Initiation Of Antihypertensive Therapy Research Articles

Design and rationale for a randomized, open-label, parallel clinical trial evaluating major adverse cardiovascular events (pharmacological treatment versus diet control) in patients with high-normal blood pressure: the PRINT-TAHA9 trial

BackgroundThe distinction between normal and high blood pressure remains a debated topic, with varying guidelines on when to start medication. Contemporary guidelines advocate for the initiation of antihypertensive therapy in individuals who present with high-normal blood pressure, particularly those exhibiting elevated 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores. Despite these recommendations, there is a notable lack of direct evidence supporting the efficacy of treating high-normal blood pressure to prevent major adverse cardiovascular events (MACE).MethodsThe PRINT-TAHA9 trial, a unicentric, randomized, open-label, controlled, parallel clinical study, seeks to explore the effects of intensive blood pressure control on MACE in participants with high-normal blood pressure. We will enroll 1620 adults aged 18 years and above with a systolic blood pressure range of 130–140 mmHg, diastolic blood pressure under 90 mmHg, and atherosclerotic cardiovascular disease (ASCVD) risk score exceeding 7.5%. The study will be executed in five distinct phases, with each phase enrolling between 300 and 400 participants. Participants will be randomly assigned to either the treatment group receiving antihypertensive medication (amlodipine/valsartan) and a low-salt/low-fat diet or to the control group receiving a similar diet. Follow-up visits are scheduled every 6 months over a 3-year period to monitor blood pressure, evaluate medication adherence, document any adverse events, and adjust the intervention as necessary. Cox proportional hazards regression analysis will be employed to examine the disparities between the two arms.DiscussionDespite guidelines promoting early treatment of elevated blood pressure, the debate continues due to insufficient evidence that such interventions significantly reduce the occurrence of MACE. This trial seeks to address this critical evidence gap.Trial registrationThe PRINT-TAHA9 trial was registered in October 2019 with the Iranian Registry of Clinical Trials (IRCT.ir) under the registration number IRCT20191002044961N1. https://irct.behdasht.gov.ir/trial/43092.

STOPPING ANTIHYPERTENSIVE TREATMENT AMONG HYPERTENSIVE PATIENTS IN PRIMARY CARE: THE STOP-TRIAL

Objective: Objective: Frequently antihypertensive therapy (AHT) is initiated without the confirmation of high blood pressure (BP) outside the office. Such AHT initiation based solely on office BP measurements may lead to overtreatment of otherwise non-hypertensive people who do not have a clinical indication for AHT. Therefore, identifying people in whom AHT can be safely discontinued is clinically important. The STOP-Trial aimed to identify factors associated with one-year normal BP maintenance after discontinuation of monotherapy or low-dose dual AHT among people with controlled BP and no cardiovascular target-organ damage. Design and method: Design and Method: We performed a multicenter non-randomized open-label trial screening people without target organ damage on AHT. AHT could be discontinued if BP was confirmed as controlled based on repeated home blood pressure measurements (HBPM) (i.e.,<135/85mmHg). The primary endpoint was one-year normal BP maintenance as assessed by HBPM. Results: Results: Among 401 screened individuals, 218(54.4%) were included after confirming they had controlled BP in HBPM and AHT was consequently discontinued. Among these 218 individuals, 73(33%) exhibited normal BP in HBPM at one year without any AHT (Figure). In univariable analysis, baseline office BP measurements were not significant predictors of the primary outcome whereas HBPM were. On multivariable analysis, higher average SBP and DBP on HBPM prior to AHD stop was associated with lower rates of one-year normal BP (OR for 5 mmHg of respectively, SBP=0.72, 0.56-0.94, p=0.014, and DBP=0.56, 0.41-0.77, p=0.0003). The best cut-offs of SBP and DBP on HBPM prior to AHD stop to predict the primary outcome was SBP=122.5mmHg and DBP=74.5mmHg. Patients with SBP<122.5 and DBP<74.5mmHg at HBPM prior to AHD stop had 65% chance of normal one-year BP without treatment. Regarding safety, one patient had a severe adverse event (ischemic stroke). Conclusions: Stopping AHT was feasible in patients without cardiovascular damage who had mono or low-dose dual AHT and maintained at one year in 33% of the population. HBPM measurements under treatment predicted well the success of AHD removal and HBPM consequently appears to be an efficient tool to select patients in whom AHD discontinuation may be safely considered.

Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial)

Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval,-1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively). De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

Blood pressure cutoffs at 11–13 weeks of gestation and risk of preeclampsia

A parallel has been drawn between first-trimester placental vascular maturation and maternal cardiovascular adaptations, including blood pressure. Although 140/90 mm Hg is well-accepted as the threshold for chronic hypertension in the general obstetric population in early pregnancy, a different threshold could apply to stratify the risk of adverse outcomes, such as preeclampsia. This could have implications for interventions, such as the threshold for initiation of antihypertensive therapy and the target blood pressure level. We evaluated the relationship between various blood pressure cutoffs at 11-13 weeks of gestation and the development of preeclampsia, overall and according to key maternal characteristics. This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals, 2006-2020. Blood pressure at 11-13 weeks of gestation was classified according to American College of Cardiology/American Heart Association categories (mm Hg) as (1) normal blood pressure (systolic <120 and diastolic <80), (2) elevated blood pressure (systolic ≥120 and diastolic <80), stage 1 hypertension (systolic ≥130 or diastolic 80-89), and stage 2 hypertension (systolic ≥140 or diastolic ≥90). For blood pressure category thresholds and the outcome of preeclampsia, the following were calculated overall and across maternal age, body mass index, ethnicity, method of conception, and previous pregnancy history: detection rate, screen-positive rate, and positive and negative likelihood ratios, with 95% confidence intervals. A P value of <.05 was considered significant. There were 137,458 pregnancies screened at 11-13 weeks of gestation. The population was ethnically diverse, with 15.9% of Black ethnicity, 6.7% of South or East Asian ethnicity, and 2.7% of mixed ethnicity, with the remainder of White ethnicity. Compared with normal blood pressure, stage 2 hypertension was associated with both preterm preeclampsia (0.3% to 4.9%) and term preeclampsia (1.0% to 8.3%). A blood pressure threshold of 140/90 mm Hg was good at identifying women at increased risk of preeclampsia overall (positive likelihood ratio, 5.61 [95% confidence interval, 5.14-6.11]) and across maternal characteristics, compared with elevated blood pressure (positive likelihood ratio, 1.70 [95% confidence interval, 1.63-1.77]) and stage 1 hypertension (positive likelihood ratio, 2.68 [95% confidence interval, 2.58-2.77]). There were 2 exceptions: a blood pressure threshold of 130/80 mm Hg was better for the 2.1% of women with body mass index <18.5 kg/m2 (positive likelihood ratio, 5.13 [95% confidence interval, 3.22-8.16]), and a threshold of 135/85 mm Hg better for the 50.4% of parous women without a history of preeclampsia (positive likelihood ratio, 5.24, [95% confidence interval, 4.77-5.77]). There was no blood pressure threshold below which reassurance could be provided against the development of preeclampsia (all-negative likelihood ratios ≥0.20). The traditional blood pressure threshold of 140/90 mm Hg performs well to identify women at increased risk of preeclampsia. Women who are underweight or parous with no prior history of preeclampsia may be better identified by lower thresholds; however, a randomized trial would be necessary to determine any benefits of such an approach if antihypertensive therapy were also administered at this threshold. No blood pressure threshold is reassured against the development of preeclampsia, regardless of maternal characteristics.

Comparative analysis of methods for evaluating myocardial hypertrophy in children with arterial hypertension

Relevance: over the past decades, the prevalence of arterial hypertension (AH) in the pediatric population has increased significantly, but there are still many open questions related to the diagnosis and course of the disease, the validity of the choice of antihypertensive therapy and the risks of target organ injury. In clinical practice, patients with hypertension are observed by a team of specialists of various profiles, and a unified approach to managing the disease is not always formed between them. Underestimation of risk factors, late detection of target organ injury and untimely start of antihypertensive therapy significantly increase the risks of an unfavorable, progressive course of the disease, aggravating the further prognosis. Strict adherence to the methods of diagnosing the disease and its potential consequences recommended by the professional community of pediatric cardiologists ensures an adequate initiation of drug therapy, which allows not only to control the course of hypertension, but also to prevent the development of long-term complications. Objective: to analyze the indicators obtained using the formula recommended by pediatric cardiologists compared to the routine method for detecting left ventricular myocardial remodeling in children with AH. Materials and methods: a cross-sectional, cohort, non-randomized study, which included 92 patients with newly diagnosed primary arterial hypertension, who were not receiving antihypertensive therapy at the time of the examination. The standard linear dimensions of the walls and cavities of the heart were assessed during echocardiography. The results were evaluated by the standard Fisher’s test, the xi2 test in the Statistica 9 software. The sample excluded children-athletes, patients with secondary hypertension, overweight, congenital heart disease and cardiomyopathy. All children were tested the same according to the current Federal Clinical Guidelines “Diagnosis and treatment of arterial hypertension in children and adolescents”. Results: the usage of the recommended formula is not only significantly more often allowed to identify the early stages of LV myocardial hypertrophy, but has great sensitivity. The routine method for calculating LV remodeling showed the norm much more often even in case of severe violation of the geometry of the heart. Conclusion: untimely detection of LV myocardial hypertrophy leads to late initiation of antihypertensive therapy, underestimation of risk factors, which increases the risk of an unfavorable course of the disease and the occurrence of long-term cardiovascular complications at a young age.

