In remembrance: the life and legacy of George L. Bakris (1952-2024).

George L. Bakris passed away on 15 June 2024 at the age of 72 years. This obituary aims at honouring his life and career by describing the stages in his personal and professional pathway, presenting some of his many remarkable accomplishments, and highlighting his exceptional clinical skills, mentorship, and friendship.

Physician and patient adherence in hypertension trials: a point of view on an important issue to resolve.

INTRODUCTION: Randomized controlled trials (RCTs) are important sources of evidence that strongly influence guidelines for patient management, including for elevated blood pressure in adults. AREAS COVERED: Critical questions regarding the interpretation of hypertension trial results have recently increased, especially for concerns over methodology. In particular, investigator adherence to the protocol and patient adherence to investigational drugs are often far from optimal. These issues may be ignored or underreported because physicians' behavior during trials is often not monitored and patients' medication adherence is neither measured adequately nor reported or analyzed in the final report or in the publication. This situation may lead to misinterpretations of study results and misevaluations of the safety and efficacy profile of new drugs. In this short review, the problem of measuring, reporting, and analyzing drug adherence in RCTs is discussed and illustrated with several examples in the field of hypertension. EXPERT OPINION: The main conclusion is that drug adherence should always be measured in clinical trials, possibly with more than one method. In addition, prespecified analyses of adherence data should be included in the statistical plan of all trials to improve their overall quality.

Optimizing drug adherence in hypertension: More than a mind game.

Poor drug adherence to prescribed drug treatments and lifestyle recommendations is a major determinant of poor blood pressure control reported around the World. Prevalence rates of antihypertensive medication nonadherence are highly variable depending on the studied population and may reach up to 40%. Remarkably, the phenomenon stays often undiagnosed and unaddressed mainly because physicians have limited tools to perform a reliable diagnosis. In this review oriented toward practicality, 5 principal aspects of nonadherence will be addressed with a special emphasis on psychological factors influencing adherence patterns, both from a patient's and physician's perspectives.

Rationale for the Inclusion of ß-Blockers Among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines.

We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension ß-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown.

A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

A new, deep learning-based method for the analysis of autopsy kidney samples used to study sex differences in glomerular density and size in a forensic population.

Artificial intelligence (AI) is increasingly used in forensic anthropology and genetics to identify the victim and the cause of death. The large autopsy samples from persons with traumatic causes of death but without comorbidities also offer possibilities to analyze normal histology with AI. We propose a new deep learning-based method to rapidly count glomerular number and measure glomerular density (GD) and volume in post-mortem kidney samples obtained in a forensic population. We assessed whether this new method detects glomerular differences between men and women without known kidney disease. Autopsies performed between 2009 and 2015 were analyzed if subjects were aged ≥ 18 years and had no known kidney disease, diabetes mellitus, or hypertension. A large biopsy was taken from each kidney, stained with hematoxylin and eosin, and scanned. An in-house developed deep learning-based algorithm counted the glomerular density (GD), number, and size. Out of 1165 forensic autopsies, 86 met all inclusion criteria (54 men). Mean (± SD) age was 43.5 ± 14.6; 786 ± 277 glomeruli were analyzed per individual. There was no significant difference in GD between men and women (2.18 ± 0.49 vs. 2.30 ± 0.57 glomeruli/mm2, p = 0.71); glomerular diameter, area, and volume also did not differ. GD correlated inversely with age, kidney weight, and glomerular area. Glomerular area and volume increased significantly with age. In this study, there were no sex differences in glomerular density or size. Considering the size of the kidney samples, the use of the presented deep learning method can help to analyze large renal autopsy biopsies and opens perspectives for the histological study of other organs.

Rationale of treatment recommendations in the 2023 ESH hypertension guidelines.

No abstract available.

Use of individual antihypertensive drug classes and combination therapies during the COVID-19 pandemic in Poland: a cross-sectional, nationwide study in the years 2019-2021.

INTRODUCTION: The 2018 European Society of Cardiology / European Society of Hypertension guidelines recommended the use of combination therapy, especially in the form of single­pill combinations (SPCs), for treatment of hypertension. OBJECTIVES: We assessed adherence to these recommendations after their publication and during the COVID­19 pandemic in Poland. PATIENTS AND METHODS: The frequencies of using individual antihypertensive drug classes and their combinations were analyzed for the years 2019, 2020, and 2021 in all patients who filled at least 1 prescription for an antihypertensive drug, using information from a database covering all prescriptions filled in Poland. RESULTS: In the years 2019, 2020, and 2021, a total of 10 328 341, 9 478 949, and 9 637 595 patients, respectively, fulfilled the inclusion criteria. There was a continuous decrease in the rate of patients meeting the criteria for coprescribing 2 or more antihypertensive drugs in the consecutive years (59.3%, 49%, 45.6%, respectively, in 2019, 2020, and 2021; P <0.001). In 2019, 2020, and 2021, a combination of renin­angiotensin system blockers, calcium channel blockers and / or diuretics was respectively used by 41.7%, 40.9%, and 42% of the patients taking 2 antihypertensive drugs (P <0.001), and by 15.2%, 17.2%, and 18.5% of the patients taking 3 antihypertensive drugs (P <0.001). There was an increase in the use of ß­blockers over the study period (62%, 62.8%, and 63.7%, respectively, in 2019, 2020, and 2021; P <0.001). Double SPCs were used by 28%, 28.7%, and 29.8% of the patients (P <0.001), and triple SPCs by 2.6%, 2.9%, and 3.4% of the patients (P <0.001), respectively, in 2019, 2020, and 2021. CONCLUSIONS: During the COVID­19 pandemic, a decrease in the frequency of combination treatments and an increase in the frequency of dual and triple SPC use were observed. Despite the slow increase in the frequency of prescribing the guideline­recommended drug combinations, their use remains suboptimal.

Medical Measures in Hypertensives Considered Resistant.

BACKGROUND: Patients with resistant hypertension are the group of hypertensive patients with the highest cardiovascular risk. METHODS: All rules and guidelines for treatment of hypertension should be followed strictly to obtain blood pressure (BP) control in resistant hypertension. The mainstay of treatment of hypertension, also for resistant hypertension, is pharmacological treatment, which should be tailored to each patient's specific phenotype. Therefore, it is pivotal to assess nonadherence to pharmacological treatment as this remains the most challenging problem to investigate and manage in the setting of resistant hypertension. RESULTS: Once adherence has been confirmed, patients must be thoroughly worked-up for secondary causes of hypertension. Until such possible specific causes have been clarified, the diagnosis is apparent treatment-resistant hypertension (TRH). Surprisingly few patients remain with true TRH when the various secondary causes and adherence problems have been detected and resolved. Refractory hypertension is a term used to characterize the treatment resistance in hypertensive patients using ≥5 antihypertensive drugs. All pressor mechanisms may then need blockage before their BPs are reasonably controlled. CONCLUSIONS: Patients with resistant hypertension need careful and sustained follow-up and review of their medications and dosages at each term since medication adherence is a very dynamic process.