bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are metabolically healthy obese individuals really a benign cardiovascular group? An analysis of 162,590 participants with measures of arterial stiffness in UK BIOBANK
Authors: Ananda R , Solomon B , Ray K K 
Published: October 2024

Abstract

Background
There is conflicting evidence as to whether so called metabolically healthy but overweight and obese individuals are at increased cardiovascular risk or mortality.

Purpose
We assessed whether metabolic health correlates with vascular health among these individuals using severity of arterial stiffness as a proxy for vascular health and cardiovascular risk.

Methods
Participants in UK Biobank with body-mass index (BMI) and arterial stiffness index (ASI) recorded at initial assessment between 2006-2010, and free from stroke and myocardial infarction and not underweight (BMI&lt;18.5kg/m2) were included. Participants were stratified by BMI (normal, overweight, obese) and presence of metabolic abnormalities (hypertension, diabetes, dyslipidaemia). The primary outcome was the severity of ASI analysed using multivariate-adjusted linear regression.

Results
Of 162,590 participants, 55.0% were female, mean age was 57 years (SD 8), 42.5% were overweight and 24.4% obese. Within the normal BMI strata, 50.7% had ≥1 metabolic abnormality. Compared to individuals with normal BMI and no metabolic abnormalities (ref group), increased weight or metabolic abnormalities were similarly associated with higher ASI; adjusted β-coefficient [β] 0.35, 95%CI 0.30 to 0.40 for participants with normal BMI and ≥1 metabolic abnormality; β 0.32, 95%CI 0.26 to 0.37 for overweight participants without metabolic abnormalities. Obese individuals with no metabolic abnormalities had higher ASI (β 0.65; 95%CI 0.57 to 0.74) but was lower than overweight participants with metabolic abnormalities (β 0.80; 95%CI 0.75 to 0.84). Obese participants with metabolic abnormalities had the highest ASI (β 1.07; 95%CI 1.02 to 1.12) among all six metabolic combinations, p&lt;0.001 for each vs ref group. Sensitivity analysis suggested higher ASI with increasing number of metabolic abnormalities within BMI categories.

Conclusion
Excess weight and metabolic abnormalities, are independently associated with adverse measures of vascular health to a similar degree, suggesting that the so called metabolically healthy obese are not a benign group. Primary prevention strategies should be considered in overweight, or obese individuals even if metabolic abnormalities are absent.
A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis
Authors: Maneechote C , Pratchayasakul W , Arunsak B , Chattipakorn S C , Chattipakorn N 
Published: October 2024

Abstract

Background
The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated.

Purpose
To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models

Methods
Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein.

Results
HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F).

Conclusion
A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.
Relationship between obesity and hypertrophic or dilated cardiomyopathy: the role of sex
Authors: Antonopoulos A , Panagiotopoulos I , Terentes-Printzios D , Omer M , Mentias A , Lazaros G , Tsioufis K , Elgendy I , Vlachopoulos C 
Published: October 2024

Abstract

Background
Evidence suggests an association between obesity and the risk for cardiomyopathy development, however robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large scale epidemiological real-world data.

Methods and Results
We analyzed data from the Nationwide Inpatient Sample (NIS) of U.S. hospitalizations for the years 2015-2019. There were a total of n=46,934 admissions with a diagnosis of HCM and n=170,924 with DCM. There was a significant interaction between cardiomyopathies’ diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p&lt;0.001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p&lt;0.001). After adjustment for age, sex, race, and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalized patients with a body mass index (BMI) ≥30kg/m2 there was an odds ratio (OR) of 1.68 (95%CI: 1.55-1.81, p&lt;0.001) for HCM andOR=1.82 (95%CI: 1.79-1.84, p&lt;0.001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p&lt;0.001 for both) and it was non-significant in females.

Conclusions
The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and hypertrophic or dilated cardiomyopathy, which should be further investigated.Cardiomyopathy-obesity
Activation of fibroblast growth factor 21 by Canagliflozin reduces high-fat diet associated obesity-related cardiac injury: a translational study from bench to bedside
Authors: Liu P Y , Vairaperumal T , Lee Y T , Tsai T Y 
Published: October 2024

Abstract

Aims/hypothesis
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are indicated for the treatment of type 2 diabetes, and evidence shows that they may confer a cardioprotective effect to reduce the incidence of cardiovascular conditions in obese type 2 diabetes patients. The mechanisms underlying this effect remain unclear, but an SGLT2i, canagliflozin (CANA), has been reported to increase levels of fibroblast growth factor-21 (FGF21) and enhance activation of its downstream target proteins. We thus aimed to study whether the effect on FGF21 by CANA can reduce obesity-related cardiac injury.

