bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma trimethylamine-n-oxide associates with reduced hippocampal volume and cognitive impairment in atrial fibrillation
Authors: Ziswiler T , Lee P , Luciani M , Diteepeng T , Allemann M , Aeschbacher S , Pirpamer L , Duering M , Von Eckardstein A , Mueller D , Conen D , Kuehne M , Bonati L H , Osswald S , Beer J H
Published: October 2024

Background/Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia in modern society and affected patients appear particularly vulnerable to cognitive dysfunction. Yet, the pathomechanism of this association other than thromboembolism (TE) is not fully understood. We have shown earlier an association of cognitive dysfunction with the gut microbiome derivate trimethylamine-N-oxide (TMAO), which predominantly results from the consumption of red meat. We therefore hypothesized that TMAO may affect hippocampal volume (HV) as a brain structure relevant for cognition.

Purpose

To demonstrate the structure-function correlation of high TMAO levels with reduced cognitive function and lower HV in a large cohort of patients with atrial fibrillation.

Methods

We included 1’736 patients with confirmed AF from the Swiss-AF-cohort with both, available blood samples for TMAO measurement and with brain magnetic resonance imaging (bMRI) for the determination of HV at baseline. TMAO levels were measured by liquid chromatography-mass spectrometry (LC-MS). bMRI were obtained by 1.5 or 3 Tesla scanners. HV was assessed by the FreeSurfer software (v 7.4.0) subregion segmentation module and normalized by using Sequence Adaptive Multimodal SEGmentation (SAMSEG) to determine the segmentation based intracranial volume. Patients were divided into TMAO quartiles (Q1: 0.6-3.8, Q2: 3.8-5.5, Q3: 5.5-8.5, Q4: 8.5-164.3μmol/l). Their TMAO levels were compared with their HV (unit = mm3) in linear mixed effect models adjusted for multiple covariates (model 1: age, sex, total intracranial volume (ICV), education level; model 2 = model 1 + smoking status, body mass index (BMI), alcohol consumption, physical activity; model 3 = model 2 + hypertension, coronary artery disease, previous stroke, geriatric depression scale). We assessed both unilateral HV (right = RHV, left = LHV) and bilateral HV standardized by the individual total ICV.

Results

Overall mean age was 72.5 years (+/-8.4 SD), 27.2% were female. Most of the patients were well educated (39.4% advanced, 48.8% middle education) and 44% never smoked. After multivariable adjustments, patients in the highest TMAO quartile showed a significant reduction of bilateral HV volume of 93.4mm3 (95% CI -179.0 to -7.8, p = 0.03). The RHV appeared more affected and was significantly reduced by 48.2mm3 (CI -93.4, -3.0, p=0.04), whereas LHV was decreased by 44.2mm3 (-89.4, 1.0, p=0.06) in the highest TMAO quartile.

Conclusion(s)

TMAO negatively associates with bilateral HV in patients with AF. Our results suggest a structure-function-correlation between high TMAO levels and cognitive dysfunction. The findings may be relevant for the high TMAO-exposed patients and advocates for the importance of (possible dietary) prevention in AF.
Efficacy of diet with low glycemic index on coronary artery disease
Authors: Uzokov J , Alyavi B A , Payziev D D , Abdullaev A X
Published: October 2024

Background

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide, with dietary factors playing a significant role in its pathogenesis. The glycemic index (GI) of foods has been implicated in cardiovascular health, with low GI diets hypothesized to reduce the risk of CAD and improve outcomes [1]. However, the efficacy of low glycemic index diets in patients with established CAD remains uncertain.

Objective

This study aimed to assess the efficacy of a low glycemic index diet on coronary artery disease by evaluating changes in cardiovascular biomarkers and major adverse cardiovascular events (MACE) using Kaplan-Meier analysis and Cox regression models.

Material and Methods

A randomized controlled trial was conducted involving 156 patients with established coronary artery disease (Aged 43-75 years, mean age 62.4±12.7 years, male=57%). Participants were randomized to either a low glycemic index diet group or a control group receiving standard dietary advice. Changes in cardiovascular biomarkers, including lipid profiles, inflammatory markers, and glycemic control parameters, were assessed at baseline and follow-up visits. Major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, were recorded over a median follow-up period of 6.2±2.4 years. Kaplan-Meier analysis and Cox regression models were used to evaluate the association between adherence to a low glycemic index diet and MACE.

