.77)than it did in those aged≥65(HR=1.18,95%CI:1.05–1.32).Significant two-way interactions of sex and aTRH,and age and aTRH on risk of CVD were observed(P<0.05).The observed joint effect of aTRH and ages≥65 years(HR=1.85,95%CI:1.22–2.48)in males was less than what was expected for both additive and multiplicative models(HR=4.10,95%CI:3.63–4.57 and 4.88,95%CI:3.66–6.31),although three-way interaction of sex,age,and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance(P>0.05).CONCLUSION aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age.Further studies are warranted to test these mechanisms.

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.

Relationship between Serum Uric Acid Levels and Kidney Arteriole Resistance in Patients with Type 2 Diabetes Associated with Hypertension

Objectives To investigate the relationship between serum uric acid levels and arteriole resistance detected with the color Doppler energy imaging (CDEI) and to explore the risks of impaired regulation of vascular tone by uric acid in kidneys of hypertension patients. Methods In 12 healthy control cases, 28 non-diabetic hypertension (nNIDDM +H) cases and 25 type 2 diabetic hypertension (NIDDM+H) cases, uric acid (UA) levels were measured with uricase-peroxidase method. Arteriole resistance index (RI) and pulsate index (PI) in separate sections of renal artery included MAR, SRA, IRA were detected using CDEI with 2.1~4.2 Hz Doppler transducer in kidneys. Results In comparison, UA was significantly higher in non-diabetic hyper- tension group and diabetic hypertension group than in control group (P<0.01, separately). UA levels was also significantly higher in NIDDM+H group than in nNIDDM+H, P < 0.029. RI in separate sections of renal artery was significantly higher in nNIDDM+H, or NIDDM+H group than in control group ( all P < 0.01) , and it was significantly higher in NIDDM +H than nNIDDM+H groups (P < 0.05 and P < 0.01). In nNIDDM +H and NIDDM +H groups UA levels and IRA-RI could be elevated significantly following with the impaired heart function being aggravated (χ2 = 13.028, P=0.005, χ2=13.29, P=0.004); the dosage of HCT being increased (χ2 =14.216, P=0.001, χ2 = 14.661, P=0.001); the levels of GHbA1 being excessed unnormally (P=0.000). The correlation between UA and IRA-RI in both hypertension groups were directly related, in nNIDDM+H group r=0.842, P=0.000, in NIDDM+H group, r=0.797, P=0.000. Conclusions Uric acid levels and IRA-RI in hyper-tension patients were directly related. Uric acid levels and IRA-RI could be partly dependent on the severity of heart dysfunction, diuretic dose, and serum glucose status of diabete patients in long-term. Uric acid and the xanthine oxidase metabolic pathway may contribute to impaired regulation of arteriole tone in hypertension patients.

Computed tomography-guided chemical renal sympathetic nerve modulation in the treatment of resistant hypertension: A case report

BACKGROUND Resistant hypertension(RH)has always been a difficult problem in clinical diagnosis and treatment.At present,there is no recognized safe and effective minimally invasive treatment.CASE SUMMARY An 80-year-old woman was admitted to hospital due to trigeminal neuralgia(TN).The patient had a history of RH for more than 10 years and her blood pressure(BP)was not well-controlled.Before the treatment for TN,we decided to perform chemical renal sympathetic denervation with ethanol in the Pain Department of our hospital.One year after the operation,she stopped taking antihypertensive drugs,and her BP was satisfactorily controlled within 4 years after surgery.CONCLUSION Computed tomography-guided chemical renal sympathetic modulation may be a feasible method for the treatment of RH.

Endovascular denervation(EDN):From Hypertension to Non-Hypertension Diseases

Recently,the use of endovascular denervation(EDN)to treat resistant hypertension has gained significant attention.In addition to reducing sympathetic activity,EDN might also have beneficial effects on pulmonary arterial hypertension,insulin resistance,chronic kidney disease,atrial fibrillation,heart failure,obstructive sleep apnea syndrome,loin pain hematuria syndrome,cancer pain and so on.In this article we will summarize the progress of EDN in clinical research.

A Very Severe Obstructive Sleep Apnea Syndrome: In a Cause of Resistant Hypertension with One Sample Case

When blood pressure values remain above the target in a hypertensive patient treated concomitantly with three anti-hypertensive drugs including a diuretic, maximum well-tolerated doses, this is a resistant arterial hypertension. In this case, it is advisable to look for a secondary cause such as a drug intake that influencing the blood pressure or the presence of obstructive sleeping syndrome (OSAS). We report a clinical case of a patient with a high cardiovascular risk at the age of 50, hypertensive and diabetic, with dyslipidemia and obesity. He was on anti-hypertensive triple therapy at an optimal dose. Her diabetes was balanced with 6.4% glycated hemoglobin. Dyslipidemia has being treated. Despite healthy diet including a low sodium diet and weight loss, blood pres- sure target was not reached. With self-measurement, the mean arterial pressure was 180/110 mmHg and on ABPM it was 167/113 mmHg. The ventilatory polygraphy finds a severe OSA with an IAH = 56.6. Treatment with PCP (Con- tinuous positive pressure) allowed this patient to control blood pressure. The search for OSA should be systematic in face of resistant hypertension, in par- ticular in overweight or obese patients.

