Lack Of Blood Pressure Control Research Articles

A Cross-Sectional Study of the Trends in Cardiovascular Mortality Among African Americans With Hypertension.

Background and Objective In the United States, hypertension remains a significant cause of cardiovascular disease mortality and morbidity, affecting various racial and ethnic groups. High blood pressure is a common health concern, given its high frequency among all populations and racial groups in the United States; nevertheless, the condition remains untreated in most individuals. It affects a significant number of individuals in the African American community and contributes to a notable proportion of deaths. Arguably more prevalent, severe, and tends to occur earlier in African Americans compared to some other races. This lack of blood pressure control may contribute to the increasing mortality rates associated with hypertension-related cardiovascular diseases in the United States, while notable race and sex disparities persist. This study aims to compare the number of deaths caused by each cardiovascular disease (hypertension) in African Americans to those of people of other races. Methodology To understand the impact of hypertension on mortality rates among different racial groups, this study utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER)dataset, which includes death certificates filed in the United States. The research focused on individuals aged 25 years or older with a mention of hypertension and cardiovascular disease as the underlying cause of death between 1999 and 2019. The study analyzed hypertension-associated deaths by different cardiovascular disease subtypes, such as ischemic heart disease, heart failure (HF), and cerebrovascular diseases that include acute ischemic attacks, which are the most frequent in the United States, with specific assessments for African Americans, White, and other races' decedents. Results The study findings indicated that African American males had higher mortality rates from cardiovascular diseases compared to African American females. The prevalence of hypertension was also higher among African Americans (87.47%) compared to Whites (30.33%), Asian/Pacific Islanders (40.26%), and American Indians/Alaska Natives (61.18%). Additionally, the study identified regional variations in mortality rates, with states like Arizona, California, Texas, Florida, and Washington having higher rates, while Vermont, North Dakota, and Wyoming had lower rates. The northwest region had lower mortality compared to the western and southwestern regions. Conclusions Within the studied period, there was an increase in the prevalence of mortality due to hypertension amongst African Americans when compared to other races. These findings underscore the pressing need to address the increasing prevalence of hypertension and mortality rates among African American. More efforts should focus on prevention of CVD and hypertension and the associated risk factors based on the World Health Organization (WHO) recommendations, which include the promotion of healthy lifestyle behaviors, improvement of access to quality healthcare,and implementation ofculturally sensitive interventions tailored for African American communities.

CARDIOVASCULAR RISK PROFILE OF REFRACTORY HYPERTENSION DIAGNOSED BY ABPM AND HBPM IN A COHORT OF RESISTANT HYPERTENSION

Objective: Refractory hypertension (RefHT) is considered an extreme phenotype of resistant hypertension (RHT) and has recently been defined as uncontrolled blood pressure (BP) despite the use of 5 or more antihypertensives including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. The objective of this study is to evaluate the clinical profile and characterize the cardiovascular (CV) risk involved through the analysis of hypertension-mediated organ damage (HMOD) and established cardiovascular disease. Design and method: This is a cross-sectional study of a historical cohort of patients with RHT who underwent a standardized protocol consisting of: a questionnaire to record cardiovascular risk factors (physical inactivity, smoking, obesity, dyslipidemia, and diabetes), hypertension-mediated organ damage (albuminuria, chronic kidney diseases (CKD) stage 3, left ventricular hypertrophy (LVH) diagnosed by transthoracic echodopplercardiogram, and arterial stiffness measured by pulse wave velocity) and established CV diseases (coronary diseases, stroke, heart failure, peripheral arterial disease, and CKD stage 4 or 5). All of them were submitted to 24-hour ABPM and 5-day HBPM (triplicate morning and evening measurements). Results: A total of 354 patients (23.9% male; mean age 60.4 ± 11.1 years old) was included in the study. The prevalence of RefHT was 20.3% (72 patients) by ABPM and 18.9% by HBPM (67 patients). In both groups, refractories were younger with higher levels of albuminuria. Refractory patients diagnosed by the ABPM had a higher prevalence of stroke (18.1% vs 9.6%) and established CV diseases (45.8% vs 33.7%) than resistant patients. We did not observe differences regarding LVH (75.0% vs 71.8%), arterial stiffness (13.1% vs 16.4%) and CKD stage 3 (22.2% vs 27.0%). In turn, refractory patients diagnosed by HBPM had a higher prevalence of heart failure (7.5% vs 2.8%), also showing similar prevalence of LVH (76.1% vs 71.6%), arterial stiffness (12.7% vs 16.4%), and CKD stage 3 (22.4% vs 26.8%). Conclusions: Refractory hypertensives presented a cardiovascular risk profile similar to resistant hypertensives, despite the lack of blood pressure control. Possibly the pharmacological treatment with spironolactone acting on the neurohumoral axis of hypertension may have an impact on the clinical course and survival of these patients.

