Antihypertensive Research Articles

Amlodipine increases risk of primary open-angle glaucoma

BackgroundThe use of calcium channel blockers is associated with primary open-angle glaucoma (POAG) in a statistically meaningful but minor way. In general, those who had received calcium channel blocker medication were at a 23% increased risk of developing glaucoma in comparison to those who had never taken the antihypertensive drugs. We wished to confirm this association and examine POAG genes that might be involved, since the genetics has not yet been analyzed.MethodsWe used MedWatch and UK Biobank data to evaluate the effects of amlodipine on POAG and intraocular pressure (IOP). We analyzed three POAG-associated single-nucleotide polymorphisms: rs9913911, an intron variant in growth arrest-specific 7 (GAS7), one of the genes that influences IOP; rs944801, an intron variant within CDKN2B-AS1, and rs2093210, an intron variant within SIX6, known to be associated with vertical cup-disc ratio, an important optic nerve head parameter that is often used to define or diagnose glaucoma.ResultsAmlodipine use in MedWatch doubled the prevalence of POAG, from 0.0805 to 0.177%, a small but significant increase. Multivariate analysis by logistic regression of UK Biobank data revealed that POAG risk was significantly increased with age, male sex, major alleles of rs9913911 (GAS7) and rs944801 (CDKN2B-AS1), and minor allele of rs2093210 (SIX6). Amlodipine increased POAG risk by 16.1% (P = 0.032). Amlodipine has not been associated with increased IOP. We confirmed this lack of association and in addition found that GAS7, associated with IOP, was not associated with POAG risk and amlodipine. But CDKN2B-AS1 and SIX6, POAG genes not associated with IOP, were associated with POAG and amlodipine.ConclusionsAmlodipine, a frequently prescribed drug and first line treatment for hypertension, has a potentially hazardous relationship with POAG. Knowledge of this link can guide the prescribing of alternate drugs for hypertensive individuals who have glaucoma or are at risk for it. Diuretics and β-blockers are not associated with POAG or increased IOP and could be substituted for amlodipine in hypertensive patients at risk POAG.Trial registrationNone.Graphical

Prevalence and Related Factors of Dizziness Among Older Adults: A Cross-Sectional Study in Ardakan City, Iran.

Dizziness and balance disorders are directly related to aging in humans- Dizziness is one of the most important factors causing the burden of disability after the age of 65. Bearing in mind the increase in the elderly population in Iran and the world and the prevalence of dizziness in old age, early diagnosis of dizziness and determination of the factors affecting its severity facilitate its treatment and are effective in preventing its adverse consequences. To determine the prevalence of dizziness and its related factors among older adults in Ardakan city, Yazd province, Iran, in 2022. This cross-sectional study was conducted in four comprehensive health centers of Ardakan city with the participation of 260 elderly people aged ≥60 years, who were randomly included in the study. Data were collected using a series of questionnaires which were completed by interviewing the participants. The variables of this study included demographic information, information related to the dizziness status, diseases, medications, use of mobility aids, physical activity level, fear of falling, quality of life and depression. The prevalence of dizziness among older adults of Ardakan city was 48.5%. In terms of the severity of dizziness, 38.8% had substantial dizziness, and 9.6% had mild dizziness. Dizziness was significantly related to physical activity (p<0.05), fear of falling (p <0.01), depression (p <0.05), history of falling (p <0.01), use of mobility aids (p <0.01), age (p<0.01), education level (p<0.01), gender (p <0.05) and diseases such as high blood pressure (p<0.05), hypothyroidism (p <0.01) and ear diseases(p <0.01). Also, elderly people with dizziness used significantly more medications such as sedatives (p<0.01), antihypertensive drugs (p <0.05) and cytotoxic drugs (p <0.01). About half of the older adults experience dizziness, and this problem is associated with depression, fear of falling, history of falling, low physical activity, age, female gender, ear diseases, high blood pressure, and hypothyroidism. In addition, the use of medications such as anti- hypertensives, sedatives and cytotoxic drugs is related to dizziness. Families with elderly people, doctors and healthcare workers need to be educated and pay more attention to the above.

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. Objective: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59 nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62) than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Evaluation of Various Experimental Models in Antihypertensive Drug Development: Recent Update

Evaluation of Various Experimental Models in Antihypertensive Drug Development: Recent Update

Unveiling Wide Spectrum Therapeutic Implications and Signaling Mechanisms of Valsartan in Diverse Disorders: A Comprehensive Review.