Comparison of a 5 F Microtube-Irrigated Ablation Catheter and a General Ablation Catheter in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To assess the effectiveness of catheter-based renal denervation for reducing blood pressure in patients with resistant hypertension using a 5 F microtube-irrigated ablation catheter.Methods:Sixty patients with resistant hypertension were divided into two groups:a microtube-irrigated ablation catheter group and a general ablation catheter group.We conducted 12-month follow-up of all patients and recorded clinical blood pressure,ambulatory blood pressure,medication use,and biochemistry test results in both groups at the baseline and at the 12-month follow-up.Results:All patients underwent renal denervation.At the 6-month follow-up,ambulatory blood pressure in the mi-crotube-irrigated ablation catheter group was signifi cantly lower than in the general ablation catheter group(systolic blood pressure 142.0±14.4 mmHg vs.150.8±17.9 mmHg,P=0.04;diastolic blood pressure 81.2±7.0 mmHg vs.87.6±8.0 mmHg,P=0.002).At the 12-month follow-up,the between-group difference in ambulatory blood pressure was not statistically signifi cant.At the 12-month follow-up,the number of antihypertensive drugs and diuretics used in the microtube-irrigated ablation catheter group was less than in the general ablation catheter group(P=0.043).There was no statistical difference between the two groups in the results of biochemistry tests and echocardiography.Conclusion:The microtube-irrigated ablation catheter is more effective in treating hypertension than the general ablation catheter at the 6-month follow up and thus fewer antihypertensive drugs were used in the microtube-irrigated ablation catheter group than in the general ablation catheter group.

Main Renal Artery Plus Branch Ablation in the Treatment of Resistant Hypertension with Renal Denervation

Objective:To study the safety and effi cacy of denervation of renal artery branches in the treatment of resistant hy-pertension.Methods:Sixty patients with resistant hypertension were enrolled.The patients were randomly assigned to the main renal artery plus branch ablation group or the main renal artery ablation group.The clinical data and operation-related parameters,including number of ablation points,temperature,and average energy,were recorded.Ambulatory blood pressure was taken for all patients at the baseline and at 6 months after treatment.Offi ce blood pressure was recorded before treatment and after treatment every 3 months for 2 years.Results:Sixty patients with resistant hypertension were enrolled in this study.There were 30 patients in each group.Angiography was performed after ablation.No renal artery complications,such as stenosis and dissection,occurred in the two groups.There was no signifi cant difference in age,sex,BMI,comorbid disease,and medication between the two groups(P>0.05).The number of ablation points for the main renal artery plus branch ablation group was greater than that for the main renal artery ablation group.The offi ce blood pressure and 24-hour blood pressure were signifi cantly lower 6 months after treatment than before treatment in both groups(P<0.05).Offi ce blood pressure in the main renal artery plus branch ablation group was lower than that in the main renal artery ablation group during the 3-12-month follow-up period,with a statistical difference.However,as the follow-up time increased,the difference disappeared.Conclusion:The results of this study show that main renal artery plus branch ablation is a safe interventional method,but there was no obvious advantage on long-term follow-up compared with only main renal artery ablation.

Effects of telmisartan on hypertensive patients with dyslipidemia and insulin resistance

The benefits of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) beyond blood pressure reduction have been proven through many large studies (HOPE, LIFE) in high risk CVD patients;1 post hoc studies have shown reductions in new onset type 2 diabetes mellitus (DM). ……

True Resistant Hypertension among Treated Hypertensive Black Patients.A Clinical-Based Cross-Sectional Study