Results

Preliminary analysis demonstrated significant improvements in cardiovascular biomarkers, including reductions in LDL cholesterol, triglycerides, and inflammatory markers, in the low glycemic index diet group compared to the control group (p < 0.05). Kaplan-Meier analysis revealed a lower incidence of MACE in patients adherent to the low glycemic index diet compared to non-adherent patients (log-rank p < 0.05). Cox regression analysis confirmed the independent association between adherence to a low glycemic index diet and reduced risk of MACE after adjusting for confounding factors (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.95; p < 0.001).

Conclusion

Our findings suggest that a low glycemic index diet may be efficacious in reducing cardiovascular risk and improving outcomes in patients with coronary artery disease. Adherence to a low glycemic index diet was associated with favorable changes in cardiovascular biomarkers and a reduced risk of major adverse cardiovascular events. Further research is warranted to confirm these findings and elucidate the mechanisms underlying the cardioprotective effects of low glycemic index diets.
Prevalence of cardiomyopathies and myocardial scar in patients with non-complicated premature ventricular beats: a CMR study
Authors: Alos B , Coulibaly D , Christiaens L , Bouleti C
Published: October 2024

Introduction

Frequent or symptomatic premature ventricular beats (PVBs) in subjects with no personal or family history of cardiac disease or sudden death is a recurrent motive for cardiac magnetic resonance (CMR) prescriptions. This represents a significant burden on healthcare services, given the low availability of CMR technique. If CMR is a recommended imaging modality in patients with history of cardiac arrest due to ventricular arrhythmia, sustained ventricular arrhythmias or when first-line tests are abnormal, its diagnostic value in this specific setting has not been evaluated.

Purpose

To determine the prevalence of significant CMR abnormalities (myocardial fibrosis, arrhythmogenic cardiomyopathies) in patients with no personal nor family history of cardiac disease and non-complicated PVBs.

Methods

Between September 2010 and July 2021, 416 healthy adults with no personal nor family cardiac disease history underwent CMR at our institution to explore non complicated PVBs, and were retrospectively included (Figure 1). Right and left ventricular (RV/LV) function and dimensions were systematically evaluated on CMR, as the presence of myocardial late gadolinium enhancement (LGE). Criteria for cardiomyopathies (hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), ARVD), the presence and location of myocardial fibrosis were looked after.

Results

A total of 605 patients were referred for CMR to explore frequent PVBs, representing 14% of all tests performed during this period. Among them, 12 patients (3%) presented significant myocardial abnormalities possibly related to PVBs: 2 patients had sequelae of myocardial infarction and 3 of myocarditis, 1 patient had criteria of HCM and 1 of ARVD, finally 5 presented non-specific myocardial fibrosis (septal mid-wall LGE). In addition, after a mean follow-up of 5 years, there was no death in patients with abnormal CMR, and only 2 patients underwent transcatheter ablation for focal non complicated but symptomatic PVBs. There was no hospitalization for heart failure.

Conclusion

In patients with non-complicated PVBs and no history of cardiac disease, the rate of cardiomyopathy pattern or myocardial scar on CMR is very low (3%). In this specific population, events were very rare: frequent isolated PVBs, even when associated with myocardial abnormalities, were a benign condition in our study. Given the high volume of patients referred for this indication in daily practice (14% of total CMRs in our center), the limited availability and high costs of CMR, and the difficulties of CMR sequences acquisition in the context of frequent PVBs (possibly leading to misdiagnosis), these data suggest that we should refine the selection of patients undergoing CMR for PVBs exploration.
Exercise-induced cardiac troponins in long-distance walkers: a preliminary observation.
Authors: Lamers S , Janssen S L J E , Vroemen W H M , Berge K , Denessen E J S , Aengevaeren V L , Bekers O , Hopman M T E , Eijsvogels T M H , Mingels A M A
Published: October 2024

Background

Elevated concentrations of cardiac troponin (cTnT and cTnI), the preferred biomarker to diagnose myocardial infarction, can be detected in other (cardiac) conditions and even post-exercise. Whether these exercise-induced elevations reflect a (patho)physiological process, as well as their clinical implications, is unknown. In this preliminary study, pre- and post-exercise high-sensitivity cTn (hs-cTnT and hs-cTnI) concentrations were investigated in long-distance walkers.

Purpose

Gain insight of elevated cTnT and cTnI concentrations post-exercise in long-distance walkers.