Valsartan is an orally active non-peptide angiotensin receptor antagonist, an effective and well-tolerated anti-hypertensive drug. Besides its antihypertensive action, it has clinical implications in many other disorders, like heart failure (HF), arrhythmia, chronic kidney disease (CKD), diabetic complications (DM), atherosclerosis, etc. Besides angiotensin receptor blocking activity, valsartan reduces circulating levels of biochemical markers, such as hs-CRP, which is responsible for its anti-inflammatory and anti-oxidant activity. Moreover, valsartan also acts by inhibiting or inducing various signalling pathways, such as inducing autophagy via the AKT/mTOR/S6K pathway or inhibiting the TLR/NF-kB pathway. The current review exhaustively discusses the therapeutic implications of valsartan with specific emphasis on the mechanism of action in various disorders. The article provides a detailed spectrum of the therapeutic profile of valsartan and will likely be very useful to researchers working in the relevant research areas.

Risk of developing hyperkalemia in patients with hypertension treated with combination antihypertensive therapy - a retrospective register-based study.

The risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated. In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on eGFR groups, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies. A total of 793 patients with hyperkalemia were matched to 3598 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 1.95 (95% CI, 1.39-2.72) compared to RASi + thiazides (reference). CCB + thiazides (OR, 0.76 [95% CI, 0.45-1.28]) and CCB + RASi + Thiazid (OR 0.81 [95% CI, 0.51-1.28]) were among the others not significantly associated with hyperkalemia. Combinations of BB + RASi + MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment. Patients treated with BB + RASi + MRA within 90 days of treatment initiation, were associated with an increased hyperkalemia risk. When treating hypertensive patients with combination antihypertensive therapy, identifying and monitoring patients with a high risk of dyskalemias is a crucial goal to avoid serious adverse effects and detrimental outcomes related to dyskalemia.

Guanethidine Enhances the Antibacterial Activity of Rifampicin Against Multidrug-Resistant Bacteria

The escalating global threat of antibiotic resistance necessitates innovative strategies, such as the combination of antibiotics with adjuvants. Monotherapy with rifampicin is more likely to induce resistance in pathogens compared to other antibiotics. Herein, we found that the antihypertensive drug guanethidine enhanced the activity of rifampicin against certain clinically resistant Gram-negative bacteria, resulting in a reduction of up to 128-fold in the minimum inhibitory concentration. In infected animal models, this combination has achieved treatment benefits, including increased survival and decreased bacterial burden. The antimicrobial mechanism of guanethidine in synergy with rifampicin involves the disruption of the outer membrane of Gram-negative bacteria, leading to dissipation of the proton motive force. This results in an increase in reactive oxygen species and a reduction in ATP synthesis, severely disturbing energy metabolism and ultimately increasing bacterial mortality. In summary, guanethidine has the potential to become a novel adjuvant for rifampicin, offering a new option for the treatment of clinical Gram-negative bacterial infections.

Effect of antihypertensive drug classes in metabolic syndrome

Background: Metabolic syndrome (MetS) affects approximately 35% of the adult population of United States as well as categorized by the synchronized existence of hypertension, hyperglycemia, obesity and dyslipidemia. Now a days, this is the main cause of leading CVD (cardiovascular disease) risk in an individual. Raised blood pressure is the record common component of this syndrome and this incidence increases with age. Objective: This research was carried out to recommend the characterizations for the metabolic syndrome along with the occurrence of hypertension in this disorder. Additionally, indications concerning the properties of metabolic of the diverse antihypertensive drug modules and their consequence on metabolic syndrome will be demonstrated. Methods: A comprehensive trial in different patients were performed to identify data from clinical investigations for the occurrence, patho-physiology and treatment of hypertension in MetS. Results: Hypertension existing in almost 79% Pakistani patients alon with metabolic syndrome. The usage of thiazide diuretics, and beta-blockers salts, is dejected in the present community; though, latest signs recommend its use under precise circumstances. The Ca. channel inhibitors appear to apply a unbiased outcome on Metabolic syndrome. Whereas, renin angiotensin scheme inhibitors are supposed to be of the utmost advantage. Even though, variances occur among various agents of this class. Conclusion: Debate still exists about the ideal anti-hypertensive treatment in Metabolic syndrome. Due to the huge occurrence of hypertension in Pakistani community, still, further investigations and data is in dire need for this treatment.

