bluuebunny/crossref_metadata_2025 huggingface dataset:
THROMBOXANE-DEPENDENT CORONARY VASOCONSTRICTION IN OBESE MICE: ROLE OF PEROXYNITRITE
Authors: Villa Elisa , Rios Amelia , Escalante Bruno
Published: June 2022

Objective:

Obesity leads to chronic oxidative stress promoting the development of cardiovascular diseases including endothelial dysfunction, which might occur through the cyclooxygenase (COX) pathway. This study aimed to investigate the role of peroxynitrite in the generation of COX-derived products and its role in coronary vascular responses.

Design and method:

We evaluated arachidonic acid (AA)-dependent coronary vascular responses in isolated hearts from control and obese C57BL/6 mice and explored COX metabolism using the COX-2 inhibitor indomethacin and 1-benzylimidazole, inhibitor of thromboxane synthase (TXS). COX, TXS, and TXA2 receptor (TP) protein expression was assessed in heart homogenates. The release of TXA2 in the coronary circulation was also evaluated. In addition, the possible involvement of peroxynitrite on increased coronary response was explored by detecting peroxynitrite by coumarin boronic acid (CBA) and 3-nitrotyrosine protein expression. Alterations in TXS, and TP receptor protein expression were also evaluated in heart homogenates from obese mice treated with the peroxynitrite scavenger FeTMPyP.

Results:

Arachidonic acid (AA) dependent coronary vasoconstriction in isolated hearts, increased from 31.06 ± 2.67 mmHg in control mice to 88.99 ± 6.09 mmHg in obese mice. Both, indomethacin and 1-benzylimidazole reduced the vasoconstriction response in control and obese mice. TXA2 released during AA-induced vasoconstriction phase was increased in heart perfusates from 76.1 ± 18.42 pg/mL in control mice to 203.6 ± 29.8 pg/mL in obese mice. COX- 2, TXS and TP receptor protein expression was increased in hearts from obese mice (1.96 ± 0.25, 0.70 ± 0.07, 1.22 ± 0.19 arbitrary units, respectively) compared with control mice (0.17 ± 0.02; 0.06 ± 0.02; and 0.29 ± 0.06 arbitrary units, respectively). Moreover, nitrotyrosine and peroxynitrite levels were higher in obese mice, compared with control mice. Increase in coronary vasoconstriction, TXA2 release as well as protein expression was prevented with FeTMPyP treatment in obese mice.

Conclusions:

Peroxynitrite-dependent induction of COX-2 and TXS protein expression in heart tissue from obese mice may lead to increased TXA2 coronary circulation, thereby increasing coronary vasoconstriction.
ENDOTHELIUM-SPECIFIC DEFICIENCY OF POLYCYSTIN-1 PROMOTES HYPERTENSION AND CARDIOVASCULAR DISORDERS
Authors: Guerrot Dominique , Hamzaoui Mouad , Groussard Deborah , Nezam Dorian , Mulder Paul , Richard Vincent , Bellien Jeremy
Published: June 2022

Objective:

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2, encoding polycystins 1 and 2. In ADPKD, hypertension and cardiovascular (CV) disorders are highly prevalent but their mechanisms are partially understood. The objective of this study was to determine whether hypertension and the CV disorders of ADPKD are a consequence of the endothelial deficiency in the polycystin complex, rather than to the kidney disease, as is currently believed.

Design and method:

Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells (Cdh5-CreERT2;Pkd1fl/fl) to specifically determine the role of endothelial polycystin-1 in ADPKD. We nalysed the endothelial phenotype associated with Pkd1 deficiency, invasive and non-invasive blood pressure, vascular function on isolated vessels, and echocardiography. The impact on the development of a model of aorto-cava arterio-venous fistula and on the CV consequences of superimposed chronic kidney disease were nalysed to further establish the clinical relevance of our results.

Results:

As expected, transgenic mice presented normal kidney structure and function. Endothelial deletion of Pkd1 induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arterio-venous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodelling and heart hypertrophy.

Conclusions:

Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension independently of kidney cysts and of impaired kidney function, impairs arterio-venous fistula development and potentiates the cardiovascular alterations associated with chronic kidney disease. It establishes the endothelium as a significant contributor to cardiovascular disease in ADPKD.
DISENTANGLING THE SHARED HERITABILITY OF THE PREDISPOSITION TO HYPERTENSION AND TYPE 2 DIABETES
Authors: Timasheva Yanina , Balkhiyarova Zhanna , Prokopenko Inga
Published: June 2022

Objective:

Genome-wide association studies (GWAS) identified over 900 genetic loci for blood pressure traits and over 200 for type 2 diabetes (T2D). Hypertension and T2D often manifest in the shared setting of metabolic syndrome, which also includes obesity, hyperlipidemia, and increased coagulability. We aimed to dissect shared genetic factors contributing to the comorbidity of these conditions using multi-phenotype approach.

Design and method:

Using GWAS summary statistics, we defined 1,855 single nucleotide variants (SNVs) associated with 17 endophenotypes related to blood pressure, T2D, and glycaemic traits. We identified 242 T2D association signals represented by 561 T2D/glycaemic SNVs overlapping with 1189 SNVs associated with blood pressure trats and located within 100 kb distance. Using hierarchical clustering, we defined groups of shared loci affecting circadian rhythm (MTNR1B), cell-mediated autoimmunity (CDKAL1 and G6PC2), insulin signalling and cell metabolism (KCNJ11), cell cycle regulation and apoptosis (BCL2), inflammation, calcium ignalling and regulation of eating behavior (NUCB2).

