bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of glycated hemoglobin A1c on cardiovascular risk in patients with and without coronary artery disease
Authors: Olesen K K W , Thrane P G , Hansen M K , Gyldenkerne C , Maeng M 
Published: November 2023

Abstract

Background
Diabetes is defined according to the level of glycated hemoglobin (HbA1c) based on the risk of microvascular complications. However, HbA1c has been associated with increased risk of macrovascular complications at lower HbA1c levels than the conventional cut-off for "microvascular" diabetes. In patients without known diabetes, it is unsettled when HbA1c becomes a marker of macrovascular complications in non-diabetes patients with and without coronary artery disease (CAD).

Purpose
We tested the hypothesis that the HbA1c cut-off for macrovascular complications differ for patients with versus without CAD.

Methods
We included every patient undergoing coronary angiography in Western Denmark from 2011-2021 without known diabetes prior to examination. Follow-up was censored if it exceeded 10 years. We examined the risk of atherosclerotic cardiovascular disease (ASCVD, a composite of myocardial infarction and ischemic stroke) and HbA1c using Cox regression. We modeled the relation between ASCVD and HbA1c using restricted cubic splines with 38 mmol/mol as reference. In a separate analysis, we stratified patients by HbA1c levels (&lt;30 mmol/mol, 31-38 mmol/mol (reference), 39-47 mmol/mol, and ≥48 mmol/mol) and CAD.

Results
We included 56,927 patients without known diabetes at the time of angiography, of whom 1,225 (2.2%) had undiagnosed, untreated diabetes, i.e. HbA1c ≥48 mmol/mol. Mean HbA1c was 38 mmol/mol. In patients without CAD we did not observe any association between HbA1c and ASCVD (Figure 1). In contrast, we observed a U-shaped relationship between HbA1c and ASCVD in patients with CAD. The lowest risk of ASCVD was observed at HbA1c 35 mmol/mol, which was followed by a steady incline with higher HbA1c levels. When categorizing HbA1c, the adjusted ASCVD risk was significantly increased in patients with CAD and HbA1c 39-47 mmol/mol (aHR 1.09, 95% CI 1.01-1.19), with HbA1c ≥48 mmol/mol (aHR 1.60, 95% CI 1.32-1.94) having the highest ASCVD risk (Figure 2).

Conclusions
The current study provides two novel findings. Firstly, HbA1c provides no prognostic information concerning risk of ASCVD when CAD is absent. Secondly, a U-shaped relationship between HbA1c and ASCVD was found in patients where CAD is present. The lowest risk of ASCVD was observed at HbA1c 35 mmol/mol and the risk steadily increased with higher (and lower) HbA1c levels. Thus, the risk of ASCVD associated with HbA1c starts much earlier than the conventional 48 mmol/mol HbA1c cut-off for diabetes, but the relationship exists only when CAD is present.Figure 1Figure 2
Incident cardiovascular disease in women with type 1 or type 2 diabetes by history of hypertensive disorders of pregnancy
Authors: Timpka S , Pihlsgard M , Enhorning S , Mattsson K 
Published: November 2023

Abstract

Background
Whereas a history of a hypertensive disorder of pregnancy is associated with incident cardiovascular disease, the extent to which this is relevant for women with diagnosed diabetes is unknown.

Purpose
To analyse the risk of incident cardiovascular disease by a history of hypertensive disorders of pregnancy in women with diagnosed type 1 or type 2 diabetes and to examine the extent to which any associated risk was contingent on the level of clinical risk factor control.

Methods
By using nationwide register data (The Swedish Medical Birth Registry and The Swedish Diabetes Registry) between 1998 to 2021, we retrieved information on pregnancy history and cardiovascular disease (myocardial infarction, stroke, and heart failure), in all women with diabetes aged 18 to 69 years who had their first delivery registered. Risk of incident cardiovascular disease was estimated using Cox regression models. In further analyses, we categorized patients by number of risk factors (glycated hemoglobin and low-density lipoprotein cholesterol levels, albuminuria, smoking, and blood pressure) within target ranges.

