bluuebunny/crossref_metadata_2025_split huggingface dataset:
INITIAL EGFR DECLINE AND LONG-TERM RENAL FUNCTION DURING BLOOD PRESSURE LOWERING THERAPY: A PATIENT LEVEL META-ANALYSIS OF THE SPRINT AND ACCORD-BP RANDOMIZED CONTROLLED TRIALS
Authors: Collard Didier , Brouwer Tom , Engberink Rik Olde , Zwinderman Aeilko , Vogt Liffert , Van Den Born Bert-Jan 
Published: April 2021

Objective:
Lowering blood pressure (BP) can lead to an initial decline in renal function. Guidelines recommend treatment adjustment when the estimated glomerular filtration rate (eGFR) decreases by more than 20%. However, there is ongoing debate how much can be accepted. We determined the relation between initial eGFR and BP decrease, and subsequent eGFR during follow-up in participants from ACCORD-BP and SPRINT.

Design and method:
Diabetic and non-diabetic patients at increased cardiovascular risk were randomized to intensive (<120) or standard (<140 mmHg) systolic BP-targets. We determined the relation between initial decline in mean arterial pressure (MAP) and eGFR. Subsequently, we stratified patients to BP-target and initial eGFR decrease and assessed the relation with annual eGFR-decline after 1 year.

Results:
In total 13266 patients, aged 66.2 year, 39% female and with mean eGFR 76.4 ml/min/1.73m2, with 41126 eGFR measurements were analyzed. The >20% stratum consisted of 669 (10%) in the intensive and 334 (5%) participants in the standard group. Up to 10 mmHg MAP decrease, there was no significant change in eGFR, with a lower bound of 26% based on 95% of the participants. Hereafter, there was a linear association between MAP and eGFR with an initial eGFR decrease of 3.4% (95%CI 2.9–3.9%) per 10 mmHg MAP decrease, with a lower eGFR bound increasing to 46% after 40 mmHg MAP decrease (figure 1). There was no significant difference in eGFR slope (p = 0.37) after stratification to treatment allocation and initial eGFR decline, with an annual eGFR decrease of 1.24 (95%CI 1.09–1.39), 1.20 (95%CI 0.97–1.43) and 1.14 (95%CI 0.77–1.50) in the 5, 5–20% and >20% stratum during intensive and 0.95 (95%CI 0.81–1.09), 1.23 (95%CI 0.97–1.49) and 1.17 (95%CI 0.65–1.69) ml/min/1.73m2/year during standard treatment.

Conclusions:
In patients at high cardiovascular risk, we found no association between initial eGFR and annual eGFR decline during BP-lowering treatment. The observed degree of initial eGFR decline was strongly dependent on the achieved BP decrease, suggesting that the achieved BP difference should be taking into account when interpreting the eGFR decline during antihypertensive therapy.
IN-HOSPITAL DIURETIC USE IS ASSOCIATED WITH WORSE OUTCOME IN PATIENTS WITH COVID-19
Authors: Pengo M. , Stefanini G , Pivato C , Soranna D , Zambra G , Zambon A , Torlasco C , Bilo G , Condorelli G , Parati G 
Published: April 2021

Objective:
Background: Hypertension is associated with increased risk of severe COVID-19 and increased mortality. The knowledge about the impact of blood pressure lowering medications on outcomes is still incomplete: whilst studies about renin-angiotensin-aldosterone system inhibitors did not show association with increased mortality, less is known about the impact of other antihypertensive classes. Diuretics, in particular, are frequently used in patients with hypertension thus we aimed to investigate the association between diuretics and mortality in a cohort of COVID-19 patients hospitalized in two referral centers in the Lombardy region (Istituto Auxologico Italiano and Humanitas Research Hospital).

Methods:
Data of confirmed COVID-19 patients, with information available about drug treatment and outcomes, were pooled together. Socio-demographic, clinical features, and medications pre and during hospitalization were retrieved, patients were classified according to the use of diuretics before and/or during hospitalization. The effect of diuretic use before and during hospitalization on death was estimated by means of a multiple Poisson regression model with robust variance and reported as Relative Risk (RR) and 95% confidence interval (95% CI).