Results:

We identified 35 signals associated with two or more cardiometabolic phenotypes, including rs560887 in G6PC2 gene related to higher fasting glucose levels pulse pressure (PP); rs7756992 in CDKAL1 leading to elevated systolic blood pressure (SBP), increased T2D risk, but lower body mass index (BMI); rs635634 in ABO influencing many metabolic endophenotypes, most notably leading to increased risk of T2D and stroke; rs5219 in KCNJ11 increasing risk of T2D, related to elevated SBP and PP; and rs12454712 in BCL2 related to higher SBP and abdominal obesity, and to lower T2D susceptibility and lower BMI.

Using functional enrichment analysis, we identified pathways significantly associated with hypertension, T2D, and glycaemic traits. Top associated pathways included detection of stimulus involved in sensory perception (GO:0050906), sensory perception of chemical stimulus (GO:0007606), detection of chemical stimulus involved in sensory perception (GO:0050907), sensory perception of smell (GO:0007608), detection of chemical stimulus involved in sensory perception of smell (GO:0050911), and detection of chemical stimulus (GO:0009593).

Conclusions:

Our results highlight the shared pathways involved in blood pressure and glucose metabolism regulation and the development of T2D, suggesting common biological mechanisms.

The study was supported by the megagrant from the Government of Russian Federation No. 075-15-2021-595
ASSESSING THE IMPACT OF IMMUNOSUPPRESSIVE THERAPIES ON INCIDENCE OF HYPERTENSION IN PATIENTS WITH RHEUMATOID ARTHRITIS AND OTHER AUTOIMMUNE DISEASES: A SYSTEMATIC REVIEW
Authors: Alosaimi Hani , Maffia Pasquale , Padmanabhan Sandosh , Guzik Tomasz
Published: June 2022

Objective:

To compare the effects of different classes of immunosuppressant therapies and anti-cytokine therapies on risk of hypertension in patients with Rheumatoid Arthritis and other Autoimmune diseases.

Design and method:

Meta-analysis and systematic reviews of randomised-control trials (RCTs) were identified using relevant electronic databases to assess current approaches towards the analysis of the effects of anti-interleukin-6, anti-interleukin-17, and methotrexate therapies in adult with regard to hypertension on all available RCTs.

Results:

In the studies where anti-IL6 was compared with placebos, the pooled estimates from the meta-In the studies where anti-IL6 was compared with placebos, the pooled estimates from the meta-analysis showed no statistically significant difference in the risk of hypertension between anti-IL6 and a placebo (RR = 1.2, 95% CI 0.82; 1.73, P = 0.35)). when anti-IL6 was compared to other active drugs, no statistically significant difference was observed in the risk of hypertension between groups (RR = 1.48, 95% CI 0.97; 2.25, P = 0.07)

In the anti-IL17 studies, the pooled estimates from the meta-analysis showed that the risk of hypertension with anti-IL17 and the placebo drugs was also not significantly different (RR = 1.23, 95% CI 0.92, 1.65, P = 0.16)

Where methotrexate was compared to a placebo, there was no significant difference in the risk of hypertension (RR = 1.09, 95% CI 0.65; 1.84, P = 0.73), and only low and non-statistically significant heterogeneity was observed between such studies (I2 = 42%, P = 0.14). However, when methotrexate was compared to other active drugs, a statistically significant difference was observed in terms of the risk of hypertension between groups (RR = 0.45, 95% CI 0.34; 0.61, P < 0.001) in favour of methotrexate.

Conclusions:

Anti-Interlukin-6 agents and anti-Interlukin-17 agents do not seem to affect the risk of occurrence of hypertension when compared to either placebo or other active drugs, while methotrexate appears to reduce the risk of high blood pressure in comparison other anti-inflammatory treatments.
THE EFFECT OF BIOFEEDBACK ON HYPERTENSION AND DIABETES: PRELIMINARY RESULTS FROM A SYSTEMATIC REVIEW
Authors: Jenkins S. , Gupta P. , Khunti K. , Cross A.
Published: June 2022

Objective:

Biofeedback is a mind-body intervention that uses a device to provide feedback on physiological responses, such as heart rate variability. Through training and practice, participants can learn to exert an element of control over autonomic responses. There is a wealth of research on biofeedback in a range of health conditions, this review focuses on hypertension and diabetes.

Methods:

The systematic review aimed to evaluate the effectiveness of biofeedback on systolic and diastolic blood pressure and psychological wellbeing in patients with hypertension and/or diabetes. The review was preregistered on PROSPERO and followed the PICO search strategy. The following databases were searched: MEDLINE, PsycINFO, CINHAL, PubMed, Embase and Cochrane Central Register of Controlled Trials. Selection criteria included randomised control trials, diagnosis of hypertension/diabetes, inclusion of pre and post intervention measurements and recordings of blood pressure, Hba1c or blood glucose.

Results:

A total of 1189 papers were retrieved, 32 papers met the inclusion criteria. Sample sizes ranged from 10 to 301 with a total of 1425 participants, 48% female and mean age 50.16 (±8.16) and 48.71 (±9.19) in experimental and control group respectively. Of the 32 papers, 28 investigated hypertension and 4 papers looked at diabetes. Of the 28 hypertension studies, 13 showed significant findings in favour of biofeedback. The analysis excluded 11 papers due to incomplete data. Biofeedback was significantly associated with reduced systolic blood pressure (-3.62 mmHg, [-6.33, -0.90], p value < 0.0001; Figure 1) and diastolic blood pressure (-4.15 mmHg, [-6.04, -2.26], p value < 0.0001). Biofeedback modalities included galvanic skin response, heart rate variability, thermal, electromyography, blood pressure and heart rate. Intervention length ranged from 10 days to 4 months, and follow up ranged from 1 week to 12 months. Of the 4 diabetes papers, 2 showed significant findings in favour of biofeedback. A total of 7 papers recorded psychological wellbeing measurements (i.e. depression and anxiety). However, only two reported incorporation of psychological/wellbeing targeted intervention components.

