bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUBSTANTIAL CHANGES IN CARDIOVASCULAR HEALTH OCCUR FROM ADOLESCENCE TO EMERGING ADULTHOOD
Authors: Park Chloe , Taylor Hannah , Rapala Alicja , Williams Suzanne , Jones Siana , Howe Laura , Chaturvedi Nish , Hughes Alun 
Published: April 2021

Objective:
17–24 years is a distinct period of lifestyle change. However little is known regarding changes in cardiovascular (CV) health during this time. We explored changes in Left ventricle (LV) structure and function, arterial stiffness, compliance and resistance in a large population-based birth cohort and investigated associations with body composition, haemodynamics and lifestyle choices.

Design and method:
724 participants had repeated echocardiography, blood pressure (BP) and body composition (using DEXA) measures aged 17y and 24y. Change in key outcomes and exposures from 17–24y were derived. Principal Component Analysis (PCA) was applied to reduce intercorrelated exposures into groups of independent factors. Principal Component (PC) 1: contained factors relating to change in blood pressure, PC2: change in body size (body mass index, fat mass and lean mass), and PC3: lifestyle (smoking and alcohol)). Linear regression assessed associations between PCs and change in CV outcomes.

Results:
From 17–24y systolic BP, pulse pressure and alcohol use decreased. All other exposures increased (Table). Indexed LV mass (LVMI) and systolic function (cardiac output (CO), Tissue Doppler peak S) increased, while diastolic function declined (Mitral E:e’). Pulse wave velocity (PWV) and compliance (TAC) increased, peripheral resistance (TPR) decreased. In age and sex adjusted regression analysis PC2 had the strongest association with all LV changes. Vascular changes (PWV,TPR) were most strongly associated with PC1. While PC3 showed the weakest associations. All associations remained after further adjustment for socioeconomic status, birth weight and education

Conclusions:
Substantial CV changes occur from adolescence to emerging adulthood. Changes in body size and composition have a considerable effect on LV structure and function, while changes in vascular health are associated with changing haemodynamics. These results imply that despite being relatively early in the life-course, this is an important time to control CV risk factors to improve future CV health.
A NEW GENETIC RISK SCORE FOR BLOOD PRESSURE STRONGLY ASSOCIATES WITH THE INCIDENCE OF HYPERTENSION AND CARDIOVASCULAR ENDPOINTS IN TWO SWEDISH COHORTS
Authors: Giontella Alice , Sjögren Marketa , Lotta Luca , Overton John , Baras Aris , Center Regeneron Genetics , Cristiano Fava , Melander Olle 
Published: April 2021

Objective:
The clinical value of the polygenetic component of blood pressure is commonly questioned. We constructed a new BP-GRS, including the most recently published variants genome wide significantly associated with either systolic or diastolic blood pressure (SBP, DBP), to investigate its association to the incidence of hypertension and cardiovascular endpoints in two urban-based cohorts: the Malmö Diet and Cancer (MDC, n = 29295) and Malmö Preventive Project (MPP, n = 9367).

Design and method:
The genotyping was performed with the Illumina GWAS chip (GSA array v1) and a weighted BP-GRS858 based on 858 SNPs was calculated, normalized, and divided into deciles. Logistic regression and survival Cox Regression models were used to test the associations of the new BP-GRS858 with outcomes.

Results:
At baseline, we found a difference of 11.2 mmHg (SBP) and 6 mmHg (DBP) between the top and the bottom deciles of BP-GRS858. In MPP, the top vs bottom decile of BP-GRS858 was associated with a doubled risk of incident hypertension (OR, 95%CI: 2.2, 1.7–2.8, p-value: 2.0E-10). In MDC, when comparing the top and bottom deciles of BP-GRS858, significant association was found between the age and sex adjusted BP-GRS858 and the incidence of total cardiovascular events (HR, 95%CI: 1.5; 1.3–1.7; p-value: 1.5E-12), stroke (HR, 95%CI: 1.6, 1.4–1.8; p-value: 2.1E-9), coronary artery disease (HR, 95%CI: 1.5, 1.4–1.8; p-value:1.3E-11), heart failure (HR, 95%CI: 1.5, 1.3–1.8, p-value: 2.5E-5), atrial fibrillation (HR, 95%CI: 1.2–1.1,1.4; p-value: 0.001) and total mortality (HR, 95%CI: 1.1, 1.0–1.2; p-value: 0.009). Most of these associations remained significant after adjusting for traditional risk factors, including hypertension.

Conclusions:
Our findings confirm that adding novel genetic variants into a polygenic BP-GRS, despite very low effect sizes of individual variants, increases its predictive performance. GRS858 contributes with clinically meaningful predictive information regarding future hypertension and CVD risk. Given that the exposure to high polygenetic risk starts at birth, we suggest that the BP-GRS858 might be useful to identify children or adolescents who would benefit from early hypertension screening and treatment.
AFFERENT PEPTIDERGIC NERVE FIBERS – IMPORTANCE FOR THE SALT METABOLISM BEYOND THE KIDNEYS?
Authors: Ditting Tilmann , Rodionova Kristina , Reeh Peter , Schmieder Roland , Schiffer Mario , Amann Kerstin , Ott Christianroland , Veelken Roland 
Published: April 2021

Objective:
Sodium can be accumulated without commensurate water retention in the skin (non-osmotic sodium storage). Macrophages play a pivotal role in this context and their depletion can induce salt-sensitive hypertension. On the other hand renal afferent peptidergic nerves are involved. Since the skin is also densely innervated by afferent peptidergic nerves we hypothesized that high salt diet might enhance the release of neuropeptides from these nerve fibers.

Design and method:
In a cross-over design, two groups of rats (n = 6, each) were fed either low salt diet (LS; 0.2%) with free access to tab water for 14 days or high salt diet (HS; 8%) with free access to 0.9% saline as drinking water. After 14 days a skin sample (3x3 mm) of the groin area was excised, and the diet was switched for another 14 days. Then a contralateral skin sample was taken. Tissue analyzed in an organ-bath and calcitonin gene related peptide (CGRP) content in the supernatant was measured with ELISA.

Results:
After two baseline measurements within 5 min, the tissue was superfused with hypertonic saline (4.5%) for 5 min, and three further samples of the supernatant were taken every 5 min. Baseline CGRP release was similar with both diets (LS 11.9 ± 1.5 vs HS 13.6 ± 1.5ng/g skin). Maximum release was higher with HS diet (LS 17.5 ± 1.8 vs HS 29.8 ± 1.3ng/g skin; P < 0.05). After diet switch the results were similar: baseline LS 9.4 ± 1.2 vs HS 10.1 ± 3 however, in rats previously on HS diet release tended to be higher with LS diet, nevertheless with HS diet the release was higher again (LS 19.7 ± 2.1 vs HS 29.3 ± 1.7; P < 0.05).

Conclusions:
High sodium diet sensitized neuropeptide release from peptidergic sensory nerves in the skin. Hence peptidergic afferent nerves might be an integrated body-wide system involved in sodium handling in very different target areas like skin and kidney. Putative peptidergic mechanisms (vasoregulation, chemotaxis) remain to be determined in this respect.
INTROGRESSION OF A BROWN NORWAY CHROMOSOME 2 FRAGMENT INTO DAHL SALT-SENSITIVE RATS EXERTS ANTI- AND PRO-INFLAMMATORY EFFECTS UNDER A NORMAL AND HIGH-SALT DIET, RESPECTIVELY
Authors: Berillo Olga , Ouerd Sofiane , Rehman Asia , Richer Chantal , Sinnett Daniel , Kwitek Anne E. , Paradis Pierre , Schiffrin Ernesto L. 
Published: April 2021

Objective:
Chromosome 2 (Chr2) introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (SB2) reduced blood pressure (BP) and vascular inflammation under normal-salt diet (NSD). We hypothesized that BN Chr2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high-salt diet (HSD).

Design and method:
Four- to 6-week-old male SS and congenic rats containing the BN Chr2 distal (SB2a) and middle segment (SB2b) were fed NSD or HSD (4% NaCl) for 8 weeks. BP was determined by telemetry, reactive oxygen species generation using dihydroethidium staining, and vascular cell adhesion molecule 1 and monocyte chemoattractant protein-1 expression and monocyte/macrophage infiltration by immunofluorescence in aorta or perivascular fat. RNA was extracted from aorta and used for small and total RNA-sequencing. Differentially expressed genes (DEGs) were identified with fold change > 1.3 and fold discovery rate < 0.05 and some of them were validated with reverse transcription-quantitative PCR (RT-qPCR).

Results:
SS Systolic BP was 145 ± 2 mm Hg under NSD and 168 ± 1 mm Hg under HSD, which was lower in SB2a and SB2b SBP (125 ± 3 and 127 ± 6, P < 0.05) under NSD but similar under HSD. Examination of inflammation markers revealed that SB2a presented less and more inflammation under NSD and HSD, respectively, compared to SS. DEGs were identified in SB2a vs. SS uniquely under NSD (27) and HSD (608) and under both diet (7), and in SB2b vs. SS uniquely under NSD (133) and HSD (9) and under both diet (12). DEGs encoded within BN Chr2a were identified uniquely under NSD (2) and HSD (8), and in both diets (3). RNA-sequencing and RT-qPCR validation identified two DEGs encoded within BN Chr2 distal segment that could play a role in the vascular inflammation. These were down-regulated glutamyl aminopeptidase (Enpep) that was anti-inflammatory under NSD and up-regulated heparan sulfate 2-O-sulfotransferase 1 (Hs2st1) that was pro-inflammatory under HSD.

Conclusions:
Two DEGs encoded within introgressed BN Chr2 distal segment were identified: Enpep associated with decreased vascular inflammation under NSD, and Hs2st1, associated with elevated vascular inflammation under HSD.
THE STUDY ON THE CARDIAC AND VASCULAR CHARACTERISTICS AND THEIR RELATIONSHIPS TO THE COGNITIVE FUNCTION IN PERIMENOPAUSAL WOMEN WITH HYPERTENSION
Authors: Shi Hongxia , Yu Jing 
Published: April 2021

Objective:
To explore the relationship and characteristics of cardiac, vascular and cognitive function in perimenopausal women with hypertension.

Design and method:
Female patients with hypertension aged 45–60 years old in Lanzhou University Second Hospital were selected as the case group (N = 355). And 355 age-matched healthy perimenopausal women were selected as control group. All subjects were surveyed by questionnaire for general characteristics. The blood pressure, heart rate, body mass index (BMI), waist-hip ratio and serum lipid including total cholesterol (TC), triglyceride (TG) and LDL cholesterol (LDL-C) were measured at the same time. Echocardiography was used to measure cardiac structure and function. The cardio-ankle vascular index (CAVI) and ankle-arm index (ABI) were detected also. The cognitive functions of all subjects were evaluated by mini-mental state examination (MMSE). All data were analyzed by SPSS20.0 software.

Results:
1) The influence factors of perimenopausal hypertensive women were less education and faster heart rate. 2) Compared with healthy group, there were significant difference on the left atrial diameter (LAd) [(33.11 ± 3.37) vs (28.91 ± 2.45)mm], and left ventricular posterior wall thickness (LVPWT) [(11.23 ± 1.22) vs (9.02 ± 0.86)mm] in perimenopausal hypertensive women (P < 0.05). 3) Hypertensive female also showed the significant differences in E/e’ [(8.08 ± 1.34) vs (7.46 ± 1.18)], interval e’ [(8.11 ± 1.70) vs (9.00 ± 1.75)cm/s] and lateral e’ [(10.46 ± 2.43) vs (11.42 ± 2.80)cm/s] (P < 0.05). 4) CAVI was higher in hypertension group than that of control group (P < 0.05). 5) More mild cognitive impairment patients were found in hypertension group than that of the control group(p < 0.05). 6) The main influencing factors of cognitive function among perimenopausal women with hypertension were age, menopause and the vascular dysfunction(p < 0.05).

Conclusions:
Family history of hypertension, high salt intake, alcohol abuse, poor education, heart rate and menopause may be the affect factors of hypertension among perimenopausal women. The influencing factors of cognitive function probably are age, arteriosclerosis and menopause, and also may promote the cognitive dysfunction among perimenopausal women with hypertension.
SATURATED FATTY ACIDS IN ERYTHROCYTE MEMBRANES IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
Authors: Marcon Denise , Tagetti Agela , Giontella Alice , Monamì Giada , Branz Lorella , Bortolotti Stefano , Piona Claudia , Morandi Anita , Trento Laura , Minuz Pietro , Maffeis Claudio , Fava Cristiano 
Published: April 2021

Objective:
Type 1 diabetes mellitus (T1DM) is associated with early development of atherosclerosis. The aim of this study was to assess the association between saturated fatty acids (SFAs) contained in erythrocyte membranes and some indices of vascular damage in a sample of adolescents with T1DM.

Design and method:
Participants in regular follow-up at the Paediatric Diabetology Unit of Verona were sent for evaluation at the Vascular Laboratory of the General Medicine & Hypertension Unit Central blood pressure (BP), Pulse Wave Velocity (PWV) and Pulse Wave Analysis (PWA) were measured by the SphygmoCor Xcel, carotid Intima Media Thickness (cIMT) and carotid distensibility (DC) by ultrasound and elaborated with a dedicated hardware. Blood samples were evaluated for erythrocyte membrane SFA, expressed as a percentage of total Fatty Acids (FAs).

Results:
Hundred and forty-seven adolescents (78 males and 69 females, mean age 17,25 ± 1,93 years) were studied. Fifteen patients were classified as hypertensive (10,2%) according to current European Guidelines. Thirteen patients had central systolic BP (cSBP) (8,8%), 60 cIMT (40,8%), 49 (33,3%) DC and 1 PWV (0,7%) above the 95th percentile for sex and age/height. We observed a correlation between total SFAs and cSB and z-cSBP (r = 0,260 and 0,269 respectively, p < 0,05), not confirmed when each SFA was analysed separately. Furthermore, a positive correlation between total SFAs and either PWV or z-PWV was detectable (r = 0,241 and 0,251 respectively, p < 0,05). The latter association remained significant even after adjustment for age, sex, Body Mass Index (BMI), duration of diabetes, HbA1c, total cholesterol, triglycerides-HDL ratio. Total SFAs were also associated with BMI (r = 0,191, p < 0,05).

Conclusions:
Erythrocyte membrane FAs are associated with vascular (cSBP and PWV) and anthropometric parameters in patients with T1DM. The amount of SFAs in membranes does not depend only on diet, as they are also neo-synthetized from glucidic precursors. Thus, it can be speculated that a bad glycemic control could translate into a higher substrate amount to produce the different SFAs. Further studies are needed to better understand the mechanisms and the regulations of these pathways
THE IMPORTANCE OF B2 CELLS IN THE HYPERTENSION AND PATHOPHYSIOLOGY OF PLACENTAL ISCHEMIA DURING PREGNANCY
Authors: Lamarca Babbette , Herrock Owen , Fitzgerald Sarah , Lemonb James , Deer Evangelin , Ibrahim Tarik , Campbell Nathan , Amaral Lorena 
Published: April 2021

Objective:
Preeclampsia (PE), is characterized by placental ischemia, inflammation, hypertension and IUGR. Antibodies activating the angiotensin II type I receptor (AT1-AA) activate cytolytic Natural Killer cells (NK) and cause clinical features of PE. The Reduced uterine perfusion pressure (RUPP) pregnant rat model of PE has elevated AT1-AA, NK cells and blood pressure. B cell depletion or AT1-AA epitope binding protein (‘n7AAc’) improved hypertension and AT1-AA activity and NK cells in RUPP rats. One unanswered question is the importance of B2 cells vs B1 cells in the production of the AT1-AA and thus the pathology of PE.

Design and method:
To test this hypothesis, splenic B Cells and B2 cells were isolated from RUPP rats on Gestation Day (GD) 19 and transferred into NP rats on GD12. Blood pressure (MAP) and cNKs were measured by flow cytometry on GD19. To test the role of AT1-AA in the hypertension, ‘n7AAc’ was administered to a group of recipient rats on GD14.

Results:
MAP increased in NP+RUPP B cells to 117 ± 1 mmHg, n = 10, and to 111 mmHg ± 3, n = 8, in NP+RUPP B2 cells, compared to NP rats, n = 10 (p < 0.001). ‘n7AAc’ attenuated hypertension in response to total RUPP B cells (99 mmHg ± 6, n = 5)(p < 0.01) and in response to RUPP B2 s (100 mmHg ± 5, p = 0.08). Circulating and placental cNKs were elevated with total RUPP B cells and RUPP B2 cells compared to NP. Circulating cNKs were elevated in NP+RUPPBcells (6 ± 2.5, n = 5)(p < 0.01) and in NP+RUPP B2 cells (8 ± 3.33, n = 4)(p < 0.01) compared to NP (0.67 ± 0.33, n = 10). Placental cNKs were elevated in NP+RUPPBcells (2.32 ± 0.73, n = 6)(p < 0.01) and in NP+RUPP B2 cells (1.33 ± 0.24, n = 3)(p < 0.01) compared to NP (0.2250 ± 0.133, n = 10).

Conclusions:
We conclude that RUPP total B Cells and RUPP B2 cells cause hypertension and NK cell activation via secretion of the AT1-AA during pregnancy. However, our studies do not rule out the importance of B1 cells in hypertension and AT1-AA production during PE or RUPP. Future studies from our laboratory will further examine B1 cells in the pathology of PE.
LOW DOSE SPIRONOLACTONE PROTECTS EXPERIMENTALLY-INDUCED POLYCYSTIC OVARIAN SYNDROME FROM INSULIN-RESISTANT METABOLIC DISTURBANCES
Authors: Adeyanju Oluwaseun , Falodun Timothy 
Published: April 2021

Objective:
Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats.

Design and method:
Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days.

Results:
Results showed that LET treatment induced PCOS characterized by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations.

Conclusions:
Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism. In conclusion, this study shows for first time, the protective effect of spironolactone at this dose against insulin resistance and metabolic disturbances induced by experimental PCOS. The protective mechanisms appears to be through suppression of elevated circulating testosterone. Therefore, SPL alone at this very low dose might be very effective as against its combination with other known anti-androgenic drugs in the treatment of characteristic features of PCOS.
SODIUM INTAKE, LIFE EXPECTANCY AND ALL-CAUSE MORTALITY
Authors: Messerli Franz , Hoftetter Louis , Syrogiannouli Lamprini , Rexhaj Emrush , Siontis George , Seiler Christian , Bangalore Sripal 
Published: April 2021

Objective:
Since dietary sodium intake has been identified as a risk factor for cardiovascular disease and premature death, a high dietary sodium intake can be expected to curtail life span. We tested this hypothesis by analyzing the relationship between sodium intake and life expectancy as well as survival in 181 countries worldwide.

Design and method:
We correlated age-standardized estimates of country specific average sodium consumption with healthy life expectancy at birth and at age of 60 years, and all-cause mortality for the year of 2010, after adjusting for potential confounders such as gross domestic product per capita and body mass index. We considered global health estimates as provided by World Health Organization.

Results:
Among the 181 countries included in this analysis, we found a positive correlation between sodium intake and healthy life expectancy at birth (R2 = 0.661, p < 0.001), as well as healthy life expectancy at age 60 (R2 = 0.600, p = 0.048). Conversely, all-cause mortality correlated inversely with sodium intake (R2 = 0.597, p < 0.001), Figure 1. In a sensitivity analysis restricted to 46 countries in the highest income class, sodium intake continued to correlate positively with healthy life expectancy at birth (R2 = 0.533, p < 0.001) and inversely with all-cause mortality (R2 = 0.497, p < 0.001).
Figure 1: Relation of sodium intake (grams/day) for the year of 2010 and healthy life expectancy at birth (in years) and age-standardized death rates (ASDR) for all-cause mortality in 181 countries worldwide. Schematic pattern of change in life expectancy and all-cause mortality with sodium intake in 181 countries worldwide. Note that proposed upper limits by some organizations such as AHA, WHO and ESC are associated with rather low life expectancy and high mortality.

Conclusions:
Our observation of sodium intake correlating positively with life expectancy and inversely with all-cause mortality worldwide and in high income countries argues against dietary sodium intake being a culprit of curtailing life span or a risk factor for premature death. These data are observational and should not be used as a base for nutritional interventions.