Blood Pressure-lowering Drugs Research Articles

Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? A critical review.

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.

Effect of long-term antihypertensive therapy on myocardial strain: a meta-analysis.

Evidence on the impact of blood pressure (BP)-lowering drugs on left ventricular (LV) mechanics in hypertension is still limited. We performed a meta-analysis of speckle-tracking echocardiographic studies in order to provide a new piece of information on this topic. The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search for articles published from the inception up to 31 October 2021. Studies were identified by using MeSH terms and crossing the following search items: 'myocardial strain', 'left ventricular mechanics', 'speckle tracking echocardiography', 'systolic dysfunction', 'left ventricular hypertrophy', 'systemic hypertension', 'BP lowering drugs,' 'antihypertensive therapy'. A total of 1140 hypertensive patients (mean age 55.4 years, 50% men, follow-up 6-36 months) were included in eight studies. Pretreatment and posttreatment pooled SBP/DBPs were 148.4 ± 3.5/88.7 ± 2 vs. 127.4 ± 1.9/77.8 ± 0.9 mmHg. Corresponding values for ejection fraction (EF), LV mass (LVM) index, and global longitudinal strain (GLS) were 64 ± 2.3 vs. 65.9 ± 1.7% (SMD: 0.14 ± 0.03, CI 0.08- 0.20, P = 0.001); 108.4 ± 11.2 vs. 100.2 ± 11.0 g/m2 (SMD: -0.27 ± 0.10, CI -0.46 to -0.08, P < 0.01); -17.7 ± 0.6 vs. -19.6 ± 0.4%, (SMD 0.26 ± 0.03, CI 0.20-0.32, P < 0.0001), respectively. A meta-regression analysis showed a significant relation between GLS improvement and the extent of reduction of LVMI (P = 0.0003), but not of SBP (P = 0.27). Our meta-analysis suggests that antihypertensive treatment has a clear beneficial effect on LV mechanisms, and the improvement in GLS is mainly related to the reduction in LVMI rather than SBP.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs.

In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

Pharmacotherapy in Clinical Trials for Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

ObjectiveThere is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events.MethodsA systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome.OutcomesA total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: −0.81 mm/y, 95% CI: −1.19 to −0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: −0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: −0.27 mm/y, 95% CI: −0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: −1.11mm/year, 95%CI: −2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%).ConclusionIn conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

Trend in Blood Pressure Control Post Antihypertensive Drug Initiation in the U.S.

The aim of this study is to evaluate the temporal trends in systolic blood pressure control over 18 months after blood pressure‒lowering drug initiation in the U.S. From U.S. nationally representative electronic health records, 1,036,775 adults initiating and continuing blood pressure‒lowering drugs for ≥18 months during 2006-2018 were identified (January 2021). Prevalence trends of cardiovascular disease, diabetes, and depression at blood pressure‒lowering drug initiation, blood pressure‒lowering drug therapy intensification over 18 months, and the adjusted probability of achieving systolic blood pressure control 6 months after baseline and sustaining the control for over 18 months were evaluated. At blood pressure‒lowering drug initiation, the prevalence of diabetes and depression consistently increased during the study period across all age groups, particularly in those aged 18-49 years, whereas the prevalence of cardiovascular disease was stable. Adjusted probabilities of achieving sustainable systolic blood pressure control by age group were 0.62 (95% CI=0.61, 0.63) for ages 18-39 years, 0.55 (95% CI=0.55, 0.56) for ages 40-49 years, 0.50 (95% CI=0.49, 0.50) for ages 50-59 years, 0.43 (95% CI=0.42, 0.43) for ages 60-69 years, and 0.37 (95% CI=0.37, 0.38) for ages 70-80 years. Those with cardiovascular disease or cardiovascular disease and diabetes had approximately 20% lower adjusted probability of achieving systolic blood pressure control (31%/29%) than those without these conditions (52%, p<0.01). Those with depression had a 4% higher probability of systolic blood pressure control than those without the condition (49% vs 45%, p<0.01). In the U.S., only 30%-50% of the population are achieving sustainable blood pressure control over 18 months after blood pressure‒lowering drug initiation, with no indication of improvement in control over the last decade.