The role of baroreflex activation therapy in patients with resistant hypertension

Resistant hypertension has become an interesting and controversial topic in the last decade. According to the European Guidelines for the management and treatment of hypertension, resistant hypertension is defined as the lack of blood pressure control despite the control of risk factors and good compliance with a treatment with at least three antihypertensives in the maximum tolerated doses, one of which is a diuretic, at patients in whom possible causes of secondary arterial hypertension were excluded. In the official position of the AHA (American Heart Association) on this subject, resistant HTN is considered as HTN uncontrolled with three antihypertensive drugs or HTN controlled but requiring at least four drugs. Although the medical world has a complex arsenal of antihypertensive preparations, with them it is not possible to correct the values in a good part of the patients. A solution would be the development and study of the effectiveness of baroreflex activation therapy.

Challenges of providing health services to patients with cardiovascular diseases during disasters in Iran: A qualitative study.

Cardiovascular diseases are the most common causes of death in the world. Because of the rate of emergencies and disasters in the country, this study was conducted to investigate the challenges of providing health services to cardiovascular patients in emergencies and disasters in Iran. This conventional content analysis study was conducted in 2020. Subjects were selected from among 16 Iranian experts) epidemiologists, cardiologists, PhD in Disaster Health, and PhD in Nursing (using purposeful and snowball sampling methods. Data were collected using semi-structured interviews and were analyzed by the content analysis. The results were obtained after analyzing the data in the pre-emergency phase (lack of training on medication and nutrition, lack of training vulnerable groups, lack of databases of cardiovascular patients, and lack of identification of patients before disasters), the emergency response phase (lack of sleep and rest patterns, lack of health forces, lack of blood pressure control, lack of proper nutrition, increased medication needs, and lack of mental health interventions), and the post-emergency phase (lack of planning, lack of management of patients' mental problems). Developing strategies for planning, training, providing resources, and mental health during the three phases of the emergency management cycle for specific groups such as cardiovascular patients together with empowering these patients in the event of disasters is one of the key strategies which can be used after curbed emergencies and disasters to reduce the rate of mortality.

Factors associated with uncontrolled blood pressure in hypertensive Brazilians

Uncontrolled hypertension has a high prevalence and is related to numerous negative health outcomes. This study aimed to investigate the factors associated with the lack of blood pressure control in hypertensive Brazilians treated in public and private services. This is an analytical, multicentric, and national cross‐sectional study, carried out with adult hypertensive patients, monitored in 45 outpatient clinics (September 2013 to October 2015) in a prospective record interview, clinical, and anthropometric assessment. Outcome variables included uncontrolled pressure (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg). Simple and multiple logistic regression analyses were performed. Two thousand six hundred forty‐three participants were assessed with a mean age of 61.6 ± 11.9 years, 55.7% of women, and 46.4% with uncontrolled blood pressure (BP). The following were associated with uncontrolled BP: age over 60 years (OR: 1.31 [1.11–1.55]); practice of irregular physical activity (OR: 1.28 [1.06–1.55]); attending the emergency room for hypertensive crises in the last six months (OR: 1.80 [1.46–2.22]); increased body mass index (OR: 1.02 [1.01–1.04]); low adherence to drug treatment (OR: 1.22 [1.04–1.44]) and menopause (OR: 1.36 [1.07–1.72]). The following were negatively associated: fruit consumption (OR: 0.90 [0.85–0.94]); presence of dyslipidemia (OR: 0.75 [0.64–0.89]), acute myocardial infarction (OR: 0.59 [0.46–0.76]), and peripheral arterial disease (OR: 0.52 [0.34‐0.78]). Factors associated with difficult‐to‐control blood pressure are the same that increase the risk for hypertension, while the presence of atherosclerotic disease and its outcomes were associated with better control.