Methods

From 478 participants, walking 30-50 km on the first day of the 4Daagse 2023, blood-samples were collected pre- and <6h post-exercise. In addition, health and exercise questionnaires were conducted. Hs-cTnT (Roche) and hs-cTnI (Abbott) concentrations were determined and the unisex, female and male Upper Reference Limit (URL) were according to package inserts (Roche: 14 ng/L, 9 ng/L, 16 ng/L, Abbott: 26 ng/L, 16 ng/L, 34 ng/L).

Results

Participants (51% female) were 57±7.6 years (mean±SD). At baseline, median [IQR] hs-cTnT and hs-cTnI were 5.9 [4.5-8.0] and 1.7 [1.1-2.9] ng/L, which increased significantly post-exercise to 8.7 [6.4-12.4] ng/L (P<0.001) and 5.2 [3.1-9.5] ng/L (P<0.001). Pre-exercise, the unisex-URL for hs-cTnT was exceeded by 4.4% walkers and for sex-specific URLs, this resulted in 6.6% females and 3.8% males. For hs-cTnI, the unisex-URL was exceeded by 0.6%, as for sex-specific URLs, 0.8% females and 1.3 % males surpassed. Post-exercise, hs-cTnT URLs were exceeded by 18.2%, 35.1%, 16.5% and as for hs-cTnI post-exercise, 7.3%, 11.6%, 3.8% for unisex, female and male. Alternatively, the absolute median delta difference was 2.4 [0.9-4.6] ng/L for hs-cTnT and 3.0 [1.6-5.7] ng/L hs-cTnI.

Conclusion

Post-exercise long-distance walkers had significantly increased hs-cTnT and hs-cTnI concentrations, in particular in women when using sex-specific cutoffs. In order to understand clinical implications of these findings, status of cardiac vascular diseases, risk-factors and exercise characteristics will be analyzed in the future.
Trends in risk factor prevalence in young adults experiencing acute coronary syndrome
Authors: Segal O , Dobrecky-Mery I , Muslavi O , Meir Y , Koppel F
Published: October 2024

Introduction

While for many decades the prevalence of coronary artery disease (CAD) and acute coronary syndrome (ACS) has been declining, it seems as this trend has reached a plateau, mostly in developing countries, but also in developed countries due to reasons such as immigration and unhealthy lifestyle concomitant to the pandemic of obesity and metabolic syndrome. Still, CAD remains the leading cause of death globally. Preventive cardiology guidelines addressed adequate control of traditional risk factors in order to reduce CAD burden, mortality and morbidity but to lesser extent fewer resources were invested for the younger population in their third or fourth decade for implementing this practical guideline. As global obesity pandemic emerged over the past decades, it emphasizes the need to re-evaluating risk factors, particularly the role of obesity and metabolic syndrome, in contributing to the rising incidence of ACS among the younger population.

Purpose

The study aims to analyze trends in risk factors among young adult which presented with ACS from 2005 to 2022. Results may inform targeted interventions and deepen understanding of ACS pathophysiology and severity.

Methods

The study encompassed 712 patients hospitalized between 2005 and 2022. Comparable groups were analyzed, including temporal changes, ST-elevation myocardial infarction (STEMI) vs. non-ST-elevation myocardial infarction (NSTEMI), different age groups, and various ethnicities. Categorical values were thoroughly examined, yielding insightful results.

Results

Temporal changes revealed that patients presenting with ACS before 2014 exhibited a higher incidence of Dyslipidemia and familial history (p=0.002 and p=0.005). Conversely, in the latter period, overweight and diabetes were more significant (p<0.001 and p=0.0176). In the STEMI vs. NSTEMI group, smoking was more prevalent in the STEMI group (p=0.0449), while diabetes, Dyslipidemia, and hypertension were more significant for the NSTEMI group (p=0.022, p=0.009, p<0.001). For the age group, the only observed difference was in hypertension for the 40-45 and 45-50 age group (p=0.0463). In the ethnicity group, individuals of Arab origin exhibited higher rates of smoking and familial cardiac background (p<0.001 and p=0.03), while in the non-Arab group, obesity was more significant (p<0.001).