Associations between Life's Essential 8 and gallstones among US adults: A cross-sectional study from NHANES 2017-2018.

Cardiovascular illness and gallstones are closely related. Our goal was to determine whether gallstones and the updated LE8 score, which measures cardiovascular health among US adults, are related. 3,570 adults participated in the 2017-2018 National Health and Nutrition Examination Survey, which provided the data for our study. Based on the criterion provided by the American Association for Cardiovascular Health (AHA), LE8 score (range 0-100) was calculated and classified as low (0-49), moderate (50-79), and high (80-100) cardiovascular health. Gallstones were derived from the questionnaire. Multivariate logistic modeling explored the independent relationship between LE8 score and gallstones. There was a negative correlation between LE8 score and gallstones. Specifically, the odds of gallstones dropped by 15% for each 10-unit increase in LE8 score (OR = 0.85; 95% CI, 0.77-0.94). Smooth curve fitting detected a saturation effect between LE8 score and gallstones, with a minimum threshold of 66.25 points associated with both. There was a noticeably stronger inverse relationship between gallstones and LE8 score in those under 60 years of age and not taking antihypertensive or lipid-lowering drugs. Lower LE8 scores may be a potential risk factor for the development of gallstones and could also be a target for risk assessment and intervention.

Nyctanthes arbor-tristis Improves Blood Pressure via Endothelial Pathway: In Silico, Ex Vivo, and In Vivo Evidence.

Systemic hypertension, a common metabolic disorder, poses significant health risks despite the availability of antihypertensive drugs. Nyctanthes arbor-tristis has garnered increasing attention for its perceived efficacy and safety, though its mechanisms of action and the bioactive compounds responsible for its antihypertensive effects remain elusive. Therefore, this study aims to elucidate the antihypertensive activity of N. arbor-tristis leaves in rats and explore associated mechanism through in silico, in vitro, ex vivo, and in vivo studies. The methanolic extract of N. arbor-tristis leaves (MENAT) was fractionated and subjected to qualitative and quantitative phytochemical screening, including total phenolic content (Folin-Ciocalteu method), total flavonoid content (Aluminum chloride method), and total alkaloid content (spectrometric method). Antioxidant studies were conducted using DPPH, FRAP, and H2O2 assays. The most promising fraction (WNAT) was analyzed using LC-MS, and the identified compounds were used for molecular docking studies against cGMP and eNOS. Further, aortic ring assays were conducted to assess ex vivo vasorelaxant activity (rat aortic strip assay) and the underlying mechanisms of WNAT. Later, in vivo studies using a DOCA-salt-induced hypertension model in Wistar rats, along with molecular analyses (RT-PCR), were performed to validate the antihypertensive claims of N. arbor-tristis. In vitro studies demonstrated that the water extract of N. arbor-tristis leaves (WNAT) exhibited strong antioxidant activity and contained key phytochemicals. LC-MS analysis revealed the presence of 19 major compounds, including betulinic acid and arbortristosides. Molecular docking studies indicated that arborside C exhibited a strong affinity for both eNOS and cGMP. Ex vivo studies involving rat aortic strips showed that WNAT induced vasodilatory activity, which is associated with parasympathetic and nitric oxide-related pathways. In vivo experiments further supported WNAT's antihypertensive properties through improvements via amelioration of rat blood pressure and histological features, biochemical markers, morphometric parameters, and gene expression in hypertensive rats. In conclusion, WNAT effectively lowers blood pressure through modulation of the endothelial pathway and warrants further studies to attain its clinical utility in hypertensive subjects.

Efficacy of Panchakarma therapy and lifestyle modification in essential hypertensive patients to reduce anti-hypertensive dependency

