bluuebunny/crossref_metadata_2025_split huggingface dataset:
RATIONALE AND DESIGN OF THE PROSPECTIVE IN-HOSPITAL DETECTION OF ELEVATED BLOOD PRESSURE STUDY (INDEBP)
Authors: Vischer Annina , Hausknecht Katharina , Socrates Thenral , Mayr Michael , Breidthardt Tobias , Burkard Thilo 
Published: May 2024

Objective:
There is a large gap in evidence on how to handle asymptomatically elevated blood pressure (BP) values during non-cardiac hospitalization. Recent data suggests that initiation or up-titration of antihypertensive drugs during hospitalization poses a risk of adverse events, possibly due to over-diagnosis and treatment. The aim of the study is to elucidate the prevalence of new persistent or uncontrolled arterial hypertension (AHT) four weeks after hospital discharge in patients with elevated BP values during hospitalization and to demonstrate safety of postponement of treatment.

Design and method:
This is a single-center, open-label, prospective, two-phase observation-intervention study. Patients with asymptomatically elevated BP values during non-cardiac hospitalization will be included. The study contains two subsequent periods. In a first control phase, adjustment of BP treatment will be at the discretion of the treating physician without any interference by the study physicians. In the second intervention phase, the patients’ pre-hospital antihypertensive treatment will not be changed during hospitalization. Only bail out medications for safety reasons will be permitted. Four weeks after hospital discharge, all patients will receive a 24h BP measurement (ABPM) (Figure). Patients with new or uncontrolled AHT on ABPM will be offered treatment recommendations according to current guidelines. We plan to enroll 400 participants in each phase. The primary endpoint will be the proportion of new persistant or uncontrolled AHT according to mean ABPM. Furthermore, prevalence of adverse events consisting of intracerebral bleeding, ischemic stroke, myocardial infarction, cardiovascular death or cardiovascular re-hospitalization, falls, acute kidney injury, or electrolyte disturbances will be analyzed.

Results:
Study received Ethical Committee approval by October 2023 with the first-patient-in November 16th 2023. During the first week we screened 21 patients with enrolment of 6. Main reason not to participate is the lack of consent to attend the ABPM installation due to their poor health.

Conclusions:
This is the protocol of a new study assessing the outcome of postponement of antihypertensive treatment in patients and adding new insights into the management of asymptomatic BP elevations during non-cardiac hospitalizations.
EVALUATING THE IMPACT OF OMEGA-3 FATTY ACID SUPPLEMENTATION ON LIPID PROFILES IN ADULTS WITH PPARG POLYMORPHISMS: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: Pokushalov Evgeny , Ponomarenko Andrey , Bayramova Sevda , Garcia Charlotte , Pak Inessa , Shrainer Evgenya , Johnson Michail , Miller Richard 
Published: May 2024

Objective:
To assess the effects of fish oil supplementation on cardiovascular markers among adults with PPARG gene polymorphisms in a randomized, double-blind, placebo-controlled trial.

Design and method:
A cohort of 102 individuals, aged 40-75 with LDL-C 70-190 mg/dL, was randomized to receive either 2000 mg of omega-3 fatty acids or a placebo daily for 90 days. Adherence, dietary and lifestyle constancy were monitored, and lipid and metabolic panels were evaluated at baseline and study conclusion.

Results:
Ninety-nine participants completed the trial. In the omega-3 group with PPARG polymorphisms, LDL-C was reduced by 15.4% (95% CI: -19.8% to -11.0%), compared with a 2.6% decrease in the placebo group (95% CI: -4.1% to -1.1%; p<0.01). In the omega-3 group without PPARG polymorphisms, LDL-C was reduced by 3.7% (95% CI: -6.9% to -0.6%), not significantly different from the placebo group's reduction of 2.9% (95% CI: -5.1% to -0.8%; p=0.28). The reduction in LDL-C was notably 11.7% greater in those with PPARG polymorphisms than in those without (95% CI: -19.3% to -4.0%; p<0.01). Triglycerides decreased by 21.3% in omega-3 recipients with PPARG polymorphisms (95% CI: -26.5% to -16.2%; p<0.01), with no significant changes in HDL-C, total cholesterol, or hsCRP levels in any groups. Minor allele frequencies and baseline characteristics were comparable, ensuring a balanced genetic representation.

