bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHARACTERISTICS OF HEALTHY VASCULAR AGEING (HVA) AND EARLY VASCULAR AGEING (EVA) IN GENERAL POPULATION. EH-UH STUDY (CROATIAN SCIENTIFIC FOUNDATION)
Authors: Glavic Mihaela Marinovic , Blagus Luka , Bosnjak Vito , Frkanec Stjepan , Katic Luka , Domislovic Viktor , Matasin Marija , Kos Jelena , Vrkic Tajana Zeljkovic , Pecin Ivan , Jelakovic Ana , Premuzic Vedran , Dika Zivka , Karanovic Sandra , Kriksic Valentina , Capak Krunoslav , Stevanovic Ranko , Jelakovic Bojan 
Published: April 2021

Objective:
Arterial stiffness (cfPWV) is acknowledged biomarker of ageing. It was reported that ePWV correlated almost identical with the measured cfPWV and had significant predictive value for cardiovascular (CV) events in hypertensive patients. In a subgroup of population ageing process is faster (EVA), while slower in subjects with HVA). Our aim was to analyze characteristics of EVA and HVA in general Croatian population using ePWV.

Design and method:
In a stratified random sample of 1087 subjects from the general Croatian adult population which was enrolled in a nationwide survey (EH-UH 1) from 2000–2005 analyses on ePWV were done and subjects were followed-up for 17 years. ePWV was calculated using this formula: ePWV = 9.587–0.402 × age+4.560 × 10-3 × age2–2.621 × 10-5 × age2 × MBP+3.176 × 10-3 × age × MBP-1.832 × 10-2 × MBP. MBP = (DBP)+ 0.4 (SBP - DBP). HVA was defined as the lowest 10% and EVA as the highest 10% of the standardized PWV distribution, adjusted for age quintiles. Subjects with MI, stroke/TIA and DM were excluded. Mortality data were collected from National Public Health Institute records.

Results:
Subjects with EVA were older with higher systolic/diastolic BP, heart rate and ePWV, more obese, having more frequently dyslipidemia and hypertension, were less educated and less physically active (all p < 0.001). Contrary to women, EVA in men was not associated with age, obesity, level of education and dyslipidemia (p > 0.05). In the whole group, and in both gender, there were no differences between HVA and EVA in income, smoking, alcohol consumption, residency (urban vs.rural; continental vs. Mediterranean) (p > 0.05). More women than men had HVA till the menopause (X2 = 13.867;p = 0.001) but after that we failed to find difference between genders. There were significantly more CV/stroke deaths in EVA vs. HVA in the women (X2 = 8.743; p = 0.003) but not in men.

Conclusions:
High BP and heart rate, and physical inactivity were found to be associated EVA in both gender. Obesity, older age (menopause), dyslipidemia and lower level of education were characteristics of EVA in women but not in men. EVA in women but not in men was associated with more CV/stroke deaths.
RELATIONSHIP BETWEEN VASCULAR AGEING AND LEFT VENTRICULAR CONCENTRIC GEOMETRY IN COMMUNITY-DWELLING ELDERLY: THE NORTHERN SHANGHAI STUDY
Authors: Maimaitiaili Rusitanmujiang , Teliewubai Jiadela , Zhao Song , Tang Jiamin , Chi Chen , Zhang Yi , Xu Yawei 
Published: April 2021

Objective:
There have been few recent studies regarding vascular ageing and its relationship between left ventricular (LV) geometry. Moreover, the association of abnormal LV geometry with various kinds of vascular ageing has not yet been systematically analysed. Thus, the study aimed to further elucidate this relationship.

Design and method:
In this study, 3363 elderly participants (43.6% male, aged 71.1 ± 5.9 years; 56.4% female, aged 71.1 ± 6.1 years) derived from the Northern Shanghai Study were enrolled. Vascular ageing criteria included arteriosclerosis, defined as cf-PWV > 10 m/s or ba-PWV > 1800 cm/s, peripheral atherosclerosis was defined as ABI < 0.9, cIMT greater than 0.9 mm or carotid plaque indicating carotid artery abnormality. Micro-albuminuria was defined as urinary albumin to creatinine ratio (UACR) above 30 mg/g. Decreased eGFR was defined as eGFR less than 60 mL/min per 1.73 m2

Results:
When vascular ageing parameters were respectively adjusted for age and gender, arteriosclerosis, micro-albuminuria, and peripheral atherosclerosis were significantly associated with concentric remodelling, eccentric left ventricular hypertrophy (LVH), and concentric LVH (P < 0.045), but not with decreased eGFR or abnormal cIMT and presence of plaque. Peripheral atherosclerosis was strongly associated with left ventricular concentric geometry (LVCG) when considering other covariates (risk factors, diseases, and treatments) (P < 0.012).