Elevated blood pressure, antihypertensive medications and bone health in the population: revisiting old hypotheses and exploring future research directions

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomised trials is insufficient to establish causal associations for blood pressure and use of blood pressure–lowering drugs with bone health outcomes, particularly with the risks of osteoporosis and fractures. The availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches provide opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical techniques, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on the risks of low bone mineral density and fractures. As elevated blood pressure is highly prevalent and blood pressure–lowering drugs are widely prescribed, even small effects of these exposures on bone health outcomes could be important at a population level.

PENGARUH JARAK TANAM DAN PEMBERIAN PUPUK ORGANIK CAIR DI GROW TERHADAP PERTUMBUHAN DAN HASIL TANAMAN BAWANG DAYAK (Eleutherine americana Merr)

Dayak onion has many benefits, namely anti-inflammatory, stopping the bleeding, anti-breast cancer, heart disease prevention, immunostimulant, anti-tumor, high blood pressure-lowering drugs (hypertension), and diabetes. Dayak onion bulbs contain flavonoids, saponins, polyphenols, alkaloids, glycosides, steroids, phenolics, tannins, triterpenoids, and quinones. DI Grow liquid organic fertilizer is the latest generation of organic fertilizer in agriculture. This fertilizer contains nutrients at a balanced level and also plant growth regulators such as auxin, gibberellin, and cytokinin. This research aims to find out the interaction and the main effect of planting distance and DI Grow liquid organic fertilizer to the growth and the yield of Dayak onion. The research was carried out in the Experimental farm of the Faculty of Agriculture, Islamic University of Riau, Pekanbaru. This research was carried out during 7 months, starting from April to November 2018. The experimental design is a Completely Randomized Factorial Design. The observed parameters are the relative growth rate, net assimilation rate, the number of clump tubers, clump wet weight, and clump dry weight. The results showed that the interaction between planting distance and DI Grow fertilizer did not significantly affect on all the observed parameters. The main effect of planting distance and DI Grow fertilizer was found on all parameters with the best treatment at a planting distance of 25x30 (J4) and DI Grow fertilizer dose of 9 ml/L of water (D3).

Abstract P128: Direct Observed Therapy In Suspected Resistant Hypertension Is Safe

Introduction: Direct observed therapy (DOT) has emerged as a method for assessment of adherence, particularly in patients with apparent treatment-resistant hypertension (ATRH), in clinical care as well as research. We have previously demonstrated that direct observed therapy resulted in controlled hypertension in 30% of patients with ATRH. In this study we report on the safety of DOT in terms of change in blood pressure (BP) and hypotensive symptoms. Methods: Patients with ATRH were enrolled in a prospective study of DOT, which was followed by ambulatory blood pressure monitoring on the same day and at one month. DOT was performed by administering all prescribed BP lowering drugs, supervised by a nurse in an outpatient clinic setting. BP and vitals were measured at baseline and every 30 minutes until BP plateau based on two consecutive BP readings. All BP measurements during DOT were performed using an automated oscillometric BP device. In this study, we report the change in BP during DOT, with incidence of orthostatic symptoms, and decrease in systolic BP &gt; 20 mm Hg as outcomes of interest. Results: 50 patients underwent DOT, 32 men, mean age 62 years on median 4 BP lowering drugs (range 3 to 7). The mean baseline BP was 146/77 mm Hg , and the lowest BP during DOT was 129/68 mm Hg. The median decrease in systolic BP was 14 mm Hg (range 0 to 60) and diastolic BP was 8 mm Hg (range 0 to 37). 5 patients (10%) developed orthostatic symptoms during DOT, none of which required any interventions, and resolved with continued observation. A decrease of &gt; 20 mm Hg in systolic BP was seen in 19 patients (38%), and a systolic BP of &lt; 110 mm Hg was seen in only 6 patients (12%). Conclusions: DOT caused decrease in BP by &gt;20 mmHg in about 40% of patients. While these large acute decreases in BP were largely asymptomatic, close observation of BP is required until peak BP lowering effect wanes. As decrease in BP is driven by the degree of non-adherence and number of prescribed BP lowering drugs, our safety record has limitation dictated by the number of subjects enrolled, and relatively small number of patients with more than 5 BP lowering drugs.

