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Hypertension is the key leading risk factor for death globally, affecting ∼1.3 billion adults, particularly in low- and middle-income countries. Most people living with hypertension have uncontrolled high blood pressure, increasing their likelihood of cardiovascular events. Significant issues preventing blood pressure control include lack of diagnosis, treatment, and response to existing therapy. For example, monotherapy and combination therapy are often unable to lower blood pressure to target levels. New therapies are urgently required to tackle this issue, particularly those that target the mechanisms behind hypertension instead of treating its symptoms. Acting via an increase in systemic and tissue-specific inflammation, the immune system is a critical contributor to blood pressure regulation and is considered an early mechanism leading to hypertension development. Here, we review the immune system's role in hypertension, evaluate clinical trials that target inflammation, and discuss knowledge gaps in pre-clinical and clinical data. We examine the effects of anti-inflammatory drugs colchicine and methotrexate on hypertension and evaluate the blockade of pro-inflammatory cytokines IL-1β and TNF-α on blood pressure in clinical trials. Lastly, we highlight how we can move forward to target specific components of the immune system to lower blood pressure. This includes targeting isolevuglandins, which accumulate in dendritic cells to promote T cell activation and cytokine production in salt-induced hypertension. We discuss the potential of the dietary fibre-derived metabolites short-chain fatty acids, which have anti-inflammatory and blood pressure-lowering effects via the gut microbiome. This would limit adverse events, leading to improved medication adherence and better blood pressure control., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Hypertension is associated with an increased activity of matrix metalloproteinase (MMP)-2 in the vasculature, which, in turn, proteolyzes extra- and intracellular proteins that lead to vascular dysfunction. The activity of sarcoplasmic reticulum calcium ATPase (SERCA) is decreased in the aortas of hypertensive rats. Increased activity of MMP-2 proteolyzed SERCA in rat heart during ischemia and reperfusion injury, thus impairing cardiac function. Therefore, we examined whether increased activity of MMP-2 in early hypertension contributes to proteolyze SERCA in the aortas, thus leading to maladaptive vascular remodeling and dysfunction., Main Methods: Male Sprague-Dawley rats were submitted to two kidney-one clip (2K-1C) or Sham surgery and treated with doxycycline. Systolic blood pressure (SBP) was assessed by tail-cuff plethysmography. After 7 days, aortas were collected for zymography assays, Western blot to SERCA, ATPase activity assay, vascular reactivity, Ki-67 immunofluorescence and hematoxylin/eosin stain., Key Findings: SBP was increased in 2K-1C rats and doxycycline did not reduce it, but decreased MMP-2 activity and prevented SERCA proteolysis in aortas. Cross sectional area, media to lumen ratio and Ki-67 were all increased in the aortas of hypertensive rats and doxycycline decreased Ki-67. In 2K-1C rats, arterial relaxation to acetylcholine was impaired and doxycycline ameliorated it., Significance: doxycycline reduced MMP-2 activity in aortas of 2K-1C rats and prevented proteolysis of SERCA and its dysfunction, thus ameliorating hypertension-induced vascular dysfunction., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interest associated with this publication., (Copyright © 2024. Published by Elsevier B.V.)

In modern clinical practice, less than half of patients with new-onset heart failure (HF) undergo ischemic evaluation and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of coronary heart disease (CHD) event treated with or without revascularization, considering possible treatment-mediator interaction. The causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) included 42,418 participants (age 66.9 ± 7.7, 35.6% black, 53.2% men). A new CHD event (myocardial infarction or angina) that occurred after randomization but before the incident HF outcome was the mediator. Incident symptomatic congestive HF (CHF) and hospitalized/fatal HF (HHF) were the primary and secondary outcomes, respectively. Logistic regression (for mediator) and Cox proportional hazards regression (for outcome) were adjusted for demographics, cardiovascular disease history, and risk factors. During a median 4.5-year follow-up, 2,785 patients developed CHF, including 2,216 HHF events. Participants who developed CHD events had twice the higher incidence rate of CHF than CHD-free (28.5 vs 13.9 events/1,000 person-years). The proportion of reference interaction indicating direct harm because of a CHD event for lisinopril (234% for CHF, 355% for HHF) and amlodipine (244% for CHF, 468% for HHF) was greater than for chlortalidone (143% for CHF, 269% for HHF). In patients with revascularized CHD events, chlortalidone and amlodipine eliminated 21% to 24% and lisinopril eliminated -45% of HHF. Antihypertensive treatment could not eliminate harm from CHD events treated without revascularization. In conclusion, the antihypertensive drugs (chlortalidone, lisinopril, and amlodipine) prevent HF not principally by preventing CHD events but by way of other pathways. HF is moderated but not mediated by CHD events. Revascularization of CHD events is paramount for HF prevention., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)-II-induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling. By using subcutaneous osmotic minipumps, mice were treated with PBS or Ang-II in combination with or without RvD2 for two weeks. Mice receiving RvD2 gained less blood pressure increase compared to Ang-II alone. Surprisingly, however, examination of intracardiac arteries revealed that RvD2 treatment in combination with Ang-II exacerbated Ang-II-induced fibrosis. Measures of vascular smooth muscle cell dedifferentiation correlated with the level of vascular remodeling, indicating that this dedifferentiation, including increased proliferation and migration, is a contributing factor. RNA sequencing of left ventricle cardiac tissue supported these findings as pathways related to cell proliferation and cell differentiation were upregulated in mice treated with Ang-II in combination with RvD2. Additionally, the RNA sequencing also showed upregulation of pathways related to SPM metabolism. In line with this, Mass spectrometry analysis of lipid mediators showed reduced cardiac levels of the arachidonic acid derived metabolite leukotriene E4 in RvD2 treated mice. Our study suggests that continuous infusion through osmotic minipumps should not be the recommended route of RvD2 administration in future studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bente Halvorsen reports financial support was provided by South-Eastern Norway Regional Health Authority. Kirsten Holven reports financial support was provided by Throne-Holst Foundation for Nutrition Research. Maria Belland Olsen reports financial support was provided by Nansenfondet. Kirsten B Holven reports a relationship with Sanofi that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Uncontrolled hypertension causes significant morbidity and mortality worldwide. Several prescribing guidelines have been created to address this, however, prescriber adherence to guidelines is influenced by various sociodemographic patient factors. This study aims to determine the effects of these patient factors on prescriber adherence to antihypertensive prescription guidelines., Methods: A secondary analysis of data from the first wave of The Irish Longitudinal Study on Ageing (TILDA), was conducted. Participants were included if they reported previous hypertension diagnoses. Antihypertensive medication regimes were compared with the prescribing guidance in the 2011 NICE hypertension guidelines. The effects of patient sociodemographic factors on prescriber adherence to guidelines, and the effect of prescriber adherence on blood pressure control (≥ 140/90 mmHg), were determined using binomial logistic regression models., Results: A total of 2992 participants were included in this analysis; 54.9% female with mean age 65.7 years (±9.23). Male sex and older age, and lower socioeconomic status were associated with increased prescriber guideline adherence. Prescribers were less likely to adhere to guidelines in female patients ≥ 55 years (Relative Risk [RR] 0.75 [0.62, 0.91]), and female patients across all age groups (RR 0.80 [0.67, 0.95]). Better blood pressure control was seen with medication regimes adherent to prescription guidelines (140.38 (±18.98)/83.09 (±11.02) mmHg adherent vs. 141.66 (±19.86)/84.77 (±11.71) mmHg non-adherent)., Conclusions: This study highlights the effect of patient sex on prescriber adherence to antihypertensive prescription guidelines, emphasizing a larger issue of systemic undertreatment of females observed within healthcare. Further research is needed to determine the reasons for such differences in hypertensive care., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Increasingly, pharmacists are asked to incorporate social determinants of health (SDoH) identification and referral into clinical practice. However, to date, no studies have evaluated clinical changes from embedding SDoH screening into the delivery of comprehensive medication management (CMM) in patients with chronic conditions., Objective: To examine the clinical effectiveness of implementing a clinical pharmacist-led SDoH screening and referral process as part of CMM encounters across a network of 7 Federally Qualified Health Centers (FQHCs)., Methods: We used a retrospective cohort design to evaluate the effectiveness of integrating SDoH screening into CMM across a network of 7 FQHCs. A difference-in-difference approach was used to compare the effectiveness of CMM between patients with and without SDoH needs on the probability of achieving clinical control for blood pressure (<140 systolic/90 diastolic mm Hg) and diabetes (<9% hemoglobin A1c)., Results: Among 807 patients receiving CMM in 2023, 595 (74%) were screened for SDoH. 55.1% of patients screened had 1 or more SDoH, most commonly facing barriers related to insurance (22.0%), language (11.3%), transportation (9.1%), health behaviors (7.1%), income/employment (5.9%), and food insecurity (5.6%). Comparing patients with SDoH needs with those without, the proportion of patients controlled at baseline was 66.3% vs 72.3% for hypertension and 39.0% vs 75.4% for diabetes, respectively. Following a CMM encounter, the proportion of patients who achieved blood pressure control increased 7.6% more ( P = 0.225) among patients with SDoH needs than in those without SDoH, whereas diabetes control rates increased 13.3% more ( P = 0.143)., Conclusions: Although not statistically significant, the results of this pilot evaluation suggest the potential for meaningful clinical improvements from screening and referral of SDoH needs as a part of CMM encounters. These results should be corroborated using a larger, more robust study design.