Design and method:
From the pooled sample of 637 patients, a final sample of 502 patients with complete data was analyzed (mean age 67 years, 67% males, 54% patients with hypertension). Among hypertensive patients, 64% were not treated with diuretics either pre- or during hospitalization (Reference group), 15% had diuretic treatment only during hospitalization (Group A), 9% only pre-hospitalization (Group B) and 12% both pre- and during hospitalization (Group C).
After adjusting for confounders (age, sex, respiratory rate at admission, number of comorbidities, number of other drugs taken during hospitalization, orotracheal intubation), use of diuretics only during hospitalization was significantly associated with mortality (Figure 1).

Conclusion:
Our data show an association between diuretic use only during hospitalization and worse outcome in patients with COVID-19. Such association needs to be further investigated in order to possibly improve outcomes in patients admitted for COVID-19
Figure 1: Relative Risks and 95% confidence intervals of patients treated with diuretics only during hospitalization (Group A), only during pre-hospitalization (Group B) and during both pre- and hospitalization (Group C). The subgroup of patients not treated with diuretics neither pre- nor during hospitalization was taken as the reference group.
IMPACT OF COVID-19 LOCKDOWN ON VASCULAR STIFFNESS TRAJECTORIES IN FRANCE AND GERMANY
Authors: Bruno Rosa Maria , Pepin Jean-Louis , Empana Jean-Philippe , Yang Rui-Yi , Vercamer Vincent , Jouhaud Paul , Escorrou Pierre , Boutouyrie Pierre 
Published: April 2021

Objective:
Aim of the study is to investigate the impact of COVID-19 lockdown on trajectories of vascular stiffness among a large population of users of a connected bathroom scale, allowing reliable measurements of pulse wave velocity (PWV).

Design and method:
Pulse wave velocity (PWV) recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analyzed. We compared two demonstrative countries: France, who applied strict lockdown rules (n = 26,196) and Germany, who applied partial lockdown (n = 26,847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors (HBPM). Linear growth curve modeling and clustering trajectories analyses were performed.

Results:
During lockdown a significant reduction in PWV, weight, BP and physical activity was observed in the overall population. PWV reduction was significantly greater in France than in Germany, corresponding to an improvement of 5.2 months in vascular age.
In the French population three clusters of PWV trajectories were identified: decreasing (21.1%), stable (60.6%) and increasing PWV (18.2%). Decreasing and increasing PWV clusters had both higher PWV and vascular age at baseline compared to stable PWV cluster. Only decreasing PWV cluster showed a significant weight reduction (-400 g), whereas living alone was associated with increasing PWV.

Conclusions:
Total lockdown induced a reduction in vascular stiffness in a significant proportion of French smart scale users. Impact on long term behaviors and cardiovascular health remains to be established.
DIFFERENTIAL PREVALENCE AND ASSOCIATIONS OF CHRONIC KIDNEY DISEASE BY FIVE ESTIMATORS IN A SOUTH AFRICAN POPULATION-BASED STUDY
Authors: Peer Nasheeta , George Jaya , Lombard Carl , Steyn Krisela , Levitt Naomi , Kengne Andre-Pascal 
Published: April 2021

Objective:
The aim was to determine the prevalence, distribution, concordance and associations of chronic kidney disease (CKD) assessed by five glomerular filtration rate (GFR) formulae in urban black residents of Cape Town.

Design and method:
In this population-based cross-sectional study, stratified for age and gender, data collection included administered questionnaires, clinical measurements and biochemical analyses, including serum creatinine and cystatin C levels. GFR was based on the CKD Epidemiology Collaboration (CKD-EPI) equations (CKD-EPI creatinine (CKD-EPIcr), CKD-EPI cystatin C (CKD-EPIcys), CKD-EPI creatinine-cystatins (CKD-EPIcr-cys)), Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formula (CGF). GFR <60 mL/min/1.73 m2 defined CKD.

Results:
Mean estimated GFR, among 392 men and 700 women, was between 114.0 (CKD-EPIcr) and 135.4 mL/min/1.73 m2 (CGF) in men, and between 107.5 (CKD-EPIcr-cys) and 173.4 mL/min/1.73 m2 (CGF) in women. CKD prevalence ranged from 2.3% (CKD-EPIcr and MDRD) to 5.1% (CKD-EPIcys) in men and 1.6% (CGF) to 6.7% (CKD-EPIcr-cys) in women. Correlations between different estimates of GFR were positive and significant, and there were no significant differences between any two coefficients. The kappa statistic was high between CKD-EPIcr and MDRD (0.934), and CKD-EPIcys and CKD-EPIcr-cys (0.815), but fair-to-moderate between the other equations (0.353–0.565). In the basic regressions, older age and body mass index >30 kg/m2, but not gender, were significantly associated with CKD-EPIcr-defined CKD. In the presence of these three variables, but in separate models, hypertension, heart rate >90 beats/minute, diabetes and increasing low-density lipoprotein cholesterol were significant predictors of prevalent CKD by CKD-EPIcr and MDRD (except for diabetes). Metabolic syndrome, in the model with age and gender only, was significantly associated with CKD-EPIcr- and MDRD-defined CKD. No cardio-metabolic variable was associated with CKD determined by CKD-EPIcys, CKD-EPIcr-cys or CGF.