CHANGES IN CLINICAL PROFILE OF REFRACTORY HYPERTENSIVES AFTER THE INTRODUCTION OF SPIRONOLACTONE

Objective: To characterize prevalence and clinical profile of patients with RfHTN among a historical cohort of patients with RHTN in 2 moments: before and after the introduction of spironolactone. Design and method: A cross-sectional analysis was performed during the pre-spironolactone period (before 2005) with 1,048 participants with RHTN (72.3% women, average age: 61.2 ± 11.3 years). All of them were submitted to a standard protocol including clinical and laboratory tests, 24-hour ABPM, echocardiogram, and pulse wave velocity. In a second analysis, refractory patients were evaluated after the introduction of spironolactone (post-spironolactone period – after 2005). The statistical analysis included bivariate comparisons between patients with RHTN and those with RfHTN, as well as logistic regressions to assess independent correlations of RfHTN pre- and post-spironolactone. Results: In the initial cross-sectional analysis (pre-spironolactone), RfHTN prevalence was 14%. Age < 60 years, smoking, obesity and left ventricular hypertrophy (LVH) were independently correlated with RfHTN. After the introduction of spironolactone, prevalence increased to 17.6%. It was observed that refractory patients using spironolactone presented less aortic stiffness, lower prevalence of LVH, cerebrovascular disease and peripheral arterial disease (PAD), what might indicate a reduced cardiovascular risk despite the lack of blood pressure control. Refractory patients have also presented higher magnitude of white-coat effect, reflecting an exacerbated sympathetic activity. Age < 60 years and lower prevalence of PAD were correlated with RfHTN in the post-spironolactone period. Conclusions: The use of spironolactone seems to reduce cardiovascular risk despite the lack of blood pressure control.

WHAT ARE THE FACTORS ASSOCIATED WITH UNCONTROLLED BLOOD PRESSURE IN BRAZILIAN HYPERTENSIVE PATIENTS?

Objective: Uncontrolled arterial hypertension (AH) is defined by BP > or = 140/90 mmHg. It has a high prevalence, is associated with the causes of pseudoresistance and is related to several complications and negative health outcomes. Thus, the objective of this study was to investigate the factors associated with the lack of blood pressure control in hypertensive Brazilians treated in public and private services. Design and method: Cross-sectional, analytical, multicenter and national study, carried out with hypertensive adults and elderly individuals, followed by 45 outpatient clinics, included from September 2013 to October 2015 and submitted to interview, clinical and anthropometric evaluation. The outcome variable was uncontrolled pressure (BP > or = 140mmHg systolic and/or > or = 90 mmHg diastolic). Simple and multiple logistic regression analysis was performed. Results: A total of 2,643 participants with a mean age of 61.6 (11.9), 55.7% female and 46.4% with uncontrolled BP were evaluated. Uncontrolled BP was associated: age over 60 years (OR: 1.31 [1.11 - 1.55]); practice of irregular physical activity (OR: 1.28 [1.06 - 1.55]); attending the emergency room for hypertensive crises in the last six months (OR: 1.80 [1.46 - 2.22]); increase in body mass index (OR: 1.02 [1.01 - 1.04]); low adherence to drug treatment (OR: 1.22 [1.04 - 1.44]) and menopause (OR: 1.36 [1.07 - 1.72]). The following were negatively associated: fruit consumption (OR: 0.90 [0.85 - 0.94]); presence of dyslipidemia (OR: 0.75 [0.64 - 0.89]), acute myocardial infarction (OR: 0.59 [0.46 - 0.76]) and peripheral arterial disease (OR: 0.52 [0.34 - 0.78]). Conclusions: Factors associated with non-BP control were: advanced age, increased body mass index, practice of irregular physical activities, need for emergency care and low adherence to pharmacological treatment and protective factors: presence of acute myocardial infarction and peripheral arterial disease, and higher daily fruit intake.