Purpose: Hydrochlorothiazide (HCTZ) exposure has been linked to increased skin cancer in Caucasian (white) populations, especially squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC). This study aimed to evaluate and compare skin cancer risks associated with HCTZ- and other antihypertensives use., Methods: This retrospective cohort study utilized Taiwan's National Health Insurance Research Database. We identified patients aged 20 years and older, newly receiving antihypertensive medications between 2004 and 2015. We calculated the medication possession ratio (MPR) for the first 2 years of treatment to determine patient eligibility and treatment classification, whereby only patients with MPR above 80% were included. These were subsequently categorized by the type of antihypertensives they received, namely HCTZ, other thiazide diuretics, non-thiazide diuretics or non-diuretic antihypertensives. Cox proportional hazards model was used to evaluate skin cancer risks, and these were then classified as SCC or BCC., Results: Our study included 41 086, 27 402, 19 613, and 856 782 patients receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio: 0.84; 95% CI: 0.54-1.33), non-thiazide diuretics (0.93; 0.51-1.67), and non-diuretic antihypertensives (0.91; 0.66-1.26). We observed a higher SCC risk in the HCTZ group, compared to other thiazides (1.24; 0.74-2.08), non-thiazide diuretics (1.32; 0.70-2.51), and non-diuretic antihypertensives (1.23; 0.87-1.73), although the confidence intervals (CIs) were wide and crossed the null., Conclusions: We concluded that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population., (© 2024 John Wiley & Sons Ltd.)

We describe a 17-year-old woman diagnosed with severe hypertension during routine follow-up after the prescription of a combined oral contraceptive pill. Initially, due to her age, the estradiol-containing contraception, and high-level sport practice, physicians suspected drug-induced hypertension. Blood tests showed hypokalemia, and further investigations revealed pseudoaldosteronism. After the exclusion of toxic causes, Liddle syndrome was suspected and confirmed by genetic testing. Optimal therapeutic management was limited by anti-doping rules. This case report emphasizes the need for an early and systematic workup for causes of secondary hypertension in young patients and underlines diagnostic and therapeutic challenges in the management of hypertension in athletes., Competing Interests: None.

Objectives: Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide-Ang II (Ang P) by pyridoxal-5'-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B 6 derivative and, therefore, could be a cost-effective drug against hypertension., Methods: Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT 1 R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently., Results: Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT 1 R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not., Conclusion: PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B 6 might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain., Methods: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI)., Results: During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23)., Conclusions: This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

The focus of antihypertensive therapy in older adults should be on lowering the systolic blood pressure (SBP) to the patient's "optimal" benefit-based target goal. Applying benefit-based therapy to the majority of adults aged 65 years or older who are at high cardiovascular disease or cognitive impairment risk favors an SBP goal of less than 130 mm Hg, and for some, a goal of 120 mm Hg may be considered., Competing Interests: Disclosure The author discloses funding from the National Institutes of Health and royalties from McGraw-Hill Publishing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The authors conducted a review of pharmacologic therapy in older adults with hypertension. They reviewed the evidence supporting their use in older adults, understanding the physiologic changes and potential adverse drug effects associated with aging and antihypertensive medication use, exploring guideline recommendations for antihypertensive use in older adults, and evaluating the associated risks and benefits of specific classes of antihypertensive medications., Competing Interests: Disclosure The work of Dr O.M. Todd is funded by the UK National Institute for Health and Care Research (NIHR) via an Academic Clinical Lectureship. The work of Dr. M. Knight is funded by the UK NIHR via a Specialized Foundation Programme. The work of Dr. J. Sheppard receives funding from the Wellcome Trust, United Kingdom/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z), the National Institute for Health and Care Research, United Kingdom (NIHR), and from the British Heart Foundation, United Kingdom (refs: PG/21/10,341; FS/19/13/34,235). The work of Dr. A.P. Bress is supported by R01AG74989, K24AG080168, and R01AG065805 from the National Institute on Aging, United States (Bethesda, MD) and R01HL139837 from the National Heart, Lung, and Blood Institute, United States (Bethesda, MD). This research was funded in part by the Wellcome Trust [211182/Z/18/Z]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to the high prevalence of older individuals with multiple morbidities, polypharmacy, and exposed to unnecessary or inappropriate treatments that can cause potentially serious adverse effects, better medication management should be an objective of all health professionals. This is particularly important in older patients with hypertension. Antihypertensive deprescribing and non-pharmacological strategies have been disseminated as viable and safe alternatives for improving the quality of care for hypertension in the older population., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Systolic blood pressure (SBP) lowering reduces major cardiovascular disease (CVD) and all-cause mortality. However, the optimal target for SBP lowering remains controversial., Methods: We included trials with random allocation to an SBP <130 mm Hg treatment target and CVD as the primary outcome. Data were extracted from each study independently and in duplicate using a standardized protocol. Random-effects meta-analysis was used to obtain pooled hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality comparing SBP <130 and ≥130 mm Hg treatment targets. A secondary analysis compared the same outcomes for randomization to an SBP target of <120 or <140 mm Hg., Results: Seven trials, including 72 138 participants, met the eligibility criteria. Compared with an SBP target of ≥130 mm Hg, an SBP target of <130 mm Hg significantly reduced major CVD (HR, 0.78 [95% CI, 0.70-0.87]) and all-cause mortality (HR, 0.89 [95% CI, 0.79-0.99]). Compared with an SBP target of <140 mm Hg, an intensive SBP target of <120 mm Hg significantly reduced major CVD (HR, 0.82 [95% CI, 0.74-0.91]), but all-cause mortality was marginally insignificant (HR, 0.85 [95% CI, 0.71-1.01]). Adverse events were significantly more likely in the intensive SBP target groups, but the absolute risks were low., Conclusions: This study suggests targeting an SBP <130 mm Hg significantly reduces the risks of major CVD and all-cause mortality. The findings also support an SBP target of <120 mm Hg, based on a smaller number of trials., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023490693., Competing Interests: None.

