bluuebunny/crossref_metadata_2025 huggingface dataset:
HYPERTENSION CHANGES THE ASSOCIATIONS BETWEEN HYPERURICEMIA AND OTHER CARDIOVASCULAR RISK FACTORS
Authors: Ruf Ruslan , Grinshtein Yuri , Shabalin Vladimir
Published: April 2021

Objective:

The present study analyzed the interrelations of gender, hypertension, and associations between hyperuricemia and other cardiovascular risk factors.

Design and method:

Within the scope of the ESSE-RF study, we formed a randomized representative sample of 1603 inhabitants of Krasnoyarsk Krai aged 25–64. The protocol of the study provided the questionnaire, anthropometry, office blood pressure measurement, and biochemical blood analysis (lipids, glucose, creatinine, and uric acid).

We registered hyperuricemia at serum uric acid levels higher than 360 micromoles/l in females and 400 micromoles/l in males. At measured blood pressure 140/90 mm Hg or more, or if a person took antihypertensive medications, we registered hypertension.

Statistical calculations included descriptive statistics (the percentage of people having hypertension or hyperuricemia and 95% confidence intervals), chi-square to check group disparities for significance, and logistic regression to analyze the associations of hyperuricemia and other cardiovascular risk factors. We considered disparities and associations significant at p =<0.05.

Results:

We found 30.7% (28.4%; 33.0%) of the sample having hyperuricemia. It was more prevalent in males compared to females (49.9% (45.9%;53.9%) versus 18.2% (15.7%;20.7%); p < 0.001) and in hypertension compared to normal blood pressure (57.7% (53.3%;62.2%) versus 45.7% (42.7%;48.7%); p < 0.001).

Regression analysis found more factors associated with hyperuricemia in males compared to females. The table shows additional disparities between normal blood pressure and hypertension.

Conclusions:

Krasnoyarsk Krai population demonstrated the high prevalence of hyperuricemia and its association with several metabolic and nutritional factors, including dyslipidemia and renal dysfunction. Hypertension and gender changed the amount and structure of the factors associated with hyperuricemia.
ALTERED EXPRESSION OF LUNG EPITHELIAL ION AND FLUID TRANSPORTERS DURING PROGRESSION OF PULMONARY HYPERTENSION IN THE MONOCROTALINE MODEL
Authors: Zirova Katarina , Kmecova Zuzana , Veteskova Jana , Podzubanova Martina , Klimas Jan , Krenek Peter
Published: April 2021

Objective:

Recent studies have evaluated a significant incidence of pleural effusions in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) co-diagnosed with isolated right-sided heart failure (RHF). Coincidence of pleural effusions and RHF in these patients significantly increased mortality rate during follow-up. However, mechanism of pleural effusions formation has not been fully explained. Therefore, we examined expression of lung epithelial ion and fluid transporters responsible for alveolar fluid clearance (AFC), which may contribute to lung fluid accumulation under pathological conditions and potentially formation of pleural effusions.

Design and method:

12-weeks old male Wistar rats were subcutaneously injected with monocrotaline (60 mg/kg, MCT) or vehicle (CON). The relative expression of AFC transporters: Na+/K+-ATPase alpha1, alpha2, beta1, beta3 subunits, epithelial sodium channel (ENaC) alpha, beta, gama subunits, cystic fibrosis transmembrane conductance regulator (CFTR) were determined by RT-qPCR 1, 2, 4 weeks after MCT application and also in end-stage disease (animals sacrificed after acute health deterioration, ∼ 4 weeks after MCT application) where pleural effusions were observed.

Results:

Increase in lung weight was observed from second week after MCT application and was more profound in end-stage disease (by 26 % compared to fourth week, p < 0.05). A downregulation of all three pore-forming subunits of ENaC was observed in end-stage disease, accompanied by downregulation of small beta3 subunit of Na+/K+-ATPase. Expression of catalytic alpha2 subunit of Na+/K+-ATPase gradually decreased with disease progression from first week after MCT (-80% in end-stage vs. CON, p < 0.05). On the other hand, we observed upregulation of CFTR (by 80%) and beta1 subunit of Na+/K+ATPase (by 79% vs. CON, p < 0.05) mainly in end-stage disease.

Conclusions:

Downregulation of lung epithelial ion and fluid transporters contributing to AFC is predominantly limited to higher stages of PH with a marked downregulation in end-stage. These expression alterations may contribute to overall lung weight increase observed in end-stage disease. However, observed early alpha2 subunit of Na+/K+-ATPase downregulation could participate on the pathogenesis of PH while upregulation of beta1 subunit and CFTR in end-stage disease could represent a compensatory mechanism.
EXOSOMAL MICRORNA-26A RESPONSE TO TGF-B1 STRESS IN HYPERTENSION
Authors: Martínez-Arroyo Olga , Ortega Ana , Perez-Hernandez Javier , Chaves Felipe J. , Redon Josep , Cortes Raquel
Published: April 2021

Objective:

In a previous work we established an exosomal miRNA signature associated to urinary albumin excretion (UAE) in hypertension, which included microRNA (miRNA) miR-26a, and obtaining cell signaling (MAPK, calcium, p53), TGF-ß and VEGF pathways as the most regulated biological processes. The aim of this work was to validate the exosomal miR-26a changes and its potential association with TGF-ß in human podocytes.

Design and method:

This prospective study analysed the miR-26a levels in 52 hypertensive patients, 24 with UAE (162,8 ± 168.2 mg/g creatinine; mean age 52.7 ± 8.4 years) and 28 normoalbuminuric (mean age 54.5 ± 5.6 years). Exosomes were isolated by differential ultracentrifugation from urine and plasma and miRNA levels were calculated by qRT-PCR. Urinary levels of TGF-ß1 were quantified by ELISA. Finally, human podocytes cultures were stimulated with recombinant human TGF-ß1 at several concentrations (5 ng/mL, 10 ng/mL and 15 ng/mL) for up 24 h to assess miR-26a changes in exosomal and cellular fractions.