Conclusions:

The preliminary findings highlight the high heterogeneity between existing trials in biofeedback modality, intervention length, follow up and details reported. The results show biofeedback had a significant effect on systolic and diastolic blood pressure. There is limited research on biofeedback and diabetes. This systematic review will inform the protocol development of a biofeedback feasibility trial in patients with hypertension and anxiety. A key finding is the limited use of psychological wellbeing based intervention components, despite study measurements and correlating hypotheses. This is an important element we will integrate within our biofeedback intervention.
CEREBRAL OXYGENATION DURING EXERCISE ACROSS DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE
Authors: Theodorakopoulou Marieta , Zafeiridis Andreas , Dipla Konstantina , Faitatzidou Danai , Koutlas Aggelos , Alexandrou Maria-Eleni , Polychronidou Georgia , Chalkidis Georgios , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2022

Objective:

Cognitive impairment and reduced exercise tolerance are common in patients with chronic kidney disease (CKD), in part due to reduced brain function. Proper brain function relies on sufficient blood flow and oxygen supply by the cerebral vasculature. A reduction in cerebral oxygenation of more than 10% may deteriorate brain function and influence the decision to continue exercise. This study aims to examine the cerebral oxygenation and blood volume during a mild physical stress as an index of brain activation in patients at different stages of CKD and controls without CKD.

Design and method:

This is a preliminary analysis of an observational study enrolling patients with CKD stage 2–4 (matched for age and sex within the different stages) and controls without CKD. All participants underwent a 3-min intermittent handgrip exercise (HG) at 35% of their maximal voluntary contraction. Changes in prefrontal oxygenation (oxyhemoglobin-O2Hb) and deoxyhemoglobin-HHb) and total blood volume (total hemoglobin-tHb) were continuously recorded during HG-exercise by near-infrared spectroscopy (NIRS).

Results:

A total of 59 participants are included in this preliminary analyses (n = 11 controls, n = 15 stage 2 CKD, n = 18 stage 3 CKD and n = 15 stage 4 CKD patients). During HG-exercise, O2Hb significantly increased (p < 0.001) and HHb remained relatively unchanged in all groups compared to pre-exercise values. However, this O2Hb increase was progressively lower with advancing CKD Stages (controls: 2,58 ± 1,43 stage 2: 1,51 ± 1,31 stage 3: 1,29 ± 0,97 stage 4: 0,95 ± 0,92, p = 0.006) (Figure). During HG, tHb (an index of microvascular blood volume) increased significantly in controls, stage 2, and 3 CKD patients (p < 0.05) but not in stage 4 CKD patients (p = 0.100). As before this tHb increase was progressively lower with advancing CKD stages (p = 0.030). Controlling for age differences between groups did not alter the above observations.

Conclusions:

Brain activation/response during a mild physical task appears to decrease with advancing CKD as suggested by the smaller rise in cerebral oxygenation and blood volume. This may contribute both impaired cognitive function and reduced exercise tolerance with advancing CKD.
AUGMENTED PROSTAGLANDIN E2 SIGNALING CAUSES PODOCYTE DAMAGE AND ALBUMINURIA-LIKE PHENOTYPE IN A ZEBRAFISH DISEASE MODEL OF GLOMERULAR HYPERFILTRATION
Authors: Kourpa Aikaterini , Mangelsen Eva , Bolbrinker Juliane , Schulz Angela Martina , Rothe Michael , Kreutz Reinhold , Panakova Daniela
Published: June 2022

Objective:

Prostaglandins (PGs) are important active lipids synthesized from arachidonic acid with the participation of cyclooxygenases (COXs) and specific prostaglandin synthases. Prostaglandin E2 (PGE2), the most abundant prostaglandin in the kidney, plays a crucial role in renal homeostasis and the pathogenesis of chronic kidney diseases. Augmented PGE2 signaling that may occur in podocytes during increased fluid flow shear stress as observed during glomerular hyperfiltration, results in glomerular filtration barrier (GFB) permeability defects, ultimately leading to albuminuria. The cellular mechanisms that precede podocyte damage are not fully resolved. Here, we deploy a zebrafish model to study the role of PGE2 signaling in glomerulus and its effects on GFB integrity and function.

Design and method:

To model the outcome of increased PGE2 signaling in podocytes, zebrafish embryos were exposed to 16,16-dimethyl PGE2 (dmPGE2, 125 μM) or DMSO vehicle after the complete formation of GFB, i.e. from 72 hours post fertilization (hpf) to 96 hpf. To probe the PGE2 pathway, embryos were treated with the selective PGE2 receptor (EP) type 2 (EP2) and EP4 antagonists PF04418948 and ONO-AE3-208 or the COX inhibitor indomethacin. Zebrafish embryos of Tg(fabp10a:gc-EGFP) were used to evaluate the functional role of GFB integrity and albuminuria phenotype, while embryos of Tg(wt1b:EGFP) in combination with angiography using BSA-conjugated AlexaFluor555 allowed glomerular morphological analysis. In vivo stereomicroscopy, confocal laser scanning microscopy, and electron microscopy were used to analyze GFB at cellular as well as ultrastructural level. Statistical analysis was performed using GraphPad software.

Results:

Stimulation with dmPGE2 causes an albuminuria-like phenotype in zebrafish embryos, mimicking the suggested PGE2 effects during glomerular hyperfiltration in rodent models. The albuminuria-like phenotype could be significantly suppressed by the combined and separate inhibition of the EP2 and EP4 receptors as well as by indomethacin treatment. Although the glomerular ultrastructure appeared unaffected, high-resolution confocal imaging showed impaired podocyte intercalation around the glomerular capillaries after dmPGE2 exposure. Importantly, these specific podocyte defects were restored after blockage of EP2 and EP4.

