bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating trimethyllysine predicts total and cardiovascular mortality in patients with and without coronary heart disease
Authors: Bjornestad E O , Dhar I , Svingen G F T , Svenningsson M M , Pedersen E R , Tell G S , Ueland P M , Orn S , Laaksonen R , Nygaard O 
Published: October 2021

Abstract

Background
The carnitine precursor trimethyllysine (TML) is associated with the microbiota-derived metabolite trimethylamine N-oxide (TMAO) and predicts future cardiovascular events in patients with established coronary heart disease (CHD).

Purpose
To examine circulating TML as a predictor of total and cardiovascular mortality in two independent cohorts of subjects with or without CHD.

Methods
By Cox regression modelling, risk associations were examined in 6393 subjects in the community-based Hordaland Health Study (HUSK). A replication study was performed among 4117 patients undergoing coronary angiography for suspected stable angina pectoris in the Western Norway Coronary Angiography Cohort (WECAC).

Results
During a median follow-up of 10.9 years in the HUSK-cohort, 884 (13.8%) subjects died, of whom 287 from cardiovascular causes. After adjustments for traditional cardiovascular risk factors, the hazard ratio (HR) (95% CI) for total mortality comparing the 4th vs. 1st TML-quartile was 1.66 (1.31–2.10, p&lt;0.001). Particularly strong associations were observed with cardiovascular mortality (HR [95% CI] 2.04 [1.32–3.15, p=0.001]). Corresponding risk estimates in the WECAC-cohort (median follow-up of 10.3 years) were 1.35 (1.10–1.66, p=0.004) for total and 1.45 (1.06–1.98, p=0.02) for cardiovascular mortality. Additional adjustments for plasma TMAO did not materially influence the risk estimates in either cohort, and no effect modification by TMAO was observed.

Conclusions
Circulating TML is associated with increased risk of total and cardiovascular mortality in both subjects with and without CHD.

Funding Acknowledgement
Type of funding sources: None.
Inter-relationships of different electrocardiographic indicators of left ventricular hypertrophy in 25,000 Chinese adults
Authors: Chaikovsky I , Lebedev E , Du H , Chen Y , Ponomarev V , Guo Y , Bian Z , Li L , Chen Z , Clarke R 
Published: October 2021

Abstract

Background
Several electrocardiographic (ECG) indices have previously been proposed to diagnose left ventricular hypertrophy (LVH). Such indices utilize different criteria, including increased QRS voltage, prolonged QRS duration, left axis deviation, and LAFB and LBBB-like patterns in varying combinations. However, the inter-relationships of these different electrocardiographic indices of LVH with each otherare not fully understood.
The purpose of this study is to estimate the relationships between the different LVH indices.

Methods
Electronic tracings of 12-lead ECGs recorded in 24,786 adult participants in the China Kadoorie Biobank recorded in 2014 were accessed to detect presence of LVH. ECG parameters of LVH, including individual and combinations of such parameters (voltage-only criteria such as Sokolov-Lyon, Cornell, Gubner as well as scores such as Romhilt-Estes point score) were estimated using customized computer software (Cardiolyse Oy, Finland) and compared proprietary LVH point score algorithms (Mortara, USA). Relationships between the different indices were assessed using a correlation matrix to explore associations between individual parameters and combined indices of such parameters. The matrices were used to construct heat maps and identify clustering of individual parameters.

Results
Overall, approximately 10% of the population had LVH assessed by Mortara algorithms. This graph shows that along with the free standing peaks, the rest are divided into two clusters of interconnected individual parameters. In the center of the largest cluster is the parameter, reflecting R-peak magnitude in aVL lead. In the center of another cluster was the left ventricular strain pattern, as described in Romhilt-Estes point score system. Overall, the Sokolov-Lyon index and LVH point score in Veritas algorithm had the strongest relationships with each other, but the Gubner and Cornell indices had relatively weak correlations with the other indices (Table 1). The mean correlation coefficient between five combined LVH indices was as follows: Veritas (Mortara) – 0.58, Sokolov-Lyon – 0.56, Romhilt-Estes – 0.45, Gubner – 0,32, Cornell – 0,3.

Conclusions
Parameters such as R-peak magnitude in aVL and left ventricular strain pattern were the most strongly related with each other. Aggregate indices, such as the Sokolov-Lyon index and LVH point score in Veritas algorithm were the most strongly related with all other indices, but the Gubner and Cornell indices were only weakly correlated. The results reinforce the utility of Sokolov-Lyon index and Mortara algorithms as the optimum measures of LVH.

Funding Acknowledgement
Type of funding sources: None.
Characteristics of patients with a lipoprotein(a) assessment – a health insurance claims database analysis
Authors: Laufs U , Schorr J , Klebs S 
Published: October 2021

Abstract

Background
Elevated lipoprotein(a) [Lp(a)] has been established as marker of cardiovascular [CV] risk, however, it is not commonly assessed.

Purpose
The aim of the study was to characterize patients who underwent their first Lp(a) testing regarding sociodemographic characteristics and clinical outcomes.

Methods
A retrospective analysis was performed on data from 4 million individual patients in a local database that provides complete, longitudinal, anonymized claims data. The data are representative of the German population in terms of age and gender. Lp(a) billing codes documented in the ambulatory setting were used to identify adult patients in 2015 to 2018 (index quarter defined as the first Lp(a) test in the respective year). These patients must not have had any Lp(a) test in the year prior to the index quarter. Patient data needed to be available for at least 1 year before and 1 year after the Lp(a) test or until death, whichever came first. Patients were followed for a maximum of four years.

Results
Within the four-year period, 36.609 patients (0.83% of the analysis set) had an Lp(a) test, of whom the majority (58%) were women. 50% of the women (median age 49 years) and 32% of the men (median age 56 years) were younger than 50 years.
The most prevalent comorbidities (based on International Classification of Diseases, version 10, German modification) at index were: dyslipidemia (E78) 46%, essential hypertension (I10) 46%, dorsalgia (M54) 25%, overweight/obesity (E66) 18%, chronic ischemic heart disease (I25) 16%, type 2 diabetes mellitus (E11) 15%, other coagulation defects (D68) 14%, depressive episodes (F32) 14%; disorders of refraction and accommodation (H52) 13%, somatoform disorders (F45) 13%, other non-toxic goiter (E04) 13%, other hypothyroidism (E03) 13%, and chronic kidney disease (N18) 11%.
The rates of cardiovascular events and procedures are listed in the table below.

Conclusions
Lp(a) tests are rarely performed in Germany. Women are more often tested than men, and in women this is done at a younger age. The data suggest that CV events/ CV hospitalizations frequently trigger the first Lp(a) assessment. The population tested displayed a high prevalence of cardiovascular comorbidities. The data identify an opportunity to better characterize the CV risk by testing Lp(a) once in a lifetime independent of prior CV events as recommended by current European Society of Cardiology/European Atherosclerosis Society guidelines.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The analysis has been funded by Novartis Pharma GmbH, Nuremberg.
Comparison of coronary atherosclerotic features in response to achieving LDL-C &lt;55 mg/dl between non-diabetic and diabetic patients: insights from the REASSURE-NIRS registry
Authors: Iwai T , Katoka Y , Murai K , Hosoda H , Honda S , Fujino M , Yoneda S , Otsuka F , Nishihira K , Kanaya T , Asaumi Y , Murata S , Miyamoto Y , Yasuda S , Noguchi T ,   REASSURE-NIRS Registry
Published: October 2021

Abstract

Introduction
Current ESC guideline recommends achieving LDL-C &lt;1.4 mmol/l in very high-risk subjects. Despite fabvourable anti-atherosclerotic effects of lowering LDL-C, its efficacy is diminished in type 2 diabetic patients. Whether response of coronary atheroma to on-treatment LDL-C &lt;1.4 mmol/l differs in diabetic and non-diabetic subjects has not been elucidated yet.

Methods
The REASSURE-NIRS registry is an on-going multi-center registry to enroll CAD subjects receiving PCI under the guidance of near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS: DualProTM, Nipro, Tokyo, Japan) imaging. Culprit lesions in 557 CAD patients who already received a statin were evaluated by NIRS/IVUS. Maximum 4-mm-lipid-core burden-index (maxLCBI4mm) and plaque calcification grade at culprit sites were measured. Calcification grade at each 1-mm cross-sectional image was defined as follows: calcium arc 0° = 0, 0–90° = 1, 90–180° = 2, 180–270° = 3, 270–360° = 4. MaxLCBI4mm and the averaged calcification grade were compared in diabetic and non-diabetic subjects stratified according to on-treatment LDL-C level, respectively.

