bluuebunny/crossref_metadata_2025_split huggingface dataset:
In patients with type 2 diabetes chronic kidney disease is a modifiable cardiovascular risk factor
Authors: Agarwal R , Pitt B , Rossing P , Anker S D , Filippatos G , Ruilope L M , Kovesdy C P , Tuttle K , Vaduganathan M , Wanner C , Bansilal S , Gebel M , Joseph A , Lawatscheck R , Bakris G 
Published: October 2022

Abstract

Background/Introduction
Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) events. The modifiability of CKD-associated CV risk in patients with T2D across a spectrum of CKD stages remains unknown.

Purpose
To test whether CKD, as defined jointly by estimated glomerular filtration rate (eGFR) and albuminuria (urine albumin-to-creatinine ratio [UACR]), is a modifiable CV risk factor in patients with T2D. Furthermore, to estimate the population-wide reduction in first CV events in the US if all eligible patients were treated with finerenone.

Methods
We estimated the incidence rates of CV events (composite of CV death, non-fatal stroke, non-fatal myocardial infarction, or hospitalisation for heart failure) over a median follow-up of 3.0 years in 13,026 patients with CKD and T2D, treated with finerenone or placebo, in a joint analysis by eGFR and UACR categories. Patients were from FIDELITY, a prespecified pooled analysis of two phase III trials, and had an eGFR ≥25 ml/min/1.73 m2 and UACR 30–5000 mg/g at screening.The potential impact of finerenone treatment on the US population was evaluated by simulating the number of first CV events that could be prevented per year with finerenone, using incidence rates from FIDELITY and prevalence rates of CKD in patients with T2D from the National Health and Nutrition Examination Survey (NHANES).

Results
Lower eGFR and higher UACR categories were associated with higher incidences of CV events in finerenone and placebo recipients (Figure). Finerenone reduced CV risk versus placebo (hazard ratio 0.86; 95% CI 0.78–0.95; p=0.0018) without evidence of moderation of risk reduction by combined eGFR and UACR categories (p interaction = 0.66; Figure 1). Using NHANES, a total of 6.4 million treatment-eligible individuals with CKD and T2D were identified; 75% had CKD with an eGFR ≥60 ml/min/1.73 m2 and 25% had CKD with an eGFR &lt;60 ml/min/1.73 m2. Simulations using this NHANES population projected that 1 year of finerenone treatment could prevent 38,359 CV events in US patients with CKD and T2D, with 66% of events prevented in patients with eGFR ≥60 ml/min/1.73 m2.

Conclusions
Higher albuminuria and lower eGFR are associated with increased CV risk in patients with T2D. Across a range of eGFR and albuminuria categories, CV risk is modifiable. Therefore, CKD is a modifiable CV risk factor in part mediated by mineralocorticoid receptor overactivation. UACR screening to identify patients with T2D and albuminuria with an eGFR ≥60 ml/min/1.73 m2 is likely to provide a significant opportunity for population benefits.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Bayer AG
COVID-19 and the autonomic nervous system
Authors: Xuereb R A , Xuereb R G , Barbara C , Fava S , Magri C J 
Published: October 2022

Abstract

Background
COVID-19 infection has been shown to have an adverse impact on the cardiovascular system. Cardiac injury, as indicated by elevated cardiac troponin and NT-proBNP levels have been confirmed in COVID-19 cases. There is still ambivalent data on the effect of left ventricular function. Cases of left ventricular impairment, persistent hypotension, acute myopericarditis, myocarditis, arrhythmia and heart failure have been reported in the short term, but there is a significant lacuna when it comes to medium and long-term follow-up of subjects previously infected with COVID-19.

Purpose
To assess any residual myocardial and autonomic injury in subjects previously infected with COVID-19 at a median follow-up of 5 months.