Methods
1) Animal study: Sixteen-week-old normal diet and high-fat diet male mice were treated with or without 30 mg/kg CANA once a day for 24 weeks, and were subsequently examined for body weight, blood glucose levels, adipose tissue changes, lipid accumulation in the liver, and cardiac function.
2) Cell study: An in vitro study that treated H9c2 cardiomyocyte cells cultured in a simulated high-lipid environment containing palmitic acid (PA) with FGF21 recombinant protein was also conducted to examine protein expression profiles. Furthermore, the effect of CANA on FGF21 expression.
3) Human clinical trial: A randomized double-blinded control trial (NCT 05764811) was performed to test effect of CANA on MRI liver fibrosis scores of obese type 2 diabetes patients (n = 40).

Results
1) High-fat diet mice treated with CANA for 24 weeks had lower average body weight than untreated controls (34 g vs. 40 g, p &lt; 0.001). In addition, CANA treatment stimulated FGF21 protein production in liver tissue and plasma at higher levels for both normal diet and high-fat diet mice, and reduced expression levels of proteins associated with fibrosis and apoptosis.
2) H9c2 cardiomyocyte culture studies suggested that a simulated high-lipid environment with PA caused higher expression of apoptotic proteins, but the addition of FGF21 recombinant protein significantly reduced apoptosis signalling. 3) MRI before and after 4 weeks of CANA treatment in obese type 2 diabetes patients showed a significant reduction in liver fibrosis scores for those receiving CANA treatment.

Conclusion
CANA treatment stimulated FGF21 protein expression and reduced fibrosis and apoptosis signalling protein expression. Moreover, reductions in liver fibrosis scores were observed in obese type 2 diabetes patients treated with CANA. Taken together, this suggests that CANA-induced FGF21 expression may exert a cardioprotective effect against fibrosis and apoptosis and can potentially reduce the risk of obesity-related cardiac injury.
Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes
Authors: Nesti L , Chiriaco M , Sacchetta L , Moriconi D , Santoni L , Forotti G , Chiriaco G , Natali A , Solini A , Trico D 
Published: October 2024

Abstract

Background
Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes.

Methods
We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a &lt;10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up.

Results
Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip.

Conclusions
Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves
Association between normal range UACR and insulin resistance and prediabetes among US adults:
Authors: Wu S , Yang Y , Zhu J 
Published: October 2024

Abstract

Background
Recent studies have shown that urine albumin-to-creatinine ratio (UACR) within the normal range is associated with increased risk of hypertension, diabetes, cardiovascular death and all-cause death. However, the relationship between normal range UACR and the prevalence of insulin resistance (IR) and prediabetes has not been explored.

Methods
The study included 14,208 US adults with normal range UACR values and without diabetes from the National Health and Nutrition Survey (1999-2018). The outcome variables included IR and prediabetes, as defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis were conducted to examine the relationship of UACR with IR and prediabetes.

Results
The weighted multivariate linear regression analysis showed that a 1-standard deviation (SD) increment in ln (UACR) was positively associated with fasting plasma glucose (FPG) (β = 0.02, 95% CI: 0.01, 0.04), glycosylated hemoglobin (β = 0.01, 95% CI: 0.00, 0.02), fasting serum insulin (FSI) (β = 0.50, 95% CI: 0.31, 0.68), and homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.14, 95% CI: 0.09, 0.19). The weighted multivariate logistic regression analysis revealed that a 1-SD increment in ln (UACR) was significantly associated with an increased prevalence of prediabetes (OR = 1.10, 95% CI: 1.04-1.15), but not with IR (OR = 1.05, 95% CI: 0.99-1.12). With the lowest quartile of UACR as a reference, ORs (95% CIs) for IR in the second, third, and fourth quartiles were 1.10 (0.86, 1.15), 1.15 (0.98, 1.33), and 1.12 (0.95, 1.32), respectively, and ORs (95% CIs) for prediabetes were 1.35 (1.19, 1.52), 1.32 (1.14, 1.53), and 1.44 (1.24, 1.66), respectively. Subgroup analysis indicated that smoking had a significant impact on the association between UACR and prediabetes. The association between UACR and prediabetes was more significant in smokers than in non-smokers (P for interaction = 0.03). RCS regression analysis revealed a non-linear positive dose-response association between UACR and indicators of diabetes.

Conclusion
Elevated UACR, even within the normal range, was positively associated with indicators of diabetes and increased prevalence of prediabetes among US adults. Smoking had a significant impact on the association between UACR and prediabetes, with a more pronounced association observed among smokers.uacr with diabetes markersUacr with ir and prediabetes
Prognostic outcomes of masld and obesity in acute myocardial infarction
Authors: Kong G , Koh J , Wong E , Zhang A , Ping C , Yeo T C , Yip J , Foo R , Chan M Y , Loh P H , Chew N W S 
Published: October 2024

Abstract

Background
Patients with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have an increased risk of cardiovascular disease. This study seeks to examine the prognostic significance of obesity and MASLD in patients presenting with acute myocardial infarction (AMI).