Conclusions:
The varying CKD prevalence estimates, on account of different GFR equations used, underscores the need to improve accuracy of CKD diagnoses. Moreover, considering the significant associations of cardio-metabolic diseases with CKD-EPIcr- and MDRD-defined CKD, screening for CKD should be incorporated into the routine assessment of high-risk patients such as those with hypertension or diabetes.
PREVALENCE OF TYPE 2 DIABETES MELLITUS AMONG KNOWN HYPERTENSIVES AT THE REGIONAL HOSPITAL BAMENDA, CAMEROON
Authors: Ngeh Etienne , Atabon Fidelis Ako 
Published: April 2021

Objective:
To evaluate the prevalence of type 2 diabetes mellitus (T2DM) and the associated risk factors among hypertensive patients with known and or unknown diabetes status. Secondly, to indirectly evaluate the impact of adopting diabetes screening in routine practice for all patients diagnosed with hypertension in the clinical settings.

Design and method:
This cross-sectional study was conducted on a sample of 150 hypertensive patients attending the diabetes/hypertension clinic of the Regional Hospital Bamenda. Blood pressure and glycemic blood measurements were assessed in all participants. A complete clinical history and physical exam were conducted and a data collection tool was completed. Prevalence of T2DM was obtained from fasting blood sugar, health reports and diabetes medications. Data was entered and analyzed descriptively in the form of frequency and percentage tables with the aid of SPSS 23.0 software.

Results:
The prevalence of T2DM among hypertensive patients in the was 44.7% (n = 67/150) with gender prevalence rates of 20.6% and 24% among males and females respectively in the studied sample (P = 0.002). T2DM prevalence increases with age, body mass index and duration of being hypertensive. Base on age, the prevalence increases from 9% in those 30–39 years and peak at 31.3% in those over 70 years. T2DM prevalence were 25.3%, 22.4%, 23.4%, and 28.4%, for BMI<18.5 kg/m2, 18.5–24.9 kg/m2, 25.0–29.9 kg/m2, and >30 kg/m2. The prevalence of unrecognized DM was 32.8% in hypertensive patients. Also, more than half of the subjects (56.7%) suffering from DM (38 out of 67 persons) had poorly controlled hypertension, contrasted with only about one third 27.7% (23 out of 83) of the non-diabetic participants with poorly controlled hypertension.

Conclusions:
The prevalence of DM in patients with hypertension was more than 8times that of the general population. The prevalence of unrecognized DM was equally very high in hypertensive patients. These findings demonstrate that hypertensive patients should regularly submit to T2DM screening for timely DM diagnosis. Therefore, major recommendations would be to adopt strict strategies to improve diabetes screening among hypertensive patients to minimize both the health and economic burdens associated with undiagnosed T2DM.
COMBINATION THERAPY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Gaman Mihnea-Alexandr , Dobrica Elena Codruta , Cozma Matei Alexandru , Diaconu Camelia Cristina 
Published: April 2021

Objective:
According to practice guidelines, heart failure with reduced ejection fraction (HFrEF) patients should receive combination therapy. Diuretics, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), beta-blockers (BB) and digoxin are employed in HFrEF treatment. In patients with type 2 diabetes mellitus (T2DM) and HFrEF, clinical guidelines are not always respected, since many physicians fear the adverse effects of ACEI (hyperkalemia) and BB (altered response to hypoglycemia). We aimed to investigate the use of combination therapy in patients with HFrEF and T2DM.

Design and method:
Retrospective, observational study on patients referred between January-June 2017 to the Internal Medicine Department of an emergency hospital in Romania. Patients were identified by a database search of diagnostic codes of discharge diagnoses. The patients’ characteristics/medical prescriptions were retrieved from their medical records.