The inflammatory status of the kidneys, vasculature, and perivascular adipose tissue (PVAT) has a significant influence on blood pressure and hypertension. Numerous micronutrients play an influential role in hypertension-driving inflammatory processes, and recent reports have provided bases for potential targeted modulation of these micronutrients to reduce hypertension. Iron overload in adipose tissue macrophages and adipocytes engenders an inflammatory environment and may contribute to impaired anticontractile signalling, and thus a treatment such as chelation therapy may hold a key to reducing blood pressure. Similarly, magnesium intake has proven to greatly influence inflammatory signalling and concurrent hypertension in both healthy animals and in a model for chronic kidney disease, demonstrating its potential clinical utility. These findings highlight the importance of further research to determine the efficacy of micronutrient-targeted treatments for the amelioration of hypertension and their potential translation into clinical application., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: There are no recent estimates for hypertension-associated medical expenditures. This study aims to estimate hypertension-associated incremental medical expenditures among privately insured US adults., Methods: We conducted a retrospective cohort study using IQVIA's Ambulatory Electronic Medical Records-US data set linked with PharMetrics Plus claims data. Among privately insured adults aged 18 to 64 years, hypertension was identified as having ≥1 diagnosis code or ≥2 blood pressure measurements of ≥140/90 mm Hg, or ≥1 antihypertensive medication in 2021. Annual total expenditures (in 2021 $US) were estimated using a generalized linear model with gamma distribution and log-link function adjusting for demographic characteristics and cooccurring conditions. Out-of-pocket expenditures were estimated using a 2-part model that included logistic and generalized linear model regression. Overlap propensity score weights from logistic regression were used to obtain a balanced sample on hypertension status., Results: Among the 393 018 adults, 156 556 (40%) were identified with hypertension. Compared with individuals without hypertension, those with hypertension had $2926 (95% CI, $2681-$3170) higher total expenditures and $328 (95% CI, $300-$355) higher out-of-pocket expenditures. Adults with hypertension had higher total inpatient ($3272 [95% CI, $1458-$5086]) and outpatient ($2189 [95% CI, $2009-$2369]) expenditures when compared with those without hypertension. Hypertension-associated incremental total expenditures were higher for women ($3242 [95% CI, $2915-$3569]) than for men ($2521 [95% CI, $2139-$2904])., Conclusions: Among privately insured US adults, hypertension was associated with higher medical expenditures, including higher inpatient and out-of-pocket expenditures. These findings may help assess the economic value of interventions effective in preventing hypertension., Competing Interests: None.

Aims: Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats., Methods: Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II-dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry., Results: Metformin treatment increased the production of short-chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end-diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1-like gene expression in macrophages, reinforcing anti-inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure., Conclusion: Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Resistant hypertension is characterized by elevated blood pressure (BP) despite using 3 antihypertensive agents. Ambulatory BP monitoring (ABPM) detects the presence of white-coat resistant hypertension (24-hour BP <130/80 mm Hg). The aim of the study was to evaluate risks of death in resistant hypertension compared with controlled hypertension, as well as in ABPM-confirmed (24-hour BP ≥130 or 80 mm Hg), versus white-coat resistant hypertension., Methods: We selected 8146 patients with controlled hypertension (office BP <140/90 mm Hg while being treated with ≤3 antihypertensive drugs) and 8577 with resistant hypertension (BP ≥140 or ≥90 mm Hg while being treated with ≥3 drugs). All-cause and cardiovascular mortalities (median follow-up, 9.7 years) were compared between groups, as well as between patients with white-coat (3289) and ABPM-confirmed (5288) resistant hypertension. Hazard ratios (HRs) from Cox models after adjustment for clinical confounders were used for comparisons., Results: Compared with controlled hypertension, resistant hypertension was associated with an increased risk in all-cause (HR, 1.21 [95% CI, 1.12-1.30]) and cardiovascular mortalities (HR, 1.33 [95% CI, 1.17-1.51]) in confounder-adjusted models. Compared with white-coat, ABPM-confirmed resistant hypertension was associated with an increased risk of all-cause (HR, 1.45 [95% CI, 1.32-1.60]) and cardiovascular (HR, 1.68 [95% CI, 1.43-1.98]) mortalities. When ABPM-confirmed and white-coat resistant hypertension were separately compared with controlled hypertension, only the former was associated with an increased risk of death and cardiovascular death (HR, 1.36 [95% CI, 1.26-1.48] and 1.56 [95% CI, 1.36-1.79]), respectively., Conclusions: ABPM-confirmed resistant hypertension is associated with an increased risk of death and cardiovascular death with respect to both controlled hypertension and white-coat resistant hypertension., Competing Interests: None.

Hypertension and cancers are the most common causes of death in humans, as well as common co-diseases among elderly population. Studies have shown that hypertension is associated with carcinogenesis. The renin-angiotensin-aldosterone system (RAAS) is a crucial regulatory system of blood pressure, fluid, and electrolyte homeostasis, which plays an essential role in the pathogenesis of hypertension, whose mechanism is relatively clear. Studies have indicated that RAAS also widely exists in cancer tissues of different systems, which can affect the risk of cancers by stimulating cancer angiogenesis, participating in cancer-related oxidative stress, and regulating cancer-related immunity. Therefore, inhibiting RAAS activity seems beneficial to decreasing the risk of cancers. As one of the most commonly used antihypertensive drugs, RAAS inhibitors have been widely used in clinical practice. However, the conclusions of clinical studies on the relationship between RAAS inhibitors and cancers are not entirely consistent, which has been widely concerned by clinicians. The latest findings suggest that while RAAS inhibitors may reduce the risk of digestive cancers, respiratory cancers, urological cancers, gynecological cancers, and skin cancers, ACEIs may increase the risk of lung cancer, endometrial cancer, basal cell carcinoma, and squamous cell carcinoma. This article comprehensively reviews animal experiments, clinical studies, and meta-analyses on the relationship between RAAS inhibitors and cancers, to provide references for related studies in the future., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Both blood pressure-lowering medication and sodium reduction are effective in hypertension control, but whether the effect of sodium reduction differ across blood pressure-lowering medications 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, age, baseline sodium and blood pressure levels, and study duration., 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 β-blockers, renin-angiotensin-aldosterone system inhibitors, and dual therapy groups. No significant subgroup differences were observed across subgroups defined by 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., Competing Interests: G.A. MacGregor is the unpaid Chair of Consensus Action on Salt, Sugar and Health (CASSH), World Action on Salt, Sugar and Health (WASSH) and Blood Pressure UK. F.J. He is an unpaid member of CASSH and WASSH. S. Pombo-Rodrigues is the campaign lead for CASSH. The other authors report no conflicts.