MO093: Dietary Sodium Restriction Reduces Nocturnal Blood Pressure in Treatment Resistant Hypertensive Patients

Abstract BACKGROUND AND AIMS High blood pressure (BP) is an essential contributor to the risk of cardiovascular disease (CVD) and death. Hence, diagnosing and treating patients with high BP is paramount if the number of cardiovascular related death should be reduced. High nocturnal BP and blunting of normal nocturnal BP decrease have stronger correlation to the risk of CVD than high day time BP. Lowering nocturnal BP is assumed to reduce the risk of CVD. Patients with treatment resistant hypertension (TRH) represent a subgroup of hypertensive patients characterized by lack of BP control despite antihypertensive treatment. These patients are at particular risk of CVD and target organ damage. Patients with TRH are more likely to experience BP increase as a response to sodium loading than other individuals. Lifestyle modification is an important treatment angle in hypertensive patients. It is, in particular, central to reduce sodium intake, as high sodium intake increases the risk of TRH. Thus, in this study we aimed to analyse if self-performed dietary sodium restriction could be implemented in patients with TRH. Moreover, we aimed to analyse the effect of this attempted restriction on nocturnal BP and 24 h BP, on plasma levels of BNP and nitric oxide, and on body water content. METHOD Patients with TRH from 20 to 70 years with normal renal function were invited for participation in this cross-over interventional study. Patients were screened with 24 h ambulatory BP monitoring initiated after observed intake of usual antihypertensive medication, and they were included if 24 h systolic BP/diastolic BP ≥ 130/80 mmHg. Study participation included two periods of 14 days; a standard period with usual diet and an interventional period with instructed dietary sodium restriction and handed-out sodium-reduced bread. For both periods, all antihypertensive medication was dosed and handed out and ingested in the morning. At the end of each period, patients were examined with 24 h BP monitoring, 24 h urine collection (sodium excretion), blood samples (nitric oxide and BNP) and bioimpedance measurement (body water content). RESULTS Baseline characteristics of the fifteen included patients are shown in Table 1. Eleven of the patients were male. Patients had been treated for hypertension for a mean of 12.5 (7) years and excreted a mean of 11.2 grams of salt at baseline [192 (86) mmol sodium]. All patients but one reduced sodium excretion at follow up. Table 2 shows the effect of sodium restriction on BP, nitric oxide, BNP and body water content. Sodium excretion was reduced to 91 mmol/24 h, which equals 5.3 g of salt. BP (24 h, day and nocturnal) decreased significantly as well as body water content and plasma levels of BNP. These changes were, however, not correlated. Plasma levels of nitric oxide increased, but it was not related to the changes in BP. Nocturnal fraction of 24 h sodium excretion increased after sodium restriction; however, this was not correlated to changes in nocturnal BP. Renal function and urinary potassium excretion both remained unchanged. Four patients experienced side effects; three reported newly onset dizziness at follow-up; two of them had 24 h BP reduction > 10 mmHg systolic. One patient had increased creatinine and potassium at follow-up. CONCLUSION In a population of 15 treatment resistant hypertensive patients, we demonstrated that self-performed dietary sodium restriction could be implemented. Urinary sodium excretion was reduced significantly to 5.3 g/24 h. Nocturnal BP was reduced significantly; dipping status was, however, unchanged. Increased plasma levels of nitric oxide may be evidence of improved endothelial function. Hence, by the local vasodilating effect, NO may be one of the involved mechanisms in BP decrease following a sodium restriction. Reduced extracellular water content and BNP may be other explainable effects of BP reduction after inducing sodium restriction.

Diagnostics and treatment of resistant arterial hypertension

Resistant arterial hypertension is diagnosed when three antihypertensives assignment does not result in achieving target blood pressure, which for most patients is the level below 140/90 mm Hg, wherein one of the medicaments must be diuretic and all drugs must be assigned to optimal or maximum tolerated doses. Despite the high prevalence of resistant arterial hypertension, the lack of blood pressure control is often associated with an inadequate selection of antihypertensive therapy, blood pressure misjudgement or failure of patients to medical recommendations. Therefore, before carrying out diagnostic measures necessary to consistently assess the adequacy of patients receiving therapy that inherent in the definition of RAH and exclude pseudoresistance.

