bluuebunny/crossref_metadata_2025 huggingface dataset:
IS BP LOAD ON AMBULATORY MONITORING A PREDICTOR OF TARGET ORGAN DAMAGE IN YOUTH? THE SHIP AHOY STUDY
Authors: Hamdani Gilad , Ferguson Michael , Lande Marc , Meyers Kevin , Samuels Joshua , Flynn Joseph T. , Urbina Elaine M.
Published: April 2021

Objective:

Ambulatory BP monitoring (ABPM) is increasingly utilized for the diagnosis of hypertension (HTN). Pediatric guidelines consider BP load (% of reading above the ‘normal’ threshold) in risk-stratification of the ABPM phenotype. We sought to determine if load was an independent predictor of target organ damage (TOD) in youth.

Design and method:

Casual BP, ABPM, anthropometrics, echo for LV mass index (LVMI), systolic strain, diastolic function (E’/e’ ratio) and pulse wave velocity (PWV) for arterial stiffness (PWV) were measured in 367 adolescents (mean 15.6 + 1.7 years, 63% white, 58% male). ABPM was performed with Ontrak device (Spacelabs Inc., Snoqualmie, WA). Subjects were stratified by load (low <25% = 215, mid 25-<50% = 62, high >=50% =47) according to sex- and height-specific pediatric cut points. ANOVA was used to evaluate differences in CV risk factors and TOD across load groups. General linear models were used to evaluate load as an independent predictor of TOD after adjusting age, demographics, body mass index (BMI), and mean daytime SBP on ABPM.

Results:

There was a graded increase in most clinic and ambulatory BP means and loads across load groups (all p < 0.05). There was only a trend for higher LVMI (p = 0.06) and reduced strain (p = 0.05) in low vs high load groups. Diastolic function (E/e’) was lower in high vs low and mid groups and there was a graded increase in arterial stiffness (PWV) across load groups. Daytime SBP load was an independent determinant of all forms of TOD after adjusting for age and sex but lost significance for LVMI after adjusting for BMI%. Load remained a significant determinant of PWV & E/e’ after adjusting for BMI% and mean daytime ambulatory SBP. Load group was also a significant determinant of PWV and E/e’ even after adjustment for age, sex, BMI% and daytime ambulatory SBP (all p < 0.0001).

Conclusions:

Daytime SBP load adds to prediction of diastolic dysfunction and arterial stiffness but not LVMI or systolic function. Increased load on ABPM may indicate need for advanced imaging to detect early TOD in youth with HTN.
EXCESS ALDOSTERONE RELATIVE TO PLASMA RENIN AND ANGIOTENSIN II ASSOCIATES POSITIVELY WITH CENTRAL SYSTOLIC BLOOD PRESSURE IN YOUNG BLACK AFRICANS
Authors: Gafane-Matemane Lebo , Mokae Nametsegang , Breet Yolandi , Schutte Aletta E.
Published: April 2021

Objective:

Populations of African ancestry usually present with a suppressed renin-angiotensin-aldosterone system (RAAS) attributed to excessive sodium retention and subsequently experience early and severe forms of hypertension-mediated organ damage. Central systolic blood pressure (cSBP) was previously found to be higher in young black adults as compared to their white counterparts. In the current study, we investigated associations of cSBP with a detailed RAAS profile in a healthy young population stratified according to ethnicity and sex.

Design and method:

This study included apparently healthy black men (N = 285) and women (N = 304), white men (N = 278) and women (N = 305) aged 20–30 years old. The SphygmoCor XCEL was used to derive cSBP. Aldosterone and equilibrium angiotensin levels were measured by LC-MS/MS and used for calculating angiotensin derived markers for plasma renin activity (PRA-S, Angiotensin I + Angiotensin II), angiotensin-converting enzyme (ACE-S, Angiotensin II/Angiotensin I), and two markers for adrenal effects of angiotensin II, the aldosterone-to-renin ratio (ARR-S, Aldosterone/PRA-S) and the aldosterone-to-angiotensin II-ratio (AA2-R, Aldosterone/Angiotensin II). Sodium and potassium were determined from 24-hour urine and then used to calculate sodium-to-potassium ratio.

Results:

Young black men and women presented with lower RAAS components and higher cSBP and urinary sodium-to-potassium ratio as compared to their white counterparts (all P < = 0.001). In forward stepwise multiple regression analyses, we observed the following associations: In black women, cSBP associated positively with ARR-S (β=0.269; P = 0.001) and AA2-R (β=0.263; P = 0.001), and negatively with PRA-S (β=-0.311; P < 0.001) and angiotensin II (β=-0.311; P < 0.001). In black men we observed a negative association between cSBP and PRA-S (β=-0.181; P = 0.047). None of the associations were present in white men and women.

Conclusions:

Positive associations of cSBP with the ratio of aldosterone to both PRA-S and angiotensin II in healthy young black women suggest that excess aldosterone may have deleterious effects on central blood pressure in this population group, which may lead to early target organ damage. The absence of any association between cSBP and RAAS components in white adults indicates an ethnic disparity in central pressure regulation.
GENES MEDIATING CELL GROWTH IN ALDOSTERONE-PRODUCING ADENOMAS
Authors: Yang Yuhong , Tetti Martina , Mulatero Paolo , Schneider Holger , Reincke Martin , Williams Tracy Ann
Published: April 2021

Objective:

Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism. Somatic mutations explain the excess aldosterone production in the majority of patients with APA with mutations in KCNJ5 encoding a potassium channel the most prevalent in most reported populations. Mechanisms driving cell proliferation are largely undefined.

Design and method:

Quantitative transcriptome analysis using RNA-seq was used to identify differentially expressed genes between macro-APAs (n = 9, diameter >= 30 mm) and micro-APAs (n = 12, diameter <= 10 mm). Validation of RNA-seq data by TaqMan real-time PCR was performed for 14 genes in a broader cohort of APAs (NMD, no mutation detected, n = 28; KCNJ5-mutated, n = 43).

Results:

Hierarchical cluster analysis of the 500 genes with largest coefficient of variation indicated sample clustering based on genotype (KCNJ5 or NMD) and APA diameter. Differential expression of 155 and 348 genes was found between micro- and macro-APAs with KCNJ5 mutations and NMD, respectively. Among the top 5 overrepresented Gene Ontology terms (biological process), cell death was exclusively enriched in NMD micro- vs NMD macro-APAs. The expression levels of 10 genes were validated with a potential function related to cell growth. Expression of BEX1 (a reported tumour suppressor) was 2.8-fold down regulated in macro-APAs relative to micro-APAs (P < 0.001), and a linear negative correlation of BEX1 expression with APA diameter was observed in NMD APAs (r = -0.501, P = 0.007). Genes involved in beta-catenin signalling, SFRP2, DKK1 and TSPAN12 were 5.9-fold (P < 0.001), 1.8-fold (P = 0.007) and 8.3-fold (P < 0.0001) down regulated, respectively, in macro-APAs compared with micro-APAs. BAI1 and CCL21 were also down regulated in macro-APAs relative to micro-APAs (3.3-fold, P = 0.026; 2.6-fold, P = 0.145, respectively). Additionally, the expression of TMPRSS3 (r = 0.727, P < 0.001), BMP4 (r = 0.389, P = 0.041) and FBXL21 (r = 0.761, P < 0.001) showed a linear positive correlation with adenoma diameter in NMD subgroup.

Conclusions:

APA display distinct transcriptome profiles according to adenoma diameter which may help identify genes involved in APA tumour cell growth.
TELMISARTAN IMPROVES MYOCARDIAL REMODELING IN RATS WITH HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY THROUGH INHIBITING LEPTIN AUTOCRINE INDUCED BY ANGII AND ACTIVATING PPARGAMMA
Authors: Chen Hui , Li Min , Liu Lei , Zh Danjun , Tian Gang
Published: April 2021

Objective:

The mechanism of left ventricular hypertrophy (LVH) in hypertension is complex. This study was to investigate the role of telmisartan in improving myocardial remodeling in hypertensive LVH and explore the potential molecular mechanism.

Design and method:

Eight-week male Sprague-Dawley (SD) rats were used to establish hypertensive LVH model through abdominal aortic constriction. Telmisartan was intragastrically administered 6weeks after surgery. Cardiac fibroblasts were used in vitro experiments under the treatment of angiotensin II (AngII), leptin or different inhibitors. The cardiac function and myocardial remodeling level were evaluated in rats, and the AngII-AT1R-ROS-ERK1/2-AP-1 pathway, leptin-JAK2/STAT3-TGF-β1/Smad3 pathway, and the metabolism-related parameters of collagen fibers were detected in cardiac fibroblasts.

Results:

Telmisartan treatment could alleviate left ventricular diastolic dysfunction (Table 1), reduce myocardial local RAAS and leptin level (Table 2), improve myocardial fibrosis and inhibit the activation of leptin-JAK2/STAT3-TGF-β1/Smad3 pathway in hypertensive LVH rats (Figure 1). AngII could increase the expression of leptin and induce AP-1 nuclear transposition in cardiac fibroblasts, and AT1R antagonist telmisartan, ROS scavenger NAC, ERK1/2 inhibitor PD98059 or AP-1 inhibitor SR11302 could inhibit leptin synthesis and secretion induced by AngII (Figure 2). Leptin could induce collagen metabolic disorders in cardiac fibroblasts, which could be partly restored by JAK2 inhibitor AG-490, STAT3 inhibitor S3I-201 or telmisartan. Telmisartan could reduce leptin synthesis and secretion as good as leptin antagonist, and improve collagen metabolism disorder induced by AngII better than leptin antagonist (Figure 3). Telmisartan could increase the expression of PPAR-γ to almost 3-fold of the control group. When pretreated with PPAR-γ inhibitor GW9662, telmisartan couldn’t restore the collagen metabolic disorders and the increased expression of P-STAT3 stimulated by leptin (Figure 4).

Conclusions:

Telmisartan can improve myocardial remodeling in hypertensive LVH rats via two ways: one is inhibiting leptin autocrine induced by local AngII as AT1R antagonist, the other is inhibiting leptin downstream signaling molecular STAT3 phosphorylation as PPAR-γ agonist (Figure 5). These findings demonstrate the crosstalk between myocardial local RAAS and leptin, and reveal a new molecular mechanism of telmisartan in improving myocardial remodeling in hypertensive LVH.
PROXIMAL TUBULE-SPECIFIC DELETION OF AT1A RECEPTORS ATTENUATES ANGIOTENSIN II-INDUCED HYPERTENSION BY INCREASING GLOMERULAR FILTRATION AND THE PRESSURE-NATRIURESIS RESPONSE
Authors: Li Xiao , Leite Ana , Zheng Xiaowen , Zhao Chunling , Zhuo Jia
Published: April 2021

Objective:

The present study tested the hypothesis that Ang II and AT1a receptors in the proximal tubules are required for normal blood pressure homeostasis and full development of Ang II-induced hypertension.

Design and method:

Six groups (n = 7–12 per group) of adult male wild-type (WT) and PT-Agtr1a-/- mice were infused with or without Ang II for 2 weeks (1.5 mg/kg/day, i.p.). Glomerular filtration rate (GFR) was measued using fluorescein-labeled sinistrin, and natriuretic responses were determined under basal conditions and after Ang II infusion.

Results:

Basal systolic blood pressure were ∼13 ± 3 mmHg lower in PT-Agtr1a-/- than WT mice (P < 0.01). However, basal GFR was higher in PT-Agtr1a-/- mice (WT: 160.4 ± 7.0 μl/min vs. PT-Agtr1a-/-: 186.0 ± 10 μl/min, P < 0.01). Basal 24 h urinary Na+ excretion (UNaV) was higher in PT-Agtr1a-/- than WT mice (P < 0.01). In response to Ang II infusion, both WT and PT-Agtr1a-/- mice developed hypertension with similar pressor response to Ang II in WT (43 ± 3 mmHg, P < 0.01) and PT-Agtr1a-/- mice (39 ± 5 mmHg, P < 0.01). However, systolic blood pressure was still 16 ± 3 mmHg lower in PT-Agtr1a-/- mice (P < 0.01). Ang II decreased GFR to 132.2 ± 7.0 μl/min in WT mice (P < 0.01), and to 129.4 ± 18.6 μl/min in PT-Agtr1a-/- mice (P < 0.01), respectively. In WT mice, UNaV increased from 139.3 ± 22.3 μmol/24 h in the control group to 196.4 ± 29.6 μmol/24 h in the Ang II-infused group (P < 0.01). In PT-Agtr1a-/- mice, UNaV increased from 172.0 ± 10.2 μmol/24 h in the control group to 264.7 ± 35.4 μmol/24 h in the Ang II-infused group (P < 0.01). The pressor response to Ang II was attenuated, while the natriuretic response was augmented by losartan in WT and PT-Agtr1a-/- mice (P < 0.01). Finally, proximal tubule-specific deletion of AT1a receptors significantly augmented the pressure-natriuresis response and natriuretic responses to acute saline infusion (P < 0.01) or a 2% high salt diet for 2 weeks (P < 0.01).