Background and Objective: 24-h ambulatory blood pressure monitoring (ABPM) aids to precisely identify patients with true resistant hypertension (tRH). The present study was aimed to assess the frequency and correlates of tRH among patients with clinically suspected RH. Methods: Medical records of treated hypertensive patients referred in four healthcare centers for BP control evaluation by 24-h ABPM were reviewed to assess the prevalence of tRH. Inclusion criteria were age ≥ 18 years, clinical diagnosis of RH. Data on demographic, clinical, laboratory, 2D-echocardiography and 24-h ABPM parameters were retrieved from patient’s medical records. True RH (tRH) was defined as office blood pressure (BP) ≥ 140/90 mmHg and 24-h ambulatory BP ≥ 130/80 mmHg. Simple and multiple linear regression analyses were used to assess factors associated with systolic BP (SBP) as a proxy of RH among patients with tRH. P 0.05 defined the level of statistical significance. Results: Of 636 patients referred for BP control evaluation by 24-h ABPM, 75 (11.7%) had suspected RH by office BP measurements. After 24-h ABPM, pseudo or apparent RH (aRH) and tRH were observed in 15 (2.3%) and 60 (9.4%) patients, respectively. BMI (p = 0.007) and blood glucose (p = 0.024) were positively associated with SBP whereas a negative association was observed with eGFR (p = 0.022) among tRH hypertensive patients in multiple regression analysis. Conclusion: True RH was a common finding among patients with clinical RH and associated with obesity and silent target organ, especially kidney dysfunction. The present study highlights the diagnostic and prognostic importance of 24-h ABPM among patients with clinical RH.

Study on Features of Insulin Resistance in Patients with Coronary Heart Disease

Objective Researching the features of insulin resistance in patients with coronary heart disease (CHD) . Methods The study included 20 healthy subjects (control group), 53 CHD patients without (Group A) and 24 with essential hypertension (Group B) . Oral glucose tolerance test was administered to all subjects. Venous blood samples were taken during fasting and at 30, 60, 120 and 180 min after the glucose load (100g). All samples were assayed for glucose, insulin and C - peptide. Results The glucose, insulin, and C - peptide curves were at a hierarchy of Group B > Group A > the control group. Insulin - sensitivity - index was at an inverse hierarchy (-4. 31±0.55, -4. 05±0.47, - 3. 82±0. 42, respectively) . The ratio of the area under the C - peptide to the insulin was at a hierarchy of control group (3. 84±0. 81)> Group A (2. 84±0. 93)> Group B (2.26±0. 67), P < 0. 01) . As to insulin and C - peptide releasing types, most subjects of the control group had common type, while the predominant response type was pure - high in Group A, delayed - and delayed - high in Group B. Conclusions There are insulin resistance, insulin - C - peptide separation and changes of insulin and C - peptide releasing types in CHD patients. Insulin resistance is more severe when with hypertension. The hyperinsulinemia in CHD might be due to the over - secretion of insulin, also due to slow clearance in the patients accompanied by hypertension.

肾脏去神经技术:历史,现状和前景（英文）

Renal denervation is a new technique approved effective for resistant-hypertension treatment.The common renal denervation system consists of a generator and a flexible catheter.During this minimally invasive procedure,the interventionalist uses a steerable catheter with a radio frequency(RF)energy electrode tip.The RF energy is delivered to the renal artery via standard femoral artery access.A series of 2-minute ablation are delivered in each renal artery to distroy the nerves system.The procedure does not involve a permanent device implant.By deactivating the renal nerves,and therefore reducing sympathetic nerve transmission,a significant and reliable reduction in blood pressure could be achieved.In this review,potential complications and future sights of renal denervation are also discussed.

The add-on effect of a Chinese herbal formula for patients with resistant hypertension: study protocol for a pilot cohort study

BACKGROUND： Despite a recent American Heart Association （AHA） consensus statement emphasizing the importance of resistant hypertension （RH）, its control is still a challenge for conventional medicine. The Chinese herbal formula, Qutan Huayu Fang, has been used effectively to assist antihypertensive agents in blood pressure control, but its effect for RH patients is still unclear. This pilot study aims to explore the effects of taking the formula in addition to antihypertensive medication in the management of RH. METHODS/DESIGN： A prospective cohort study will be conducted in two first-class hospitals of traditional Chinese medicine （TCM）. Eligible RH patients will be classified as the experimental group （n = 100） and the control group （n = 100） based on the interventions they receive. Participants taking antihypertensive agents and the Chinese herbal formula will be in the experimental group and those taking antihypertensive agents alone will be in the control group. The whole study will last 24 weeks, including an 8-week observation and follow-up at 24 weeks. The primary outcomes, assessed against patient baseline conditions, will be the reduction of systolic blood pressure and diastolic blood pressure as well as changes in TCM symptoms and signs. These outcomes will be assessed at weeks 2, 4, 6, and 8. The reductions of blood pressure will also be assessed at week 24. Cardiac events and mortality rate will be secondary outcomes and will be assessed at weeks 8 and 24. Any adverse reactions will be recorded during the study. The causal inference method will be used to assess the effectiveness of the inclusion of TCM herbal medicine in the management of patients with RH. DISCUSSION： This study will determine whether the Chinese herbal formula is helpful for RH patients treated with antihypertensive agents and the findings will provide a basis for further confirmatory studies TRIAL REGISTRATION NUMBER： ClinicalTria/s.gov Identifier NCT01904695