Results:

We found a decrease in the levels of miR-26-5p in plasma and urinary exosomes of patients con increased UAE (p < 0.05 and p < 0.01, respectively). In addition, miR-26a-5p correlated inversely with UAE levels, both in urinary and plasma exosomes (r = -0.49, p < 0.01; r = -0.53, p < 0.01). Our patients also showed a significant increase in urinary levels of TGF-ß1 (2-fold increase, p < 0.05) in hypertensive patients with UAE. Finally, we analysed the effect in vitro of TGF-ß1 stress. Significant changes in scaffolding of podocytes, such as an increase of vimentin levels, has been also observed. Finally, significant down-regulated miR-26a expression in exosomes from podocytes after TGF-ß1 stimulation (5 – 15 ng / mL): 2.23, 1.96 and 1.7-fold decrease, with p < 0.001 and p < 0.05, respectively. No significant changes were obtained at intracellular level.

Conclusions:

Our results show that miR-26a-5p is decreased in urinary and plasma exosomes of microalbuminuric patients. In addition, exosomal miR-26a podocyte release is associated with TGF-ß1 pathway, key molecule in the development and maintenance structure of the glomerular filtration barrier and fibrosis.
ANGIOTENSIN II MODULATES MONOCYTE-TO-MACROPHAGE DIFFERENTIATION: EFFECT ON THP-1-LIKE MACROPHAGE CELL PHENOTYPE, POLARIZATION AND REACTIVE OXYGEN SPECIES GENERATION
Authors: Barhoumi Tlili , Boudjellal Mohammad , Mahmud Azra
Published: April 2021

Objective:

Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension, a highly prevalent cardiovascular(CV) risk factor associated with increased CV morbidity and mortality. One of the main effector cells in innate immune response are macrophages and several studies have reported their implication in pathophysiology of hypertension. In the vasculature and kidney, macrophage-derived reactive oxygen species (ROS) and inflammatory cytokines cause endothelial dysfunction, resulting in vascular oxidative stress and impairment of sodium excretion. Furthermore, angiotensin (Ang) II infusion is known to induce hypertension and vascular damage, particularly endothelial dysfunction, inflammation and oxidative stress. Renin angiotensin system (RAS) stimulation triggers monocyte activation and migration. ROS and cytokines secreted by macrophages can modulate blood pressure(BP) by triggering vascular endothelial dysfunction. Angiotensin II receptors are expressed in immune cells like T cells and monocytes. The aim of our study was to explore the effect of angiotensin II on THP-1-like macrophage cell phenotype, polarization and ROS generation.

Design and method:

THP-1-like macrophage cells were incubated with Ang II (100 nM) for 48 h. Cell phenotype analysis was performed using flow cytometry after intracellular and extracellular staining with CD11c, CD64, CD206, HLA-DR, CD116 and TNFa. We determined the effect of Ang II stimulation on ROS generation by macrophages using Cell Rox kit; viability and apoptosis using immunofluorescence and cell phenotyping using flow cytometry.

Results:

There was a significant increase in ROS generation in cells incubated with Ang II compared with control. Ang II induces THP-1-like macrophage polarization by increasing HLA-DR, CD11c and TNFa and decreasing CD206 markers. Ang II significantly increases apoptosis in a time-dependent fashion from 24 to 72-h and changed cell CD inflammatory markers after 24-h incubation.

Conclusions:

Differences in ROS generation, phenotype and polarization of THP-1-like macrophage cells in presence of Ang-II may underlie the role of monocyte/macrophages in vascular inflammation. The downstream pathways may be a potential therapeutic target for ang-II induced inflammation and vascular damage in hypertension.
REGIONAL AORTIC VASCULAR DYSFUNCTION IN A RODENT MODEL OF METABOLIC SYNDROME
Authors: Ameer Omar Ziad , Salman Ibrahim M , Alwadi Aiman Yahya
Published: April 2021

Objective:

Obesity and diabetes constitute a hallmark of metabolic syndrome that is directly linked to vascular dysfunction and high blood pressure (BP). Accordingly, we aimed to investigate regional functional changes in thoracic and abdominal aortic responses in a rat model of high fat diet (HFD) and streptozotocin (STZ)-induced diabetes mellitus.

Design and method:

Five weeks old male Wistar Albino rats (n = 24) were fed with either HFD (45 kcal% fat) or control diet (10 kcal% fat) for 10 weeks. At 10 weeks of age, 40 mg/kg STZ and saline were injected intraperitoneally into the HFD and control groups, respectively. At the end of the treatment, rats were euthanized to assess vasoconstrictor and vasodilator responses of dissected aortic segments.

Results:

Conscious tail-cuff systolic BP was higher in the HFD relative to control (154 ± 6 mmHg vs. 110 ± 4 mmHg, p < 0.001). Oral glucose tolerance test (oGTT) generated greater AUCs in the HFD rats relative to controls (64,361 ± 383 vs. 14,169 ± 398, p < 0.001). Abdominal aortic vasoconstriction (N/g) to norepinephrine (NE, 1E-9 – 3E-5 M) and the depolarizing signals of high potassium (KCl, 5 – 120 mM) was greater (p < 0.05) in the HFD group compared with controls. Thoracic aortic vasoconstrictor responses (N/g) to NE, but not KCl, were greater (p < 0.05) in the HFD group as compared to controls. Abdominal, but not thoracic, endothelium-dependent vasorelaxation to acetylcholine (1E-10 – 1E-5 M) was blunted (p < 0.05) in the HFD group relative to controls. In contrast, thoracic and abdominal aortic responses to sodium nitroprusside (SNP)-induced endothelium-independent relaxation remained comparable between groups.