Background: Anti-hypertensive drugs are associated with a plethora of adverse reactions which can lead to poor treatment adherence, increased morbidity and mortality rates, and significant economic burden. The blood pressure management program (BPMP) is an Ayurvedic treatment strategy that combines Panchakarma with diet management. Thus, the current study sought to assess the efficacy of the BPMP in essential hypertensive patients to reduce anti-hypertension dependency. Methods: A retrospective, observational, single-centre study was conducted between December 2018 and September 2023 in Maharashtra, India. Patients aged 30-75 years diagnosed with primary/essential hypertension regardless of gender participated in the BPMP and were included in the study. Follow-up was conducted after 90 days. Day 1 and day 90 data were compared. Results: A total of 59 patients were assessed. Daytime ambulatory blood pressure monitoring (ABPM) systolic blood pressure decreased (day 1: 123.71±11.83 mmHg and day 90: 123.12±12.36 mmHg), night-time ABPM systolic blood pressure decreased (day 1: 114.76±13.41 mmHg and day 90: 114.31±14.40 mmHg), daytime ABPM diastolic blood pressure decreased (day 1: 77.03±8.28 mmHg and day 90: 76.31±9.45 mmHg, and night-time ABPM diastolic blood pressure decreased (day 1: 69.53±8.32 mmHg and day 90: 68.42±8.85 mmHg). Nocturnal dipping decreased (day 1: 7.08±8.19 and day 90: 6.08±8.99). Dependency on allopathic medication also decreased. Conclusions: The Ayurveda-based BPMP effectively reduces blood pressure and dependency of allopathic medication. It also improves quality of life of patients diagnosed with primary/essential hypertension.

Prescribing patterns of antihypertensive drugs by clinicians at the National Referral Hospital outpatient department, Thimphu, Bhutan

Introduction: Around 1.28 billion adults aged 30-79 years have hypertension, globally. Of these, two-thirds are in low and middle-income countries, with only 21% having it under control. In Bhutan, there are 362.4 people per 10,000 population with hypertension. Antihypertensive medications must be appropriately prescribed to prevent the complications of hypertension. Methods: A cross-sectional study of the prescriptions of antihypertensive medications at Jigme Dorji Wangchuck National Referral Hospital was undertaken to characterize the current prescribing patterns. Results: Nine monotherapy, 18 dual therapy, 19 triple therapy and 2 multiple combination therapy with antihypertensive drugs were noted during the study period spanning April to December 2023. Nearly half (59.1%) of the hypertensive patients were treated with monotherapy, 36.3% with dual therapy, 4.3% with triple therapy and 0.3% with multiple combination therapy. The proportion of patients who had their blood pressure under control was 42.45%, with females slightly outnumbering males (26.66% versus 15.79%). However, there was no statistically significant difference in blood pressure control between females and males and also between patients who received monotherapy or combination therapy. Conclusion: The study found the prescription of a wide range of drugs, both alone and in combination, to treat hypertension. The proportion of patients with controlled blood pressure was 42.45%.

Assessment of adherence to antihypertensive medication and its associated factors: a cross-sectional study

Background: Hypertension is a silent killer. India is home to approximately 220 million hypertensive individuals. Poor adherence to medication may lead to complications and add to the burden of disease. So, this study aims to assess medication adherence and its associated factors. Methods: This hospital based cross sectional study was conducted at Urban Health Training center. Patients who attended Out Patient Department over the period of three months were enrolled in the study. Morisky Medication Adherence four-point scale (MMAS-4) was used to study compliance, while JAMOVI software was used for data analysis. Results: Around half (45%) of the patients had high adherence to anti-hypertensive medication. Various sociodemographic factors like age, gender, education, occupation, family history, personal history and duration of hypertension were considered. A significant association was observed between age and duration with adherence. Conclusions: There was significant association between age and poor adherence. Timely interventions are necessary to reinforce good compliance to antihypertensive drugs.

Antihypertensive treatment during pregnancy and maternal and fetal outcomes

Abstract Introduction Arterial hypertension affects about 5-10% of pregnancies and has detrimental effects on pregnancy outcomes in both the mother and fetus. The study aimed to analyse the outcomes of pregnancy in women treated for arterial hypertension in pregnancy in the Czech Republic. Methodology Nationwide data on all births and abortions in the period 2012-2022 in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ) and the National Registry of Reimbursable Health Services (NRHZS). Women who had the diagnosis I10 within one year before pregnancy and were prescribed any antihypertensive drug from selected ATC groups (C02, C03, C07, C08, C09) were classified as pre-existing hypertension. Women diagnosed with O13 or I10 during pregnancy were classified as pregnancy induced hypertension. Hypoxia in the new-born was defined as pH &amp;lt;7.1 or Apgar score &amp;lt;8 present after delivery. For all factors, univariate logistic regression was used to calculate the odds ratios (OR) of adverse outcomes. Results There were total of 1,154,648 deliveries in the 11-year period. 95,215 women had hypertension in pregnancy, out of these 21,094 (22.2%) were treated with antihypertensive drugs. Odds ratios for caesarean section, pre-term delivery, low birth weight, new-born hypoxia and pre-eclampsia in women using different antihypertensive classes and drugs are shown in the Table. Risk of maternal and fetal complications was found to be higher with calcium channel blockers (mainly amlodipine) compared to methyldopa and beta blockers. Among beta blockers, bisoprolol had the most favourable safety profile. Although used in limited numbers, diuretics, verapamil, ACE-inhibitors and angiotensin receptor blockers (ARBs) appeared to be comparably safe to methyldopa. Combination of multiple antihypertensive drugs was associated with higher risk of adverse outcomes. Conclusion Bisoprolol, verapamil and diuretics seem to have the risk of adverse maternal and fetal outcomes comparable to methyldopa. Amlodipine and multiple antihypertensive drug combinations are associated with increased risk.Table

