bluuebunny/crossref_metadata_2025_split huggingface dataset:
CARDIOVASCULAR RISK FACTOR TRAJECTORIES AND INCIDENT CARDIOVASCULAR DISEASE IN OLDER ADULTS: THE KAILUAN STUDY
Authors: Chen Chaolei , Huang Yuqing , Wu Shouling , Feng Yingqing 
Published: May 2024

Objective:
Long-term condition and longitudinal accumulation of cardiovascular risk factor (CRF) may be associated with adverse outcomes in the elderly, but the previous evidence is scarce. We studied the associations of CRF trajectories, their accumulation, with incident cardiovascular disease (CVD) in older adults.

Design and method:
From 2006, a population-based cohort of 8505 older adults have been repeatedly followed up for 14 years (until 31 December 2020). Blood pressure, serum lipids, height and weight, and blood glucose were assessed in all follow-ups and their trajectories from 2006 to 2010 were identified using latent class growth mixture modeling. Main outcome was incident CVD, which was a composite of coronary revascularization, myocardial infarction, heart failure, or stroke. The associations of CRF trajectories and incident CVD were studied for individual CRF trajectory and their accumulation, using Cox proportional hazards regression models.

Results:
We identified 3, 4, 2, 2 trajectories for systolic blood pressure (SBP), body mass index (BMI), total cholesterol (TC), and fasting blood glucose (FBG), respectively. Compared with low-increasing SBP, the multivariable-adjusted hazard ratio (HR) and 95% CI were 1.35 (1.19-1.54) for moderate-increasing SBP and 1.54 (1.28-1.86) for high-increasing SBP. Compared with low-stable BMI, the HRs (95% CIs) were 1.30 (1.11-1.53), 1.41 (1.19-1.66), 1.35 (1.07-1.71) for moderate-stable, elevated-stable, and high-stable BMI, respectively. Compared with low-stable TC, the HR (95% CI) were 1.19 (1.06-1.33) for high-stable TC. Compared with low-stable FBG, the HR (95% CI) were 1.38 (1.17-1.63) for high-stable FBG. A positive association was observed for the CRF trajectory accumulation with incident CVD (P for trend < 0.001), with HRs (95% CIs) of 1.54 (1.16-2.04), 2.15 (1.63-2.83), 2.58 (1.93-3.45) and 2.92 (1.95-4.36) for 1, 2, 3, 4 high CRF trajectories, respectively. Sensitivity analyses showed consistent results after excluding those who ever used antihypertensive, antidiabetic, or lipid-lowering drugs during 2006 to 2010, excluding events within the first year of follow-up, and considering death as competing risk.

Conclusions:
Longitudinal higher CRF trajectory was independently associated with higher CVD risk in older adults. Besides, the higher the number of adverse CRF trajectories, the higher was the observed CVD risk.
HDL CHOLESTEROL AND CARDIOVASCULAR EVENTS ON HYPERTENSIVE PATIENTS
Authors: Leão António , Abecassis Francisca , Beirão Pedro , Broa Ana Luísa , Cunha Vitória 
Published: May 2024

Objective:
Evaluate cardiovascular events on hypertensive patients and their HDL-cholesterol levels

Design and method:
Retrospective single-center study including first visits of adult patients in a hypertension clinic of a tertiary hospital during 2015 and their follow-up until 2020.
Patients without follow-up and/or information about HDL cholesterol levels were excluded.
Information on demographics, comorbidities, blood pressure control (<140/90mmHg), number of drugs, and cardiovascular events were analyzed.
Subjects were divided in 3 groups: Group 1 - HDL <40mg/dL; Group 2- 40-80 mg/dL and Group 3 - >80mg/dL.

