Blood Pressure-lowering Drugs Research Articles

MEDICAL VERSUS SURGICAL TREATMENT IN PATIENTS WITH NON-FUNCTIONING KIDNEY

Objective: Non-functioning kidney (NFK) can be responsible in whole or in part for hypertension. Patients with a lateralized renin secretion can be treated either medically or surgically. Objective: assess the benefice of nephrectomy over medical treatment in the management of lateralized NFK in hypertensive patients diagnosed after renal vein sampling (RVS). The profit is based on the blood pressure (BP) control, the number of BP lowering drugs or the daily-defined dose (ddd). Design and method: We conducted an observational retrospective study at the Hypertension Unit at Georges-Pompidou European Hospital in France, between January 2004 and January 2021, that analyzes RVS in hypertensive patients. We studied the data (N = 68) at the time of diagnosis and at two follow up visits: the first after RVS or nephrectomy (V1) and the last visit (V2). Results: At V1, in patients with a lateralized NFK: - 18 underwent nephrectomy: 11 vascular disease, 4 urologic disease, 2 trauma and 1 another cause.- 5 were treated medically: all had a vascular disease In patients who underwent nephrectomy, between the diagnosis, V1 and V2 (N = 12) respectively: In patients with medical treatment, between the diagnosis, V1 and V2 (N = 4) respectively: a) systolic BP dropped from 189 to 170,33 to 133,33 mmHgb) number of molecules increased from 3 to 4,8 at V1 and V2c) ddd increased from 63,35 to 118,3 to 267d) at V1 and V2: 1 had a controlled HTN Conclusions: In patients with lateralized NFK, nephrectomy helps in the control of the BP and reduces systolic BP, number of drugs and ddd. The effect on the BP control seems not to be maintained on the long term. Further studies, with a bigger sample, are needed to define subgroups that can benefit the most from nephrectomy.

Heterogeneity in Blood Pressure Response to 4 Antihypertensive Drugs

Hypertension is the leading risk factor for premature death worldwide. Multiple blood pressure-lowering therapies are available but the potential for maximizing benefit by personalized targeting of drug classes is unknown. To investigate and quantify the potential for targeting specific drugs to specific individuals to maximize blood pressure effects. A randomized, double-blind, repeated crossover trial in men and women with grade 1 hypertension at low risk for cardiovascular events at an outpatient research clinic in Sweden. Mixed-effects models were used to assess the extent to which individuals responded better to one treatment than another and to estimate the additional blood pressure lowering achievable by personalized treatment. Each participant was scheduled for treatment in random order with 4 different classes of blood pressure-lowering drugs (lisinopril [angiotensin-converting enzyme inhibitor], candesartan [angiotensin-receptor blocker], hydrochlorothiazide [thiazide], and amlodipine [calcium channel blocker]), with repeated treatments for 2 classes. Ambulatory daytime systolic blood pressure, measured at the end of each treatment period. There were 1468 completed treatment periods (median length, 56 days) recorded in 270 of the 280 randomized participants (54% men; mean age, 64 years). The blood pressure response to different treatments varied considerably between individuals (P < .001), specifically for the choices of lisinopril vs hydrochlorothiazide, lisinopril vs amlodipine, candesartan vs hydrochlorothiazide, and candesartan vs amlodipine. Large differences were excluded for the choices of lisinopril vs candesartan and hydrochlorothiazide vs amlodipine. On average, personalized treatment had the potential to provide an additional 4.4 mm Hg-lower systolic blood pressure. These data reveal substantial heterogeneity in blood pressure response to drug therapy for hypertension, findings that may have implications for personalized therapy. ClinicalTrials.gov Identifier: NCT02774460.