Conclusions:
Vascular ageing parameters such as arteriosclerosis, micro-albuminuria, and peripheral atherosclerosis are significantly and independently associated with left ventricular concentric geometry in community-dwelling elderly Chinese population, suggesting the importance of vascular ageing during early clinical assessment of abnormal LV geometry change and serious cardiovascular events.
URINARY METABOLIC PHENOTYPE OF BLOOD PRESSURE
Authors: Posma Joram Matthias , Stamler Jeremiah , Garcia-Perez Isabel , Chan Queenie , Wijeyesekera Anisha , Daviglus Martha , Van Horn Linda , Holmes Elaine , Nicholson Jeremy , Elliott Paul 
Published: April 2021

Objective:
Metabolic phenotyping (metabolomics) captures systems-level information on metabolic processes by simultaneously measuring hundreds of metabolites using spectroscopic techniques. Concentrations of these metabolites are affected by genetic (host, microbiome), environmental and dietary factors and may provide insights into biochemical pathways underlying raised blood pressure (BP) in populations.

Design and method:
Two separate, timed 24hr urine specimens were obtained from 2,031 women and men, aged 40–59, from 8 USA population samples in the INTERMAP Study. Proton Nuclear Magnetic Resonance (1H NMR) was used to characterize a urinary metabolic signature; this was unaffected by diurnal variability and sampling time as it captures end-products of metabolism over a 24hr period. Demographic, population, medical, lifestyle and anthropometric factors were accounted for in regression models to define a urinary metabolic phenotype associated with BP.

Results:
29 structurally identified urinary metabolites covaried with systolic BP (SBP), after adjustment for demographic variables, and 18 metabolites with diastolic BP (DBP), with 16 metabolites overlapping between SBP and DBP. These included metabolites related to energy metabolism, renal function, diet and gut microbiota. After adjustment for medical and lifestyle covariates, 22/14 metabolites remained associated with SBP/DBP. Joint covariate-metabolite penalized regression models identified Body Mass Index, age and family history as most important contributors, with 14 metabolites, including gut microbial co-metabolites, also included in the model. Metabolites were mapped in a symbiotic metabolic reaction network, that includes reactions mediated by 3,344 commensal gut microbial species, to highlight affected pathways (Figure). Significant single nucleotide polymorphisms (SNPs) from genome-wide association studies on cardiometabolic risk factors were mapped to genes in this network. This revealed multiple subnetworks of gene-metabolite pairs related to BP and related cardiometabolic factors and includes 54 SNPs directly related to reactions in the network. These 54 SNPs were then used as instrumental variables to test for possible causative metabolite-BP associations in an external cohort (Airwave Study).

Conclusions:
These results highlight the complex interplay between human genes, the microbiome and metabolites associated with BP and other cardiometabolic risk factors.
87 RARE VARIANTS ASSOCIATED WITH BLOOD PRESSURE IN META-ANALYSIS OF ∼1.32 MILLION INDIVIDUALS
Authors: Feofanova Elena 
Published: April 2021

Objective:
Elevated blood pressure (BP) is a major risk-factor for cardiovascular disease worldwide with complications accounting for ∼10.7 million premature deaths annually. Most prior genetic studies of BP explored Single Nucleotide Variants (SNVs) with minor allele frequency [MAF] > 0.01, with the majority of identified SNVs being non-coding, the causal gene for a majority of the known BP loci remaining unknown. We aimed to explore the role of rare variants on BP, elucidate candidate causal BP genes, to further our understanding of BP regulation.

Design and method:
The Exome array facilitates analyses of rare (MAF < = 0.01) coding variants with potential functional consequences. Over 80% of SNVs on the array are rare, ∼6% are low-frequency (0.05 > = MAF > 0.01) and ∼80% are missense, implicating a candidate causal gene through changes to the amino acid sequence. We performed an Exome Array-Wide Association Study (EAWAS) of ∼247,000 SNVs in ∼1.32 million participants from 95 studies to identify SNVs associated with SBP, DBP, PP and hypertension. We additionally performed a rare variant Genome-Wide Association Study (RV-GWAS) of ∼29 million imputed and genotyped SNVs in ∼670,000 participants (UKBiobank, MVP).

Results:
We discovered 105 new BP-associated genomic regions, containing 9 rare SNV-BP associations in the EAWAS and 23– in the RV-GWAS (P < 5 × 10–8). A further 55 rare variants were independent novel SNVs within known BP-associated loci in the RV-GWAS. Eighty seven BP-associated rare variants highlight potential candidate causal genes (e.g. GATA-binding protein-5, Phospholipase-C Beta-3), with 17% located in or near potentially druggable genes (encoding proteins predicted to be modulated by a drug-like molecule, e.g. Nuclear Receptor subfamily-3 group-C member-2, Natriuretic Peptide-A). Both rare and common BP-associated variants were enriched in regions of active chromatin in foetal tissues, linking foetal development with BP regulation in later life. Multivariable Mendelian randomisation highlight inverse effects of elevated SBP and DBP on large artery stroke.

Conclusions:
Our study is the largest analysis of rare variants to date, revealing candidate genes at new and previously reported BP loci, highlighting potential therapeutic targets. We also report new observations from both rare and common loci enriching our understanding of genetic BP regulation in health and disease.
METFORMIN AND LOSARTAN PREVENT PERIVASCULAR ADIPOSE TISSUE ALTERATIONS AND PROSTANOIDS RELEASE IN A MODEL OF METABOLIC SYNDROME IN THE RAT
Authors: Puyó Ana María , Lee Hyun Jin , Donoso Adriana S. , Cantú Silvana M. , Peredo Horacio A. , Choi Marcelo R. 
Published: April 2021

Objective:
A high-fat diet plus fructose overload (HFF) in rats is an experimental model that resembles human metabolic syndrome (MS). Mesenteric vascular bed (MVB) is a source of prostanoids (PR). Metformin (M) and losartan (L) are used for MS and high blood pressure (BP) treatment respectively. We analyze M and L effects on MVB PR release and perivascular adipose tissue (PVAT), and its relationship to BP.

Design and method:
Six groups (n = 6 each) of male Sprague-Dawley rats were studied for 9 weeks: C (control): standard diet (SD) and tap water to drink; HFF: high-fat diet (50% w/w bovine fat added to SD) plus fructose solution (10% w/v) to drink; CL and HFFL: L treated (30 mg/Kg/day L); CM and HFFM: M treated (500 mg/Kg/day). MVBs were dissected and the released PR were measured by HPLC (ng PR/mg tissue). Adiposity index (AI) was calculated as MVB adipose tissue weight/body weight x 100.

Results:
HFF elevated systolic BP (mmHg, 150 ± 3 vs. C: 119 ± 2, p < 0.01) and AI (%, 1.8 ± 0.1 vs C 0.7 ± 0.1, p < 0.01). L and M prevented those increases BP: (HFFL 112 ± 1 and HFFM 125 ± 1 vs. HFF, p < 0.01); AI (HFFL 1.00 ± 0.05 and HFFM 1.30 ± 0.04 vs. HFF, p < 0.01). HFF also increased vasoconstrictor prostaglandin (PG) F2alpha (ng PR/mg of tissue, 165 ± 11 vs. C: 84 ± 4, p < 0.01) and thromboxane (TX) B2 (153 ± 14 vs. C: 63 ± 2, p < 0.01), as well as the inflammation marker PGE2 (165 ± 11 vs. C 84 ± 4, p < 0.01) release; prevented by L and M (PGF2alpha, HFFL 100 ± 3 and HFFM 98 ± 6 vs. C, p < 0.05; TXB2, HFFL 83 ± 3 and HFFM 69 ± 3 vs. HFF, p < 0.05 and p < 0.01; PGE2, HFFL 105 ± 5 and HFFM 97 ± 2 vs. HFF, p < 0.05).

Conclusions:
Some possible mechanisms by which losartan and metformin avoid the blood pressure increase with this dietary modification could be the prevention of adipose tissue accumulation and the imbalance between vasodilator and vasoconstrictor prostanoids release in mesenteric vascular bed.
EFFECT OF OBESITY ON VENTRICULAR MASS INDEX AND DIASTOLIC DYSFUNCTION IN YOUNG PATIENTS WITH HYPERTENSION
Authors: Chen Xin , Zhang Xiaofang , Yu Jing 
Published: April 2021

Objective:
To investigate the effect of obesity on left ventricular mass index and diastolic dysfunction in young patients with hypertension.

Design and method:
A total of 166 young patients with hypertension (113 males and 53 females) diagnosed at the Lanzhou University Second Hospital from January 2018 to March 2019 were enrolled, aged 16–44 (34.25 ± 7.085) years old. According to the difference of body mass index (B M I), they were divided into 3 groups: the normal group (18.5 Kg/m2<=B M I < 24 Kg/m2; N = 58), the overweight group (24 Kg/m2<=B M I<28 Kg/m2; N = 62) and the obese group (B M I>=28 Kg/m2; N = 46). Detection of height, weight, 24 h ambulatory blood pressure, fasting blood glucose(F B G), blood lipid, uric acid (U A) and left ventricular structure and diastolic function index were performed. Variance analysis was used to compare the above data between groups, Pearson correlation analysis was used to analyze the influencing factors of ventricular remodeling and diastolic dysfunction.

Results:
(1) With the increase of B M I,U A (P < 0.05),L VD-s (P < 0.01), L VD-d (P < 0.01),L VS-D (P < 0.01),D (P < 0.01)and L V MI (P < 0.05) all increased in turn, the obese group was significantly higher than the overweight group, but the difference between the normal and the overweight group was not statistically significant (P > 0.05). (2) E/e’ in obese group was higher than that in normal group (P < 0.05) and there was no significant difference between the any other two groups (P > 0.05). (3) In young patients with hypertension: U A was significantly positively correlated with L V D-s, L V D-d, L VS-D, D and L V MI (both P < 0.01 or P < 0.05). (4) In the obese group, U A was positively correlated with E/e’ (P < 0.05), and the correlation was not observed in normal and overweight group (P > 0.05).

Conclusions:
Among young patients with hypertension, obese patients have higher U A, higher L V M I and more pronounced left ventricular diastolic dysfunction; moreover, U A is independently associated with ventricular remodeling in all subjects but correlates with ventricular diastolic dysfunction only in obese individuals.
PULSE WAVE REFLECTION AND GENDER DIFFERENCE IN OBESE INDIVIDUALS
Authors: Junli Zuo , Huijuan Chao , Audrey Adji , Alberto Avolio , F Orourke Michael 
Published: April 2021

Objective:
Although obesity is considered a cardiovascular risk factor due to its association with metabolic syndrome, recent studies in obese subjects with heart failure have shown that they have reduced adverse outcomes compared to non-obese individuals. This is consistent with the “obesity paradox”. However, body mass index (BMI) conventionally used to classify obesity, does not distinguish body shape or body fat distribution. This study aimed to explore the association between BMI and/or central obesity parameters and measures of arterial hemodynamics to assess the effect of obesity on function of large arteries.

Design and method:
Data was obtained from 832 normal individuals and stable patients with regular heart rate attending an outpatient health assessment clinic at Ruijin North Hospital, Shanghai. Subjects were divided into 3 groups according to their Body Mass Index (BMI < 24 normal, 24–28 overweight, > 28 obese; Chinese classification). Radial arterial waveforms and carotid-femoral pulse wave velocity (cfPWV) (SphygmoCor, AtCor Medical, Sydney) were measured with subjects recumbent, and calibrated to brachial cuff systolic (BSP) and diastolic pressure (BDP).

Results:
Central augmentation pressure (CAP), augmentation index (CAIx, a measure of wave reflection) and pressure amplification were lowest in the obese group (p < 0.001). BSP, CSP and cfPWV were highest in the overweight group, but only in females (p < 0.05). In males, CAP, CAIx and pressure amplification were significantly less as BMI increased (p < 0.05). In both sexes, central obesity measure of weight-to-height ratio (WHtR) was significantly different between BMI classes (p < 0.05). WHtR may be more appropriately correlated with hemodynamic parameters despite remaining differences between sexes (p < 0.05).

Conclusions:
Obesity in humans is associated with changes in the arterial pressure waveforms that are opposite of those usually described in aging and aortic stiffening. Differences are more obvious in males than females, and features of the “obesity paradox” are apparent when obesity is defined by BMI class only. Further study is warranted to investigate differences of associations between males and females, and effect of central obesity in males and females.
DIETARY INFLUENCE OF SYSTOLIC AND DIASTOLIC BLOOD PRESSURE IN THE TWINSUK COHORT
Authors: Louca Panayiotis , Berry Sarah E. , Spector Timothy D. , Padmanabhan Sandosh , Menni Cristina 
Published: April 2021

Objective:
Hypertension is a major modifiable risk factor for cardiovascular morbidity and mortality. Clinical and population-based studies show that several dietary components affect blood pressure and modification of these nutritional factors provide an important strategy to control blood pressure and reduce rates of hypertension. In this study, we examined the association between different nutrient intake and blood pressure in a cohort of adult twins.