Abstract P195: Association Of Unmet Social Needs With Antihypertensive Medication Prescription And Dietitian Referral: Interim Analysis Of The Study Of The Epidemiology Of Pediatric Hypertension Registry (SUPERHERO)

HTN is a significant public health concern with increasing prevalence in youth. Optimizing BP control with both lifestyle counseling and antihypertensive medications improves health outcomes. However, adequate BP control remains difficult in majority of patients, in part due to a lack of understanding of how social determinants of health affect dietitian referral and initiation of antihypertensive therapy. We performed a cross-sectional analysis of baseline EHR data from the SUPERHERO Registry in youth who received initial care from sub-specialists for HTN disorders defined by ICD-10 codes from 1/1/2015-12/31/2022. We excluded those with pregnancy, kidney transplantation, and dialysis. We examined the association of individual-level social drivers (transportation, finances, food access housing) with the likelihood of antihypertensive medication prescription and dietitian referral at initial visit in youth with HTN disorders using unadjusted generalized linear models. Of our large cohort of 11,580, only 47 youth had at least one unmet social need (0.4%). Participants with at least one unmet social need were 1.81 times more likely to be prescribed antihypertensive medication (95% CL 0.94- 3.48; p= 0.08) and 6.73 times more likely to be referred to a dietitian (95% CL 3.7-12.25). We found that children with at least one unmet social need were more likely to be referred to a dietitian at the initial visit than those without an unmet social need. The small number of participants with unmet social needs might reflect poor screening or documentation practices. It is imperative that screening for unmet social needs is incorporated into clinical practice in youth with HTN disorders.

A clinical case of drug-induced arterial hypertension caused by glycyrrhizic acid

Background: In clinical practice, drug-induced arterial hypertension (AH) often remains undiagnosed, since the identification of an ethical disease in this form of AH avoids the initiation of antihypertensive therapy. A critical part in the differential diagnosis of hypertension and planning of long-term strategies for managing a patient requires a thorough study of the properties of the drugs taken and the pathophysiological mechanisms that depend on the increase in high blood pressure against the background of taking one or another substance. Clinical case description: Assumption of pregnancy in a random 57-year-old Caucasian female patient with AH syndrome and history of AD crisis during the year. Against the background of two-component antihypertensive therapy, indapamide 2.5 mg + telmisartan 80 mg, increased blood pressure. From the anamnesis of life, it is noteworthy that the patient should keep records with a hepatologist; with a diagnosis of chronic viral hepatitis C with moderate activity, she takes Phosphogliv. Physical examination confirmed the presence of grade 2 hypertension; no signs of target organ detection were found. Laboratory and instrumental research showed cytolytic syndrome of minimal activity (AST, 74.8 U/l; ALT, 60.5 U/l), hypokalemia (K+ 2.1 mmol/l), unknown etiology, aldosterone within the normal range, metanephrine (80.4 pg/ml at a rate of 64 pg/ml), and normetanephrine (276 pg/ml at a rate of 176 pg/ml) in blood plasma are increased. MSCT of the kidneys and adrenal glands revealed no enlarged formations. Drug-induced arterial hypertension was clinically diagnosed. Concomitant diseases: Chronic viral hepatitis C, moderate activity. Varicose veins, venous infection of the extremities. Dynamics and outcome. After the abolition of glycyrrhizic acid, blood pressure and potassium levels in the blood plasma returned to normal, which is not recommended to take antihypertensive drugs. Conclusion: An exceptional clinical situation is a pronounced manifestation of a rare side effect of glycyrrhizic acid in the form of drug-induced hypertension.

S-32-3: RECENT IDACO ANALYSIS ON THE RISK OF PROGRESSION TO SUSTAINED HYPERTENSION FROM WHITE-COAT HYPERTENSION OR MASKED HYPERTENSION