Micellar eco-friendly HPLC method for simultaneous analysis of ternary combination of aspirin, atorvastatin and ramipril: application to content uniformity testing

BackgroundCardiovascular disease medications such as aspirin (ASP), statins like atorvastatin (ATR), and blood pressure-lowering drugs including ACE inhibitors like ramipril (RAM) have been included in the World Health Organization (WHO) Essential Medicines List (EML) for many years. Therefore, there is a strong demand to develop a simple, rapid, and sensitive analytical method that can detect and quantitate the ternary mixture of these analytes in pharmaceutical preparations in a short run time. Lately, the analytical community focused on eliminating or reducing hazardous chemicals and solvents usage.ResultsA green, fast, selective, and cost-effective micellar HPLC method was established and validated for the concurrent determination of ternary combination of ASP, ATR, and RAM in the pure form and pharmaceutical preparations. Resolution of the three drugs was achieved by using a monolithic column and a micellar mobile phase consists of 0.3% triethylamine (TEA) in 90: 10 an aqueous solution of 0.12 M sodium dodecyl sulfate (SDS): n-propanol, (v/v). The pH was adjusted to 2.5 using orthophosphoric acid and a flow rate of 1.5 mL/min. was applied. To ensure method reproducibility, Valsartan (VAL) was utilized as an internal standard (IS). The UV detection of the studied drugs was performed at 210 nm. Good linearity for the three drugs was obtained over the concentration ranges of 1.0-200.0 mg/mL, 0.5-200.0 mg/mL, and 5.0-100.0 mg/mL with correlation coefficients of 0.9998,0.9999 and 0.9999 for ASP, ATR, and RAM respectively. The method sensitivity was revealed by the relatively small values of limits of detection (LOD) (0.19, 0.13 and 0.30 mg/mL) and limits of quantitation (LOQ) (0.63, 0.44 and 0.99 mg/mL) for ASP, ATR, and RAM, respectively. The retention times of ASP, ATR and RAM were 1.50, 2.3 and 4.3 min., respectively.ConclusionsThe suggested technique was employed for the analysis of the three drugs in their prepared tablets maintaining the recommended pharmaceutical ratio without any interference from excipients. The method was further extended to content uniformity testing of RAM. The results were validated according to international council for harmonisation (ICH) guidelines.

Benefit of treatment based on indapamide mostly combined with perindopril on mortality and cardiovascular outcomes: a pooled analysis of four trials.

The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs). Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment. The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity ( I2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%). Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.

PS-C20-1: NIGHT-TIME BLOOD PRESSURE-LOWERING DRUG TREATMENT FOR THE PREVENTION OF CARDIOVASCULAR DISEASE IN DIABETES: A PROPOSED RANDOMISED CONTROLLED TRIAL

Rationale: An increase of 20 mmHg in night-time blood pressure (BP) and a pattern of a higher BP at night than during the day was independently associated with an increased risk of 21% and 48% cardiovascular disease respectively. This association was more likely to present in type 2 diabetes mellitus (DM) patients. Objectives: This proposed study aims to examine the effect of taking night-time BP lowering drug treatment targeting night-time BP profile as compared to the conventional once-daily morning dose on the prevention of cardiovascular disease event in diabetes. Design: A Prospective Randomized Open-label with Blinding of Endpoint assessment. Methods: Men and women diagnosed with type 2 DM patients who are 60 years or over in Australia will be included in the trial. As per the current Australia guideline, these individuals meet the criteria to initiate BP lowering drug treatment for CVD prevention. The trial will be conducted as a “digital clinical trial” for participant recruitment, retention and data collection through an interactive web page platform. Participants will be referred by their health practitioners. Eligible participants will be randomised to either night-time or morning dosing treatments with a 1:1 ratio: a) Taking all of their usual once-daily dose of BP-lowering medications at bedtime (between 20:00 and midnight) or b) Taking a once-daily dose of BP-lowering medications upon awakening (between 06:00 and 10:00). The primary endpoint is the occurrence of any first major CVD events after randomisation. We expect to complete the participant recruitment over the first two years and finalise the analysis after an average follow-up of 5 years. Results: We are finalising the project protocol and have applied the proposed project to relevant research grants. An ethics application has also been prepared. We plan to run a one -year pilot trial and then transfer to the full study. Conclusion: The outcomes of this study will contribute to Level 1 evidence on the effect of night-time BP-lowering drug treatment in the prevention of cardiovascular disease in diabetes. Due to the nature of pragmatic design, our research outcomes are straightforward and could be adopted in current practice without any further cost. Changing the ingestion time of BP-lowering drug treatment from morning to night-time is very cost-effective and promises to reduce the financial and clinical burden of CVD and DM on the healthcare system.

