Subgroup Of Hypertensive Patients Research Articles

HYPERTENSIVE HEART DISEASE, WHAT ARE THE FACTORS PRECIPITATING ITS EARLY ONSET?

Objective: Hypertension is a well-established risk factor for cardiovascular disease. It causes left ventricular pressure overload, and changes in cardiac geometry and LV hypertrophy. This study is intended to assess the clinical and echocardiographic factors associated with and predictive for early impairment of left ventricular function as assessed using global longitudinal strain evaluation in hypertensive patients. Design and method: Cross-sectional descriptive study, with a total number of 130 hypertensive and with the objective of evaluating the study of longitudinal function by 2D strain in patients with systemic hypertension with preserved LVEF and the determination of predictors the decrease GLS in this population. This work is to make a complete study echo cardiographic, including LVEF biplane Simpson method, calculation of left ventricular mass indexed and relative parietal thickness, analysis diastolic function and the study of longitudinal strain of the LV by the speckle tracking technique (calculation of GLS) Results: The prevalence of left ventricular hypertrophy (LVH) was found in (66%). half of the patients (49%) presented a concentric hypertrophy, It was clearly noted that 73%of the patients had a relative wall thickness (RWT)> 0.42. Alterations in diastolic function were detected in 89% of the group, 18% had severe diastolic dysfunction with elevation in filling pressure. Analysis of the longitudinal systolic function of the left ventricle took the average GLS as a reference value. The mean GLS was found to be -16.9 ± 3.2%, within a range between -25% and-11.6%. Low GLS values (>-17%) were found in 45.5%. In particular, 34.4% of the patients had no left ventricular hypertrophy (LVH) and 50.7% of them presented LVH. The average systolic and diastolic blood pressures, taken at the time of echocardiographic analysis, were found higher in the subgroup of hypertensive patients with low GLS. Statistical analysis revealed significant correlation between the decrease in GLS and diabetes the values of blood pressure and elevated filling pressures. Conclusions: The evaluation of longitudinal systolic function by 2D strain provides new insight of myocardial function in hypertension that could improve the pathophysiological understanding and identify high-risk heart failure patients eligible for preventive strategies.

Incidence of Primary Aldosteronism in Patients with Hypokalemia (IPAHK+): Study Design and Baseline Characteristics.

Hypokalemia plays a central role for case finding, course, treatment decision, and prognosis of patients with primary aldosteronism. However, to date there is a lack of high-level evidence about the incidence of primary aldosteronism in hypokalemic patients. The IPAHK+study is an epidemiological, cross-sectional, monocentric study to provide evidence on the incidence of PA in a hypokalemic population. The aim of the current analysis was to describe the baseline characteristics of the first 100 patients eligible for study inclusion. The recruitment of patients with hypokalemia (≤3 mmol/l) is carried out continuously on a referral-basis by the central laboratory of the University Hospital Zurich through an automated suitability testing and data delivery system. The careful evaluation of the first 100 reported patients was based on the available reporting system. Out of 28 140 screened patients, 222 (0.79%) were identified with a serum potassium value of≤3 mmol/l (mean 2.89±0.02 mmol/l). Mean potassium levels were slightly lower in non-hypertensive subjects compared to hypertensive subjects (mean difference 0.07 mmol/l, p=0.033), while no significant difference was found between the sexes and patients with and without the diagnosis of primary aldosteronism, atrial fibrillation, or the use of diuretics. The incidence of PA was 4% in the total population studied and 7.5% in the subgroup of hypertensive patients. In conclusion, the continuous enrollment of patients from the IPHAK+hypokalemia registry into the IPAHK+trial will provide evidence about the actual incidence of primary aldosteronism in a hypokalemic outpatient population.

Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Spirulina is a microalga that presents various important pro-health properties, for instance lowering blood pressure in the research. The study aims to appraise the efficacy of Spirulina administration on systolic (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved by a systematic search of PubMed, Web of Science, and the Cochrane Library databases from inception to June 2021 according to a standardized protocol. The effect size of each study was counted from mean and standard deviation before and after the intervention and shown as Un-standardized mean difference and 95% confidence interval. Sensitivity analyses were performed. Meta-analysis on 5 RCTs with 230 subjects was eligible. The amount of Spirulina ranged from 1 to 8 g per day, and intervention durations ranged from 2 to 12 weeks. Data analysis indicated that Spirulina supplementation led to a significant lowering of SBP (Mean Difference (MD): −4.59 mmHg, 95% Confidence Interval (CI): −8.20 to −0.99, I square statistic (I2) = 65%) and significant lowering of DBP (MD: −7.02 mmHg, CI: −8.86 to −5.18, I2 = 11%), particularly in a subgroup of hypertensive patients. Spirulina administration might have a supportive effect on the prevention and treatment of hypertension. More exact randomized controlled trials are needed to clarify the effect of Spirulina supplementation on blood pressure.

Assessment of the study of longitudinal systolic function by 2D strain in hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Center of Tlemcen Introduction Hypertension is a well-established risk factor for cardiovascular disease. It causes left ventricular (LV) pressure overload, and, changes in cardiac geometry and LV hypertrophy(LVH). LVH as well as patterns of abnormal geometry have been associated with adverse outcomes. Global longitudinal strain (GLS) has been used to detect early subclinical myocardial dysfunction in a broad spectrum of cardiac conditions and thereby provides a novel approach for LV risk assessment in patients with hypertension. Purpose This study is intended to assess the clinical and echocardiographic factors associated with and predictive for early impairment of left ventricular function as assessed using GLS evaluation in hypertensive patients. Methods Cross-sectional descriptive study, with a total number of 130 hypertensive and with the objective of evaluating the study of longitudinal function by 2D strain in patients with systemic hypertension with preserved LVEF and the determination of predictors the decrease GLS in this population. A complete study echo cardiographic, including LVEF biplane Simpson method, calculation of left ventricular mass indexed and relative parietal thickness to differentiate the eccentric and concentric LVH, analysis diastolic function and finally the study of longitudinal strain of the LV by the speckle tracking technique (calculation of GLS) to seek a possible decline in the GLS and establish a possible correlation between this drop and power and LVH the diagnosis of subclinical hypertensive heart disease. Results The prevalence of left ventricular hypertrophy (LVH) was found in (66%) in this population. half of the patients (49%) presented a concentric hypertrophy, It was clearly noted that 73%of the patients had a relative wall thickness (RWT)>0.42. Alterations in diastolic function were detected in 89% of the group, 18% had severe diastolic dysfunction with elevation in filling pressure. Analysis of the longitudinal systolic function of the left ventricle took the average GLS as a reference value. The mean GLS was found to be -16.9 ± 3.2%, within a range between -25% and-11.6%. Low GLS values (>-17%) were found in 45.5% of the general population. In particular, 34.4% of the patients had no left ventricular hypertrophy (LVH) and 50.7% of them presented LVH. The average systolic and diastolic blood pressures, taken at the time of echocardiographic analysis, were found higher in the subgroup of hypertensive patients with low GLS. Very low GLS values (>-13%) were found in 11% of the general population. Statistical analysis revealed significant correlation between the decrease in GLS and diabetes the values of blood pressure and elevated filling pressures. Conclusion The evaluation of longitudinal systolic function provides new insight of myocardial function in hypertension that could improve the pathophysiological understanding and identify high-risk heart failure patients eligible for preventive strategies.

Association of rs12204590 polymorphism with the development of stroke in hypertensive patients

The stroke is one of the most serious complications of arterial hypertension (HTN). Genetic markers of the disease can be used to improve the risk stratification. According to the literature data of single nucleotide polymorphism (SNP) rs12204590 (T > A) is a new potential genetic marker for stroke, however, in published studies, cardiovascular pathology preceding stroke was not assessed. Objective. To study the association of SNP rs12204590 (T > A) with the development of stroke in patients of the East Siberian population with HTN and without HTN. Design and methods. The study involved 260 patients with stroke (age 57,0 [51,0-62,0] years) and 272 patients of the control group (age 55,0 [51,0-62,0] years). Among stroke survivors, there were 157 men and 103 women. The control group included 170 men and 102 women. 249 patients ofthe main group and 177 patients of the control group had HTN. The following risk factors for the development of stroke were present in the main group: paroxysmal supraventricular tachycardias, dyslipidemia, atherosclerosis of the brachiocephalic arteries, disorders of the hemostasis system. All participants underwent clinical, instrumental and molecular genetic research. Statistical analysis was carried out using the programs Statistica for Windows 7.0, Excel and SPSS 22. Results. The association of TA genotype SNP rs 122045 90 (T > A) with the development of stroke was confirmed in the main group, as well as in the subgroup of HTN patients who had stroke. An association of the AA genotype with stroke was found in males. Associations of the studied polymorphism with the risk factors for stroke were not identified. Conclusions. The TA genotype rs12204590 (T > A) reduces the risk of acute stroke compared to the genotypes TT and AA, which is also observed in HTN patients. The AA SNP genotype rs12204590 (T > A) increases the risk of developing stroke in males.

