bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
ASSOCIATION BETWEEN THE ATHEROGENIC INDEX OF PLASMA AND ADVERSE LONG-TERM PROGNOSIS IN PATIENTS DIAGNOSED WITH NON-ST ELEVATION ACUTE CORONARY SYNDROME
Authors: Li Mingkang , Zhang Wenkang , Zhang Minhao , Tang Chengchun
Published: May 2024

Objective:

Dyslipidemia is a key risk factor for coronary artery disease, and the atherogenic index of plasma (AIP) is a newly identified biomarker associated with lipid metabolism. However, none has addressed the association between AIP and clinical outcome in non-ST elevation acute coronary syndrome (NSTE-ACS) patients firstly implanted with drug-eluting stent (DES). Thus, we sought to evaluate the relationship between AIP and long-term prognosis in NSTE-ACS patients.

Design and method:

A total of 830 patients diagnosed with NSTE-ACS and who underwent DES were included in this study. The AIP index was calculated by log (triglycerides / high-density lipoprotein-cholesterol). Patients were divided into tertiles according to AIP levels (T 1: <0.195; T 2: 0.195∼0.252; and T 3: >0.252). The endpoints were major adverse cardiovascular events (MACE), including all-cause mortality, myocardial reinfarction, and target vessel revascularization during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were performed to examine the relationship between AIP and MACE. Moreover, Receiver operating characteristic (ROC) curve analysis was utilized to determine the optimal cut-off value of AIP for predicting MACE.

Results:

During the 12 months of follow-up, a total of 108 patients experienced MACE. The patients with higher AIP values (T 3 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (T 1 and T 2 groups) (20.2% vs. 6.2%, and 12.6% respectively; P < 0.05). The Kaplan-Meier curves reported that patients in T3 group had the highest risk of MACE relative to patients in the other groups (log-rank P < 0.001). Furthermore, the multivariate Cox regression analysis demonstrated that patients in the T3 group had a 1.422-fold increased risk of MACE compared to those in the T1 group. In addition, the ROC curve analysis revealed an optimal AIP cut-off value of 0.237 for predicting MACE in patients with NSTE-ACS.

Conclusions:

AIP is a novel and convenient independent predictor of MACE in patients with NSTE-ACS. It is necessary to monitor AIP for risk stratification in NSTE-ACS patients.
STRAIN RATE ECHOCARDIOGRAPHY IN ASSESSMENT OF CLINICAL CARDIAC STATUS IN HYPERTENSIVE PATIENTS
Authors: Karol Anubha , Karol Ajay
Published: May 2024

Objective:

Strain Rate Echocardiography (SRE) measures rate of change of contraction (LS) of cardiac fibres, the major component of overall cardiac contractility. Cardiac end organ involvement in Hypertension is omnipotent. We assessed utility of SRI in identifying clinical dysfunction of myocardial contractility in Hypertensives subjects.

Design and method:

We looked at Colour Doppler and Strain Rate Echocardiography data of 523 patients, with sequential Blood Pressure measurements(Thrice over 10 minutes). Hypertensives (n=136) constituted patients with average BP >130/80. Rest were designated as Normotensives(n=387). Left Ventricular Mass (LVM), Left Atrial Volume (LAV), Mitral E/e‘ ratio as surrogate for LV end diastolic pressure (LVEDP), were analysed for comparison. Unpaired Chi square test determined statistical significance.

Results:

Ejection Fraction were similar (56%+/-0.41 vs 58%+/-0.11). Normotensives showed positive correlation between LS and Systolic BP. However, negative correlation was observed in Hypertensives. In bothgroups, moderate inverse correlation between LVM, LVEDP versus GLS was observed. In both groups,LS was reduced in patients with high LVMi(p<0.0001), high LVEDP(p<0.003), increased LAV(p<0.01). The difference was statistically, highly significant. Difference in LS between Dippers (n=227) and Non-Dippers(n=296) was statistically not significant. However, LVM, LVEDP and LAV were higher in Non-Dippers. (p<0.001,p<0.03,p<0.02 respectively)

Conclusions:

LS measures longitudinally arranged cardiac fiber's function (predominantly sub-endocardial region) Present study showed, increased LVM and High LVEDP depresses their contractility, may lead to heart failure in future. Efforts to reduce intracardiac pressures and LV mass and Blood pressure will preserve cardiac function in hypertensives. Thus, LS estimation can identify subset who will respond to aggressive afterload reduction in hypertensives.
THE CHARACTERISTICS AND CLINICAL COURSE OF SPONTANEOUS CORONARY ARTERY DISSECTION: DIFFERENCES BETWEEN PATIENTS WITH AND WITHOUT HYPERTENSION- INSIGHTS FROM SCAD-POL REGISTRY
Authors: Kadziela Jacek , Zalewska Joanna , Michalowska Ilona , Kochman Janusz , Januszewicz Magdalena , Zarebinski Maciej , Radecki Pawel , Szybka Wojciech , Koch Rafal , Adlam David , Januszewicz Andrzej , Witkowski Adam
Published: May 2024

Objective:

Spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome of unknown etiology. Potential risk factors and comorbidities are female gender, fibromuscular dysplasia (FMD) and increased tortuosity. HTN is associated with increased coronary tortuosity and both have been shown to increase the risk of recurrence after SCAD. The aim of this study was to assess angiographic data and clinical course of SCAD in patients with HTN.

Design and method:

the study group comprised of 94 consecutive patients (97.8% females, aged 44.4 ± 9.3 years) with a history of angiographically confirmed SCAD, included in nationwide SCAD-POL registry. All medical records were gathered and angiography images reviewed, classifying SCAD type according to ESC classification. Patients (n=87) underwent head-to pelvis computed tomography angiography for FMD screening.

Results:

34 patients (97.1% females) had HTN. Hypertensive patients were characterized by increased age (48.5 ± 10.0 vs 42.1 ± 8.1 years, p<0.005), had more often hyperlipidemia (32.3 vs 11.7%, p<0.05) and more frequently were diagnosed with NSTEMI (70.6 vs 48.43%, p<0.05). FMD was diagnosed more often in patients with HTN (48.5% vs 23.7%, p<0.05). Looking at the distribution of FMD, the prevalence of FMD in cervical arteries was significantly higher in patients with HTN (28.1% vs 8.5%, p<0.05). In patients with HTN, proximal segments of coronary arteries were much less frequently affected by SCAD (11.8 vs 31.7%, p<0.05) and type 2b SCAD was more often observed (26.5 vs 10.0%, p<0.05). There were no differences in terms of PCI (32.3 vs 36.7%) and conservative management (67.6 vs 58.3%) between hypertensive and non-hypertensive subjects. Although, the left ventricle dysfunction (EF<50%) was less frequently observed at discharge in patients with HTN (10.7 vs 41.8%, p<0.01).

Conclusions:

patients with HTN were characterized by more favorable angiographic characteristics and clinical course of SCAD and higher prevalence of FMD. Further investigation of the relationship between hypertension, coronary tortuosity and the course of SCAD is merited.
ERDOSTEINE REINSTATE MYOCARDIAL NECROSIS: INNOVATORY EFFECT THROUGH MODULATION OF MAPK AND NRF 2/HO 1 PATHWAY
Authors: Kumaraguruparan Nivetha , Verma Vipin Kumar , Bhatia Jagriti , Arya D S
Published: May 2024

Objective:

Erdosteine, a mucolytic drug, proved as a potent anti-inflammatory agent via free radical scavenging, in several pre-clinical studies. To amend the effect of Erdosteine (thiol-based drug) against oxidative stress, inflammation, apoptosis/ necroptosis in a catecholamine rush-induced myocardial necrosis model was performed in male Wistar rats.

Design and method:

The 48 Male albino Wistar rats were divided into eight groups (n = 6), that is, Normal, Isoproterenol control, and 6 different erdosteine pretreatment groups at subsequent increasing doses from 5 to 160 mg/Kg followed by ISO (Isoproterenol) administration. Rats were given erdosteine orally for 28 days. Two doses of ISO (85 mg/kg), s.c. were given to Isoproterenol control and erdosteine pretreatment groups on the 27th and 28th day at 24-hour intervals. On the 29th day, hemodynamic parameters were recorded using BioPac systems BSL 4.0 MP36 software. After measuring left ventricular pressure, blood was withdrawn and the heart was excised for biochemical, histopathological and molecular parameters.