SP-4: FUTURE BLOOD PRESSURE RESEARCH

How is our body's blood pressure regulated? What exactly is the specific mechanism by which hypertension develops? To date, there is no evidence to answer these questions. Therefore, there is no fundamental cure for hypertension, and we must continue to take blood pressure-lowering drugs for the rest of our lives. So, why do we need blood pressure in the first place? It is because the heart needs to pump blood throughout the body to systemically supply necessary oxygen, nutrients, and hormones. We land animals have acquired high blood pressure during the course of evolution, enabling us to perform at a high level even in harsh environments. Humans, in particular, are able to maintain high blood pressure levels even when walking on two legs, allowing to defy gravity and deliver sufficient blood to the brain. This made humans the only high-performance creature capable of using both hands and the only one capable of running marathon distances. However, in the age of plenty, high blood pressure has become increasingly damaging to our bodies. Furthermore, in the future, when we have to live in space, underwater, or other spaces with little gravity, too high blood pressure will have an even more detrimental effect on our bodies. Thus, the development of blood pressure research is essential for the further evolution of humankind, since humans need to constantly optimize their blood pressure to adapt to changes in the environment.

Clinical Utility of Short-Term Blood Pressure Measures to Inform Long-Term Blood Pressure Management.

Decisions about hypertension management are substantially influenced by blood pressure (BP) levels measured before and soon after starting BP lowering drugs. We aimed to assess the utility of short-term BP changes in individuals in terms of long-term treatment response. Post hoc analyses of 2 randomized trials with 4-to-6 weeks active run-in for all participants, followed by randomization to active BP lowering treatment (combination perindopril±indapamide) or placebo. We categorized individuals by degree of systolic BP (SBP) change during active run-in treatment and assessed associations with subsequent postrandomization placebo-corrected BP reduction, cardiovascular events, and tolerability. We included individuals with baseline BP ≥140/90 mm Hg from the PROGRESS trial (Perindopril Protection Against Recurrent Stroke Study; 4275 individuals with cerebrovascular disease) and ADVANCE trial (The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation; 6610 individuals with diabetes). During the active run-in period, the proportion of participants with initial SBP changes in 4 categories (SBP increase, 0-9.9 mm Hg decrease, 10-19.9 mm Hg decrease, and ≥20 mm Hg decrease) were 17%, 27%, 28%, and 28% in PROGRESS and 21%, 22%, 24%, and 33% in ADVANCE. Randomization to active therapy achieved similar placebo-corrected long-term BP reductions across the 4 initial SBP change groups in both trials (P-values for heterogeneity >0.1). There was no significant difference in achieving BP <140/90 mm Hg at follow-up, major cardiovascular events, nor treatment tolerability according to the SBP change during active run-in period (all P-values >0.1). An individual's apparent BP change immediately after commencing therapy has limited clinical utility. Therefore, more emphasis should be given to use of evidence-based regimens and measures over the long-term to ensure sustained BP control. URL: https://www. gov; Unique identifier: NCT00145925.

Stakeholder perspectives on the demand and supply factors driving substandard and falsified blood pressure lowering medications in Nigeria: a qualitative study

ObjectivesAlthough substandard and falsified (SF) blood pressure (BP) lowering medications are a global problem, qualitative research exploring factors driving this in Nigeria has not been reported. This study provides information...

Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes. Methods: This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) &lt; 50% (HF EF &lt; 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use. Results: Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF &lt; 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p&lt;0.001) . Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF &lt; 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF &lt; 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05). Conclusions: In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF&lt;50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.

No prominent role for complement C1-esterase inhibitor in Marfan syndrome mice.

Marfan syndrome (MFS) is a connective tissue disorder causing aortic aneurysm formation. Currently, only prophylactic aortic surgery and blood pressure lowering drugs are available to reduce the risk for aortic rupture. Upon whole genome sequencing (WGS) of a Marfan family, we identified a complement gene C1R variant (p.Ser152Leu), which associated with the severe aortic patients. Therefore, we assessed the role of complement activation in MFS aortic tissue. Expression of various complement genes and proteins was detected in human and murine MFS aneurysm tissue, which prompted us to study complement inhibition in MFS mice. Treatment of the Fbn1C1041G/+ MFS mice with human plasma-derived C1-esterase inhibitor Cetor® resulted in reduced complement deposition, decreased macrophage influx in the aorta and lower circulating TNFα levels. However, in line with previous anti-inflammatory treatments, complement inhibition did not change aortic dilatation rate in this MFS mouse model. Thus, while complement factors/C3 activation were detected in human/murine MFS aorta, Cetor® had no effect on aortic dilatation in MFS mice, indicating that complement inhibition is not a suitable treatment strategy in MFS.