Conclusions:

Vascular functional responses are altered along the descending aorta in metabolic syndrome, exhibiting exaggerated vasocontractility and impaired endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.
GENOME-WIDE ASSOCIATION STUDY FOR PHARMACOGENETIC RESPONSE OF BLOOD PRESURE TO BETA BLOCKER AND CALCIUM CHANNEL BLOCKER DRUGS
Authors: Warren Helen , Garofalidou Tatiana , Singh Sonal , Melander Olle , Hiltunen Timo , Glorioso Nicola , Cooper-Dehoff Rhonda , Dominiczak Anna , Caulfield Mark , Padmanabhan Sandosh , Munroe Patricia
Published: April 2021

Objective:

There is substantial inter-individual variability in blood pressure (BP) responses to anti-hypertensive drugs and it is hypothesised that there could be genetic influences. One goal of pharmacogenetics is to aid in treatment selection. However very few variants have been identified. After the success of genome-wide association studies (GWAS) for BP, it is hoped GWAS could also reveal genes associated with BP treatment response.

Design and method:

A discovery analysis was performed including participants from ASCOT and NORDIL studies. Six different analyses were performed for systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) responses to monotherapy beta blockers (BBs) and calcium channel blockers (CCBs).

BP response was defined as post-treatment BP minus baseline BP. All analyses adjusted for age, sex, baseline BP and principal components. ASCOT analyses were also adjusted for dose and previous antihypertensive use, and excluded patients taking either BB/CCB drug at baseline, whereas NORDIL participants were previously untreated and subsequently treated on the same drug dose.

Genotyped data was imputed to 1000 Genomes, testing ∼7million common variants. Results from ASCOT and NORDIL were meta-analysed, with total N = 2,556 for BBs and N = 3,369 for CCBs.

Any variants reaching P < 1 × 10-5 for SBP and DBP response to BBs were tested for replication in available ICAPS consortium data (N = 1,328).

Results:

Strong correlation between baseline BP and BP response shows patients with higher BP have greater BP reduction post-treatment.

No variants reached genome-wide significance in any of the GWAS analyses, and none replicated in ICAPS data.

Lookups of ∼1,000 published BP-associated variants were performed, but none reached Bonferroni significance level. Ongoing analyses are testing BP genetic risk scores for association with treatment response.

Comparison of GWAS results shows correlation between SBP vs DBP response (r2 = 0.48) and SBP vs PP response (r2 = 0.76), but none between response to BBs vs CCBs.

Conclusions:

Despite being the largest GWAS of antihypertensive response, we found no significant associations, showing that larger studies are still required to increase power for discoveries. Model comparisons show different genes are likely to influence response to different antihypertensive drugs, with different genetic architecture.
RELATION BETWEEN APOLIPOPROTEIN E GENE POLYMORPHISM AND LIPID SPECTRUM IN HYPERTENSIVE PATIENTS
Authors: Varahabhatla Sai Krishna Ragh , Buryak Viktor
Published: April 2021

Objective:

To study the relationship between apolipoprotein E gene polymorphism and lipid spectrum modification in hypertensive patients.

Design and method:

We examined 310 hypertensive patients (177 males and 133 females) ages 56,11 ± 0,68 years and history duration 6,51 ± 0,48 years, who were administrated with any antihypertensive components and no any specific lipid-lowering medications. According to office blood pressure measurement the average brachial value was 141,33 ± 1,34/87,62 ± 0,79 mmHg. The lipid spectrum components and apolipoprotein E gene polymorphism were assessed using automatic clinical biochemical analyzer «Cobas c311» and amplifier for single nucleotide polymorphism identification «Thermal Cycler CFX96TM Real-Time PCR Detection Systems» accordingly. Statistical data were presented like mean ± standard error and 95% confidence interval. Statistically significant difference was considered in case of P < 0,05.

Results:

The average values of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoproteins (VLDL), triglycerides and indices of atherogenicity was 5,18 ± 0,08 mmol/l [5,02–5,34], 1,32 ± 0,03 mmol/l [1,27–1,37], 3,06 ± 0,07 mmol/l [2,92–3,2], 0,79 ± 0,02 mmol/l [0,75–0,83], 1,74 ± 0,05 mmol/l [1,64–1,83] and 3,21 ± 0,08 [3,05–3,38] respectively. Apolipoprotein E polymorphism was presented with alleles E2 (n = 41, 13,26%), E3 (n = 291, 93,87%) and E4 (n = 95, 30,65%) as well. Based on single nucleotide polymorphism identification there were defined next variants of genotypes: E2/E2- rarest of all genotypes (n = 2, 0,65%), E2/E3 (n = 34, 10,97%), E2/E4 (n = 5, 1,61%), E3/E3 (n = 179, 57,74%), E3/E4 (n = 78, 25,16%) and E4/E4 (n = 12, 3,87%). This way, it was found the domination of homozygous variants (n = 193, 62,26%). Besides that, overwhelming majority of them had both E3 allele and, as a result, E3/E3 genotype (n = 179, 92,75%). More over, this trend was independent of age and gender affiliation, but full spectrum of genotypes was inherent only for elderly patients (n = 105, 33,87%).

Conclusions:

The course of arterial hypertension reflects the mild degree of activity (isolated systolic hypertension) of the disease. Arterial hypertension associated with mixed-dyslipidemia (type 2b). Apolipoprotein E gene polymorphism is characterized by a wide range of alleles and genotypes among the hypertensive population. In hypertensive subjects the most common allele is E3 as well as genotype – is E3/E3 (opposite to E3/E4 in case of heterozygous variant).
HYPERURICEMIA AND TELOMERE LENGTH IN SUBJECTS WITH NEW CASES OF HYPERTENSION ACCORDING TO THE 10-YEAR PROSPECTIVE STUDY
Authors: Podpalova Olga , Generalov Igor , Podpalov Vladislav , Babenko Andrei , Kolyadko Marina , Mrochek Aleksandr
Published: April 2021

Objective:

To reveal the association of high level of serum uric acid and telomere length in 10-year prospective study using the data from Belarusian national representative survey.