Blood pressure polygenic risk scores associate with resistant hypertension in individuals with type 1 diabetes

Abstract Background Hypertension is a major risk factor of global disease burden, but treatment goals are often not met. A subset of individuals with hypertension is affected by treatment-resistant hypertension (RHTN), and they suffer from increased cardiovascular morbidity and mortality. Early identification of individuals at risk of RHTN could lead to more efficient antihypertensive drug treatment. Purpose The aim of this study was to investigate whether polygenic risk scores (PRS) for systolic (SBP) and diastolic blood pressure (DBP) predict RHTN in individuals with or without type 1 diabetes (T1D). Methods We performed association analyses between PRSs and RHTN in two Finnish cohorts: The Finnish Diabetic Nephropathy Study (FinnDiane) and the Finnish individuals of the LIFE Study (LIFE-Fin). FinnDiane is an ongoing, observational nationwide study aiming to identify genetic and clinical risk factors for complications of T1D. We included data from 778 adults (476 with RHTN and 302 with controlled hypertension). LIFE is a randomized, double-blind study evaluating long-term effects of losartan compared with atenolol in patients with signs of left ventricular hypertrophy. We used SBP and DBP data from 378 Finnish individuals (173 with RHTN and 205 with controlled hypertension) at the four-year visit of the study. In FinnDiane, RHTN was defined as SBP ≥130 or DBP ≥85 mmHg and the use of three or more antihypertensive drugs, or SBP &amp;lt;130 and DBP &amp;lt;85 mmHg and the use of four or more antihypertensive drugs. In LIFE-Fin, RHTN was defined as SBP ≥140 or DBP ≥90 mmHg and the use of three or more antihypertensive drugs. Controlled hypertension was defined as the use of three or fewer antihypertensive drugs and SBP &amp;lt;130 and DBP &amp;lt;85 mmHg in FinnDiane, and as SBP &amp;lt;140 and DBP &amp;lt;90 mmHg in LIFE-Fin. We calculated a PRS for each participant using genome-wide association study data for 1,098,015 genetic variants; the variant-specific data were derived from UK Biobank based PRS-CS-method computed PRSs (1). Results We observed significant associations of SBP and DBP PRSs with RHTN in FinnDiane (OR 1.56 [1.30; 1.87], P = 1.8e-6, and OR 1.25 [1.04; 1.50], P = 0.02, per one-SD increase of the PRS value) when adjusted for age, sex, estimated glomerular filtration rate and body mass index. The association between SBP PRS and RHTN remained significant when T1D individuals with or without albuminuria were analysed separately. Neither SBP nor DBP PRSs were significantly associated with RHTN in LIFE-Fin. Conclusion Higher SBP PRSs associate with higher risk of RHTN in individuals with T1D, with or without albuminuria, but not in nondiabetic individuals with hypertension. It remains to be investigated whether general blood pressure genetics contribute to RHTN in the general population.

