bluuebunny/crossref_metadata_2025 huggingface dataset:
NOVEL PATHOPHYSIOLOGICAL ROLES OF ALPHA-SYNUCLEIN (SNCA) IN AGE-RELATED VASCULAR ENDOTHELIAL DYSFUNCTION
Authors: Takami Yoichi , Nakagami Hironori , Yamamoto Koichi , Takeya Yasushi , Morishita Ryuichi , Takeda Shuko , Kaneda Yasufumi , Rakugi Hiromi
Published: April 2021

Objective:

Although SNCA is one of the well-known pathological molecule of synucleinopathy in neurons, its physiological roles remain to be identified. In the present study, we sought to elucidate the novel functions of SNCA in endothelium.

Design and method:

Analysis for human samples, in vitro experiments using endothelial cells (ECs), and in vivo investigation using SNCA knockout or SNCA/ApoE double knockout mice were performed.

Results:

We found SNCA was expressed in and secreted from ECs by functional screening for anti-inflammatory molecules and detectable in circulating blood. Intriguingly, the human population study revealed serum SNCA levels decreased with aging and displayed inverse correlation with blood pressure and insulin sensitivity, which indicated protective properties of circulating SNCA on vascular endothelial function. Furthermore, we also found SNCA knockout mice displayed phenotypes of metabolic syndrome such as hypertension, impaired glucose metabolism, and dyslipidemia. Based on these preliminary data, we sought to elucidate the physiological functions of endogenous and exogenous SNCA for ECs. Exogenous treatment with recombinant SNCA (rSNCA) promoted eNOS activation and nitric oxide production via Gab1/PI3K/Akt pathway in ECs, followed by cGMP production in co-cultured vascular smooth muscle cells. Treatment with rSNCA also suppressed TNF-alpha induced NF-kappaB activation in ECs. As to endogenous SNCA, replicative senescence showed attenuation of SNCA expression in ECs and siRNA-mediated silencing of SNCA induced eNOS inactivation and cell senescence assessed by beta-gal activity along with decreased Sirt1 expression and increased p53 expression. SNCA overexpression displayed NF-kappaB inactivation in ECs. In ex vivo study, aortas from SNCA knockout mice showed impairment of acetylcholine-induced relaxation possibly due to eNOS dysfunction. In in vivo study utilizing atherosclerosis model of SNCA/ApoE double-knockout mice showed exaggerated expression of inflammatory genes which play important roles in atherogenesis.

Conclusions:

In conclusion, these results indicate exogenous and endogenous SNCA in ECs might physiologically maintain cerebral vascular integrity. Aging or aggregation-related loss-of-function of SNCA in ECs might be partially correlated with age-related hypertension or clinical features of dementia with Lewy body such as fluctuating cognitive function and marked sensitivity of antipsychotic which could be modified by cerebral blood flow and vascular permeability.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN STROKE PREVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS INVOLVING 297,451 PATIENTS
Authors: Alosaimi Manal , Roos Nur Aishah Che , Alnakhli Anwar Mansour , Cleland John , Padmanabhan Sandosh
Published: April 2021

Objective

: To assess the impact of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on risk of stroke in patients with or at high-risk of cardiovascular diseases (CVD)

Design and method:

A meta-analysis of randomized-controlled trials was performed. Bibliographic databases were searched until 31 July 2019 for ACEIs & ARBs trials versus placebo or active therapy & supported with head-to-head trials in participants with or at high-risk of CVD. Only trials with at least 100 participants & at least one year's follow-up were included. Trials were excluded if they were redacted or combined ACEIs with ARBs. Outcome was fatal & non-fatal stroke: including ischaemic and haemorrhagic stroke excluded transient ischaemic attack (TIA). Dichotomous outcome data was analysed using risk ratio (RR) measure and its 95% confidence interval (CI) with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved.

Results:

This study included 72 trials with 297,451 patient-years of follow-up. Compared with placebo, both ACEIs and ARBs reduced the risk of stroke by 14% & 9%; respectively (ACEIs: RR, 0.86; 95% CI, 0.76–0.98; p = 0.02 & ARBs: RR, 0.91; 95% CI, 0.86–0.97; p = 0.003). No difference was observed when ACEIs & ARBs were compared with active (ACEIs: RR, 1.14; 95% CI, 1.04–1.26; p = 0.006 & ARBs: RR, 0.94; 95% CI 0.79–1.12; p = 0.50). Pooled data from trials comparing ARBs to ACEIs showed no difference in stroke event rates (RR, 0.96; 95% 0.87–1.06; p = 0.42). A meta-regression analysis revealed that the relative risk reduction of stroke by ACEIs (p = 0.03) and ARBs (p = 0.01) therapy was proportional to the magnitude of SBP reduction achieved.

Conclusions:

In patients with or at high-risk of CVD, evidence from placebo-controlled trials & head-to-head trials demonstrated that ARBs to be as effective as ACEIs on preventing of stroke. Cerebro-protective effect of ARBs & ACEIs therapies are strongly associated with BP reduction.
THE ROLE OF CAROTID ECHO DOPPLER IN TREATMENT AND PREVENTION OF CEREBROVASCULAR DISEASE IN NON DIABETIC AND DIABETIC POPULATION AT HIGH RISK
Authors: Revnic Cristian Romeo , Revnic Flory
Published: April 2021

Objective:

Stroke, the third leading cause of death is a cardiovascular disease that affects the blood vessels supplying blood to the brain. Diabetes mellitus which is one of the main risk factors of cerebrovascular disease (CVD). Aim: Echo Doppler evaluation of arteries in diabetic and non-diabetic elderly patients.

Design and method:

Patient selection: We selected 112 patients admitted in Neurology Clinic of Vlad Voiculescu Cerebrovascular Institute Bucharest: 63 non diabetics mean age 63 years with acute ischemic stroke (CT scan confirmed)in carotid territory or a TIA and 59 diabetic patients with risk factors: obesity and arterial hypertension mean age 62.8 included into this study, independently from the presence or absence of acute ischemic stroke investigated by CT/MRI.