Results:
Of the 104 initial participants we included 71, 43 female (60.6%) with mean age 55.9 years (18-87), which were monitorized on average for 42.5 months (3-60).
Patients were taking on average 2.67 different anti-hypertensive drugs and, by the end of follow-up, 53 (74.6%) had controlled blood pressure.
The sample included 26 (36.6%) smokers, 18 (25.3%) patients with diabetes, 9 (12.7%) with obstructive sleep apnea SAOS, 6 (8.5%) with chronic kidney disease and there were 30 (42.3%) patients with BMI > 30
HDL cholesterol mean levels were 50.98 mg/dL (24-95). Group 1 included 19 (26.8%) patients, of these 15 (78.9%) had controlled blood pressure, and 3 presented cardiovascular events during the follow-up (2 acute myocardial infarction and 1 cerebrovascular event). Within group 2 there were 47 (66.2%) patients, 36 (76.6%) with controlled blood pressure and 2 cardiovascular events occurred (acute myocardial infarction). There were no cardiovascular events on group 3, which included 5 (7%) patients, 2 of those with controlled blood pressure.

Conclusions:
Some studies established a U shaped risk of cardiovascular events on the lower and higher end of HDL cholesterol. The first relation is well established, however the optimal higher level of HDL cholesterol is not defined.
On our study the majority of patients presented controlled blood pressure and HDL-C within target levels.
There was a small number of patients with HDL cholesterol >80mg/dL and no events occurred, which is a limitation to make any conclusions. On the other hand we verified that the patients with low levels of HDL cholesterol had more events.
THE METABOLIC SCORE FOR INSULIN RESISTANCE (METS-IR) PREDICTS CARDIOVASCULAR DISEASE AND ITS SUBTYPES IN PATIENTS WITH HYPERTENSION AND OBSTRUCTVE SLEEP APNEA
Authors: Yang Wenbo , Cai Xintian , Hu Junli , Wen Wen , Heizhati Mulalibieke , Yao Xiaoguang , Yao Ling , Zhu Qing , Hong Jing , Luo Qin , Liu Shasha , Li Nanfang 
Published: May 2024

Objective:
We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index for the prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery disease and stroke) in patients with hypertension and obstructive sleep apnea (OSA).

Design and method:
A retrospective cohort study was conducted with 2031 adults with hypertension and OSA, participants from the Urumqi Research on Sleep Apnea and Hypertension study (UROSAH). The hazard ratios and 95% CIs (credibility interval) for CVD and its subtypes were estimated using multivariate Cox proportional hazards regression models.

Results:
After a median follow-up of 6.80 years (interquartile range: 5.90–8.00 years), a total of 317 (15.61%) participants developed new-onset CVD, including 198 (9.75%) incident coronary heart disease (CHD) and 119 (5.86%) incident stroke. After adjusting for as many relevant confounding factors as possible, each SD increase in METS-IR was associated with a 30% increased risk of new onset overall CVD events, a 32% increased risk of new onset CHD, and a 27% increased risk of new onset stroke. When METS-IR was assessed as tertiles, after adjustment for fully confounding factors, the highest tertiles versus the lowest tertiles were associated with a greater hazard of CVD (HR 2.05; 95% CI 1.52,-2.77), CHD (HR 1.96; 95% CI 1.35–2.84), and stroke (HR 2.24; 95% CI 1.35–3.72). The results of various subgroups and sensitivity analyses were similar. When METS-IR was added, CVD predictions were reclassified and identified more accurately than baseline models for the C-index, continuous net reclassification improvement, and integrated discrimination index. CHD and stroke showed similar results.

Conclusions:
METS-IR is a powerful predictor of CVD and its subtypes in patients with hypertension and OSA, which can facilitate the identification of high-risk individuals and provide individualized CVD prevention.
DIAGNOSTIC ACCURACY OF 24-HOUR URINARY ALDOSTERONE TO CREATININE RATIO AND 24-HOUR URINARY ALDOSTERONE FOR PRIMARY ALDOSTERONISM IN DIFFERENT AGE GROUP
Authors: Song Wei , Sun Kaiwen , Gong Minghui , Yang Minghui , Zhang Ying , Jiang Yinong 
Published: May 2024

Objective:
The aim of this study was to explore and evaluate the diagnostic accuracy of 24-hour urinary aldosterone to creatinine ratio (UACR) and 24-hour urinary aldosterone and in different age group.