Design and method:
We included 2252 adults from the TwinsUK registry not on hypertensive treatments with concurrent clinical blood pressure measurements. All subjects completed a Food Frequency Questionnaire facilitating estimated intake of 45 nutrients. Linear mixed models were used to investigate nutrient intake on systolic and diastolic blood pressure adjusting for age, gender, BMI and family relatedness. A Bonferroni correction was applied for multiple testing. A backward linear regression was then used to determine independently associated nutrients.

Results:
We identified 24 nutrients significantly associated with blood pressure after adjusting for covariates and multiple testing (Figure.1). Of those nutrients, 21 were negatively associated with SBP, 14 were negatively associated with DBP and one was positively associated with DBP. Among those with the greatest association with SBP were: riboflavin (Beta(SE): -1.39(0.34),p = 1.11x10-6), manganese (-0.55(0.2), p = 1.25x10-4) and maltose (-0.35(0.13), p = 1.35x10-4). Intake of manganese (-0.32(0.14), p = 3.85x10-4), vitamin e (-0.13(0.05), p = 3.12x10-4) and polyunsaturated fats (-0.09(0.04), p = 5.76x10-4) had the largest negative correlation with DBP, while, alcohol intake showed a positive correlation with DBP (0.03(0.01), p = 4.16x10-4). From the multivariable model, the following six nutrients were independently associated with systolic blood pressure, explaining 22% of the variance: vitamin b12 (-0.19), biotin (- 0.12), total fat (- 0.13), starch (- 0.03), total sugars (-0.04) and energy intake (-0.01). Five nutrients were independently associated with diastolic blood pressure and explained 14% of the variance, those were biotin (-0.08), magnesium (-0.01), energy intake (-0.00), carotene (-0.00) and alcohol (-0.06).

Conclusions:
Our findings confirm current understanding and extend the panel of dietary nutrients implicated in blood pressure regulation. Our new findings of dietary factors that affect blood pressure after validation offer additional diet and lifestyle approaches in hypertension prevention and management.
SEASONAL VARIATION OF MASKED UNCONTROLLED NOCTURNAL HYPERTENSION MEASURED BY NIGHTIME HOME BLOOD PRESSURE: THE J-HOP NOCTURNAL BLOOD PRESSURE STUDY
Authors: Narita Keisuke , Hoshide Satoshi , Kario Kazuomi 
Published: April 2021

Objective:
Usual daytime (morning and evening) home blood pressure (BP) monitoring can not detect nighttime hypertension. Masked uncontrolled nocturnal hypertension is defined as uncontrolled nighttime BP nonetheless controlled usual daytime home BP (HBP). Although previous studies have reported seasonal variation of nighttime BP evaluated by ambulatory BP monitoring is higher in summer than winter, seasonal variation in prevalence of masked uncontrolled nocturnal hypertension evaluated by nighttime HBP measurements remains unclear. Hence, we assessed the seasonal variation in nighttime HBP and the prevalence of masked uncontrolled nocturnal hypertension using a dataset of the Japan Morning Home-Surge BP (J-HOP) Nocturnal BP study.

Design and method:
This is a cross-sectional, post-hoc analysis using the dataset of the J-HOP Nocturnal BP study, which recruited patients with a history of or risk factors of cardiovascular disease. Participants underwent consecutive 14-day HBP measurements (morning and evening) and nighttime HBP measurements (a.m. 2, 3, and 4). We divided participants into four groups in each season. Masked uncontrolled nocturnal hypertension was defined as controlled daytime HBP (mean of morning and evening home systolic BP [SBP] < 135 mmHg and diastolic BP [DBP] < 85 mmHg) and uncontrolled nocturnal HBP (mean nighttime home SBP >= 120 or DBP >= 70 mmHg).

Results:
Among 2545 participants (age, 63.3 ± 10.3 yrs; 49% of male; antihypertensive medication use, 82.6%), 629, 596, 719, and 601 participants were enrolled in spring, summer, autumn, and winter, respectively. Nighttime home SBP/DBP were higher in summer than winter (SBP/DBP in summer, 123.3 ± 14.6/70.4 ± 8.9 mmHg; vs. in winter, 119.3 ± 14.0/69.1 ± 8.4 mmHg, p < 0.05). In 1490 participants with controlled daytime HBP, moreover, the prevalence of masked uncontrolled nocturnal hypertension was higher in summer than other seasons (summer, 55.7% vs. spring, 41.8%; vs. autumn, 42.9%; vs. winter, 39.7%, all p < 0.01). These relationships were also observed in multivariate logistic regression analysis (Table).

Conclusions:
In the present study, we revealed the prevalence of masked uncontrolled nocturnal hypertension was higher in summer than other seasons.