Conclusions:
Our study provides robust evidence supporting the modulatory role of PPARG polymorphisms in lipid metabolism in response to omega-3 fatty acid supplementation. The data obtained from this randomized, double-blind, parallel-group clinical trial unequivocally demonstrate that individuals with PPARG polymorphisms, who are at low-to-moderate cardiovascular risk and present with elevated cholesterol levels, benefit significantly from the introduction of omega-3 fatty acids into their diet. These benefits are manifested in substantial reductions in LDL-C, total cholesterol, and serum triglycerides over a three-month period.
Importantly, the findings highlight the potential for personalized nutrition strategies, suggesting that genetic profiling could be an invaluable tool in optimizing lipid-lowering interventions. Patients carrying PPARG polymorphisms showed greater improvements in lipid profiles, indicating that genetic predispositions should be considered when prescribing omega-3 fatty acid supplementation.
EFFECT OF METHYLFOLATE, PYRIDOXAL-5’-PHOSPHATE, AND METHYLCOBALAMIN SUPPLEMENTATION ON HOMOCYSTEINE AND LDL-C LEVELS IN PATIENTS WITH MTHFR, MTR, AND MTRR POLYMORPHISMS
Authors: Pokushalov Evgeny , Ponomarenko Andrey , Bayramova Sevda , Garcia Charlotte , Pak Inessa , Shrainer Evgenya , Johnson Michael , Miller Richard 
Published: May 2024

Objective:
To assess the effects of methylfolate, pyridoxal-5’-phosphate (P5P), and methylcobalamin on homocysteine and lipid levels in patients with MTHFR, MTR, and MTRR gene polymorphisms linked to CVD.

Design and method:
In a thorough randomized, double-blind, placebo-controlled study design, 54 patients between the ages of 40-75, with elevated homocysteine levels and moderate LDL-C levels, were enrolled. Stratified by their genetic makeup concerning MTHFR, MTR, and MTRR polymorphisms, participants received either an intervention comprising methylfolate, P5P, and methylcobalamin or a placebo over a 6-month period. The primary endpoint was the percent change in serum homocysteine levels, while secondary endpoints included the assessment of LDL-C, HDL-C, total cholesterol, serum triglycerides, and hsCRP.

Results:
The trial concluded with 51 participants, demonstrating high adherence and consistent dietary habits. At 6-month follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo (p<0.01 for all). Changes in HDL-C and other lipid markers were not statistically significant.
In the subgroup analysis, homozygous minor allele carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, p<0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, p<0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, p<0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, p<0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, p<0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, p<0.01).

Conclusions:
Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms. These findings underscore the potential for personalized nutrition in the management and prevention of CVD, emphasizing the role of genotype-guided therapy in clinical practice.
TO EXPLORE THE CLINICAL FRAILTY SCALE IN PREDICTING THE LONG TERM PROGNOSIS OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION AFTER IN-HOSPITAL CARDIAC REHABILITATION
Authors: Liu Yuting , Yu Wanqi , Hong Wen , Kang Sang , Li Xinni , Xiao Huoyan , Pan Jingwei 
Published: May 2024

Objective:
Patients successfully revascularized after acute myocardial infarction (AMI) underwent in-hospital cardiac rehabilitation (CR) and were assessed for their state by the clinical frailty scale (CFS) to investigate the predictive value of the CFS score on the incidence rate of major cardiovascular events within one year.