Background: Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use., Methods: Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol)., Results: The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20-23 million) to 55 million (95% CI, 51-60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes., Conclusions: The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization., Competing Interests: B.K Bellows was supported by K01HL140170 from the National Heart, Lung, and Blood Institute (Bethesda, MD). I. Hernandez discloses consulting fees from BMS and Pfizer, outside of the submitted work. A.P Bress is supported by R01AG74989, K24AG080168, and R01AG065805 from the National Institute on Aging (Bethesda, MD) and R01HL139837 from the National Heart, Lung, and Blood Institute (Bethesda, MD). W.C. Cushman has received institutional grants from George Medicines and ReCor Medical. Dr Whelton is an associated editor at Hypertension. George Institute Ventures, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin, and blood pressure–lowering drugs. George Institute Ventures has submitted patents for low-dose blood pressure combinations, on which Professor Rodgers is listed as one of the inventors. A. Rodgers has served on a Data and Safety Monitoring Board for a trial sponsored by Idorsia. George Institute Ventures Pty Ltd, the social enterprise arm of The George Institute for Global Health (TGIGH), has received investment to develop fixed-dose combination products containing aspirin, statin, and blood pressure–lowering drugs. TGIGH holds and have filed applications for combination products for the treatment of hypertension and diabetes, and Professor Rodgers is listed as one of the inventors (granted: US 10,369,15; US 10,799,487; US 10,322,117; US 11,033,544; US 11,478,462; Pending: US 17/932,982; US 18/446,268; US 17/598,122; US 17/317,614). A. Rodgers is seconded part-time to George Medicines Pty Ltd (GM), a subsidiary of George Institute Ventures. Professor Rodgers does not have a personal financial interest in these patents or products. The other authors report no conflicts.

Background: The prevalence of hypertension and uncontrolled hypertension may differ by age and sex., Methods: We included participants in the Atherosclerosis Risk in Communities study at seven study visits over 33 years (visit 1: 15 636 participants; mean age, 54 years; 55% women), estimating sex differences in prevalence of hypertension (systolic blood pressure ≥130 mm Hg; diastolic blood pressure ≥80 mm Hg; or self-reported antihypertension medication use) and uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) using unadjusted and comorbidity-adjusted models., Results: The prevalence of hypertension increased with age from 40% (ages, 43-46 years) to 93% (ages, 91-94 years). Within hypertensive individuals, the prevalence of uncontrolled hypertension was higher in men (33%) than women (23%) at ages 43 to 46 years but became higher in women than men starting at ages 61 to 64, with 56% of women and 40% men having uncontrolled hypertension at ages 91 to 94. This sex difference was not explained by differences in coronary heart disease, diabetes, body mass index, estimated glomerular filtration rate, number of antihypertension medications, classes of medications, or adherence to medications. In both sexes, uncontrolled hypertension was associated with a higher risk for chronic kidney disease progression (hazard ratio, 1.5 [1.2-1.9]; P =4.5×10 -4 ), heart failure (hazard ratio, 1.6 [1.4-2.0]; P =8.1×10 -7 ), stroke (hazard ratio, 2.1 [1.6-2.8]; P =1.8×10 -8 ), and mortality (hazard ratio, 1.5 [1.3-1.6]; P =6.2×10 -19 )., Conclusions: Sex differences in the prevalence of hypertension and uncontrolled hypertension vary by age, with the latter having implications for health throughout the life course., Competing Interests: The data reported here have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or interpretation of the US government. USRDS data were used for Table 3. The opinions presented do not necessarily represent those of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the Department of Health and Human Services, or the US Government. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government.

Background: High fruit and vegetable diets are associated with reduced chronic kidney disease and cardiovascular disease but are infrequently used in hypertension treatment. Low acid diets are also associated with reduced chronic kidney disease and cardiovascular disease, and fruits and vegetables or oral sodium bicarbonate (NaHCO 3 ) lowers dietary acid., Methods: We randomized 153 hypertensive macroalbuminuric patients receiving pharmacologic chronic kidney disease and cardiovascular disease protection to get fruits and vegetables, oral NaHCO 3 , or Usual Care. We assessed the course of kidney disease progression and cardiovascular disease risk indices over five years., Results: Chronic kidney disease progression was slower in participants receiving fruits and vegetables or oral NaHCO 3 than Usual Care [mean (SE)] [-1.08 (0.06) and -1.17 (0.07) vs. -1.94 (0.11) mL/min/1.73m 2 / year, respectively, P's< .001). Yet, systolic blood pressure was lower, and cardiovascular disease risk indices improved more in participants receiving fruits and vegetables than in those receiving NaHCO 3 or Usual Care. These cardiovascular benefits of fruits and vegetables were achieved despite lower doses of pharmacologic chronic kidney disease and cardiovascular disease protection., Conclusion: The trial supports fruits and vegetables as foundational hypertension treatment to reduce chronic kidney disease progression and cardiovascular disease risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abnormal glucose metabolism is a common disease of the endocrine system. The effects of drugs on glucose metabolism have been reported frequently in recent years, and since abnormal glucose metabolism increases the risk of microvascular and macrovascular complications, metabolic disorders, and infection, clinicians need to pay close attention to these effects. A variety of common drugs can affect glucose metabolism and have different mechanisms of action. Hypertension is a common chronic cardiovascular disease that requires long-term medication. Studies have shown that various antihypertensive drugs also have an impact on glucose metabolism. Among them, α-receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers can improve insulin resistance, while β-receptor blockers, thiazides and loop diuretics can impair glucose metabolism. The aim of this review was to discuss the mechanisms underlying the effects of various antihypertensive drugs on glucose metabolism in order to provide reference information for rational clinical drug use., (© 2024 John Wiley & Sons Ltd.)