Prediction of first cardiovascular disease event in 2.9 million individuals using Danish administrative healthcare data: a nationwide, registry-based derivation and validation study.

AimsThe aim of this study was to derive and validate a risk prediction model with nationwide coverage to predict the individual and population-level risk of cardiovascular disease (CVD).Methods and resultsAll 2.98 million Danish residents aged 30–85 years free of CVD were included on 1 January 2014 and followed through 31 December 2018 using nationwide administrative healthcare registries. Model predictors and outcome were pre-specified. Predictors were age, sex, education, use of antithrombotic, blood pressure-lowering, glucose-lowering, or lipid-lowering drugs, and a smoking proxy of smoking-cessation drug use or chronic obstructive pulmonary disease. Outcome was 5-year risk of first CVD event, a combination of ischaemic heart disease, heart failure, peripheral artery disease, stroke, or cardiovascular death. Predictions were computed using cause-specific Cox regression models. The final model fitted in the full data was internally-externally validated in each Danish Region. The model was well-calibrated in all regions. Area under the receiver operating characteristic curve (AUC) and Brier scores ranged from 76.3% to 79.6% and 3.3 to 4.4. The model was superior to an age-sex benchmark model with differences in AUC and Brier scores ranging from 1.2% to 1.5% and −0.02 to −0.03. Average predicted risks in each Danish municipality ranged from 2.8% to 5.9%. Predicted risks for a 66-year old ranged from 2.6% to 25.3%. Personalized predicted risks across ages 30–85 were presented in an online calculator (https://hjerteforeningen.shinyapps.io/cvd-risk-manuscript/).ConclusionA CVD risk prediction model based solely on nationwide administrative registry data provided accurate prediction of personal and population-level 5-year first CVD event risk in the Danish population. This may inform clinical and public health primary prevention efforts.

Chronotherapy for morning blood pressure surge in hypertensive patients: a systematic review and meta-analysis

BackgroundThe morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients.Methods A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included.ResultsA total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (− 5.30 mmHg, 95% CI − 8.80 to − 1.80), night-time SBP (− 2.29 mmHg, 95% CI − 4.43 to − 0.15), night-time DBP (− 1.63 mmHg, 95 %CI − 3.23 to − 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71).ConclusionsOur study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.

Tengdan Capsule Prevents Hypertensive Kidney Damage in SHR by Inhibiting Periostin-Mediated Renal Fibrosis.