Conclusions:

Our results support a role of augmented PGE2/EP2/EP4 signaling in the setting of glomerular hyperfiltration and albuminuria.
AWARENESS AND LIMITATIONS OF MEASURING VASCULAR AGEING IN EVERYDAY PRACTICE. A PILOT QUALITATIVE ANALYSIS FROM VASCAGENET(CA18216)
Authors: Triantafyllou Areti , Elia Stavria-Artemis , Park Chloe , Climie Rachel , Mayer Christopher C. , Weber Thomas , Panayiotou Andrie G.
Published: June 2022

Objective:

Despite current evidence demonstrating the important role of Vascular ageing (VA) in cardiovascular risk assessment, its awareness and mostly implementation in everyday practice still lags significantly. To effectively assess the need for future target strategies for health providers, a qualitative questionnaire was developed. The aim of this analysis was to identify perceptions and factors associated with omitting VA assessment in a group of clinicians and researchers.

Design and method:

An online qualitative questionnaire based on intentionally left open-ended key questions identified by a Network for Research in Vascular Ageing (VascAgeNet) COST Action(CA18216) expert working group was developed and distributed to participants working in the field of VA, in order to globally assess knowledge and perceptions. Importance of VA was evaluated on a scale 0(least important)-5(very important).

Results:

Out of the 127 responses, 104 questionnaires were complete. The mean age of participants was 42.5 ± 10.5 years, 60.6% male. 43.3% were clinicians (mostly cardiologists, internists, and endocrinologists) and 56.7% were other scientists (mostly computer scientists and physiologists). Although participants were aware of the role of VA and scored median 5/5 (very important) on the evaluation scale, only 53.8% measured it in the research setting and only 16.3% in everyday clinical practice. Amongst the most frequently identified limiting factors regarding clinical setting were time(31.5%), lack of reimbursement of tests(22.3%), cost of equipment(16.7%), guidelines(13%),validation data(5.6%) and devices(9.4%). 15.6% considered that there was no clinical benefit. Participants who measured VA in clinical practice considered VA significantly more important than those who didn’t measure it (0% vs.3.3%(1–2), 17.6% vs.39.3%(3–4), 82.4% vs.57.4%(5), respectively, p = 0.029). Similar were the results in research setting (1.8% vs.4.5%(1–2), 28.6% vs. 50.0%(3–4), 69.6% vs. 45.5%(5), respectively, p = 0.053). Table 1 presents the main results, according to the participants’ status.

Conclusions:

Although aware of the importance of VA in cardiovascular risk assessment, participants are still unable to implement it in their clinical practice. Our results identify for the first time some important factors, which informed the construction of a quantitative questionnaire for confirmation in larger populations, and could constitute a small startup for future experts’ recommendations.
EXERCISE CAPACITY AND MORTALITY RISK IN A WIDE AGE SPECTRUM COHORT OF 750,302 VETERANS
Authors: Pittaras Andreas , Faselis Charles , Doumas Michael , Grassos Haralampos , Stavropoulos Konstantinos , Imprialos Konstantinos , Papavasiliou Maria , Manolis Athanasios , Myers Jonathan , Kokkinos Peter
Published: June 2022

Objective:

Most studies that have evaluated the association between exercise capacity and the risk of all-cause mortality have focused on middle-aged Caucasian populations. We assessed mortality risk associated with fitness in male and females across a wide spectrum of age (30–95 years) and ethnicities.

Design and method:

In this retrospective cohort study, we included male and female Veterans who completed an exercise treadmill test (ETT) between 1999–2020. We assigned participants to one of ten age-specific fitness categories based on peak metabolic equivalents (METs) achieved during the ETT. The primary endpoint was all-cause mortality adjusted for age, body-mass index, ethnic origin, sex, cardiovascular disease, cardiovascular risk factors and medications. We assessed mortality from Veterans Affairs records up to Dec 31, 2020. We compared groups with Cox proportional hazard model.

Results:

We assessed 750,302 Veterans, ages 30–95 years (mean 61.3 years, SD 9.8 years). During a median follow-up of 9.8 years (IQR 5.6–14.0), 164,288 died with an average yearly mortality rate of 22 deaths per1,000 person-years. The exercise capacity-mortality risk association was independent, inverse, and graded for all ages, ethnicities, and men and women. Compared to the least fit group for each age decile, mortality risk was 50% lower at peak exercise capacities of approximately 10.0 METs for those 30–49 years, 8.0 METs for septuagenarians, and 7.0 METs for octogenarians. The lowest mortality risk was observed at approximately 14.0 METs with no additional decline or increase in risk beyond this level. Being unfit, defined having exercise capacity below the median (<8.5 METs), was associated with > 2 times higher mortality risk compared to fit (>8.5 METs), and was higher than the risk of the traditional cardiac risk factors examined.

Conclusions:

Higher Exercise Capacity is independently associated with lower mortality risk for all ages, ethnicities, and gender. An exercise capacity < 8.5 METs carried a greater risk than that of the traditional cardiac risk factors. Approximately 50% lower risk was noted in all age categories, commensurate to an exercise capacity achievable by most individuals within a given age category.
IMPACT OF BODY FAT DISTRIBUTION, ADIPOCYTOKINES AND VARIABILITY IN ASSOCIATED GENES ON KIDNEY TRANSPLANT OUTCOMES
Authors: Perez Roberto Nicolas Robles , Pino Guadalupe Garcia , Luna Enrique , Tormo Maria Angeles , Mota-Zamorano Sonia , Gonzalez Luz M. , Gervasini Guillermo
Published: June 2022

Objective:

Adiposity distribution contributes to a number of pathologies. We aimed to assess whether this distribution was associated with clinical outcomes and to identify its relationship with leptin and adiponectin gene variants and plasma concentrations in renal transplant recipients (RTR).