Methods
A case-control study was performed. Cases were randomly selected subjects who were previously diagnosed with COVID-19 infection following nasopharyngeal swabbing. Controls were subjects who had not been found to be infected with COVID-19 following swabbing and were negative for COVID-19 IgG antibodies. All participants were submitted a standardised questionnaire regarding past medical history. Blood investigations were taken including NT-proBNP and troponin I levels. In addition, all participants underwent 24-hour ambulatory blood pressure monitoring (ABPM) and 24-hour ECG monitoring. The latter was used to assess both for underlying arrhythmias as well as heart rate variability (HRV), a measure of autonomic regulation of the heart. All data was analysed using SPSS version 23.0.

Results
The study comprised 259 subjects, whereby cases included 174 participants while 75 subjects were age- and gender-matched controls. The study cohort was relatively young with a mean age of 46.1±13.8 years. The median follow-up was of approximately 5 months (median 173.5 days, IQR 129–193.25 days). There was no statistically significant difference between cases and controls with regards cardiovascular risk factors and underlying medical conditions. Likewise, there was no difference in blood investigations, including troponin I and NT-proBNP levels at 5-months follow-up. No difference was noted between the two groups in both awake and asleep blood pressure (BP) readings, as well as dipping BP status. No significant arrhythmias were noted in both groups on 24-hour ECG monitoring. However, when assessing for heart rate variability, it was shown that subjects who had been previously infected with COVID-19 exhibited lower root-mean square differences of successive R-R intervals (RMSSD), p=0.028. This indicates poor vagus nerve-mediated autonomic control of the heart.

Conclusion
Subjects previously infected with COVID-19 exhibited lower HRV as exhibited by low RMSSD as compared to controls. Reduced HRV is a known biomarker for mortality and sudden death in cardiac disease. The possible long-term implications of reduced HRV in subjects previously infected with COVID-19 merits further investigation.

Funding Acknowledgement
Type of funding sources: None.
Serum magnesium is associated with long-term survival of non-ST-elevation myocardial infarction patients
Authors: Shechter M , Cohen H , Sharon A , Koren-Morag N , Grossman E , Maor E 
Published: October 2022

Abstract

Background
In Israel, the rate of drinking water from desalinated sea water has increased dramatically to 60% in the last two decades. However, desalinated water lacks magnesium. Hypomagnesemia is associated with adverse cardiovascular outcome.

Aim
To investigate the association of admission serum magnesium levels (sMg) with long-term survival of non-ST-elevation myocardial infarction (NSTEMI) patients in the light of increased use of desalinated sea water.

Methods
A single-center, retrospective cohort of consecutive petients who were hospitalized with NSTEMI as their primary clinical diagnosis between August 1, 2008 to March 31, 2021. Multivariate Cox regression model was applied for mortality risk.

Results
Study population included 5,675 NSTEMI patients with a mean age of 71±13 years (range 25 to 110), of whom 3,820 (67%) were males. Mean and median sMg levels were 2.0±0.2 (0.5–6.8), 2.0 mg/dL, respectively. During mean follow-up of 4.1±2.9 years (0–14), 2,238 (39%) patients died. Mortality rate was u-shaped when associated with sMg levels (Figure 1) and the study cohort was divided into quintiles according to the sMg levels (≤1.80; 1.81–1.94; 1.95–2.00; 2.01–2.20; ≥2.21). Patients in the highest compared to the lowest sMg quintiles had significantly higher incidence of renal dysfunction with lower eGRF EPI (62±32 vs 76±26 ml/min/1.73 m2, p&lt;0.001) and lower fasting serum glucose (102±37 vs 115±46 mg/dL, p&lt;0.001). All-cause mortality rate was the highest in the lowest and highest sMg quintiles (48%, 33%, 32%, 33% 54%, respectively, p&lt;0.00). Compared to the 2nd sMg quintile (1.81–1.94 mg/dL), with the lowest mortality risk, the lower sMg quintile was associated with a significant and indpendent 24% increased risk of death in a multivariate model (95% CI 1.07–1.44, p&lt;0.001), while the highest quintile was associated with 48% increased risk (95% CI 1.25–1.74, p&lt;0.01) (Figure 2).

