bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREVALENCE AND RISK FACTORS OF ALTERED CONTROL OF BP DURING THE NIGHT IN A LARGE HEMODIALYSIS POPULATION INVESTIGATED BY 48 HOURS ABPM
Authors: Torino Claudia , Mallamaci Francesca , Sarafidis Pantelis , Papagianni Aikaterini , Ekart Robert , Hojs Radovan , Balafa Olga , Del Giudice Antonio , Aucella Filippo , Morosetti Massimo , Tripepi Rocco , Marino Carmela , Tripepi Giovanni , Zoccali Carmine 
Published: May 2024

Objective:
Altered BP control during the night (non-dipping, reverse dipping and nocturnal hypertension) is recognised as a powerful risk factor for death and CV events in the hemodialysis (HD) population. However, these alterations have been described in relatively small studies, and the epidemiology and risk factors for the subtypes of non-dipping and nocturnal hypertension are still poorly characterised in the current literature. We investigated the problem in the large EURECAM registry, the sole that has adopted state-of-the-art 48h ABPM recording in the HD population.

Design and method:
We included in this analysis 534 HD patients enrolled in 7 centres, led by members of the EURECA-m working group in 3 European countries. 48h ABPM was measured using validated instruments (AAMI/ESH/ISO). As the European Society of Hypertension guidelines recommended, recordings were made at 15-minute intervals during the day and 30 minutes at night. Hypertension was defined as 48h blood pressure (BP)>130/80, nocturnal hypertension as a nighttime BP>120/70 mmHg, non-dipping as a night/day systolic BP fall <10%, and reverse dipping as a night/day ratio >1.

Results:
Among 534 HD patients, 317 were hypertensive and. 217 normotensive. As many as 274 patients were non-dippers (51%), 32% were reverse dippers, and 381 (71%) had nocturnal hypertension. Of note, forty-one per cent of non-dippers, 37% of reverse dippers and 19% of patients with nocturnal hypertension were normotensives. As expected, most reverse dippers (87%) had frank nocturnal hypertension. In a combined analysis of non-dippers and reverse dippers, as compared to dippers, these patients more frequently exhibited atrial fibrillation and had lower Heart Rate both pre-dialysis (72±11 vs 77±13 bpm, P=0.004) and post-dialysis (74±13 vs 78±14 bpm, P=0.03) and lower serum albumin (3.9±0.4 vs 4.0±0.3 g/dL, P=0.02) but did not differ for age and gender.

Conclusions:
In a large cohort of HD patients investigated by the state-of-the-art technique, 48hABPM alterations in the nocturnal BP profile were almost universal, and nocturnal hypertension was the more prevalent alteration, followed by non-dipping and reverse dipping. These alterations were independent of age and gender. Long-term, granular follow-up analyses are warranted to identify the prognostic value of these alterations.
BLOOD PRESSURE SCREENING IN MATA SECTOR, A RURAL AREA OF RWANDA
Authors: Hunjan Isabella , Parati Gianfranco , Bianchetti Mario G , Milani Gregorio P , Stroppa Clara , Muvunyi Bienvenu , Ntaganda Evariste , Radovanovic Dragana , Suter Paolo , Umulisa Alice , Muggli Franco 
Published: May 2024

Objective:
In rural sub-Saharan Africa, knowledge of non-communicable diseases such as high blood pressure (BP) is rather limited. This report provides information about a BP screening in Mata Sector, a rural region in Southern Province of Rwanda.

Design and method:
Community-based, house-to-house screening was performed between February and July 2020 on more than 7,000 inhabitants. The screening was conducted by a local team composed by 20 community health care workers, five community health care supervisors, and one nurse with hypertension surveillance training. BP and heart rate were recorded after 5 minutes of resting using a validated automated oscillometric OMRON M6 IT-HEM-7322-E monitor with Intelli Wrap Cuff (HEM-FL31-E) technology. The mean of the second and third value was retained.