Results:

In Isoproterenol control rats, significantly increased levels of cardiac-injury markers (CK-MB, LDH), anti-oxidant oxidant ratio (MDA, GSH, and SOD), inflammatory markers (TNF-alpha and IL-6), Reactive Oxygen Species (ROS), inflammatory proteins (MAP kinases), apoptotic proteins (Bax, Bcl-2, Caspase-3) were observed as compared with the normal group. The Pathological and ultrastructural damage were also observed more in Isoproterenol control group as compared with normal group. Furthermore, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labelling revealed an increased expression of apoptotic proteins. In Erdosteine pre-treatment groups, we found dose-dependent attenuation of inflammation, oxidation, and apoptosis. Erdosteine at 80 mg/kg countermand the detrimental effects of ISO and preserved the myocardium architecture. Erdosteine showed anti inflammatory, antiapoptotic, and antioxidant activities through the inhibition of MAPK and Nrf 2 |HO 1 pathways.

Conclusions:

Erdosteine was found protective in ISO induced myocardial necrosis through MAPK and Nrf 2 |HO 1 pathwaysand can be further used as an effective treatment against inflammation more specifically in myocardial infarction. Furthermore, more evidence is required for use of Erdosteine in clinical use.
BIO-HUMORAL AND HAEMODYNAMIC CORRELATES OF RENAL VENOUS CONGESTION IN THE HEART FAILURE SPECTRUM
Authors: Del Punta Lavinia , De Biase Nicolo’ , Filidei Francesco , Balletti Alessio , Armenia Silvia , Di Fiore Valerio , Pugliese Nicola Riccardo , Masi Stefano
Published: May 2024

Objective:

Increased central venous pressure worsens systemic congestion in heart failure (HF); this has a particular pathophysiological significance in the renal vascular bed, which can be evaluated by Doppler analysis of renal venous flow (RVF). RVF is continuous in healthy subjects and becomes discontinuous with increased fluid retention; thus, RVF evaluation allows for refined pathophysiological characterisation in HF. We sought to analyse the relationship between different RVF patterns, echocardiography-derived haemodynamics and laboratory parameters in patients at risk of or with overt HF.

Design and method:

The study enrolled 304 patients. 63 patients were at risk of developing HF, while 241 had overt HF. Among the latter, 61 patients had preserved left ventricular ejection fraction (LVEF >=50%), and 180 had reduced LVEF (<50%). All subjects underwent a baseline echocardiographic examination, lung ultrasound, Doppler-derived RVF evaluation, and laboratory evaluation of blood and urine samples.

Results:

The most prevalent cardiovascular risk factor was arterial hypertension (AH), which was present in 60% of patients at risk of developing HF and in 72% of those with overt HF.

RVF was continuous in 230 patients (76%), and discontinuous in 74 (24%; dRVF). Among the latter, 39 showed pulsatile dRVF, 18 showed biphasic dRVF (i.e., two separate phases of venous flow), and 17 showed monophasic dRVF (i.e., only during diastole). dRVF was more prevalent in patients with overt HF. Monophasic dRVF was associated with more severe haemodynamic impairment and impaired renal function, as evaluated by estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. After adjusting for clinical confounders, worsening RVF patterns were associated with increased natriuretic peptide levels, worse right ventricular-pulmonary arterial uncoupling, increased inferior vena cava diameter, and increased estimated pulmonary capillary wedge pressure (Figure). These results were confirmed in the subgroup of patients with overt HF, even after adjusting for LVEF.

Conclusions:

The evaluation of RVF patterns improves the characterisation of patients with HF. The pathophysiological significance of impaired RVF is independent of common cardiovascular risk factors and LVEF. Implementing RVF analysis in clinical practice could allow for timely identification of patients at greater risk for developing or worsening HF.
PREVALENCE AND CHARACTERISTICS OF ISOLATED NOCTURNAL HYPERTENSION IN TREATED PATIENTS
Authors: Rhee Moo -Yong
Published: May 2024

Objective:

This study aimed to identify the prevalence and characteristics of isolated nocturnal uncontrolled hypertension (INUCH) in treated patients.

Design and method:

Participants (n=701) aged >=20 on antihypertensive drugs were recruited via advertisements between August 2018 and April 2020 and underwent 3-day office (3 readings every visit) and 24-hour ambulatory blood pressure (BP) measurements. Hypertension phenotypes were categorized as controlled (CH), isolated daytime uncontrolled (IDUCH), INUCH, and day-night uncontrolled hypertension (DNUCH), according to 2023 ESH guidelines.