Background and Purpose: Maintaining mitochondrial quality is attracting attention as a new strategy to treat diabetes and diabetic complications. We previously reported that mitochondrial hyperfission by forming a protein complex between dynamin-related protein (Drp) 1 and filamin, mediates chronic heart failure and cilnidipine, initially developed as an L/N-type Ca 2+ channel blocker, improves heart failure by inhibiting Drp1-filamin protein complex. We investigated whether cilnidipine improves hyperglycaemia of various diabetic mice models., Experimental Approach: Retrospective analysis focusing on haemoglobin A1c (HbA1c) was performed in hypertensive and hyperglycaemic patients taking cilnidipine and amlodipine. After developing diabetic mice by streptozotocin (STZ) treatment, an osmotic pump including drug was implanted intraperitoneally, followed by weekly measurements of blood glucose levels. Mitochondrial morphology was analysed by electron microscopy. A Ca 2+ channel-insensitive cilnidipine derivative (1,4-dihydropyridine [DHP]) was synthesized and its pharmacological effect was evaluated using obese (ob/ob) mice fed with high-fat diet (HFD)., Key Results: In patients, cilnidipine was superior to amlodipine in HbA1c lowering effect. Cilnidipine treatment improved systemic hyperglycaemia and mitochondrial morphological abnormalities in STZ-exposed mice, without lowering blood pressure. Cilnidipine failed to improve hyperglycaemia of ob/ob mice, with suppressing insulin secretion. 1,4-DHP improved hyperglycaemia and mitochondria abnormality in ob/ob mice fed HFD. 1,4-DHP and cilnidipine improved basal oxygen consumption rate of HepG2 cells cultured under 25 mM glucose., Conclusion and Implications: Inhibition of Drp1-filamin protein complex formation becomes a new strategy for type 2 diabetes treatment., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose of Review: After decades of relying on the control of hypertension and treatment with renin angiotensin system inhibitors as the only evidence-based interventions to slow the progression of chronic kidney disease (CKD), we have entered an era when multiple effective treatment options are available. This review considers the mechanisms and benefits of these novel treatments as well as the challenges associated with achieving optimal combination therapy., Recent Findings: Over the past 5 years, large clinical trials have provided robust evidence that, when added to renin angiotensin system inhibitors, treatment with sodium glucose cotransporter 2 inhibitors reduces the rate of CKD progression and the risk of cardiovascular events in people with CKD with or without diabetes and with or without albuminuria; nonsteroidal mineralocorticoid antagonists and glucagon-like peptide-1 receptor agonists afford similar benefits in people with type 2 diabetes and CKD. The mechanisms of actions of these novel therapies suggest that combination therapy will produce additive benefits, though specific evidence is sparse., Summary: Further trials are warranted to investigate the benefits of combination therapy with novel treatments in people with CKD. Clinical implementation of optimal combination therapy will require reorganization of services to ensure that patients receive adequate education, support and monitoring., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension., Methods: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice., Conclusion: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults., Trial Registration: PACTR202107579572114., Competing Interests: Disclosures George Institute Ventures, the social enterprise arm of The George Institute for Global Health, has received investment to develop fixed-dose combination products containing aspirin, statin and blood pressure lowering drugs. George Medicines Pty Ltd (GM), an entity of George Institute Ventures, has submitted patents for low- dose blood pressure combinations, on which Professor Anthony Rodgers is listed as one of the inventors. Professor Rodgers is seconded part-time to GM. All staff employed by The George Institute for Global Health have an institutional interest to declare with respect to George Health Enterprises. None of The George Institute for Global Health staff have a direct financial interest in these investments. In the last 3 years, Professor Alta Schutte has received speaker honoraria from Abbott, Servier, Sanofi, Medtronic, Omron, and Aktiia for work unrelated to this research. Professor Huffman has planned patents for combination therapy for the treatment of heart failure. In the last 5 years, Dr Ojji has received speakers' fees for continuous medical education lectures from Novartis, Pfizer, Servier Pharmaceuticals and Boehringer Ingelheim which are unrelated to this trial., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: While monoclonal antibodies (mAbs) targeting the CGRP pathway have revolutionized migraine management due to their improved tolerance and adherence, concerns remain about their potential impact on blood pressure (BP), especially in older patients, due to CGRP-mediated vasodilation blockade. Given the growing use of these therapies in older populations, assessing their cardiovascular (CV) safety is of paramount importance., Methods: This multicentric observational prospective study focused on migraine sufferers aged ≥ 60 who began erenumab, galcanezumab, or fremanezumab for prevention. Baseline, three-month, and twelve-month BP measurements were collected. Changes in antihypertensive medication and "Newly or Worsened Hypertensive" patients (NWHP) were assessed., Results: Among 155 patients receiving anti-CGRP mAbs (40 Erenumab, 47 Galcanezumab, 68 Fremanezumab), 42.5% had hypertension history and 39% were on antihypertensive treatment. No significant systolic or diastolic BP changes occurred at any time point compared to baseline (all p > 0.05), with no differences between the three groups. After one year, 20/155 (12.9%) patients were considered NWHP; 11/20 had prior hypertension, and 5/11 adjusted antihypertensive therapy. Among 9/20 newly hypertensive patients, 5/9 had a single measurement above the normal threshold with no requirement for new pharmacological therapy. A higher baseline BP value was associated with increased BP (p = 0.002)., Conclusions: The study concludes that treatment with anti-CGRP mAbs over one year does not significantly affect BP in patients aged ≥ 60, nor does it increase the incidence of hypertension compared to general population trends. Nonetheless, continuous monitoring and further long-term studies are necessary to fullya scertain the cardiovascular safety of these medications in the elderly., (© 2024. The Author(s).)

Polypharmacy, defined here as the concomitant use of five or more medications, is a significant health issue, particularly affecting individuals with chronic diseases like hypertension (HTN). To compare individuals with and without HTN in term of polypharmacy, and to investigate correlates of polypharmacy and medication use patterns in individuals with HTN in southwest Iran. This cross-sectional study used the baseline data of 9270 participants of the Pars Cohort Study (PCS) with a mean age of 52.6 ± 9.7 years. Poisson multivariable modeling was applied to identify correlates of polypharmacy, and Lexicomp® was used to assess drug-drug interactions. Anatomical Therapeutic Chemical classification was used to describe the pattern of medication use. The prevalence of polypharmacy in individuals without hypertension was 4.7 % (4.2%-5.2 %) vs. 23.7 % (22.1%-25.3 %) in individuals with hypertension (P < 0.001). Individuals with hypertension from middle-high socioeconomic status (SES) had a 1.51-fold higher prevalence of polypharmacy than vs. low SES. Those with more than three comorbidities had a 5.18 times higher prevalence of polypharmacy than those with isolated hypertension. Calcium channel blockers were the most common antihypertensives (20.9 %). In terms of drug-drug interactions, type C interactions were most prevalent among participants with hypertension and polypharmacy (76.0 %). Our findings imply a fairly high prevalence of polypharmacy and drug-drug interactions among individuals with hypertension; to tackle this issue, we recommend a national pharmacovigilance system, training programs for primary care physicians, public education and awareness campaigns, drug-checking campaigns, targeted screenings to alter modifiable risk factors, and the use of safe combination pills., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hypertension, which stands as a leading global health challenge, demands a dynamic approach for its effective management. The traditional methods of managing hypertension, centered on periodic clinic visits for blood pressure measurement and pharmacological interventions, are increasingly being complemented and enhanced by digital technologies. The integration of wearable devices, mobile applications, personalized treatments, and telehealth solutions into healthcare system is reshaping traditional hypertension care. Digitalization of hypertension management extends to population health, in addition to individual patient benefits, aimed at preventing and controlling hypertension on a broader scale. However, this digital revolution in hypertension management brings forth challenges related to data security, data accuracy, equitable access, and standardization of devices by international regulatory agencies. Addressing these issues is equally important to ensure that the benefits of digital technologies are accessible to everyone, irrespective of socio-economic factors. This paper concludes with a forward-looking perspectives, emphasizing the potential of digitalization to modify the landscape of hypertension management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Resistant hypertension is a condition where blood pressure levels remain elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) and a diuretic. To be diagnosed as resistant hypertension, maintaining adherence to therapy is required along with confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension. The key management points of this condition include lifestyle changes such as reduced sodium and alcohol intake, regular physical activity, weight loss and discontinuation of substances that can interfere with blood pressure control. It is also recommended that current treatment be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose. It is further recommended that current drugs be replaced with a more appropriate and less difficult treatment regimen based on the patient's age, ethnicity, comorbidities and risk of drug-drug interactions. The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone, as demonstrated in the PATHWAY-2 trial and meta-analyses. Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine and beta-blockers, as well as any other antihypertensive drugs not already in use. New approaches under research are selective non-steroidal mineralocorticoid receptor antagonists such as finerenone, esaxerenone and ocedurenone, selective aldosterone synthase inhibitors such as baxdrostat, and dual endothelin antagonist aprocitentan., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Uncontrolled blood pressure is a significant public health problem associated with a high rate of mortality and morbidity worldwide. In Ethiopia, 48% of hypertensive patients have Uncontrolled blood pressure. Therefore, this study aimed to identify the determinants of uncontrolled blood pressure among adult hypertensive patients on follow-up at the Negele and Adola General Hospitals in the Guji Zone, Oromia, Ethiopia., Methods: A facility-based, unmatched case-control study was conducted in Negelle and Adola General Hospitals, Guji Zone, from January-01-30, 2023, on 384 samples. Study participants were selected consecutively as they came for treatment until the required sample size was obtained. The data were collected using an interview-administered structured questionnaire and medical chart review. The data were entered into Epi-data version 3.1 and exported to SPSS version 25 for analysis. Binary logistic regression analysis was used to model the association between the dependent and independent variables. The candidate variables with p < 0.25 in the bivariate analysis were entered into the multivariable logistic regression. An Adjusted Odds ratio (AOR) and 95% CI were used to measure the strength of the association. Finally, at p < 0.05, statistical significance was declared., Results: A sample of 384 respondents (128 cases and 256 controls) were included, for a response rate of 100%. No adherence to medication (AOR = 2.01, 95% CI = 1.16-3.44), no adherence to smoking abstinence (AOR = 1.84, 95% CI = 1.05-3.22), no adherence to weight management (AOR = 2.02, 95% CI = 1.04-3.92), poor hypertension knowledge (AOR = 2.18, 95% CI = 1.26-3.76), use of traditional medicine (AOR = 9.13, 95% CI = 5.31-15.69), and overweight (AOR = 3.35, 95% CI = 1.79-6.26) were significantly associated with uncontrolled blood pressure., Conclusion: This study revealed that no adherence to medication, smoking, weight management, poor hypertension knowledge, traditional medicine use, and being overweight were determinants of uncontrolled blood pressure. Since these are modifiable and preventable factors, there is a need to implement interventions that will enhance self-care practices in this population to improve treatment outcomes., (© 2024. The Author(s).)