Conclusions:

The present study supports the hypothesis that Ang II and AT1a receptors in the proximal tubules are required for normal blood pressure homeostasis and the development of Ang II-induced hypertension.
EPIDEMIOLOGICAL CHARACTERISTICS AND RELATED FACTORS OF FRAILTY IN CHINESE OLDER ADULTS WITH HYPERTENSION
Authors: Ma Lina , Li Yun , Tang Zhe
Published: April 2021

Objective:

Hypertension and frailty are associated and often coexist in older adults. We have previously showed that frailty is associated with poorer physical function and higher mortality in community-dwelling hypertensive older adults in Beijing Longitudinal Study of Aging. However, little is known about the effect of frailty on hypertension prevalence, treatment, and control in Chinese older adults. We aimed to explore the epidemiological characteristics and related factors of frailty in Chinese older adults with hypertension in a nationwide survey.

Design and method:

Data were from China Comprehensive Geriatric Assessment Study (CCGAS, 2011–2012) using stratified, multiple-stage, random, and cluster sampling methods. A total of 6867 community-dwelling older adults were included. Comprehensive Geriatric Assessment frailty index (CGA-FI) was measured on the basis of six variables: demographic characteristics, physical health, physical function, living behavior and social function, mental health, and cognitive function. Frailty was defined as a score lower than 0.25.

Results:

The FI was positively correlated with age in both Non-HT group (male: r = 0.375, p < 0.001, female: r = 0.340, p < 0.001) and HT group (male: r = 0.273, p < 0.001, female: r = 0.340, p < 0.001). The prevalence of hypertension in older adults with frailty was higher than those without frailty (78.3% vs 64.1%, p < 0.001). However, the awareness and treatment rates of hypertension were higher in participants with frailty than those without frailty (awareness rate: 82.9% vs 67.9%, p < 0.001; treatment rate: 68.4% vs 57.8%, p < 0.001). There was no significant difference in control rate of hypertension between HT group and Non-HT group (73.9% vs 74.2%, p = 0.872). The prevalence of frailty was significantly higher in HT than in Non-HT (13.8% vs 7.4%, p < 0.001). Logistic analysis shows that age, marriage, coronary heart disease, chronic obstructive pulmonary disease, diabetic mellitus, osteoporosis, hearing loss, exercise, depression, cognitive impairment and white blood cells were independently related factors with frailty in older participants with hypertension.

Conclusions:

The prevalence, awareness and treatment rates of hypertension were higher in older adults with frailty than those without frailty in China.
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.
A RANDOMIZED CONTROLLED TRIAL OF LIFE-MODIFICATION INTERVENTION FOCUSED ON REDUCING ALCOHOL INTAKE TO CONTROL THE HYPERTENSION IN MALE PATIENTS DURING OUTPATIENT VISIT: OSAKE STUDY
Authors: Kabayama Mai , Akagi Yuya , Tamatani Michio , Tomita Jun , Takiuchi Shin , Yamamoto Koichi , Sugimoto Ken , Rakugi Hiromi , Kamide Kei
Published: April 2021

Objective:

To verify the effectiveness of the nurse-led life-modification intervention focused on reducing alcohol in male patients with hypertension during outpatient visit.

Design and method:

We enrolled 53 male patients (20–74years old) with morning home blood pressure (HBP) of 135/85 mmHg or more with excessive drinking (alcohol > = 210 g/week or > = 60 g/day habitually) from outpatient visit (at University hospital, General hospital, and Clinic setting) in a randomized controlled trial. Patients were assigned to a nurse-led intervention (in which patients were encouraged to modifying the alcohol consumption to optimal level in addition to the usual treatment every 2 month) or to the control (in which patients were followed see by their doctor as usual). The primary outcome were mean morning HBP of 5 consecutive days at 6 months and the amount of alcohol consumption. The HBP was measured by OMRON EM7251G and recorded on the Medical link Website.