BACKGROUND: Hypertension-induced renal damage is a serious and complex condition that has not been effectively treated by conventional blood pressure-lowering drugs. Tengdan capsule (TDC) is a China FDA-approved compound herbal medicine for treating hypertension; however, its chemical basis and pharmacological efficacy have not been fully investigated in a preclinical setting. METHODS: High-performance liquid chromatography (HPLC) was used to identify and quantify the major chemical components of TDC extracted from ultrapure water. Adult spontaneously hypertensive rats (SHR) and age/sex-matched Wistar Kyoto normotensive rats (WKY) were both treated with TDC, losartan, or saline for one month, and their blood pressure (BP) was monitored at the same time by tail-cuff BP system. Biochemical indexes such as urine creatinine (CRE) and blood urea nitrogen (BUN) were determined. Kidney tissue sections were examined with (H&E), and Masson staining to evaluate the pathological effect of TDC on SHR’s kidneys. After TDC treatment, the differentially expressed proteins in the kidneys of SHR were identified by the TMT-based quantitative proteomics analysis, which may provide the targets and possible mechanisms of TDC action. In addition, Western blot analysis, RT-qPCR, and ELISA assays were carried out to further verify the proteomics findings. Finally, two different models involving in vitro renal injuries were established using human kidney HEK293 cells; and the molecular mechanism of TDC kidney protection was demonstrated. RESULTS: Seven chemical compounds, namely Notoginsenoside R1, Ginsenoside RG1, Ginsenoside Re, Ginsenoside Rb1, Sodium Danshensu, Protocatechualdehyde, and Salvianolic acid B, were identified and quantified from the water-soluble extracts of TDC by HPLC. In vivo study using rats showed that TDC effectively reduced BP, BUN, and CRE levels and attenuated renal fibrosis in SHR, and ameliorated damage to the kidneys. Proteomics and subsequent bioinformatics analyses indicated that periostin-mediated inflammatory response and TGFβ/Smad signaling pathway proteins were closely related to the therapeutic effect of TDC in rat kidneys. Western blot analysis and RT-qPCR showed that TDC markedly downregulated the mRNA and protein expression of periostin in renal tissues compared to the untreated SHR. In addition, TGF-β and COL1A1 mRNA levels also decreased in SHR renal tissues following TDC treatment. In vitro studies showed that low to medium doses of TDC down-regulated the expression of periostin in the injury model of HEK293 cell. In addition, medium to high doses of TDC significantly inhibited collagen deposition in TGFβ1-induced HEK293 cell fibrosis. CONCLUSIONS: Major components from the compound herbal medicine Tengdan Capsule are identified and quantified. TDC effectively lowers blood pressure and protects against renal damage caused by hypertension in SHR. Mechanistically, TDC blocks periostin by regulating the TGF-β/Smad signaling pathway in the kidney, both in vivo and in vitro. Preventing periostin-mediated renal fibrosis and inflammation might be a promising strategy for treating a hypertensive renal injury.

A PRACTICAL APPROACH TO SWITCH FROM A MULTIPLE PILL THERAPEUTIC STRATEGY TO A POLYPILL-BASED STRATEGY FOR SECONDARY PREVENTION IN PATIENTS WITH HYPERTENSION

Objective: The recommendation in hypertension is to initiate treatment with a combination of two blood pressure-lowering drugs in a single pill regardless of the cardiovascular (CV) risk, to add a statin in patients with established CV disease (CVD) or at moderate or high risk, and to add as well an antiplatelet agent only among those with established CVD. Some clinical guidelines nowadays endorse the polypill approach to increase the efficiency of the pharmacological treatment and decrease CV morbidity and mortality. The CNIC polypill is the only CV polypill marketed in Europe and the only approved by the EMEA for the secondary prevention of CVD. This polypill contains aspirin, ramipril, and atorvastatin. We aimed at helping clinicians to start treatment with the CNIC polypill switching from any other statin to atorvastatin, and from any angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to ramipril. Design and method: We looked for available data and recommendations to build tables of equivalent effective daily doses of two of the polypill components (ramipril and atorvastatin), and we developed a treatment algorithm based on expert opinion. Results: We provide the approximate equivalent effective daily doses of other ACEIs and ARBs with ramipril and of other statins according to atorvastatin's potency. Moreover, to guide clinicians in the management of patients for secondary prevention of CVD, we provide a treatment algorithm and detail the indications and different available preparations to start treatment with the CV polypill in patients with high BP and prior CVD, and how to associate other BP-lowering drugs or lipid-lowering drugs if need be. Finally, we give advice on how to switch and adapt the treatment of patients already on fixed-dose combinations of antihypertensive medications to initiate the CV polypill regimen. Conclusions: The multiple doses of the individual components of the CNIC polypill versions allow for increased flexibility in prescribing and use it to start treatment in patients with high BP and prior CVD, and probably also in the particular scenario of hypertensive patients at high CVD risk without previous CV event and no significant risk of major bleeding.

Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis.