Design and method:
There were 423 patients eligible and consecutively enrolled in this study. After 1:2 propensity score matching (PSM) analysis, 100 patients were in primary aldosterone (PA) group and 194 patients were in essential hypertension (EH) group. The information of clinical characteristic and biochemistry measurement were collected and analysis. Receiver operator characteristic curve (ROC) was introduced and calculated area under the curve (AUC) to explore the diagnostic accuracy and the optimal cut-off value.

Results:
There was no significant difference for the average age in PA group (53.38±11.31) and in EH group (52.77±11.25) (P>0.05). The 24-hour UACR and urinary aldosterone was higher in PA group (1.1 ug/(mmol/L) vs. 0.7 ug/(mmol/L), 6.4 ug/24h vs. 4.8 ug/24h, P<0.05) among all age group. The optimal cut-off value of 24-hour UACR was 1.2 ug/(mmol/L) with 0.702 for AUC and 0.300 for the Youden index, in contrast with 11.4 ug/24h, 0.652 and 0.257 for 24-hour UACR. For those 55 years old or below, it was the same for both the two index, while the optimal cut-off value was declined to 0.8 ug/(mmol/L) for 24-hour UACR and 2.7 ug/24h for 24-hour urinary aldosterone among those over 55 years old.

Conclusions:
24-hour UACR was a promising index and was better than 24-hour urinary aldosterone on PA diagnosing. More research is needed to explore the underlying influence factors.
DOES ENDOTHELIAL FUNCTION DIFFER AMONG SEXES IN PATIENTS WITH DIABETES OR KIDNEY DISEASE?
Authors: Renier Marie , Michielsen Matthijs , Vandecruys Marieke , Decorte Elise , Craenenbroeck Amaryllis H. Van , Cornelissen Véronique 
Published: May 2024

Objective:
Endothelial dysfunction is a known driver of disease progression in both type 2 diabetes mellitus (T2DM) and kidney disease. Brachial artery flow-mediated dilation (FMD), representing endothelium-dependent nitric oxide-mediated dilation in response to increased shear stress, is considered gold standard to quantify macrovascular dysfunction non-invasively. As evidence is mounting that men are more likely to suffer from macrovascular dysfunction than women, we hypothesized that this would be reflected in patient populations with T2DM and/or kidney disease.

Design and method:
Preliminary baseline data was collected from 2 ongoing randomized controlled trials in patients with T2DM and in kidney transplant recipients (KTRs) 3 months post-transplantation. FMD was assessed with the semi-automated UNEX EF device under standardized conditions. Biochemical analyses were done using routine techniques. Images were manually analyzed by a single researcher (MR) using PCAnalysis software (version 1.0.14).

Results:
Twenty-five subjects, 13 with T2DM and 12 KTRs were included. As expected, patients with T2DM had a higher BMI, higher HbA1c but higher eGFR compared to KTRs (Table 1). Compared to KTRs, patients with T2DM presented with a significantly worse FMD (FMD= 4.50% [IQR=5.77]) vs 10.88% [6.48]). Overall, no significant difference in FMD between men and women was found (p=0.11), but higher values could be observed in females (FMD= 9.08% [IQR=6.97] vs 4.50% [7.88]). As depicted in Figure 2, this tendency was also observed in the 2 subgroups: KTRs (M: FMD = 9.07% [IQR=9.62] | F: 11.92% [5.16]) and T2DM (M: FMD = 3.90% [IQR=5.00%] | F: 7.09% [6.83]).