Update on trials examining effects of night-time blood pressure lowering drug treatment on prevention of cardiovascular disease

Current evidence on benefits of night-time blood pressure (BP) lowering drug treatment on cardiovascular disease (CVD) prevention attributable to the Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC) trial and Bedtime hypertension treatment improves cardiovascular risk reduction (Hygia) trials has raised concern on their validity and methodology. In this commentary, the authors have updated the progress of the ongoing trials that were planned to examine the effect of night-time BP lowering drug treatment on CVD prevention. As compared to MAPEC and Hygia trials, three pragmatic trials the Blood Pressure Medication Timing (BPMedtime) trial (US), the Treatment In Morning versus Evening (TIME) trial (UK), Bedmed and Bedmed-frail (Canada) were planned without ambulatory BP monitoring. The BPMedtime trial was stopped after the pilot phase due to underestimated sample size and insufficient funds. TIME trial (UK) had a similar issue when changing the sample size from 10,269 to more than 20,000 participants. The TIME trial was completed and the initial results showing that protection against heart attack, stroke and vascular death is not affected by whether antihypertensive medications are taken in the morning or evening. The full study of the TIME trial is published in December 2022. Bedmed and Bedmed-frail trials are ongoing and will be completed in 2023. Time of taking BP lowering drug should be determined by patients at their convenience to improve the adherence. There was no difference in adverse effects of taking BP lowering drugs at night or morning. Evidence on the effect of night-time treatment on CVD events is inconsistent. The results from ongoing trials in Canada will contribute evidence to the use of BP lowering drug treatment for the prevention of CVD.

Impact of Arterial Hypertension and Use of Antihypertensive Pharmacotherapy on Mortality in Patients Hospitalized due to COVID-19: The CRACoV-HHS Study.

Background:Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19.Methods:We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed.Results:The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2–0.3]; P<0.001) compared to nontreated hypertensives (n=1305).Conclusions:Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure–lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.

Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Controversy exists as to whether the threshold for blood pressure-lowering treatment should differ between people with and without type 2 diabetes. We aimed to investigate the effects of blood pressure-lowering treatment on the risk of major cardiovascular events by type 2 diabetes status, as well as by baseline levels of systolic blood pressure. We conducted a one-stage individual participant-level data meta-analysis of major randomised controlled trials using the Blood Pressure Lowering Treatment Trialists' Collaboration dataset. Trials with information on type 2 diabetes status at baseline were eligible if they compared blood pressure-lowering medications versus placebo or other classes of blood pressure-lowering medications, or an intensive versus a standard blood pressure-lowering strategy, and reported at least 1000 persons-years of follow-up in each group. Trials exclusively on participants with heart failure or with short-term therapies and acute myocardial infarction or other acute settings were excluded. We expressed treatment effect per 5 mm Hg reduction in systolic blood pressure on the risk of developing a major cardiovascular event as the primary outcome, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal ischaemic heart disease, or heart failure causing death or requiring hospitalisation. Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios (HRs) separately by type 2 diabetes status at baseline, with further stratification by baseline categories of systolic blood pressure (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg). To estimate absolute risk reductions, we used a Poisson regression model over the follow-up duration. The effect of each of the five major blood pressure-lowering drug classes, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, β blockers, calcium channel blockers, and thiazide diuretics, was estimated using a network meta-analysis framework. This study is registered with PROSPERO, CRD42018099283. We included data from 51 randomised clinical trials published between 1981 and 2014 involving 358 533 participants (58% men), among whom 103 325 (29%) had known type 2 diabetes at baseline. The baseline mean systolic/diastolic blood pressure of those with and without type 2 diabetes was 149/84 mm Hg (SD 19/11) and 153/88 mm Hg (SD 21/12), respectively. Over 4·2 years median follow-up (IQR 3·0-5·0), a 5 mm Hg reduction in systolic blood pressure decreased the risk of major cardiovascular events in both groups, but with a weaker relative treatment effect in participants with type 2 diabetes (HR 0·94 [95% CI 0·91-0·98]) compared with those without type 2 diabetes (0·89 [0·87-0·92]; pinteraction=0·0013). However, absolute risk reductions did not differ substantially between people with and without type 2 diabetes because of the higher absolute cardiovascular risk among participants with type 2 diabetes. We found no reliable evidence for heterogeneity of treatment effects by baseline systolic blood pressure in either group. In keeping with the primary findings, analysis using stratified network meta-analysis showed no evidence that relative treatment effects differed substantially between participants with type 2 diabetes and those without for any of the drug classes investigated. Although the relative beneficial effects of blood pressure reduction on major cardiovascular events were weaker in participants with type 2 diabetes than in those without, absolute effects were similar. The difference in relative risk reduction was not related to the baseline blood pressure or allocation to different drug classes. Therefore, the adoption of differential blood pressure thresholds, intensities of blood pressure lowering, or drug classes used in people with and without type 2 diabetes is not warranted. British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School.