In the general population, the cardiovascular risk is increased in patients with masked hypertension (MH), whereas in individuals with white-coat hypertension (WCH) it is virtually the same as in the normotensive individuals. However, no conclusive evidence exists as to whether WCH and MH are accompanied by a greater rate of development of a sustained hypertensive state, i.e. hypertension both in and outside the clinical environment. We investigated the risk of progression to sustained hypertension in initially untreated participants of cohort studies included in the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) study. Within the IDACO, 5 populations comprising 1081 individuals had ambulatory (ABP) and conventional (CBP) blood pressure measured at baseline and at follow up. We excluded from the analysis subjects on BP-lowering treatment at baseline (n = 252) and individuals with untreated sustained hypertension at baseline (n = 80), leaving 749 subjects included in the current analysis. The cut-off value for elevated CBP was &gt; = 140/90 mm Hg and for daytime ABP &gt; = 135/85 mm Hg. At baseline, 110 individuals (14.7%) was defined as MH, 64 subjects as WCH (8.5%), and 575 (76.8%) as normotensives. MH patients were older (50 vs 45 years compared to normotensives, P &lt; 0.01) and more frequently male (50.9 vs 31.5% compared to normotensives, P &lt; 0.01). During median follow-up of 9.7 years, there were 264 incident cases of sustained hypertension. In the analyses adjusted for cohort, sex, age, body mass index, smoking and drinking, both MH (HR 2.23, 95%CI 1.57 to 3.17) and WCH (HR 1.84, 95%CI 1.37 to 2.47) significantly increased risk of progression to sustained hypertension. In conclusion, long-term risk of progression to sustained hypertension is 2-fold higher in individuals with masked hypertension or white coat hypertension at baseline as compared to normotensive subjects at baseline. However, this observation might be due to more frequent initiation of antihypertensive therapy in both groups.

Tight vs liberal control of mild postpartum hypertension: a randomized controlled trial

High-quality evidence to inform the management of postpartum hypertension, including the optimal blood pressure threshold to initiate therapy, is lacking. Randomized trials have been conducted in pregnancy, but there are no published trials to guide management in the postpartum period. This study aimed to test the hypothesis that initiating antihypertensive therapy in the postpartum period at a threshold of 140/90 mm Hg would result in less maternal morbidity than initiating therapy at a threshold of 150/95 mm Hg. We performed a pragmatic multicenter randomized controlled trial of patients aged 18 to 55 years with postpartum hypertension. Patients with chronic hypertension, gestational hypertension, and preeclampsia without severe features were randomized to 1 of 2 blood pressure thresholds to initiate treatment: persistent blood pressure of ≥150/95 mm Hg (institutional standard or "liberal control" group) or ≥140/90 mm Hg (intervention or "tight control" group). Our primary outcome was composite maternal morbidity defined as: severe hypertension (blood pressure ≥160/110 mm Hg) or preeclampsia with severe features, the need for a second antihypertensive agent, postpartum hospitalization >4 days, and maternal adverse outcome secondary to hypertension as evidenced by pulmonary edema, acute kidney injury (creatinine level ≥1.1 mg/dL), cardiac dysfunction (eg, elevated brain natriuretic peptide level) or cardiomyopathy, posterior reversible encephalopathy syndrome, cerebrovascular accident, or admission to an intensive care unit. Secondary outcomes included hospital readmission for hypertension, persistence of hypertension beyond 14 days, medication side effects, and time to blood pressure control. We calculated that 256 women would provide 90% power to detect a relative 50% reduction in the primary outcome from 36% in the standard blood pressure threshold group to 18%, with a 2-sided alpha set at 0.05 for significance. Data were analyzed using R statistical software. A total of 256 patients were randomized, including 128 to the "tight control" group (140/90 mm Hg) and 128 to the "liberal control" group (150/95 mm Hg). Patients in the "tight control" group had a higher body mass index at delivery (37.1±9.4 vs 34.9±8.1; P=.04); other demographic and obstetrical characteristics were similar between groups. The rate of the primary outcome was similar between groups (8.6% vs 11.7%; P=.41; relative risk, 0.73; 95% confidence interval, 0.35-1.53). The rates of all secondary outcomes and the individual components of the primary and secondary outcome measures were also similar between groups. In the postpartum period, initiation of antihypertensive therapy at a lower blood pressure threshold of 140/90 mm Hg did not decrease maternal morbidity or improve outcomes compared with a threshold of 150/95 mm Hg.

PSUN115 Features of Metabolic and Hemodynamic Parameters in Obese Patients with True and Pseudo-Resistant Hypertension

