Blood pressure targets, medication consideration and special concerns in elderly hypertension part I: General principles and special considerations.

To achieve a consensus on optimal blood pressure (BP) targets for older adults remains challenging, necessitating a trade-off between cardiovascular benefits and the risk of impaired organ perfusion. Evidence suggests that age and frailty have a minimal influence on the cardiovascular benefits of intensive BP control in community-dwelling elderly. Nonetheless, an increased incidence of acute kidney injury with intensive BP control has been observed in octogenarians. Therefore, it is recommended to maintain systolic BP below 130 mmHg for hypertensive patients aged 65-80 years. If well-tolerated, a systolic BP target below 120 mmHg can be recommended for patients with chronic kidney disease (CKD). However, no conclusive evidence supports a stringent BP target for patients aged 80 years and older. The selection of antihypertensive medications for elderly patients requires consideration of their cardiovascular condition and potential contraindications. Combination therapy may be necessary to achieve the desired BP target. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the primary choices for patients with CKD. Newer generation mineralocorticoid receptor antagonists may further reduce the risk of cardiovascular or renal events in this population. In conclusion, managing hypertension in elderly patients requires a personalized approach that balances cardiovascular benefits with potential risks, considering individual health profiles and tolerability.

Repurposing antihypertensive drugs for pain disorders: a drug-target mendelian randomization study.

Objective: Addressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections. Methods: A comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW's multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference. Results: Our analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research. Conclusion: The findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Background: Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide. Methods: A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use. Findings: Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%). Interpretation: Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access.

Current use of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors for hypertension in patients with chronic kidney disease with proteinuria: a cross-sectional study based on real-world data.

Japanese guidelines recommend angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) as first-line therapy in hypertensive patients with chronic kidney disease (CKD) and proteinuria, but calcium channel blockers in patients with stage G4-5 CKD aged ≥75 years; however, the implementation of these guidelines in clinical practice is unclear. We investigated the actual use of these agents in this patient population. We conducted a cross-sectional study using the DeSC database, which includes anonymous information from various health insurance systems in Japan. A total of 34,362 hypertensive patients aged <75 years with CKD stage G1-G5 with urinary protein ≥1+ or aged ≥75 years with CKD stage G1-G3 with urinary protein ≥1+, for whom Japanese guidelines recommend first-line ARBs/ACEIs, were included in the analysis. Prescription rates of ARBs and ACEIs were calculated overall and separately for each age group and glomerular filtration rate category. The mean participant age was 65.8 ± 14.8 years, including 24,585 patients (72%) <75 years and 9777 (28%) ≥75 years. Of these, 9529 were prescribed ARBs/ACEIs (prescription rate 28%). The prescription rate was lower in patients aged <75 years with CKD stage G1-G5 (prescription rate 23%) compared with patients aged ≥75 years old with CKD stage G1-G3 (prescription rate 41%) (p < 0.001). Patients with CKD stage G1 had the lowest prescription rates for ARBs/ACEIs in both age categories. These results indicate that, despite guideline recommendations, ARBs/ACEIs are insufficiently prescribed for patients with hypertension associated with CKD with proteinuria. ARBs and ACEIs were only used in 28% of hypertensive patients aged<75 years (CKD stage G1-G5) or aged ⩾75 years (CKD stage G1-G3), with urinary protein ⩾1+, for whom Japanese guidelines recommend ARBs/ACEIs. The prescription rate was lower in the younger compared with the older patients.

Molecular Imaging of Renin Activity using Fluorogenic Nanoprobes for Precision Antihypertensive Therapy.

Life-threatening hypertension remains inadequately controlled in clinics due to its heterogenous renin levels. Rapid stratification of hypertension through renin analysis is crucial for effective personalized treatment, yet an ultrasensitive detection approach is currently lacking. Here, we report activatable renin nanoprobes (ARNs) for non-invasive and ultrasensitive profiling of renin activity and guiding antihypertensive treatment decision through near-infrared fluorescence (NIRF) in vivo imaging and in vitro urinalysis. ARNs are intrinsically non-fluorescent due to NIRF reporter connected to a gold nanocluster through a renin-responsive peptide. In hyperreninemia mouse models, ARNs specifically react with renin to liberate the renal clearable NIRF reporter for accurate renin detection that outperforms the gold standard radioimmunoassay. Such specific and sensitive detection also enables imaging-based high-throughput screening of antihypertensive drugs. In hypertensive rat models, ARNs enable ultrasensitive detection of both plasma and urinary renin, facilitating renin-guided precision treatment and significantly improving hypertension control rate (90% versus 58%). Our nanoprobe platform holds great potential for assisting clinicians in rapidly and accurately classifying hypertensive patients and improving outcomes through tailored treatment selection.