Results:

The carotid Echo-Doppler examination applying a 4 MHz transducer for extracranial and transcranial vascular Doppler investigation performed in both groups of patients revealed that simple carotid plaques, bilateral carotid stenoses (CS), and unilateral CS associated with contralateral carotid occlusion (CO) occurred with higher frequency in the non-diabetic patients, than in diabetic ones. On the other hand, the remaining other findings, such as unilateral CS, unilateral CO, S/O of intracranial carotid artery (ICA) and vertebral/subclavian S were more frequent in the diabetic group.

Conclusions:

The findings allow us to conclude that the correct and early treatment of diabetes as well as a possible lowering of the risks for cerebrovascular disease are obligatory steps in the primary and secondary prevention of the cerebral ischemic events in diabetic patients with carotid atheromatous lesions. There are several approaches to reduce the risk of stroke in diabetics and physical exercise is a low cost with maximum benefit upon health status contributing to lowering of high blood pressure, and of HDL. This consideration may help the physicians to have a deeper understanding of the pathophysiology, and to implement the necessary treatment and prevention of CVD in the diabetic population of high-risk.
CENTRAL SYSTOLIC PRESSURE AND EXECUTIVE FUNCTION IN CHILDREN AND ADOLESCENTS WITH PRIMARY AND SECONDARY HYPERTENSION
Authors: Stabouli Stella , Chrysaidou Katerina , Kotsis Vasilios , Chainoglou Athanasia , Gidaris Dimos , Zafeiriou Dimitrios
Published: April 2021

Objective:

The aims of the present study were to assess executive function performance in children and adolescents with primary and secondary hypertension and to investigate for associations with central systolic pressure and mean ambulatory blood pressure (BP) levels.

Design and method:

The study population included 46 pediatric patients with secondary hypertension, and 46, age and sex matched, patients with primary hypertension who underwent ambulatory BP monitoring, pulse wave analysis, and assessment of executive function using Behavior Rating Inventory of Executive Function (parent version, BRIEF, and self-reported version, BRIEF SR).

Results:

Patients with secondary hypertension had higher T scores in BRIEF parent metacognition (MI) (51.19 ± 8.92 vs. 47.56 ± 7.49, p < 0.05), and BRIEF-SR MI scales (49.62 ± 9.08 vs. 42.09 ± 7.88, p = 0.001) compared to primary hypertensives. The groups did not differ in means of BRIEF parent and BRIEF-SR Behavior Regulation Index (BRI) T scores, as well as day and night mean arterial pressure (MAP) z scores, prevalence of ambulatory hypertension, and pulse wave velocity (PWV) z score. However, those with secondary hypertension tented to have higher central systolic pressure (cSP) z scores (p = 0.053), and lower body mass index (BMI) z score (p < 0.001). In the ANCOVA analysis cSP z score was associated with BRIEF parent MI (B = 0.95, 95%CI 0.02–1.87, p < 0.05), and BRI T scores (B = 1.14, 95%CI 0.07–2.21, p < 0.05), and BRIEF-SR MI T score (B = 1.481, 95%CI 0.393–2.569, p < 0.05), independent of night MAP z score, age, sex, SES, hypertension group (primary/secondary), and antihypertensive treatment (yes/no).

Conclusions:

Central systolic pressure associates with executive function performance in hypertensive youth independent of hypertension etiology and seems to have pivotal role in the lower metacognition scores in the secondary hypertension group.
FETUIN A DEFICIENCY IS ASSOCIATED WITH ARTERIAL DAMAGE IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION
Authors: Skrzypczyk Piotr , Stelmaszczyk-Emmel Anna , Szyszka Michal , Ofiara Anna , Panczyk-Tomaszewska Malgorzata
Published: April 2021

Objective:

Circulating calcification inhibitors: fetuin A (FA) and osteoprotegerin (OPG) together with soluble ligand of the receptor activator of nuclear factor kappa-B (sRANKL) have been linked to vascular calcifications and subclinical arterial damage. The aim of the study was to evaluate the relationship between FA, OPG, sRANKL and arterial damage in children with primary hypertension (PH).

Design and method:

We performed cross-sectional analysis of FA, OPG, sRANKL, peripheral and central blood pressure (BP), ambulatory blood pressure monitoring (ABPM), parameters of arterial damage including common carotid artery intima media thickness (cIMT), pulse wave velocity (PWV), augmentation index normalized to heart rate of 75 beats per minute (AIx75HR) and ECHO-tracking (ET) analysis of carotid artery stiffness in 60 patients with PH (age: 14.84 ± 3.05 years) and 20 healthy children (age 14.11 ± 2.99 years).

Results:

Children with PH had significantly higher peripheral and central BP, BP in ABPM, thicker cIMT, higher PWV, and AIx75HR. FA was significantly lower in patients with PH compared to healthy peers (340.57 ± 70.43 vs. 389.19 ± 99.22 [mg/mL], P = 0.019) without differences in OPG, sRANKL, and OPG/sRANKL and OPG/FA ratios. In children with PH, FA level correlated negatively with cIMT Z-score and ET AIx; sRANKL level correlated negatively with ABPM, systolic blood pressure (SBP), SBP load, diastolic BP load, and AIx75HR; OPG/sRANKL ratio correlated positively with SBP load, while OPG/FA ratio correlated positively with ET AIx. In multivariate analysis FA was a significant determinant of cIMT [mm] and cIMT Z-score (beta = -0.208, 95%CI (-0.407 - -0.009), P = 0.041 and beta = -0.224, 95%CI (-0.435 - -0.013), P = 0.038, respectively).

