bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Mellitus influence in Lipoprotein(a) gene expression and association to coronary artery disease
Authors: Sa D , Mendonca M , Sousa F , Abreu G , Rodrigues M , Henriques E , Freitas S , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Palma Dos Reis R 
Published: October 2024

Abstract

Introduction
Lp(a) and type 2 diabetes mellitus are both known and established risk factors for the development of coronary artery disease (CAD). Lp(a) levels are 75% to 95% heritable and predominately determined by single-nucleotide variants at the LPA gene; rs3798220 is one of the most studied variants and accounts for a significant portion of Lp(a) levels. Whether diabetes could influence the LPA rs3798220 account for Lp(a) levels is unknown.

Aim
Evaluate whether there is a different association between polymorphism LPA rs3798220 T&gt;C and Lp(a) levels and their association with CAD in diabetic and non-diabetic populations.

Methods
3,209 subjects (mean age 59.3±8.9 years, 76.3% male were selected from the data set of the Research Center. The LPA rs3798220 T&gt;C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This genetic variant has a minor allele frequency (MAF) &lt;2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Lp(a) biochemical levels were measured in all participants. From the 3,209 participants, 810 had diabetes, and 2399 were no diabetics. For each group, chi-squared tests were used to determine the association of CAD prevalence by genotype, and t-tests were used to evaluate differences in CAD prevalence by Lp(a) levels.

Results
In non-diabetic subjects, LPA TC was significantly associated with CAD in non-diabetic subjects compared with TT (p&lt;0.0001). Similarly, Lp(a) was higher in the CAD population (37.2±39.7) compared to the healthy population (25.6±30.0) (p&lt;0.0001). In diabetic group, Lp(a) was higher in the CAD population (38.5±41.4) compared to the population without CAD (23.9±29.2) (p&lt;0.0001). Nevertheless, there was no difference in genotype between CAD and non-CAD patients (p=0.710).

Conclusion
The LPA rs3798220 T&gt;C variant in non-diabetic group can explain high Lp(a) levels and their association with CAD. However, in patients with diabetes, Lp(a) is elevated in CAD patients besides the fact that no significant genotype differences were displayed. Non-genetic influences like behavioural factors or even epigenetic changes may probably explain high Lp(a) levels in this population.
The association of steatotic liver disease with recurrent ischemic events in patients with chronic coronary syndrome: a multicenter cohort study
Authors: Zeng G , Yuan J 
Published: October 2024

Abstract

Background/introduction
A panel of multi-society experts has proposed new subcategories under the term steatotic liver disease (SLD), replacing the exclusive term non-alcoholic fatty liver disease with the new nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prognostic impact of SLD subtypes in patients with chronic coronary syndrome (CCS) remains unknown.

Purpose
We aimed to investigate the associations between SLD subtypes and recurrent event risks in CCS patients.

Methods
Our analysis included a total of 9,448 patients with CCS from a large multicenter nationwide cohort. Hepatic steatosis was defined as hepatic steatosis index ≥36 and ultrasound evidence. Patients were categorized into four groups based on the evidence of steatosis, cardiometabolic risk factors and alcohol intake: 1) no SLD; 2) MASLD; 3) MASLD with increased alcohol intake (MetALD) and 4) SLD with other causes. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stroke and unplanned revascularization.

Results
The prevalence of no SLD, MASLD, MetALD and SLD with other causes in our population was 37.3%, 47.7%, 14.7% and 0.3%, respectively. During a median follow-up of 2.0 years, 759 (8.0%) MACCE events occurred. After multivariable adjustment, MASLD (HR 1.25, 95%CI 1.06-1.48), MetALD (HR 1.31, 95%CI 1.04-1.65) and SLD with other causes (HR 2.81, 95%CI 1.04-7.57) were all significantly associated with higher MACCE risks compared to no SLD.

Conclusions
A significant proportion of SLD was observed in CCS patients. Patients with various SLD subcategories all had higher risks of recurrent events.
Empagliflozin's role in reducing ventricular repolarization heterogeneity: insights into cardiovascular mortality decline from the EMPATHY-HEART trial
Authors: Lauretti C , Luciano G , Fernandes A E , Caramelli B 
Published: October 2024

Abstract

Introduction
The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM). Predictive measures for fatal arrhythmias are often inadequate, highlighting the need for novel non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index, which measures variations in ventricular repolarization, has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH.

Methods
Participants were adult outpatients with T2DM and CHD, exhibiting a baseline TWH of at least 80 µV. They received a 25mg daily dose of empagliflozin and were evaluated clinically, including ECG measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was the alteration in TWH following empagliflozin administration, assessed via the Wilcoxon test, with a significance threshold of p&lt;0.05.

Results
An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 144 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing mostly Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced median TWH from 116 to 103 µV (p=0.01), as detailed in Figure 1.

Conclusion
The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population.Table 1 Figure 1
Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)
Authors: Bilo G , Villafuerte F C , Zanotti L , Soranna D , Nava S , Rusconi V , Pengo M F , Croce A , Lombardi C , Macarlupu J L , Bermudez D , Sosa J M , Carcamo C P , Zambon A , Parati G 
Published: October 2024

Abstract

Introduction
Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries.