Results
In total, 1804 (19.7%) of 9179 women with type 1 diabetes, and 5311 (10.6%) of 50,244 of women with type 2 diabetes, had their first delivery complicated by a hypertensive disorder of pregnancy. The risk for any cardiovascular disease event was higher in women with a previous hypertensive disorder of pregnancy in both diabetes groups: for type 1 diabetes the adjusted hazard ratio was 1.25 (95% confidence interval [CI]: 1.03 – 1.52) and for type 2 diabetes 1.20 (95% CI: 1.07 – 1.35). The risk decreased stepwise by improved risk factor profile: from a 7-fold and 4-fold higher risk in type 1 and type 2 diabetes patients, respectively, compared to women with diabetes but without a hypertensive disorder of pregnancy, to negligible risk differences (both groups) with adequate risk factor control.

Conclusions
A history of hypertensive disorder of pregnancy was associated with increased risk of incident cardiovascular disease in women with diabetes, but not in those with adequate risk factor control. Our findings emphasise the importance of preventive care in these patients, as well as a health care provider with access to information about reproductive history.
Change in hbA1c following treatment with and the short-term risk of major adverse cardiovascular outcomes
Authors: Zareini B , Soerensen K K S , Pedersen-Bjergaard U P B , Torp-Pedersen C T P 
Published: November 2023

Abstract

Background
Post-hoc analyses from glucagon-like peptide-1 receptor agonist (GLP1-RA) trial populations have shown a benefit on cardiovascular outcomes from reduction in glycated hemoglobin (HbA1c). It is of interest to see if this finding translates into a cohort of real-world GLP1-RA users.

Purpose
To study among new GLP1-RA users, how reaching a Hba1c below 53 mmol/mol six months after initiation affects the risk of major adverse cardiovascular outcomes (MACE), compared with a HbA1c above 53 mmol/mol.

Methods
We included new GLP1-RA users six months after initiation of treatment, with an available HbA1c value 0-6 months before and 0-6 months after GLP1-RA initiation, from the Danish registries between 2010-2022. HbA1c levels pre- and post-treatment were categorized as above 53 mmol/mol or below 53mmol/mol. The primary outcome was defined as a composite of myocardial infarction, stroke, and all-cause death. Patients were followed from index (6 months after GLP1-RA initiation) until the outcome, a total of 1 years, or end-of-study (31.12.21), whichever comes first. Crude 1-year risks were compared using the Kaplan Meier estimator, or the Aalen Johansen estimator if competing risk was present. The effect of HbA1c below 53 mmol/mol versus a HbA1c above 53 mmol/mol on MACE was estimated using a Cox regression model adjusted for age, sex, educational level, baseline comorbidities, type 2 diabetes duration, and baseline cardiovascular disease including heart failure. Hospitalization for hyperglycemia was also evaluated using a Cox regression.

Results
A total of 4,081 new GLP1-RA users (median age: 58y [IQR:50;66], 52% males) were included, 3,090 had a post-treatment HbA1c below 53 mmol/mol and 991 had a post-treatment Hba1c above 53 mmol/mol. During a median follow-up of 1 year (IQR:1.0,1.0), the crude 1-year risk of MACE in persons with a HbA1c below 53 mmol/mol was 6.4% (95% confidence interval [CI]: 5.5;7.2) and 9.5% (7.7;11.3) in persons with HbA1c above 53 mmol/mol, yielding a hazard rate of 0.69 (0.54;0.88). No interaction between pre-and post HbA1c was found (p=0.59). The hazard rate of hospitalization for hypoglycemia was 0.76 (0.45:1.23) for persons reaching HbA1c level below 53 mmol/mol compared to patients with a HbA1c above 53 mmol/mol, with no interaction between pre- and post HbA1c observed (p =0.052).

Conclusion
A HbA1c level below 53 mmol/mol, among GLP1-RA users reduced the 1-year rate of MACE and did not significantly increase the 1-year rate of hospitalization for hypoglycemia.
Impact of the coronary artery calcium score on the cardiovascular preventive management of asymptomatic patients with diabetes
Authors: Boukhris M , Macia A , Sow M A , Boulogne C , Salle L , Aboyans V 
Published: November 2023

Abstract

Background
Coronary artery calcium (CAC) scoring with non-contrast computed tomography is increasingly used for cardiovascular risk stratification and provides a measure of coronary atherosclerotic burden of particular interest for risk stratification in patients with diabetes. We aimed to assess the impact of CAC on the management of asymptomatic patients with diabetes.