Opinions on hypertension care and therapy adherence at the healthcare provider and healthcare system level: a qualitative study in the Hague, Netherlands

ObjectivesHypertension is a common cause of cardiovascular morbidity and mortality. Although hypertension can be effectively controlled by blood pressure-lowering drugs, uncontrolled blood pressure is common despite use of these medications....

Quality of life following renal sympathetic denervation in treatment-resistant hypertensive patients: a two-year follow-up study

Objective. Hypertension is a significant health burden. In the last 10 years, renal sympathetic denervation has been tested as a potential treatment option for a select group of patients with treatment-resistant hypertension. The aim of this study was to broadly assess the quality of life in patients undergoing renal sympathetic denervation with two years’ follow-up. Materials and methods. Patients with treatment-resistant hypertension being treated by hypertension specialists were eligible for inclusion in this study. Bilateral renal sympathetic denervation was performed with the Symplicity Catheter System. Quality of life was measured using standardised questionnaires (Short Form 36, 15 D and a single-item question) and an open question before denervation, after six months and after two years. Results. A total of 23 patients were included. The typical participant was male, 53 years, had a mean office blood pressure of 162/108 mmHg, body mass index of 32 kg/m2, and was prescribed 4.8 blood pressure lowering drug classes. At baseline, both physical and mental aspects of quality of life were affected negatively by the treatment-resistant hypertension. Over time, there were modest improvements in quality of life. The largest improvements were seen at six months. Simultaneously, the mean number of blood pressure lowering drug classes was reduced to 4.2. Conclusion. Following renal sympathetic denervation treatment, some aspects of health related quality of life showed an improved trend during follow-up. The observed improvement may reflect the impact of a reduced number of blood pressure lowering drug classes. Clinical Trial Number registered: NCT01630928

56-LB: Racial/Ethnic Differences in the Use of Blood Pressure–Lowering Drugs Associated with Different Risk levels of Type 2 Diabetes among U.S. Adults without Diabetes