Transforming Growth Factor-β1, Arterial Stiffness and Vascular Age in Patients With Uncontrolled Arterial Hypertension

Lack of blood pressure control leads to a higher incidence of hypertension-mediated target organ damage (HMOD). One of the markers of HMOD is an increased arterial stiffness, an independent predictor of cardiovascular complications. However, abstract numbers showing the level of arterial stiffness do not give patients a clear understanding of the risk of their condition. In order to increase patient compliance, the term "vascular age" (VA) was introduced. Arteriosclerosis plays the main role in increasing VA. The greatest interest, according to the literature, in the study of this issue is in arteriosclerosis caused by transforming growth factor β1 (TGF-β1)-the effect of TGF-β1 on the culture of smooth muscle cells leads to their proliferation and growth; also, TGF-β1 increases the amount of collagen and accelerates the degradation of elastin. We included 140 people in the study: 80 patients with controlled arterial hypertension (CAH), 30 with uncontrolled arterial hypertension (UAH), and 30 patients who formed the control group. All patients underwent a determination of arterial stiffness and VA using the cardio-ankle vascular index (CAVI), a corrected (blood-pressure independent) cardio-ankle vascular index (CAVI0) and the concentration of TGF-β1 was measured. The TGF-β1 value in the UAH group was 22.6 (25th percentile=20.6; 75th percentile=25.6) ng/mL, and in the control group it was 17.4 (25th percentile=11.8; 75th percentile=19.3) ng/mL. In the CAH group, an intermediate value was noted-19.2 (25th percentile=17.2; 75th percentile=24.7) ng/mL. The CAVI in the UAH group was 9.2 (25th percentile=8.5; 75th percentile=9.9), in the control group-7 (25th percentile=6.5; 75th percentile=7.5). In the CAH group, the average CAVI was 7.8 (25th percentile=7.0; 75th percentile=8.5). The CAVI 0 in the UAH group was 14.8 (25th percentile=12.0; 75th percentile=15.6), in the control group - 9.7 (25th percentile=8.8; 75th percentile=9.7). In the CAH group, the average CAVI was 11.1 (25th percentile=10.1; 75th percentile=13.6). Vascular age in the UAH group was 71.5 (25th percentile=64; 75th percentile=74) years, in the CAH group 59 (25th percentile=49; 75th percentile=69) years, and in both groups (UAH, CAH), VA was significantly higher than the chronological age (p<0.05). In the control group, the VA did not significantly differ from the chronological age (p>0.05) and it was 54 (25th percentile=44; 75th percentile=59) years. A significant relationship was found between the TGF-β1 level and CAVI (CAH r=0.777; UAH r=0.753; p<0.05), CAVI 0 (CAH r=0.625; UAH r=0.502; p<0.05) and VA in patients with AH (CAH r=0.649; UAH r=0.753; p<0.05). In patients in the UAH group, there was an increase in the concentration of TGF-β1, an increase in the arterial stiffness and in VA in comparison with patients in the CAH group and the control group. The relationship between TGF-β1 and the arterial stiffness and VA was revealed in patients with hypertension.

Adherence to antihypertensive medication after referral to secondary healthcare: A prospective cohort study.

Nonadherence (NAd) to antihypertensive medication is associated with lack of blood pressure control and worsened long-term outcomes. Increased access to a programme for high-risk cardiovascular patients has the potential to reduce NAd and improve clinical outcomes. We evaluated implementation NAd prevalence and risk factors among severely hypertensive patients after 12-month-long access to secondary healthcare centres. The Morisky Green Levine Scale (MGLS) was used to analyse antihypertensive medication NAd in a prospective cohort of 485 patients. Logistic regression models evaluated the influence of ecological model factors on NAd. The majority of patients were female, had low health literacy, a low family income and a mean age of 61.8±12.5years. Prevalence of NAd fell from 57.1% at programme entry to 28.3% (P<.001) at the end of the study. After access to a secondary healthcare centre, we observed better blood pressure control, an increase in the number of pills/day and a higher number of antihypertensive medications. Predictive variables of NAd were age (OR 1.027; CI 1.003-1.051; P=.023), low health literacy (OR 1.987; CI 1.009-3.913; P=.047), systolic blood pressure (OR 1.010; CI 1.003-1.021; P=.049), dosages≥2 times/day (OR 1.941; CI 1.091-3.451; P=.024) and patient satisfaction with the healthcare team (OR 0.711; IC 0.516-0.980; P=.037). Greater access to health services is associated with a reduction in NAd to antihypertensive medication and better blood pressure control. NAd was correlated with modifiable variables such as treatment complexity and, for the first time, team satisfaction, suggesting that implementation of similar programmes may limit NAd in similar patient groups.