[Accurate determination of three new antihypertensive drugs illegally added to food using ultra-high performance liquid chromatography-tandem mass spectrometry].

Effective strategies are required to address food safety issues related to the illegal addition of antihypertensive drugs to food and claims of antihypertensive function. In this study, a novel ultra-high performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of three antihypertensive drugs (azilsartan, candesartan cilexetil, and lacidipine) in 12 food matrices (pressed candies, solid beverages, alternative teas, tea drinks, biscuits, jellies, mixed liquors, oral liquids, medicinal teas, tablets, hard capsules, and soft capsules). Initially, mass spectrometry parameters, such as the collision energies of the three antihypertensive drugs, were optimized. Subsequently, the response intensities and chromatographic separation conditions of the three drugs in different mobile phases were compared. In addition, to enhance the recoveries, various extraction solvents and purification methods, including solid-phase extraction (SPE) columns and the QuEChERS technique, were investigated. In the developed method, sample determination involved three steps. First, the sample was extracted using 0.2% (v/v) formic acid in acetonitrile and then filtered using high-speed centrifugation, in addition, the extracted solution of alternative tea and medicinal tea was purified using the QuEChERS technique. Second, the supernatant was diluted with water, and filtered through a 0.22 µm polytetrafluoroethylene (PTFE) membrane. Finally, the analytes were separated on an Agilent Eclipse Plus RRHD C18 column (50 mm×2.1 mm, 1.8 µm) using a 5 mmol/L ammonium formate aqueous solution and acetonitrile as the mobile phases under gradient elution conditions and then detected using UHPLC-MS/MS with positive electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. Methodological validation showed good linear relationships for all three antihypertensive drugs in the investigated concentration ranges, with correlation coefficients (r2) greater than 0.996. The limit of detection (LOD) and limit of quantification (LOQ) of lacidipine were 0.02 mg/kg and 0.04 mg/kg, respectively, whereas those of the other two drugs were 0.01 mg/kg and 0.02 mg/kg, respectively. In the 12 food matrices, the average recoveries of the drugs ranged from 86.6% to 107.5% with relative standard deviations (RSDs) of 1.1%-10.9% (n=6) at low, medium, and high spiked levels. Furthermore, this method was successfully applied to the analysis of real food samples. Overall, the newly developed method is simple, rapid, sensitive, accurate, and suitable for the qualitative and quantitative determination of antihypertensive drugs in different food matrices. This work could provide technical support for food safety agencies in implementing measures against the illegal addition of antihypertensive drugs to food.

Association of antihypertensive drugs with periodontitis: a comprehensive drug-target Mendelian randomization study.

AIMS: The aim of this study was to elucidates the nuanced interactions between antihypertensive medications and the risk of periodontitis using Mendelian randomization (MR) analysis method. METHODS: Our study adopted a drug-target Mendelian randomization method to assess the long-term effects of nine antihypertensive drug categories on the risk of periodontitis in both acute and chronic cases. We selected genetic variants located in or near genes relevant to the targets of these drugs and associated with systolic blood pressure (SBP) to simulate the influence of antihypertensive treatments. Genetic information on SBP and periodontitis susceptibility was extracted from extensive genome wide association studies for both acute and chronic conditions. Additionally, we conducted a secondary analysis using expression quantitative trait loci for the genes of interest as alternative proxies.Colocalizaion analysis was performed to explore shared variants between antihypertensive drugs and periodontitis. RESULTS: Our analysis revealed that the use of angiotensin converting enzyme inhibitors with an increased risk of acute periodontitis (odds ratio [OR] [95% confidence interval]: 1.43 [1.11, 1.85] per 1 mmHg reduction in SBP; p = 5.93×10-3) and loop diuretics with a decreased risk of chronic periodontitis (OR: 0.94 [0.90, 0.98]; p = 2.94×10-3). Moreover, genetically mimicking the use of a suggestive protective effect of thiazides and related diuretics on acute periodontitis was observed in both acute (OR: 0.95 [0.90, 0.99]; p = 0.021) and chronic (OR: 0.98 [097, 1.00]; p = 0.045) periodontitis. Colocalizaion analysis revealed antihypertensive drugs and periodontitis shared causal variants in ACE and SLC12A2 locus. CONCLUSION: The research indicates that loop diuretics might decrease the risk of 31 periodontitis, while angiotensin-converting enzyme inhibitors could heighten the risk. Further investigations are required to evaluate the potential of reusing antihypertensive drugs for periodontitis prevention.

Exploring biological activities of novel Schiff bases derived from amlodipine and in silico molecular modeling studies.