2019 Consensus Statement of the Taiwan Hypertension Society and the Taiwan Society of Cardiology on Renal Denervation for the Management of Arterial Hypertension.

Sympathetic overactivity, an essential mechanism of hypertension, in driving sustained hypertension derives mostly from its effects on renal function. Percutaneous renal denervation (RDN) is designed to disrupt renal afferent and efferent sympathetic nerves to achieve sustained blood pressure (BP) reduction. Since 2017 onward, all three proof-of-concept, sham-controlled RDN trials demonstrated that RDN achieved consistent and clinically meaningful BP reductions [approximately 10 mmHg in office systolic BP (SBP) and 6-9 mmHg in 24-hour SBP] compared to sham operation in patients with mild to moderate or uncontrolled hypertension. There were no serious adverse events. The registry data in Taiwan showed similar 24-hour BP reductions at 12 months following RDN. The Task Force considers RDN as a legitimate alternative antihypertensive strategy and recommends 1) RDN should be performed in the context of registry and clinical studies (Class I, Level C) and 2) RDN should not be performed routinely, without detailed evaluation of various causes of secondary hypertension and renal artery anatomy (Class III, Level C). RDN could be performed in patients who fulfill either of the following BP criteria: 1) office BP ≥ 150/90 mmHg and daytime ambulatory SBP ≥ 135 mmHg or diastolic BP (DBP) ≥ 85 mmHg, irrespective of use of antihypertensive agents (Class IIa, Level B), or 2) 24-hour ambulatory SBP ≥ 140 mmHg and DBP ≥ 80 mmHg, irrespective of use of antihypertensive agents (Class IIa, Level B), with eligible renal artery anatomy and estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2. Five subgroups of hypertensive patients are deemed preferred candidates for RDN and dubbed "RDN i2": Resistant hypertension, patients with hypertension-mediated organ Damage, Non-adherent to antihypertensive medications, intolerant to antihypertensive medications, and patients with secondary (2ndary) causes being treated for ≥ 3 months but BP still uncontrolled. The Task Force recommends assessment of three aspects, dubbed "RAS" (R for renal, A for ambulatory, S for secondary), beforehand to ascertain whether RDN could be performed appropriately: 1) Renal artery anatomy eligibility assessed by computed tomography or magnetic resonance renal angiography if not contraindicated, 2) genuine uncontrolled BP confirmed by 24-hour Ambulatory BP monitoring, and 3) Secondary hypertension identified and properly treated. After the procedure, 24-hour ambulatory BP monitoring, together with the dose and dosing interval of all BP-lowering drugs, should be obtained 6 months following RDN. Computed tomography or magnetic resonance renal angiography should be obtained 12 months following RDN, given that renal artery stenosis might not be clinically evident.

Association of allostatic load with health-related quality of life in patients with arterial hypertension: a cross-sectional analysis.

Allostatic load (AL), as a marker of cumulative stress, is associated with higher morbidity and mortality, and reduced health-related quality of life (HrQoL) in healthy adults. In patients with hypertension, AL and its association with HrQoL have not been investigated. Therefore, this study aimed to (1) explore AL in a cohort of hypertensive patients and to (2) determine its association with HrQoL, while controlling for other health-related variables. Cross-sectional data from the Styrian Hypertension Study were analysed and included 126 participants (50% female) with a history of arterial hypertension; the mean age was 60.9 years (standard deviation 9.9). AL was derived from a set of 10 biomarkers including neurophysiological, neuroendocrine, metabolic, cardiovascular and inflammatory parameters. The 36-Item Short Form Health Survey (SF-36) was administered for assessment of HrQoL. Additional health-related variables included sociodemographic data, lifestyle factors and comorbidities. Calculation of AL resulted in sum scores based on 10 binary variables, which were used to categorise patients as either “low AL” (<3) or “high AL” (≥3). Multivariate adjusted analyses revealed that higher AL was associated with better HrQoL with regard to the mental health domain F(1,1243) = 7.017; p = 0.009). All other components of HrQoL were not related to AL. In contrast to results in healthy populations, we found a positive association between AL and the mental health domain of HrQoL. This finding suggests a specific coping pattern among a subgroup of hypertensive patients, possibly influencing their clinical management and outcome.

Prevalence of diabetes and dyslipidemia in hypertensive patients in the area of Blida (Algeria)

PurposeDiabetes mellitus (DM) and lipid disorders (LD) in hypertensive patients are associated with an increased risk of cardiovascular complications requiring follow-up and more aggressive therapeutic strategies. The main objective of this study was to describe the prevalence of DM and LD in adult hypertensive patients followed in specialized consultation of hypertension in the region of Blida (North Algeria) during the period from January 2013 to June 2017. Materials and methodsWe included 3268 hypertensive patients (1453 men and 1815 women), mean age of 58.3±13.8years. Descriptive statistics were used to estimate means by sex and age for subgroups [under 30, 30–39, 40–49, 50–60, over 70]. A linear regression was used to determine annual trends. The age and sex specific results were adjusted to the general population data of the city of Blida for a period of 4years and each year studied. ResultsThe mean prevalence of diabetes was 21.8% and glucose tolerance was 10.9% without significant trend of increase during the study period in the overall population and according to sex, while in the subgroup of hypertensive patients over 60, there has been an increase in the prevalence of diabetes and a decrease in glucose tolerance over the 4 years (R2=0.78, P=0.05 and R2=0.95, P=0.005, respectively). The mean prevalence of LD for the study period was 16.1% without significant trend at 4years. The increase in total cholesterol combined with the increase in low-density lipoprotein (LDL) levels was the most common disorder (32.2%). There was no significant difference in LD prevalence and characteristics in subgroups by sex. Age group analysis showed a greater increase in the frequency of lipid disorders in patients over 60years of age (R2=0.80, P=0.001). ConclusionsOver the 4years of study, age over 60 was associated with an increase in the prevalence of metabolic disorders in hypertensive patients. This trend may explain the poor control of BP. Above all, it must be taken into account for the requirement to achieve therapeutic objectives that effectively reduce the risk of cardiovascular complications occurring in these high-risk patients whose number is becoming increasingly important.

P3553Biomarkers of kidney injury, vascular stiffness and kidney fibrosis in gender subgroups of hypertensive patients

P3553Biomarkers of kidney injury, vascular stiffness and kidney fibrosis in gender subgroups of hypertensive patients

Mechanical Deformation in Patients with Systemic Arterial Hypertension

Background: Systemic arterial hypertension represents the mayor risk factor for several cardiovascular diseases. In a large number of patients it affects the left ventricle by a compensating hypertrophy and posteriorly when this mechanism is insufficient, it leads to heart failure and therefore the patient requires regular echocardiographic monitoring. Subclinical dysfunction of the left ventricle exists even in asymptomatic hypertensive patients with preserved left ventricular ejection fraction. Objectives: The main aim of our study was focused in the assessment of left ventricular mechanical deformation in 20 patients with systemic arterial hypertension and 21 healthy controls. Results: A total of 41 subjects were studied, 22 women and 19 men. The hypertensive group consisted of 20 patients and the healthy control group of 21 subjects. The echocardiographic findings that had significative differences between hypertensive patients and healthy controls were left ventricle mass index, E/A ratio, E/e´ ratio and systolic pulmonary arterial pressure. In patients with hypertension, the radial deformation had a significative reduction, p=0.002, but the longitudinal deformation was statistically decreased (p=0.008), only in the subgroup of hypertensive patients with left ventricular hypertrophy. Conclusion: The patients with systemic hypertension require a close follow-up in order to identify the most accurate echocardiographic parameter for diagnosis of subclinical dysfunction. In our study, the global radial deformation was significatively diminished in the hypertensive patients and the global longitudinal deformation was decreased only in the subgroup of hypertensive patients with left ventricular hypertrophy.