Design and method:

Anthropometric parameters were measured in 236 RTR by bioelectrical impedance analysis, allograft function and post-transplant complications were retrieved from records. Blood samples were drawn to measure plasma leptin/adiponectin levels and to seek for polymorphisms in the leptin receptor (LEPR) and adiponectin (ADIPOQ) genes. Logistic regression models were applied to identify associations.

Results:

The waist-to-height ratio (WHr) displayed a significant association with delayed graft function (DGF), acute rejection (AR) and post-transplant diabetes mellitus, with OR values of 2.04 (1.02–4.08) p = 0.045; 3.08 (1.22–7.79) p = 0.017 and 2.79 (1.16–6.74) p = 0.022, respectively. Waist circumference was linked to DGF [OR = 1.03 (1.01 – 1.053), p = 0.025] and AR [OR = 1.041 (1.01 – 1.073), p = 0.009]. Leptin levels were significantly higher in patients who experienced AR [19.91 ± 23.72 vs. 11.22 ± 16.42 ng/ml; OR = 1.021 (1.01–1.04), p = 0.017]. The ADIPOQ rs1501299TT genotype showed a significant association with higher WHr (0.63 ± 0.11 vs. 0.59 ± 0.87 for GG/GT genotypes; p = 0.015) and WC values (102.3 ± 14.12 vs. 96.38 ± 14.65 for GG/GT genotypes; p = 0.021).

Conclusions:

We have shown that WC, and especially WHr, are associated with adverse outcomes in renal transplant and hence may be useful parameters in RTR monitoring. In turn, these anthropometric parameters were affected by variability in the ADIPOQ gene, suggesting this polymorphism could be a useful marker of transplanted patients at risk.
MATERNAL OBESITY AND GESTATIONAL DIABETES ARE ASSOCIATED WITH DNA METHYLATION ALTERATIONS IN THE OFFSPRING THROUGHOUT THE FIRST YEAR OF LIFE
Authors: Alba-Linares Juan José , Fernández-Pérez Raúl , Ponce-Zanon Francisco , García-Carbonell Nuria , Gomez-Zafra Rafael , Fernández-Fraga Mario , Lurbe-Ferrer Empar
Published: June 2022

Objective:

Obesity is a chronic metabolic disease of increasing prevalence and health importance in modern societies, which represents an added risk for the development of multiple pathologies. Moreover, epidemiological studies have shown how maternal obesity or gestational diabetes during pregnancy constitutes an important risk factor related to the appearance of cardiovascular and metabolic diseases in the offspring. Furthermore, this period of life is especially sensitive to extrinsic and intrinsic influence, so epigenetic remodelling may help explain the molecular mechanisms that underlie epidemiological findings. The main objective of this work was to determine the DNA methylation landscape of children born to mothers with obesity and gestational diabetes across their first year of life.

Design and method:

We have characterized the methylome of blood samples from a paediatric cohort of 39 subjects consisting of children born to mothers who suffered from obesity or obesity with gestational diabetes during pregnancy and healthy controls. We performed longitudinal measurements throughout the first year of life (0, 6 and 12 months; total N = 92) using Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 CpG sites. The design allowed us to carry out both cross-sectional and longitudinal analyses in order to derive DNA methylation alterations associated with developmental and pathological-related epigenomics.

Results:

We have identified abundant DNA methylation alterations during child development from birth to 6 months and, to a lesser extent, until 12 months of age. At the same time, using cross-sectional analyses, we have identified DNA methylation biomarkers that discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes during pregnancy compared to their healthy counterparts. Moreover, our longitudinal design allowed us to determine that these alterations are at least maintained during the first year of life. In addition, gene enrichment analyses revealed that these DNA methylation alterations are associated with regions and genes related to feeding behaviour, appetite, metabolism and cell signalling.

Conclusions:

Our results support the existence of an intrauterine-mediated maternal obesity effect with an impact on the childhood methylome and possible functional implications.
PSYCHOLOGICAL DETERMINANTS OF DRUG ADHERENCE AND SEVERITY OF HYPERTENSION IN PATIENTS WITH RESISTANT VS. CONTROLLED HYPERTENSION
Authors: Persu Alexandre , Georges Coralie M.G. , Ritscher Sabrina , Pappaccogli Marco , Petit Géraldine , Lopez-Sublet Marilucy , Bapolisi Achille , Monaco Silvia Di , Wallemacq Pierre , Rabbia Franco , Toennes Stefan W. , De Timary Philippe
Published: June 2022

Objective:

In a pilot study including 35 patients with resistant hypertension, we documented associations between psychological profile, drug adherence and severity of hypertension. The current study aims to confirm and expand our findings in a larger sample of patients with resistant hypertension, using controlled hypertensive patients as comparator.

Design and method:

Patients with resistant hypertension were enrolled in hypertension centers from Brussels and Torino. Psychological profile was assessed using five validated questionnaires. Drug adherence was assessed by high-performance liquid chromatography-tandem mass spectrometry analysis of urine samples, and drug resistance by 24-hour ambulatory blood pressure adjusted for drug adherence.

Results:

The study sample otalised 144 patients, including 81 resistant and 63 controlled hypertensive patients. Mean adherence level was significantly lower in the resistant group (78.9% versus 92.7% in controlled patients, p-value = .022). In resistant hypertensive patients, independent predictors of drug adherence assessed by regression analysis were somatization, smoking status, acceptation and living with a partner, accounting for 46% of variability in drug adherence. Independent predictors of severity of hypertension were somatization, smoking status, admissions to emergency department and acceptation, accounting for 67% of variability in severity of hypertension. In contrast, in patients with controlled hypertension, the single predictors of either drug adherence or severity of hypertension were number of years of hypertension and, for severity of hypertension, alcohol consumption, accounting for only about 15–20% of variance.