Methods
We studied consecutive asymptomatic patients who underwent CAC for cardiovascular risk stratification for diabetes, from 01/2014 to 12/2020. The study population was subdivided according to the CAC score into 4 subgroups: CAC=0, CAC 1-99, CAC 100-399 and CAC ≥400. We focused on the prescription of aspirin, lipid-lowering therapy (LLT) and glucagon-like peptide-1 receptor agonists (GLP1-RA) before and within 6 months after CAC estimation.

Results
We studied 371 patients (mean age 59.9 ± 10.6 years, 49.3% males). The study population was subdivided according to CAC as follows: CAC = 0 (N=90, 24.3%); CAC 1-99 (N=111, 29.9%); CAC 100-399 (N=70, 18.9%); CAC ≥400 (N=100, 26.9%). Patients with higher CAC (100-399 and CAC ≥400) were older, more often males and had higher prevalence of hypertension and dyslipidaemia. At baseline, the prescription of aspirin and lipid-lowering drugs was statistically higher in presence of CAC&gt;100 (all p&lt;0.001) while no difference was found regarding GLP1-RA prescription among the 4 subgroups (Figure). After CAC estimation, we found no modification in prescription of aspirin in patients with CAC=0 and CAC 1-99. Conversely, aspirin prescription significantly increased from 27.1% to 41.4% and from 40 to 56% in CAC 100-399 and CAC≥400 (p=0.002 and p&lt;0.001), respectively. Similarly, significant changes (initiation or intensification) of LLT were only observed in presence of CAC 100-399 and CAC≥400 ([8.6% and 7.1%; p=0.031] and [19% and 20%; p&lt;0.001], respectively) (Figure). No significant change was found regarding GLP1-RA prescription before and after CAC estimation in the 4 subgroups.

Conclusion
CAC represents an interesting tool to stratify asymptomatic patients with diabetes but there is room for improvement in preventive management of those stratified at the highest risk levels. Important efforts should be made to introduce the use of GLP1-RAs among cardiologists.Figure
Metabolic syndrome and long-term heart rate variability: a systematic review and meta-analysis
Authors: Ortiz-Guzman J E , Molla-Casanova S , Arias-Mutis O J , Calvo C , Bizy A , Such-Miquel L , Genoves P , Serra P , Chorro F J , Zarzoso M 
Published: November 2023

Abstract

Introduction
Metabolic syndrome (MS) is defined as the convergence over time of a group of non-communicable chronic diseases (hypertension, diabetes, dyslipidemia, obesity). There is agreement that MS is related to pathological changes in the behavior of the autonomic nervous system (ANS). Heart rate variability (HRV) is a very useful tool for assessing autonomous behavior, widely used and that could be useful for the diagnosis and monitoring of MS. However, to date, there are no quantitative analyses using meta-analysis (MA) that have addressed the changes that MS causes on the ANS. Therefore, the objective of this systematic review and MA is to evaluate changes in long-term HRV in patients with MS, in order to characterize the cardiac autonomic dysfunction induced by this pathological condition and the most frequently reported explanatory variables.

Methods
We searched PubMed, Web of Science and Scopus electronic databases for original works with long-term HRV recordings (24-h holter) that compared people with MS (MS+) versus healthy people as a control group (MS-). The search was carried out between June 25th, 2022 and September 1st, 2022. In the databases selected, the terms used were "metabolic syndrome" linked to "heart rate variability" (HRV), "cardiac autonomic control", "cardiac autonomic function", or "cardiac autonomic modulation". This systematic review and MA was performed according with PRISMA guidelines and registered at the International Prospective Register of Systematic Reviews (CRD42022358975). Results are reported as standard mean difference [95% CI].

Results
Thirteen articles were included in the qualitative synthesis and seven of them met required criteria to be included in the MA. MS decreased SDNN (-0.33 [-0.57, -0.09], p=0.008), LF (-0.40 [-0.51, -0.28], p&lt;0.0001), VLF (-0.35 [-0.50, -0.21], p p&lt;0.0001)) and TP (-0.24 [-0.43, -0.05], p=0.01). The MA did not find significant differences in rMSSD (-0.09 [-0.31, 0.13], p=0.41), HF (-0.29 [-0.61, 0.03], p=0.07) and LF/HF (-0.04 [-0.45, 0.36], p=0.84). No article reported information by gender. In the case of the non-linear variables, the information reported was not enough to carry out the MA, but the qualitative analyses showed no change in SD1 of the Poincare plot and a decrease in the multiscale entropy. For the SD2 of the Poincare plot and alfa-1 of the detrended fluctuation analyses, the results are not conclusive.

Conclusions
The analysis of HRV (time-domain) in long recording periods showed that patients with MS have lower values in the SDNN and no significant changes in rMSSD. Regarding the frequency domain analysis, we found that MS induced a significant decrease in LF, VLF and TP. The MA did not show changes in HF and LF/HF, and quantitative analyses of non-linear parameters could not be performed.
Outcomes of diabetic patients with acute coronary syndromes treated with aspirin in primary prevention
Authors: Costa H , Espirito Santo M , Fernandes R , Carvalho D , Bispo J , Guedes J , Azevedo P , Vinhas H , Mimoso J , Jesus I 
Published: November 2023

Abstract

Introduction
The use of aspirin in primary prevention (PP) remains a matter of international debate. In type 2 diabetes mellitus (DM2) patients with high/very high cardiovascular (CV) risk, low dose aspirin may be considered for PP (class IIb, evidence level A) in european guidelines in the absence of hemorrhagic contraindication.

Objectives
Our aim was to analyze in-hospital and one year follow-up (FU) outcomes of acute coronary syndrome (ACS) DM2 patients without previous atherosclerotic CV disease (ASCVD) treated with vs without aspirin in primary prevention.

Methods
A retrospective analysis was carried out of DM2 patients without established ASCVD admitted with ACS included in the Portuguese Registry of ACS between 2010-2021. Patients were divided in two groups regarding the use of aspirin in primary prevention (with-AG and without-NAG). Composite primary outcome (re-infarction, heart failure, shock, death – in-hospital) and secondary outcomes (one-year all-cause mortality and mortality/rehospitalization) were compared in both groups. Independent predictors of primary outcome were assessed by multivariate logistic regression. Survival analysis and cox regression were used to compare and identify predictors of secondary outcomes. P value &lt; 0.05 indicates statistical significance.

Results
A total of 4517 patients were analyzed, mean age 68±12 years, 64.8% male. AG showed higher rates of hypertension (89.9%, p&lt;0.001), dyslipidemia (74.1%, p&lt;0.001), history of heart failure (9.2%, p&lt;0.001), valvular disease (3.9%, p=0.002) and chronic renal disease (12.3%, p&lt;0.001). STEMI presentation was more frequent in NAG (48%, p&lt;0.001). Multivessel disease (mainly three vessels disease) was more frequent in AG (32.7%, p&lt;0.001), but anterior descendent (AD) as culprit artery was more common in NAG (40.3%, p=0.013). Both groups had no difference in major hemorrhage occurrence. Primary outcome was more frequent in AG (18.6%, p=0.034). One-year all-cause mortality and mortality/rehospitalization were higher in AG (9.90%, p=0.004 and 32.9%, p=0.017, survival analysis). Independent predictors of primary outcome were aspirin in primary prevention (OR 1.38, p=0.026), age (OR 1.59, p&lt;0.001), valvular disease (OR 4.46, p&lt;0.001), STEMI at presentation (OR 2.20, p&lt;0.001), LVEF &lt;40% (OR 4.40, p&lt;0.001) and Killip-Kimball class &gt; I (OR 12.9, p&lt;0.001). Aspirin in primary prevention (HR 1.84, p=0.004), chronic lung disease (HR 5.68, p&lt;0.001), and Killip-Kimball class &gt; I (HR 3.27, p&lt;0.001) were predictors of one-year all-cause mortality.

Conclusion
DM2 patients with ACS treated with aspirin in primary prevention had worst in-hospital and one-year FU outcomes. Although with higher rates of three vessels disease, PP with aspirin showed less AD disease and STEMI presentation, with similar major clinical hemorrhage.
Effect of sodium-glucose co-transporter inhibitors on arterial stiffness in patients with type 2 diabetes mellitus
Authors: Szigeti J , Bukva M , Gaszner B 
Published: November 2023

Abstract

Introduction
Selective sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). In addition to glucose homeostasis the impaired arterial stiffness may participate in this morbidity and mortality.