Conclusions:

In children with PH arterial damage is related to fetuin A deficiency.
AN UNUSUAL CASE OF ACUTE MITRAL REGURGITATION WITH LUPUS NEPHRITIS AND EXTRA PULMONARY TUBERCULOSIS
Authors: D'souza Monisha , R. Arunachalam
Published: April 2021

Objective:

Systemic lupus erythematosus belongs to the group of autoimmune disorders which can affect multiple organ systems of the body during its chronic course. It is commonly associated with cardiac manifestations. The characteristic abnormalities among cardiac lesions include Libman-

Sacks endocarditis and pericarditis, while myocarditis is relatively uncommon. Among valvular lesions, the most common complication is mitral valve regurgitation.

Design and method:

A 27 year old lady with systemic lupus erythematosus, on treatment since 1 year, was referred to our hospital with the suspicion of development of Lupus nephritis and tubercular pleural effusion. She was started on anti-tubercular therapy based on the pleural fluid analysis. As tuberculosis is prevalent in our country and her pleural fluid showed raised adenosine deaminase levels, anti-tubercular therapy was modified for renal safety but continued. Her previous reports showed the presence of subnephrotic proteinuria in urine for 6 months. She presented to the emergency department with complaints of breathlessness and chest discomfort. Her initial blood workup revealed new-onset derangement in renal parameters. Lupus nephritis was suspected.

Results:

She developed a worsening of breathlessness and was shifted to the ICU. She was given intravenous pulse steroids and monitored. Her renal dysfunction improved. She developed paroxysmal nocturnal dyspnoea with persistent tachycardia and tachypnea. A trans-thoracic echocardiogram was done which revealed a massive loculated pericardial effusion. She was conservatively managed and then shifted to the ward. After a few days, she developed sudden onset pulmonary edema and was shifted back to the ICU. Echocardiogram was repeated which showed new-onset acute severe mitral regurgitation with central jet. The patient was medically managed. Her symptoms improved and she was initiated on mycophenolate mofetil and discharged. Two months later she was admitted for renal biopsy. Lupus nephritis was confirmed. She is now on regular follow-up with significant clinical improvement.

Conclusions:

Systemic Lupus Erythematosus can involve multiple organ systems rapidly and simultaneously with a predisposition to developing other infections. This increases the risk of morbidity and mortality. Early diagnosis and timely initiation of therapy are essential in improving the survival outcomes of the patient.
IN-HOSPITAL BLOOD PRESSURE VARIABILITY AS A PREDICTOR OF LONG-TERM CARDIOVASCULAR MORTALITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: ONE-YEAR FOLLOW-UP STUDY
Authors: Konstantinou K. , Tsioufis K. , Koumelli A. , Mantzouranis M. , Kolokathis K. , Milkas A. , Fragoulis C. , Kalos T. , Andrikou I. , Kasiakogias A. , Dimitriadis K. , Thomopoulos K. , Kouremeti M. , Tousoulis D.
Published: April 2021

Objective:

The impact of blood pressure variability (BPV) on cardiovascular morbidity and mortality has been examined through the prism of heart failure and hypertension, but not in the setting of myocardial infarction (MI). The aim of this study is to determine the association between in-hospital short-term BPV and long-term cardiovascular outcomes in MI patients.

Design and method:

A total population of 260 patients (82.2% male; mean age: 63.8 years;71.3% hypertensives, 48.1% STEMI)underwent 24-hambulatory BP measurement during hospitalization for MI. At one year a follow-up was scheduled in order to assesscardiovascular mortality. The parameters of BPV analyzed were: a) 24-h standard deviation (SD), b) the coefficient of variation (CV) and c) the average real variability (ARV) of systolic and diastolic BP.

Results:

Cardiovascular death was independently predicted by SD SBP (HR = 2.406; 95% CI: 0.865–3.947; P = 0.002)and CV SBP (HR = 3.093; 95% CI: 1.833–4.354; P < 0.001) in the entire population and separately in STEMI group[(HR = 5.485; 95% CI: 2.958–8.012; P < 0.001) and (HR = 5.521; 95% CI: 3.230–7.813; P < 0.001) respectively]but not in the NSTEMI one. ARV failed to predict mortality in either group or the entire population. Multivariate regression models were conducted for both SD SBP and CV SBP in the STEMI group,in which, both remained potent predictors of cardiovascular mortality independently ofgender, age, hypertension, DM, smoking, low density lipoprotein (LDL-C) andGFR[(HR = 6.131; 95% CI: 3.716–8.546; P < 0.001) and (HR = 5.870; 95% CI:3.609–8.131; P < 0.001) respectively].

Conclusions:

In the setting of MI, in-hospital BPV was associated with cardiovascular mortality during the one-year follow-up. These findingscould suggest a clinical need for further individualization of BP regulation in the integrative ACS management.
IMPACT OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS ON CORONARY HEART DISEASE EVENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 299,871 PATIENTS
Authors: Alosaimi Manal , Roos Nur Aishah Che , Alnakhli Anwar Mansour , Cleland John , Padmanabhan Sandosh
Published: April 2021

Objective:

To evaluate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on risk of myocardial infarction (MI), angina & heart failure (HF) in patients with or at high-risk of cardiovascular disease (CVD).

Design and method:

A meta-analysis of randomized-controlled trials was performed. Bibliographic databases were searched until 31 July 2019 to identify all trials of ACEIs & ARBs versus control (placebo or active) & supported with head-to-head trials. Trials with at least 100 participants & at least one year's follow-up were eligible. Studies were excluded if they were redacted or combined ACEIs with ARBs. Outcomes were MI, angina pectoris & HF. Dichotomous data was analysed using risk ratio (RR) measure and its 95% confidence interval (CI) with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved.