Conclusion

The observed changes in the distribution of risk factors among patients with CAD align with global trends, indicating an increase in obesity. Belonging to the overweight population, prior to obesity, pose a prominent risk factor for ACS. Smoking remains a significant factor, with higher rates in patients presenting with STEMI, aligning previous research and re-emphasize the importance of prevention. Different demographic groups may exhibit distinct risk factors contributing to the common endpoint of CAD. Tailored intervention strategies considering diverse risk profiles are essential for effective coronary disease prevention.
The incremetal predictive value of pulse wave velocity over score2 in the setting of primary cardiovascular prevention: a 6-year follow-up study
Authors: Ikonomidis I , Thymis J , Georgiopoulos G , Pavlidis G , Katogiannis K , Kostelli G , Vlastos D , Triantafyllidi H , Delialis D , Mavraganis G , Lambadiari V , Stamatelopoulos K
Published: October 2024

Background

Arterial stiffness has been shown to be an independent additive predictor to several traditional risk factors regarding cardiovascular events.

Purpose

We studied in a prospective cohort whether arterial stiffness has an additive value to SCORE2 in predicting cardiovascular risk.

Methods

In 747 healthy subjects, we measured carotid-to-femoral pulse wave velocity (PWV), a marker of aortic stiffness. We prospectively documented the incidence of cardiovascular events (major adverse cardiovascular events [MACE]-death, stroke and myocardial infarction) during a 6-year follow-up period.

Results

Sixty MACE were recorded. Increased values of PWV predicted greater risk for MACE in a model including diabetes, smoking, hypertension, hyperlipidemia, sex and age (hazard ratio (HR)=1.09; 95%CI=1.03 – 1.14; p<0.001, Chi-square change = 8.05; p=0.004; c-statistic increased from 0.74 (0.66 – 0.81) to 0.77 (0.71 – 0.83), p=0.025). PWV was an independent and additive predictor of events when added in a model encompassing the SCORE2 and diabetes (HR=1.07; 95%CI=1.04 – 1.11; p<0.001, Chi-square change = 43.12; p<0.001, c-statistic increased from 0.73 (0.66 - 0.80) to 0.76 (0.70 - 0.82); p=0.014). Also PWV predicted significantly the occurrence of events in all subgroups of each risk factor (for smokers and non-smokers: HR=1.31 and HR=1.11 respectively; for participants with hypertension and participants without hypertension: HR=1.23 and HR=1.12 respectively; for participants with hyperlipidemia vs participants without hyperlipidemia: HR=1.19 and HR=1.12 respectively; for participants with diabetes and participants without diabetes HR=1.19 and HR=1.12 respectively) (p<0.05 for all subgroups).

Conclusion

PWV confers an additive prognostic value to SCORE2 in primary prevention.
Association of neutrophil-percentage-to-albumin ratio with mortality in cardiovascular disease patients complicating abnormal glucose metabolism
Authors: Zhang Y , Shi C , Li Y , Zhang Z , He P , Liu Y
Published: October 2024

Background

Cardiovascular disease (CVD) patients complicated with abnormal glucose metabolism are at especially higher risk of cardiovascular mortality. Therefore, it is critical to identify and manage CVD patients complicated with abnormal glucose metabolism at higher risk of mortality to improve the overall prognosis of such population. Evidence regarding neutrophil-percentage-to-albumin ratio (NPAR) and survival outcomes in CVD patients complicated with abnormal glucose metabolism remains scarce.

Purpose

To prospectively evaluate the association of NPAR with cardiovascular and all-cause mortality in CVD patients complicating abnormal glucose metabolism.

Methods

This study included 3,897 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Mortality status was determined by access to NHANES public-use linked mortality files. Multivariate Cox proportional hazards regression analysis, threshold effect analysis, and stratified analysis were performed to examine the association of NPAR with cardiovascular and all-cause mortality. The prognostic value of NPAR was further assessed by time-dependent receiver operating characteristic (ROC) curve analysis.

Results

During a median follow-up period of 76 months, there were 703 cardiovascular deaths and 1,727 all-cause deaths. After adjusting for confounders, NPAR was positively nonlinear associated with cardiovascular and all-cause mortality. Furthermore, the thresholds of NPAR were identified for cardiovascular and all-cause mortality as 14.10 and 14.49, respectively. When the NPAR exceeded the thresholds, a 1-unit increase of NPAR was associated with a 16% and 18% greater hazard ratio (HR) for cardiovascular (HR = 1.16, 95% confidence interval (CI) = 1.08–1.23, P < 0.001) and all-cause mortality (HR = 1.18, 95% CI = 1.13–1.22, P < 0.001), respectively. The time-dependent ROC curve analysis showed that the NPAR had moderate prognostic value and outperformed the neutrophil-to-lymphocyte ratio for predicting short-term survival outcomes.