Purpose
The aim of this study was to investigate the effect of administration of SGLT2i therapy on arterial stiffness parameters, including aortic pulse wave velocity (PWV) and central systolic blood pressure (SBPao), which have significant prognostic value for predicting cardiovascular events.

Methods
Our prospective, observational study included 40 patients with T2DM (mean age: 60.3±9.9 years, 24 males). Biochemical and arterial stiffness parameters were analysed before starting SGLT2i therapy (14 patients on dapagliflozin, 25 patients on empagliflozin, 1 patient on ertugliflozin), at 3, 6 months and an average of 3.3±1.3 years follow-up period. Arterial stiffness parameters were determined using an invasively validated oscillometric based Arteriograph (AG) method. Changes in the variables and their interrelation was analysed by repeated data ANOVA and multivariate linear regression.

Results
Significant decrease in PWV and HgbA1c were observed 3 months after the initiation of SGLT2i therapy (PWV: 10.68±1.35 m/s vs. 10.05±1.40 m/s and HgbA1c: 7.86±0.55 vs. 6.83±0.66 %, p&lt;0,05) and this long-term effect continued during the 3.3-years follow-up period (PWV: 9.96±1.25 m/s and HgbA1c: 7.19±0.81 %, p&lt;0,005, Figure 1). Pearson's correlation analysis and multivariate linear regression analysis showed no association between decreased PWV and BMI, brachial diastolic blood pressure (DBPb) while significant, but weak correlation was observed with HgbA1c and brachial systolic blood pressure (SBPb) (r=0.22-0.26, p&lt;0.05, Figure 2). SBPao results showed non-significant decrease and a subsequent non-significant long-term increase comparing to baseline during the 3.3 years follow-up.

Conclusion
Short and long-term SGLT2i therapy in T2DM significantly improved PWV values and this effect is independent of changes in SBPao. All these findings emphasize the clinical relevance of arterial stiffness as a biomarker in the SGLT2i induced beneficial effect on the vasculature, however further clarification, long-term evaluation needed to define the role of PWV in the prediction of cardiovascular events.Figure 1Figure 2
Exercise capacity of the patients after cardiac surgery with special reference to left atrium incision
Authors: Kanazawa M , Miura M , Sawada S , Funaki T , Anzai J , Uchimura K , Komaru K , Kagaya Y , Saito H , Sato K , Kondo M , Kawatsu S , Endo H , Oda K , Nakamura A 
Published: November 2023

Abstract

Background
Chronotropic incompetence (CI) is sometimes observed during exercise in patients who underwent cardiac surgery, however, little is known which factors affect to the incidence of CI and exercise capacity of those patients.

Purpose
We hypothesized that the incidence of CI is higher in patients with left atrium incision (LAI) as compared with those without LAI, which is caused by impairment of cardiac sympathetic nerves by LAI. The purpose of this study is to elucidate whether LAI causes CI, and if so, to analyze which factor determine the exercise capacity of the patients with LAI.

Methods
We performed cardiopulmonary exercise testing in total 157 patients who had undergone elective cardiac operation (46 patients with LAI, 111 patients without LAI). We analyzed chronotropic response index (CRI), parameters of exercise capacity, echocardiography, and blood hemoglobin concentration (Hb).

Results
The value of CRI was significantly reduced in the patients with LAI as compared with those without LAI (0.24±0.22 vs. 0.45±0.17, respectively, p&lt;0.001). Exercise capacity such as peak oxygen uptake (peak VO2), anaerobic threshold showed no significant difference between two groups. In patients with LAI, peak VO2 showed significant correlations between peak oxygen pulse (peak VO2/HR; r=0.34, p&lt;0.05), Hb (r=0.43, p&lt;0.005) and left atrium dimension (LAD) measured by echocardiography (r=-0.56, p&lt;0.001).

Conclusions
The present study demonstrated that higher incidence of CI was observed in patients with LAI as compared with those without LAI. Moreover, peak VO2 of patients with LAI showed significant correlations with peak VO2/HR, Hb and LAD. These results suggest that 1) LAI may impairs cardiac sympathetic nerves and causes CI, 2) peak VO2/HR and its component Hb are important factors which determine exercise capacity of patients with CI, 3) LAD which indicates left atrial function may also affect exercise capacity of patients with CI.