Prevalence and clinical profile of refractory hypertension in a large cohort of patients with resistant hypertension.

Refractory hypertension (RfHT) is an extreme phenotype of resistant hypertension (RHT) and is considered uncontrolled blood pressure (BP) despite the use of five or more antihypertensives. The objective of this study was to characterize the prevalence and clinical profile of RfHT patients in a historical cohort of patients with RHT at two different times: before and after the introduction of spironolactone. First, this cross-sectional study evaluated 1048 RHT patients (72.3% females, mean [SD] age: 61.2 [11.3] years) referred to a hypertension clinic (prespironolactone period). All patients were submitted to a standard protocol including clinical and complementary exams. Second, the analysis evaluated patients after the introduction of spironolactone (postspironolactone period). Statistical analysis included bivariate comparisons between patients with RHT and patients with RfHT and logistic regressions to assess the independent correlations of RfHT. A total of 146 patients (13.9%) remained refractory despite the use of at least five antihypertensives (prespironolactone period). After the introduction of spironolactone, the prevalence increased to 17.6%. For any criterion, RfHT patients were younger and more obese. In the initial period, current smoking and left ventricular hypertrophy were independently correlated with RfHT. Furthermore, after spironolactone use, RfHT patients had lower aortic stiffness and peripheral artery disease (PAD), pointing to a lower cardiovascular risk despite the lack of BP control. Younger age and lower prevalence of PAD correlated independently with RfHT. In conclusion, there was a high prevalence of RfHT, especially in younger and obese patients, and spironolactone use seemed to reduce cardiovascular risk despite the lack of BP control.

Prognostic model of the adaptive changes from hypertensive cardiopathy: from mild diastolic dysfunction to depressed systolic function.

By definition, hypertensive cardiopathy is a series of complex and variable effects responsible for the chronic elevation of blood pressure in the heart. It stands out within a broad spectrum of cardiovascular diseases associated with hypertension. To evaluate the capacity to predict the development of adaptive changes to hypertensive cardiopathy within ten years following diagnosis of the condition, using a model based on prognostic factors. A prospective cohort study was conducted in hypertensive patients. The patients were followed at the specialized hypertension physicians office of the specialty policlinic attached to Carlos Manuel de Céspedes University Hospital, in the Bayamo Municipality, Granma Province, Cuba, from 1 January 2008 to 31 December 2018. Coxs proportional regression model showed a significant statistical relationship between most of the factors and the development of the adaptive changes in hypertensive cardiopathy within ten years of follow-up after the diagnosis of this condition. The lack of blood pressure control (Hazard ratio: 2.090; confidence interval 95%: 1.688 to 2.588; p: 0.000) followed by stage 2 of hypertension (hazard ratio: 1.987; confidence interval 95%: 1.584 to 2.491; p: 0.000) were the main factors. Internal validation of the model, discriminant capacity (C- statistic: 0.897) and calibration Hosmer-Lemeshow (χ2: 5.384; p: 0.716), was acceptable. We develop a model to predict the progression of hypertensive cardiopathy from grade I to grade IV with adequate discriminatory capacity. The model is based on prognostic factors, among which characteristic effects of arterial hypertension, diabetes mellitus, and chronic kidney disease stood out.

Predicting Interactions between Rifampin and Antihypertensive Drugs Using the Biopharmaceutics Drug Disposition Classification System.