Renal denervation： a new therapeutic approach for resistant hypertension

Objective To review the advances in studies on renal denervation. Data sources References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Study selection Articles with keywords ＂renal denervation＂ and ＂resistant hypertension＂ were selected. Results Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformite Europ6enne mark is also included in this review. Conclusions Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

Consensus of Chinese Specialists on Diagnosis and Treatment of Resistant Hypertension

INTRODUCTION Resistant hypertension has become a challenge in the treatment of hypertension.As the population continues to age and obesity,sleep apnea hypopnea syndrome,and chronic kidney disease increase in incidence,resistant hypertension has become an increasingly common issue in clinical practice.Failure to control blood pressure can impair target organs such as the heart,brain,and kidney,facilitating the occurrence of clinical cardiovascular events.

Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension

This study investigated the effect of catheter-based renal sympathetic denervation （RD） on left ventricular hypertrophy （LVH） and systolic and diastolic function in patients with resistant hypertension. LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear

Efficacy and safety of renal denervation for resistant hypertension:A systematic review and meta-analysis

Background Renal denervation has a tortuous history.Significant reductions in blood pressure following denervation of the renal artery were observed in early trials,but subsequent denervation under sham surgery was found to be neutral.Methods This study was performed according to search results by CNKI,WANFANG DATA,EMBASE database,Pubmed,Medline,the Cochrane Central Register of Controlled Trials,Clinicaltrials.gov,and World Health Organization International Clinical Trials Registry Platform from database inception to June 20,2019.For continuous outcomes,heterogeneity were assessed by Cochran’s Q test and random-effect models weighted for the inverse of the variance.Dichotomous data were analyzed using relative risk(RR)with 95%CIs.Safety was assessed by assessing the risk of major adverse events from stratified contingency tables.Results 10 randomized controlled trials with a total of 1323 individuals were included in the quantitative analysis.Pooled analyses indicated that renal denervation was associated with a significantly greater reduction of office systolic blood pressure[mean difference(MD):-5.61 mm Hg,95%CI:-9.03 to-2.19,Z=3.21,P=0.0001]and 24-hour systolic blood pressure(MD:-4.40 mmHg,95%CI:-14.03 to-3.83,Z=5.09,P<0.00001)than controls.Renal denervation was not associated with an increased risk of major adverse events(RR:1.12,95%CI:0.72 to 1.64,Z=0.66,P=0.51),and estimated glomerular filtration rate(e GFR)[MD:0.35 mL/(min·1.73 m2),95%CI:-2.05 to2.74,Z=0.28,P=0.78]from baseline to 6 months is statistically insignificant with significant heterogeneity.Conclusions In selected resistant hypertension patients maintained on antihypertensive drugs,renal denervation with the SYMPLICITY systems did significantly decrease blood pressure.Renal denervation was not associated with an increased risk of major adverse events.

Screening for significant atherosclerotic renal artery stenosis with a regression model in patients undergoing transradial coronary angiography/intervention

Objective:Early detection of atherosclerotic renal artery stenosis (ARAS) is clinically important with respect to blood pressure control, prevention of renal insufficiency, and even improving survival. We investigated whether the presence of significant ARAS (luminal diameter narrowing ≥70%) could be predicted using a logistic regression model before coronary angiography/intervention. Methods:Initially, we developed a logistic regression model for detecting significant ARAS based upon clinical and angiographic features and biochemical measurements in a cohort of 1 813 patients undergoing transfemoral coronary and renal angiography. This model was then prospectively applied to an additional 495 patients who received transradial renal angiography to ascertain its predictive accuracy for the presence of significant ARAS. Results:Multivariate regression analysis revealed that older age (≥65 years), resistant hypertension, type 2 diabetes, creatinine clearance (Ccr) ≤60 ml/min, and multivessel coronary disease were independent predictors for significant ARAS. A logistic regression model for detecting ARAS by incorporating conventional risk factors and multivessel coronary disease was generated as:P/(1 P)=exp( 2.618+1.112[age≥65 years]+1.891[resistant hypertension]+0.453[type 2 diabetes]+0.587[Ccr≤60 ml/min]+2.254[multivessel coronary disease]). When this regression model was prospectively applied to the additional 495 patients undergoing transradial coronary and renal angiography, significant ARAS could be detected with a sensitivity of 81.2%, specificity of 88.9%, and positive and negative predictive accuracies of 53.8% and 96.7%, respectively. Conclusions:The logistic regression model generated in this study may be useful for screening for significant ARAS in patients undergoing transradial coronary angiography/intervention.