Results:

Of 650 participants with valid BP data, INUCH prevalence was 32.3% (34.9% in patients with office BP <140/90 mmHg), with a higher prevalence of men and drinkers than CH. INUCH patients exhibited higher office systolic (SBP) and diastolic BP (DBP) than CH. INUCH prevalence was higher in patients with office BP <140/90 mmHg (34.9% vs. 18.9% for >=140/90 mmHg). INUCH rates decreased across office BP categories (37.6% in optimal, 38.5% in normal, 27.9% in high-normal, and 18.9% in uncontrolled office BP), while DNUCH increased (10.6% in optimal, 24.2% in normal, 53.5% in high-normal, and 71.7% uncontrolled office BP). Among INUCH patients, 48.1% had isolated uncontrolled DBP, 8.6% had isolated uncontrolled SBP, and 43.3% had both. Those with isolated uncontrolled DBP were younger (p=0.016), more males (p=0.017), and drinkers (p=0.006) than those with isolated uncontrolled SBP and DBP. Multivariate analysis in patients with office BP <140/90 mmHg revealed age and alcohol drinking as positive and high-normal OBP as negative INUCH factors. Isolated uncontrolled DBP and uncontrolled SBP and DBP were significantly associated with INUCH. Brachial-ankle pulse wave velocity was significantly higher in INUCH patients than in CH patients after excluding patients with isolated uncontrolled DBP.

Conclusions:

The considerable INUCH occurrence in normal/optimal office BP patients implies treatment challenges. The association of alcohol consumption with INUCH underscores moderation in hypertension treatment. Although the prognostic significance of INUCH with isolated uncontrolled DBP was undetermined, distinguishing between isolated uncontrolled DBP and uncontrolled SBP seems necessary in evaluating the prognostic significance of INUCH.
ARTERIAL HYPERTENSION AND BLOOD PRESSURE RESPONSE TO EXERCISE IN ATHLETES
Authors: Jelínek Libor , Moravcová Katarína , Ozana Jaromír , Sovová Markéta , Václavík Jan , Jiravský Otakar , Jiravská-godula Bogna , Pesová Petra , Puskasová Kristina , Sovová Eliska
Published: May 2024

Objective:

Arterial hypertension is one of the most important risk factors for cardiovascular disease and the most common pathological finding in the examination of athletes. On the other hand, physical activity leads to a reduction in blood pressure and is thus an essential part of a regimen in the treatment of hypertension.

People who wish to engage in sport at the competitive level should be pre screened by a stress test. A number of those examined have resting hypertension and a part has an exaggerated response to exercise.

Our aim was to determine what proportion of the tested athletes had each hypertensive phenotypes and exercise BP hyperresponsiveness. Furthermore, we wanted to compare the prevalence of arterial hypertension between different types of sporting activity - mixed, endurance, strength and skill.

Design and method:

We retrospectively analyzed data from 1,733 adult athletes who underwent stress testing at two sports medicine centers between 2019 and 2023. The mean age was 24.9 years, 69% of the subjects were male and the relative performance was on average 4.08 W/kg. Clinical data at rest and during exercise were measured and recorded. Subsequently, the data were statistically processed.

Results:

A total of 431 (24.9%) subjects met the criteria for arterial hypertension when resting blood pressure was measured. Z 182 (10.5%) had isolated systolic hypertension and 104 (6%) had isolated 19 (1.1%) subjects had exertional hypertension. Elevated diastolic blood pressure occurs significantly more frequently in athletes with skill or strength type sports than in athletes with mixed type sports (24.0% and 24.2% vs. The hypertensive response to exercise occurs significantly more frequently in athletes with strength-type sports than in athletes with mixed-type sports (4.5% vs. 0.7%, p = 0.006).

Conclusions:

The higher incidence of resting and exertional arterial hypertension in specific types of sports should lead to more intensive diagnosis and care for these specific types of athletes.

The definition of exertional pressure hyperreaction is currently inconsistent. Longer follow-up of individuals with borderline and pathological values could lead to more effective indication for testing and subsequent treatment and regimen measures.
MOLECULAR MECHANISM OF PDE3A SIGNALING IN HYPERTENSION WITH BRACHYDACTYLY (HTNB)
Authors: Tiannan Liu , Enno Klussmann , Kerstin Zuhlke , Anastasiia Sholokh , Ranjan Pati Swaroop , Alexander Blume , Altuna Akalin , Yumi Sunaga -Franze Daniele , Tatiana Borodina
Published: May 2024

Objective:

Hypertension with brachydactyly (HTNB) is a syndrome characterized by progressive hypertension, brachydactyly type E, and blood vessel hyperplasia. HTNB is caused by mutations in the gene encoding phosphodiesterase 3A (PDE3A). The mutations cause hypertension by increasing vascular smooth muscle cell (VSMC) proliferation and compromising relaxation of second-order mesenteric arteries. cAMP signaling occurs in defined cellular compartments where PDE3A hydrolyzes and thereby limits cAMP levels. The objective of this project is the elucidation of molecular mechanism of mutant PDE3A-induced hypertension to identify novel therapeutic strategies targeting PDE3A signaling compartments for the treatment of hypertension.