Results:
The study group (70.81 ± 9.49 years, range 38–92 years) included 100 patients with HFrEF and T2DM: 47 women (47.00%), 53 men (53.00%); NYHA functional classification: 63 (63.00%) NYHA class II, 18 (18.00%) NYHA class III, 19 (19.00%) NYHA class IV. Patients were prescribed BB in 86 cases (86.00%), diuretics in 70 cases (70.00%), ACEI in 50 cases(50.00%), digoxin in 25 cases (25.00%) and ARB in 19 cases (19.00%). 19 patients (19%) received a combination of beta-blocker+diuretic+ACEI, 15 patients (15%) received a combination of beta-blocker+diuretic+ACEI+digoxin, 11 patients (11%) received a combination of beta-blocker+diuretic and 10 patients (10%) received a beta-blocker alone (Table 1).34 (34%) patients received a combination of 2 drugs, 27 (27%) patients received a combination of 4 drugs, 23 (23%) patients received a combination of 3 drugs and 16 patients (16%) were prescribed monotherapy. Combination therapy included a BB in 76 cases, an ACEI in 49 cases and BB+ACEI in 43 cases.

Conclusions:
In our study, almost two-thirds of patients with HFrEF and T2DM received combination therapy. The most prescribed combination was the association of a beta-blocker, a diuretic and anangiotensin-converting enzyme inhibitor. More than two-thirds of the patients with HFrEF and T2DM received a beta-blocker and a half received an angiotensin-converting enzyme inhibitor (in monotherapy or as part of the combination therapy).
CHOLECALCIFEROL SUPPLEMENTATION AMELIORATES IMMUNE DYSFUNCTION IN OBESE HYPERTENSIVE PATIENTS
Authors: Santos Catarina , Monteiro Andreia , Esgalhado Andre , Fonseca Mafalda , Castelo-Branco Miguel 
Published: April 2021

Objective:
Reduction of T regulatory cells (Treg) and upregulation of T helper 17 cells (Th17) contributes to obesity-associated hypertension. Since vitamin D is a modulator of the immune system, we hypothesized that supplementation with cholecalciferol in hypertensive patients may lead to a shift to a more anti-inflammatory immune status.

Design and method:
a 24-week randomized, open, parallel groups clinical trial including 36 patients with hypertension and overweight or obesity was conducted to evaluate the effects of cholecalciferol in peripheral Treg and Th17 cells. Patients were randomized to receive cholecalciferol according serum vitamin D (VD) levels plus usual therapy or usual therapy alone. The levels of Treg and Th17 on week 0 and 24 were obtained as well as body mass index (BMI), waist circumference, serum free VD, lipids, HbA1c, T helper 1 (Th1) cells and monocytes.

Results:
18 men, average age 57.1 ± 5.5 years, BMI 34.5 ± 5.1 Kg/m2 and waist circumference 113.8 ± 10.7 cm. Sixteen patients (44.4%) had grade 1 obesity, seven (19.4%) grade 2 and six (1.6%) grade 3 obesity. The remaining had 7 had 25 < BMI < 30 Kg/m2. All patients were on antihypertensive drugs and mean value of vitamin D at the beginning of the trial was 15.7 ± 5.1 ng/mL. After supplementation serum VD levels rose to 26.9 ± 5.6 ng/mL (p = 0.000) and serum free VD levels from 5.2 ± 1.2 to 6.2 ± 3.3 ng/mL (p = 0.044). At 24 weeks the average ± SD values of the different cells between active and control groups were: Tregs 6.1 ± 1.5 and 6.8 ± 1.8; p = 0.226, respectively, Th17 cells 1.8 ± 0.8 and 2.7 ± 1.2; p = 0.017, Th1 cells 35.4 ± 18.1 and 30.3 ± 9.2; p = 0.299 and monocytes 5.7 ± 1.3 and 6.4 ± 2; p = 0.215.