Conclusions:
Although no significant differences in vascular function between sexes were detected, our preliminary data showed a tendency for higher FMD-values in women; both in T2DM and KTRs. This supports the statement that male subjects seem to suffer more from macrovascular dysfunction. Further research is needed to elucidate the underlying pathways via which sex impacts the disease process in T2DM and kidney disease and to evaluate how personalized preventive lifestyle measures might differentially impact on outcome.
DIGITAL OPTICAL QUANTIFICATION OF EXTRAVASCULAR FLUID AND OEDEMA SEVERITY IN HYPERTENSION AND HEART FAILURE
Authors: Matskeplishvili Simon , Gurfinkel Yu , Sasonko M , Yakimov B , Dyachuk L , Usherzon M , Shirshin E 
Published: May 2024

Objective:
Early diagnosis of fluid retention as a complication of arterial hypertension severity and prediction of acute decompensation is complicated due to the absence of specific symptoms and objective measurable criteria. Here we present a new non-invasive indicator of the hypertension severity based on the digital high-resolution soft tissue optical imaging in nail-fold capillaries.

Design and method:
One hundred and twenty-nine (129) adults with arterial hypertension were enrolled in the study, including 79 patients with NYHA I–III functional classes of heart failure, and 50 healthy subjects. Vital digital capillaroscopy (VDC) of the nail-fold was performed following a 12-hour overnight fasting in a temperature-controlled room. Nail-fold capillaries and pericapillary tissue were assessed using a ultra-high resolution digital capillaroscope equipped with a high-speed CCD-camera on fingers of the left hand gently fixed into the device. We measured the linear size (mm) of perivascular zone (PZ) around nail-fold capillaries. Additionally, double-photon digital tomography with Fluorescence Lifetime IMaging (FLIM) was used to investigate the molecular PZ composition.

Results:
We observed significant differences in the linear size of the PZ in patients with arterial hypertension complicated with heart failure and the control group. The absolute dimension of PZ outperformed standard echocardiographic parameters. Only in patients with arterial hypertension and moderate-severe heart failure there was an echocardiographic evidence of systolic LV dysfunction with reduced LVEF (42±12%). This was confirmed by the distribution of subjects in the control and study groups by the PZ size and bivariate density analysis. FLIM confirmed that the PZ size is mostly determined by accumulation of extravascular free water.

Conclusions:
This simple VDC measurement of the linear size of nail-fold perivascular zone has high sensitivity and specificity in identification pericapillary edema in hypertensive patients. The positive predictive value of this parameter exceeds that for all other non-invasive parameters, namely, LVEF. Dimension of the PZ is determined by amount of extravascular free water as confirmed by FLIM. This approach could be of interest for monitoring of hypertension treatment, providing important information of diuretic titration to prevent patient decompensation with very early diagnosis of the interstitial fluid retention.
PULSE PRESSURE DYNAMICS: UNRAVELING THE IMPACT ON TARGET ORGAN DAMAGE, INDEPENDENT OF MEAN ARTERIAL PRESSURE
Authors: Mahmud Azra , Khan Danyal , Iqbal Mohammad Naveed 
Published: May 2024

Objective:
As individuals age, pulse pressure (PP) naturally increases due to arteriosclerosis and diffuse vascular stiffening. In the absence of an identifiable cause, a wide PP signals target organ damage (TOD) and adverse clinical outcomes. While hypertension is endemic in South Asia, there is paucity of data regarding determinants of PP and relationship with TOD in this region. We therefore aimed to explore the determinants of PP in an ambulatory patient population.

Design and method:
We analysed electronic medical records of subjects (n=8,362, 64% females 64%) attending a Medicine outpatient Department (OPD) at Shalamar Hospital, a tertiary care hospital, in Lahore, Pakistan during the period September 1st, 2021 to September 30th, 2023. Haemodynamic data included single measure of systolic and diastolic BP and heart rate. HTN was defined according to ESH and ACC guidelines. History of CVD included ishaemic heart disease and stroke. Relationshp between variables was analysed using univariate and multivariate analysis. Pp was analysed both as a continuous and categorical variable (>50, mm Hg).