Conclusion
Admission low sMg is associated with long-term all-cause mortality in NSTEMI patients. Additionally, long-term mortality is also high in NSTEMI patients with renal dysfunction-induced high sMg levels.

Funding Acknowledgement
Type of funding sources: None.
Admission serum magnesium levels associated with short- and long-term clinical outcomes in COVID-19 patients
Authors: Segev A , Sagir A , Matezky S , Segev A , Atar S , Shechter M 
Published: October 2022

Abstract

Introduction
In the face of the global pandemic coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use.

Purpose
To evaluate the association between serum magnesium levels (sMg) on admission and clinical outcomes in hospitalized COVID-19 patients.

Methods
We retrospectively analyzed all consecutive patients admitted to our medical center with a primary de novo diagnosis of COVID-19.Demographic, clinical and laboratory data were extracted from the electronic medical record. Clinical outcomes were compared between five groups of patients according to the quintiles of sMg on hospital admission.

Results
From 2,433 consecutive COVID-19 patients during the years 2020–2021, we included 1,522 patients with sMg on admission (1–3 day of hospitalization) (58% male, 69±17 years old). Patients were followed for a mean of 10±7 months. A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, chronic kidney disease, andhigher levels of inflammatory markers (Table 1). Both low and high sMg levels were associated with lower oxygen saturation during hospitalization. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4thquintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p&lt;0.001 for all) (Figure 1).

Conclusions
Both low and high sMg levels were associated with worse short- and long-term clinical outcomes and all-cause mortality in a large cohort of hospitalized COVID-19 patients. Thus, admission sMg levels may play a prognostic role in risk stratificationof COVID-19 patients.

Funding Acknowledgement
Type of funding sources: None.
Stress related neural activity: potential mechanism contributing to benefit of physical activity on heart failure incidence
Authors: Alhamam A , Gharios C , Zureigat H , Abohashem S , Osborne M , Tawakol A 
Published: October 2022

Abstract

Background
We previously observed that: 1) physical activity (PA) decreases stress-related neural activity (SNA) in a dose-dependent manner and 2) resting SNA predicts incident heart failure (HF). Thus, we hypothesize that PA may decrease the risk of incident HF in part through its beneficial effect on SNA.

Methods
Self-reported PA data were acquired from Partners Biobank participants. Metabolic equivalent of task-minutes per week (MET*minutes/week) were calculated and participants were categorized according to their adherence to current PA recommendations (&lt;500 and ≥500 MET-min/wk). In a subset with clinically indicated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging (n=744), SNA was measured as a ratio of amygdalar to ventromedial prefrontal cortical activity. Subsequent HF and baseline CVD risk factor data were obtained using International Classification of Diseases Codes. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between PA vs HF risk. Mediation analysis was used to test whether PA's impact on SNA significantly mediated the association between PA and HF.

Results
Among 50,363 participants (median age 59 years [IQR 42, 70], 40% male), 13,850 (11.6%) were diagnosed with HF over a median period of 3.1 years. PA within recommendations was associated with lower risk of subsequent HF (hazard ratio (HR) [95% confidence interval (CI)]: 0.849 [0.760, 0.948], p=0.004, Figure 1) in a model adjusted for CVD risk factors and history of myocardial infarction. As noted previously, higher SNA associated with higher risk of subsequent HF (HR [95% CI]: 1.34 [1.08, 1.66], p=0.007); and PA within guideline recommendations (vs.below) associated with lower SNA (Zscore ± SD: −0.14±0.92 vs 0.02±1, p=0.037). Moreover, mediation analysis shows that exercise reduces HF risk in part via reductions in SNA, accounting for 9% of the total relationship between exercise and HF risk (p&lt;0.05, Figure 2).

Conclusion
PA associates with reductions in: A) stress-associated neural activity and B) subsequent HF risk. Moreover, the mechanism by which PA reduces HF risk may involve salutary effects on stress-related neural pathways.

Funding Acknowledgement
Type of funding sources: None.
Association of smartphone-recorded steps over years and change in cardiovascular risk factors among working aged adults
Authors: Hamaya R , Mori M , Miyake K , Lee I 
Published: October 2022

Abstract

Backgrounds
Evidence indicates a causal role of physical activity (PA), including steps, in decreasing cardiovascular disease (CVD) risk. However, few data exist on long-term steps and their relation to changes in CVD risk factors.

Objectives
To examine the associations of long-term smartphone-recorded steps and changes in CVD-related biomarkers in a large cohort of working aged adults.

Methods
The present analysis made use of data two national database and a commercial app database. Participants who underwent an annual health check-up between April 2015 and November 2020 and a second health check-up 24 to 35 months thereafter, and whose daily step data were available, were included. We evaluated the associations between smartphone-recorded daily steps over two years following the initial health check-up and two-year changes in the following CVD risk factors: weight, waist, blood pressure (BP), lipid and glucose metabolism biomarkers. Generalized additive models were used to investigate the non-linear relationships of steps and changes in CVD risks. Models were adjusted for baseline steps and other confounders. The present study design is summarized in Figure 1.

Results
A total of 15,708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. Differences in weight were almost linearly associated with two-year steps in men (estimate [SE] per 1000 steps/day: −0.33 [0.029] kg), and inversely related only above 5,000 steps/day in women (−0.18 [0.054] kg) (Figure 2). Similar trends were observed in waist. An inverse linear association with systolic BP was observed in men (−0.34 [0.097] mmHg) but not in women. Greater steps were associated with favorable change in HDL cholesterol and triglycerides (0.61 [0.068] and −3.4 [0.61] mg/dL in men; 0.64 [0.17] and −2.3 [0.67] mg/dL in women), while negative changes in LDL cholesterol was evident in men only (−0.59 [0.17] mg/dL). A significant negative association with HbA1c was observed only in women (−0.012 [0.0043] %). In the secondary analyses of the associations between one-year steps and one-year (i.e., 12 to 23 months) changes in CVD related biomarkers (N=26,884), the relationships were weaker and less robust compared with those in two-year analyses.

Conclusions
In a large cohort of Japanese adults, smartphone-recorded steps over years were associated with beneficial changes in CVD risk factors, with some differences between men and women in the associational patterns. The sex differences might highlight the undercount of steps among women who may be less likely to always carry their phone [1], or true sex differences in the effects of steps. The findings support the benefit of long-term PA for CVD health and suggest a useful role of smartphone-recorded steps for monitoring CVD risk over the long term.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): DeSC Healthcare Inc., Tokyo, Japan
Protective effect of N-acetyl cysteine on vascular function of young individuals after a bout of resistance exercise: a randomized placebo-controlled study
Authors: Mavraganis G , Georgiopoulos G , Sakelliou A , Delialis D , Patras R , Sianis A , Dimopoulou A M , Oikonomou E , Athanasopoulos S , Kanakakis I , Fatouros I , Mitrakou A , Stamatelopoulos K 
Published: October 2022

Abstract

Background
High intensity resistance exercise may temporarily induce vascular dysfunction mediated by pro-oxidant and pro-inflammatory pathways. Whether antioxidant supplements ameliorate this dysfunction has not been clarified.

Purpose
In the present study we aimed to evaluate the effect of the antioxidant N-acetyl cysteine (NAC) on vascular function after a bout of high-intensity resistance exercise in healthy young individuals.

Methods
In this randomized, cross-over, placebo-controlled study, ten healthy male volunteers (mean age 24.2±2.1 years) who exercised regularly were randomized to a daily oral administration of NAC or placebo during an 8-day recovery after an acute intense eccentric exercise protocol. In order to estimate changes in vascular parameters of interest -pulse wave velocity (PWV) and flow-mediated dilation (FMD)-, measurements were performed pre-exercise and across 6 pre-specified time points post-exercise (from 2 to 120 hours) in both arms. Blood samples were collected at baseline, immediately after exercise, 2 hours after exercise, and daily for eight consecutive days thereafter for the measurement of cellular components of the immune system.

Results
Muscle exercise induced a significant decrease in FMD in the placebo arm (F=2.74, p=0.017). This phenomenon was evident until 48 hours after exercise while FMD progressively returned to baseline values thereafter. In contrast, in the NAC arm, FMD did not decrease significantly (p&gt;0.05 for all time-points). By linear mixed model analysis, a higher increase in CD4 cells levels correlated with preserved FMD (coefficient=0.025, p=0.046) in the placebo arm whereas this association was not significant (coefficient=0.004, p=0.811) in the NAC arm. PWV did not present significant fluctuations before and after exercise in either arm (p&gt;0.05 for all comparisons).

Conclusion
A bout of eccentric exercise in young regularly training individuals induced endothelial dysfunction peaking at 48 hours, possibly partly mediated by an attenuated CD4 response. NAC exerted protective action on FMD, indicating that oxidative stress may be implicated in vivo in this setting.

Funding Acknowledgement
Type of funding sources: None.
Peak oxygen uptake in cardiopulmonary exercise testing was associated with left ventricular diastolic dysfunction in patients with preserved ejection fraction
Authors: Ojima S , Kubozono T , Kawasoe S , Kawabata T , Salim A A , Ikeda Y , Ohishi M 
Published: October 2022

Abstract

Background
Heart failure with preserved ejection fraction (EF) remains a poor prognosis as same as heart failure with reduced EF. Peak oxygen uptake (VO2) by cardiopulmonary exercise testing (CPET) is a useful parameter for predicting cardiovascular diseases prognosis. Furthermore, though there are some reports that CPET parameters are associated with indicators of diastolic dysfunction, each of these indicators has some limitations. Recently, recommendations for the evaluation of left ventricular diastolic function by echocardiography were reported from the ASE/EACVI. However, no reports have examined the association between exercise tolerance indices and diastolic dysfunction based on these recommended variables.

Purpose
To examine the relationship between peak VO2 and diastolic dysfunction using the recommendation from ASE/EACVI in cardiovascular diseases patients with preserved EF

Methods
We recruited 214 patients who were performed both CPX and echocardiography. EF ≥50% was 99 patients. All patients underwent 0W warm-up and 10W ramp on an upright electrical bicycle ergometer. Diastolic dysfunction was assessed using the recommendations for the evaluation of diastolic function by ASE/EACVI. We used abnormal cutoff values are annular e' velocity: septal e' &lt;7 cm/s, lateral e' &lt;10 cm/s, average E/e' ratio &gt;14, left atrial volume index &gt;34 ml/m2, and peak tricuspid regurgitation (TR) velocity &gt;2.8 m/s. Diastolic dysfunction is present if more than half of the available parameters meet these cutoff values.

Results
Mean age was 57±14 years old, the portion of women was 69%. The portion of diastolic dysfunction was 16%. In univariable logistic regression analysis, age, log BNP, septal e' &lt;7 cm/s or lateral e' &lt;10 cm/s, peak TR velocity &gt;2.8 m/s, and the presence of diastolic dysfunction were significantly associated with peakVO2 &lt;14 ml/min/kg. In multivariable logistic regression analysis, the presence of diastolic dysfunction was an independent risk factor for peak VO2 &lt;14 ml/min/kg (OR 5.03 CI 1.32–19.2, p=0.018). Furthermore, we investigated the association between each variable of diastolic dysfunction and peak VO2 and found that low septal and lateral e'velocity and high TR peak flow velocity were significantly associated with peak VO2 &lt;14 ml/min/kg.

Conclusions
In preserved EF, low peak VO2 was significantly associated with diastolic dysfunction assessed by the recommendations from the ASE/EACVI.

Funding Acknowledgement
Type of funding sources: None.