PP.32.18] PREVALENCE OF DIABETES AND LIPID DISORDERS IN HYPERTENSION PATIENTS REFERRED TO SPECIALIZED CARDIOLOGICAL CENTRE

Objective: Diabetes mellitus (DM) and lipid disorders in hypertensive patients are associated with higher risk of cardiovascular complications and poor outcome and require more aggressive treatment strategies and follow-up. The main objective of this study was to describe trends in prevalence of DM and lipids disorders in adult hypertensive patients referred to specialized cardiology clinic during the period of January 2010 - December 2014. Design and method: Data included 59268 (21153 males and 38115 females) patients, mean age 58.3 ± 13,8 years, referred to specialized clinic due to uncontrolled hypertension. Descriptive statistics were used to estimate the means in gender and age [under 35 years (n = 4079), 35–49 (n = 8566), 50–65 (n = 26381), older than 65 (n = 20242) years] subgroups. Linear regression was employed to determine the yearly trends. Age and gender-specific results were adjusted to Saint-Petersburg general population data for 5-years period and every studied year. Results: The average prevalence of known lipid disorders for the studied period was 3,7% (2160 patients) without any significant 5-years trends. Increased level of total cholesterol in combination with increased low density lipoprotein levels was the most frequent disorder (917 cases; 42,7%). There were no significant changes in prevalence and characteristics of lipids disorders in gender subgroups. Analysis of age groups demonstrated increase in lipid disorders frequency in patients over 65 years (R2 = 0,80; p = 0,04). The average prevalence of known diabetes was 14,5% (8592 patients) and impaired glucose tolerance 0,9% (518 cases) without any significant trends during studied period in overall population and in gender subgroups. While in subgroup of hypertensive patients over 65 years there was an increase in prevalence of diabetes and impaired glucose tolerance during the last 5 years (R2 = 0,78, p = 0,05 and R2 = 0,95 p = 0,005, respectively). Conclusions: During the last 5 years age older than 65 was associated with increase in prevalence of metabolic disorders in difficult to control hypertension. These trends can be important for the total risk reduction in the elderly and explain poor blood pressure control in this subgroup.

Effect of community health worker-provided targeted education with regular follow-up of hypertensive patients on blood pressure control: 24-month results of a longitudinal study in Bangladesh

Context: Sustainability of blood pressure (BP) control by trained community health workers (CHWs) in a low awareness setting is yet to be explored. Aim: The aim of this study is to assess the effect of CHW-provided targeted education with regular follow-up of hypertensive patients on BP control. Materials and Methods: We conducted a longitudinal study on hypertension in a semi-urban and a rural district in Bangladesh. Adult hypertensive individuals (n = 287) were identified. Trained CHWs regularly followed up and provided specific health messages on BP control through quarterly group meetings and individual counseling. We assessed mean BP changes and control status (systolic BP [SBP] <140 mmHg and diastolic BP [DBP] <90 mmHg) at around every 6 months for 24 months. A subgroup of hypertensive patients (n = 118) age >40 years was compared with an unmatched comparison group (n = 226) under usual care. Results: Both SBP and DBP of hypertensive patients under intervention were significantly reduced compared to baseline. The intervention subgroup had a significant lower SBP (149.1 ± 17.7 mmHg vs. 141.3 ± 20.34 mmHg; P = 0.004) and DBP (86.7 ± 13.32 mmHg vs. 91.31 ± 13.54 mmHg; P = 0.003) compared to comparison group. Proportion achieved BP control was higher (44.1% vs. 26.7%, P = 0.001) in the intervention subgroup. Patients who visited qualified providers within a year were 2 times more likely to be under better BP control. Conclusion: Targeted education with regular follow-up of hypertensive patients by trained CHWs has the potential to reduce BP and enhance BP control in settings with low awareness.