Introduction: Hypertension, a prevalent cardiovascular disease globally, poses significant health risks and economic burden. Evolving treatment targets necessitate more intensive strategies, such as low-dose triple or quadruple drug combinations. However, a systematic comparison of different low-dose antihypertensive combinations is still lacking. The aim of the present study is to systematically and comprehensively evaluate the blood pressure-lowering effect and the associated safety of diverse low-dose polypharmacy combinations in patients with hypertension., Methods and Analysis: In this systematic review and network meta-analysis, randomised controlled trials comparing diverse low-dose polypharmacy combinations with placebo or active treatments in patients with hypertension will be eligible for inclusion. The primary outcomes are a reduction in systolic/diastolic blood pressure, the rate of target blood pressure, adverse effects, serious adverse effects and all-cause dropout after treatment. PubMed, Web of Science, Embase, Cochrane Library, Chinese Science Citation Database, Wanfang Medical Network, VIP Database and clinical trial registries will be systematically searched for relevant studies published from inception date to 18 January 2024. No language restrictions will be applied during the search process. Two independent reviewers will identify eligible trials and extract the data. Traditional pairwise meta-analysis will be conducted to analyse direct comparisons. A frequentist approach will be used to analyse the primary outcome for network comparisons, and cumulative rank probabilities will present the treatment hierarchy of all endpoints. Sensitivity analysis will be conducted using a Bayesian framework under a random-effects model. Subgroup analyses will be conducted according to sample size, quality of study and sponsorship, if the data allow. The Cochrane Risk of Bias Tool 2.0 will be used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation system will be used to assess the strength of evidence., Ethics and Dissemination: Since this study relies solely on published literature, no ethics approval is necessary. The results will be submitted to a peer-reviewed journal., Prospero Registration Number: CRD42024503239., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Evidence has suggested that clevidipine may provide faster blood pressure (BP) reduction with less volume than nicardipine in stroke and cardiothoracic surgery patients, but its use in hypertensive crises has not been well established. The primary objective of this study was to compare the treatment success of clevidipine and nicardipine in hypertensive crisis., Methods: This was a multicenter, retrospective cohort study including patients who received either clevidipine or nicardipine for treatment of hypertensive crisis. The primary outcome was the time from infusion start to attainment of goal BP, defined as the higher value of the guideline-directed 25% reduction in BP or the physician-ordered goal. Secondary outcomes were the time from infusion start to guideline-directed 25% reduction in BP, drug and total volume intake, the time from order entry to BP goal attainment, the number of BP and heart rate excursions, intensive care unit (ICU) length of stay, and study medication cost., Results: In total, 182 patients were included in the study (103 receiving nicardipine and 79 receiving clevidipine). Time to goal BP was similar between the groups (35 vs 33 minutes for clevidipine vs nicardipine, respectively; P = 0.37). Time to guideline-directed 25% reduction was also similar (P = 0.42). Volume from study drug was significantly less with clevidipine (222 vs 518 mL; P = 0.01); however, the total volume received in the ICU was similar (3,370 vs 3,383 mL; P = 0.43). Percent time in the goal BP range was similar (43.1% vs 42.3%). The cost of clevidipine was $199.37 per vial (based on the average wholesale price as of June 2023). This cost was 682% higher than that for a bag of nicardipine., Conclusion: Time to goal BP was similar for clevidipine and nicardipine in this population. Any decreases in medication-associated volume with clevidipine were no longer evident when all volume sources were considered. These results show that clevidipine may not provide meaningful benefit in this heterogenous population. The difference in cost does not seem justified given the lack of improvement in clinically relevant outcomes., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety., Methods: In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed., Findings: The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant., Interpretation: A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice., Funding: George Medicines., Competing Interests: Declaration of interests AR, AS, AES, CG, MS, XL, and NW are employed at The George Institute for Global Health (TGI), which holds an interest in George Medicines via its social enterprise arm, George Institute Ventures. None of the TGI staff has a personal financial interest in George Medicines. AR is seconded part-time to George Medicines. TGI holds patents for ultra-low-dose, fixed-dose combination products for the treatment of hypertension and diabetes, and AR is listed as one of the inventors (granted: US 10 369 156, US 10 799 487, US 10 322 117, US 11 033 544, US 11 478 462; pending: US 17/932 982, US 18/446 268, US 17/598 122, US 17/317 614, US 17/527 084, US 17/527 085, US 17/527 087). AR does not have a financial interest in these patents. None of the other authors has a financial interest in George Medicines or has received funding for their independent contribution to the GMRx2 programme. AR reports consulting fees as a data and safety monitoring board member for Idorsia; and a fellowship grant from the National Health and Medical Research Council of Australia (GNT 1160743). AES reports consulting fees or speaker honoraria from OMRON Healthcare, Aktiia, Medtronic, Servier, Abbott, Sanofi, Sun Pharmaceuticals, Novartis, and Skylabs; being co-chair of the National Hypertension Taskforce Australia; being a board member for Hypertension Australia and the Australian Cardiovascular Alliance; and an investigator grant from the National Health and Medical Research Council of Australia (GNT 2017504). DBO reports speaker honoraria from Novartis, AstraZeneca, Servier, Swipha, and Boehringer Ingelheim for speaking at educational meetings. KN reports speaker and consulting honoraria from Bausch Health, Berlin-Chemie/Menarini, Egis, Idorsia, Janssen, Gedeon Richter, Gilead, Krka, Novo Nordisk, Polpharma, Recordati, Sandoz, and Servier; and honoraria from or participation on advisory boards for Polpharma and Zentiva. MPS reports consulting fees or travel and research support from Medtronic, Abbott, Recor, Novartis, Servier, Pfizer, and Boehringer Ingelheim; and being current President of Hypertension Australia and Treasurer of the World Hypertension League. WCC reports institutional grants from Recor and George Medicines; and consulting fees from Alnylam Pharmaceuticals. NRP reports consultancy fees from Servier and Aktiia; support for research projects and staff from Servier and Pfizer; support for arranging and speaking at educational meetings from AstraZeneca, LRI-Therapharma, Napi, Servier, Sanofi, EVA Pharma, Pfizer, Emcure, Dr Reddy's Laboratories, and Zydus; and support by the National Institute for Health Research Senior Investigator Awards, Biomedical Research Centre funding, and the British Heart Foundation Research Centre Excellence Award. DEG reports funding to his department as part of the EU Horizon Hypermarker project. BW reports trial steering committee appointments for Novartis and AstraZeneca; lecture fees for Servier and Novartis; and an unremunerated role as President of the International Society of Hypertension. JTW reports institutional grants from the National Institutes of Health, the Ohio Department of Medicaid, and the Agency for Healthcare Research and Quality; travel support and participation on an advisory board for Medtronic; being chair of the data safety monitoring board for the IMPACTS MIND Trial at Tulane University; and being on the Northeast Ohio Neighbourhood Health Center Community Board of Directors. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Objective: Hypertension is a prevalent chronic condition often treated with multiple medications, leading to polypharmacy, which can heighten the risk of adverse drug reactions and contribute to psychological issues like depression. This study aimed to investigate the relationship between polypharmacy and depressive symptoms in hypertensive patients using data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Materials and Methods : This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2017 and March 2020. Results : Among 2543 hypertensive participants, 12.3% met the criteria for depression. The findings revealed that patients using 11 or more medications were ten times more likely to experience depressive symptoms compared to those taking 1 to 2 medications (OR = 10.06, p < 0.001). Additionally, younger age (18 to 45 years), female gender, and lower educational attainment were significantly associated with higher rates of depressive symptoms. Specifically, females were 1.47 times more likely to experience depression compared to males ( p = 0.032). Conclusions : This research highlights the substantial impact of medication burden on mental health among hypertensive patients, emphasizing the need for tailored clinical interventions for this vulnerable population.