Lack of blood pressure control is often seen in hypertensive patients concomitantly taking antituberculosis medications due to the complex drug-drug interactions between rifampin and antihypertensive drugs. Therefore, it is of clinical importance to understand the underlying mechanisms of these interactions to help formulate recommendations on the use of antihypertensive drugs in patients taking these medications concomitantly. Our objective was to assess the reliability of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to predict potential interactions between rifampin and antihypertensive drugs and thus provide recommendations on the choice of antihypertensive drugs in patients receiving rifampin. Evidence-based in vitro and in vivo predictions of drug-drug interactions. We systematically evaluated interactions between rifampin and antihypertensive drugs using the theory of the BDDCS, taking into consideration the role of drug transporters and metabolic enzymes involved in these interactions. We provide recommendations on the selection of antihypertensive drugs for patients with tuberculosis. Antihypertensive drugs approved by the U.S. Food and Drug Administration and the China National Medical Products Administration were included in this study. The drugs were classified into four categories under the BDDCS classification. Detailed information on cytochrome P450 (CYP) enzymes and drug transporters for each antihypertensive drug was searched in PubMed and other electronic databases. This information was combined with the effects of rifampin on CYP enzymes and drug transporters, and the direction and relative extent of the potential interactions between rifampin and antihypertensive drugs were predicted. Recommendations were then made using the theory of BDDCS. A thorough systematic literature review was performed, and data from all published human studies and case reports were summarized for the validation of our predictions. Interventional and observational studies published in PubMed and two Chinese databases (CNKI and WanFang) through December 16, 2019, were included, and data were extracted for validation of the predictions. Using the BDDCS theory, class 3 active drugs were predicted to exhibit minimal interactions with rifampin. On reviewing case reports and pre-post studies, the predictions we made were found to be reliable. When antituberculosis medications that include rifampin are started in patients with hypertension, it is recommended that the use of calcium channel blockers and classes 1 and 2 β-blockers be avoided. Angiotensin-converting enzyme inhibitors, olmesartan, class 3 β-blockers, spironolactone, and hydrochlorothiazide would be preferable because clinically relevant interactions would not be expected. Application of the BDDCS to predict interactions between rifampin and antihypertensive drugs for patients with both tuberculosis and hypertension was found to be reliable. It should be noted, however, that based on the CYP enzyme and drug transporter information we reviewed, the mechanisms of all of the interactions could not be elucidated, and the predictions are only based on theory. The real effects of rifampin on antihypertensive drugs need to be further observed. More studies in both animals and humans are needed in the future.

Factors associated with the changes from a resistant to a refractory phenotype in hypertensive patients: a Pragmatic Longitudinal Study.

Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01-1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42-1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01-1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47-7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.

The Potential Role of Obstructive Sleep Apnoea in Refractory Hypertension.

This review seeks to present an overview of the recently found association between refractory hypertension (RfH) and obstructive sleep apnoea (OSA). RfH was recently defined as an extreme phenotype of resistant hypertension characterized by the lack of blood pressure control despite using ≥ 5 antihypertensive drugs at optimal doses. Current data support that the pathophysiological pathway of both types of hypertension is different. The main mechanism involved in resistant hypertension is fluid retention whereas in the case of RfH is the sympathetic over-activity. OSA is now recognized as a cause of hypertension (especially in the case of difficult-to-treat hypertension). It seems that the biological mechanism linking OSA and arterial hypertension is the sympathetic over-activity related to the respiratory events (apnoeas and hypopnoeas) during the night. So, it is not surprising that, although the literature is scarce, some studies have found a very high prevalence of OSA and an excess of sympathetic activity in patients with RfH. Finally, a very recent study demonstrated that continuous positive airway pressure (CPAP) treatment, which controls sympathetic activation in OSA patients, achieves very significant reductions in blood pressure levels in RfH patients, even greater than in those with resistant (non-refractory) hypertension. The prevalence of OSA in patients with RfH is very high. CPAP treatment achieves a clinically significant reduction in blood pressure levels in those patients with RfH (especially in night readings). Patients with RfH must be sent to a sleep unit for a study.