Abstract Given the negative contribution of obesity-associated metabolic disorders to the formation of cardiovascular complications, adequate blood pressure (BP) control is very important in patients with arterial hypertension (AH) and obesity comorbidity. Objective to conduct a comparative assessment between metabolic and hemodynamic parametersinobese patients with true and pseudo-resistant AH. Methods The study included 302 patients with uncontrolled AH and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP (they received the fourth drug spironolactone). All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results A comparative assessment of BP levels was carried out between non-resistant and resistant patients: at the initial stage of enrolling patients, there was no significant difference in BP between non-resistant and subsequently resistant patients; after 3 months of follow-up (after prescribing double fixed combinations), there was a significant difference in the indicators of both office and out-of-office BP in resistance and non-resistance; despite the achievement of target BP levels after 6 months of therapy, in the presence of resistance, both office, home and most ABPM indicators were significantly higher than in non-resistance. An assessment of the possible causes of pseudo-resistance showed that most often, pseudo-resistance was observed in patients with non-compliance with recommendations to increase physical activity (55.26%) and reduce the calorie intake of food consumed (44.77%), as well as with poor compliance to the prescribed therapy (42.11%). At the same time, high salt intake, chronic kidney disease, obstructive sleep apnoea, and the white-coat phenomenon also contributed to the formation of pseudo-resistance. More than half of the patients (63.16%) had a combination of several factors that could contribute to the formation of pseudo-resistance. If at the stage of enrolling patients into the study and 3 months after the start of therapy there was no significant difference in BP levels between true and pseudo-resistant patients, then after 6 months of antihypertensive therapy, patients with true resistance had significantly higher levels of office SBP (p&amp;lt;0.01) and 24 h average SBP according to ABPM data (p&amp;lt;0.05) compared with pseudo-resistant patients. Obese patients with true resistance had also significantly lower BMI and LDL-cholesterol (p&amp;lt;0.05) as well as higher levels of aldosterone and SBP (p&amp;lt;0.05) compared with pseudo-resistance. Conclusions Even when target BP levels in antihypertensive therapy are achieved, obese resistant patients are characterized by higher levels of office and out-of-office BP, compared with non-resistance. Compared with pseudo-resistance, the presence of true resistance in obesity is associated with higher SBP and aldosteron levels, as well as lower BMI and LDL-cholesterol. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Abstract P118: Metabolic And Hemodynamic Disorders In Obese Patients With True And Pseudo-resistant Hypertension

Objective: to conduct a comparative assessment between pseudo-resistant and true resistant hypertension (RH) in obesity. Methods: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target blood pressure (BP) in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP (they received the fourth drug spironolactone). All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results: In the absence of a difference in BP levels, patients who subsequently become resistant, already at the stage of inclusion, significantly more often had circadian rhythm (CR) violations with a predominance of the non-dipper CR. Despite the target BP achievement after 6 months, in the majority (91.42%) of non-RH patients, the CR normalized, while in RH a normal CR was only in 60.87%. At the stage of enrolling patients into the study and 3 months after the start of therapy there was no significant difference in BP levels between true and pseudo-RH, then after 6 months of therapy, patients with true RH had significantly higher office SBP levels (p&amp;lt;0.01) and 24 h average SBP according to ABPM data (p&lt;0.05) compared with pseudo-RH. Already at the stage of inclusion in the study, the normal CR in true RH was significantly less common than in pseudo-RH, and during the prescribed therapy, a similar trend persisted: after 6 months of therapy, 71.05% of pseudo-RH had a normal CR, while with true RH - only about half of the patients. Obese patients with true RH had also significantly lower BMI and LDL-cholesterol (p&lt;0.05) as well as higher levels of aldosterone and SBP (p&amp;lt;0.05) compared with pseudo-RH. Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese patients with RH are characterized by more pronounced CR disturbances and higher levels of office and out-of-office BP, compared with non-RH. Compared with pseudo-RH, the presence of true RH in obesity is associated with higher SBP and aldosteron levels, as well as lower BMI and LDL-cholesterol.

Why take organ damage in hypertension seriously?

The focus of recent European guidelines has been early initiation of antihypertensive therapy in risk groups, rapid achievement of target blood pressure with fixed combinations of antihypertensive drugs, and the best possible management of an individuals cardiovascular risk. Early intervention in the development of hypertension-mediated organ damage (HMOD) has been shown to have an effect on the subsequent reduction in the risk of cardiovascular events. The point of HMOD origination correlates with the magnitude and duration of blood pressure elevation, and there is no clearly defined boundary from which vascular damage begins to develop. A reduction in blood pressure with pharmacotherapy demonstrably decreases the risk of ischaemic heart disease, stroke, as well as the mortality rate (1). Large clinical trials have consistently shown a significant reduction in the risk of these complications with antihypertensive medications across the entire spectrum from mild to severe hypertension, including hypertension in the elderly as well as isolated systolic hypertension (2). Based on the latest knowledge, a reduction in blood pressure by a mere 5 mm Hg has a cardioprotective effect even in normotensive individuals, which fundamentally changes the view on the diagnosis and definition of hypertension as a disease (3).