Results:

We identified 32 trials of ACEIs, 38 of ARBs compared with control & 8 direct comparison trials. Altogether, trials enrolled 299,871 patient-years of follow-up. Compared with control, ACEIs had a 16% lower MI risk (RR, 0.84; 95% CI, 0.79–0.90; p < 0.00001) & 17% lower HF (RR, 0.83; 95% CI, 0.76–0.92; p = 0.0003); while no such benefit was seen for angina (RR;1.02; 95% CI, 0.94–1.11; p = 0.63). ARBs was reduced risk of HF by 14% (RR, 0.86; 95% CI 0.81–0.91; p < 0.00001). While, no benefit was appeared with MI risk (RR,0.97; 95% CI 0.89–1.06; p = 0.55) & angina (RR, 0.99; 95% CI 0.88–1.11; p = 0.87). Trials comparing ARBs with ACEIs revealed no difference in outcomes. The meta-regression suggested that independently of BP reduction, ACEIs had a 11% lower MI (RR,0.89; 95% CI 0.81–0.98; p = 0.02) & ARBs provide a 15% reduction in HF (RR, 0.85; 95% CI 0.77–0.93; p = 0.001). Whereas, prevention of HF by ACEIs was explained mainly by SBP reduction achieved (p = 0.01).

Conclusions:

In patients with or at high-risk of CVD, ARBs and ACEIs reduced risk of HF. However, they did not appear to be case for angina. Moreover, ACEIs result in a further reduction of MI whereas ARBs had no such benefit. However, evidence from direct comparison trials suggests similar effects on all outcomes.
ISOLATED SYSTOLIC HYPERTENSION AND COMBINED SYSTOLIC-DIASTOLIC HYPERTEN-SION FOR PREDICTION OF NEW-ONSET DIABETES MELLITUS - DATA FROM A 8-YEAR-FOLLOW-UP STUDY
Authors: Tsioufis K. , Dimitriadis K. , Liatakis I. , Koutra E. , Leontsinis I. , Kouremeti M. , Iliakis I. , Karaminas N. , Thomopoulos K. , Tousoulis D.
Published: April 2021

Objective:

Isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension (CH) are related with increased cardiovascular risk, while new-onset diabetes mellitus (NOD) is linked with atherosclerosis progression. To compare the predictive role of ISH and CH for the incidence of NOD in a cohort of essential hypertensive patients.

Design and method:

We followed up 1435 non-diabetic essential hypertensives with office systolic blood pressure (BP)> or = 140 mmHg [mean age 57 years, 730 males, office BP=153/92 mmHg] for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent echocardiographic study and blood sampling for estimation of metabolic profile. Patients with baseline ISH exhibited office systolic BP > or =140 mmHg and office diastolic BP <90 mmHg, while those with CH had office systolic BP > or = 140 mmHg and office diastolic BP> or =90 mmHg. Moreover, NOD was defined if at one or more of the follow-up visits a previously non-diabetic patient reported being on insulin or an oral hypoglycemic drug or if casual plasma glucose concentration > or = 200 mg/dl or fasting glucose concentration > or = 126 mg/dl or 2-h post load glucose > or = 200 mg/dl during an oral glucose tolerance test.

Results:

The incidence of NOD over the follow-up period was 4.2% (n = 60). Patients with ISH (n = 460) compared to those with CH (n = 975) were older (65 ± 11 vs 54 ± 10 years, p < 0.0001), had at baseline lower waist circumference (94.5 ± 11 vs 99 ± 13 cm, p < 0.0001), office systolic BP (149 ± 12 vs 155 ± 13 mmHg, p < 0.0001), office diastolic BP (80 ± 8 vs 98 ± 6 mmHg, p < 0.0001), while did not differ regarding left ventricular mass index, glucose and lipid levels (p = NS for all). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio = 2.143, p = 0.016) and CH (hazard ratio=1.272, p = 0.029) predicted NOD. However, in multivariate Cox regression model, CH did not turn out to be an independent predictor of NOD.

Conclusions:

In essential hypertensive patients, ISH but not CH exhibits independent prognostic value for NOD. These findings support that ISH constitutes a hypertensive phenotype of increased metabolic risk needing careful evaluation and treatment.
PREDIABETES IN NAÏVE GREEK HYPERTENSIVE PATIENTS
Authors: Papadakis J.A. , Papanikolaou K. , Theodorakopoulou V. , Papakitsou I. , Psicharaki F. , Vrentzos G.
Published: April 2021

Objective:

Prediabetes subjects have increased risk for diabetes and cardiovascular disease. Aim of our study was to find the incidence of prediabetes, in naive hypertensives in Greece.

Design and method:

We studied 688 [304 (44.2%) were men] hypertensives, who were under neither antihypertensive nor lipid-lowering medications, and they were not diabetics. Their median age was 55 (range: 15–82) years. Prediabetes was defined by ADA criteria (fasting glucose: 100–125 mg/dl).

Results:

Two hundred forty five out of 688 patients (35.6%) met the criteria for prediabetes. It was more prevalent in males than in females (42.4% vs 30.2%, p = 0.001). On the contrary, there was no statistically significant difference in the age between the 2 groups.

Subjects with prediabetes had significantly higher body mass index (BMI) (31.5 + 5.8 vs 30.3 + 5.0; p = 0.01) when compared with the rest hypertensives.

Hypertensives with prediabetes had significantly higher systolic blood pressure (SBP) levels than the others (158.4 + 18.5 vs 155.2 + 18.6; p < 0.05), while there was no significant difference in diastolic blood pressure levels (95.0 + 11.0 vs 94.7 + 11.3; p = 0.70) between the 2 groups.

There was no significant difference in total, high density, and low density cholesterol and triglycerides serum levels between the two groups.

On the contrary hypertensives with prediabetes had significantly increased all liver functional tests than those without.