Results:
BP was normal (<140/90 mm Hg) in 6,340 (88%) and elevated in 863 (12%) individuals with 95% of unawareness. Grade 1 (140–159/90–99 mm Hg) hypertensive BP readings were detected in 697 (81%), grade 2 (160-179/100-109 mm Hg) in 134 (16%), and grade 3 (more or equal to 180/more or equal to 110 mm Hg) in 32 (3.7%) participants. The prevalence of hypertensive readings was significantly age-dependent. Additionally, a slightly greater proportion of participants with high BP (14% versus 11%) had a body mass index (BMI) more or equal to 25.0 kg/m2. Also resting heart rate was higher in individuals with high BP (82 versus 77 beats/min).

Conclusions:
Although individuals identified with occasionally elevated BP values need further confirmatory measurements to establish the diagnosis of hypertension, these data suggest that high BP represents a noteworthy and preventable reason of concern within sub-Saharan Africa
IMPACT OF LIFESTYLE FACTORS ON HYPERTENSION RISK: INSIGHTS FROM THE KOREAN GENOME AND EPIDEMIOLOGY STUDY (2001-2016)
Authors: Ahn Song Vogue 
Published: May 2024

Objective:
This study evaluates the relationship between various lifestyle factors and the incidence of hypertension, using longitudinal data to provide comprehensive insights into preventive strategies.

Design and method:
We analyzed data from 5,759 participants without hypertension at baseline, drawn from the Korean Genome and Epidemiology Study between 2001 and 2016. The analysis focused on lifestyle variables, including dietary habits, physical activity, smoking status, alcohol consumption, sleep duration, and shift work. Cox proportional hazard models were employed to assess the impact of these lifestyle factors on the risk of incident hypertension.

Results:
Our findings indicate significant lifestyle contributors to hypertension, with sodium intake emerging as the most influential factor. For men, the highest population attributable fraction (PAF) of 22% was observed for sodium intake exceeding 4,000 mg, followed by 13% for low physical activity and 12% for alcohol consumption. Among women, a sodium intake above 4,000 mg had the largest influence, with a PAF of 15%, followed by 12% for shift work and 8.4% for low physical activity.

Conclusions:
The study emphasizes the critical role of lifestyle modifications in preventing hypertension. It supports the development of targeted public health strategies and interventions aimed at promoting healthy lifestyle choices to mitigate the risk of hypertension.
WHOLE GENOME SURVIVAL ANALYSIS OF 144,286 PEOPLE FROM UK BIOBANK IDENTIFIES NOVEL LOCI ASSOCIATED WITH BLOOD PRESSURE
Authors: Saluja Sushant , Darlay Rebecca , Eales James , Tomaszewski Maciej , Lennon Rachel , Keavney Bernard , Khanfar Amjad , Prestes Priscilla , Cordell Heather 
Published: May 2024

Objective:
Hypertension is a leading heritable cardiovascular risk factor worldwide associated with over 1000 common single nucleotide polymorphisms (SNPs). However, these SNPs only explain about half of its heritability, suggesting the presence of yet-to-be-identified genetic factors influencing this trait. This study used longitudinal UK Biobank data to discover novel genetic loci related to hypertension, addressing limitations in cross-sectional GWAS approaches.

Design and method:
The study sourced disease outcomes from diverse records (in-patient, self-reported, primary care, death registry, and time-to-event data) within the UK Biobank. It spanned from October 2010 (the last participant's enrolment) to the latest ’Essential hypertension’ diagnosis on October 2022, encompassing 12 years of follow-up. Utilizing whole genome sequence (WGS) data, our analysis employed the R package ‘SPACox’ for a genome-wide survival analysis, integrating Age, Age2, Sex, BMI, and 10 principal components as covariates. The WGS data underwent rigorous quality control (QC) measures, excluding SNPs with low call rates(<0.90), Hardy–Weinberg equilibrium test P-values<1×10-15, or minor allele frequencies less than 0.01.