Design and method:

In 2007/2008 a 10-year prospective analysis of 3500 randomized individuals living in a district of Vitebsk started (coverage of the survey was 97.9%). In 2012/2013 there was a second screening of this population (coverage of the survey was 84.3%) respectively. In 2017/2018 a 10-years prospective analysis included subjects with newly diagnosed hypertension in the second screening. Examination of these patients included standard questionnaires for detection of cardiovascular risk factors, measurements of blood pressure, blood chemistry, electrocardiography, echocardiography, ultrasound examination of brachiocephalic vessels, real-time PCR for the detection telomere length of peripheral blood lymphocytes.

Results:

We examined population of 2171 persons with normal blood pressure and 1257 persons with hypertension in 2007/2008. 286 new cases of hypertension developed in 5 years (14,4% of men and 12,2% of women). According to multifactorial regression analysis we revealed significant positive relationship between the frequency of new cases of hypertension and IV quartile of serum uric acid level (339–527 mmol/l) (df = 1; c2Wald = 5,1; p < 0,05) as well as other risk factors, adjusted for age and sex. Regression analysis of 170 randomized subjects showed that the IV quartile of uric acid level (339–527 mmol/l), determined at first screening, was associated with the I quartile of telomere length in 10 years in subjects with newly diagnosed hypertension adjusted for age and sex (df = 1; c2Wald = 4,9; p < 0,05).

Conclusions:

Level of serum uric acid > = 339 mmol/l was a risk factor for the development hypertension in 5 years in randomized urban population and detection of lower level of telomere length in 10 years in persons with new cases of hypertension.
AGT, ACE, AGTR1, UMOD AND ADIPOQ GENES POLYMORPHISMS INTERACTIONS IN PREHYPERTENSION
Authors: Simicevic Livija , Josipovic Josipa , Milicic Borna , Djacic Kresimir , Domislovic Viktor , Gelemanovic Andrea , Jelakovic Ana , Zivka Dika , Karanovic Sandra , Bozina Tamara , Lovric Jasna M. , Jelakovic Bojan
Published: April 2021

Objective:

Prehypertension (PHT) is recognized as a cardio-renal risk factor, and associated with progression to hypertension (HT). Studies of the genetic background of PHT have not been fully elucidated and the results suggested a possible role of genes involved in the etiopathogenesis of HT. The lack of data has prompted this study to hypothesize that hypertension and metabolic syndrome-related AGT rs2004776, ACE rs1799752, AGTR1 rs5186, UMOD rs13333226, ADIPOQ rs266729 and rs17300539 gene polymorphisms are more commonly found in subjects with PHT, than in subjects with optimal and normal blood pressure (BP).

Design and method:

A total of 601 subjects were included in this cross-sectional, observational study; 319 with high normal BP (PHT, 120–139/80–89 mmHg), ages 20–45, and 282 individuals with normal and optimal BP as a control group (NT).

Results:

The results indicated that the AGT, ACE, AGTR1, UMOD, and ADIPOQ gene polymorphisms were not found more frequently in PHT subjects than in NT. A significant difference was found in the number of rs266729 ADIPOQ heterozygous carriers; there were less carriers in the PHT group (35.1%) than in the NT group (44.7%), P < 0.03. The significance of the heterozygous model (CG vs GG/CC) of rs266729 ADIPOQ polymorphism in PHT in terms of reduced risk was observed (OR 0.66; 95% CI 0.47–0.92; P = 0.01). PHT was significantly associated with following haplotypes: hIAGCA ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729:AGTR1 (OR 1.56; 95%CI 1.08–2.24; P = 0.02), hIAGC ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.45; 95%CI 1.07–1.96; P = 0.02), hIAG ACE:UMOD:ADIPOQ_rs17300539 (OR 1.30; 95%CI 1.00–1.68; P = 0.05), hAGC UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.37; 95%CI 1.07–1.77; P = 0.01) and hAG UMOD:ADIPOQ_rs17300539 (OR 1.42; 95%CI 1.07–1.90; P = 0.02). Results emphasized two significant models of gene-gene-other determinants interactions with PHT, one model included creatinine, total cholesterol, alpha-1-microglobulin, ADIPOQ rs17300539 and UMOD rs13333228; and the second model includes ADIPOQ rs17300539, AGT rs2004776, cardiovascular risk, sex, BMI, and the gene-gene interaction AGTR1:ADIPOQ_rs266729:UMOD:ACE.

Conclusions:

The finding of five significantly related gene-gene interactions, as well as the discovery of their haplotypes that increase the PHT risk, and the finding of two gene-gene-other determinants interactions models, confirmed the good selection of genes, particularly UMOD and ADIPOQ, involved in various biological pathways responsible for controlling BP.
LIDDLE SYNDROME – DETECTION OF NOVEL MUTATION IN A FAMILY WITH HYPERTENSION
Authors: Filipovsky Jan , Mares Stepan , Pesta Martin , Hrabak Jaroslav
Published: April 2021

Objective:

Liddle syndrome is a rare monogenic form of arterial hypertension with autosomal dominant inheritance. It is caused by mutation of genes coding one of three subunits of epithelial sodium channel (ENaC), which is located in distal nephron. Under physiological conditions, its expression and activity is regulated to maintain fluid and electrolytes homeostasis by reabsorbing Na+. Mutated channel cannot be degraded and therefore, it is accumulated on cell membrane; this results in enhanced sodium reabsorption. The most common clinical presentation of Liddle syndrome is early onset of hypertension, hypokalemia, suppressed plasma renin activity and low plasma aldosterone level. Up to now, 36 mutations causing Liddle syndrome were described.

Design and method:

Genetic assessment was performed in a Czech family of three generations (n = 14, see Figure) where hypertension and tendency to hypokalemia was present in several members. We used PCR amplification of specific alleles of SCNN1B and SCNN1G genes which was followed by Sanger sequencing.

Results:

We present a novel mutation causing Liddle syndrome: Tyr604∗ in beta-subunit of epithelial sodium channel. This mutation is supposed to generate a premature stop codon at position 604, resulting in truncated beta-subunit of EnaC. It was found in 7 members of the family: I-1, II-1 and 2, and III-1 to 4. Phenotypes of these subjects were different: from severe hypertension and hypokalemia (subjects I-1 and III-3, manifestation in 10 and 5 years, respectively) to normotension with normal potassium levels (III-1 and 2, now aged 8 and 10 years, respectively); however, all the seven subjects with mutation had hypoaldosteronism (serum level < 0.13 ng/ml).