Abstract 9850: Cardioprotective Role of Zofenopril in Hypertensive Patients With Acute Myocardial Infarction: A Pooled Individual Data Analysis of Four Randomized, Double-blind, Controlled, Prospective Studies

Introduction: the SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies demonstrated that early administration of zofenopril following acute myocardial infarction (AMI) is prognostically beneficial compared to placebo or other angiotensin-converting enzyme inhibitors (ACE-inhibitors). Hypothesis: In the present meta-analysis of individual data of four SMILE studies we evaluated the cumulative efficacy of zofenopril on cardiovascular (CV) morbidity and mortality in the subgroup of hypertensive patients. Methods: 1880 (53.1%) of the 3542 patients had a positive history for hypertension. 449 hypertensives and 486 normotensives were treated with placebo (SMILE 1 and 3), 980 and 786 with zofenopril 30-60 mg/die (all four studies), 451 and 390 with lisinopril 5-10 mg/die (SMILE 2) or ramipril 10 mg/die (SMILE 4). Treatment was continued for 6 to 48 weeks. For the purpose of this pooled analysis the primary study endpoint was set to 1-year combined occurrence of death or hospitalization for CV causes. Results: the risk of CV events was significantly reduced by 35% with zofenopril vs. placebo [HR: 0.65; 95% CI: 0.49-0.86; p=0.003) in hypertensive patients and by 41% in normotensive patients (0.59; 0.44-0.79; p=0.0001). The other ACE-inhibitors reduced CV morbidity and mortality as well, though the reduction (-17%) was not statistically significant vs. placebo either in hypertensives (0.83; 0.57-1.21; p=0.338) or normotensives (reduction: -24%; HR: 0.76; 0.50-1.15; p=0.194). Treatment with zofenopril of hypertensive and normotensive patients was associated with a non-statistically significant reduction in the risk of CV outcomes as compared to the other ACE-inhibitors (hypertensives: 0.78; 0.60-1.01; p=0.062; normotensives: 0.77; 0.55-1.10; p=0.1509. Conclusions: in high-risk cardiac patients with arterial hypertension, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared to placebo, with an efficacy similar to that of other ACE-inhibitors, such as lisinopril and ramipril.

PP.LB02.10

Objective: The SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies demonstrated that early administration of zofenopril following acute myocardial infarction (AMI) is prognostically beneficial compared to placebo or other angiotensin-converting enzyme inhibitors (ACE-inhibitors). In the present meta-analysis of individual data of four SMILE studies we evaluated the cumulative efficacy of zofenopril on cardiovascular (CV) morbidity and mortality in the subgroup of hypertensive patients. Design and method: 1880 (53.1%) of the 3542 patients had a positive history for hypertension. 449 hypertensives and 486 normotensives were treated with placebo (SMILE 1 and 3), 980 and 786 with zofenopril 30–60 mg/die (all four studies), 451 and 390 with lisinopril 5–10 mg/die (SMILE 2) or ramipril 10 mg/die (SMILE 4). Treatment was continued for 6 to 48 weeks. For the purpose of this pooled analysis the primary study endpoint was set to 1-year combined occurrence of death or hospitalization for CV causes. Results: The risk of CV events was significantly reduced by 35% with zofenopril vs. placebo [HR: 0.65; 95% CI: 0.49–0.86; p = 0.003) in hypertensive patients and by 41% in normotensive patients (0.59; 0.44–0.79; p = 0.0001). The other ACE-inhibitors reduced CV morbidity and mortality as well, though the reduction (−17%) was not statistically significant vs. placebo either in hypertensives (0.83; 0.57–1.21; p = 0.338) or normotensives (reduction: −24%; HR: 0.76; 0.50–1.15; p = 0.194). Treatment with zofenopril of hypertensive and normotensive patients was associated with a non-statistically significant reduction in the risk of CV outcomes as compared to the other ACE-inhibitors (hypertensives: 0.78; 0.60–1.01; p = 0.062; normotensives: 0.77; 0.55–1.10; p = 0.1509). Conclusions: In high-risk cardiac patients with arterial hypertension, zofenopril treatment is associated with a clinically relevant reduction in long-term CV morbidity and mortality, compared to placebo, with an efficacy similar to that of other ACE-inhibitors, such as lisinopril and ramipril.

Rebuttal from Markus P. Schlaich, Yusuke Sata and Murray D. Esler.