Impact of changes in left heart geometry on predicting new-onset atrial fibrillation in patients with hypertension

Abstract Background Hypertension-induced left ventricular hypertrophy (LVH) increases end-diastolic LV pressure and contributes to left atrial enlargement (LAE), which are associated with development of atrial fibrillation (AF). However, the impact of LVH and LAE and their regression following antihypertensive therapy on AF incidence remains unclear. Purpose This study aimed to investigate the impact of changes in the LVH and LAE status on the occurrence of new-onset AF (NOAF). Methods This retrospective analysis included patients with sinus rhythm who underwent echocardiography at hypertension diagnosis and after 6–18 months. LVH was defined as LV mass index &amp;gt;115 g/m2 (men) and &amp;gt;95 g/m2 (women), and LAE was defined as LA volume index &amp;gt;42 ml/m2. LVH and LAE regression was defined as the absence of LVH and LAE on follow-up echocardiography, respectively. The occurrence of NOAF was assessed in relation to changes in LVH and LAE status. Results Among the 1,464 patients included in the study, 163 (11.1%) patients developed NOAF during a median follow-up of 63.8 months (interquartile range, 35.9–128.5 months). On average, 12 electrocardiograms per patient were reviewed for AF detection. New-onset LVH (adjusted HR 1.88, 95% CI 1.20–2.94, P=0.006) and LAE (adjusted HR 1.89, 95% CI 1.05–3.40, P=0.034) were significant predictors of NOAF. Conversely, regression of LVH (adjusted HR 0.51, 95% CI 0.280.91, P=0.022) or LAE (adjusted HR: 0.30, 95% CI 0.15–0.63, P=0.001) after antihypertensive therapy was associated with a reduced risk of NOAF. The risk of NOAF was higher in patients with LVH and LAE together (adjusted HR 4.30, 95% CI 2.81–6.56, P&amp;lt;0.001) than in those with either LVH or LAE, or those with neither, as determined by follow-up echocardiography. Conclusion In patients with hypertension and sinus rhythm, regression of LVH and LAE following antihypertensive therapy is associated with a decreased incidence of NOAF, whereas newly developed LVH or LAE is associated with a higher risk of NOAF. The changes in left heart geometry can serve as a predictive marker for NOAF in patients with hypertension.

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with &amp;gt;10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p&amp;lt;0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Control of arterial hypertension in the context of metabolically-associated disease: challenges and opportunities in Ukraine

Abstract Background/Introduction Arterial hypertension is a prevalent, but modifiable cardiovascular (CV) risk factor. Effective control of blood pressure (BP) is associated with decreased rates of CV morbidity and mortality, as was convincingly demonstrated in randomized clinical trials. There is a substantial gap between BP control in clinical trials and real clinical practice due to multiple factors – e.g. lack of awareness, low medication compliance, side effects of medications, and insufficient availability of medical care – to name the few. The association between poor BP control and metabolically associated disease (MAD) like diabetes and obesity is widely acknowledged and considered the key challenge in effective management of arterial hypertension. Purpose To determine patterns of awareness and control of arterial hypertension in the context of MAD in Ukrainian outpatient patient sample. Methods We enrolled 309 subjects (108 with MAD and 201 without MAD). MAD was defined as the presence of type 2 diabetes and/or overweight/obesity. All subjects were consented for the structured interview and triple sitting BP measurement with an automated device. Results MAD-positive and MAD-negative groups were comparable by age (54.4±1.34 vs 51.8±1.2 years, p=0.29), systolic BP (141.3±2.0 vs 137.4±1.6 mm Hg, p=0.082), diastolic BP (85.2±1.2 vs 82.5±0.9 mm Hg, p=0.13). Presence of MAD was associated with increased odds of having BP&amp;gt;139/89 mm Hg (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.04-2.67, p=0.035), better awareness on hypertension (OR 2.65, CI 1.64-4.28, p=0.0001), and less prevalent normotension (OR 0.51, CI 0.31-0.84, p=0.008). Among MAD-positive patients without history of HTN, 50% actually had elevated office BP, although it did not reach statistical significance as compared to MAD-negative subjects (OR 1.32 CI 0.68-2.56, p=0.42, see Picture 1). Less MAD-positive patients did not take any antihypertensive drugs (37.0% vs 56.7%, difference -19.7%, CI -8.03 to -30.51%, p=0.001), and more of them were taking 3 antihypertensive drugs (17.6% vs 7.5%, difference 10.1% CI 2.58-18.85. p=0.007). Only 53.7% of MAD-positive subjects and 39.8% of MAD-negative subjects claimed they were taking BP-lowering medications on a regular basis (p=0.02). There was no difference in achievement of BP control between MAD-positive and MAD-negative groups (39.2 vs 38.7% for subjects who were aware of HTN, 31.9 vs 31.3% of all hypertensive individuals, p=NS for both). More MAD-positive than MAD-negative subjects admitted they consume alcohol several times per week or daily (22.2 vs 12.4%, p=0.025). Conclusions MAD disease is associated with more prevalent HTN and better awareness on elevated BP. MAD requires more intensive BP-lowering therapy to achieve target BP, but the compliance to medications is suboptimal.Patterns of awareness and BP control