Initial Antihypertensive Treatment Strategies and Therapeutic Inertia

In many hypertensive patients, treatment is not upgraded despite lack of blood pressure control because of therapeutic inertia. Information is limited, however, on the extent of this phenomenon in real-life medicine. We studied 125 635 patients (age 40-85 years) from the Lombardy region (Italy) who started antihypertensive treatment with 1 drug (n=100 982) or a 2-drug fixed-dose or free combination (n=24 653). A log-binomial regression model was used to estimate the prevalence ratio of combination therapy in relation to the initial treatment strategy. In the initial monotherapy group, patients under drug combinations were 22%, 27%, 32%, and 36% at 6 months, 1, 2, and 3 years later. In the initial combination treatment group, the corresponding percentages were 85%, 82%, 79%, and 78%. This translated into a markedly greater covariate-adjusted propensity of being under a multidrug prescription throughout the follow-up: 3.92 (95% CI, 3.84-4.00) after 6 months and 3.18 (3.12-3.25), 2.56 (2.51-2.60), and 2.23 (2.19-2.27) after 1, 2 and 3 years of treatment. In a propensity score analysis, initial 2-drug combination treatment was also associated with significant reductions in the risk of death (-20%, 11% to 28%) and hospitalization for cardiovascular events (-16%, 10% to 21%) compared with initial monotherapy. Thus, in real life, a large number of patients prescribed initial monotherapy fails to move to combination treatment, as recommended by guidelines. This implies that therapeutic inertia frequently prevents proper treatment uptitration, thereby playing a major role in the low rate of hypertension control that exists worldwide.

Refractory Hypertension Is not Attributable to Intravascular Fluid Retention as Determined by Intracardiac Volumes.

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P=0.003) and had a greater proportion of women (75.0% versus 43%; P=0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m2; P<0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P=0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P<0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention.

Evaluation of endothelial function by VOP and inflammatory biomarkers in patients with arterial hypertension.

Hypertension is associated with microcirculatory impairment. Our objectives were to evaluate endothelial function and inflammatory biomarkers in patients with resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to normotensives (control group-CG). Three groups, 25 patients each, have been investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C-reactive protein (CRP). Patients not using statins and with or without blood pressure control were also analyzed. RH group showed smaller percentage increase of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than controls (p < 0.05), but no significant difference could be detected between MMH and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH and MMH groups showed higher resistance averages compared to controls (p < 0.05). Uncontrolled BP in hypertensive patients showed worse results for blood flow and resistance. Endothelial-independent vasodilatation was not affected. Endothelin levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was significantly higher only in RH compared to CG (p < 0.05). In conclusion patients with severe hypertension and lack of blood pressure control showed greater impairment of endothelial function with higher CRP and endothelin levels.

PP.10.20] FLUORESCENCE ANALYSIS OF URINE SAMPLES FOR EVALUATION OF PHARMACOLOGICAL ADHERENCE IN RESISTANT HYPERTENSION

Objective: Resistant hypertensive subjects (RH) present blood pressure (BP) above 140/90 mmHg, despite the use of three or more antihypertensive agents of different classes, including if possible a diuretic. The lack of BP control caused by non-adherence to medication can be falsely interpreted as resistance to drug treatment. Although it is well established that adherence to treatment is critical to achieve BP control, some practical difficulties, such as application of a direct and simple method with low cost and feasibility in the clinical setting still happen. Our goal was to test a simple method to evaluate the medication adherence of RH. Design and method: Twenty-one patients referred to the Resistant Hypertension Clinic (Campinas, Brazil) had the triamterene included in their current prescription and were followed for 30 days period. We performed two random home visits to collect urine samples and test whether the patient took the medication in that day. Office BP, ambulatory BP monitoring (ABPM), home BP measurement (HBPM), biochemical data, and Morisky Adherence Scale (MMAS-8) were systematically acquired. Triamterene and its metabolite were measured by fluorimetric method. According to the fluorescence of urine, the subjects were divided between adherent and nonadherent. Results: We found 9 compliant patients and 12 (57%) non-adherents. No differences were found between groups with respect to baseline characteristics or medications in use; the Kappa test showed concordance between MMAS-8 and fluorescence methods by 0.61 (95% CI 0.28–0.94; p < 0.01).Non-adherent patients had higher office (81 ± 11 vs 73 ± 6 mmHg, p = 0.03), baseline 24-h ABPM (75 ± 9 vs 66 ± 7 mmHg, p = 0.01), post protocol 24-h ABPM (74 ± 9 vs 67 ± 6 mmHg, p = 0.03) and HBPM (77 ± 9 vs 67 ± 8 mmHg, p = 0.01) than their counterparts. Conclusions: Non-adherence to antihypertensive therapy is prevalent in resistant hypertension even if the patients are followed-up in specialized clinics. The fluorimetry method to detect triamterene intake in RH showed to be safe, feasible and easy to assess non-adherence and also associated with clinical parameter.