Conclusions:

Our results suggest that more than one third of naive hypertensives had prediabetes. These subjects had higher SBP levels and they were more obese. They had also increased liver functional tests, without any difference in their lipid profile.
QUINAPRIL AMELIORATES CARDIAC REMODELING IN DIABETIC RATS VIA SUPPRESSION OF EGR1 AND STAT3 ACTIVATION
Authors: Kökény Gábor , Fázsy Zseni , Fazekas Krisztina , Rosivall László
Published: April 2021

Objective:

RAAS over activation in diabetes may induce myocardial hypertrophy and extracellular matrix accumulation even without hypertension, and ACE-inhibitors are widely used to manage blood pressure. STAT3 activation is known to promote experimental kidney remodeling, but its role in diabetic myocardium has not been elucidated. Experimental evidence shows that EGR1 contributes to myocardial remodeling, yet the effect of ACE-inhibition on myocardial EGR1 in diabetes is still unknown. Thus, we investigated whether the ACE-inhibitor quinapril could influence myocardial EGR1 and STAT3 activation in diabetic rats.

Design and method:

Male Sprague-Dawley rats (250–300 g, n=12) were ip. injected with 60 mg/kg streptozotocin to induce type-1 diabetes (DM). Half of DM rats was treated with 50 mg/kg/day quinapril in drinking water (Q) for 8 weeks. Non-diabetic littermates served as negative controls (CTL). Experimental groups were as follows (n = 6/group): 1) CTL; 2) DM; 3) DM+Q. At harvest, plasma renin activity (PRA) was assessed and myocardium was processed for histology, immunohistochemistry, mRNA and protein expression analyses. Data are presented as mean ± SD, analyzed using Kruskal-Wallis test with Dunn's post-hoc test.

Results:

PRA was elevated in diabetic groups regardless of treatment (CTL:1.3 ± 0.2, DM:2.2 ± 1.0, DM+Q:1.8 ± 1.1 ng/ml/h, p < 0.05), accompanied by myocardial (pro)renin receptor (PRR) mRNA overexpression (fold expression, CTL:1.0 ± 0,2, DM:1.8 ± 0.9, DM+Q:1.7 ± 0.5, p < 0.05). However, quinapril reduced collagen-1 mRNA expression (CTL:1.0 ± 0.3, DM:1.3 ± 0.4, DM+Q:0.7 ± 0.3, p < 0.01) and fibronectin immunoreactivity, accompanied by reduced matrix remodeling shown by the expression of both tissue inhibitor of metalloproteases TIMP1 and TIMP2 (TIMP1, CTL:0.9 ± 0.1, DM:1.6 ± 0.7, DM+Q:1.0 ± 0.5, p < 0.05; TIMP2, CTL:1.0 ± 0.1, DM:1.8 ± 0.5, DM+Q:1.1 ± 0.4, p < 0.05). Immunoblots showed that quinapril also attenuated diabetes induced EGR1 protein expression (CTL:1.0 ± 0.4, DM:1.8 ± 0.5, DM+Q:0.5 ± 0.2, p < 0.01) and STAT3 phosphorylation (CTL:1.0 ± 0.1, DM:1.4 ± 0.2, DM+Q:0.6 ± 0.1, p < 0.01), accompanied by reduced TIMP1 protein expression (CTL:0.9 ± 0.1, DM:1.5 ± 0.3, DM+Q:0.9 ± 0.3, p < 0.05) that correlated with STAT3 activity (R-square: 0.4, p = 0.03).

Conclusions:

In our rat model of type-1 diabetes, chronic quinapril treatment significantly attenuated cardiac remodeling via its direct inhibitory effect on the profibrotic myocardial EGR1 and STAT3. These results underscore the tissue-specific, blood pressure-independent beneficial effects of ACE inhibition in diabetes.
DAPAGLIFLOZIN, PIOGLITAZONE AND THEIR COMBINATION EFFECTED LEVELS OF LIPOPROTEINS AND ADIPOKINES IN PLASMA AND THEIR GENE EXPRESSION IN FAT IN RATS WITH DIABETES MELLITUS TYPE 1
Authors: Kralova Eva , Marusakova Margareta , Hadova Katarina , Klimas Jan
Published: April 2021

Objective:

Patients with diabetes mellitus type1 (DM1) have a relative insulin deficiency with elevated triacylglycerides (TAG) production. Adipokines are important in fat distribution, inflammation, and endothelial function. Dapagliflozin (Dapa) and pioglitazone (Pio) are oral hypoglycemic drugs for the treatment of DM2. They have also pleiotropic effects on lipid profile and body weight. The effect of these drugs on lipoproteins and adipokines levels in DM1 is poorly understood.

Design and method:

DM1 in male Wistar rats was induced by a single dose of streptozotocin (STZ). Animals were then divided into five groups: Controls, diabetic animals (DM), DM treated with Dapa, DM treated with Pio, DM treated with combination DapaPio. Therapies were mixed in rat chow. Control and DM groups received standard chow. After 6 weeks of treatment serum glucose and lipid levels were determined. Visceral adipose tissue (VAT) gene expression of leptin (Lep), adiponectin (AdipoQ), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), tumor necrosis factor-alpha (TNFa) and interleukin 6 (IL6) were measured by RT qPCR and their levels in plasma were determined by ELISA method.

Results:

STZ injection led to a significant increase in both fasting and postprandial glucose levels and all levels of lipoproteins except high-density lipoproteins (HDL), which were decreased. We also found decreased levels of Lep, AdipoQ, LPL, and IL6, and increased HSL and TNFa in plasma in DM group. These results were supported by the same significant changes in gene expression in VAT. A combination of DapaPio resulted in a significant decrease in serum levels of both glucose levels. Pio and DapaPio administration decreased TAG and total cholesterol and increased HDL. Lep, AdipoQ, LPL and IL6 plasma levels were increased, and HSL, TNFa were decreased after administration of Dapa, Pio and their combination. Both monotherapy and combination significantly modulated Lep, TNFa and IL6 gene expression in VAT.