Comparison of the predicting value for incident cardiovascular events by vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity

Abstract Background There is a good correlation between brachial-ankle pulse wave velocity（baPWV）and carotid-femoral pulse wave velocity (cfPWV). Whether baPWV has the same predictability for cardiovascular risk as cfPWV in calculating vascular age remains to be clarified. Purpose This study examines which vascular age calculated by baPWV or cfPWV has a stronger association with the risk of cardiovascular events. Methods This prospective cohort study included 5725 participants from a community atherosclerosis cohort in Beijing, China. Vascular age was the predicted age in a multivariable regression model, including classical cardiovascular risk factors (sex, systolic and diastolic blood pressure, glycemia, triglyceride, low density lipoprotein cholesterol, waist, body mass index, heart rate, smoking) and treatment (anti-hypertensive agents, hypoglycemic agents, lipid-lowering agents) and pulse wave velocity. Residuals between chronological age and vascular age were defined as ∆-age, and the 10th and 90th percentiles of ∆-age were used as cutoffs to define supernormal vascular aging, normal vascular aging, and early vascular aging, respectively. The major adverse cardiovascular event was a composite of myocardial infarction, stroke, and cardiovascular death. The study used Cox proportional hazards regression to examine the association between vascular age and major adverse cardiovascular events. Results During the median 3-year follow-up period, 172 endpoint events were observed. After adjusting for age and sex, ∆-age as a continuous variable calculated by baPWV was significantly and increasingly associated with cardiovascular events (every 1-year increase led to a rise of 1.04% [95% confidence interval [CI]: 1.00%-1.08%; p=0.03] in cardiovascular events risk). After adjusting for age, sex, smoking, body mass index, hypertension, diabetes, dyslipidemia, anti-hypertensive agents, lipid-lowering agents, hypoglycemic agents, family history of atherosclerotic cardiovascular disease, and estimated glomerular filtration rate, early vascular aging group calculated by baPWV had an increased risk of cardiovascular events (hazard ratio: 1.76; 95% CI: 1.19-2.62 p=0.005), compared with the normal vascular aging group. In contrast, no significant results were observed in vascular age calculated by cfPWV. Conclusion(s) Vascular age calculated by baPWV has a stronger predictive ability for cardiovascular events than that calculated by cfPWV in the Chinese population. Considering baPWV is a simple and convenient method, it is recommended for vascular age calculation.

Serum from Hypertensive Patients Induces Cancer-Supporting Phenotype of Vascular Endothelium In Vitro

Background/Objectives: Large-scale epidemiological studies have established a bidirectional association between hypertension and cancer. However, the underlying mechanisms explaining this connection remain unclear. In our study, we investigated whether serum from patients with hypertension (HT) could enhance the aggressiveness of cancer cells in vitro through alterations in endothelial cell phenotype. Methods: Experiments were performed using EAhy926 endothelial cells and ovarian (SKOV-3), colorectal (SW480), pancreatic (PSN-1), breast (MCF-7), and lung (A549) cancer cell lines. Results: This study showed that conditioned medium (CM) produced by EAhy926 cells, when exposed to serum from patients with untreated hypertension (HT-CM), promotes the proliferation, migration, and invasion of every cancer cell line tested. In addition, endothelial cells subjected to HT serum promote the adhesion of all cancer cell types except PSN-1. An intensified transendothelial invasion of cancer cells was accompanied by decreased expression of junctional proteins (connexin 43, E-cadherin, occluding, desmoglein) in HT serum-treated endothelial cells. Quantitative analysis of the secretome of endothelial cells subjected to HT serum showed that they secrete increased amounts of CCL2, CXCL1, CXCL8, bFGF, HGF, IL-6, PAI-1, and TGF-β1. Moreover, cancer cells exposed to HT-CM display increased mRNA expression for several pro-cancerogenic agents, including CXCL8, tPA, and VEGF. Conclusions: Our report shows that hypertension may potentiate cancer cell aggressiveness by modulating endothelial cell phenotype. Further tests with antihypertensive drugs are required to assess whether effective treatment of hypertension can mitigate its cancer-promoting potential.