Understanding differences in risk factors can assist in identifying means to reduce racial/ethnic disparities in type 2 diabetes (T2D) prevalence. Different types of blood pressure (BP) lowering drugs are associated with different levels of T2D risk. This study examined the utilization of BP-lowering drugs among US adults aged 18 and over without diabetes with diagnosed hypertension by racial/ethnic group. We used self-report or ICD-10 diagnostic codes to identify our study population using the 2016-2019 Medical Expenditure Panel Survey. The high T2D risk drugs included beta-blockers and diuretics and the low-risk drugs were ACEI and ARBs. We calculated the percentage of high-risk and low-risk drug use in non-Hispanic Black (NHB) , non-Hispanic White (NHW) , Hispanic, and Asian persons. Logistic regression was used to compare the uses of two drug types across different racial/ethnic groups, controlling for demographics, history of cardiovascular and renal diseases, insurance, duration of hypertension, and general health measurements. We have identified 18,283 individuals, with a mean age of 60.7 and 52.4% were females. Compared with NHB, NHW persons (adjusted odds ratio (aOR) :0.90, 95% CI: 0.58-0.98) , Hispanic (aOR:0.62, 95% CI: 0.56-0.70) , and Asian (aOR:0.54, 95% CI: 0.46-0.64) persons were less likely to receive high-risk drugs. Meanwhile, NHW (aOR: 1.19, 95% CI: 1.09-1.29) , Hispanic (aOR:1.14, 95% CI: 1.03-1.27) , and Asian (aOR:1.19, 95% CI: 1.02-1.40) persons were more likely to use low-risk drugs than NHB persons (all p&amp;lt;0.05) . The highest use of high-risk BP-lowering drugs and the lowest use of low-risk BP-lowering drugs by NHB persons could increase their risks of T2D and contribute to disparities in T2D prevalence between NHB and other racial/ethnic groups. Future studies can quantify the effect of the BP-lowering drug choices on T2D disparities. Disclosure H. Shao: Board Member; BRAVO4HEALTH, LLC. K. Alkhuzam: None. J. Guo: None. T. Jiao: None. S. M. Smith: None. P. Zhang: None. E. W. Gregg: None.

Repositioning of the Angiotensin II Receptor Antagonist Candesartan as an Anti-Inflammatory Agent With NLRP3 Inflammasome Inhibitory Activity.

Aberrant activation of the NLRP3 inflammasome promotes the pathogenesis of many inflammatory diseases. The development of the NLRP3 inflammasome inhibitors from existing drugs for new therapeutic purposes is becoming more important. Candesartan is an angiotensin II receptor antagonist widely used as a blood pressure-lowering drug; however, the inhibitory potential of candesartan on the NLRP3 inflammasome has not yet been investigated. We demonstrated that candesartan significantly inhibited the NLRP3 inflammasome and pyroptosis in macrophages. Mechanistic analysis revealed that candesartan inhibited the expression of NLRP3 and proIL-1β by suppressing NF-κB activation and reducing the phosphorylation of ERK1/2 and JNK1/2. Candesartan reduced mitochondrial damage and inhibited the NLRP3 inflammasome assembly by suppressing NLRP3 binding to PKR, NEK7 and ASC. In addition, candesartan inhibited IL-1β secretion partially through autophagy induction. Furthermore, oral administration of candesartan reduced peritoneal neutrophil influx, NLRP3 and ASC expression in peritoneal cells, and lavage fluid concentrations of active caspase-1, IL-1β, IL-6 and MCP-1 in uric acid crystal-injected mice. These results indicated that candesartan has board anti-inflammatory effects and has the potential to be repositioned to ameliorate inflammatory diseases or NLRP3-associated complications.

Most commonly prescribed blood pressure lowering drug linked with increased risk of skin cancer.

To the Editor, Hydrochlorothiazide (HCTZ) is the most commonly prescribed antihypertensive drug that belongs to a diuretic class.1 It mainly works by increasing the removal of excess water and salts from the body into the urine and by this function it is most widely used alone or in combination with other medications to treat patients with uncontrolled blood pressure and edema that results from numerous medical conditions like heart, Liver and kidney diseases. It also helps treat other ailments like diabetes insipidus, renal tubular acidosis and reduce the risk of kidney stones in patients with high calcium levels in urine. Despite its various uses and benefits, HCTZ comes with a heavy price of undesirable side effects like fatigue, lethargy, gastrointestinal discomfort and is known to cause hyperuricemia and hypokalemia associated with increased blood glucose.2 Furthermore, HCTZ increases the skin sensitivity to sunlight. However, recent research has revealed a more worrisome side effect of HCTZ that needs to be highlighted. In 2017, a nationwide study conducted in Denmark involving more than 70,000 patients with Basal cell carcinoma and 8000 patients with squamous cell carcinoma found a considerably increased risk of developing Non melanoma skin cancer, particularly among the users of HCTZ.3 A recent study also substantiated that a total of 135 squamous cell carcinoma events per 100,000 person years were reported in new users of HCTZ.4 These alarming figures raise a question mark on the safety of HCTZ use. Moreover, HCTZ is now classified as a carcinogenic agent for humans by the International Agency for Research on Cancer and the U.S. Food and Drug Administration has also permitted changes to the HCTZ drug label to warn the health care workers and patients of the risk of non-melanoma skin cancer. 5, 6 Unfortunately in Pakistan, HCTZ is still heavily used as a diuretic and people are not much aware of this new fact. In view of these findings and the fact that HCTZ is among the most generally prescribed drugs in Pakistan, its potential indication of causing skin cancer would impose a serious public health concern so the responsibility lies on the cardiologists, nephrologists and other medical physicians to be aware of this possible hazardous outcome of HCTZ use and should be cautious while prescribing it to patients who are at risk of developing skin cancer or who have had a history of skin cancer.