Conclusions:

A new mutation causing Liddle syndrome is described. It is manifested with different severity and mild forms that are not manifested in early childhood exist; thus, Liddle syndrome may be more frequent among adult hypertensive subjects than currently supposed. Proper diagnosis is important as the patients respond well to treatment with ENaC blocker amiloride.
ASSOCIATION OF ARTERIAL STIFFNESS WITH AGT, ACE, NOS3, TNF, MMP9, CYBA POLYMORPHISM IN HEALTHY ADULTS
Authors: Akopyan Anna , Kirillova Karina , Turchina Tatiana , Samokhodskaya Larisa , Strazhesko Irina , Orlova Iana
Published: April 2021

Objective:

Arterial stiffness (AS) is a prominent risk factor for cardiovascular diseases. It is known that different polymorphisms are associated with cardiovascular diseases, while there is insufficient evidence that genetic traits lead to arterial wall changes, including AS. The aim of this study was to find the association between increased AS and polymorphisms that are associated with cardiovascular diseases and are involved in renin-angiotensin-aldosterone system, chronic inflammation and oxidative stress in healthy adults.

Design and method:

We investigated 153 healthy adults, mean age 50.56 ± 13.14 years, 35% male, 22% smokers. Increased AS was defined as pulse wave velocity (PWV) > 10 m/s. Measurements were performed by applanation tonometry using SphygmoCor device (AtCor, Australia). Insulin resistance was diagnosed if HOMA IR was > 2,5. Leucocyte telomere length (LTL) were measured by real-time PCR. AGT, ACE, NOS3, TNF, MMP9 polymorphisms were detected by real-time PCR using DNA technologies (Russia) standard kits, and CYBA polymorphism was detected by Applied Biosystems (USA) standard kit. Associations of genotypes and alleles with increased PWV were studied using chi-square or Fisher's exact test. Multiple logistic regression models were created to identify the effect of genotype and risk factors on PWV.

Results:

Increased AS was associated with D-allele (OR = 1.89, 95% CI: 1.16–3.12, p = 0.014) and DD-genotype (OR = 3.42, 95% CI: 1.39–9.36, p = 0.005) of ACE Ins > Del polymorphism. ACE Ins > Del polymorphism predicted increased AS along with sex, age and LTL. The results of multiple logistic regression analysis are represented in the table.

Conclusions:

In healthy adults increased AS is strongly associated with DD-genotype of ACE polymorphism, sex, age and leucocyte telomere length
HYPERTENSION CAUSED WITH LONG-TERM UNCONTROLLED USING OF NASAL DECONGESTANTS. HOW SAFE ARE OVER-THE-COUNTER DRUGS FOR SELF-MEDICATION?
Authors: Schelkanovtseva Ekaterina , Ermolaev Alexander , Mironova Olga
Published: April 2021

Objective:

Elevated blood pressure is known to increase the cardiovascular risks. High blood pressure (BP) can be both a consequence of incorrect drug use and other forms of hypertension. Over-the-counter (OTC) drugs can carry a potential risk, but still in a number of countries the OTC drugs can be bought without a doctor‘s prescription.

Design and method:

A 46-year-old man presented with headache, palpitation, high BP of 160/100 mmHg. These symptoms worsened during last month. The patient was working as a coal miner for 23 years. Bad habits: smoking for 10 years with pack of cigarettes a day. He was diagnosed essential hypertension five years ago and asthma four years ago. He referred to a physician. Mono-therapy of losartan 25 mg twice a day was prescribed, but there was no persistent effect of it. Physical examination: BMI 30.7 kg/m2, office BP 150/100 mmHg, heart rate 92/minute. By chemistry: creatinine 109.11 mkmol/l, GFR 95.4 ml/min (CKD-EPI), total cholesterol 3,86 mmol/l, triglycerides 3.09 mmol/l, HDL 0.88 mmol/l, VLDL 1.4 mmol/l, LDL 1.4 mmol/l. Blood count with a normal range. Ambulatory BP measurements for 24 hours on monotherapy of losartan: the mean pressure per day 143/87 mmHg, a non-dipping BP profile. Both eyes hypertension retinopathy was revealed. He did not have a left ventricular hypertrophy on echocardiogram. The patient revealed the use of OTC nasal decongestants for 20 years to treat the presence of chronic nonallergic rhinitis. The patient was advised to exclude the nasal decongestants. The office BP was 115/80 mm/Hg in the morning and 125/85 mm/Hg in the evening since 10 days after exclusion of nasal drops.

Results:

A nasal septal deviation was recently revealed. Septoplasty led to successful reduce of his nasal symptoms. On follow-up visit the patient had normal BP level without any antihypertensive therapy.

Conclusions:

This clinical case demonstrates the importance of drug regulation and potential harm for the OTC drugs use by the general population without of medical appointments. Notably, the importance of using a proper talk with patients suffering hypertension and to suggest a questionnaire aimed at detection of secondary reasons.
MAY MEASUREMENT MONTH: DATA FROM A NATIONAL SCREENING PROGRAMME IN OMAN IN 2017 AND 2018
Authors: Al-Riyami Hassan , Nadar Sunil , Al-Riyami Adil , Panakkal Benny , Mohammed Shafeeq , Gb Nagaraju , Sharma Sn , Beaney Thomas , Ster Anca , Poulter Neil
Published: April 2021

Objective:

Hypertension is a major cardiovascular risk factor yet many patients remain undiagnosed. The aim of the May Measurement Month (MMM) screening programme was to identify individuals with undiagnosed hypertension.