To preclinically study the effectiveness of new antihypertensive drugs, various animal hypertension models are used. However, most of them do not correspond to primary hypertension, which develops in people with age. We used male Wistar rats of 4, 10, 12 and 18 months old. The animals were divided according to systolic blood pressure (SBP) into normotensive (SBP ≤ 114 mmHg) or hypertensive (SBP ≥ 115 mmHg). Within hypertensive animals, two cohorts were distinguished-with SBP below and above 125 mmHg. The animals received 100 µg/kg of taxifolin intraperitoneally for 7 days. A significant difference was shown between animals with SBP above and below 115 mmHg, as well as between cohorts of hypertensive animals with SBP above and below 125 mmHg within each age. The number of animals with elevated SBP increased with age both for clusters with an SBP above 115 mmHg and for cohorts with an SBP above 125 mmHg. Administration of taxifolin led to a significant decrease in the SBP only in hypertensive animals. A physiological model of age-related hypertension was obtained in male Wistar rats. It has been shown that hypertension develops and worsens with age. In preclinical studies, it should be taken into account that drugs may have different effects depending on the initial SBP of the animals.

Objectives: Antihypertensives reduce the risk of myocardial infarction and stroke. Restrictions during the COVID-19 pandemic limited access to healthcare, which may have had a negative impact on drug prescribing. This study aimed to assess the effect of the COVID-19 pandemic on the initiation of antihypertensive drugs., Design: Interrupted time series study using a segmented linear regression model., Setting: Swedish population assessed through linked national healthcare registers., Participants: 720 300 new users of antihypertensives., Intervention: March 2020, COVID-19 pandemic onset., Main Outcomes Measures: The change in the initiation of antihypertensives expressed as monthly cumulative incidence, stratified by age and sex. Data on dispensed prescriptions of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors (ACEi) and angiotensin receptor blockers were extracted from the Swedish Prescribed Drug Register, from March 2018 to November 2021. Initiation (new use) was defined as having no previous dispensations before March 2019. Monthly cumulative incidence in March 2019-November 2021 was calculated as the number of patients initiating each drug class in each month divided by the population., Results: The start of the pandemic was associated with an immediate drop in the initiation of any antihypertensive, but no sustained effects were observed, as the incidence continued to increase in the postinterruption period by +0.02% each month in both sexes. The immediate drop was statistically significant for ACEi in both sexes and all antihypertensive classes except diuretics in patients >65 years. А significant postintervention trend change was observed for initiation of diuretics (+0.013% overall), driven mainly by a significant increase in patients >65 years. Similar findings were also observed for diuretics in females (+0.02%) and ACEi (+0.03%) in patients >65 years., Conclusions: The pandemic had an immediate negative short-term effect, but we found no major long-term negative influence of the COVID-19 pandemic on initiation of any type of antihypertensive drugs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Laboratory experiments have indicated that calcium channel blockers (CCBs) inhibit the entry and replication of influenza A virus in cells. However, no clinical studies have assessed the incidence of influenza among patients receiving CCBs. This study aimed to investigate the association between CCB use and the incidence of influenza among patients with hypertension using administrative claims data in Japan., Design: Retrospective cohort study., Setting: Administrative health insurance claims database of Kumamoto Prefecture, Japan., Participants: 360 515 patients with hypertension (10th edition of the International Classification of Diseases code I10) who were prescribed CCBs and 171 142 patients who were prescribed angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) between 2012 and 2016., Primary Outcome: We compared the incidence of influenza between the CCB and ACEI/ARB groups using high-dimensional propensity-score (HD-PS) matching., Results: A total of 166 814 HD-PS matched pairs were obtained. Before HD-PS matching, the CCB group had a significantly lower influenza incidence than the ACEI/ARB group in the overall analysis (2.4% vs 2.5%, p=0.007; risk ratio 0.95, 95% CI 0.92 to 0.99). However, no significant difference was observed between the two groups after HD-PS matching (2.4% vs 2.5%, p=0.067; risk ratio 0.96, 95% CI 0.92 to 1.00); only in 2012 did the CCB group have a significantly lower likelihood of influenza than the ACEI/ARB group., Conclusions: No significant difference was observed in the influenza incidence between the CCB and ACEI/ARB groups. A direct comparative study between background-matched patients with and without CCBs is warranted to confirm the effect of CCBs on reducing the incidence of influenza., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease, development of end-stage renal disease, and all-cause mortality. It affects around 10% of the population worldwide. The prevalence of hypertension in people with CKD ranges from 22% in stage 1 to 80% in stage 4. Elevated arterial blood pressure is one of the major independent risk factors for adverse cardiovascular events. Thereby, reducing blood pressure to below standard targets may be beneficial but could also increase the risk of adverse events. The optimal blood pressure target in people with hypertension and CKD remains unknown., Objectives: Primary: to compare the effects of standard and lower-than-standard blood pressure targets for hypertension in people with chronic kidney disease on mortality and morbidity outcomes. Secondary: to assess the magnitude of reductions in systolic and diastolic blood pressure, the proportion of participants reaching blood pressure targets, and the number of drugs necessary to achieve the assigned target., Search Methods: We used standard, extensive Cochrane search methods. We searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, one other database, and two trial registers up to 8 February 2023. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions., Selection Criteria: We included randomized controlled trials (RCTs) in people with hypertension and CKD that provided at least twelve months' follow-up. Eligible interventions compared lower targets for systolic/diastolic blood pressure (130/80 mmHg or lower) to standard targets for blood pressure (140 to 160/90 to 100 mmHg or lower). Participants were adults with CKD and elevated blood pressure documented in a standard way on at least two occasions, or already receiving treatment for elevated blood pressure., Data Collection and Analysis: We used standard Cochrane methods. Our critical outcomes were: total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease. Important outcomes were: participant withdrawals due to adverse effects, and number of participants with a doubling of serum creatinine level or at least a 50% reduction in the glomerular filtration rate (GFR) at the end of the study. We used GRADE to assess the certainty of the evidence for the critical outcomes. This review received no funding., Main Results: We included six RCTs that contributed data for meta-analysis, involving 7348 participants overall (range 840 to 4733 people per study). The mean follow-up was 3.6 years (range 1.0 to 8.0 years). Three