Arterial hypertension or hypertension type of neurocirculatory asthenia in persons of military age

The authors raise the urgent problem of the discrepancy between the conceptual apparatus and strategies for the management of military age persons with high blood pressure, examined by military medical examination, and the current recommendations on arterial hypertension of the Russian Society of Cardiology. The reader's attention is focused on the preventive concept of the Russian Society of Cardiology: the desire for early diagnosis of hypertension and the initiation of treatment even with grade 1 hypertension in the absence of target organ damage. The authors propose consideration of a medical examination of males aged 1827 years, registered or not registered in the military, as one of the effective tools for the early diagnosis of arterial hypertension. The urgency of the problem is due to the unfavorable phenotype of arterial hypertension at a young age, in which target organ damage is involved early in the pathological process. The above excerpts from the Regulations on the military medical examination No. 565 draw the attention of readers to two articles of paragraph 9 of the disease schedule: 43hypertension and 47neurocirculatory asthenia, characterized by increased blood pressure, creating confusion in the diagnosis. Literature data are presented confirming the ambiguity of the interpretation of elevated blood pressure in the group of people aged 1827 years, the complexity of the diagnosis, and differential diagnosis of hypertension and neurocirculatory asthenia. At the same time, the diagnosis of neurocirculatory asthenia, according to the literature, is established quite often in this age group and reaches 75% in the structure of cardiovascular disease. The results of studies by Russian scientists, indicating a subclinical lesion of target organ damage in young people with neurocirculatory asthenia with hypertensive reactions, call into question the appropriateness of this diagnosis and management strategy. With modern diagnostic capabilities, an unreasonable lengthening of the examination time for people of military age, examined by a military medical examination to confirm the diagnosis of hypertension and timely initiation of antihypertensive therapy, is emphasized. The question is raised about the correctness and expediency of using the term "neurocirculatory asthenia" in people of military age with high blood pressure.

Different faces of resistant hypertension in obesity

Background: The aim was to conduct a comparative assessment between pseudo-resistant (due to different causes) and true resistant hypertension (RH) in obesity. Material and methods: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target blood pressure (BP) with dual therapy were switched to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP (they received the fourth drug, spironolactone). All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results: Despite the achievement of target BP after 6 months of therapy, patients with resistant hypertension had significantly higher BP and more pronounced disturbances of the circadian rhythm compared with non-resistant patients. After 6 months of therapy, patients with true resistance had significantly higher SBP compared with pseudo-resistant patients. The normal circadian rhythm in patients with true resistance was significantly less common than in patients with pseudo-resistance. Compared with pseudo-resistance, the presence of true resistance in obesity was associated with higher SBP and aldosterone levels, as well as lower body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C). Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese resistant patients are characterized by more pronounced disturbances of the circadian rhythm and higher levels of office and out-of-office BP, compared with non-resistant patients. New data were obtained in the difference in the systolic blood pressure (SBP) levels (significantly higher with true resistance) and LDL-C (significantly lower with true resistance).

DISTURBANCES OF THE CIRCADIAN RHYTHM AND BLOOD PRESSURE LEVELS IN OBESE PATIENTS WITH TRUE AND PSEUDO-RESISTANT HYPERTENSION

Objective: The aim was to conduct a comparative assessment of the circadian rhythm abnormalities and blood pressure (BP) levels between pseudo-resistant and true resistant hypertension (RH) in obesity. Design and method: The study included 302 patients with uncontrolled hypertension and obesity. Initial treatment efficacy was assessed 3 months after dual therapy was administered. Those patients who did not reach target BP in dual therapy were transferred to triple therapy. Among patients who received triple therapy, 69 people did not reach target BP. All patients were additionally examined 6 months after the initiation of antihypertensive therapy. Results: In the absence of a difference in BP, patients who subsequently become resistant, already at the stage of inclusion, significantly more often had a violation of the circadian rhythm with a predominance of the non-dipper rhythm. Despite the achievement of target BP after 6 months of therapy, in the majority (91.42%) of patients without resistance, the circadian rhythm normalized, while resistant patients had a normal circadian rhythm only in 60.87%. At the stage of enrolling patients into the study and 3 months of therapy there was no significant difference in BP between true and pseudo-resistance, then after 6 months of therapy, patients with true resistance had significantly higher office SBP (p &lt; 0.01) and 24 h average SBP according to ABPM data (p &lt; 0.05) compared with pseudo-resistant patients. Already at the stage of inclusion in the study, the normal circadian rhythm in true resistance was significantly less common than in pseudo-resistance; during the prescribed therapy, a similar trend persisted: after 6 months of therapy, 71.05% of pseudo-resistant patients had a normal circadian rhythm, while with true resistance only about half of the patients had a normal circadian rhythm. Conclusions: Even when target BP levels in antihypertensive therapy are achieved, obese patients with RH are characterized by more pronounced disturbances of the circadian rhythm (most often non-dipper) and higher levels of office and out-of-office BP, compared with non-resistant patients. Compared with pseudo-resistant patients, the presence of true resistance in obesity is associated with higher SBP levels and a higher incidence of circadian rhythm disturbances.

Toward the Development of Personalized Syndrome Discriminant Systems: A Discriminant System for Hypertension with Liver Yang Hyperactivity Syndrome.

Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered pathophysiology of hypertension in individuals with liver Yang hyperactivity syndrome (HLYH) in response to effective treatments to better understand this disorder. The primary aim of this study was to construct a personalized syndrome discriminant system based on data capable of informing management strategies prior to the initiation of antihypertensive therapy or the implementation of screening strategies in at-risk HLYH. Based on the successful replication of HLYH rat models, we extracted the core discriminant factors of the disorder through the integration of physical signs, biochemical indicators, and metabolic markers. Macro and micro information was correlated to construct a syndrome discriminant system. At the macroscopic level, HLYH rat models characterized by elevated blood pressure were found to be associated with significant changes in water intake, pain threshold, retention time on a rotating platform, and body surface temperature. A total of 27 potential biomarkers and 14 metabolic pathways appeared to reflect the primary metabolic characteristics. Through the integration of these data, we successfully constructed a combined macro-micro personalized syndrome discriminant system, which provides a foundation for research regarding the risk loci of HLYH. Our findings also broaden our understanding of the biological pathways involved in HLYH.

Hypertensive response to exercise - to treat or not to treat?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hypertensive response to exercise (HRE) is often documented in individuals without known cardiovascular disease. However, its impact on patient prognosis and the necessity of treatment are still not clear. Objective We aimed to evaluate the impact of a hypertensive response (HRE) on exercise test (ET) on clinical prognosis and outcome. Methods This was a single-center retrospective study of patients with HRE on stress exercise testing (STE) performed between January 2012 and December 2015. In our center, we define HRE as systolic blood pressure (SBP) &amp;gt; 210mmHg in men and &amp;gt;190mmHg in women, diastolic blood pressure (DBP) &amp;gt; 90mmHg or an increase in baseline systolic BP at least 60 mmHg in men or 50 mmHg in women, during exercise. Demographic, clinical, echocardiographic, electrocardiographic data were collected, and results were obtained using Chi-square and Student-t tests; logistic regression. Results We evaluated 500 patients who underwent STE, 457 of which had hypertensive response vs 43 patients without HRE (mean age 57 ± 11 vs 61 ± 8 years, p = 0,01). Among the two groups there were no differences between gender (76.5% men vs 69.7%) and race nor between the cardiovascular risk factors, namely hypertension, diabetes and dyslipidaemia. We evaluated their responses in STE and their outcomes, with a mean follow-up of 60 ± 22 months. In the univariate and multivariate analysis, presence of Sokolow-Lion criteria of left ventricular hypertrophy in the ECG was associated with HRE during the exam (OR 5.26; CI95% 2.4-11.6; p &amp;lt; 0.001). In patients who had previously known hypertension, therapy with calcium channel blockers seemed to protect against hypertensive response prior to ET (OR 0.48, CI95% 0.24-0.97, p = 0.004) compared to other antihypertensive drugs. Regarding the clinical outcomes, patients with HRE were associated with an increased risk of developing heart failure (p = 0.027) (versus patients without HRE) during follow up but failed to predict adverse outcomes such as acute coronary syndrome, atrial fibrillation or stroke. Within the patients with HRE in ET, 78 patients did not have an established diagnosis of HTA (mean age 49 ± 12.16 years, 75.6% men). In these patients we observed initiation on antihypertensive therapy after ET on 27.6% patients, but on univariate and multivariate analysis, starting therapy with anti-hypertensives did not have a significant impact on incidence of stroke, AF, HF, hospitalization for cardiovascular events or death. Conclusions We did not observe any significant differences among the studied groups regarding prognosis, except for the highest incidence of heart failure in patients with HRE. Initiation of antihypertensive therapy in patients with HRE failed to modify outcomes, however our sample was underpowered, so, further studies are required in order to clarify the value of treatment in patients with HRE.

INFLUENCE OF ANTIHYPERTENSIVE TREATMENT ON RAAS PEPTIDES IN NEWLY DIAGNOSED HYPERTENSIVE PATIENTS

Objective: Recently, the influence of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) gained increasing attention, especially since concerns were raised regarding a potential influence of RAAS inhibitors on Corona Virus Disease 2019 (COVID-19). Our objective was to study the effect of recently initiated antihypertensive drugs on Angiotensin (Ang) II (1–8) and Ang (1–7) as markers of the pro-inflammatory ACE/Ang II/Ang Type 1 receptor (AT1R) axis and the counteractive ACE2/Ang (1–7)/Mas R axis in patients with newly diagnosed hypertension. Design and method: Randomized, open-label trial investigating RAAS peptide profiles after initiation of antihypertensive treatment with either perindopril, olmesartan, amlodipine, or hydrochlorothiazide. Ang II and Ang (1–7) concentrations were measured at 8am and 12am at day of treatment initiation and after four weeks of treatment. Results: 80 patients were randomized in a 1:1:1:1 fashion. Between the four substances, we found significant differences for the concentrations of Ang II (p &lt; 0.0005 for 8 and 12am) and Ang (1–7) (p = 0.019 for 8am and &lt;0.0005 for 12am) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p &lt; 0.0005) and amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001) (Figure panel A). Ang (1–7) was increased by perindopril and olmesartan (p = 0.008 and 0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317 and 0.109) (Figure panel B). Conclusions: Initiation of antihypertensive therapy causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptide shifts upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.