Design and method:

This study was part of a global screening programme with screening centers set up in various hospitals and public areas in Muscat, Oman during the months of May 2017 and 2018. Screening was done according to the MMM protocol with three blood pressure (BP) readings taken along with a questionnaire of demographic, lifestyle and other risk factors. Hypertension was defined according to the European Society of Hypertension 2018 guidelines,(systolic BP(SBP) greater than140mmHg and/or diastolic BP(DBP) greater than 90mmHg)

Results:

A total of 13,621 individuals (age 40.8 + 12.6 years, 30.1 % male, 88.4% arab ethincity) were screened over the two month period. The mean of the first BP was 132.1 + 19.1/ 81.1 + 12.2 mmHg. The average of the second and third readings, where available (n = 5,934, age 41.5 + 14.3 years, 64.4% male) was 128.5 + 17.7/79.1 + 11.1 mmHg. This was significantly lower than the first BP reading alone (p < 0.001 for both SBP and DBP). Women were more likely to have only one reading. Further analysis was done only where three BP readings were available. In those with 3 BP readings, 1438 individuals (of which 471 were on antihypertensive medication) had BP in the hypertensive range. This works out to 47.7% of patients on medications(n = 988) having uncontrolled BP. The remaining 967 were newly diagnosed hypertensive. The number of hypertensives in our sample therefore was 1,955, giving a proportion of 32.9% of hypertensive individuals (of those with three BP readings) in our sample. Pregnant women had significantly lower BP than non pregnant women. By binary logistic regression, the factors predicting BP in the hypertensive range were age, sex, previous stroke, but not diabetes, previous MI or ethnicity

Conclusions:

In Oman, the proportion of individuals having hypertension is comparable to previous estimates and surveys. A high proportion of individuals on treatment still have uncontrolled BP. More needs to be done to educate the public regarding the need for better BP control.
BLOOD PRESSURE RESPONSE TO AN ISOMETRIC CONTRACTION AND 3 MINUTE OF TREADMILL TEST PREDICTS LEFT VENTRICULAR HYPERTROPHY IN NORMOTENSIVES
Authors: Pittaras Andreas , Faselis Charles , Grassos Haralampos , Poulimenos Leonidas , Doumas Michel , Stavropoulos Konstantinos , Kyfnidis Konstantinos , Samuel Immanuel , Pyriovoli Georgia , Kallistratos Manolis , Imprialos Konstantinos , Manolis Athanasios , Kokkinos Peter
Published: April 2021

Objective:

Left ventricular hypertrophy (LVH) is associated with a significant increase in major CV event. Recent evidence supports the presence of LVH independent of BP and other confounders.

The presence of LVH, especially in those with normal resting BP, is likely to remain undetected in this cohort for two main reasons: 1) The misconception that LVH only occurs when hypertension is present and, 2) The non-invasive methods to screen for LVH either have poor sensitivity (EKG) or are relatively costly and labor intensive (Echo, MRI). We hypothesized that BP response in isometric contraction, and exercise treadmill test, will be significantly associated with cardiac structure and function, providing an inexpensive and practical screening method to identify pts at high risk of LVH.

Design and method:

In 344 men and 46 women, normotensives with no ECG-LVH, we assessed BP response: 1) during an isometric contraction (HGR) using 50% of the maximum force generated (1-RM) and 2) at 3 min of exercise treadmill test (ETT). Cardiac structure was assessed via echocardiogram. We used a logistic regression to determine the relationship between HGR-BP, ETT-BP and LVH, with LVH as the dependent variable. The model was adjusted for age and resting BP.

Results:

Both HGR-SBP/DBP, and ETT-3min-SBP/DBP were significant predictors of LVH (p < 0.05).

Inflection point analysis identified a HGR-SBP/DBP threshold of 146/84mmHg and ETT-SBP/DBP threshold 141/78 mmHg.

Beyond these thresholds, the probability of LVH increased by 3% for every 1 mmHg change in SBP and 6% in DBP for HGR, and 2% & 4% for ETT-SBP/DBP respectively.

The sensitivity and specificity of HG-SBP test was 90% and 79%

The sensitivity and specificity of ETT-SBP-3 min test was 90% and 82%

Conclusions:

Both HGR-SBP/DBP and ETT-3min-SBP/DBP were strong predictors of LVH in normotensive subjects with no evidence of ECG-LVH, having clinically significant sensitivity and specificity.
NONINVASIVE MEASUREMENTS OF NORMAL VALUES OF STROKE VOLUME AND TOTAL PERIPHERAL RESISTANCE IN AN ELDERLY POPULATION ACCOUNTING FOR AGE AND SEX DIFFERENCES
Authors: Woodford Stephen , Avolio Alberto , Butlin Mark
Published: April 2021

Objective:

Clinical management guidelines generally provide ideal ranges for stroke volume (SV) and total peripheral resistance (TPR) [1] and rarely provide detailed normal values addressing age and sex, particularly in the elderly population. This has likely impact on anaesthesia management in surgery and critical care and may impact other clinical fields. This study quantifies SV and TPR in older age.

Design and method:

1051 (579 female) participants 50–100 years old presenting for a range of surgeries were studied at rest pre-surgery. SV was determined noninvasively using either the Vigileo Flotrac (Edwards Life Sciences) or Uscom 1A (USCOM) device. Coupled with blood pressure measurement, SV and TPR were calculated and cross-sectional differences were quantified in relation age, sex, and body mass and surface area.

Results:

At any age, SV and TPR differed in males and females and correlated with body mass index and body surface area. In both sexes, SV decreased and TPR rose for each decade. In females between the 6th and 10th decades, mean resting SV fell from 84 ± 14 mL to 40 ± 6 mL (outside “normal” range of 60–100 ml [1]), and TPR rose from 1200 ± 240 dynes.sec/cm5 to 2720 ± 480 dynes.sec/cm5 (above “normal” range of 1000–1500 dynes.sec/cm5 [1]). In males, mean resting SV fell from 111 ± 23 mL to 64 ± 10) mL (within “normal” range) and TPR rose from 1040 ± 160 dynes.sec/cm5 to 1600 ± 240 dynes.sec/cm5 (marginally above “normal” range) [1].