SummaryBackgroundSome studies have suggested a link between antihypertensive medication and cancer, but the evidence is so far inconclusive. Thus, we aimed to investigate this association in a large individual patient data meta-analysis of randomised clinical trials.MethodsWe searched PubMed, MEDLINE, The Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from Jan 1, 1966, to Sept 1, 2019, to identify potentially eligible randomised controlled trials. Eligible studies were randomised controlled trials comparing one blood pressure lowering drug class with a placebo, inactive control, or other blood pressure lowering drug. We also required that trials had at least 1000 participant years of follow-up in each treatment group. Trials without cancer event information were excluded. We requested individual participant data from the authors of eligible trials. We pooled individual participant-level data from eligible trials and assessed the effects of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), β blockers, calcium channel blockers, and thiazide diuretics on cancer risk in one-stage individual participant data and network meta-analyses. Cause-specific fixed-effects Cox regression models, stratified by trial, were used to calculate hazard ratios (HRs). The primary outcome was any cancer event, defined as the first occurrence of any cancer diagnosed after randomisation. This study is registered with PROSPERO (CRD42018099283).Findings33 trials met the inclusion criteria, and included 260 447 participants with 15 012 cancer events. Median follow-up of included participants was 4·2 years (IQR 3·0–5·0). In the individual participant data meta-analysis comparing each drug class with all other comparators, no associations were identified between any antihypertensive drug class and risk of any cancer (HR 0·99 [95% CI 0·95–1·04] for ACEIs; 0·96 [0·92–1·01] for ARBs; 0·98 [0·89–1·07] for β blockers; 1·01 [0·95–1·07] for thiazides), with the exception of calcium channel blockers (1·06 [1·01–1·11]). In the network meta-analysis comparing drug classes against placebo, we found no excess cancer risk with any drug class (HR 1·00 [95% CI 0·93–1·09] for ACEIs; 0·99 [0·92–1·06] for ARBs; 0·99 [0·89–1·11] for β blockers; 1·04 [0·96–1·13] for calcium channel blockers; 1·00 [0·90–1·10] for thiazides).InterpretationWe found no consistent evidence that antihypertensive medication use had any effect on cancer risk. Although such findings are reassuring, evidence for some comparisons was insufficient to entirely rule out excess risk, in particular for calcium channel blockers.FundingBritish Heart Foundation, National Institute for Health Research, Oxford Martin School.

DDIWAS: High-throughput electronic health record-based screening of drug-drug interactions.

We developed and evaluated Drug-Drug Interaction Wide Association Study (DDIWAS). This novel method detects potential drug-drug interactions (DDIs) by leveraging data from the electronic health record (EHR) allergy list. To identify potential DDIs, DDIWAS scans for drug pairs that are frequently documented together on the allergy list. Using deidentified medical records, we tested 616 drugs for potential DDIs with simvastatin (a common lipid-lowering drug) and amlodipine (a common blood-pressure lowering drug). We evaluated the performance to rediscover known DDIs using existing knowledge bases and domain expert review. To validate potential novel DDIs, we manually reviewed patient charts and searched the literature. DDIWAS replicated 34 known DDIs. The positive predictive value to detect known DDIs was 0.85 and 0.86 for simvastatin and amlodipine, respectively. DDIWAS also discovered potential novel interactions between simvastatin-hydrochlorothiazide, amlodipine-omeprazole, and amlodipine-valacyclovir. A software package to conduct DDIWAS is publicly available. In this proof-of-concept study, we demonstrate the value of incorporating information mined from existing allergy lists to detect DDIs in a real-world clinical setting. Since allergy lists are routinely collected in EHRs, DDIWAS has the potential to detect and validate DDI signals across institutions.

Effect of Metabolic Syndrome and Individual Components on Colon Cancer Characteristics and Prognosis.