Abstract 17121: Initiation of Anti-Hypertensive Therapy and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) and a History of Hypertension (HTN)

Background: According to the ACC/AHA HF guideline, in patients (pts) with HFpEF and HTN, optimal systolic blood pressure (SBP) target is &lt;130 mm Hg. Although SBP &lt;130 has been shown to be associated with a higher risk of death in HFpEF (PMC5875342), the use of anti-HTN therapy in those with SBP ≥130 has not been well studied. We tested the hypothesis that anti-HTN therapy in pts with HFpEF, HTN and SBP ≥130 would be associated with improved outcomes. Methods: Of the 8873 hospitalized pts with HF w EF ≥50% in Medicare-linked OPTIMIZE-HF, 6781 (76%) had a history of HTN, of whom 3680 (54%) had a discharge SBP ≥130 mmHg. We assembled an inception cohort by excluding 1611 (44%) receiving anti-HTN drugs (HCTZ, hydralazine, or a CCB) before admission. Of the remaining 2069 pts, 430 (21%) received a new discharge prescription for anti-HTN drugs. Propensity scores for anti-HTN drug initiation, estimated for each of the 2069 pts, were used to assemble a cohort of 427 pairs of pts started and not started on anti-HTN therapy, balanced on 60 baseline characteristics including use of ACEI/ARBs and BBs. Results: The 854 matched pts had a mean age of 77 years, mean SBP of 149 mmHg, 67% were women, and 17% African American. 3-year all-cause mortality occurred in 45% and 53% of matched pts started vs. not started on anti-HTN therapy, resp. (HR 0.77; 95% CI, 0.64-0.94; p=0.009; Figure ). There was no association with readmissions. Conclusion: In pts with HFpEF, HTN and SBP ≥130 mm Hg, initiation of anti-HTN therapy is associated with a lower risk of death.

Impact of plasma potassium normalization on short-term mortality in patients with hypertension and hypokalemia or low normal potassium

BackgroundHypokalemia is common in patients treated with antihypertensive drugs, but the impact of correcting hypokalemia is insufficiently studied. We examined the consequences of hypokalemia and borderline hypokalemia correction in patients with hypertension.MethodsWe identified 8976 patients with hypertension and plasma potassium concentrations ≤3.7 mmol/L within 100 days from combination antihypertensive therapy initiation. The first measurement between 6 and 100 days after the episode with potassium ≤3.7 mmol/L was retained. We investigated all-cause and cardiovascular mortality within 60-days from the second potassium measurement using Cox regression. Mortality was examined for seven predefined potassium intervals derived from the second measurement: 1.5–2.9 mmol/L (n = 271), 3.0–3.4 mmol/L (n = 1341), 3.5–3.7 (n = 1982) mmol/L, 3.8–4.0 mmol/L (n = 2398, reference), 4.1–4.6 mmol/L (n = 2498), 4.7–5.0 mmol/L (n = 352) and 5.1–7.1 mmol/L (n = 134).ResultsMultivariable analysis showed that potassium concentrations 1.5–2.9 mmol/L, 3.0–3.4 mmol/L, 4.7–5.0 mmol/L and 5.1–7.1 mmol/L were associated with increased all-cause mortality (HR 2.39, 95% CI 1.66–3.43; HR 1.36, 95% CI 1.04–1.78; HR 2.36, 95% CI 1.68–3.30 and HR 2.62, 95% CI 1.73–3.98, respectively). Potassium levels <3.0 and > 4.6 mmol/L were associated with increased cardiovascular mortality. The adjusted standardized 60-day mortality risks in the seven strata were: 11.7% (95% CI 8.3–15.0%), 7.1% (95% CI 5.8–8.5%), 6.4% (95% CI 5.3–7.5%), 5.4% (4.5–6.3%), 6.3% (5.4–7.2%), 11.6% (95% CI 8.7–14.6%) and 12.6% (95% CI 8.2–16.9%), respectively.ConclusionsPersistent hypokalemia was frequent and associated with increased all-cause and cardiovascular mortality. Increase in potassium to levels > 4.6 mmol/L in patients with initial hypokalemia or low normal potassium was associated with increased all-cause and cardiovascular mortality.