Conclusions

The NPAR is a superior predictor of survival outcomes in CVD patients complicated with abnormal glucose metabolism. The thresholds of 14.10 and 14.49 for cardiovascular and all-cause mortality, respectively.
Does the LPA genotype have a role in coronary artery disease risk beyond Lp(a) values?
Authors: Sa D , Mendonca M I , Sousa F , Abreu G , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Palma Dos Reis R
Published: October 2024

Introduction

High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD.

Goal: To evaluate if LPA rs3798220 T>C is associated with CAD beyond its effect on Lp(a) levels.

Methods

We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD.

Results

Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p<0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p<0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025).

Conclusion

LPA rs3798220 T>C may be an independent risk factor for CAD beyond the effect of rising Lp(a) levels. Perhaps testing for the genetic determinants of Lp(a) relative to direct measurement of Lp(a) level could provide additional prognostic utility.
Intraindividual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate-risk
Authors: Harb T , Ziogos E , Blumenthal R S , Gerstenblith G , Leucker T M
Published: October 2024

Background

Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease and outcomes. Levels are predominantly genetically determined and repeat measurements are traditionally considered unlikely to be useful. However, the temporal variation of Lp(a) is not well characterized and it is unclear whether a single measure of Lp(a) is sufficient to assess cardiovascular risk in all individuals.

Purpose

To determine the intraindividual variability of Lp(a) and whether a repeated measure reclassified Lp(a)-specific cardiovascular risk using the European Atherosclerosis Society (EAS) consensus statement risk categories.

Methods

This retrospective cohort study analyzed initial and repeated Lp(a) measures obtained using the same laboratory assay from 609 individuals in the Nashville Biosciences database accessed through the American Heart Association Precision Medicine Platform. Categorical variables are presented as counts (%) and compared using Fisher’s exact test. Continuous variables are presented as mean ± standard deviation or median (Q1-Q3), tested for normality using the Shapiro-Wilk test, and compared using parametric and nonparametric tests where appropriate. The Spearman’s Rank correlation coefficient was used to assess the relationship between two variables. The significance level was set at p<0.05.

Results

Median age was 52.5 (37.1-62.8) years, 45% were women, 80.3% were White patients, 13.3% were Black patients, 1.6% were Asian patients, and 4.8% were other/unknown patients. In terms of relevant comorbidities, 41% had ischemic heart disease, 24.1% had chronic kidney disease, and 13.5% had liver disease. The median time between the two Lp(a) measures was 1.07 (0.5-2.1) years.

Our analysis shows a significant difference between the paired Lp(a) values (p<0.05), with 38.1% [95% CI 34.2%-42%] changing by ≥10mg/dL, and 40.5% [95%CI 36.6%-44.3%] changing by >25%. There was a positive correlation between the baseline Lp(a) levels and the absolute changes in Lp(a), (r=0.59, p<0.01). The proportions of individuals with variability are similar in those who were never on the potentially Lp(a)-altering agents (statin, niacin, or PCSK9 inhibitor drugs) (n=91), with 32% [95%CI 22.4%-41.6%] changing by ≥10mg/dL, and 34% [95%CI 24.3%-43.7%] changing by >25%. While over 90% of those whose values were initially in the EAS low-risk and high-risk categories remained in those categories, 53% of those in the intermediate "grey-zone" category transitioned to either the low (20%)- or the high (33%)- risk category (Figure).

Conclusion(s)

Temporal-related changes in Lp(a) variability were present in many individuals and should be included in calculating the expected effect sizes in future studies targeting Lp(a). A repeat Lp(a) measure may allow more precise Lp(a)-specific cardiovascular risk prediction for individuals whose initial value is in the EAS-defined intermediate "grey-zone" category.
Lipoprotein(a) metabolomic and proteomic features and atherosclerotic cardiovascular disease in young, asymptomatic adults
Authors: Goonewardena S , Jurga T J , Damodaran D D , Thyagarajan B T , Jacobs D J , Shore S S , Brandt E B , Tanriverdi K T , Freedman J F , Bittner V B , Lloyd-Jones D L J , Do R D , Rosenson R R , Shah R S , Murthy V M
Published: October 2024

Background

Lipoprotein (a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Although Lp(a) is a powerful genetic risk factor for ASCVD, the pathways that mediate this risk and the associated metabolomic and proteomic features that capture this risk are unknown.

Methods

In young, asymptomatic Coronary Artery Risk Development in Young Adults (CARDIA) participants, we defined the relationships between Lp(a) and metabolomic (n=563)/proteomic (n=184) features, derived quantitative Lp(a)-omic scores from these features, and related these quantitative scores to ASCVD phenotypes.