Metabolic syndrome (MS) is recognized as a risk factor for colon cancer (CC). However, whether the cluster of metabolic changes that define MS also influence CC prognosis remains unclear. Thus, our aim was to investigate whether the presence of MS or any of the MS individual components could provide prognostic information on tumor phenotype and survival outcomes. Clinical and pathological data from patients with CC (n = 300) who underwent surgical resection at a single tertiary hospital were retrospectively collected to evaluate presence of MS components and diagnostic criteria, CC phenotype and disease outcomes. Patients were allocated into two groups according to the presence or absence of MS (n = 85 MS vs n = 83 non-MS). The overall prevalence of MS individual components was 82.7% for increased waist-circumference (WC), 61.3% for high blood pressure (BP), 48.8% for low HDL-cholesterol, 39.9% for high fasting glucose, and 33.9% for hypertriglyceridemia. Patients in the MS group presented smaller tumors (p = 0.006) with lower T-stage (p = 0.002). High BP (p = 0.029) and hypertriglyceridemia (p = 0.044) were associated with a smaller tumor size, while low-HDL (p = 0.008) was associated with lower T-stage. After propensity score matching using age, tumor size and staging as covariates high-BP (p = 0.020) and WC (p = 0.003) were found to influence disease-free survival, but not overall survival. In conclusion, despite MS being an established risk factor for CC, our data does not support the hypothesis that MS components have a negative impact on disease extension or prognosis. Nevertheless, a protective role of BP and lipid lowering drugs cannot be excluded.

Polypill with or without Aspirin in Persons without Cardiovascular Disease

BackgroundA polypill comprising statins, multiple blood-pressure–lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease.MethodsUsing a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed.ResultsA total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups.ConclusionsCombined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.)

UV SPECTROSCOPY DETERMINATION OF CILAZAPRIL AND HYDROCHLOROTHIAZIDE ACTIVE AGENTS USED IN THE TREATMENT OF HYPERTENSION

Background: Antihypertensive and diuretic drugs are widely used in patients to regulate high blood pressure. Objective of current study was to prepare various cilazapril and hydrochlorothiazide mixtures, to create a matrix effect in the drug and to determine the determination of these active substances in drug samples after optimum conditions. &#x0D; Method: In the spectrophotometric method, 100 mgL−1 solutions were prepared in cilazapril, hydrochlorothiazide in methanol + 0.1 m HCL solvent and then mixtures of these solutions were prepared between specific ppm. The absorbance’s of the solvent against the blind were read at 0.1 nm intervals. After the mixture, tablet (drug) sample was prepared and chemometrics methods were applied to the values obtained by saving the absorbance values.&#x0D; Results: It was observed that the main component analysis applied as a result of spectrophotometric determination of various mixtures of cilazapril and hydrochlorothiazide used in the study gave correct results. These results were validated using various chemometric parameters.&#x0D; Conclusion: The proposed chemometric method can be used in routine analysis in industrial laboratories.&#x0D; &#x0D; Peer Review History: &#x0D; Received 7 November 2020; Revised 8 Decembe; Accepted 4 January, Available online 15 January 2021&#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file: Comments of reviewer(s): &#x0D; Average Peer review marks at initial stage: 5.5/10&#x0D; Average Peer review marks at publication stage: 7.0/10&#x0D; Reviewer(s) detail:&#x0D; Dr. Ali Abdullah Al-yahawi, Al-Razi university, Department of Pharmacy, Yemen, alyahawipharm@yahoo.com&#x0D; Dr. U. S. Mahadeva Rao, Universiti Sultan Zainal Abidin, Terengganu Malaysia, raousm@gmail.com&#x0D; Similar Articles:&#x0D; VALIDATION OF HPLC AND UV VISIBLE METHODS FOR FEW SELECTED BLOOD PRESSURE LOWERING DRUGS AND THEIR FORMULATIONS

Elevated Blood Pressure, Antihypertensive Medications and Bone Health in the Population: Revisiting Old Hypotheses and Exploring Future Research Directions