Results:
The analysis included 21,248 hypertension cases and 123,038 controls, totalling 144,286 participants, with 58.0% women (average age - 55.3±0.0279 years). Post-genotype QC, 6,319,822 million SNPs underwent analysis, revealing 31 variants (P-value<5×10–08), including 29 new SNPs—15 in Fibrillin-2 (FBN2) and 2 in Junctophilin-2 (JPH2) genes. Subsequent Mendelian randomization studies, employing two identified SNPs (rs17677724 and rs1014754), revealed a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression was causally linked to increased blood pressure (P-Value =1.66×10-06, 3.19×10-06). Thereafter, FinnGen dataset PheWAS analysis reaffirmed rs17677724's (Beta = 0.492, P = 7.4×10-09) and rs1014754's (Beta = 0.0225, P = 4.8×10-05) positive association to hypertension, among 2,727 traits assessed in 377,277 individuals. Lastly, rs1014754 associated positively with kallistatin (Beta = 0.031, P = 0.0225) while rs17677724 negatively associated with Renin (Beta = -0.036, P = 0.0435), in the Fenland study (10,708 participants, 10.2 million variants, 4775 protein targets), suggesting a counter-regulatory response to high blood pressure.

Conclusions:
Our genome-wide time-to-event analysis unveils new genetic loci associated with hypertension, illuminating their role in hypertension via FBN2 and JPH2 expression.
THE POTENTIAL ROLE OF CYP2D6∗10(C.100 C>T) GENE POLYMORPHISM IN KIDNEY INJURY OF PATIENTS WITH HYPERTENSION COMPLICATED WITH NON-ELEVATED CYSTATIN C
Authors: Jiang Yufeng , Zhou Yafeng 
Published: May 2024

Objective:
This study aims to investigate the potential role of CYP2D6∗10 (c.100 c>t) gene polymorphism in renal function injury among hypertensive patients without elevated cystatin C.

Design and method:
A cohort of hypertensive patients without elevated cystatin C was recruited, and the CYP2D6∗10 genotype was analyzed. The objective was to evaluate the association between CYP2D6∗10 gene polymorphism and renal function injury by comparing patients with different genotypes. Genetic equilibrium was assessed using the Hardy-Weinberg equilibrium test. Polymorphic genotype frequencies between case and control groups were examined using the Chi-square test, with statistical significance set at p<0.05.

Results:
Among the hypertensive patients in the study, a significant correlation was observed between CYP2D6∗10 genotype and renal function injury (p<0.05) in codominant model and super-dominant model. Patients with the CYP2D6∗10 genotype exhibited more severe renal function damage.

Conclusions:
This study proposes CYP2D610 gene polymorphism as a potential predictor of renal function injury in hypertensive patients with normal cystatin C levels. Further research is crucial to validate this association and delve into the specific mechanisms through which the CYP2D610 genotype influences renal function injury in hypertensive individuals.
A GENETIC RISK SCORE OF EARLY-ONSET TYPE 2 DIABETES PREDICTS EARLY DEATH AND BENEFITS OF INTENSIVE GLYCEMIC CONTROL IN ADVANCE TRIAL
Authors: Hamet Pavel , Haloui Mounsif , Attaoua Redha , Simon Paul H G , Chalmers John , Zoungas Sophia , Woodward Mark , Grobbee Diederick E , Tremblay Johanne 
Published: May 2024

Objective:
Context: Early-onset type 2 diabetes (T2D) increases rapidly worldwide, alongside obesity, and carries an excess risk of microvascular complications and early death compared to when it started later in life. We have developed a multi-polygenic risk score (multiPRS) that predicts the risk of major micro- and macrovascular complications of T2D. We showed that individuals with high multiPRS scores for macrovascular events benefited more from tight blood pressure control while those with high multiPRS scores for microvascular events benefited from glycemic control. Early-onset T2D is genetically determined. Objective: To develop a genetic risk score that identifies individuals who are more susceptible to early-onset T2D and assess whether they could benefit from tight glycemic control.

Design and method:
We developed a genetic risk score (GRS) composed of 22 SNPs associated with early-onset T2D. We analysed 545 participants of European descent of ADVANCE with the highest GRS values and 526 subjects with the lowest GRS for early-onset T2D.