Aim
To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru.

Methods
Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: &lt;500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis.

Results
The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800).

Conclusions
Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.
Fitness to fly: assessing cardiac disease among Air Force pilots
Authors: Certo Pereira J , Monge J , Baptista A , Reis P , Dores H 
Published: October 2024

Abstract

Introduction
Aviation is a risk activity, particularly in pilots with cardiovascular (CV) disease. The occurrence of acute clinical events during flight may have catastrophic implications, justifying the relevance of cardiologic evaluation in Aviation Medicine. However, the evidence about the impact of CV diseases in this population is scarce.

Aim
To study the cardiac causes of incapacitation among pilot candidates and pilots of the Portuguese Air Force (PoAF) over a period of 20 years.

Methods and results
A retrospective analysis of cardiac causes of incapacitation between January 1999 and December 2018 was performed, both in PoAF candidates and pilots. In this period, the overall number of candidates was 2529 and the number of PoAF pilots was 760. Among the candidates, 41% (N=1086) were considered unfit, of which 4% (N=39) due to cardiac causes (all men aged 17-25), namely valvular diseases (N=27) and conduction/heart rhythm disturbances (N=12). Among the pilots, 2% (N=18) were considered unfit, mainly due to cardiac disease (50%; N=9). These pilots considered unfit pilots due to cardiac disease were men with mean age of 47±9 (30-60) years old, all unfit due to acute myocardial infarction, none occurring during flight.

Conclusion
Cardiac diseases were an uncommon cause of incapacitation among the pilot aviator candidates, but it was the main cause among the pilots of the PoAF during two decades, all due to acute myocardial infarction. Cardiac evaluation in Aviation Medicine is essential, focusing on CV risk stratification and preclinical detection of coronary artery disease.Figure 1
Defibrillator shocks and their effect on objective asian patient outcomes: results of the painfree SST clinical trial
Authors: Kondo Y , Sears S F , Bart G , Sterns L D , Schloss E J , Meijer A , Auricchio A , Kurita T 
Published: October 2024

Abstract

Background
The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, the effect of ICD shock on device-measured activity is unknown. The aim of this analysis was to analyze the acute and long-term effects of ICD shock on objective behavioral data.

Methods
The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). Patient physical activity was determined from the device built-in accelerometer. The device translates the accelerometer output into a count of active minutes, which is stored as a daily total value in device memory for a rolling window of 425 days. Obviously, activity is measured only after device implantation. Early after implant, activity is reduced due to the procedure and thus not representative. Therefore, no baseline can be reported for activity. The follow-up activity data was analyzed with a linear mixed model, with a random effect for patient and an auto-regressive correlation matrix for subsequent measurements of individual patients.

Results
Figure 1 shows average daily activity between 90 days before and 90 days after a shock. The dashed vertical line indicates the day of shock. Both patients from Asia and from other countries show a drop in activity after a shock with recovery in the subsequent 30-60 days. The curve for Asian patients is more variable than the curve for other countries due to the lower number of patients (there were 33 Asian patients with shocks contributing data). Figure 2 shows average daily activity before and after ATP therapy. Any post shock measurement is excluded. Contrary to the temporary reduction in activity around a shock (Figure 1), ATP therapies do not seem to have an impact on activity. In patients from the other countries, activity is significantly reduced when patients are hospitalized (-66.3 minutes/day, p&lt;0.0001), but not in Asian patients (-5.1 minutes/day, p=0.71). Both in Asian and other countries, activity is significantly reduced after an ICD shock (Asian: -47.5 minutes/day, p=0.0002; Other countries: -21.5 minutes/day, p&lt;0.0001). The effect of shock for Asian is greater than the other countries (p=0.054). In the month after the shock there is a significant recovery, +34.8 minutes/day in Asian patients (p=0.0077) and +7.7 minutes/day in patients from other countries (p=0.031). The recovery is trended to be bigger in Asian patients (p=0.058).

Conclusions
ICD shocks have a lasting adverse impact on objective, device-measured physical activity, particularly among Asian individuals. Successful management of patients with an ICD necessitates specific attention to clinically relevant behavioral outcomes, aiming to expedite recovery and facilitate a return to activities of daily living, with a particular focus on the Asian population.
A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality
Authors: Carlen A , Lindow T , Cauwenberghs N , Elmberg V , Brudin L , Ekstrom M , Hedman K 
Published: October 2024

Abstract

Purpose
Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test.

Methods
We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) &gt;40kg/m², as well as tests with resting SBP &lt;80mmHg or &gt;200mmHg, exercise SBP &lt;100 mmHg, &lt;2 SBP measurements during the second half of the test or a test duration &lt;4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of &lt;2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase &gt;15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication.

Results
Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2).