Blood pressure and blood sugar-lowering effects of purified gambir on diabetic hypertensive Wistar Kyoto rats.

Antioxidants protect people from diabetes and its cardiovascular complication. Purified gambir (Uncaria gambir Roxb.) is a potential medicinal plant for treating this condition based on the antioxidant activity of its catechin compound. This study tries to reveal the potential activity of purified gambir as a blood pressure-lowering drug while lowering blood glucose in diabetic hypertensive rats induced by oral NaCl-Prednisone and Alloxan. Rats were induced by oral NaCl 0.8% and Prednisone 5mg/kg BW for 14days to obtain hypertensive condition. Alloxan 125mg/kg BW was given intra peritoneal injection on the 8th day to obtain diabetic hypertensive condition. The animal was divided into five groups, normal control group treated with vehicle, treatment groups were treated with purified gambir at dose of 2.5; 5 and 10mg/kg BW respectively, while the positive control group were treated with a combination of captopril-glibenclamide at dose of 2.25 and 0.45mg/kg BW. All animals were treated orally for 14days. Fasting blood glucose and cardiovascular parameters (SBP, DBP, MAP, HR, BF and BV) were measured on days 1, 3, 7, and 14. NO level were measured on day 0 and day 14. Data were analyzed using two-way ANOVA followed by Duncan Multiple Range Test. The purified gambir has blood pressure and blood sugar-lowering activity (p<0.05). The NO levels of the treatment group also increased significantly (p<0.05). This study indicated that purified gambir could be an alternative medicine to manage blood glucose and blood pressure in the diabetic hypertensive model.

IN SILICO IDENTIFICATION TESTING OF TRITERPENE SAPONINES ON CENTELLA ASIATICA ON INHIBITOR RENIN ACTIVITY ANTIHYPERTENSIVE

The renin-angiotensin-aldosterone system (RAAS) has an essential role in the occurrence of hypertension. Two drugs that act on SRAA are ACE Inhibitor and ARB. ACE inhibitor and ARB are two antihypertensive drugs that act on RAAS. However, both drugs are not fully effective because they produce incomplete suppression of RAAS. The therapeutic potential of the two drugs is limited, so it is necessary to find out other drugs that are more effective in inhibiting the RAAS system. Renin-inhibitors are evolving as options that can inhibit at the highest levels in RAAS. Discontinuation of renin inhibitor therapy does not cause rebound hypertension as in ACEIs and ARBs. The search for natural renin inhibitors began to be carried out as an alternative to aliskiren. Renin-inhibitors derived from natural ingredients generally come from the class of saponin compounds or polyphenol compounds. One of Indonesia's native plants that contain saponins and polyphenols is Centella asiatica. Thus, research on the antihypertensive potential of these plants was carried out. It is expected that the Centella asiatica plant has a renin inhibitor effect as a blood pressure-lowering drug derived from herbs but has the same effect as aliskiren. The research method was carried out in silico to test the activity of compounds that have potential as antihypertensives in the Centella asiatica plant. The method used is molecular docking, with the docking software used being Molegro Virtual Docker (MVD) 6.0. The results showed that madecasoside and asiaticoside from the Centella asiatica plant have intense renin inhibitor activity, with a mean re-rank score of-105.27 and-93.67, respectively. The conclusion is that madecasoside has similarities with aliskiren with a re-rank value of-105.27. The smallest re-rank value indicates the similarity and strong protein binding between the tested ligand compound and the comparison protein.