Extreme positions are rarely useful and almost invariably hinder rather than facilitate progress in clinical science. Dr Jordan (Jordan, 2014) and Dr Paton (Ratcliffe et al. 2014) and their colleagues seem to share this view and, while making a strong case for each of their points, have provided a reasonably balanced appraisal of the evidence surrounding the interventional approaches for resistant hypertension under debate. Importantly, we seem to share common ground in the view that resistant hypertension is a relevant clinical problem, that non-adherence to prescribed medication is common, that alternative and perhaps device-based therapeutic approaches are needed, and that sympathetic overactivity is a major contributor to the pathophysiology of resistant hypertension thereby providing a logical therapeutic target. Our views differ in how this is best achieved. Dr Jordan elegantly reviews the role of baroreflex circuits in long-term blood pressure (BP) control and how electrical carotid sinus stimulation (CCS) may ameliorate resistant hypertension. While highlighting potential advantages of CCS such as the ability of stimulation adjustment, it becomes clear from his pathophysiological considerations that sympathetic inhibition, specifically suppression of efferent renal sympathetic nerve activity, is an important mediator of CCS-induced depressor responses (Iliescu et al. 2012). Why not target the renal nerves directly when this can be achieved safely with catheter-based approaches (Esler et al. 2010; Bhatt et al. 2014)? Carotid body (CB) denervation is the least developed and investigated approach, which does not negate the physiological relevance of chemoreceptor activation and its role in modulation of both sympathetic nerve activity and blood pressure. Dr Paton promotes the concept of CB tonicity driving sympathetic vasomotor activity chronically, particularly in the scenario of hypertension (Paton et al. 2013). Surgical resection of the CB has been performed to alleviate dyspnoea in patients with obstructive airway disease and coincidentally, a BP reduction was observed in a subgroup of hypertensive patients (Nakayama, 1961). Clearly, recent experimental data is more convincing (McBryde et al. 2013). Nevertheless, evidence for a pivotal role of CB-related mechanisms in human resistant hypertension is weak and the concept far from proven. Major concerns that need to be addressed relate to the potential attenuation or loss of hypoxic ventilatory drive and the potentially serious procedural complications. In keeping with the hypothetical ideals for an interventional approach brought forward by Dr Paton, we would argue that renal denervation remains the most promising therapeutic approach despite the recent setback from a suboptimally conducted clinical trial (Bhatt et al. 2014).

Renal Nerve Ablation for Hypertensive Patients with Chronic Kidney Disease

Among current epidemics, chronic kidney disease (CKD) is accompanied with high morbidity and mortality rates inherently associated with the thriving comorbidities of hypertension and cardiovascular disease. In this mutually reinforcing triad, adequate control of high blood pressure emerges as extremely important for decreasing patients' complication rates and prolonging life expectancy. However, hypertension control in this particular group of patients is often proven an arduous task, presenting high rates of resistance. Sympathetic nervous system (SNS) overactivity is implicated not only in the pathophysiological basis of difficult-to-treat hypertension, but also in the development and progression of renal disease, thus rendering SNS a prime therapeutic target in CKD. As renal nerve ablation (RNA) is finding its place among other invasive procedures in the cardiovascular arena, the potential therapeutic impact of this innovative treatment modality is gradually expanding from resistant hypertension to other high blood pressure-related clinical conditions like CKD. Encouraging results of clinical trials testing efficacy and safety of renal nerve ablation in resistant hypertensives provide the opportunity to apply the procedure in other subgroups of hypertensive patients. Available data regarding renal function of study participants suggest the safe implementation of RNA in patients with renal disease, but both unexplored benefits as well as potential hazards should be taken into account and critically evaluated. While renal denervation has been tested in selected cases of patients with renal disease, the results of large, multicenter trials evaluating the effects of this procedure on large cohorts of patients with CKD are eagerly anticipated.