Conclusions:

SV and TPR as reported by the Vigileo Flotrac and Uscom 1A devices move outside the generally accepted “normal” range for older individuals. This may either be due to the algorithms used for noninvasive calculation of SV and TPR, or may mean that “normal” values need to be revisited for older individuals, which will require confirmatory evidence by direct or invasive methods.

[1] Parrillo, J.E. & Dellinger, R.P., 2008. Principles of Diagnosis and Management in the Adult, Philadelphia: Mosby Elsevier.
QUANTITATIVE METHODS FOR ASSESSING CONTRACTILE RESERVE IN PATIENTS WITH HYPERTENSION AND DIASTOLIC HEART FAILURE
Authors: Hristova-Tselova Krasimira , Tselov Nikolay , Tsonev Svetlin , Marinov Rumen
Published: April 2021

Objective:

We assessed the effect of several hemodynamic parameters and it changes during handgrip maneuvers in patients with different stages of diastolic heart failure during chemotherapy and their improvements after 4 months follow up (4mFU) treatment with single pill combination of ACE inhibitor ACE) and beta –blocker (BB).

Design and method:

The study population included 65 patients- female / mean age of 45 ± 12 years/ 55 with breast cancer and undergoing chemotherapy / 30 pts with HFpEF and 25 pts with HFmrEF / and 10 pts with HFnEF and without chemotherapy. Following maximal squeeze by 100%, during the next 3 minutes patients were instructed to apply pressure at 50%. The global longitudinal strain and MAP and HR were performed at basal level, 1st, 2nd and 3rd minutes during handgrip stress test. The contractility /force/ of LV were also calculate as ratio SBP / ESV.

Results:

Heart rate (HR) and mean arterial pressure (MAP) increased significantly after handgrip maneuver / from 75 ± 6 beats /min to 101 ± 12 beats/ min, 109 ± 15 mmHg to 118 ± 19 mmHg, p < 0,05 /. Pulmonary artery systolic(s) and diastolic (d) pressure (PAP),pulmonary capillary wedge pressure (PCWP), cardiac index (CI), LVEF did not change significantly (p > 0,5) after handgrip maneuvers. On the other hand, LV force (SBP/ ESV ratio), MAP and HR decreases significantly (p < 0,01) in group with HFmrEF. In same group were found significantly decreased GLVLS at 2nd and 3rd minutes during stress- test comparable with other 2 groups with HFpEF and HFnEF. After 4mFU and treatment with 5/5 mg doses combination of ACE / BB were found improvement in parameters: HR /p < 0,001/, MAP /p < 0.01/ and contractile reserve as well as LV force /p < 0, 01/ and GLVLS /p < 0,001/.

Conclusions:

Patients with good LV reserve had a rise in stroke –work with little or no change in LVEDP. Patients with poor contractile reserve had a fall in stroke- work reserve together with a substantial rise in LVEDP. The treatment with combination with small doses ACE/BB is a big challenge in patients with HFmrEF and HFpEF to improve the contractile reserve.
AORTIC STIFFNESS AND LEFT VENTRICULAR MASS ASSESSED BY CARDIOVASCULAR MAGNETIC RESONANCE IN ADOLESCENTS WITH WHITE COAT HYPERTENSION, SPURIOUS HYPERTENSION AND TRUE HYPERTENSION
Authors: Sarnecki Jedrzej , Obrycki Lukasz , Feber Janusz , Litwin Mieczyslaw
Published: April 2021

Objective:

Cardiovascular magnetic resonance (CMR) is the gold standard for the noninvasive assessment of left ventricular mass (LVM) and it permits the evaluation of aortic stiffness (AS).

Our aim was to assess LVM and AS in adolescents with suspected arterial hypertension (AH), who were divided into the following groups: white coat hypertension (WCHT), spurious hypertension (sHT) and true hypertension (tHT).

Design and method:

LVM, pulse wave velocity in the proximal (proxPWV) and whole thoracic aorta (thPWV) were assessed by CMR imaging in 72 patients with suspected AH (15 girls, mean age 16.4 ± 1.5years).

Based on the results of 24-hour ambulatory blood pressure monitoring AH or WCHT was diagnosed. AH group was further subdivided into sHT, defined as isolated systolic hypertension with normal central blood pressure (cBP), and tHT defined as elevated cBP.

Results:

WCHT was diagnosed in 42 and AH in 30 patients (12 sHT; 18 tHT).

Comparison of WCHT with AH revealed significantly higher LVM index (LVMI, 63.8 ± 11.3 vs 72.6 ± 8.8 g/m2), LVMI z-score (0.4 ± 0.8 vs 1.0 ± 0.7), proxPWV (3.9 ± 0.8 vs 4.5 ± 1.4m/s), proxPWV z-score (0.3 ± 1.1 vs 1.0 ± 1.6) and thPWV (3.7 ± 0.7 vs 4.2 ± 0.8m/s) in AH group (p < 0.05 for all comparisons).

LVMI/LVMI z-scores were significantly higher in both sHT (72.8 ± 10.8 g/m2 / 0.96 ± 0.79) and tHT (72.5 ± 7.5 g/m2 / 0.99 ± 0.64) as compared to WCHT (63.6 ± 11.3 g/m2 / 0.34 ± 0.82). Patients with sHT also had significantly higher thPWV (4.4 ± 0.8m/s) compared to WCHT (3.7 ± 0.7m/s) and tHT (4.0 ± 0.8m/s).

Conclusions:

Both tHT and sHT are associated with greater LVM and AS than WCHT. This supports the argument that sHT is not a benign phenomenon.
ARTERIAL STIFFNESS IN CHRONIC AUTOIMMUNE LIVER DISEASES. A PILOT STUDY
Authors: Premuzic Vedran , Knezevic-Stromar Ivana , Sesa Vibor , Premuzic Marina , Ostojic Rajko , Jelakovic Bojan
Published: April 2021

Objective:

Chronic inflammatory disease increase arterial stiffness and are associated with accelerated atherosclerosis. Our aim was to determine augmentation index (AIx) and pulse wave velocity (PWV) in patients with chronic autoimmune liver disease.

Design and method:

We have enrolled 38 patients (3m 35w; age 58.7 ± 9.6) with chronic autoimmune liver disease (autoimmune hepatitis 4, primary biliary cholangitis 24, primary sclerosing cholangitis 10). Office blood pressure (BP) was using Omron M6; PWV and AIx by Arteriograph. The assessment of liver cirrhosis was determined with FibroScan. Fasting blood and 24-hour urine samples were collected. Hypertension was diagnosed in 42.1% patients (18.7% were treated) and diabetes in 8.4%.

Results:

PWV was 9.7 m/s while AIx was also increased (32.8%). PWV was positively correlated with age, sedimentation rate, CRP and central systolic BP and negatively with eGFR. AIx was positively correlated with heart rate and central systolic BP. Linear regression analysis showed positive association of Aix with duration of disease, sedimentation rate, total cholesterol,triglycerides and FibroScan stiffness. PWV was positively associated with age, duration of disease, sedimentation rate, total cholesterol and triglycerides. We found that patients with PWV > 9 m/s were significantly older, had higer sedimentation rates, lower GFR, higher total cholesterol, LDL cholesterol, systolic/diastolic BPr and central systolic BP values.

Conclusions:

Patients with chronic autoimmune liver diseases have increased arterial stiffness than general population which confirmed our hypothesis on impact of chronic inflammation on increased arterial stiffness. However, this should be confirmed on larger number of patients.
WHITE-COAT HYPERTENSION AND ARTERIAL STIFFNESS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Premuzic Vedran , Jelakovic Mislav , Prijic Radovan , Jelakovic Ana , Cukovic-Cavka Silvija , Krznaric Zeljko , Jelakovic Bojan
Published: April 2021

Objective:

Our aim was to analyze cardiovascular (CV) risk factors, target-organ damage, arterial stiffness and ABPM in patients with inflammatory bowel disease (IBD).

Design and method:

A total of 120 IBD patients (77 Crohn; 43 ulcerative colitis; age 37.1 ± 4.2; men 58.3%) were enrolled. Office blood pressure (BP) (Omron M6), pulse wave velocity (PWV) and aortic augmentation index (AIx) (Arteriograph) and ABPM (SpaceLab 90207) were measured in all patients. Hypertension was defined as BP > 140/90 mmHg. None of patients used antihypertensive drugs. Chronic kidney disease (CKD) = eGFR < 60 ml/min/1.73m2 (CKD Epi); microalbuminuria (MA) = 24-h albuminuria > 30 mg/dU.

Results:

Dyslipidemia, left ventricular hypertrophy, CKD and MA were found in 10%, 0.83%,1.67% and 15% of patients, respectively. PWV > 8m/s was found in 45% of patients. In the linear regression model age and duration of IBD were only positive predictors of higher PWV. On logistic regression older patients and patients with longer duration of IBD had OŔs for PWV > 8 m/s of 0.94 [CI 0.89, 0.99] and 0.99 [CI 0.98, 1.00]. In the whole group of patients older age and longer duration of IBD had OŔs for TOD (0.93 [CI 0.89, 0.96]; 0.99 [CI 0.98, 1.00]). White coat hypertension (WCH) was found in 38 subjects (31.7%), while 1 patient had masked hypertension. There were 41.7% non-dippers. We failed to find differences in traditional CV risk factors between WCH and normotensives. However, patients with WCH had significantly higher values of central systolic BP, AIx and PWV. PWV and non-dipping pattern were associated with WCH (OR 0.69 [CI 0.52, 0.92] and 2.50 [CI 1.08, 5.77].

Conclusions:

The most important finding of our study is high prevalence of WCH which was associated with PWV, Aix and higher central systolic BP. The second important result is higher prevalence of patients with PWV above the cut off value which was associated with age and the duration of IBD but not with other traditional risk factors. We confirmed that traditional CV risk factors are not frequently present in IBD patients indicating that inflammation is important determinant of arterial stiffness in IBD.
VASCULAR IMAGING IN TAKAYASU DISEASE
Authors: Abid Dhia El Hak , Thabet Maissa , Jihed Anoun , Monia Karmeni , Fatma Ben Frej , Amel Rezgui , Chedia Laouani
Published: April 2021

Objective:

Assessment of the radiological characteristics in a series of Tunisian patients with Takayasu disease.

Design and method:

Retrospective study of records of patients with Takayasu arteritis who were admitted in our department between 1997 and 2017. The diagnosis was established according to the criteria of the American College of Rheumatology (1990).

Results:

We have included 26 patients (5 men and 21 women). The average age at the time of diagnosis was 34.27 years (extremes: 16 - 46 years). The occlusive phase lesions were assessed with Doppler ultrasound (n = 21), Computed Tomography Angiography or CTA (n = 19) and Magnetic Resonance Angiography or MRA (n = 7). The main observed abnormalities were: parietal thickening (n = 19), stenosis (n = 19) and aneurysmal dilation (n = 5). Arterial damage predominated in the left subclavian artery (n = 22), the right subclavian artery (n = 19) and the left common carotid artery (n = 11). The aorta was affected in its ascending portion (n = 9), its arch (n = 9), its descending thoracic portion (n = 8) and its abdominal portion (n = 5). The right and left axillary arteries were affected in seven and eight cases respectively. Lesions of the humeral artery were noted on the right and left sides, in four cases each. The left renal artery was more frequently affected (ten cases on the left side versus eight cases on the right side). Digestive vascular impairment concerned three patients. A pulmonary arteritis was noted in one case. The lesions were angiographically classified: type 1 (n = 6), type 2A (n = 1), type 2B (n = 1) and type 5 (n = 18).

Conclusions:

The results obtained in our series are in line with the literature data. Doppler ultrasound and CTA were the most commonly used radiological modalities. The access to other types of imaging, particularly the MRA and the Positron Emission Tomography or PET-Scan, remains limited in our context due to problems of cost and availability.