Blood pressure and bone metabolism appear to share commonalities in their physiologic regulation. Specific antihypertensive drug classes may also influence bone mineral density. However, current evidence from existing observational studies and randomized trials is insufficient to definitely suggest likely causal associations between blood pressure levels and use of blood-pressure lowering drugs on bone health outcomes, particularly on the risks of osteoporosis and fractures. Nevertheless, the availability and access to relevant large-scale biomedical data sources as well as developments in study designs and analytical approaches are providing opportunities to examine the nature of the association between blood pressure and bone health more reliably and in greater detail than has ever been possible. It is unlikely that a single source of data or study design can provide a definitive answer. However, with appropriate considerations of the strengths and limitations of the different data sources and analytical approaches, we should be able to advance our understanding of the role of raised blood pressure and its drug treatment on bone health outcomes. As elevated blood pressure and use of blood pressure-lowering drugs are highly prevalent, even small effects of these exposures on bone health outcomes could be important at a population level.

Giving Watermelon Juice on the Reduction of Blood Pressure of Young Adult Hypertension

The incidence of hypertension in Southeast Sulawesi tends to increase each year. Many people with hypertension are tired of taking blood pressure-lowering drugs because they are addictive and have side effects. The objective of the study was to understand the effect of watermelon juice supplementation to decrease blood pressure on early adult hypertension sufferers in the working area of the Public Health Center of Poasia Kendari city. This study was a true experiment through pretest-posttest with a control group design. The sample size was 30 people who were determined by purposive sampling technique and was allocated by matching within 15 people for both treatment and control groups. The statistical test result showed that there were different blood pressure both systolic and diastolic blood pressures before and after receiving watermelon juice supplementation for 7 days with the dose was twice 350/gr/glass/day on treatment group with significance value ? = 0,000 (? = 0,05). Meanwhile, for the control group, there was no different blood pressure before and after receiving supplementation with significance value ? = 1,000 (? = 0,05) for systolic pressure and ? = 0,499 for diastolic one. There was different blood pressure after receiving watermelon juice supplementation between treatment and control groups with significance value ? =0,031 (? = 0,05) for systolic pressure and p = 0,012 for diastolic one. Hence, it’s concluded that there was a significant effect of watermelon juice supplementation to decrease the blood pressure on early adult hypertension sufferers.

Applicability of Blood Pressure-Lowering Drug Trials to Real-World Patients With Cardiovascular Disease.

This study aimed to assess applicability of blood pressure-lowering drug trials to real-world secondary preventive care. We applied the eligibility criteria of the landmark blood pressure-lowering drug trials (EUROPA, PEACE, HOPE-peripheral arterial disease [PAD], PRoFESS, and PROGRESS) to patients with coronary artery disease (CAD; n=5155), peripheral arterial disease (PAD; n=1487), and cerebrovascular disease (n=2515) participating in the UCC-SMART cohort. Baseline differences according to trial eligibility were assessed. Differences in risk of all-cause mortality and a composite of cardiovascular death, myocardial infarction, and stroke (major adverse cardiovascular event) were calculated using Cox proportional hazard models, adjusted for age, sex, and cardiovascular risk factors. Seventy-five percent of UCC-SMART patients with CAD would have been eligible for EUROPA, 84% for PEACE, 59% of patients with PAD for HOPE-PAD, 17% of patients with cerebrovascular disease for PRoFESS, and 100% for PROGRESS. Eligible patients were older (average difference ranging 1.4-14.6 years across trials). Eligible patients with CAD were at lower risk of major adverse cardiovascular event after adjustment for age, sex, and cardiovascular risk factors in PEACE (hazard ratio, 0.65 [95% CI, 0.53-0.79]) and of mortality in both EUROPA (hazard ratio, 0.72 [95% CI, 0.62-0.82]) and PEACE (0.63 [95% CI, 0.51-0.78]). Adjusted mortality and major adverse cardiovascular event risks were not different between eligible and ineligible patients with PAD and cerebrovascular disease in HOPE-PAD, PRoFESS, and PROGRESS. The majority of real-world patients with CAD, PAD, or cerebrovascular disease would be eligible for landmark trials on blood pressure-lowering drugs. Patients with CAD ineligible for the EUROPA and PEACE trials are at higher adjusted mortality and major adverse cardiovascular event risks, which may limit applicability of their results to ineligible patients.