studies were publicly funded, two were privately funded, and one had both public and private funding. All RCTs provided individual participant data. None of the included studies blinded participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure target. However, an independent committee blinded to group allocation assessed clinical events in all studies. Critical outcomes. Compared with standard blood pressure targets, lower targets likely result in little to no difference in total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.76 to 1.06; 6 studies, 7348 participants), total serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 7348 participants), and total cardiovascular events (RR 1.00, 95% CI 0.87 to 1.15; 5 studies, 6508 participants), all with moderate-certainty evidence. Compared with standard blood pressure targets, lower targets may result in little to no difference in cardiovascular mortality (RR 0.90, 95% CI 0.70 to 1.16; 6 studies, 7348 participants) and progression to end-stage renal disease (RR 0.94, 95% CI 0.80 to 1.11; 4 studies, 4788 participants), both with low-certainty evidence. Important outcomes. We found little to no differences in: participant withdrawals due to adverse effects; and the number of participants with a doubling of serum creatinine level, or at least a 50% reduction in GFR at the end of the study. Exploratory outcomes. Compared to the standard blood pressure target groups, participants in the lower target groups achieved lower systolic and diastolic blood pressure values after one year, and required a higher number of antihypertensive drugs at the end of the studies. A higher proportion of participants in the standard blood pressure target groups achieved the targets they were assigned than did participants in the intensive target groups., Authors' Conclusions: Compared to a standard blood pressure target, lower blood pressure targets probably result in little to no difference in total mortality, total serious adverse events, and total cardiovascular events, and may result in little to no difference in total cardiovascular mortality or in the progression to end-stage renal disease in people with hypertension and CKD. However, the evidence underpinning these conclusions has several limitations. All studies were open design, blood pressure measurement was performed at a medical office, and there was scant information about adverse events. Future research should include high-quality adverse event data, report results for people with different levels of proteinuria, and consider out-of-office blood pressure monitoring. Several studies are ongoing, and may provide new evidence for this topic in the near future., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Hypertension afflicts most patients with chronic kidney disease (CKD) and contributes to kidney disease progression, cardiovascular disease, and death in this patient population. The evidence and clinical guidelines support lowering blood pressure (BP) goals in patients with CKD. We evaluated if BP control improved among US adults with CKD., Methods and Results: In the NHANES (National Health and Nutrition Examination Survey) for the periods 2011 to 2014, 2015 to 2016, and 2017 to 2020, we identified individuals with CKD defined as estimated glomerular filtration rate 20 to 59 mL/min per 1.73 m 2 or urinary albumin/creatinine ratio≥30 mg/g. The following systolic BP categories were evaluated: <120, 120 to 129, 130 to 139, and ≥140 mm Hg. All measures were tested for differences between year groups accounting for sample strata, clusters, and weights. During the periods of 2011 to 2014, 2015 to 2016, and 2017 to 2020, the prevalence of CKD was stable at 14%, 13%, and 13%, respectively ( P =0.4). Among those with CKD, the proportion of individuals with self-reported hypertension or taking BP medications increased from 66 in 2011 to 2014, to 69 and 86% in 2015 to 2016 and 2017 to 2020, respectively ( P <0.0001). Although the number of BP medications prescribed increased significantly over time, less than half of the individuals with CKD had well-controlled BP based on the current guidelines., Conclusions: Although BP recognition has improved among those with CKD, a significant number of individuals with CKD do not meet their BP goal.

Background: Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first-line β-blocker use without a compelling condition has fallen out of favor in US guidelines., Methods and Results: This serial cross-sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (<140, 140 to <160, and ≥160 mm Hg), as well as trends in subgroups (age, sex, race and ethnicity, and comorbidities warranting β-blocker use). Among 2 832 684 eligible Veterans (average age 61 years, 95% men, 65% non-Hispanic White, and 8% with cardiovascular disease), from 2000-2004 to 2015-2019, initial monotherapy increased across all pretreatment systolic BP levels (<140 mm Hg: 62.1% to 66.4%; 140 to <160 mm Hg: 70.7% to 76.8%; ≥160 mm Hg: 64.2% to 69.7%). Initiation of dual therapy decreased across all pretreatment systolic BP levels (<140 mm Hg: 25.0% to 24.2%; 140 to <160 mm Hg: 20.4% to 17.6%; ≥160 mm Hg: 22.7% to 22.0%). Among 2 521 696 Veterans (89% of overall) without a β-blocker-indicated condition in 2015 to 2019, 20% initiated a β-blocker, most commonly as monotherapy., Conclusions: More than half of US Veterans diagnosed with hypertension with a pretreatment systolic BP ≥160 mm Hg were started on antihypertensive monotherapy. There are disparities between guideline-recommended first-line treatments and the actual regimens initiated for newly diagnosed Veterans with hypertension.

Aim: This study aimed to investigate the effects of pain management according to the World Health Organization (WHO) analgesic ladder on pain severity, pain interference, and blood pressure (BP) in treated hypertensive patients with chronic musculoskeletal pain., Background: Pain management can affect BP control owing to the proposed mechanism by which persistent pain contributes to increased BP. However, there are inadequate studies investigating the benefit of pain management in controlling both pain and BP in hypertensive patients who have chronic pain., Methods: In this cross-sectional study, demographic data and pain characteristics (resting pain score on the numerical pain rating scale, pain severity, and pain interference subscale of the Brief Pain Inventory) were collected via face-to-face interviews. BP was measured thrice on the same day. Data on pain medications taken in the previous 1 month were retrieved from the medical records. Participants were categorized into three groups following pain management patterns according to the WHO analgesic ladder: no, partial, and complete treatment. Multivariate logistic regression analysis (MLRA) was used to analyse the association between the variables and uncontrolled BP., Findings: Among 210 participants, the mean (standard deviation) age was 68 (15.5) years, and 60.47% had uncontrolled BP. The resting pain score, pain severity, and pain interference subscale scores of the complete treatment group were significantly lower than that of the partial treatment group ( P = 0.036, 0.026, and 0.044, respectively). The MLRA revealed that pain management patterns were associated with uncontrolled BP (adjusted odds ratio [AOR]: 6.75; 95% confidence interval [CI]: 2.71-16.78; P < 0.001) and resting pain scores (AOR: 1.17; 95% CI: 1.04-1.38; P = 0.048). Our findings suggest that pain management patterns adhering to the WHO analgesic ladder can reduce pain severity and pain interference and also control BP in hypertensive patients with chronic musculoskeletal pain.