Design and method:
A graded CR scheme was developed in a total of 501 patients with AMI, who were treated in the cardiology center of Shanghai Sixth People’s Hospital from May 2020 to May 2022, and the CFS score was assessed based on the CR condition of the patients before discharge. Patients were then categorized into three groups (norm group, vulnerable group, and frail group) according to their CFS score. The difference in one-year major cardiovascular event (all-cause death and re-hospitalization for heart failure) rates among these groups was compared. Logistic regression analysis was performed to explore risk factors affecting cardiovascular events, and an ROC curve was generated to analyze the risk factors in predicting one-year cardiovascular event rates. Finally, an optimal prediction model was developed.

Results:
The CFS score in AMI patients was positively correlated with age and peak proBNP and inversely correlated with gender difference (P <= 0.001). There were significant differences in the incidence of all-cause death between the frail group and the norm group (P = 0.002), whereas there was no significant difference between the vulnerable group and the norm group (P > 0.05). There was no significant difference in re-hospitalization for heart failure among the three groups (P = 0.710). The CFS score could sensitively predict the 1-year risk of all-cause death in AMI patients (β = 1.89, OR = 6.61, P = 0.001), and the risk model combined with the CFS score had the best predictive effect (AUC = 0.845, P = 0.000).

Conclusions:
In-hospital CR along with assessment using the CFS score can effectively identify AMI patients with a high risk of death.
ACHIEVED SYSTOLIC BLOOD PRESSURE BELOW 130 MMHG PRESERVES KIDNEY FUNCTION IN DIABETIC AND NON-DIABETIC HYPERTENSIVE PATIENTS WITHOUT CARDIAC HYPERTROPHY
Authors: Olsen Eirik , Soraas Camilla L. , Schmieder Roland E. , Jamerson Kenneth , Macdonald Thomas , Mancia Giuseppe , Heimark Sondre , Mehlum Maria H. , Mariampillai Julian , Liestol Knut , Larstorp Anne C , Hoieggen Aud , Kjeldsen Sverre E. , Rostrup Morten , Mo Rune , Julius Stevo , Weber Michael A. 
Published: May 2024

Objective:
Kidney function is preserved by achieving systolic blood pressure (SBP) primarily <140mmHg and possibly <130mmHg in hypertensive patients. We aimed to investigate kidney function when achieving SBP 130-139 and <130mmHg in type-2 diabetic and non-diabetic hypertensive patients without cardiac hypertrophy who participated in a major prospective hypertension outcome trial.

Design and method:
Of the 15,245 study participants, 13,803 patients were without cardiovascular events during the first six months after randomization with roll-over from previous medications to blinded study drugs and had a minimum of 3 subsequent BP visits during 4-6 years. Of these, 2,458 patients with cardiac left ventricular hypertrophy (LVH) by ECG were not included in the present analysis because, as previously reported, they had increased cardiac and all-cause mortality at average achieved SBP <130mmHg. Of the remaining 11,345 patients, 3932 had diabetes. Cox analyzes adjusted for baseline covariates compared the pre-specified kidney endpoints 50% rise of se-creatinine (worsening kidney function, WKF) and end-stage renal disease (ESRD, dialysis and/or transplantation) for patients who achieved average SBP 130-139 and <130mmHg with those who remained with SBP >=140mmHg.

Results:
Patients with diabetes had less WKF at SBP 130-139mmHg (HR=0.50, 95% CIs 0.34-0.72, n=1605, p<0.001) and at SBP <130mmHg (HR=0.43, CIs 0.23-0.80, n=599, p=0.008). They also had less ESRD at SBP 130-139mmHg (HR=0.32, CIs 0.12-0.88, p=0.03) with similar trend at SBP <130mmHg (HR=0.21, CIs 0.03-1.65) which was significant for the 3rd quartile of SBP (135mmHg) (HR=0.09, CIs 0.01-0.71, p=0.02) and for the 4th quartile of SBP (126mmHg) (HR=0.12, CIs 0.02-0.92, p=0.04). Patients without diabetes (n=7413) also had less WKF at SBP 130-139mmHg (HR=0.58, CIs 0.40-0.83, n=3258, p=0.003) and at SBP <130mmHg (HR=0.38, CIs 0.21-0.68, n=1542, p<0.001). For ESRD the trend was similar as for diabetes at 3rd quartile of SBP (135mmHg) (HR=0.37, CIs 0.14-1.00, p=0.05) and at 4th quartile of SBP (126mmHg) (HR=0.23, CIs 0.07-0.75, p=0.02).

Conclusions:
In high-risk hypertensive patients above 50 years, with and without type-2 diabetes, but without cardiac hypertrophy, we found stepwise less worsening of kidney function and end-stage renal disease with lower average achieved systolic BP from >=140mmHg to 130-139mmHg to <130mmHg.
OBSTRUCTIVE SLEEP APNEA AND AUTONOMIC DYSFUNCTION
Authors: Berger Abel , Caruso Gustavo , Sivori Martin , Iriarte Javier , Sanchez Ramiro , Ramirez Agustin 
Published: May 2024

Objective:
To investigate 1) the relationship between sympathetic nervous system activity and the Apnea Hypopnea Index (AHI), a simplified outpatient OSA identifier.

Design and method:
A cross-sectional, observational analytical study including patients with suspected OSA were invited to participate.
The office blood pressure (BP) measurement was performed thrice automatically (Omron Hem 742). After, the respiratory evaluation was performed (Apnealink plus) and patients with AHI >5 were identified having OSA and included in the study.
Finally, a 2h continuous beat-to-beat BP recording was carried out (FINAPRES device) 1h at rest and 1h behaving quiet activities. Then, BP and PI (Pulse Interval) mean values and respective variabilities were calculated SBPvar, DBPvar and Pivar.
From the original beat to beat recording, a frequency analysis (Fast Fourier Analysis) was performed and the power of the High (HF) and Low (LF) Frequency components calculated, as representatives of the vagal and sympathetic activity, respectively. A similar protocol was followed with 50 normotensive subjects without OSA (NT).

Results:
A total of 23 patients with OSA were enrolled (Mean age 49.17±2.93 years; 42.8% women)
OSA patients showed a higher BMI (37.6±1.66) and BP (135.4±3.18 / 86.1±2.2mmHg) than NT (BMI: 26.74±0.56 Kg/m2, p=0.02; BP: 126.82±1.25 / 72.95±1.43 mmHg; p=0.05).
In OSA patient higher SBPvar and PI (Systolic Blood Pressure variability, Pulse interval variability).only when performing quiet activities (12.1±0.79 / 6.9±0.61mmHg and 71.0±7.37msec) than in NT subjects (11.4±0.30 / 6.4±0.25mmHg; p=0.004 62.6±3.11msec; p=0.02).
Instead higher BPvar or PIvar values were observed at rest, only during quiet activity, OSA patients showed higher SBPvar (13.9±0.81mmHg, p=0.004) and PIvar (90.4±8.82msec, p=0.002) when compared to NT subjects (11.4±0.30).
Finally, the AHI showed a significant correlation with SBPvar (r=0.593, p=0.01), DBPvar (r=0.655, p=0.01, and PI var (0.535, p=0.02). A significant negative correlation was found between AHI and the HF/LF relationship at rest (r=-0.0.26) and when standing up (Physiological Tilting; r=-0.27).

Conclusions:
Compared to normotensive subjects, OSA patients showed an altered autonomic activity represented by an increase in BP and PI variabilities. This was associated with an increased OSA prevalence in patients with increased sympathetic activity.
IMPACT OF IRON DEFICIENCY ON CLINICAL,BIOCHEMICAL AND ECHOCARDIOGRAPHIC PARAMETERS IN HEART FAILURE PATIENTS
Authors: Siddiqi Zeba , Rao Nidhi , Wani Irshad 
Published: May 2024

Objective:
Iron deficiency (ID) is prevalent in HF irrespective of the presence of anemia. Objective was to study the impact of iron deficiency on clinico- biochemical and echocardiographic parameters of heart failure patients.

Design and method:
Sixty adult heart failure patients were included in observational study with consent.
Excluded were anemia not attributed to ID,IV iron or blood transfusion administered in last 3 months,Oral iron supplements in previous 4 weeks, dyspnea of non cardiac origin,clinical evidence of ACS, TIA or stroke within the last 30 days,CABG, PTCA, cardiac device implant/resynchronisation therapy or any other cause leading to significant blood loss within the last 30 days.
Demographic information and medical history including NYHA grade of Dyspnea at presentation were noted. Iron studies,Nt proBNP levels and echocardiography were performed and appropriate statistical tests were applied.

Results:
Mean Age of cases was 57 (+/-5) years. Most common presenting symptom was breathlessness in 49(81.7%)patients followed by leg swelling in 46 (76.7%) and chest pain in 34 (56.7%)where as among the signs on examination; raised JVP was recorded in 18 (30%),hepatomegaly in 30(50%), splenomegaly in 17(28.3%),ascites in 19(31.7%),S3 gallop rhythm and basal lung crepitations in 10(16.6%) and 47(78.3%)patients respectively.
Majority of patients were in grade2 NYHA.
Iron Deficiency as determined by serum ferritin of <100 μg/mL or ferritin 100-300 μg/ml but transferrin saturation less than 20% was present in 43(71.7%)patients whereas in 17 patients(28.3%) it was not observed. Mean serum Iron was 36.417μg/dl,mean serum ferritin was 242.89 μg/ml and mean transferrin saturation was 17.25%.
Mean Hb was 10 gm% and mean NTProBNP was 11,324.65 picogm/ml.Mean Ejection fraction was 38%(+/- 12.75%).NtProBNP levels did not show any correlation with iron profile whereas LVEF showed a significant correlation with serum Iron as well as transferrin saturation (p <0.001). Serum iron and Transferrin saturation were significantly reduced with the progression of severity grade (p<0.006&0.001 respectively).

Conclusions:
Targeting iron deficiency in HF can improve outcomes as it targets mitochondrial dysfunction. This makes ID stand out as a therapeutic target in HF since it is relatively easy to diagnose and treat.
SYSTEMIC DISEASES ARE A GROUP OF INFLAMMATORY ILLNESSES THAT CAN DAMAGE THE ARTERIAL WALL ASSESSED ACCORDING TO NON-INVASIVE ARTERIAL TONOMETRY
Authors: Paterno Carlos Alberto 
Published: May 2024

Objective:
Objective: Hypertensive Cardiovascular Disease is a complex, multifactorial, and chronic illness, frequently beginning during childhood or adolescence, could develop functional and/or structural organ damage by the increase of arterial stiffness and the curve volume/pressure that in turn can raise the stress into the ventricular-arterial coupling and the appearance of arrhythmias. The aim of this study was to assess systemic inflammatory diseases according to non-invasive arterial tonometry and their possible complications.

Design and method:
Design & Method: This cross-sectional study registered 339 patients, women 77%, both sexes, presented various systemic inflammatory diseases such as Psoriasis (123), Rheumatoid Arthritis (26), Celiac disease (13), Sjögren's disease (9), Crohn's disease (7), Ulcerative colitis (10), Endometriosis (10), Polycystic Ovary Syndrome (141). Anthropological data, Systolic/Diastolic Blood Pressure, and Heart Rate were measured. Central Hemodynamic Parameters (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure) and the difference between the maximum normal level and the observed value of the Augmentation Index (Diff-AIx), the surrogated value of arterial stiffness, were assessed with the SphygmoCor System-PVX, according to established protocols by sex and age.