Aim: Calcium channel antagonists are of considerable interest in treating elevated blood pressure and its pathologies.Materials & methods: Schiff base derivatives of amlodipine were produced to check its urease inhibition potentials as well antibacterial and antioxidant activities. Structural illustration along with chemical characterization were achieved by spectral techniques (1H NMR, FTIR, 13C NMR) and docking studies also performed.Results & conclusion: 3g displayed remarkable anti-hypertensive activity compared with parent drug. 3b, 3f and 3g showed urease inhibition potentials. These compounds can aid as lead for further investigations since they exhibited comparable or superior interactions.

[Box: see text].

Outcome of COVID-19 infection in patients on antihypertensives: A cross-sectional study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) infection frequently have hypertension as a co-morbidity, which is linked to adverse outcomes. Antihypertensives may affect the outcome of COVID-19 infection. AIM: To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection. METHODS: A total of 260 patients were included, and their demographic data and clinical profile were documented. The patients were categorized into nonhypertensive, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), calcium channel blocker (CCB), a combination of ACEI/ARB and CCB, and beta-blocker groups. Biochemical, hematological, and inflammatory markers were measured. The severity of infection, intensive care unit (ICU) intervention, and outcome were recorded. RESULTS: The mean age of patients was approximately 60-years-old in all groups, except the nonhypertensive group. Men were predominant in all groups. Fever was the most common presenting symptom. Acute respiratory distress syndrome was the most common complication, and was mostly found in the CCB group. Critical cases, ICU intervention, and mortality were also higher in the CCB group. Multivariable logistic regression analysis revealed that age, duration of antihypertensive therapy, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and interleukin 6 were significantly associated with mortality. The duration of antihypertensive therapy exhibited a sensitivity of 70.8% and specificity of 55.7%, with a cut-off value of 4.5 years and an area under the curve of 0.670 (0.574-0.767; 95% confidence interval) for COVID-19 outcome. CONCLUSION: The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection. However, the duration of antihypertensive therapy is associated with poor outcomes.

The impact of the COVID-19 Pandemic on hypertension phenotypes (ESH ABPM COVID-19 study).

OBJECTIVE: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM). DESIGN AND METHODS: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits. RESULTS: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period. CONCLUSION: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes.

Anti-hypertensive medications and erectile dysfunction: focus on ß-blockers.

PURPOSE: Although anti-hypertensive medications, including thiazides and ß-blockers (BBs) in particular, have been suggested to cause erectile dysfunction (ED) their real contribution is still conflicting. The aim of this paper is to summarize available evidence providing an evidence-based critical analysis of the topic. METHODS: An overall comprehensive narrative review was performed using Medline, Embase and Cochrane search. In addition, to better understand the impact of BBs on ED a specific systematic review was also performed. RESULTS: The negative role of centrally acting drugs, such as clonidine and α-methyldopa, is well documented althuogh limited controlled trials are available. Angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), and calcium-channel-blockers (CCBs) have neutral (CCBs) or even positive (ACEis and ARBs) effects on erectile function. Despite some preliminary negative reports, more recent evidence does not confirm the negative impact of thiazides. BBs should be still considered the class of medications more often associated with ED, although better outcomes can be drawn with nebivolol. CONCLUSION: Sexual function should be assessed in all patients with arterial hypertension, either at diagnosis or after the prescription of specific medications. A close related patient-physician interaction and discussion can overcome possible negative outcomes allowing a successful management of possible side effects.

Optimal treatment for women with acute hypertension in pregnancy; a randomized trial comparing intravenous labetalol versus nicardipine.

OBJECTIVES: Blood pressure control in severe hypertension of pregnancy is crucial for mother and neonate. In absence of evidence, guidelines recommend either intravenous labetalol or nicardipine. We compared the effectiveness and safety of these two drugs in women with severe hypertension in pregnancy. STUDY DESIGN: We performed an open label randomized controlled trial. Women with a singleton pregnancy complicated by severe hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 110 mmHg) requiring intravenous antihypertensive treatment were randomized to intravenous labetalol or intravenous nicardipine. The primary outcome was a composite adverse neonatal outcome defined as severe Respiratory Distress Syndrome (RDS), Broncho Pulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH) IIB or worse, Necrotizing Enterocolitis (NEC), or perinatal death defined as fetal death or neonatal death before discharge from the neonatal intensive care unit (NICU). Based on a power analysis, we estimated that 472 women (236 per group) needed to be included to detect a difference of 15% in the primary outcome with 90% power. The study was halted prematurely at 30 inclusions because of slow recruitment and trial fatigue. RESULTS: Between August 2018 and April 2022, we randomized 30 women of which 16 were allocated to intravenous nicardipine and 14 to intravenous labetalol. The composite adverse neonatal outcome was not significantly different between the two groups (25 % versus 43 % OR 0.28 (95 % CI 0.05-1.43), p = 0.12)). Respiratory distress syndrome occurred more often in the labetalol group than in the nicardipine group (42.9 % versus 12.5 %). Neonatal hypoglycemia occurred more often in the nicardipine group than in the labetalol group (31 % versus 7 %). Time until blood pressure control was faster in women treated with nicardipine than in women treated with labetalol (45 (15-150 min vs. 120 (60-127,5) min). CONCLUSION: In our prematurely halted small RCT, we were unable to provide evidence for the optimal choice of treatment for severe hypertension to improve neonatal outcome and/or to obtain faster blood pressure control. Differences in Respiratory distress syndrome and neonatal hypoglycemia between the groups might be the result of coincidental finding due to the small groups included in the study. A larger randomized trial would be needed to determine the safest and most efficacious (intravenous) therapy for severe hypertension in pregnancy. This study emphasizes the challenges of conducting a RCT for the optimal treatment for these women.

GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.

BACKGROUND: Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. METHODS: To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. RESULTS: The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. CONCLUSIONS: The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.

Blood Pressure-Lowering Medications, Sodium Reduction, and Blood Pressure.

BACKGROUND: Both blood pressure-lowering medication and sodium reduction are effective in hypertension control, but whether blood pressure-lowering medication modifies the effect of sodium reduction is unclear. This study aims to evaluate the dose-response effect of sodium intake reduction on blood pressure in treated hypertensive individuals and the impact of different classes of blood pressure-lowering drugs. METHODS: We searched multiple databases and reference lists up to July 9, 2024. Randomized controlled trials with a duration of ≥2 weeks comparing the effect of different levels of sodium intake (measured by 24-hour urinary sodium excretion) on blood pressure in hypertensive individuals treated with constant blood pressure-lowering medications were included. Instrumental variable meta-analyses based on random effects models were conducted to evaluate the dose effect of sodium reduction on blood pressure. Subgroup analyses were performed based on the class of blood pressure-lowering drugs. RESULTS: We included 35 studies (median duration of 28 days) with a total of 2885 participants. For every 100 mmol reduction in 24-hour urinary sodium excretion, systolic blood pressure decreased by 6.81 mm Hg (95% CI, 4.96-8.66), diastolic blood pressure decreased by 3.85 mm Hg (95% CI, 2.26-5.43), and mean arterial pressure decreased by 4.83 mm Hg (95% CI, 3.22-6.44). The dose-response effects varied across classes of blood pressure-lowering medications, with greater effects observed in the ß-blockers, renin-angiotensin-aldosterone system inhibitors, and dual therapy groups. No significant subgroup differences were observed based on age, baseline 24-hour urinary sodium excretion, blood pressure levels, or study duration. CONCLUSIONS: Pooled evidence suggests a dose-response relationship between sodium reduction and blood pressure in treated individuals with hypertension, influenced by the class of blood pressure-lowering medications.

Exploring the chemical space around chrysin to develop novel vascular CaV1.2 channel blockers, promising vasorelaxant agents.

The flavonoid chrysin is an effective vascular CaV1.2 channel blocker. The aim of this study was to explore the chemical space around chrysin to identify the structural features that can be modified to develop novel and more effective blockers. Four derivatives (Chrysin 1-4) were synthesised and a functional, electrophysiology and molecular docking approach was pursued to assess their binding mode to CaV1.2 channels and their activity in vascular preparations. Methylation of the 5- and 7-OH of the chrysin backbone caused a marked reduction of the Ca2+ antagonistic potency and efficacy. However, C-8 derivatives showed biophysical features similar to those of the parent compound and, like nicardipine, bound with high affinity to and stabilised the CaV1.2 channel in its inactivated state. The vasorelaxant effects of the four derivatives appeared vessel-specific, addressing the molecules' derivatization towards different targets. In conclusion, the scaffold of chrysin may be considered a valuable starting point for the development of innovative vascular CaV1.2 channel blockers.

Pulmonary Edema Following Nifedipine Use in Pregnancy: A Case Report.

Calcium channel blockers are generally considered safe for use during pregnancy. They have several indications, including second-line therapy for lowering blood pressure and tocolytic therapy. We present the case of a 24-year-old woman, G1P0, with a twin gestation at 22 weeks, who presented with acute respiratory distress. Her symptoms occurred shortly after starting nifedipine as tocolytic therapy. Investigations revealed signs of volume overload and pulmonary edema. Extensive cardiac and infectious workups were normal. Obstetrical ultrasound did not show any signs of ovarian hyperstimulation syndrome. Based on these findings, she was diagnosed with acute pulmonary edema following tocolytic therapy with oral nifedipine. Nifedipine was stopped, and intravenous furosemide was started, resulting in rapid clinical improvement. We are reporting this case to raise awareness of this rare but life-threatening adverse event associated with nifedipine use in pregnant patients.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Antihypertensive medications and dementia in older adults with hypertension.

Background: Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults. Methods: A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use. Results: Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, 'any' AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and ß-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk. Conclusions: Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and ß-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults.