bluuebunny/crossref_metadata_2025 huggingface dataset:
SLEEP PATTERNS AND CARDIOVASCULAR HEALTH IN CHINESE CHILDREN AND ADOLESCENTS
Authors: Dong Hongbo , Yan Yinkun , Liu Junting , Zhao Xiaoyuan , Cheng Hong , Hou Dongqing , Huang Guimin , Mi Jie
Published: April 2021

Objective:

Despite accumulating evidence showing that sleep patterns are correlated with cardiometabolic risks, their relations to cardiovascular health (CVH) in children and adolescents remains inconclusive. Therefore, we aimed to investigate the associations of sleep duration and bedtime with CVH among Chinese children and adolescents.

Design and method:

Data were obtained from a population-based cross-sectional study, with 7,220 Chinese children and adolescents aged 6–18 years were included for analysis. The scores and levels of behavioral (smoking, body mass index, physical activity, and diet), biological (total cholesterol, blood pressure, and glucose), and global CVH were evaluated according to the American Heart Association's recommendation. Information on sleep duration and timing were collected by questionnaires. Subjects with sufficient sleep duration (> = 9 hours in individuals aged 6–12y or >8 hours in those over 13y) and early bedtime (22:00 before) were defined as having optimal sleep patterns. Generalized additive models and logistic regressions were performed to estimate the relationship between CVH and sleep patterns.

Results:

For boys, positive dose-response relations were found between sleep duration and all three CVH scores, but negative associations were observed for bedtime. Compared with boys with optimal sleep patterns, those with insufficient sleep duration and late bedtime had lower odds of ideal biological CVH (OR = 0.680, 95% CI: 0.525–0.881, p = 0.004) and ideal global CVH (OR = 0.681, 95% CI: 0.525–0.883, p = 0.004). Though similar results were also showed in girls, no statistically significant association was noted between sleep pattern variables (duration and timing) and any CVH scores or levels.

Conclusions:

Sufficient sleep duration and early bedtime are associated with desirable cardiovascular health in children and adolescents, especially for boys. However, causal interpretation cannot be made and associations might be bidirectional.
NO SIGNIFICANT DIFFERENCE SEEN IN QUALITY OF LIFE MEASURED BY SF-36 QUESTIONNAIRE BETWEEN PATIENTS WHO REACHED TARGET 24 HOUR BLOOD PRESSURE AND WHO DID NOT
Authors: Kantola Ilkka , Kantola Taru
Published: April 2021

Objective:

To clarify if a difference is noticed in quality of life between Finnish drug-treated hypertensive patients who reached target daytime systolic and diastolic blood pressure (below 140/90 mmHg) compared to those who did not.

Design and method:

SF-36 quality of life questionnaire was filled out by 106 hypertensive patients (47 females, 59 males, aged 66.2 (7.5) years). All used at least one antihypertensive agent. 24 hour ambulatory blood pressure (ABPM) and pulse wave- velocity (PWV) were performed and laboratory tests taken. Sixty-four of the patients reached ABPM daytime systolic and diastolic blood pressure (<140/90 mmHg) and 42 did not.

Results:

No significant difference was seen between the groups in any SF-36 quality of life parameters (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health or the mean of them).

The mean 24-hour ambulatory systolic blood pressure (SBP) was 142.9 (10.3) mmHg and diastolic blood pressure (DBP) 79.9 (7.1) mmHg in the patients who did not reach the target and 129.1 (7.7) mmHg and 77.4 (6.1) mmHg in the patients who reached (p = 0.0001). No significant difference was seen in age, weight, waist-hip ratio, carotid-femoral PWV, lipid values, GHbA1c or serum creatinine. Carotid-femoral PWV was 11.8 (3.8) and 11.5 (2.9) m/s. The mean (SD) of the eight SF-36 questionnaire scores was 71.8 (19.1) and 73.3 (19.8) (maximum 100). All SF-36 parameters correlated significantly (p < 0.001) to each other.

The high mean of the quality of life parameters correlated in the patients who did not reach the target to male gender, low 24-hour ABPM SBP standard deviation (SD), mean arterial BP SD, low daytime SBP SD and diastolic BP SD and mean BP SD. The high mean of the quality of life parameters correlated in the patients who reached the target to waist-hip ratio, type 1 diabetes mellitus, no change in carotid artery, low carotid-radial PWV and high 24-hour heart rate.

Conclusions:

The SF-36 scores of the Finnish drug-treated hypertensive patients did not differ markedly between those who reached blood pressure target and those who did not reach.
CILNIDIPINE DECREASES LEFT ATRIAL VOLUME INDEX SUPERIOR THAN ATENOLOL IN THE PATIENTS WITH HYPERTENSION
Authors: Chung Wook-Jin , Jang Albert Youngwoo , Ryu Seung-Kee , Park Su Jung
Published: April 2021

Objective:

This study was designed as a prospective, randomized, double-blind, parallel-group to test whether cilnidipine achieves greater left ventricular (LV) mass reduction and improves LV diastolic function than does atenolol.

Design and method:

Seventy-two patients with uncomplicated essential hypertension and increased LV mass index at screening echocardiography were randomly assigned and forced-titrated to 20 mg/d cilnidipine or 100 mg of atenolol for 36 weeks. Echocardiography, ambulatory blood pressure monitoring, biochemical studies including NT pro-BNP and 24-hours urine microalbumin were measured at baseline and after 36-weeks therapy.

Results:

Clinical examination and blinded echocardiogram in a per-protocol analysis of 28 cilnidipine-treated and 26 atenolol-treated patients revealed similar reductions in systolic/diastolic pressure (-16.5/8.9 mmHg versus -23.9/14.8 mmHg) and LV mass index (-21.4 g/m2 versus -19.5 g/m2). Interestingly, cilnidipine-treated group showed reduction on left atrial (LA) volume index but atenolol-treated group showed more enlarged LA (-5.1 % versus 7.3 %, p = 0.035).

Conclusions:

Both cilnidipine and atenolol similarly and effectively reduced blood pressure and LV mass index. However, only cilnidipine reduced LA volume index, whereas atenolol increased. Cilnidipine may provide more beneficial effect on the management in essential hypertension with diastolic dysfunction.
IN PATIENTS'S PREFERENCES TO ASPIRIN COMPARING WITH ANTIHYPERTENSIVE MEDICATION AND STATINS FOR PRIMARY PREVENTION
Authors: Rotar Oxana , Alieva Asiiat , Boiarinova Mariia , Erina Anastasia , Tolkunova Kristina , Solntsev Vladislav , Konradi Alexandra
Published: April 2021

Objective:

According to recent data of Russian epidemiological studies and screening campaigns hypertension control and statins use in primary prevention is still poor. The aim of our study was assess of aspirin and statin use comparing with antihypertensive medication in Russian residents in terms of MMM19.

Design and method:

An opportunistic cross-sectional survey of volunteers aged 18 years from 21 Russian Regions (n = 5274) was performed in terms of international campaign MMM19. 1,834 of the residents were men (34.8%). 49.2% of the respondents were younger than 25 years, therefore, considering significant differences in age, further analysis of the data was performed among participants over 25 years (n = 2681). The questionnaire was being completed on presence of diabetes mellitus, history of cardiovascular complications, smoking and alcohol intake. Information regarding intake and omission of antihypertensive medication, aspirin, statins were clarified. Blood pressure (BP) was measured three times with automated and manual sphygmomanometers and mean value was calculated.

Results:

Only 73.6% hypertensive patients take antihypertensive therapy and 44.8% of them achieved target BP of less than 140/90 mm Hg. Data regarding statins and aspirin intake in participants with hypertension and diabetes is presented in table.

Conclusions:

Despite insufficient hypertension control and current guideline positions against aspirin prescribing for primary prevention – 42,7% of hypertensives take aspirin. Only half of the patients having diabetes with automatically indicated high or very high risk are taking statins. Independently of diabetes presence patients are more likely to take aspirin comparing with statins. It is remarkably that 18,3% of hypertensives prefer aspirin than antihypertensive medication.
ACUTE MYOCARDIAL INFARCTION AND STROKE PREVENTION WITH AMLODIPINE/ ATORVASTATIN SINGLE-PILL THERAPY FOR PATIENTS WITH HYPERTENSION AND DYSLIPIDEMIA
Authors: Nakaya Hideaki , Sasamura Hiroyuki , Saito Ikuo , Inoue Yukie , Kobayashi Makoto , Itoh Hiroshi
Published: April 2021

Objective:

To evaluate the effect of suppressing the onset of Acute Myocardial Infarction (AMI) and Stroke by using combination tablet of Amlodipine Besilate/ Atorvastatin Calcium Hydrate (Caduet Combination Tablets) or combined use of Amlodipine Besilate and Atorvastatin Calcium Hydrate against patients with Hypertension and Dyslipidemia.

Design and method:

We build a Markov Model of considering the long-term treatment by using combination tablet of Amlodipine 5 mg/ Atorvastatin 10 mg or combined use of Amlodipine 5 mg and Atorvastatin 10 mg.

The target patients were 60 years old with Hypertension (Systolic Blood Pressure 152mmHg) and Dyslipidemia (Total Cholesterol 288 mg/dL).

The analyzed cycle was set for one year and we performed the simulation for the lifetime treatment.

The medication adherence for the well treated group was 82.4% in the Combination Tablet treatment group and 61.0% in the combined treatment group. Medication adherence for the poor treated group was based on hypothesis as each clinical efficacy index was the same as before treatment.

Results:

The incidence of AMI and stroke during the lifetime in combination tablet treatment group was estimated to be 21.8% in male and 24.1% in female for patients without diabetes or smoking. For patients without diabetes but smoking, it was 35.8% and 40.6%. For patients with diabetes but no smoking, it was 31.1% and 48.5%. For patients with both diabetes and smoking, it was 47.4% and 68.5%.

On the other hand, the incidence of AMI and stroke during the lifetime in combined treatment group was 24.7% in male and 27.5% in female for patients without diabetes or smoking. For patients without diabetes but smoking, it was 39.4% and 44.9%. For patients with diabetes but no smoking, it was 34.5% and 53.1%. For patients with both diabetes and smoking, it was 51.0% and 72.0%.

The incidence of AMI and stroke was lower in the combination tablet treatment group compared to the combined treatment group in both men and female.

Conclusions:

Treatment with combination tablet against patients with hypertension and dyslipidemia improves the medication adherence which resulted in suppressing the onset of AMI and stroke.
COMMUNITY PHARMACIST INTERVENTION (PHARMAFIT PROTOCOL) SIGNIFICANTLY REDUCES CARDIOVASCULAR RISK IN OBESE PATIENTS
Authors: González Leonor Huete , Lista Francisco Javier Manzano , Alonso Isabel Aránguez , Alfonso Marisol Férnandez
Published: April 2021

Objective:

Cardiovascular disease is the leading cause of death worldwide and is strongly associated with obesity. Health education, nutritional follow-up, and modification of life style habits are key interventions for achieving reduction of cardiovascular risk (CVR) in obese patients. The hypothesis of this study is that an intervention in the community pharmacy prevents and/or reduces metabolic alterations associated with obesity thus leading to a reduction in CVR in this population.

Design and method:

A before-and-after interventional study was performed in a Spanish community pharmacy. Obese patients (BMI > 30 kg/m2 and waist circumference > 102 cm for men or >88 cm for women) with (group A, n = 30) or without (group B, n = 14) comorbidities were asked to participate. In the first visit following variables were determined on-site: anthropometric values (weight, height, waist circumference), blood pressure, glycemic (glucose, HbA1c) and lipid parameters (total cholesterol, HDL-c, LDL-c, triglycerides). Interventions (PharmaFit Protocol) consisted in a 24-month follow-up focusing i) on adherence to nutritional guidelines and modification of life style habits (monthly), and ii) on anthropometric variables, blood pressure, and biochemical determinations (bi-monthly). Feedback was provided to the primary care physician or specialist. CVR was estimated by REGICOR score.

Results:

Anthropometric variables significantly decreased in all groups. Plasma glucose levels were significantly reduced in group A without changes in HbA1c. Lipid parameters significantly improved in group A, whereas HDL-c significantly raised in all groups. REGICOR score was significantly reduced in group A female (13.8 ± 1.6 vs 5.8 ± 1, p < 0.0001) and male (12.7 ± 1.7 vs 4.4. ± 0.6, p < 0.005) patients, and in group B female patients (3.5 ± 0.7 vs 1.9 ± 0.4, p < 0.001).

Conclusions:

Community pharmacist intervention, delivered as a 24-month follow-up combining health and dietary education has a highly positive impact on CVR reduction in obese patients. This study stresses the importance of pharmacist intervention in both the reversal and prevention of CV disease when targeting obese patients.
VARIANT GAMMA 6+ GAMMA-DELTA T CELLS PLAY A ROLE IN ANGIOTENSIN II-INDUCED HYPERTENSION
Authors: Mahmoud Ahmad Usama Moha , Caillon Antoine , Paradis Pierre , Schiffrin Ernesto
Published: April 2021

Objective:

We previously demonstrated that a small subpopulation of T cells considered (innate-like), expressing the γδ T-cell receptor (TCR) plays a key role in hypertension and vascular injury. γδ T cells can be subdivided according to the TCR variant (V) subtype that is generally specific for a tissue. A subpopulation of lungs and skin γδ T cells that are Vγ6+ and produce interleukin (IL)-17A was shown to respond promptly to pneumococcal infection and skin inflammation. However, γδ T cell Vγ subtypes involved in hypertension are still unknown. We hypothesized that the Vγ6+ γδ T cell may play a role in angiotensin (Ang) II-induced hypertension and vascular injury.

Design and method:

Eleven- to 13-week-old C57BL/6J male mice were infused or not with Ang II (490 ng/kg/min, SC) for 14 days, (n = 5–14). The γδ T cell Vγ subtypes were profiled and markers of activation of Vγ6+ γδ T cells were determined by flow cytometry.

Results:

In spleen and mesenteric lymph nodes (MLNs) the most abundant γδ T cells Vγ were Vγ1/2+ and Vγ4+ followed by Vγ6+,Vγ5+ and Vγ7+. In thoracic aortic (TA) perivascular adipose tissue (PVAT), the most abundant γδ T cell Vγ was Vγ6+ followed by Vγ4+, Vγ1/2+, Vγ5+ and Vγ7+. In mesenteric artery (MA) PVAT, the most abundant γδ T cell Vγ subtype was Vγ6+ followed by Vγ4+, Vγ7+, Vγ5+ and Vγ1/2+. Ang II increased the frequency of Vγ6+ γδ T cells in the spleen (1.5-fold, P < 0.01) and TA PVAT (1.6-fold, P < 0.01), whereas it only tended to increase them in MA PVAT. The frequency of IL-17 producing effector memory (CCR6 + CXCR3–CD44 + CD69 + ) Vγ6+ γδ T cells were increased in spleen (1.7-fold, P < 0.01) and trended to be elevated in mesenteric PVAT in Ang II-infused mice compared to control mice.

Conclusions:

Vγ6+ γδ T cells were the most abundant Vγ subtype in PVAT. IL-17 producing effector memory Vγ6+ γδ T cells may play a role in Ang II-induced hypertension. Targeting a γδ T cell variant subtype could be a therapeutic approach to reduce inflammation in hypertension.
CLINICAL CHARACTERISTICS OF YOUNG ADULTS WITH HYPERTENSION REFERRED TO A SPECIALIST HYPERTENSION CLINIC
Authors: Kennedy Cormac , Farnan Richard , Aftal Zainab , Hall Mary , Hemyrck Linda , Stinson John , O’Connor Patricia , Hennessy Martina , Barry Michael
Published: April 2021

Objective:

Objective: Compared to older adults, young adults (18–39 years) with hypertension have poorer awareness of their conditions, are less likely to be treated and much less likely to have their blood pressure (BP) controlled as a result. The objective of this study was to identify the clinical characteristics of the young hypertensives, the extent of treatment and its success in achieving guideline BP targets.

Design and method:

Design: A pragmatic observational study of patients referred with hypertension to our clinic.

Method:

Consent for inclusion in the study was be requested from all patients attending the specialist hypertension clinic at St James Hospital from June to September 2019. Clinical details will be recorded to characterise the groups of interest. Details to be recorded from the patients first and most recent visit including demographics, referral information, co-morbidities, investigations and treatments. The study was approved by the local research ethics committee (Tallaght hospital, Dublin). T-tests and Chi-squared tests were applied as appropriate.

Results:

Results: 236 patients were recruited for the study of which 63 (26.7%) were young adults. The mean age of the young group was 32.1 years and the BMI was 30.3 kg/m2. 75% were either obese or overweight, both in line with the rest of the study cohort. 76% had a family history of hypertension. The young group were more likely to have controlled BP at a cut-off of 140/90mmHg (69.5 v 50.3%;p = 0.014) but this group were taking less anti-hypertensive medications compared to those forty years or older (1.41 drugs v 2.28;p < 0.001). While the young group were more likely to have controlled BP according to the new AHA guidelines (27.1% v 13.3%;p = 0.025; cut-off 130/80mmHg), the figures were similar for both groups when the ESH guidance was used due to a higher cut-off for those over 65 years (27.1 v 28.5%).

Conclusions:

Conclusions: This study suggests that younger patients with hypertension require less anti-hypertensive treatment to achieve BP control. It did not identify subgroups of patients within the young group, however, the group is notable for the extent of overweight and obese patients referred to the clinic.
UTILIZATION OF ANTIHYPERTENSIVE DRUGS AS MONOTHERAPY AND COMBINED THERAPY IN BRAZIL: A POPULATION BASED STUDY
Authors: da Silva Brunna Raphaelly Amaral , Bricola Alice Aparecida Olim , Fontanella Andréia Turmina , Borges Rogério Boff , Costa Karen Sarmento
Published: April 2021

Objective:

Our objective was to describe the use of antihypertensive drugs in Brazil with a focus on the combination of two drugs.

Design and method:

Secondary data analysis from the National Survey on Access Use and Promotion of Rational Use of Medicines (PNAUM 2014), a nationwide cross-sectional population-based study, focused on the use of medicines in Brazil with a total of 41,433 interviews. The sample consists of all antihypertensive drugs cited as used to treat hypertension. The I Brazilian Positioning about Combination of Antihypertensive Drugs 2013 was used as a criteria to identify the combinations as Preferential: ACEI (Angiotensin-converting enzyme inhibitors) + CCB (Calcium channel blockers), ACEI + Diuretic, ARB (Angiotensin II receptor blockers) + CCB (dihydropyridine derivates), ARB + Diuretic; Acceptable: Diuretic + BB (beta-Blockers), CCB (dihydropyridine derivates) + BB, CCB + Diuretic, RI (Renin inhibitor)+ Diuretic, RI + CCB, Diuretic Thiazide + Potassium-sparing Agent; Less usual: ACEI + BB, ARB + BB and Unusual combinations: CCB (non-dihydropyridine derivates) + BB, ACEI + ARB, ACEI + RI, ARB + RI, Antiadrenergic agents, centrally acting + BB. The Statistical Analysis System (SAS) version 9.4 was used.

Results:

A total of 45 antihypertensive drugs was related. Diuretics (47.2% 95%CI 45.5–48.8), ACEI (38.1% 95%CI 36.4–39.8) and ARB (37.1% 95%CI 35.5–38.7) were the most used drugs, regardless the treatment as monotherapy or combined therapy. As monotherapy the three classes cited was the most used, however in a different percentage: ACEI (37.1% 95%CI 35.0–39.4), ARB (28.1% 95%CI 26.1–30.2) and Diuretics (14.5% 95%CI 12.9–16.1). Considering people under therapy with two drugs and the I Brazilian Positioning about Combination of Antihypertensive Drugs criteria, the preferential combinations represented 66.3% (95%CI 63.8–68.8), acceptable 19.2% (95%CI 17.1–21.2), less usual 10.1% (95%CI 8.5–11.8), unusual combinations 1.4% (95% CI 0.9–1.9) and other combinations 3.0% (95%CI 1.9–4.1). The most preferential combinations were ARB + Diuretic 30.3% (95%CI 27.8–32.8) and ACEI + Diuretic 28.0% (95%CI 25.5–30.5). In general, Brazil is using antihypertensives according to the guidelines of hypertension.

Conclusions:

In general, Brazil is using antihypertensives according to the guidelines of hypertension.
INHIBITION OF ACE C-DOMAIN AND NEPRILYSIN AS A NEW THERAPY IN HYPERTENSION
Authors: Alves-Lopes Rheure , Montezano Augusto , Neves Karla , Harvey Adam , Rios Francisco , Arendse Lauren , Camargo Livia , Graham Delyth , Poglitsch Marko , Ehlers Mario , Sturrock Edward , Touyz Rhian
Published: April 2021

Objective:

Dual inhibitors of neutral endopeptidase (NEP) and ACE (omapatrilat) have potent blood pressure-lowering actions, with angioedema as a side effect, due to bradykinin accumulation. Here we assessed whether a C-domain specific ACE inhibitor, lisinopril-trp (lis-trp), which specifically inhibits Ang II production while maintaining bradykinin metabolism, in combination with a NEP inhibitor (sacubitril), influences blood pressure, vascular function and the RAAS system in hypertension.

Design and method:

Ang II was measured by LC-MS/MS (liquid chromatography). WT and AngII-dependent hypertensive mice (TTRhRen) received vehicle, sacubitril, lis-trp, lisinopril, sacubitril + lisinopril, sacubitril + lis-trp and omapatrilat for 4 weeks. Blood pressure (BP) was measured by tail-cuff and vascular function/structure of mesenteric arteries by myography.

Results:

Increased AngII levels in TTRhRen mice (pg/g: WT 254.90 ± 46.94 vs TTRhRen 623.70 ± 58.21) was reduced by lis-trp (309 ± 33.84), p < 0.05. Systolic BP was increased in TTRhRen mice (WT 107.5 ± 4.04 vs TTRhRen 135.3 ± 3.99) and reduced by sacubitril + lis-trp (117.0 ± 1.08) and omapatrilat (113.6 ± 2.52), p < 0.05. Hypercontractility in TTRhRen mice (WT 9.42 ± 0.20 vs TTRhRen 10.84 ± 0.19) was reversed by sacubitril + lis-trp (9.43 ± 0.39 p < 0.01), with no change in endothelial dysfunction (WT 92.72 ± 5.1 vs TTRhRen 65.05 ± 3.21 vs TTRhRen + sacubitril + lis-trp 61.04 ± 6.89, p < 0.05). Omapatrilat decreased contraction and improved vasodilation, which may contribute to angioedema. Additionally, sacubitril + lis-trp reversed hypertension-associated inward hypertrophic vaxscular remodelling (CSA um2: LinA3 2832000 ± 248200 vs sacubitril + lis-trp 1693000 ± 199700). These effects were similar to those of omapatrilat (CSA um2: 2286333 ± 44796.66).

Conclusions:

The combination of a C-domain selective ACEi plus a NEP inhibitor reduces blood pressure, normalises vascular contraction and prevents vascular remodelling in an endothelium-independent manner.
EFFECTS OF ANGIOTENSIN RECEPTOR BLOCKERS THERAPY ON LEFT VENTRICULAR HYPERTOPHY AND NT-PROBNP LEVEL IN HYPERTENSIVES
Authors: Popescu Liuba , Ciobanu Nicolae , Caraush Alexandru , Sasu Diana
Published: April 2021

Objective:

To evaluate the effect of valsartan, eprosartan or losartan on LVH and NT-proBNP levels in patients with hypertension and preserved ejection fraction

Design and method:

This is randomized, prospective and double-blind study involved 154 hypertensive patients (56,5% men; mean age 53,6 ± 0,5 years) with concentric LVH remodeling (LV mass > 115 g/m2 and 95 g/m2 in men and women, respectively), which were eligible criterions to randomize to receive medication into three groups: valsartan (n = 48), eprosartan (n = 54), losartan (n = 52) over a follow-up period of 24 months. Echocardiography, ambulatory blood pressure monitoring and NT-proBNP assessments were performed at baseline and after 24 months treatment.

Results:

Despite similar effects on ambulatory blood pressure levels, significant differences on LV mass index were found between valsartan, eprosartan and losartan treatment (mean decrease 27.0 g/m2 vs 35 g/m2 and 24.0 g/m2, respectively, p < 0,001), and there was positive correlation of changes in ambulatory systolic blood pressure with LV mass index (r = 0,5; p < 0,001). Eprosartan-based therapy induced a greater reduction in NT-proBNP levels (-45,6%, p < 0,001) from baseline than in the valsartan (-28,9%, p < 0,01) and losartan group (- 26,5%,, p < 0,01).

Conclusions:

The findings of this study showed that all three agents progressively reduced LVH, but the reduction was significantly greater in the eprosartan group. Additionally, eprosartan was associated with a greater reduction of NT-proBNP levels.
STRUCTURAL BASIS FOR SUBSTRATE SPECIFICITY AND DOMAIN MOBILITY IN ACE – OPEN FOR BUSINESS
Authors: Sturrock Edward , Cozier Gyles , Lubbe Lizelle , Acharya Ravi
Published: April 2021

Objective:

Angiotensin-1-converting enzyme (ACE) is a zinc metallopeptidase that is well known for its role in cardiovascular physiology. Through its cleavage of peptides angiotensin I and bradykinin, ACE is involved in the renin-angiotensin-aldosterone and kinin systems, respectively. However, ACE also catalyses the cleavage of a variety of substrates, and thus participates in numerous other physiological functions. The aim of this study was to investigate the hinging mechanism of ACE and the molecular basis for its hydolysis a wide range of substrates with exo- and endopeptidase activity.

Design and method:

Minimally glycosylated N- and C-domain human ACE proteins (N389 and G13 respectively) and N389- S2-Sprime-nACE were produced by expression in cultured mammalian CHO cells and purified to homogeneity. ACE domains were crystallised and X-ray diffraction data were collected at the Diamond Light Source. Initial phases for the native structure were obtained by molecular replacement with PHASER.

Results:

In the present study, we present the high resolution crystal structures of native and S2-Sprime mutant ACE N-domains in an open conformation, and a closed C-domain structure where the C-terminus of a symmetry-related molecule is observed inserted into the active site cavity and binding to the zinc ion.

Conclusions:

Human ACE hydrolyzes a wide range of peptide substrates of varying lengths with carboxypeptidase, and endopeptidase activity. The crystal structures presented in this study shed light on how the ACE domains structurally achieves this diversity of activities. We have crystallized the first open nACE structure, demonstrating that ACE opens like ACE2 to give a wide groove that allows peptides to easily access the binding site. The shape of the groove encourages peptides to adopt an extended linear conformation, and there are likely to be interactions starting near the edge of the groove that are specific for the different peptide substrates that orientate and position them for the different types of hydrolysis. The cACE structure, showing C-terminal insertion from a symmetry related molecule, explains how sACE is capable of cleaving long peptides that are too big to be enclosed within the non-prime binding lobe.
SEX DIFFERENCES IN ANGIOTENSIN II-INDUCED HYPERTENSION AND KIDNEY INJURY: ROLE OF AT1A RECEPTORS IN THE PROXIMAL TUBULE OF THE KIDNEY
Authors: Leite Ana Paulo , Li Xia , Zhuo Jia
Published: April 2021

Objective:

Sex differences are widely recognized to play a critical role in cardiovascular, blood pressure and renal responses to the vasoactive peptide angiotensin II (Ang II) via activation of AT1 (AT1a) receptors. However, it is not known whether there are sex differences in the pressor and renal responses to Ang II in the absence of AT1a receptors in the proximal tubules of the kidney. In the present study, we tested the hypothesis that there are significant sex differences in Ang II-induced hypertension and kidney injury using male and female wild-type and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-).

Design and method:

To test our hypothesis, twelve groups (n = 8–12 per group) of adult male and female wild-type and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic pump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in extrarenal tissues or the proximal tubules of the kidney, respectively.

Results:

Minor sex differences were found in body wt., heart wt., or kidney wt. between male and female wild-type and PT-Agtr1a-/- mice. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P < 0.01), while basal 24 h urinary Na+, K+, and Cl- excretion were significantly higher in male and female PT-Agtr1a-/- mice than wild-type controls (P < 0.01) without significant sex differences between different strains. Both male and female wild-type and PT-Agtr1a-/- mice developed time-dependent hypertension (P < 0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female wild-type and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in male and female PT-Agtr1a-/- mice (P < 0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in male and female wild-type and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P < 0.01).

Conclusions:

In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without significant sex differences involved.
DIETARY FIBRE REDUCES INTESTINAL PH AND EXHIBITS CARDIOVASCULAR‐PROTECTIVE EFFECTS THROUGH A PROTON‐SENSING RECEPTOR
Authors: Xie Liang , Dinakis Evany , Muralitharan Rikeish , Nakai Michael , Zhang Xiaoyue , Jama Hamdi , Paterson Madeleine , Robert Remy , Mackay Charles , Marques Francine
Published: April 2021

Objective:

Dietary fibre lowers blood pressure (BP) and risk of cardiovascular disease and death via production of acidic metabolites by the gut microbiota. The mechanisms involved, however, are still elusive. Here, we aimed to understand the role of intestinal pH and the proton-sensing receptor GPR65 in the cardiovascular protection by dietary fibre.

Design and method:

Intestinal pH of C57BL/6 (WT) mice was measured after a 7-day dietary intervention with different levels of dietary fibre. The impact of pH and GPR65 on production of an inflammatory cytokine, TNFa, was determined by flow cytometry. We also determined the cardiovascular phenotype of male and female naïve WT and Gpr65-/- mice, including BP, tissue weights, sodium handling and immune cell infiltration.

Results:

Compared to the control diet, high fibre diet significantly reduced pH in caecum (control 6.84 ± 0.12 vs high fibre 6.03 ± 0.07; P < 0.001) and colon (7.10 ± 0.12 vs 5.95 ± 0.12, P < 0.001), while a diet lacking fibre significantly elevated pH (caecum, 7.37 ± 0.05, P = 0.001; colon, 7.53 ± 0.07, P = 0.030). Acidic pH inhibited the production of the pro-inflammatory TNFa by both CD4+ and CD8+ T cells (pH 6 vs pH 7; P < 0.001). Deletion of GPR65 increased TNFa production, particularly at acidic pH (CD4+, P = 0.002; CD8+, P < 0.001). Compared to WT controls, male and female Gpr65-/- mice had higher BP (mean arterial pressure; males WT 76.57 ± 3.26 vs Gpr65-/- 87.69 ± 2.18, P = 0.013; females WT 73.40 ± 2.41 vs Gpr65-/- 82.27 ± 2.56, P = 0.018; mmHg), and significant cardiac (Males, P < 0.001; Females, P = 0.001), renal (Males, P = 0.003; Females, P = 0.003) and splenic (Males, P = 0.002; Females, P = 0.002) hypertrophies when adjusted to tibia length. Male Gpr65-/- mice exhibited compromised capability in handling sodium (P < 0.001) and water (P = 0.028). Furthermore, male Gpr65-/- mice had increased infiltrations of CD4+ T cells (P = 0.015) and gamma-delta T cells (P = 0.038) in the kidneys, suggesting an increased susceptibility to renal inflammation.

Conclusions:

We determined that dietary fibre reduces large intestine pH. Low pH inhibits TNFa production in a partially GPR65-dependent way. Gpr65-/- mice exhibited spontaneous cardiovascular disorders including higher BP. This supports that the cardiovascular protection by dietary fibre is likely to be through pH regulation and GPR65. This is a highly novel mechanism that regulates BP.
ARTERIAL HYPERTENSION IN YOUNG PEOPLE REVEALING SYSTEMIC AFFECTIONS
Authors: Thabet Maissa , Romdhane Wiem , Anoun Jihed , Zorgati Hend , Hassine Imen Ben , Karmeni Monia , Fredj Fatma Ben , Mzabi Anis , Laouani Chadia
Published: April 2021

Objective:

Arterial hypertension in young patients can reveal or be a complication involving multiple mechanisms (coarctation of the aorta, inflammatory stenosis and / or thrombosis of the renal artery, vasculitis of arteries of different sizes, glomerular nephropathies, fibrosis retro peritoneal …) many systemic conditions.

Design and method:

We retrospectively studied hypertension in 16 patients under 40. Data were collected retrospectively from 16 patients, under 40 years old, and hospitalized d in an internal medicine department for systemic diseases.

Results:

These were 2 men and 14 women. The average age was 34 years and 8 months (range 16–40 years).

The systemic conditions identified were: systemic lupus erythematosus (7 cases), Takayasu disease (4 cases), systemic sclerosis (1 case), Sjögren syndrome (1 case), Behçet's disease (1 case), Buerger's disease (1 case) and cryoglobulinemia (1 case).

Conclusions:

Hypertension in young patients revealing a systemic disorder is rare and has complex mechanisms. Its etiological treatment depends on the specific context of each identified condition, on surgical treatment and / or long-term medical treatment.
HYPERTENSION DURING EARLY PREGNANCY IMPAIRS GENETIC PRIMING OF UTERINE ARTERIES PRIOR TO REMODELLING IN RODENTS
Authors: Scott Kayley , Morgan Hannah , McBride Martin , Graham Delyth , Delles Christian
Published: April 2021

Objective:

During pregnancy the uterine spiral arteries undergo major vascular remodelling to ensure sufficient uteroplacental perfusion to support the fetus. In pregnancies complicated by hypertensive disorders this remodelling is deficient leading to impaired uteroplacental blood flow and poor maternal and fetal outcomes. Evidence suggests that the uterine arteries can be ‘primed’ by changes in gene expression and maternal factors to ensure appropriate remodelling takes place.

This study aimed to examine the early-pregnancy associated gene expression changes in the uterine arteries (UAs) of stroke-prone spontaneously hypertensive rats (SHRSP) compared to their normotensive counterparts, Wistar-Kyoto rats (WKY).

Design and method:

SHRSP and WKY females were time-mated with males of the relevant strain. On gestational day (GD)6.5 dams were sacrificed, the UA collected and processed for RNA-sequencing alongside age-matched virgin controls (n = 3/group). Structure & function were assessed by wire and pressure myography. Gene expression changes were investigated using Ingenuity Pathway Analysis (IPA®) with padj > 0.05.

Results:

No structural or functional differences were observed in UAs between strains (SHRSP, WKY) or pregnancy (NP, P) using myography. SHRSP UAs showed a greater number of differentially expressed genes (DEGs) across pregnancy than WKY. WKY UAs exhibited an expression pattern of reduced Ca2+ handling and RAAS components with an increase in ATP production between NP and P states. SHRSP P UAs showed an increased expression of DEGs related to immune response, ROS production and downstream effectors of the RAAS in comparison to SHRSP NP UAs. These changes were not shared between strains.

Conclusions:

These results suggest SHRSP UAs experience gene expression changes in inflammation and oxidative stress pathways in early pregnancy that may induce failed priming of the UA. This may subsequently contribute to adverse vascular remodelling and placental ischaemia in later gestation characteristic of hypertensive pregnancies.
DIETARY SODIUM INTAKE DOES NOT ALTER RENAL POTASSIUM HANDLING AND BLOOD PRESSURE IN HEALTHY YOUNG MALES
Authors: Olivier Valerie , Pechere Antoinette , Feraille Eric
Published: April 2021

Objective:

High salt intake and potassium deficiency are involved in the pathogenesis of hypertension and cardiovascular diseases. The effects of sodium intakes on renal handling of potassium are scarcely studied. The objective of this study is to assess the renal handling of potassium in condition of low, normal and high sodium intake.

Design and method:

In a cross-over study, we assessed the effect of sodium on renal potassium handling in 16 healthy males assigned to three 7-day periods on low (LSD, 3 g NaCl/d), normal (NSD, 6 g NaCl/d) and high (HSD, 15 g NaCl/d) sodium diet with constant potassium intake. Contributions of distal NaCl co-transporter and epithelial sodium channel in the collecting system on potassium and sodium handling were assessed at steady-state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively.

Results:

Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg, (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 ml/min under LSD to 187.00 ± 49.10 under HSD, (P = 0.005). Twenty-four hours potassium excretion remained stable on all sodium intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h), and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all 3 diets.

Conclusions:

Neither spontaneous nor diuretic-induced potassium excretion were influenced by sodium intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal sodium handling was dependent on dietary sodium intake.
INTERRELATION OF INDICATORS OF LEFT VENTRICULAR-ARTERIAL COUPLING AND PARAMETERS OF LOCAL ARTERIAL STIFFNESS IN THE POSTINFARCTION PERIOD
Authors: Salyamova Lyudmila , Kvasova Olga , Galimskaya Vera , Khromova Angelina , Burko Nadezhda , Oleynikov Valentin
Published: April 2021

Objective:

To study the correlations between the parameters of the left ventricular-arterial coupling (LVAC) and the parameters of local arterial stiffness in patients after STEMI 6 months after revascularization.

Design and method:

125 patients (mean age 51.2 ± 8.8 years) after STEMI were included in the study. The diagnosis was confirmed by biomarkers of myocardial necrosis, ECG, coronary angiography. Echocardiography was performed at the 7–9th day and 6 months after STEMI (MyLab, Esaote, Italy), followed by calculation of LVAC indices: arterial elastance (Ea), left ventricular elastance (Ees), LVAC index (Ea/Ees). The study of the right and left common carotid arteries (CCA) was carried out on a MyLab ultrasound scanner (Esaote, Italy) using high-frequency RF signal technology. The following parameters were recorded: QIMT - intima-media thickness, DC - lateral distensibility coefficient, stiffness index β, loc Psys - local SBP, locPdia - local DBP, locPWV - local pulse wave velocity, AP - amplification pressure.

Results:

In the study of the correlation of LVAC indices with the CCA rigidity parameters recorded on 7–9th day from the STEMI, a relationship was revealed only between Ees and LocPsys (r = 0.40; p = 0.01), Ees and LocPdia (r = 0, 26; p = 0.004). After 6 months of follow-up, a closer relationship between the LVAC and the parameters of the local CCA stiffness was diagnosed. The Ea indicator correlated with DC (r = -0.23; p = 0.009), PWV (r = 0.21; p = 0.02), LocPsys (r = 0.33; p = 0.0002), LocPdia (r = 0.26; p = 0.004) and AP (r = 0.19; p = 0.03). The Ees indicator was found to be associated with LocPsys (r = 0.38; p = 0.00001), LocPdia (r = 0.27; p = 0.002), AP (r = 0.22; p = 0.01).

Conclusions:

After 6 months, there was a closer correlation between the LVAC indices and the parameters of local pressure and rigidity. This is probably partly due to the remodeling of the cardiovascular system in the postinfarction period and the inclusion of compensatory-adaptive mechanisms that ensure the contractile function of the heart.
BLOOD PRESSURE RESPONSES TO STRESS AFTER CHRONIC PHYSICAL EXERCISE: A SYSTEMATIC REVIEW WITH META-ANALYSIS
Authors: Mariano Igor , Amaral Ana Luiza , Ribeiro Paula , Puga Guilherme
Published: April 2021

Objective:

To assess the effects of physical exercise interventions on blood pressure (BP) responsiveness to laboratory stress tests.

Design and method:

This is a systematic review with meta-analysis that examined the effect of at least 4 weeks of exercise training on adults BP responsiveness to stressor tasks. For quantitative analysis, a random-effects model by Hunter Smith method was used. The searches were performed in 4 digital databases (PUBMED, LILACS, EMBASE and PsycInfo) and 19 studies and 2 event abstracts were included, totaling 857 individuals (12 studies and 516 individuals, in the quantitative phase).

Results:

Regarding qualitative analyses, 66.7% of the full text and abstracts showed favorable BP responses (either in SBP, DPB and/or MBP) after chronic exercise training, and the most frequent stressor test was the Arithmetic task, used in 33.3% of studies. Besides that, no asymmetries were found in the funnel graphs that would infer publication bias. Favorable metanalytic results for the exercises were found in systolic BP (SBP; mean effect size = -0.47 [-0.69; -0.24]) and diastolic BP (DBP; mean effect size = -0.35 [-0.58; -0.12).

Conclusions:

In summary, chronic physical exercise lowers SBP and DBP responsiveness to laboratory stress tests. So, these results associated with information from previous studies reinforce the idea that physical exercise is a valid strategy to control not only BP at rest but also its levels under stress, reducing hypertensive peaks of these individuals.
SECONDARY CAUSES OF HYPERTENSION IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
Authors: Kvapil Tomas , Václavík Jan , Benesova Klara , Jarkovsky Jiri , Kocianova Eva , Kamasova Monika , Jelinek Libor
Published: April 2021

Objective:

Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite concurrent use of three antihypertensive agents (at full or maximum tolerated doses) of different classes, one of which is a diuretic. The prevalence of secondary causes of hypertension among patients with resistant hypertension is not exactly known.

Design and method:

We retrospectively analysed the hospital records of patients with resistant arterial hypertension, who underwent complete laboratory and imaging examinations to exclude the secondary etiology of arterial hypertension. Standard descriptive statistics were used for statistical evaluation.

Results:

Among the 600 patients with resistant hypertension, secondary etiology of hypertension was found in 160 (27,5%). The most frequent cause was primary aldosteronism in 93 cases (58% relatively), followed by renovascular hypertension (30 cases, 18.8%), renal parenchymal hypertension (25 cases, 15,6%). Less common causes were pheochromocytoma (3,1%), hyperreninism (3.1%), hypercortisolism (0,6%). Obstructive sleep apnoea has been found in 75 (12.5%) patients.

Conclusion:

Secondary etiology was much more frequent (27,5%) in our group of patients with resistant hypertension than in non-selected hypertensive population (5–15%).

Conclusions:

This work was supported by IGA_LF_2019_036, IGA_LF_2020_039
HYPERTENSION ASSOCIATED RISKS DURING THE COVID-19 PANDEMIC: THE PATIENTS’ PERCEPTION
Authors: Ioannidis Antonios , Fragkiskou Afroditi , Paraskelidou Maria , Pechlevanis Apostolos
Published: April 2021

Objective:

Soon after the outbreak of the pandemic, uncontrolled hypertension was recognized as a risk factor for severe COVID-19 while concerns were raised that RAAS-i may increase the susceptibility and the severity of disease. The study aims to assess patients’ perception on risks associated with hypertension.

Design and method:

Hypertension patients visiting the emergency (non-COVID) department or the outpatient clinics of a tertiary hospital in Northern Greece were invited to participate by completing a short questionnaire. This observational study was conducted during the first and the much more forceful ongoing second wave. The Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) were used to measure the frequency and severity of depression and anxiety.

Results:

373 hypertensive patients (205 women, 55.0%) participated (mean age 63.6 ± 9.4 years), with 341 (91.4%) taking RAAS-i. About half (191, 51.2%) were taking RAAS-i for hypertension, while the rest for other indications. The vast majority (364, 97.6%) were alert that hypertension was a risk factor for COVID-19, although only 1 in 8 were informed that it mainly implied uncontrolled/untreated hypertension. Most of the patients (347, 93.0%) had heard that antihypertensive drugs might be harmful (mainly from TV reports), though only 199 (58.4%) of the patients taking RAAS-i knew they were taking such drugs. Moreover, 176 patients (47.2%), mostly during second wave, conducted their doctor and eventually 17 altered therapy. Participants during second wave reported higher chances of getting COVID-19, with the majority believing they are more susceptible and expecting more severe disease. The mean Beck's anxiety and depression score was 10.7 ± 7.1 and 12.2 ± 9.3 respectively, with the prevalence of significant anxiety (BAI> = 10) or depression (BDI> = 17) reaching 11% (41 patients) and 6.2% (23 patients), with as expected, higher scores for second wave patients. Disturbingly, only 20 patients (5.4%) had been informed of the position of major scientific.

Conclusions:

Greek patients are concerned of hypertension association with COVID-19 although not properly informed that it implies mainly uncontrolled/untreated hypertension. Hypertensive patients seem worried about the pandemic which is mirrored into anxiety and depression scores. Nevertheless they lack information from scientific societies.
THE PREVALENCE OF ARTERIAL HYPERTENSION AMONG PATIENTS HOSPITALIZED WITH COVID-19
Authors: Eruslanova Kseniia , Akapyan Anna , Malaya Irina , Strojesko Irina , Leonov Nikolay , Kotovskaya Julia , Runikhina Nadejda , Tkacheva Olga
Published: April 2021

Objective:

To estimate the prevalence of arterial hypertension (AH) among patients admitted to the hospital with COVID-19 pneumonia and to discover the relationship between AH and the risk to be placed in ICU and mortality.

Design and method:

The study included 542 patients aged 18 to 98 years old with verified COVID-19 pneumonia by CT of the chest and PCR diagnosis of COIVD-19. Arterial hypertension was diagnosed by past medical history.

Results:

The patients’ age was 58 ± 15 years (n = 542), 53,9 (n = 292) of them were women. There were 49,3% (n = 267) patients with AH. The prevalence of AH was higher among women (63% (n = 169) compare to 37% (n = 98) of men) and older adults. The average age of patients with AH was 65,3 ± 14,5 years old compared to 50,1 ± 14,5 years old among patients without hypertension (p < 0,01). There was no statistical difference in NEWS scores between patients with and without arterial hypertension (p > 0,05). 16% of patients with AH were transferred to ICU, while only 10% without AH needed to be placed in ICU (p < 0,05). However, the mortality was higher in patients with arterial hypertension (8,6% compared to 0,7%, p < 0,05%).

Conclusions:

Arterial hypertension is relatively common among patients with COVID-19 pneumonia and is associated with higher mortality. However, arterial hypertension is more prevalent among older adults, and more detailed analysis should be performed to exclude confounding bias.