Conclusions:

Psychological factors, mostly related to somatization and expression of emotions are strong, independent predictors of both drug adherence and severity of hypertension in resistant but not in controlled hypertensive patients.
IS BASAL NITRIC OXIDE ACTIVITY OF THE RENAL VASCULATURE ALTERED? ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL COMPARING TWO COMBINATION THERAPIES
Authors: Kannenkeril Dennis , Ott Christian , Bosch Agnes , Striepe Kristina , Pietschner Robert , Schiffer Mario , Schmieder Roland E.
Published: June 2022

Objective:

Recently we demonstrated that a combination therapy with empagliflozin and linagliptin in patients with type 2 diabetes mellitus (T2DM) induce changes in renal hemodynamics. The purpose of this study was to analyze the influence of basal nitric oxide (NO) activity of the renal vasculature on the described changes of the renal hemodynamic profile.

Design and method:

In this study patients with T2DM were nalysing to receive either empagliflozin and linagliptin (E+L group, n = 50) or metformin and insulin glargine (M+I group, n = 46), for 3 months. Renal hemodynamics were assessed with constant-infusion input-clearance technique with p-aminohippuric acid for renal plasma flow (RPF) and inulin for glomerular filtration rate (GFR) at baseline and after treatment. Due to withdrawal of inulin from the market during the study, GFR and filtration fraction (FF) were measured only in a sub-group of patients (E+L: n = 34; M+I: n = 31). Intraglomerular hemodynamics were calculated according the model established by Gomez. The basal NO activity in the renal circulation has been assessed by nalysing change in RPF in response to intravenously administrated NG-monomethyl-l-arginine (NO inhibitor).

Results:

After 3 months of treatment, we did not observe any change in basal NO activity compared to baseline in either of the groups. In the E+L group, we found a correlation between basal NO activity of the renal vasculature after 3 months of treatment and change in RPF (r = -0.535, p < 0.001), renal blood flow (r = -0.468, p = 0.001) and renal vascular resistance (r = 0.377, p = 0.007) induced by treatment. Similar correlations with change in FF (r = 0.639, p < 0.001), preglomerular (r = 0.350, p = 0.046) and postglomerular resistance (r = 0.588, p < 0.001) have been found. No such relationships were found in the M+I group after 3 months and with basal NO activity at baseline in both treatment groups.

Conclusions:

Basal NO emerged as a determinant of the renal hemodynamic response in the combination therapy of empagliflozin and linagliptin, but not in the combination therapy of insulin and metformin.
ASSOCIATION BETWEEN ADMISSION BLOOD PRESSURE, INCIDENT CARDIOVASCULAR EVENTS AND EARLY MORTALITY IN PATIENTS WITH REVASCULARIZED CRITICAL LIMB ISCHEMIA
Authors: Gaisset Roxane , Lin Franck , Lazareth Isabelle , Mourad Jean-Jacques , Priollet Pascal , Emmerich Joseph , Yannoutsos Alexandra
Published: June 2022

Objective:

Patients with critical limb ischemia (CLI) present a high-risk of cardiovascular events and death. Hypertension is one of the most prevalent risk factors in this population. This study investigated the association between blood pressure (BP) level at hospital admission, major cardiovascular events (MACE) and one-year mortality in patients undergoing percutaneous revascularization for CLI.

Design and method:

This retrospective analysis of an ongoing cohort study included 285 consecutive patients ospitalised from November 2013 to December 2018. Major cardiovascular events, defined as heart failure, acute coronary syndrome, ischemic stroke and sudden death, were collected during the first year following revascularization. Multivariate analysis identified factors independently associated with MACE occurrence and one-year mortality. A p < = 0.05 was considered statistically significant.

Results:

The study included 157 men (55%) and 128 women (45%), mean age of 77.8 ± 12 years. Treated hypertension was present in 222 (78%) patients (admission systolic BP 132 (±18.2) mmHg, diastolic BP 69.9 (±7.79) mmHg, pulse pressure 62.3 (±15.8) mmHg and mean BP 90.7 (±9.77) mmHg); diabetes was present in 137 (48%) patients; 112 (39%) patients had known coronary heart disease (CHD) and 20 (7%) patients were dialysis dependent.

During one-year follow-up after revascularization, 75 (26.3%) patients presented a MACE. Peri-operative mortality rate was 4% (12 patients, of whom 6 patients died from MACE).

At one-year, cumulative mortality rate was 26.7% (76 patients) mostly from MACE.

Twenty-three patients (8%) experienced major limb amputation.

In multivariate analysis, the occurrence of MACE was associated with an increased mortality risk (HR 7.06 (2.99–17.51), p<0.001). Of the four BP indexes, systolic BP (p = 0.01), mean BP (p = 0.02), pulse pressure (p = 0.02), but not diastolic BP, were significantly and inversely correlated with 1-year mortality. Decompensated heart failure and CHD were both associated with incident MACE in multivariate analysis, independently of confounders.

Conclusions:

Incident MACE were prevalent in the year following endovascular procedure in patients with CLI and were associated with an increased risk of mortality. There is an inverse association between admission BP and one-year mortality, independently of the occurrence of MACE. Decompensated heart failure and CHD are important contributors for the occurrence of MACE.
PREVALENCE AND CLINICAL CORRELATES OF FRAILTY IN HYPERTENSIVE OLDER ADULTS
Authors: Rivasi Giulia , Tortu Virginia , D’Andria Maria Flora , Turrin Giada , Ceolin Ludovica , Capacci Marco , Mossello Enrico , Ungar Andrea
Published: June 2022

Objective:

To assess the prevalence of frailty among hypertensive older adults according to the most widely used frailty measure tools and to investigate the clinical correlates of frailty.