Result
The proportion of diabetic (n=293, HbA1c; 6.9±0.9%) and non-diabetic patients (n=264) with on-treatment LDL-C &lt;1.4 mmol/l was 8.54 and 16.67%, respectivey (p=0.01). In non-diabetic patients, achieving LDL-C &lt;1.4mmol/L was associated with a lower maxLCBI4mm, whereas, in diabetic patients, maxLCBI4mm was numerically smaller under achieving LDL-C &lt;1.4 mmol/l, but this comparison did not meet statistical significance (Figure 1). Furthermore, a greater degree of calcification grade in non-diabetic patients was observed in association with on-treatment LDL-C level (Figure 2). However, plaque calcification at diabetic coronary atheroma was not necessarily induced under achieving stricter LDL-C goal. Subgroup analysis demonstrated that diabetic patients with body mass index ≥25 (odds ratio = 0.15; 95% CI: 0.18–1.19, p=0.04), estimated glomerular filtration rate &lt;60 (mL/min/1.73m2) (odds ratio = 0.31; 95% CI: 0.10–0.90, p=0.03) and non-insulin use (odds ratio = 0.36; 95% CI: 0.14–0.87, p=0.02) benefit from achieving LDL-C &lt;1.4 mmol/l.

Conclusion
Achieving LDL-C &lt;1.4 mmol/l was associated with more stabilized atheroma in non-diabetic patients with CAD, whereas these favourable effects were not observed in diabetic subjects. Our findings suggest the potential need to modify additional atherogenic risks for stabilizing diabetic coronary atheroma under achieving LDL-C &lt;1.4 mmol/l.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Clinical features of familial hypercholesterolaemia in children and adults – the PMMHRI Registry
Authors: Lewek J , Starostecka E , Konopka A , Sosnowska B , Banach M ,   the PMMHRI Registry
Published: October 2021

Abstract

Background
Familial hypercholesterolaemia (FH) affects approximately 150,000 people in Poland. However, there are many patients still unaware of this diagnosis. On the other hand, it might lead to early cardiovascular mortality and morbidity due to the lifetime exposure to high levels of LDL-C. Therefore, increased awareness of FH is very important.

Purpose
We aimed to evaluate the clinical features of FH in children and adults based on the preliminary data from the Polish Mother's Memorial Hospital Research Institute (PMMHRI) Registry.

Methods
The registry of children and adults with FH conducted in PMMHRI (2nd largest, supra-regional hospital in Poland) was established to investigate the clinical characteristics, management and clinical outcomes data of FH patients. All consecutive patients with diagnosed (genetically and/or phenotypically) FH were included in the study.

Results
Of 103 patients with FH, there were 16 children aged 9±3 and 87 adults aged 41±16; 59% were female. The diagnosis of FH in adults was late – at the mean age of 41 years. Among children with FH, as compared with adults, the levels of highest TC and LDL-C ever were similar. However, children presented higher mean levels of total cholesterol, LDL-C and HDL-C measured at baseline visit (Table). Interestingly there was no difference in BMI between children and adults (Table). Among adults, chronic coronary syndrome was diagnosed in 11.5% patients, from which 5.7% patients had a history of myocardial infarction and 7% patients required revascularization. The prevalence of chronic coronary disease, peripheral artery disease as well as stroke in family history was definitely higher (in 44 patients – 50%, 17 patients – 20% and 22 patients – 25%, respectively). Most of adult patients at baseline visit were prescribed statins (rosuvastatin or atorvastatin). 14 patients (13.6%) declared statin intolerance, most of them complained of muscle pain, 4.6% patients reported hepatic disturbances. The frequency of statin use in children was lower – 56% children were prescribed statin, 19% declared statin intolerance with muscle pain as the side-effect of treatment. Ezetimibe, as a part of combination therapy, was taken by 29% adult patients. PCSK9 inhibitors were prescribed (within drug program) for 11.5% adult patients. Fibrates were prescribed for 13.7% adult patients, the same was for n-3 fatty acids.

Conclusions
Despite definitely younger age of FH diagnosis children present higher mean levels of LDL cholesterol than adults. Therefore, the lifetime exposure to LDL cholesterol starts at a very young age. As a result, there is a need to the earlier initiation of therapy and strict monitoring of the atherosclerosis progression. On the other hand, late diagnosis of FH in adults is an unmet need, that might be associated with poorer prognosis.

Funding Acknowledgement
Type of funding sources: None.
Association of glycated haemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE consortium
Authors: Sinning C , Makarova N , Schnabel R , Ojeda F , Felix S B , Koenig W , Peters A , Rathmann W , Brenner H , Kuulasmaa K , Wilsgaard T , Blankenberg S , Soderberg S , Ferrario M M , Thorand B ,   BiomarCaRE
Published: October 2021

Abstract

Background
Glycated haemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment; however, its role in predicting cardiovascular outcomes in the general population remains uncertain.

Purpose
The additional use of glycated haemoglobin A1c (HbA1c) as a biomarker might highlight subjects of the general population with an increased risk for cardiovascular outcomes with cardiovascular disease, cardiovascular mortality or overall-mortality.

Methods
Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analysed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular diseases (CVD), and overall mortality in the study population, in non-diabetic (N=32,477), and diabetic participants (N=3,703).

Results
Kaplan-Meier curves showed higher event rates with increasing continuous log-transformed HbA1c levels. Cox regression analysis revealed significant associations between HbA1c (in mmol/mol) log-transformed divided by interquartile range and the examined outcomes, with a hazard ratio (HR) of 1.12 (95% confidence interval (CI): 1.04–1.20, p=0.0019) for cardiovascular mortality, 1.10 (95% CI: 1.04–1.16, p&lt;0.001) for CVD, and 1.09 (95% CI: 1.05–1.14, p&lt;0.001) for overall mortality per one unit increase.
An increased risk of CVD was observed in subjects without diabetes with increased HbA1c levels (HR 1.09; 95% CI: 1.01–1.16, p=0.021). An HbA1c cut-off value of 39.89 mmol/mol (5.8%), 36.62 mmol/mol (5.5%), and 38.80 mmol/mol (5.7%) for cardiovascular mortality, CVD, and overall mortality, respectively, was determined for selecting individuals at an increased risk.

Conclusion
HbA1c was demonstrated to be an independent prognostic biomarker for all investigated outcomes in the general European population. An approximately linear relationship was observed between an increase of HbA1c levels and the outcomes. Elevated HbA1c levels were also associated with the outcomes in participants without diabetes (i.e. HbA1c levels &lt;6.5% (&lt;48mmol/mol) which underlines the importance of HbA1c levels in the overall population.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union Seventh Framework ProgrammeEuropean Union FP 7 project CHANCES Kaplan-Meier curves for the outcomesPenalised cubic splines HbA1c/time event
Relationship between heart rate variability, low grade inflammation and glycated hemoglobin. A sugary sweet story
Authors: Hadad R , Akobe S F , Weber P , Haugaard S B , Sajadieh A 
Published: October 2021

Abstract

Background
Low grade inflammation (LGI) is significantly associated with microvascular complications in diabetes mellitus (DM). Reduced and impaired Heart rate variability (HRV) is a strong marker of autonomic dysfunction and neuropathy and strongly associated with microvascular disease in DM. New studies and observations indicate that the diabetic neuropathic process starts early during pre-diabetes. On the other hand, HRV and LGI are closely interrelated. Our aim was to evaluate whether LGI or hyperglycemia (i.e. high HbA1c) is associated with the autonomic dysfunction or reduced HRV among people with diabetes and pre-diabetes.

Methods and materials
This study is based on The Copenhagen Holter Study, in which 678 community dwelling subjects aged 55 – 75 years who were free of previous cardiovascular disease, except from well controlled hypertension, and who underwent a 48-hours Holter recording. Analysis of HRV including night-time HRV were available for 653 participants and this population included 133 people with well-controlled and newly recognized T2DM (mean HbA1c 55 mmol/mol (7.2%)) and 386 people with pre-diabetes defined as HbA1c between 39 mmol/mol (5.7%) and 47 mmol/mol (6.4%). We selected high-sensitive CRP, as markers of LGI. As measures of HRV we used the standard deviation of normal-to-normal (N-N) beats (SDNN), the root mean square of N-N beats (RMSSD) which has been acknowledged to be best linked to vagal parasympathetic tone, and the mean time between N-N complexes (meanNN) which represents the average 24-hour heart rate (60.000/meanNN = average 24-hour HR in beats/min)

Results
Measures of HRV were associated with HgbA1c among both people with T2DM and pre-diabetes. Among people with pre-diabetes HbA1c was inversely associated with 24-hour RMSSD (r=−0.11, p=0.03) and night-time SDNN (r=−0,13, p&gt;0.01), while among T2DM HgbA1c was only associated with 24-hour RMSSD (r=−0.21, p=0.02). These association stayed significant when adjusted for sex, age, BMI, smoking, HOMA-ir, hs-CRP and systolic blood pressure in multiple linear regression (Table 1). LGI was only associated with HRV in diabetes. HbA1c was not associated with any measures of HRV or LGI among people with normal glucose metabolism.

Conclusion
HRV is closely and inversely associated with HbA1c in both diabetes and prediabetes, but only in diabetes LGI is associated with HRV. This indicates that the process of autonomic dysfunction/neuropathy starts at an early phase during pre-diabetes and probably provoked by postprandial hyperglycemia, while in diabetes both HbA1c and LGI are associated with HRV showing that LGI is activated later in the disease process probably provoked by long-term postprandial hyperglycemia, indicating treatment of hyperglycemia and postprandial hyperglycemia in the prediabetes state may be helpful.

Funding Acknowledgement
Type of funding sources: None.
Out-of-hospital cardiac arrest and ambient air pollution: a dose-effect relationship and a predictive role in OHCA risk
Authors: Gentile F R , Primi R , Baldi E , Compagnoni S , Mare C , Contri E , Reali F , Bussi D , Facchin F , Currao A , Bendotti S , Savastano S 
Published: October 2021

Abstract

Background
Pollution has been suggested as a precipitating factor for cardiovascular diseases via a series of different mechanisms. However, data about the link between the different air pollutants and the risk of out-of-hospital cardiac arrest (OHCA) are limited and controversial.

Purpose
The primary aim of this study is to examine the impact of short-term exposure to particulate and gaseous pollutants on the incidence of OHCA in a vast metropolitan and rural area that encompasses four provinces of the Po Valley in Northern Italy, one of the most polluted areas in Italy and Europe due to its levels of industrialization and high population density. The secondary aim of this study is to look for a dose-effect curve, which could help predict OHCA incidence based on the concentration of pollutants in a specific area.

Methods
This is a retrospective analysis of prospectively collected data both in the OHCA registry (Lombardia CARe) and in the database of the regional agency for environmental protection (ARPA) of the Lombardy region. All medical OHCAs and the mean daily concentration of pollutants including fine particulate matter (PM10, PM2.5), benzene (C6H6), carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3) were considered from January 1st to December 31st, 2019 in the southern part of the Lombardy region (provinces of Pavia, Lodi, Cremona and Mantua; 7863 km2; about 155ehab724.2654 inhabitants). Days were divided into high or low incidence of OHCA according to the median daily incidence. A Probit dose-response analysis and both uni- and multivariable logistic regression models were provided for each pollutant.

Results
The median daily incidence of OHCA was 0.3 cases/100,000 inhabitants. Benzene was the pollutant with the greatest difference between days at high and low incidence of OHCA [0.7 (IQR 0.4–1.2) vs 0.4 (IQR 0.3–0.7), p&lt;0.001], whereas SO2 had the lowest and least significant difference between the two periods [3.2 (IQR 2.8–3.6) vs 3.1 (IQR 2.7–3.5), p=0.046]. O3 showed a countertrend, being significantly higher in the low-incidence period [29.9 (IQR 10.9–61.7) vs 56.1 (IQR 25.5–74.1), p&lt;0.001] as well as temperature [10.1— (IQR 5.2–14.8) vs 15.1 (IQR 8.9–23.3), p&lt;0.001]. By using the Probit regression analysis and after adjusting for temperature, a dose-response relationship was demonstrated for all the tested pollutants.

Conclusions
Our results clarify the link between pollutants and the acute risk of cardiac arrest suggesting the need of both improving the air quality and integrating pollution data in future models.

Funding Acknowledgement
Type of funding sources: None.