Conclusions:

DM1 in rats influenced not only glucose levels but also lipoproteins and adipokines in plasma, which could be affected by Dapa, Pio and DapaPio. Therapy can also change the gene expression of Lep, AdipoQ, TNFa, and IL6 in adipose tissue in rats with DM1.
INFLUENCE OF GONADAL STEROIDS ON AMBULATORY BLOOD PRESSURE IN TRANSSEXUALS
Authors: Stojanovic Milos , Miletic Jasmina Ciric Marija , Zarkovic Milos , Stojkovic Mirjana , Beleslin Biljana , Vujovic Svetlana
Published: April 2021

Objective:

The effects of hormone therapy on systolic blood pressure in transsexual women are inconsistent, with most studies showing an increase. In transsexual men, testosterone therapy consistently increases systolic blood pressure and may increase diastolic blood pressure. During or following testosterone treatment in transgender men some studies observed a slight increase in systolic and diastolic blood pressure. During testosterone treatment other studies found a modest increase only in systolic blood pressure and one reported a decrease in systolic and diastolic blood pressure levels. In one study, treatment in transgender men blood pressure was expressed as mean arterial pressure, and no changes were observed. However, one study reported two case of hypertension, with return to normal blood pressure values after cessation of testosterone therapy.

Design and method:

The aim of this study was to see is there significant ambulatory blood pressure (ABPM) changes in transsexual women and in transsexual men? We have analysed ambulatory blood pressure changes in 43 male to female (MTF) and in 36 female to male (FTM) transsexuals. Validated Meditech ABPM 05 device was used to measure 24 h blood pressure changes.

Results:

In transsexual women we have found 3.2% decrease in systolic and 2.3% in diastolic blood pressure levels during or following hormone therapy. In transsexual men, testosterone therapy dependably increases 3.6% systolic and 3.2% diastolic blood pressure.

Conclusions:

Our findings support evidence of blood pressure lowering effect of oestrogens and increase of blood pressure with administration of androgens in transsexuals.
SUBTLE CORTISOL HYPERSECRETION IS ASSOCIATED WITH GLUCOSE HOMEOSTASIS AND INSULIN RESISTANCE IN NON-DIABETIC ESSENTIAL HYPERTENSIVE PATIENTS
Authors: Catena Cristiana , Da Porto Andrea , Colussi Gianluca , Bulfone Luca , Vivarelli Cinzia , Sechi Leonardo A.
Published: April 2021

Objective:

Patients with Cushing's syndrome (CS) and subclinical Cushing's syndrome (SCS) have a higher prevalence of cardiovascular complications than general population. Increased prevalence of impaired glucose tolerance has been reported in patients with SCS. Excess cortisol secretion can inhibit insulin secretion and impair insulin sensitivity and glucose uptake. We sought that a mild cortisol hypersecretion or an impairment in circadian cortisol rhythm might be associated with glucose homeostasis or insulin-resistance in essential hypertensive (EH) patients.

Design and method:

In 155 non-diabetic EH patients we measured fasting glucose and insulin, calculated the HOMA-index, performed an oral glucose tolerance test (OGTT), calculated the area under the curve for glucose (GAUC) and insulin (IAUC), glucose level at 2-h of OGTT (G120), plasma cortisol level at 8 AM, 5 PM and 11 PM, and after overnight suppression with 1 mg of dexamethasone (DST), 24-h free urinary cortisol and plasma ACTH.

Results:

GAUC and G120 were associated with both 11 PM and post-DST cortisol levels. Fasting insulin level, HOMA-index and IAUC were associated with post-DST cortisol level. These associations were independent of age, adiposity, plasma potassium and ACTH levels, alcohol intake and physical activity.

Conclusions:

In non-diabetic EH patients free of overt CS or SCS, glucose uptake and insulin resistance are associated with subtle cortisol hypersecretion.
THE EXTRACELLULAR ROLE OF REF-1 AS ANTI-INFLAMMATORY FUNCTION
Authors: Jeon Byeong Hwa , Lee Yu Ran , Jo Hee Kyoung , Lee Eun Ok
Published: April 2021

Objective:

Apurinic/apyrimidinic endonuclease/redox factor-1 (Ref-1), a multifunctional protein secreted from stimulated cells, has been identified as a new serological biomarker. Active secretion of Ref-1 in cultured medium occurs in response to intracellular acetylation in cultured human embryonic kidney cells. The presence of plasma Ref-1 in lipopolysaccharides (LPS)-induced endotoxemic rats has also been reported. Despite recent reports on the role of Ref-1 in inflammation, the biological function of secreted Ref-1 remains unknown, especially in vivo. This study aimed to evaluate the possible roles of secreted Ref-1 in lipopolysaccharide-induced systemic inflammation in vivo.

Design and method:

We generated a secretory Ref-1 adenoviral vector system, AdPPT-LS-Ref-1, by conjugation of preprotrypsin leading sequence (PPT-LS) with full-length Ref-1 sequences. Plasma Ref-1 or secreted Ref-1 levels were evaluated with sandwich ELISA.

Results:

TNF-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells and lipopolysaccharide (LPS)-induced cyclooxygenase-2 in Raw264.7 cells was inhibited by secretory Ref-1, and this inhibitory effect was abrogated following neutralization of Ref-1 with anti-Ref-1 antibody. Plasma Ref-1 levels following administration of AdPPT-LS-Ref-1 (2 × 10^9 ifu, i.p.) for 24 h were substantially higher than those of Adgal (84.6 ± 7.2 ng/ml vs. 4.4 ± 1.5 ng/ml). Treatment with LPS (10 mg/kg, i.v. for 6 h) markedly increased VCAM-1 expression, cathepsin or myeloperoxidase activity, which were significantly suppressed by treatment with AdPPT-LS-Ref-1. Furthermore, LPS-induced cytokines, such as TNF-alpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractant protein 1, were significantly inhibited in AdPPT-LS-Ref-1-treated mice. However, LPS-induced myeloperoxidase activities were not suppressed by treatment with the redox mutant of secretory Ref-1, AdPPT-LS-Ref-1 (C65A/C93A), or wild-type AdRef-1.