Methods
This study compared the clinical characteristics and outcome of patients with and without obesity and MASLD at a tertiary centre in Singapore. Patients were stratified by their obesity and MASLD statuses into four groups. Obesity was defined as BMI ≥27.5. MASLD was defined as hepatic steatosis, which was determined using Hepatic Steatosis Index, and at least one of the five metabolic criteria. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality, adjusted for age, sex, ethnicity, previous AMI, AMI type, and left ventricular ejection fraction.

Results
A total of 5702 patients with AMI were included in this study. Among the cohort, 3803 were non-obese and without MASLD, 343 were non-obese with MASLD, 638 were obese without MASLD, and 918 were obese with MASLD. The mean follow-up duration was 3.1 ± 2.4 years. Non-obese patients with MASLD were most likely to develop complications of heart failure, cardiogenic shock, and stroke. On 30-day follow-up, there were no significant differences in all-cause mortality (p=0.312). However, on long-term follow-up, non-obese MASLD patients had the highest mortality (9.6%, p=0.019). After adjusting for confounders, patients who were non-obese with MASLD, and patients who were obese with MASLD, remained independently associated with higher long-term all-cause mortality (HR 1.400, 95% CI 1.077-1.820 and HR 1.222, 95% CI 1.005-1.485 respectively), with non-obese patients without MASLD as the reference.

Conclusions
This study demonstrates that regardless of obesity status, patients with MASLD have poorer outcomes in AMI. With its high metabolic burden, it is important to identify patients with MASLD for risk stratification and targeted treatment.Adjusted long-term all-cause mortality
Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus
Authors: Ikonomidis I , Katogiannis K , Kountouri A , Pavlidis G , Thymis J , Korakas E , Kostelli G , Katsanaki E , Michalopoulou E , Vlachomitros D , Pliouta L , Balampanis K , Lambadiari V 
Published: October 2024

Abstract

Background
Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM.

Methods
We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results
At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&gt;0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p&lt;0.05), in PWV (−9.3%, p&lt;0.05), in cSBP (−6%, p&lt;0.05) and in GLS (+4%, P&lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P&gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&lt;0.05).

Conclusions
Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.
Effects of sodium-glucose contrasporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on arterial stiffness, coronary flow reserve and liver steatosis in diabetes
Authors: Ikonomidis I , Michalopoulou E , Pavlidis G , Prentza V , Katogiannis K , Kostelli G , Katsanaki E , Vlachomitros D , Kountouri A , Korakas E , Pliouta L , Thymis J , Lambadiari V 
Published: October 2024

Abstract

Background
Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) present an increased risk of cardiovascular disease. Sodium-glucose contrasporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to significantly decrease the risk of cardiovascular complications.

Purpose
The aim of the study was to investigate the effect of treatment with SGLT-2i or GLP-1RA on cardiovascular function and liver steatosis and fibrosis in patients with T2DM and NAFLD.

Methods
Forty patients with T2DM and NAFLD (mean age: 58 ± 11 years) were randomized to receive SGLT-2i (dapagliflozin; n = 20) or GLP-1RA (dulaglutide; n = 20). At baseline and after 6 and 12 months of treatment, we measured: (1) perfused boundary region (PBR) of the sublingual microvessels with a diameter 5-25μm using Sidestream Dark Field camera (Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. (2) Pulse wave velocity (PWV) using Complior (ALAM Medical), (3) coronary flow reserve (CFR) using Doppler echocardiography, (4) LV global longitudinal strain (GLS) using speckle-tracking echocardiography, (5) controlled attenuation parameter (CAP) score to assess steatosis grade and liver stiffness (E) to evaluate fibrosis score using liver elastography (FibroScan, Echosens), and (6) NAFLD fibrosis score (NFS).

Results
At baseline, patients between the two groups had similar age, sex, HbA1c, steatosis grade, fibrosis score and markers of cardiovascular function (p &gt; 0.05). Compared with baseline, all patients had reduced PBR, PWV, CAP, E and NFS and increased CFR and GLS (p &lt; 0.01) after 12-month treatment. In the whole study population, the percentage reduction of CAP and NFS was correlated with the corresponding decrease of PBR (r = 0.248 and r = 0.387), PWV (r = 0.290 and r = 0.281) and with the increase of GLS (r = -0.320 and r = -0.295) after 12-month treatment (p &lt; 0.05 for all correlations). Both treatments with SGLT-2i and GLP-1RA reduced markers of liver steatosis and fibrosis (Table).

Conclusion
Both treatments with SGLT-2i and GLP-1RA improve cardiovascular function and reduce liver steatosis in patients with T2DM and NAFLD after 12 months.