Conclusions:
in overweight and obese hypertensive patients supplementation with cholecalciferol at regular doses reduces the levels of Th17 cells. Although statistically non-significant a decrease in monocytes was also observed. The reduction of Treg was unexpected, the significance of which should be clarified in future studies.
ANGIOTENSIN II INCREASES FORMATION OF NEUTROPHIL EXTRACELLULAR TRAPS: ROLE IN HYPERTENSION AND DIABETES
Authors: Landry Chloé , Thibodeau Jean -François , Gutsol Alexey , Kennedy Christopher Rj , Burger Dylan 
Published: April 2021

Objective:
Endothelial dysfunction plays a central mechanistic role in the pathogenesis of hypertension and diabetes. However, the molecular determinants of endothelial dysfunction are not fully understood. Peptidylarginine deiminases (PADs) irreversibly convert arginine to citrulline in protein, generating neoantigens that are unrecognizable to the immune system. PAD4, an isoform predominantly expressed in neutrophils is upregulated in autoimmune and coronary artery disease. PAD4 activation, in turn, promotes vascular injury through the formation of neutrophil extracellular traps (NETs), networks of chromatin and protein-containing extracellular fibres released to fight infection. Whether PAD4 activity is altered in hypertension and diabetes and whether this contributes to disease pathogenesis is not known. The objective of the present study was to examine the effect of angiotensin II on formation of neutrophil extracellular traps in vitro and in an animal model of hypertension and diabetes.

Design and method:
Neutrophil-like cells were generated from differentiation of the HL-60 cell line and then treated with angiotensin II (10-7 M) for 24 hours. NET formation was assessed by Western blot analysis of citrullinated histone H3 (a primary component of NETs). We further assessed NET formation in mice expressing human renin under the control of the transthyretin promoter (TTRhRen) intercrossed with OVE26 diabetic mice [i.e. hypertensive-diabetic, HD mice] and compared with wild-type (WT) FVBN/J mice. We examined levels of citrullinated histone H3, neutrophil elastase, and PAD4 expression in the kidney of HD and WT mice by immunohistochemistry.

Results:
Treatment of neutrophil-like cells with angiotensin-II increased levels of citrullinated histone H3 by ∼2-fold. Similarly, in HD mice we observed a significant increase in citrullinated histone H3 (P < 0.0001), in neutrophil elastase (P < 0.0001), and in PAD4 protein levels (P < 0.0001) compared with WT. Increased PAD4 activity was associated with the presence of albuminuria, renal interstitial fibrosis and reduced glomerular filtration rate.

Conclusions:
Taken together these data suggest that angiotensin II induces NET formation leading to renal accumulation in hypertension and diabetes. PAD4 may therefore play a role in target organ injury in hypertension and diabetes.
CLINICAL IMPLICATION OF ASSESSING QUANTITATIVE PLASMA CONCENTRATIONS OF ANTIHYPERTENSIVE DRUGS
Authors: Peeters-Kalicharan Laura , Feyz Lida , Daemen Joost , Van Gelder Teun , Koch Birgit , Versmissen Jorie 
Published: April 2021

Objective:
Dried blood spot (DBS) analysis is a novel analytical method for therapeutic drug monitoring (TDM) to identify non-adherence to antihypertensive drugs. This study was conducted to evaluate the clinical applicability of measuring drug concentrations of eight antihypertensive drugs, using DBS and venipuncture. Furthermore, this study aimed to provide more insight into the between-patient variability in drug concentrations.

Design and method:
In a previous study a TDM method for eight antihypertensive drugs and four of their metabolites (table 1) was validated in patients assumed to be adherent. The present data was retrieved from this validation study. False negative values from DBS compared to a venipuncture were determined to assess drug adherence. A Generalized Estimating Equation (GEE) was used to assess the influence of covariates including gender, dose, age, weight, and the time interval between drug intake and sampling on the Cplasma (drug concentration in plasma).

Results:
A total of 135 patients (mean age of 59 ± 12 years, 59% male) were included. The number of samples per drug ranged from 38 (enalaprilate) to 85 (hydrochlorothiazide). When drug concentrations from DBS and plasma were compared, no real false negative values were found. A high variability in Cplasma between patients was observed, especially at peak concentrations with a fold change reaching from 2.3 (canrenone) to 35.2 (losartan-carboxylic acid) (table 1). The time of intake was significantly related to the height of the Cplasma in 7 of the 8 measured drugs with a p-value < 0.05 with the exception of hydrochlorothiazide, but the influence of dose, weight, age and sex on drug levels differed largely between the measured drugs.

Conclusions:
DBS is a reliable and convenient method to assess non-adherence to antihypertensive drugs in clinical practice. The Cplasma of the eight antihypertensive drugs in this study show a large inter-individual difference and therefore low plasma concentrations do not necessarily mean non-adherence. Non-adherence can only be confirmed if drug levels are undetectable, i.e. values below the lower limit of detection.