Design and method:

A prospective observational study was conducted involving consecutive hypertensive patients aged 75 or older referred to a Hypertension clinic or a Memory clinic in Florence, Italy. The following frailty measure tools were applied: Fried Frailty Phenotype (FFP), Frailty Index, Clinical Frailty Scale (CFS), Frailty Postal Score (FPS), Short Physical Performance Battery (SPPB), gait velocity. The Cohen’s kappa coefficient was calculated to assess the agreement among measures. Multiple logistic regression was used to identify clinical variables independently associated with frailty (“correlates of frailty’’).

Results:

The study sample included 121 participants (mean age 81, 60% female). Frailty prevalence varied according to the definition used, ranging from 33% according to the FPS up to 50% according to the CFS. The Cohen’s kappa coefficient indicated moderate agreement of the FFP with the Frailty Index and the SPPB, and of the Frailty Index with the CFS and the SPPB (K = 0.60–0.79). Agreement was minimal or weak among the remaining measures (K < 0.60). At multivariable analysis, using a walking aid and reporting depressive symptoms at the Geriatric Depression Scale were independently associated with frailty, regardless of the frailty measure used. Correlates of frailty also included dementia, disability in instrumental activities of daily living (Frailty Index, CFS, gait velocity) and the comorbidity burden (Frailty Index, gait velocity). Regular physical activity was inversely associated with frailty when defined according to the FFP, the Frailty Index and the FPS.

Conclusions:

Frailty is common among older adults with hypertension, although prevalence varies depending on the definition used. Agreement among different frailty measures was moderate-to-weak. Multiple correlates of frailty were identified, including factors that are not routinely assessed in hypertensive patients, such as depressive symptoms and disability. Depressive symptoms and walking aids could represent frailty markers in hypertensive older adults, irrespective of how frailty is defined.
ASSESSMENT OF THE KNOWLEDGE ABOUT HYPERTENSION IN THE TUNISIAN ELDERLY
Authors: Mzoughi Khadija , Bergaoui Zeineb , Soltani Chayma , Belkahla Noufeil , Bouzidi Hela , Kammoun Sofien , Zairi Ihsen , Labbene Sonia , Mrad Imtinene Ben , Kraiem Sondos
Published: June 2022

Objective:

Knowledge about hypertension is a key point for treatment observance. The aim of our study was to evaluate the ducation about hypertension in the Tunisian elderly

Design and method:

We conducted a descriptive study including 101 Tunisian hypertensive treated subjects, aged 65 years and over, followed on outpatient basis between November and December 2019. The knowledge about hypertension was assessed by a questionnaire submitted to the patients in the interview time.

Results:

Twelve percent of the patients had information about hypertension and 18% had a good knoldege of their treatment.

The information source was the doctor in 6.9% of cases, followed in 2% by relatives.

Forty-five percent of patients did not know their blood pressure targets and 65% of patients were unable to name at least two dietary measures to put in place as part of blood pressure control.

Eighty-six percent of patients considered antihypertensive therapy to be lifelong therapy.

Eighty-nine percent of patients knew the dosage and schedule for their medication.

About antihypertensive medication, 89% thought it was beneficial, 5.9% thought it was not beneficial, and 5% said they did not know.

Conclusions:

Our study shows a big lack in the knowledge about hypertension in the ducati showing that an ducational strategy has to be put on.
PHYSICAL PERFOMANCE IN HYPERTENSE ELDERLY PEOPLE AND RISK OF FALL
Authors: D’Amico Ferdinando , Grasso Rosetta , D’Amico Rossella
Published: June 2022

Objective:

This study assessed the physical efficiency and the risk of fall in hypertense elderly people.

Design and method:

25 women (mean age 76 + 5) and 12 men (mean age 75 + 3) with a history of Hypertension and already under specific treatment have been included opposed to a non-hypertense control group (23 women mean age 76 + 2 anni;12 men mean age 78 + 5). The design of the study included: 1) Clinical Measurement of Blood Pressure (MBP); 2) Short Physical Performance Battery (SPPB); 3) Tinetti balance and gait Scale (TS).

Results:

Among hypertense subjects 7 women and 4 men had a mean 24 + 4 Tinetti score showing a low risk of fall; 8 women and 6 men had a mean 14 + 5 score indicating a high risk of fall. 6 women and 5 men in the control group scored 25 + 3 showing a low risk of fall, while 3 women and 3 men scored average 16 + 3 showing a high risk of fall. Those hypertense subjects whose Tinetti score indicated a high risk of fall also showed significant relations between risk of fall and physical efficiency (p < 0.01) while the control group did not show a relevant connection. Hypertense patients who were also diagnosed a reduced efficiency through a mean score 6 at the SPPB in 89% cases scored an average value 12 at the TS, therefore showing a risk of fall. To improve the physical efficiency in the eldest with a high risk of fall we also proposed an occupational therapy home programme.

Conclusions:

This study shows a significant connection among hypertension and reduced physical efficiency. Therefore the evaluation of people affected by hypertension and with a high risk of fall is relevant and we strongly recommend the prevention of this risk at home via an occupational therapy programme.
BLOOD PRESSURE CONTROL AMONG AN ELDERLY NORTHERN-ITALIAN POPULATION, EFFECT OF BETA-ADDUCIN POLYMORPHISMS. A CROSS-SECTIONAL STUDY
Authors: Betti Paolo , Lanzani Chiara , Citterio Lorena , Zagato Laura , Messaggio Elisabetta , Brioni Elena , Magnaghi Cristiano , Simonini Marco , Querini Patrizia Rovere , Manfredi Angelo , Manunta Paolo
Published: June 2022

Objective:

Evaluate role of nvironmental and genetic factors on Blood Pressure (BP) control among an Italian elderly population.

Design and method:

Cross-sectional study on 1250 elderly subjects of north Italy aged over 65y, recruited in recreative centers. BP was measured with an automated device (Omron) and the average of 2nd and 3rd measure was recorded. According to ESC-ESH-2018 guidelines we defined suboptimal BP control for patients presenting with systolic BP>140 or diastolic BP>80 mmHg. Anthropometric measurements were taken, blood and urines samples for biochemical and targeted genetic analysis were acquired. Genotyping was performed by OpenArray system. All participants signed informed consent. The protocol was approved by the Ethical Committee.