Results:
The median age at diagnosis of T2D was 54.9 in the high GRS and 64.6 in the low GRS group. Compared to participants with low GRS, those with high GRS were slightly heavier with a BMI of 30.8 (5.1 SD) vs 29.6 (4.9 SD), p = 7.2 x 10-5, they received more antidiabetic drugs (n= 1.5 (0.8) vs 1.2 (0.8), p = 1.2 x 10-7) and they died 5.7 years earlier (70.8 vs 76.5 years old p = 9 x 10-7). Contrary to the low GRS group, intensive glycemic control reduced mortality significantly in the high GRS group. Combination of intensive blood pressure and glycemia control led to a relative risk reduction of 52% (p = 0.028) and a number needed to treat of only 10 in the high GRS group while no significant effects were observed in the low GRS group.

Conclusions:
This novel GRS can identify individuals at risk of early-onset T2D who can benefit from tight glycemic control while its combination with blood pressure control is the most effective in reducing cardiorenal outcomes and death rate.
AN INTRONIC POLYMORPHISM RS11773845 IN CAV1 GENE IS ASSOCIATED WITH THE RISK OF DEVELOPING ATRIAL FIBRILLATION IN UZBEK PATIENTS WITH ARTERIAL HYPERTENSION
Authors: Abdullaeva Guzal , Zakirova Darya , Radzhabova Guliruh , Sherbadalova Nigora , Pulatova Muazzam , Mashkurova Zarina , Ibrohimov Nodir , Abdullaev Alisher 
Published: May 2024

Objective:
To determine the relationship of the rs11773845 polymorphism of the CAV1 gene with atrial fibrillation (AF) in patients with arterial hypertension (AH) in the Uzbek population.

Design and method:
The study included 154 patients with paroxysmal (n=47), persistent (n=21) and permanent (n=86) forms of AF. The control group (n=91) consisted of hypertensive patients without AF. The average age of hypertensive patients with AF was 65.2±10.8 years, and control group was 63.6±10.7 years. The diagnosis of AF was based on ECG and/or Holter ECG findings using standard diagnostic criteria. Genotyping of samples for carriage of allelic variants of the rs11264280 polymorphism was carried out using the RFLP-PCR method. Relative risk (OR) was calculated using genetic models. For all analyses, p values <0.05 were considered statistically significant.

Results:
Among hypertensive patients with AF, genotype of the rs11773845 polymorphism of the CAV1 gene was revealed: AA genotype - determined in 55 (35.7%) patients, AC genotype - in 80 (52.0%), CC genotype - 19 (12.3%), χ2 =54.955, p=0.000. The allelic distribution showed a predominance of carriage of the A allele: A allele – 61.7%, C allele – 38.3%, χ2=33.662, p=1e-8. Among controls, on the contrary, the frequency of the C allele prevailed: 68.1% and 31.9% - the frequency of the A allele, χ2=47.868, p=0.000. The ratio of AA:AC:CC genotypes was as follows: 16.5%: 30.8%: 52.7%, (χ2=27.33, p=0.000) respectively. Based on the multiplicative model of inheritance, a significant accumulation of the A allele was demonstrated among 154 hypertensive patients with AF in 61.7% (χ2=40.70, p=0.000; OR=3.44, 95% CI 2.34-5.07), while the C allele was less common in 38.3% of cases. The dominant model of inheritance also demonstrated the association of AA + AC genotypes with the risk of developing AF in patients with AH, so AA + AC genotypes were more common in 87.7% (χ2 = 47.01; p = 0.000; OR = 7.93, 95% CI 4.21-14.93) than CC genotype in 12.3% of cases.