Conclusions:

Collectively, these results suggest that secreted Ref-1 has anti-inflammatory properties and that its redox cysteine residue is associated with the anti-inflammatory activity in vivo. Furthermore, our findings indicate that secretory Ref-1 may be useful as a therapeutic biomolecule against systemic inflammation.
MITOCHONDRIAL ROS MEDIATE ENDOTHELIAL DYSFUNCTION INDUCED BY CHRONIC PARATHYROID HORMONE EXPOSURE
Authors: Iaccarino Guido , Gambardella Jessica , Fiordelisi Antonella , Prevete Nella , Sorriento Daniela
Published: April 2021

Objective:

Vitamin D deficiency contributes to cardiovascular risk (CVR), with hyperparathyroidism advocated as a putative mechanism. Indeed, mounting evidence supports the hypothesis that parathyroid hormone (PTH) impairs endothelial function, even though mechanisms are not fully elucidated. The present study was designed to verify in vitro the ability of sustained exposure to PTH to cause endothelial dysfunction, exploring the underlying mechanisms.

Design and method:

In bovine aortic endothelial cells (BAECs), we evaluated the effects of PTH exposure ([0,1 nM]-24 hours) on both endothelial response to vasodilators, such as bradykinin (Bk, [30 nM]) and acetylcholine (Ach [1 mM]), and angiogenic competence.

Results:

Pretreatment with PTH impaired endothelial response to Bk, but not to Ach, in terms of cytosolic calcium fluxes and NO production. In order to explore the underlying mechanisms, we assessed the production of total and mitochondrial ROS (respectively tROS and mROS) in response to PTH (at 1 and 3 hours). PTH increased ROS generation to an extent high enough to determine oxidation of Bk-receptor B2. Conversely, the oxidation levels oxidation of M1 and M3 Ach-receptors was not affected by PTH. A mROS selective scavenger (MitoTEMPO, [5 mM]) restored the endothelial responsiveness to Bk while the well known antioxidant properties of Vitamin D ([100 nM]) failed to counteract PTH-mediated oxidative stress. PTH determined mitochondrial calcium fluxes ([Ca2+]mt) and the inhibition of Mitochondrial Calcium Uniporter with inhibitor Ru360 [10 mM] reduced mROS production and prevented the following PTH-mediated endothelial dysfunction. Angiogenic competence was evaluated by tubular formations in Endothelial Matrigel Assay and showed a significant impairment in PTH-pretreated cells ([0,1 nM]-24 hours), despite the increase in VEGF transcriptional levels. VEGF-R2 oxidation occurred in response to PTH, suggesting that even the impairment of angiogenesis was due to ROS surge.

Conclusions:

These results indicate that PTH affects endothelial function through ROS production, driven by mitochondrial calcium overload. PTH-induced oxidative stress might act as signaling modifier, altering specific pathways (Bk and VEGF) and preserving others (Ach).
DAILY CONSUMPTION OF DIFFERENT FRUITS IS ASSOCIATED WITH LOWER SYSTOLIC HOME BLOOD PRESSURE IN POPULATION-BASED STUDY
Authors: Ström Edvin , Johansson Martina Ak , Engvall Jan , Östgren Carl Johan , Nystrom Fredrik H. , Wijkman Magnus
Published: April 2021

Objective:

Fruit consumption has in epidemiological studies been associated with lower blood pressure. We studied if home blood pressure was different when eating fruit daily compared to non-daily.

Design and method:

The study design was cross-sectional. Validated food frequency questionnaires and blood pressure monitors were used. The fruits asked for were bananas, apples and pears, citrus fruits including oranges and other fruit or berries. Dichotomisation was done into daily and non-daily fruit consumption. A subgroup analysis was performed regarding self-reported hypertension diagnosis at baseline. Means and differences were analysed with independent t-test.

Results:

In total there were 5057 participants (2531 men and 2526 women). Home blood pressure values were available in 5029 cases, with a mean of 120.8 ± 13.9 / 77.9 ± 8.7 mmHg. There were 1016 individuals in the population stating they had hypertension. Missing data on fruit consumption ranged from 18.0 % in the banana group to 28.1% in other fruit or berries in the total population. The proportion of individuals with valid values eating other fruit or berries daily was 18.9% (n = 686) and non-daily consumption at 81.1% (n = 2953).

The systolic blood pressure levels for the population were on average significantly lower when consuming fruit daily. The greatest difference was when eating other fruit or berries daily (n = 679), with 116.8 ± 13.3 mmHg compared to 120.5 ± 13.8 mmHg non-daily (n = 2940, p < 0.001). The largest difference in the material was found in those with hypertension diagnosis eating other fruit or berries daily (n = 119) with 123.9 ± 13.8 mmHg compared to non-daily (n = 585) 129.7 ± 12.0 mmHg (p < 0.001).

Conclusions:

Overall the blood pressure levels were lower in those consuming fruit daily. The largest difference in systolic blood pressure was when having hypertension and eating other fruit or berries daily compared to non-daily. Due to cross-sectional design, inference analysis is not possible. Further studies on the impact of different fruit consumption on home blood pressure seem warranted, particularly in patients with hypertension.
MAY MEASUREMENT MONTH 2019. AN ANALYSIS OF BLOOD PRESSURE SCREENING RESULTS IN CRETE, GREECE
Authors: Papanikolaou John A. Papadakis Kostas , Papakitsou Ioanna , Mavrikaki Vasiliki , Theodorakopoulou Fotini Psicharaki Vasiliki , Moschou Aikaterini , Vrentzos George
Published: April 2021

Objective:

Worldwide, there is a high level of ignorance about elevated blood pressure (BP), which contributes to the large percentage of underdiagnosed and untreated hypertensive subjects. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and acting as a stimulus to improving screening programs.