Results:

746 subjects (59.9%) were on antihypertensive therapy. 385 (51.6%) had a systolic BP over 140 mmHg, and 419 (56.2%) had a diastolic BP over 80 mmHg, thus classified as on suboptimal BP control. Among those, 153 (20.4%) presented SBP> 160 or DBP > 100 (stage 2 hypertension) despite treatment. 28.6% were on optimal BP control. Factors associated with poor BP control on univariate analysis showed gender (p = 0.002), higher waist circonference (p = 0.014), high visceral fact index (p < 0.01) and minor number of total medications (p < 0.01). Age, eGFR, and urine albumin/creatinine ratio were non significantly different between the two groups. Inferential tree analysis showed that urine sodium is relevant on BP level in ‘younger’ and untreated subjects (p < 0.001). Among genetic variants, rs4984 T allele in beta-adducin gene (ADD2) was associated with poor BP control (17.3% vs 11.4%; p = 0.016). Similarly, T allele in the overall elderly subjects showed a high frequency compared to general population (EUR - 1000 Genome Project) (16% vs 12.5%; p = 0.023).

Conclusions:

Gender, visceral fat and therapies are associated with poor BP control, suggesting the relevant role of clinical management. Surprisingly, even in this elderly population, a genetic factor already associated with salt-sensitive hypertension and response to anti-hypertensive therapy as ADD2 was found related to poor BP control.

Most of of elderly patients treated for hypertension have suboptimal control of BP. Moreover, genetic factors besides environmental factors, seem to play a role in BP control even in elderly.
THE COURSE OF ATRIAL FIBRILLATION AFTER A PREVIOUS INFECTION WITH COVID-19 DEPENDING ON THE PRESENCE OF ARTERIAL HYPERTENSION
Authors: Sychov Oleg , Stasyshena Oksana , Ilchyshyna Olena , Zinchenko Yu , Getman Taisiya , Romanova Olena , Sribna Olga
Published: June 2022

Objective:

It is known that arterial hypertension (AH) is the main etiological factor in the development of atrial fibrillation (AF).

The aim of our study was to assess the course of AF after infection with COVID-19 (CI) depending on the presence of hypertension.

Design and method:

We examined 72 patients with AF, aged 64.5 + 1.2 years, who, on average, 6.2 + 0.5 months underwent CI. 59 (81.9%) people had AH (group ‘A’ patients). The remaining 13 (18.1%) patients did not have hypertension (group ‘B’ patients).

Results:

When nalysing the course of AF after CI in these groups, it was found that an increase in the frequency of AF paroxysms was observed in a significantly larger number of patients in group ‘A’ (32 out of 59 people, 54.2%) than in patients in group ‘B’ (in 3 out of 13 people, 23.1%), p < 0.001, the duration of AF paroxysms also increased more significantly in a larger number of patients in group ‘A’ (in 29 out of 59 people, 49.2%), than in patients of group ‘B’ (in 4 of 13 people, 30.8%), p < 0.001, and the surrogate indicator of deterioration in the course of AF (an increase in the frequency or duration of AF paroxysms) was also higher in group ‘A’ (in 36 of 59 patients, 61.0%), compared with group ‘B’ (5 out of 13 patients), p < 0.001.

Conclusions:

The presence of AH significantly worsens the course of AF after CI, increasing the frequency of paroxysms of this arrhythmia and their duration.
EXERCISE CAPACITY AND ATRIAL FIBRILLATION RISK IN 459,592 HYPERTENSIVES: A COHORT STUDY
Authors: Pittaras Andreas , Faselis Charles , Samuel Immanuel Babu Henry , Doumas Michael , Grassos Haralampos , Murphy Rayelyn , Myers Jonathan Jonathan , Kokkinos Peter
Published: June 2022

Objective:

To assess the association between exercise capacity and the risk of developing atrial fibrillation (AF) in hypertensive patients.

Design and method:

We identified 459,675 hypertensives (63 ± 8.6 years, females: 4.9%), free of AF, who completed a normal Bruce exercise treadmill test (ETT). We established 5 fitness categories (quartiles) based on age-specific peak metabolic equivalents (METs) achieved: Least-fit (4.5 ± 1.22 METs; n = 107,593); Low-fit (6.9 ± 1.07; n = 119,433); Moderate-fit (8.3 ± 1.19; n = 88,923); Fit (10.3 ± 0.89; n = 106,921), and High-fit (13.1 ± 1.55; n = 36,722). Hazard regression models were adjusted for age, BMI, smoking (33.5%), DM (43.6%), dyslipidemia (69.8%) and CKD (5.8%).

Results:

During a median follow-up of 9.8 ± 5.0 years, 42,639 (9.6%) developed AF (9.6 per 1000 person-years). EXCP was inversely related to AF incidence. The risk was 11% lower (HR:0.89, 95% CI, 0.88–0.90) for each 1-MET increase in exercise capacity. Compared to the Least-fit category (Referent), the HRs were 0.72 (95% CI, 0.71–0.74) for Low-fit individuals, 0.61 (95% CI, 0.60–0.63) for Moderate-fit, 0.52 (95% CI, 0.50–0.54) for Fit, and 0.45 (95% CI, 0.43–0.47) for High- fit individuals. Similar trends for those < 65 years & > 65 years of age.

Conclusions:

Our findings support that increased fitness offer a marked protection against AF. The association was inverse, independent, and graded. Significantly lower AF risk was evident in those with only modest increases in exercise capacity and declined by > 50% for individuals in the High-fit category. These findings counter previous suggestions that even moderate increases in physical activity, (recommended by guidelines), increase the risk of AF.