Results:

The number of patients randomized to intervention were 28 and control were 25 (mean age; 62.7 ± 8.8years old, 64.5 ± 5.9 respectively), and 1 patient drooped-out in each group. At baseline, the mean HBP was 143/90 mmHg in the intervention group and 144/88 mmHg in the control (n.s.). At 6 months, the mean HBP was 131/82 mmHg in the intervention group and 145/87 mm Hg in the control (SBP < 0.001, DBP = 0.09). HBP level of less than 135/85 mmHg was achieved among 55.6% of the participants in the intervention group versus 16.7% in the control (P = 0.004). At baseline, the weekly alcohol consumption was 479 ± 353 g in the intervention group and 360 ± 182 g in the control (n.s.). At 6 months, it was 256 ± 206 g in the intervention group and 413 ± 260 g in the control (p = 0.020).

Conclusions:

We confirmed the effectiveness of the nurse-led life-modification intervention focused on reducing alcohol intake to control the morning HBP in male patients with hypertension as a method of non-pharmacological treatment during outpatient visit.
CLINICAL AND ECHOCARDIOGRAPHIC FEATURES OF PATIENTS WITH HEART FAILURE WITH MID-RANGE EJECTION FRACTION COMPARED TO REDUCED AND PRESERVED
Authors: Biolcati Marco , Maloberti Alessandro , Bianchi Sofia , Giani Valentina , Pellegrinelli Claudia , Ceratti Umberto , Belli Oriana , Casadei Francesca , Musca Francesco , Sormani Paola , Santambrogio Gloria , Spano’ Francesca , De Chiara Benedetta , Giannattasio Cristina , Moreo Antonella
Published: April 2021

Objective:

The 2016 ESC guidelines classify Heart Failure (HF) according to levels of Ejection Fraction (EF) in HF with reduced EF (HFrEF, EF < 40%), HF with preserved EF (HFpEF, EF > = 50%) and the newborn HF with mid-range EF (HFmrEF, EF 40–49%). The aim of our work is to analyse clinical and echocardiographic features of patients admitted for HF when divided accordingly to their admission EF, focusing on HFmrEF.

Design and method:

We enrolled 192 patients hospitalized in the Internal Medicine of our hospital between January and September 2017. We collected data on clinical history, physical examination, laboratory tests, pharmacological treatment and echocardiographic examination; follow-up for subsequent fatal and non-fatal events ended in May 2018.

Results:

Prevalence of HFpEF (55.21%) is higher than HFrEF (23,60%) and HFmrEF (17,19%). Mean age is 80.9 ± 8.3 years, and does not differ among groups. HFpEF are more commonly female, show higher SBP at the presentation (p < 0,001), and have more non-cardiac comorbidities, such as renal dysfunction (p < 0,001), anemia (p = 0,05), chronic obstructive pulmonary disease (p = 0,036) and also atrial fibrillation (p = 0,04); in this group hypertensive aetiology is significantly prevailing (p = 0,002). On the contrary previous myocardial ischaemia and higher NT-proBNP levels on the admission (p = 0,038) are typical in HFrEF. Diastolic and systolic dysfunctions co-exist in patients and many candidates show marks of inverse remodelling. HFmrEF carry intermediate attributes (prevalence of CAD and systemic multimorbidities) and exhibit a ‘hybrid’ US hypertrophy pattern (high RWT, medium LVMi); compared to the other groups, they include the lowest trend on NYHA classification (classes I-II, p = 0,027), a less aggressive treatment with the shortest number of drugs and the shortest dosages (p = 0,04) and show decreased mortality and rehospitalization rates. During the follow-up, patients with HFmrEF experience more longitudinal transition among groups (33% becomes HFpEF and 23% HFrEF).

Conclusions:

HFmrEF share features of both HFrEF and HFpEF, with a high prevalence of hypertension and a large longitudinal transition to the other two classes.
BLOOD PRESSURE AT ADMISSION PREDICTS 1-YEAR OUTCOMES OF PATIENTS HOSPITALIZED FOR HEART FAILURE
Authors: Huang Xinghe , Liu Jiamin , Hu Shuang , Li Jing
Published: April 2021

Objective:

This study aimed to evaluate the association between admission blood pressure (BP) and 1-year clinical outcomes in patients hospitalized for heart failure (HF) stratified by left ventricular ejection fraction (LVEF).

Design and method:

In the China PEACE Prospective Heart Failure Study, 4,930 patients hospitalized primarily for HF in 52 hospitals from 20 provinces in China have been enrolled. We included 4,611 patients with available LVEF and admission BP into analysis. Heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF) were defined as LVEF < 40%, LVEF of 40–49%, and LVEF > = 50%, respectively. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at admission were categorized by 10 mmHg increments. The primary outcome was the composite of all-cause death or HF readmission within 1 year after admission. The association between BP and the outcome was estimated with Cox proportional hazard models. A generalized additive model with restricted cubic splines was used to explore the possible non-linear relationship between BP and the outcome.

Results:

In our study, there were 1,850 (40.1%), 1035 (22.4%) and 1,726 (37.4%) patients with HFrEF, HFmrEF and HFpEF, respectively. In the multivariable analysis, compared to SBP of 120–129 mmHg, SBP > = 150 mmHg was significantly associated with a lower risk in HFrEF and SBP < 110 mmHg was significantly associated with a higher risk in HFmrEF and HFpEF (Table 1). For DBP, a significant decrease in the risk was observed for DBP > = 100 mmHg and DBP of 90–99 mmHg compared with DBP of 70–79 mmHg in HFrEF and HFpEF, respectively (Table 1). SBP and DBP were inversely and linearly associated with the primary outcome in HFrEF and HFpEF. Conversely, in HFmrEF, the association between SBP or DBP with the primary outcome was nonlinear.

Conclusions:

In patients hospitalized for HF, different prognostic effects of admission BP on clinical outcomes have been found by LVEF status. In HFrEF and HFpEF, the risk of clinical outcomes increased significantly only at lower BP, however, in HFmrEF, there is a nonlinear trend between BP and clinical outcomes.
HOW MANY ADDITIONAL PHYSICIANS ARE NEEDED FOR HYPERTENSION TREATMENT IN INDIA?
Authors: Marklund Matti , Marklund Matti , Neupane Dinesh , Wu Jason Hy , Neal Bruce , Matsushita Kunihiro , Appel Lawrence J.
Published: April 2021

Objective:

To estimate the number of additional physicians needed to treat all individuals with hypertension in India.

Design and method:

We incorporated existing data and corresponding uncertainties from the Global Burden of Disease Study and two national-representative surveys (including > 1.3 adults) to estimate the number of adults (18+ years) with hypertension in India. To estimate the number of additional physicians needed to treat all adults with hypertension, we used Monte Carlo simulations and derived central estimates and 95% uncertainty intervals from the 50th, 2.5th, and 97.5th percentiles of 1,000 simulations. We varied the proportion of visits for new physicians to spend on treating hypertensive patients from 10% to 100% of all visits (i.e., full dedication to hypertension treatment), and the number of visits per patient per year from 3 to 12, the latter being the current practice to allow monthly prescription renewals. The estimated capacity of currently available physicians (n = 835,910) was 418 million visits per year, assuming 10% of visits devoted to treating hypertensive patients.

Results:

In 2014, 195 million (95% uncertainty interval: 193–197) adults in India were estimated to have hypertension. This would require over 2.3 billion visits per year assuming monthly visits (i.e., current practice), and nearly 600 million visits per year assuming 3 visits per patient per year. With the current practice of monthly visits, 3.8 million new physicians would be required if they would have the same proportion of hypertensive patients as the available physicians (e.g., 10%), or 384,921 new physicians if they only were to see hypertensive patients (Table). These numbers were considerably reduced assuming 3 visits annually per patient, yet 33,529 new physicians would be required even if they only were to see hypertensive patients.

Conclusions:

Adequate monitoring and treatment of individuals with hypertension in India will require a substantial number of new physicians. Even in the most optimistic scenario (3 visits per patient per year and full (100%) dedication of additional physician time to hypertension treatment), around 30,000 new physicians will be required. These findings indicate that another approach, e.g. task-sharing, will be required to achieve nationwide hypertension control.