Results:
Of the 8,362 subjects attending the OPD, 62% and 100% had a diagnosis of HTN as per ESH and ACC guidelines, respectively. PP>50, mm Hg was present in 56% and 45% of HTN as defined by ESH and ACC respectively. PP>50, mm Hg was associated with age (OR=2.7), female gender (OR=1.46), chronic kidney disease (CKD, OR= 3.6), CVD (OR=1.47) and diabetes mellitus (DM, OR=1.54). In a stepwise regression model, age, gender, heart rate, DM, CKD and CVD were associated with PP, independent of mean arterial pressure (R2=0.45, p<0.0001).

Conclusions:
To the best of our knowledge, this is the first large study, exploring the determinants of PP in Pakistan. While the study is retrospective, using single office BP measurements, it highlights the importance of PP as an independent predictor of TOD. Prospective studies are the need of the hour to elucidate the pathophysiology and outcome of high PP in this population.
ISOCITRATE DEHYDROGENASE 2 INHIBITION INDUCES ENDOTHELIAL SENESCENCE BY SUPPRESSION OF MITOPHAGY AND INCREASED ROS PRODUCTION
Authors: Kim Cuk Seong , Kim Minsoo , Vu Giang -Huong 
Published: May 2024

Objective:
Endothelial senescence impairs vascular function and thus is a primary event of age-related vasculature diseases. Isocitrate dehydrogenase 2 (IDH2) plays an important role in inducing alpha-ketoglutarate (alpha-KG) production and preserving mitochondrial function. However, the mechanism and regulation of IDH2 in endothelial senescence have not been elucidated.

Design and method:
We confirmed vascular endothelial senescence using human umbilical vein endothelial cells(HUVECs) and IDH2 Knockout mouse.

Results:
We demonstrated that downregulation of IDH2 induced accumulation of miR-34b/c, which impaired mitophagy and elevated mitochondrial reactive oxygen species (ROS) levels by inhibiting mitophagy-related markers (PTEN-induced putative kinase 1 (PINK1), Parkin, LC-II/LC3-I, and p62) and attenuating Sirtuin deacetylation 3 (Sirt3) expression. The mitochondrial dysfunction induced by IDH2 deficiency disrupted cell homeostasis and the cell cycle and led to endothelial senescence. However, miR-34b/c inhibition or alpha-KG supplementation restored Sirt3, PINK1, Parkin, LC-II/LC3-I, p62, and mitochondrial ROS levels, subsequently alleviating endothelial senescence.

Conclusions:
This study demonstrates that IDH2 deficiency is critical for the suppression of alpha-KG levels, which induced endothelial senescence via miR-34b/c inhibition of mitophagy and mitochondrial ROS elevation in endothelial cells (Figure 7). Therefore, the IDH2/alpha-KG/miR-34b/c axis may provide a potential therapeutic target for age-related vascular diseases.
RELAXIN LIKE PEPTIDE B7-33 AND IT'S DERIVATIVES DEMONSTRATE EFFICACY IN RODENT MODELS OF PREECLAMPSIA
Authors: Uddin Mohammad Nasir , Amaral Lorena , Pantho Ahmed F , Afroze Syeda H , Kuehl Thomas J , Vora Niraj , Lindheim Steven R , Zawieja David C , Lamarca Babbette B 
Published: May 2024

Objective:
Preeclampsia (PreE) is a hypertensive pregnancy disorder, which occurs in approximately 10% of all gestations. The literature suggests potential therapeutic role of H2 relaxin in PreE. A novel H2 relaxin B-chain-only peptide variant B7-33 has recently been developed.
This single-chain peptide displayed equivalent efficacy to the natural H2 relaxin in several functional assays both in vitro and in vivo. The Aim of this study is to evaluate whether B7-33 attenuates preE syndrome in rodent models of PreE.