Conclusion
In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.
Incidental detection and quantification of coronary artery calcification in ungated thoracic computed tomography for prognostic assessment. Preliminary results from the ICARUS registry
Authors: Marcos Garces V , Minguez Diaz De Alda S , Merenciano-Gonzalez H , Villa-Sanchez C A , Perez-Pelegri M , Gavara J , Bertolin-Boronat C , Iraola-Viana D , Perez N , Rios-Navarro C , De Dios E , Canoves J , Sanchis J , Moratal D , Bodi V 
Published: October 2024

Abstract

Background
Coronary artery calcium (CAC) score improves cardiovascular risk stratification in asymptomatic individuals. However, whether CAC can be quantified in ungated thoracic computed tomography (uTCT) performed for other indications, and if this CAC score associates with cardiovascular outcomes, hasn’t been confirmed yet.

Purpose
We aim to analyse the extension of CAC and its prognostic value in terms of major adverse cardiovascular events (MACE) in patients who underwent uTCT for other indications.

Methods
We analysed a preliminary sample of 115 uTCT performed in 2015 in our hospital. We studied the presence and extension of CAC and quantified the global CAC score by Agatston method using validated software. Patients were categorized according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) categories. Cardiovascular risk factors, lipidic control and pharmacological therapy of the cohort were registered. We analysed the time to first 3P-MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, whichever occurred first. A p-value &lt;0.05 was considered statistically significant.

Results
Mean age of the cohort was 60.8±16.1 years (53% male, 53% smokers). Mean LDL-cholesterol was 121.67±34.91 mg/dL, and 35.1% received lipid-lowering therapy. In more than half (n=59, 51.3%) of the population CAC was detected. Mean CAC score was 312.99±774.48 Agatston units, and patients were categorized in CAC-DRS category 1 (n=19, 16.5%), category 2 (n=15, 13%) and category 3 (n=25, 21.7%). Patients with CAC were older (71±10.1 vs. 50.1±14.2 years, p&lt;0.001), had higher burden of cardiovascular risk factors and prevalence of chronic kidney disease (CKD; n=8, 13.6% vs. n=1, 1.8%, p=0.03) and higher levels of triglycerides (143.2±80.5 vs. 106.8±36.2 mg/dL, p=0.004), but not LDL-cholesterol. Eleven (9.6%) patients presented 3P-MACE during a mean follow-up of 6.55±2.82 years. CAC score independently predicted 3P-MACE (HR 1.06 [1.01-1.11] per 100 Agatston units, p=0.02) along with CKD (HR 6.94 [1.58-30.46], p=0.01) and basal glucose levels (HR 1.03 [1.02-1.04] per mg/dL, p&lt;0.001).

Conclusions
CAC can be incidentally detected in more than half of our unselected cohort of patients undergoing uTCT for other indications. CAC score quantification by Agatston method is feasible in uTCT and associates with a higher risk of MACE during follow-up.Incidental CAC detection in uTCT
Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use
Authors: Caglayan S , Gronnli O K , Hoye A 
Published: October 2024

Abstract
Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use

Background and importance
Adverse childhood experiences are potentially preventable and traumatic events that occur during childhood. Childhood exposure to trauma is highly prevalent and adults who had adverse childhood experiences are at increased risk of developing physical conditions. However, effect of adverse childhood experiences on health outcomes remains underrecognized.

Aim
Here, we aimed to measure the association of cumulative adverse childhood experience with adult physical condition and use of prescription medicines in general population.

Methods
We conducted a cross-sectional analysis using the population-based health study including 21083 participants at age 40 years or older. Self-reported adverse childhood experiences before age at 18 years, present or previous cardiometabolic conditions, and present or previous use of medications prescribed for cardiometabolic conditions were used in our analysis. Cox proportional hazards regression was used to estimate age, sex, smoking, education, and income-adjusted risk of cardiometabolic condition and prescription medicine use after adverse childhood experiences. Association of multimorbidity and using multiple prescription medicines with adverse childhood experience was analyzed using generalized linear model with ordinal classification.

Results
We found that having a history of adverse childhood experience was associated with increased risk of subsequent cardiometabolic conditions; hazard ratios ranged from 1.117 (95% CI, 1.054 – 1.185) to 1.341 (95% CI, 1.181 – 1.522). Furthermore, adverse childhood experience was associated with multimorbidity of cardiometabolic conditions (odds ratio [OR], 1.195; 95% CI, 1.117 – 1.279) and increased risk of using multiple prescription medicines (OR, 1.131; 95% CI, 1.057 – 1.210). Notably, we observed the dose – effect relationships of cumulative adverse childhood experience to the increased risk of 5 among 6 cardiometabolic conditions and to the increased risk of using 4 among 6 prescription medicines. Furthermore, cumulative adverse childhood experience had the dose – effect associations with multimorbidity of cardiometabolic conditions (ORs ranged from 1.120 [95% CI, 1.033 – 1.214] to 1.526 [95% CI, 1.276 – 1.825]) and using multiple prescription medicines (ORs are 1.393 [95% CI, 1.195 – 1.624] and 1.572 [95% CI 1.315 1.879]).

Conclusions
and relevance: Our findings implicate cumulative adverse childhood experience as a risk factor for later cardiometabolic conditions and use of medicines prescribed for cardiometabolic conditions. Our results are significant by suggesting inquiry into adverse childhood experience exposure during clinical consultations, services to alleviate the burden and increasing resilience in addition to strategies aimed at prevention of cardiometabolic conditions might improve health outcomes.