Design and method:

Experiments were performed with three models: thoracic aorta and second-order mesenteric artery VSMCs from wild-type and rat HTNB models, and VSMCs differentiated from human induced pluripotent stem cells carrying PDE3A mutations that cause HTNB (iPSC-VSMCs). RNA-seq, RT-qPCR and Western blotting were used to validate gene and protein expression differences of candidates. Intracellular Ca2+ signaling changes were analyzed by Ca2+ imaging.

Results:

RNA-seq and RT-qPCR results showed that several genes were differentially expressed between wild-type and HTNB VSMCs. For example, compared with wild-type, PDE3A expression was downregulated in blood vessels derived from HTNB rats, whether derived from thoracic aorta or second-order mesenteric arteries. The protein expression of regulatory subunits of protein kinase A (PKA) was decreased in the second-order mesenteric arteries of HTNB models but there was no significant change in the thoracic aorta. Ca2+ imaging of iPSC-VSMCs revealed greater contractility in cells carrying PDE3A mutations.

Conclusions:

Mutant PDE3A signaling may be a starting point for an innovative, PDE3A compartment-specific pharmacological concept for the treatment of hypertension.
SYSTOLIC BLOOD PRESSURE IS ASSOCIATED WITH ELEVATED NATIVE T1 TIME IN CARDIAC MRI SUGGESTING MYOCARDIAL FIBROSIS IN PEDIATRIC KIDNEY TRANSPLANT RECIPIENTS
Authors: Von Der Born Jeannine , Ubenauf Tim , Sugianto Rizky I. , Grabitz Carl , Memaran Nima , Babazade Nigar , Falk Jan , Renz Diane , Schmidt Bernhard Mw , Kanzelmeyer Nele , Melk Anette
Published: May 2024

Objective:

Cardiac alterations and complications are common after pediatric kidney transplantation (KTx). In adults, myocardial fibrosis is an established surrogate marker for cardiac mortality. Non-contrast native T1 time (nT1) in cardiac MRI offers the possibility to detect structural myocardial changes. Data for children after KTx is not available yet. We aimed to assess function and structure in cardiac MRI in pediatric KTx-recipients with a focus on nT1.

Design and method:

46 KTx-recipients (mean age 16±3.5 years; 7.9±5.3 years after KTx) and 46 sex- and age- matched healthy controls were examined with gadolinium-free cardiac MRI. nT1 and T2 time were measured at the interventricular septum (basal and mid-ventricular short-axis slice). Further parameters derived from MRI were: left ventricular mass index (LVMI), left ventricular ejection fraction (LV-EF) and global longitudinal strain (GLS). Multivariable linear regression analysis (co-variates: age, sex, height) was used to evaluate the association between nT1 and clinical parameters.

Results:

KTx-recipients had a significant higher nT1 than healthy controls (1198±48.8ms vs. 1155±23.4ms; p< 0.001). In 22 KTx-patients (48%) nT1 values were above the total range of controls.

T2 time showed no significant difference between the groups. KTx-recipients showed a higher LVMI z-score (LVMIz), a higher LV-EF and a lower GLS. Higher nT1 was associated with systolic blood pressure (SBP; ß=1.28; p=0.001; Fig. 1), LVMIz (ß=1.55, p<0.001) and LV-EF (ß=3.52, p=0.026) only in patients, but not in controls. Further evaluation of KTx-recipients revealed that nT1 tended to be higher with longer time on dialysis, no association was seen for time since KTx.