Design and method:
Rat Model 1. The efficacy of B7-33 was evaluated in the Reduction of Uterine Perfusion Pressure (RUPP) model as described previously. RUPP rats are randomly assigned to 4 groups (N=8/group): 1) vehicle, 2) B733; 3) B733-Fc; and 4) B733-HSA. Rats are dosed twice weekly (i.v.) from GD10 to GD 20.
Rat Model 2. Timed-pregnant rats are used, and the model is conducted as previously described. DOCA and saline administration begin at approximately GD2. Three groups of animals are studied (n=8 per group). 1) normal pregnant rats; 2) pregnant animals injected (i.p.) initially with 12.5 mg of DOCA, followed by a weekly injection of 6.5 mg, and whose drinking water was replaced with 0.9% saline; 3) rats administered DOCA and saline as for Group 2, and given B733 35 ug i.p. biweekly from GD10-20. BP, proteinuria and inflammatory markers were evaluated. Statistical comparisons were performed using analysis of variance with Duncan's post hoc test.

Results:
RUPP rats have increased MAP, plasma TNF-alpha, and plasma sFlt-1 along with decreased NO index compared to normal pregnancy. Treatment with B733 and B7-33 fusion proteins lowers MAP, TNF-alpha, and sFlt-1 back to that of normal pregnancy. B7-33 data are consistent with earlier data with serelaxin in the RUPP model. All fusions tested ameliorate hypertension in the RUPP animals. B7-33 normalizes BP and proteinuria in the DOCA rat model of preE.

Conclusions:
Both B7-33 and B7-33 fusion proteins attenuate preE syndrome in RUPP and DOCA rat models of PreE. We conclude that B7-33 is an ideal candidate for development as a novel therapeutic in preE.
HIGH PULSE PRESSURE IS A POTENTIAL HEMODYNAMIC BIOMARKER IN HYPERTENSIVE DISORDERS IN PREGNANCY
Authors: Takács Johanna , Alasztics Bálint , Járai Dóra , Rigó János , Koller Akos 
Published: May 2024

Objective:
Hypertensive disorders in pregnancy (HDP) represent a significant public health concern worldwide. In these disorders, high arterial systolic and diastolic pressures (sP and dP) have been well-appreciated, yet the pulse pressure (PP) values have received relatively less attention in the clinical practice and guidelines. We hypothesized that high PP correlates with proteinuria and intrauterine growth retardation (IUGR) and thus aimed to measure arterial blood pressure parameters, proteinuria and IUGR and investigate the relationship among them in women with HDP.

Design and method:
The data of 2132 women with HDP (age:33.05±5.24 years) were analyzed together with the blood pressure data (sP, dP and PP), proteinuria and IUGR, and correlations among them were calculated.

Results:
Three groups were formed: 1) elevated sP (n=148), 2) elevated dP (n=122), and 3) elevated sP+dP (n=1862). There was a very strong positive relationship between sP and PP (r(2130) = 0.788, p<0.001, R2=0.621), while there was no relationship between dP and PP. The relationship between sP and PP was very strong positive in the elevated sP group (r(146)=0.900, p<0.001, R2=0.810), moderate in the elevated dP group (r(120)=0.591, p<0.001, R2=0.349), and strong in the elevated sP+dP group (r(1860)=0.826, p<0.001, R2=0.682). The relationship between dP and PP was weak negative in the elevated sP group (r(146)=-0.378, p<0.001, R2=0.143), moderate in the elevated dP group (r(120)=-0.677, p<0.001, R2=0.458), and very weak positive in the elevated sP+dP group (r(1860)=0.088, p<0.001, R2=0.008). Proteinuria and IUGR occurred more frequently in the elevated sP+dP group (53.5% and 17.9%) than in the elevated sP (37.2% and 9.5%) and elevated dP (15.6% and 9%) groups.

Conclusions:
The present findings suggest that in HDP the increased PP provides the driving force for the increased cardiac output and that increases in PP are primarily due to increases in systolic blood pressure. Moreover, PP correlates with proteinuria and IUGR. These findings underline the importance of following not only systolic and diastolic but pulse pressure, as well, before, during and after pregnancy and if necessary, initiate the appropriate therapy to reduce the risk of fetal and maternal target organ damage caused by high blood pressure.