Design and method:

An opportunistic cross-sectional survey of volunteers aged = > 18 years was carried out in May 2019. Each adult individual underwent evaluation by 3 sitting BP measurements, a dedicated questionnaire regarding awareness of hypertension (HT) and control of it and other cardiovascular risk factors. Screenings sites in hospitals, shopping centres, workplaces, community centres, GP practices, and pharmacies were set up across the island of Crete as part of this initiative. HT was defined as SBP > 140mmHg and/or DBP > 90mmHg (average of 2nd and 3rd BP measurement) or previous HT diagnosis. BP control was defined as SBP/DBP < 140/90 mmHg in treated hypertensives.

Results:

During this survey, a total of 1612 participants [729 (45.2%) men] were screened for high BP and associated risk factors. Their median age was 57 (range: 18–93) years.

The prevalence of HT was 49.9% (57.9% in men and 43.4% in women; p < 0.001). Only 584 out of 805 hypertensives (72.5%) were treated. Among those on anti-hypertensive medication 70.0% were controlled.

Among hypertensive subjects, 13.7% did not have any other cardiovascular risk factor, 41.2% had dyslipidaemia, 25.8% were diabetics, 23.6% were smokers and 58.8% were obese.

Conclusions:

This study reveals that arterial hypertension prevalence continue to rise, with poor blood pressure control. There is an urgent need to conduct further national level screening campaigns to identify individuals with raised BP. This will ensure early detection and management of BP thereby reducing complications associated with it.
BLOOD PRESSURE CONTROL IN DIABETIC SUBJECTS: A NATIONWIDE EPIDEMIOLOGICAL SURVEY AMONG ITALIAN PHARMACIES CUSTOMERS
Authors: De Feo Martina , Del Pinto Rita , Grassi Davide , Ferri Claudio , Pagliacci Silvia
Published: April 2021

Objective:

The prevalence of hypertension is estimated at around 30% of the adult population in industrialized countries and is much higher in patients with diabetes mellitus. The global percentage of hypertensive individuals whose condition is treated and controlled is currently low. We analyzed data from a nationwide, cross-sectional epidemiological survey on pharmacies customers in order to have an overview of the prevalence and awareness of cardiovascular (CV) risk factors, with particular focus on hypertension and diabetes.

Design and method:

The survey was conducted in 3956 Italian pharmacies from 17 to 20 May 2018. Self-presenting participants were asked to answer a questionnaire on their clinical and demographic characteristics and lifestyle habits, and trained pharmacists measured their blood pressure (BP) according to guidelines. Prevalence of CV risk factors and hypertension rate/control according to the latest version of the European guidelines on hypertension was examined by diabetic status. Statistical analyses were performed using R (v3.5.1).

Results:

A total of 47217 subjects were enrolled in the project: 5695 diabetics and 41522 non-diabetics. Their characteristics are shown in Table 1.

Compared to non-diabetic patients, those with diabetes tended to be older, to declare a family/personal history of CV diseases/chronic kidney disease, to have prevalent/uncontrolled hypertension, dyslipidemia, higher mean systolic BP (135,96 ± 18,38 mmHg vs 128,32 ± 17,77 mmHg), and greater CV risk (p < 0.001). No significant differences in terms of salt intake, vegetable consumption, and smoking habits were recorded between the examined groups. Diabetic subjects with uncontrolled hypertension showed a lower propensity to physical activity (p = 0.016).

Conclusions:

Despite the limitations of the study design (selection bias, self-reported information, no data on medications and compliance, lack of generalizability), our results are substantially in line with the available literature, underlining that BP control is more challenging in diabetic patients, who normally present with a higher global CV risk. As lifestyle interventions (including dietary changes, weight loss, increased physical activity) appear effective both in lowering BP and reducing the incidence of diabetes, similar awareness-rising campaigns might be useful to promote CV health.
AWARENESS, TREATMENT AND CONTROL OF HYPERTENSION IN GREECE: THE EMENO NATIONAL EPIDEMIOLOGICAL STUDY
Authors: Stergiou George , Menti Ariadni , Kalpourtzi Natasa , Gavana Magdalini , Vantarakis Apostolos , Chlouverakis Gregory , Hadjichristodoulou Christos , Trypsianis Gregory , Voulgari Paraskevi , Alamanos Yannis , Karakosta Argiro , Touloumi Giota
Published: April 2021

Objective:

The evidence on the epidemiology of hypertension in Greece is limited. The EMENO nationwide epidemiological study assessed the prevalence, awareness, treatment and control of hypertension in randomly selected adults in the general population in Greece.

Design and method:

EMENO applied a multi-stage stratified random sampling method involving 577 areas throughout Greece from May 2013 to June 2016. Participants were assessed at homes visits with standardized questionnaires, blood tests and 3 seated blood pressure (BP) measurements (validated upper-arm oscillometric device Microlife BPA100 Plus). Hypertension was defined as BP >=140/90 mmHg (average of 2nd-3rd measurement) and/or use of antihypertensive drugs). Post-stratification weights were applied in order to match the age/sex distribution to the general population in Greece based on census 2011. Non-response was adjusted by inverse probability weighting.

Results:

A total of 6,006 subjects were recruited and 4,699 with complete data were analysed (mean age 49.0 ± 18.5 [SD]) years, men 48.5%, BMI 28.1 ± 5.7 kg/m2). The prevalence of HT was 39.2% and was higher in men than women (42.4% vs. 36.1%, p < 0.001). Among hypertensive patients, 32.0% were unaware (men/women 39.7/23.7, p < 0.001), 2.7% aware untreated, 34.9% treated uncontrolled (men/women 31.8/38.2, p < 0.001) and 30.4% treated controlled (men/women 25.7/35.6, p < 0.001).

Conclusions:

More than one third of the adults in the general population in Greece have elevated BP. One third of them are undiagnosed and only 30.4% are controlled with treatment. Nationwide programs are needed to prevent hypertension and improve its awareness and control in Greece.