Conclusions:

Our data suggest the presence of cardiac remodeling with myocardial fibrosis in a significant proportion of young KTx recipients. Non-contrast CMR imaging has the potential as a diagnostic adjunct in the follow-up of KTx recipients for a better risk stratification. Longitudinal studies are needed to evaluate if preventive targeting of associated factors, especially optimization of BP control, might reduce the prevalence of sudden cardiac death in young KTx recipients.
TIME IN TARGET RANGE OF SYSTOLIC BLOOD PRESSURE AND EGFR SLOPE IN PATIENTS WITH TYPE 2 DIABETES
Authors: Sheng Chang -SHENG , Cheng Yi , Tian Jingyan
Published: May 2024

Objective:

Time in target range (TTR) of systolic blood pressure, a novel measure to assess the effect of blood pressure control, is attracting attention in recent European guidelines. However, few studies have explored the renoprotective value of systolic TTR in patients with type 2 diabetes (T2D).

Design and method:

We used the database of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial, and 4409 eligible participants were enrolled in the present study. The systolic target range for the standard and intensive therapy was defined as 120 to 140 mm Hg and 110 to 130 mm Hg, respectively.

Results:

After adjustment for covariates, systolic TTR was significantly and positively associated with 2 indices of eGFR slope (P <= 0.0016), regardless of additional adjustment for systolic blood pressure average and variability. The association of systolic TTR and eGFR slope was significantly stronger in CKD patients than those without CKD (P for interaction <=0.044). When TTR was treated as a categorical variable, participants with the highest systolic TTR in the CKD group had a significantly positive association with eGFR slope (P <= 0.00046). Similar results were obtained in the further subgroup analysis.

Conclusions:

Among patients with diabetes, systolic TTR showed a significant and positive association with eGFR slope, with a stronger association observed in those with CKD. TTR reflects both blood pressure level and stability across blood pressure management, emphasizing the importance of maintaining stable blood pressure control for renoprotection in T2D patients, particularly in those with CKD.
IN NORMOTESIVE SALT SENSITIVE SUBJECTS, INSULIN RESISTANCE IS ASSOCIATED TO FUTURE HYPERTENSION. A 3 YEAR FOLLOW-UP STUDY
Authors: Sanchez Ramiro A. , Sanchez Maria J. , Pessana Franco M. , Ramirez Agustin J.
Published: May 2024

Objective:

Salt sensitive hypertension (SS) is associated to insulin resistance even in lean individuals. However, no data has been shown in normotensive offspring of hypertensive salt sensitive parents.

In a 3 year follow-up, we evaluated in normotensive SS or salt resistant (SR) offspring of hypertensive parents (offSS-HT or offSR-HT, respectively), the frequency to develop hypertension. In addition, a complete metabolic panel was performed in both groups, as well as urinary albumin excretion and creatinine clearance was calculated, as markers of kidney function.

Design and method:

43 offSS-HT (29±2 years; 20 female), and 36 offSR-HT (26±2 years; 16 female) were followed-up for 3 years. Both groups were considered lean with a BMI Higher than 25kg/m2 and a waist circumference Greater than 98 cm in males or <105 cm in females). Creatinine clearance (CrCl), 24h urinary albumin excretion, Glycemia and insulinemia before and after 60 and 120 min a glucose overload (75 g; OGTT) was measured at baseline. The area under the curve (AUC; mg/dl.min) and the HOMA index (fasting glucose (mg/dl) × fasting insulin (μU/ml)/405),were also calculated. Blood pressure (BP) and 24h urine sodium excretion were measured each year.

Results:

Blood pressure rose significantly, after 3 years in offSS-HT (11.5±4.27/9.5±3.3mmHg) compared to offSR-HT, (-0.3±2.8/-0.9±3.6; p<0.0001).

In offSS-HT, UAE was significantly higher (53±3μ.min, p<0.01) than in offSR-HT.(12±4μ.min)

At baseline fasting, 60 min and 120-min, glycemia and insulinemia post OGTT were higher in offSS-HT(140.1±18; 130±15 mg.dl and 31.8±11; 31.8±11 IU) than in offSR-HT (116.5±5: 6.5±3 mg.dl and 18.8±7; 21.3±4IU, p<0.01).

Glycemia AUC was significantly higher (258.80±25mg/dl.min) in offSS-HT compared to offSR-HT (194.39±6mg/dl.min, p<0.0001).

Similarly, HOMA-IR was higher in offSS-HT (3.26±1.36; p < 0.002) than in offSR-HT (1.52±0.27).

In offSS-HT the CrCl was significantly higher (136±8 ml.min; p<0.05) than in offSR-HT (107±6 ml.min).

Conclusions:

In offSS-HT blood pressure rise was associated to insulin resistance and glomerular hyperfiltration suggesting a familiar aggregation and a higher cardiometabolic risk when compared with offSR-HT.