Results:
Results: The mean age of women and men was 45-51 years. The mean of Systolic/Diastolic Blood Pressure among women and men was 132.5/81.6-135.2/85.9 mmHg, respectively. The Diff-AIx among women was 4.8 and among men was 5.4. The most important finding of the assessment of the systemic inflammatory diseases was the presence of hypertensive cardiovascular disease, considering the measurements of high systolic and diastolic blood pressure, and the abnormal Central hemodynamic parameters. The most important complication observed was the brief phases of atrial fibrillation during the 24-hour Holter monitoring (7.4%), the mean age of patients was 64.2 years, range of 44-88 years, and the highest percentage of each group were Ulcerative colitis (20.0%), Rheumatoid Arthritis (15.4%), and Crohn's disease (14.3%), Psoriasis (10.6%), Endometriosis (10.0%).

Conclusions:
Conclusions: The systemic diseases can damage the arterial wall and contribute to the development of Hypertensive Cardiovascular Disease. Cardiologists and clinical physicians, in the anamnesis, should include the search for inflammatory systemic diseases for a more complete clinical evaluation and therapeutic guidance.
G-PROTEIN-COUPLED RECEPTORS ANTIBODIES HAVE SUBSTANTIAL VASOREGULATIVE IMPLICATIONS IN LONG-COVID
Authors: Seibert Felix , Wiemers Lea , Stervbo Ulrik , Sander Oliver , Seidel Maximilian , Bertram Sebastian , Babel Nina , Westhoff Timm 
Published: May 2024

Objective:
The Long-COVID syndrome is associated with the generation of autoantibodies to vasoregulative G-protein coupled receptors (GPCR), playing a potential key role in this disease. How far GPCR are related to vascular dysfunction in this context remains elusive.

Design and method:
We performed a cross-sectional study, enrolling 80 patients with Long-COVID. GPCR antibodies encompassed autoantibodies against Angiotensin-II-Receptor-1 (AGTR2), Beta-1 Adrenergic Receptor (ADRB1), Beta-2 Adrenergic Receptor (ADRB2), Endothelin Receptor (EDNRA), Muscarinergic Choline Receptor 3 (CHRM3), and Muscarinergic Choline Receptor 4 (CHRM4), all measured by ELISA. Vascular endothelial function was assessed by flow mediated dilation (FMD). We checked for vascular and systemic inflammation by measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) and high-sensitive C-reactive protein (hsCRP). We performed a non-invasive pulse wave analysis to investigate central aortic blood pressure as well as nailfold capillaroscopy.

Results:
52 (65%) patients had positive antibody findings above previously established cut-off values. The median concentrations for AGTR2, ADRB1, ADRB2, EDNRA, CHRM3 and CHRM4 were 13.21 (interquartile range [IQR] 11.57-18.51) U/ml, 19.12 (IQR 16.03-27.54) U/ml, 14.18 (IQR 10.83-31.26) U/ml, 14.07 (IQR 11.30-25.19) U/ml, 13.73 (IQR 12.04-25.30) U/ml and 9.27 (IQR 7.15-13.02) U/ml, respectively. Correlation analysis showed strong and significant negative correlation of several GPCR antibodies with aortic systolic blood pressure (AGTR2 p=0.026, ADRB1 p=0.001, ADRB2 p=0.012) and aortic diastolic blood pressure (ADRB1 p=0.005, CHRM4 p=0.046). High EDNRA antibodies titers were associated with increasing FMD (p=0.038). ATGR2, ADRB2 and EDNRA had substantial negative correlation with inflammation as seen by lower hsCRP concentrations (p=0.025, p=0.001, p=0.017, respectively). None of the above mentioned antibodies were associated with Lp-PLA2 (p>0.05 each). None of the investigated subentities of nailfold capillaroscopy were significant for GPCR-antibodies.

Conclusions:
GPCR antibodies are present in Long-COVID and show various vascular implications in terms of vasorelaxation as seen in lower aortic systolic and diastolic blood pressure as well as in an amelioration of FMD. If this is the result of anti-inflammatory properties remains elusive.