Results

CARDIA subjects had a mean age of 32 years and a median follow-up of 27 years. In the overall cohort (n=3920), Lp(a) levels at year 7 (Y7) were significantly associated with ASCVD endpoints, including hs-CRP, coronary artery calcification (CAC), death, and incident CHD (Figure 1A). In the subcohort (n=2290) that had measurements of Lp(a), proteomics, and metabolomics, Y7 Lp(a) levels were associated with distinct proteomic and metabolomic features indicative of immune responses, lipoprotein metabolism, atherogenesis, and arginine/steroid biosynthesis. Using machine learning approaches, Lp(a) metabolomic, proteomic, and transomic quantitative scores were derived. After adjustment, the Lp(a) transomic score was more strongly related to incident CAC, degree of CAC, CRP, and incident CHD than Lp(a) itself (Figure 1B).

Conclusions

To our knowledge, this is the first study to examine the relationship between Lp(a), metabolomic/proteomic features, and ASCVD phenotypes in young, asymptomatic adults. The multi-omics approaches employed here provide insight into the pathobiology of Lp(a)-driven ASCVD and enable more nuanced mechanistic risk assessment compared with Lp(a) alone.
Prediction of the burden and characteristics of coronary plaques by cardiorespiratory fitness
Authors: Fossdal K , Joergensen A , Letnes J M , Wiseth R , Dalen H
Published: October 2024

Background

Cardiorespiratory fitness (CRF) and coronary plaque burden are both important predictors of mortality. Although mortality of coronary heart disease (CHD) is reduced, prevalence remains high and there is a need to improve early detection and preventive measures. How CRF relates to coronary plaque burden and composition in the general population is largely unknown.

Purpose

The aim was to study the relationship between CRF and the total coronary plaque burden, including subgroups of coronary plaques, in subjects without known CHD.

Methods

A random sample of participants from a large population-based echocardiographic reference range study aged 55-70 at baseline was included. Coronary plaque burden was assessed, on average, 4.0 years after the baseline evaluation using coronary computed tomography angiography (CCTA). The burden and characteristics of the coronary plaques were evaluated using a validated, commercially available, semi-automatic software that assessed all coronary territories including the left main, left anterior descending, circumflex, and right arteries. Coronary plaques were classified as dense calcified plaques, plaques with necrotic core, fibrous, and fibrous-fatty plaques. Baseline measures included cardiovascular risk factor assessment and measurement of peak oxygen consumption (VO2peak) assessed by treadmill cardiopulmonary exercise testing.

Linear regression models were used to assess the impact of VO2peak on coronary plaque burden. In Model 1, we adjusted for sex and age, while Model 2 also included adjustments for non-HDL cholesterol, HbA1c, systolic blood pressure, smoking status, and body mass index.

Results

Of 845 invited to undergo CCTA, 707 (51% females) underwent CT scanning. Of these, 699 scans had acceptable quality for further analyses. Table 1 shows baseline characteristics and Table 2 shows the associations of VO2peak with coronary plaque burden. In the fully adjusted Model 2, there was a significant negative association of VO2peak with total plaque burden (β -0.18, R2 15%, p<0.001), while the association was not significant in Model 1 (p=0.54). Similarly, higher VO2peak significantly predicted a lower burden of dense calcified plaques, plaques with necrotic core, and fibrofatty plaques in both models (R2 3-17%, p≤0.01). The results were consistent whether the coronary plaques were evaluated across the entire coronary arteries (down to a diameter of 1.5 mm) or solely in the proximal segments. However, the predictive power of the models was relatively low with R2 of maximum 17%.

Conclusion

In a population without known CHD, CRF explained a modest part of the variation in coronary plaque burden. Considering CRF in risk prediction may enhance coronary artery disease prevention beyond traditional risk factors.
AI-enhanced detection of coronary inflammation predicts 10-year risk for cardiac mortality and MACE in individuals with no or minimal coronary atherosclerosis on routine CCTA
Authors: Chan K , Wahome E , Nicol E , Mittal T K , Petersen S E , Pugliese F , Adlam D , Desai M , Patel P , Tomlins P , Neubauer S , Channon K M , Blankstein R , Deanfield J , Antoniades C
Published: October 2024

Background

Coronary CT angiogram (CCTA) is one of the first line investigations for patients with chest pain suspected of coronary artery disease (CAD). Current CCTA interpretations mainly focus on luminal obstruction, which is identified in the minority of patients, whereas the majority who have no or minimal atherosclerotic plaques visible on CCTA are often provided with reassurance. However, residual risk from inflammation that drives atherosclerosis and plaque vulnerability are not captured with luminal stenoses alone. Fat attenuation index (FAI) Score quantifies coronary inflammation on routine CCTA, and integrate with clinical risk factors/plaque burden in an artificial intelligence enabled risk algorithm (AI-Risk) that could help to risk stratify this patient group.