Conclusions:
The AA+AC genotypes and the A allele of the rs11773845 polymorphism of CAV1 gene associated with risk of developing AF in Uzbek patients with AH.
GENETIC VARIANCE IN HEPARAN SULFATION IS ASSOCIATED WITH SALT-SENSITIVITY: A GENE-ENVIRONMENT ANALYSIS
Authors: Oppelaar Jetta , Ferwerda Bart , Romman Mohamed , Sahebdin Ghazalah , Zwinderman Aeilko , Galenkamp Henrike , Boekholdt Matthijs , Van Den Born Bert -Jan , Engberink Rik Olde , Vogt Liffert 
Published: May 2024

Objective:
The high heritability of salt sensitivity suggests an essential role for genetic variants in the relationship between sodium intake and blood pressure (BP). Candidate gene studies have mainly focused on renal and vascular pathways, but the role of glycosaminoglycan (GAG) genes, which are crucial for salinity tolerance, remains to be elucidated.

Design and method:
Interactions between 54,126 variants in 130 GAG genes and daily sodium excretion on BP were explored in 20,420 EPIC-Norfolk subjects. UK Biobank (n=414,132) and the multi-ethnic HELIUS study (n=2,239) were used for validation. In HELIUS sodium intake was estimated with Food Frequency Questionnaires (FFQ). Urinary GAG composition in 57 Dutch origin HELIUS participants stratified by genotype were analyzed to assess the association between SNP and GAG difference. Also, urinary GAG composition in 12 healthy volunteers after a sodium intervention (7-day low (50 mmol Na+/day) and 7-day high (200 mmol Na+/day) diet) were studied to assess if differences in genotype are associated with different GAG expression.

Results:
The intron variant rs2892799, mapped to NDST3, showed the strongest interaction with sodium on mean arterial pressure (MAP) (FDR 0.03), and the intron variant rs9654628 mapped to HS3ST5 with sodium on systolic BP (FDR 0.03). These interactions were multi-ethnically validated (Fig 1A, B). When stratified for rs2892799 genotype, T-allele carriers had a significantly higher urinary expression of N-sulfated heparan sulfate epitope D0S0 (Fig1C). Conversely, upon dietary salt loading, urinary D0S0 expression differed substantially between salt-sensitive and salt-resistant individuals (Fig1D). Sodium-induced effects on this epitope were opposite in salt-sensitive in salt-resistant individuals.

Conclusions:
Genetic variants associated with NDST3 and HS3ST5 interact with relation between sodium consumption and BP. rs2892799 (NDST3) genotype results in a different expression of the N-sulfated D0S0 epitope. In turn, D0S0 expression is associated with salt-mediated BP increase, indicating that genetic GAG variation and metabolic GAG adaptation to a high salt environment might be important for human BP regulation.
THERAPEUTIC POTENTIAL OF ABATACEPT IN RAT MODEL OF CARDIAC HYPERTROPHY VIA LIDDING CD80 AND CD86: A PROFOUND EXPLORATION OF SIGNALING PATHWAYS
Authors: Parjapati Vaishali , Verma Vipin Kumar , Bhatia Jagriti , Arya D. S. 
Published: May 2024

Objective:
Abatacept (a synthetic CTLA4 analog) inhibits co-stimulation of T-cell during their activation and minimize inflammation through infiltration of immune cell at the site of injury. The drug is mainly used in psoriatic diseases and Rheumatoid arthritis. Because of its mechanism of action, we have investigated its role in the isoproterenol-induced cardiac hypertrophy model of rat which is caused by increased cardiac workload. This study hypothesized that Abatacept may reduce cardiac T-cells and further macrophage entry into the myocardium, which can prevent cardiac hypertrophy in male albino Wistar rat model of isoproterenol (ISO)-induced cardiac hypertrophy was assessed after abatacept administration through hemodynamic, structural, biochemical, and molecular investigations.

Design and method:
In this study male Wistar albino rats were divided into six groups (n=6): Group 1 Control (with PBS administration); Group 2 disease control (ISO at 3 mg/Kg s.c. was given to induce hypertrophy); Groups 3, 4, and 5 are experimental groups. Abatacept at doses of 2.5, 5, and 10 mg/kg were administered daily along with the dose of ISO at 3 mg/kg s.c. to induce hypertrophy. In Group 6 only abatacept was injected s.c. at 10 mg/kg dose each day. The experimental duration of drug administration was for 40 days to investigate the effect of abatacept in pathological Cardiac Hypertrophy. On day 41st, after hemodynamic assessments, the blood was collected and the heart was excised to investigate physiological parameters, cardiac injury markers, biochemically oxidant-antioxidant assessments, inflammation, infiltration, and apoptosis.