Prevalence and determinants of controlled hypertension in a German population cohort

BackgroundData of the German population-based cohort SHIP (Study of Health in Pomerania) were analysed to examine treatment rates, antihypertensive substances prescribed, and the proportion of hypertensive study participants reaching target values for blood pressure as well as determinants.MethodsThe study population was defined using baseline data of the cohort (collected between 1997 and 2001). Participants with blood pressure values ≥140/90 mmHg and/or antihypertensive medication with known hypertension and participants with risk-comorbidity (diabetes, stroke, angina pectoris, and/or myocardial infarction) and blood pressure values ≥130/80 mmHg were included. The analysis of treatment and target values was based on the 5-year follow-up of the cohort (collected between 2002 and 2006). Logistic regression was used to identify determinants for a normotensive blood pressure.Results3278 SHIP-participants with hypertensive blood pressure values were included (mean age: 55.5 years; SD 13.6, range 21–80 years). The raw hypertension prevalence was 50.9% (N = 1761). 58.7% (N = 1074) of all hypertensive patients reported some form of antihypertensive treatment. Thereof 65.1% (N = 728) received combination therapy. Of the patients without risk-comorbidity, 42.1% (N = 489) reached their target blood pressure values at the time of the 5-year follow-up of the cohort. Of the patients with any risk-comorbidity this proportion was only 21.7% (N = 131). Significant determinants for reaching the target values were being female and having antihypertensive combination therapy. Increasing age, having risk-comorbidities, and obesity were negatively associated with reaching the target values.ConclusionsBoth the proportion of participants receiving therapy and the number of participants reaching their target blood pressure values are very low. Combination therapy is associated with better blood pressure control as compared to mono therapy. However, even in the subgroup of hypertensive patients under combination therapy only 36% (both patients with and without comorbidity) reach target values.

The dual blockade of the renin-angiotensin system in Internal Medicine: after ONTARGET trial

BACKGROUND In the increasing progress of scientific knowledge, every new discovery is a basis for new problems. In fact, after the success of Angiotensin-Converting Enzyme (ACE)-inhibitors in different cardiovascular diseases, the evidence of the “escape” of ACE and the discovery of Angiotensin- Receptor Blockers (ARBs) became the basis for a new question: is a dual blockade of the Renin-Angiotensin System (RAS) correct? DISCUSSION The different trials carried out (also the latest ONTARGET) didn’t give reliable answers, because differences were found both in the various diseases (hypertension, heart failure, coronary disease, nephropathy, diabetic or not), and between the single drugs of the class. We can say that this combination treatment didn’t show reliable clinical efficacy yet, except in heart failure and in some subgroups of hypertensive patients, checking carefully serum electrolytes and renal function. But even though we haven’t got certain outcomes, the research goes on quickly and some other sites of modulation of RAS were identified, from its first phases (aliskiren as prototype of direct renin inhibitors).

Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion

In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. Retrospective, cross-sectional study. The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

APEX1 Regulation of Aldosterone Synthase Gene Transcription Is Disrupted by a Common Polymorphism in Humans

The genetic mechanisms underlying hypertension are unclear, but relative aldosterone excess, present in ≈10% of hypertensive patients, is known to be a heritable trait. This phenotype associates with a T/C single nucleotide polymorphism (SNP) at position -344 of the aldosterone synthase gene (CYP11B2). However, deletion of this SNP has no effect on gene transcription. We have identified another T/C SNP at -1651, in tight linkage disequilibrium with the -344 SNP and here investigate its functional effect on CYP11B2 transcription. We assessed the effect on transcriptional activity of the -1651 T/C SNP in vivo and in vitro and propose the mechanism by which transcriptional activity is altered. We demonstrated that the SNP at -1651 exerts significant allele-dependent effects on CYP11B2 transcription. We confirm binding of the transcriptional repressor APEX1 to -1651T, which is associated with reduced transcriptional activity in relation to the less strongly bound -1651C. We show that inhibiting APEX1 by small molecule inhibition or small interfering RNA (SiRNA) leads to increased CYP11B2 transcription. In addition, overexpression of APEX1 is associated with reduced transcriptional activity. Finally, we also show that -1651T associates with lower excretion rates of aldosterone metabolites in human subjects. We conclude that APEX1 is a novel transcriptional repressor of CYP11B2 and that differential APEX1 binding at -1651 of CYP11B2 results in altered gene expression. This mechanism may contribute to the observed relationship between CYP11B2 genotype and aldosterone phenotype in a subgroup of hypertensive patients.