Purpose

To evaluate the prognostic value or FAI Score and AI-Risk in the risk stratification of patients with no or minimal atherosclerosis.

Methods

In a nested cohort within the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality and major adverse cardiac events (MACE, including myocardial infarction, new onset heart failure, cardiac mortality). CADRADS 2.0 classification 0 or 1 were used to define no or minimal luminal stenoses. FAI Score was calculated for each of the 3 epicardial coronary arteries.

Results

A total of 1,678 patients had no or minimal atherosclerosis on CCTA [median (IQR) age 53(45-63), 49.8% male]. Cardiac mortality occurred in 3.1% and MACE occurred in 8.8% of the patients during the follow-up period. Patients at the lowest quartile of FAI Score or low/medium AI-Risk classification showed very low event rate during follow up. Patients with the highest quartile of LAD FAI Score showed 9 times higher risk of cardiac mortality (Panel A) and 5 times higher risk of MACE (Panel B) compared to those at lowest quartile. Similar findings were observed for LCX and RCA. Finally, integrating coronary inflammation with clinical risk factors and plaque burden, patients at very high AI-Risk classification showed 5 times higher risk of cardiac mortality (Panel C), and 4 times higher risk of MACE (Panel D) compared to those with low/medium risk classification.

Conclusion

Coronary artery inflammation measured by FAI Score could stratify the risk of patients with no or minimal coronary atherosclerosis on CCTA, and could help to guide early preventative treatments.
Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program
Authors: Moreira M , Frias D , Schmidt C , Alves Dias V , Magalhaes S , Santos M , Torres S
Published: October 2024

Introduction

Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients.

Purpose

To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation.

Methods

Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization.

Results

Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p<0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p<0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p<0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006).

Conclusions

In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.
Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events
Authors: Dykun I , Khoury M , Rassaf T , Mahabadi A A
Published: October 2024

Background

Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy.

Purpose

We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints.

Methods

We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject

Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events".

Results

A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of < vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (<3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown).

Conclusion

Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.
Changes in lipid lowering therapy one year after percutaneous coronary intervention: data from the large contemporary ZON-HR registry
Authors: Peeters D A M , Janssen S , Woelders E C I , Winkler P J C , Damman P , Luijkx J J P , Remkes W S , Van 'T Hof A W J , Van Geuns R J M
Published: October 2024

Background

Patients who underwent percutaneous coronary intervention (PCI) should receive at least high-intensity statin therapy according to current ESC guidelines to prevent ischemic events. However, previous studies have shown that about 80% of the patients using high-intensity statin monotherapy are not reaching the low density lipoprotein- cholesterol (LDL-C) target value of below 1.4 mmol/L. This means that additional lipid lowering therapy is necessary in most patients. The ‘Zuid-Oost Netherlands Heart Registry’ (ZON-HR) is a multicentre, prospective registry designed to improve secondary prevention after PCI by a patient-tailored approach.

Purpose

To describe changes in lipid lowering therapy one year after PCI in the ZON-HR.

Methods

Since November 2020 data from all patients who underwent PCI in one of the four participating ZON-HR hospitals were included. In 4811 patients one year follow-up was completed. Patients with known discharge medication and medication at one year after PCI were included in the analyses (n=3487). Combination therapy was defined as having at least two different lipid lowering medications prescribed. The association between predefined variables and combination therapy at one year post PCI was assessed with multivariable logistic regression to adjust for baseline differences.

Results

The mean age of the patients was 67.7 ± 10.7 years, 72.4% was male and the baseline LDL-C value was 2.7 ± 1.1 mmol/L. While patients with an acute coronary syndrome (ACS) had higher LDL-C values at baseline, they received combination of lipid lowering therapy at discharge less often compared to patients with a chronic coronary syndrome (CCS) (7.9% vs 11.5%, p<0.001) (table 1). After one year, both ACS and CCS patients were treated more often with combination therapy (20.1% vs 23.3%, p=0.047). However, still only about 20% of the patients were receiving combination therapy one year after PCI. In the ACS population, younger patients with higher LDL-C values at baseline and previous myocardial infarction had a higher chance of receiving combination lipid lowering therapy one year after PCI (table 2).