Results:
Abatacept effectively reduced cardiac hypertrophy by stabilizing heart function. It showed positive effects on antioxidants, minimizing cardiac injury markers (CK-MB, LDH). histopathological evidence (including H&E and MT staining), along with decreased inflammatory cytokines and inflammasome formation. Immunofluorescence staining of t-cell sub-populations were also assessed using co-staining. The analysis of anti-apoptotic, apoptotic, necrosis, autophagy, and inflammatory (MAPK/Nrf-2-HO1/Smad-Tgf-beta) supports the hypothesis of abatacept cardio-protective action.

Conclusions:
Abatacept diminishes ISO-induced cardiac hypertrophy by inhibiting oxidative stress, inflammation, and infiltration, however, enhancing cardiac function and myocardium architecture. It could be a potential preventive drug for cardiac hypertrophy or for individuals at risk of developing it.
HYPERTRIGLYCERIDEMIA IN PATIENTS WITH ACUTE AND CHRONIC CORONARY SYNDROME: PREVALENCE AND THEIR ASSOCIATION WITH EXTREME CARDIOVASCULAR RISK AND LEFT VENTRICULAR FUNCTION
Authors: Maloberti Alessandro , Rosa Antonio La , Toscani Giorgio , Caccia Andrea , Gualini Elena , Pezzoli Stefano , Morelli Martina , Busti Andrea , Colombo Valentina , Tognola Chiara , Algeri Michela , Intravaia Rita Cristina My , Pirola Roberto , Giannattasio Cristina , Garofani Ilaria 
Published: May 2024

Objective:
Hypertriglyceridemia prevalence in Acute and Chronic Coronary Syndrome (ACS and CCS respectively) patients in the era of very low LDL target is still unknow. The objective of our study is to evaluate the prevalence of triglyceride levels above 150 or 200 mg/dL despite statin therapy and LDL cholesterol at targets in ACS and CCS subjects enrolled in a Cardiac Rehabiliatitation (CR) program

Design and method:
This cross-sectional observational study was conducted at the Niguarda Hospital (Milan, Italy). Patients undergoing CR after ACS/CCS from January 1, 2012, to March 28, 2023, were included. Data on demographic, clinical, laboratory, and instrumental variables were collected.

Results:
The study population consisted of 740 patients with a mean age of 64.3±10.7 years, predominantly male (81.7%). Triglyceride levels significantly decrease during the CR period (131.1±63.8 vs 116.9±75.9 mg/dL; p < 0.001) similarly to LDL cholesterol (107.9 ± 38.8 mg/dL vs 69.9 ± 25.9mg/dL, p<0.001). 50.8% of the subjects reach the LDL cholesterol target. The percentage of patients with triglycerides >150 mg/dL at CR ends was 17.8% (15.6% when considering only patients that reach the LDL target of 55 mg/dL) while it is only 6.8% for triglycerides >200 mg/dL (5.9% when considering only patients that reach LDL target). Patients with triglycerides >150 mg/dL had higher baseline BMI, LDL cholesterol and uric acid with lower ejection fraction at CR ends. Hypertriglyceridemia significantly correlates with extreme CV risk (R= 0.08, p= 0.025). At multivariate analysis, FE (dependent variable) was significantly associated with triglycerides (beta= - 0,145, p= 0,026) and systolic BP (beta= 0,137, p= 0,032).

Conclusions:
Despite high intensity statin therapy and lower LDL cholesterol targets, a substantial proportion of patients in cardiac rehabilitation still had elevated triglyceride levels. This study highlights the potential role of Icosapent Ethyl in managing hypertriglyceridemia in these patients.