Conclusion

Additional lipid lowering medication is needed, besides high-intensity statins, in order to reach the strict LDL-C target values in very high risk patients. However, the step-up from mono- to combination lipid lowering therapy only occurs in about 10% of the patients. Lipid lowering combination therapy is prescribed more often in CCS patients compared to ACS patients, both at discharge and one year after PCI.Baseline values and combination therapyPredictors combination therapy at 1 year
Modifying effect of obesity status on the association between low-density lipoprotein cholesterol with incident hemorrhagic stroke: evidence from a community-based longitudinal cohort study in China
Authors: Zhang L , Luo X Y , Liu Y K , Fan F F , Zheng B , Zhang Y , Li J P
Published: October 2024

Background

Previous results on the association between lipids and hemorrhagic stroke were controversial. Modifying effect of obesity on the association between low-density lipoprotein cholesterol (LDL-C) and hemorrhagic stroke risk in the Chinese community-based population remains unclear.

Objectives

We aimed to investigate the association between LDL-C and hemorrhagic stroke risk in the Chinese community-based population. In addition, we aimed to explore the potential modifying effect of obesity status, particularly abdominal obesity, on this relationship.

Methods

A total of 7899 eligible subjects, without history of stroke and myocardial infarction, and any use of lipid-lowering medication at baseline, were enrolled in this study. Levels of LDL-C, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were assessed at baseline. The primary endpoint was the hemorrhagic stroke. Abdominal obesity was defined as waist circumference > 90 cm in men and > 85 cm in women.

Results

Of all participants, the mean age was 56.13 ± 8.87 years, 2848 (36.1%) were male. During a mean 9.71-year follow-up, 66 hemorrhagic strokes occurred. After multivariable adjustment (Figure 1), compared to participants with LDL-C levels 2.6 – 3.4 mmol/L, those with LDL-C levels < 1.8 mmol/L had 3.32 times the risk (hazard ratio [HR]: 3.32; 95% confidence interval [CI]: 1.24, 8.84) of incident hemorrhagic stroke. Compared with participants with TC levels 3.1 – 5.2 mmol/L, HR (95% CI) was 7.82 (2.36, 25.90) for hemorrhagic stroke in those with TC < 3.1 mmol/L. We observed no significant associations between TG or HDL-C levels and hemorrhagic stroke risk. Interaction effects were found between obesity and LDL-C for incident hemorrhagic stroke. Accordingly, significant associations between low LDL-C level (< 1.8 mmol/L) and the risk of incident hemorrhagic stroke were found only among abdominal obesity participants (HR: 3.76; 95% CI: 1.01, 13.97), or those with body mass index (BMI) > = 24 kg/m2 (HR: 3.74; 95% CI: 1.24, 11.34) (Figure 2).

Conclusions

LDL-C levels < 1.8mmol/L and TC levels < 3.1mmol/L were associated with increased risk of hemorrhagic stroke. Modifying effect of obesity status on the association between low LDL-C level and hemorrhagic stroke was observed in our study.
Cardiovascular events in patients treated with bempedoic acid vs. placebo: systematic review and meta-analysis
Authors: Mutschlechner D , Tscharre M , Huber K , Gremmel T
Published: October 2024

Aims

Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid versus placebo in patients with hyperlipidemia.

Methods

A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As primary endpoint we analysed three-point major adverse cardiovascular events (MACE) consisting of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke. The analysis was carried out using the odds ratio as the outcome measure. Due to the expected heterogeneity across studies a random-effects model was fitted to the data.

Results

Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo). Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84 [95% CI 0.76-0.96]; p<0.001; I2=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; p=0.20, I2=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; p=0.49; I2=18%).

Conclusion

Bempedoic acid reduced non-fatal MI in patients with hyperlipidemia, whereas it had no significant effect on stroke and all-cause mortality.Figure.Forest plot for three-point MACE
Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study
Authors: Thompson W , Jeong I , Basque S , Abdel-Qadir H , Austin P C , Ko D T , Famiyeh I , Chu A , Fang J , Odutayo A , Jackevicius C , Godoy L C , Lee D S , Udell J A
Published: October 2024

Introduction

Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events.

Methods

We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders.

Results

Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17).

Conclusions

In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome