bluuebunny/crossref_metadata_2025 huggingface dataset:
Histopathology and prognosis of new-onset atrio-ventricular block after coronary artery bypass graft surgery
Authors: Toiviainen A , Relander A , Lahtinen V , Ruohonen I , Lehto J , Vasankari T , Gunn J , Hollmen M , Kiviniemi T
Published: October 2024

Background

Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact.

Purpose

This study explores the association of first-degree AVB in ECG and postoperative outcome of patients with either preoperative or a new-onset AVB. Furthermore, histopathological features were analyzed to distinguish the characteristics between preoperative and postoperative AVBs compared to no AVB.

Methods

CAREBANK is a prospective study with atrial biopsies obtained at the time of open-heart cardiac surgery and long-term follow-up focusing on the adverse events. We analyzed preoperative as well as postoperative ECGs derived after index hospitalization (1-18mo) in patients undergoing CABG. The definition of first-degree AVB was PR-interval ≥200ms. The main outcome of interest was follow-up mortality. Histopathological analysis was used to assess the amount of fibrosis, cardiomyocytes, number of nuclei and macrophages.

Results

Median follow up time was 4.0 (IQR 2.7 – 5.0) years. First-degree AVB was found in 84/373 (22.5%) preoperative ECGs. Altogether 25/289 (8.7%) cases where ECG was available (after excluding preop AVB, atrial fibrillation) developed first-degree AVB after index hospitalization. New-onset first-degree AVB was associated with increased mortality (aHR 4.033 (95-CI% 1.019–15.965, p=0.047). In atrial histopathological analysis, area covered by cardiomyocytes (p=0.033) as well as area covered by nuclei (p=0.047) were smaller in those with new-onset AVB after surgery, but not in those with preoperative first-degree AVB (p=0.692 and p=0.384) as compared with controls, respectively. Similarly, the total area of fibrosis was greater in those with preoperative first-degree AVB (p<0.001), but not in those with postoperative new-onset AVB (p=0.244). When compared with controls, share of CD68 positive macrophages was similar (p=0.073), but anti-inflammatory CD206 positive M2 macrophages were absent in patients with new-onset AVB (p=0.042).

Conclusion

Patients with new-onset AVB after CABG have increased mortality in the long-term compared to those without. Histopathology identifies marked differences in macrophage populations between those with and without new-onset AVB.
An artificial intelligence-based landmark model for early detection of aortic stenosis in Cardiac MRI
Authors: Vimalesvaran K , Sanchez A , Zaman S , Galazis C , Varela M , Linton N , Howard J P , Cole G D , Bharath A A
Published: October 2024

Background

The utilisation of ratiometric intensity measures from cardiac magnetic resonance imaging (CMR) offers a promising biomarker for the diagnosis of aortic stenosis (AS)[1]. The Ao:LV ratio, an approximation of AS severity, is determined by comparing the relative blood signal intensity in the aorta and left ventricle (LV) within three-chamber (3Ch) cine sequences[1]. In patients with AS, the blood signal intensity of aortic blood above the valve is diminished compared to that within the LV in steady-state free precession (SSFP) 3Ch CMR cine. Although the Ao:LV ratio serves as a reliable indicator of AS severity, manual computation of this ratio may encounter difficulties due to visual obstructions caused by small LV cavities or prominent papillary muscles.

Purpose

This study aims to leverage artificial intelligence (AI) to automate the Ao:LV ratio analysis from 3Ch SSFP cine images and introduce the Ao:LA (aorta to left atrium) ratio, thus enhancing the diagnostic accuracy for AS severity.

Methods

Our methodology extends the ratiometric analysis to include both Ao:LV and Ao:LA ratios in three main steps: first, developing an AI-based algorithm for automated detection and tracking of cardiac landmarks; second, using these landmarks to automatically compute regions of interest (ROIs) in the cardiac chambers; and third, training and validating classification models with 5-fold cross-validation to select the most effective for AS severity classification. The final model's performance is assessed on a holdout test set. Data for model training and evaluation were sourced from CMR scans across three hospitals and two scanner types.

Results

We analysed 220 patients of which 78 patients had no AS and 122 had AS (mild AS, n = 29; moderate AS; n = 35, severe AS; n = 78). Our model yielded high efficacy in classifying AS, particularly in differentiating any grade of AS from a normal classification, which is clinically relevant. The Ao:LA ratio demonstrated a stronger correlation with AS severity class than Ao:LV, suggesting a more reliable biomarker. The proposed model demonstrated robust performance in AS classification, achieving an Area Under the Curve (AUC) of 0.845 in the automated binary classification of AS at any grade. The model exhibited a precision of 0.889, recall of 0.865, and an F1 score of 0.877 on a holdout set.

Conclusion

By the integration of AI in automating the analysis of CMR images through a novel ratiometric approach that includes Ao:LV and Ao:LA ratios, our model significantly improves the accuracy of early AS detection. This advancement enhances imaging strategies for AS evaluation, promoting more efficient and effective use of cardiac MRI sequences as a diagnostic tool for aortic stenosis. It has the potential to be implemented in real-time scanning protocols as a clinical decision support system.AI-inferred cardiac landmarks.ROC curve delineating AS prediction.
The association between periodontal disease and coronary artery disease: insights from imaging, observational and genome-wide data
Authors: Sanghvi M M , Chadalavada S , Aung N , Munroe P B , Donos N , Petersen S E
Published: October 2024

Background

Periodontal disease is the sixth most common disease worldwide. It has been suggested that it may be a contributory risk factor for coronary artery disease (CAD). From a public health perspective, prevention of periodontal disease is relatively straightforward and cost-effective: daily brushing, flossing and, where applicable, smoking cessation.

Purpose

This study utilises imaging, longitudinal and genomic data to characterise the association between periodontal disease and CAD.

Methods

481,915 individuals from the UK Biobank were included in this study, 18.9% (n = 91,022) of whom had self-reported periodontal disease. For the imaging analysis, a maximum of 59,019 had paired cardiovascular magnetic resonance (CMR) data.

Multivariable linear regression models were constructed to examine the association of periodontal disease on CMR outcomes with LV end-diastolic volume, LV mass, LV mass:volume ratio (MVR), LV ejection fraction, LV global longitudinal strain and native T1 values considered as prognostically important phenotypes. The relationship between periodontal disease and incident CAD was assessed using Cox proportional hazards regression models.

To examine the relationship of genetically-determined periodontal disease on CAD, a de novo GWAS for periodontal disease was performed and a genome-wide polygenic risk score (PRS) was constructed.

Results

Periodontal disease was associated with a significantly higher LV MVR (effect size = 0.00233, 95% confidence interval [CI] = 0.0006, 0.004) and significantly lower LV native global T1 value (effect size = -0.86 ms, 95% CI = -1.63, -0.09).

The presence of periodontal disease was independently associated with a significantly increased hazard of incident CAD (HR = 1.09, 95% CI = 1.07, 1.13) at a median follow-up time of 13.8 years (Figure 1).

Each standard deviation increase in the periodontal disease PRS was associated with increased odds of CAD (OR = 1.03, 95% CI = 1.02, 1.05) (Figure 2).

Conclusion

Using an integrated approach across imaging, observational and genomic data, periodontal disease is independently associated with biomarkers of subclinical remodelling as well as incident CAD. These findings highlight the potential importance of periodontal disease in the broader context of cardiovascular disease prevention.
Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study
Authors: Nanchen D , Tokgozoglu L , Komen J , Bardet A , Catapano A L , Ray K K
Published: October 2024

Background

Middle aged women have a faster increase in atherosclerotic cardiovascular disease (ASCVD) events than men over time. Undertreatment with guideline-recommended therapy in women may be one of the drivers for this burden.

Purpose

To compare high- or very high-risk male and female patients regarding contemporary 1-year low-density lipoprotein cholesterol (LDL-C) goal attainment, lipid-lowering therapy (LLT) intensity, and major adverse cardiovascular event (MACE) rate.

Methods

SANTORINI is an observational, prospective study that enrolled high- and very high-cardiovascular risk patients between March 2020 and Feb 2021, across 623 sites and 14 countries in Europe from primary & secondary care settings, with a further 1-year prospective follow-up. We included all patients with an LDL-C measurement at baseline and 1-year follow up (1yFU) for the current analysis. LDL-C goal attainment was defined separately for high and very-high risk categories according to 2019 ESC/EAS guidelines.

Results

Overall, 5197 males with a mean age of 65 years, and 2013 females with a mean age 66 years were included. At baseline, male patients had higher prevalence of pre-existing ASCVD (81.6% vs. 63.5%), and a lower prevalence of familial hypercholesterolaemia (8.7% vs. 17.2%) than female patients (Table 1). The proportion of patients reaching LDL-C goal improved from baseline to 1yFU, but was greater in males (22.9% and 33.3%, respectively) than females (16.9% and 24.6%, respectively). Similarly, the proportion of patients receiving no LLT decreased from baseline to 1yFU for both sexes, however, more females than males received no LLT at 1yFU (male: 20.7% to 2.7%; female: 23.9% to 3.9%). High intensity statin use increased for both sexes but was higher for males (22.2% to 27.3%) than for females (15.5% to 19.5%) at 1yFU. By contrast, PCSK9i use at baseline and 1yFU was lower for males (6.6% to 9.3%) than for females (9.8% to 13.4%). Nevertheless, the use of combination LLT at 1yFU was lower among females than males (male: 27.8% to 42.2%; female: 26.7% to 40.2%). During follow-up, MACE-4 was higher in males (5.31/100 patient years [PY]; 95% confidence interval [CI]: 4.68–5.95) than in females (3.63/100PY; 95% CI: 2.79–4.47). Similar results were observed for MACE-3 (Table 2).

Conclusions

Despite similar guideline recommendations, use of combination LLT and high intensity statin therapy was lower in female patients at high or very high cardiovascular risk than in male patients over one year of follow-up. Accordingly, female patients had lower LDL-C goal attainment both at baseline and at one-year. Nevertheless, due to intrinsic risk factors, female patients had lower rates of MACE-4 and MACE-3 than male patients.
Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study
Authors: Faggiano A , Brusamolino M , Gonzalez Santorun F , Valente F X , Olivero' R , Badia-Molins C , Limeres J , Teixido'-Tura' G , Rodenas-Alesina E , Guala A , Pontone G , Carugo S , Casas G , Ferreira-Gonzalez I , Rodriguez-Palomares J F
Published: October 2024

Background

Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined.

Purpose

This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM.

Methods

A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported.

Results

A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D).

Conclusions

CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2
T2 mapping as a marker of active myocardial injury in Anderson-Fabry disease patients
Authors: Schiavo M A , Torlasco C , Ditaranto R , Parisi V , Soranna D , Fanciullo N , Barile L , Catalano C , Di Nicola F , Ruotolo I , Serratore S , Galie' N , Lovato L , Biagini E
Published: October 2024

Background

In Anderson-Fabry Disease (AFD) with cardiac involvement, left ventricular hypertrophy (LVH) is often associated with myocardial scarring by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) imaging. Myocardial inflammation, detected as increased T2 weighted/T2 mapping (T2m) signal, has also been reported, although its role in disease progression is still unclear.

Purpose

To investigate the relationship between T2m and LGE/LVH progression in AFD patients.

Methods

67 paired CMR scans (1.5T) from 30 AFD patients were included. Three groups were defined according to LGE: no LGE at either scan (LGE-/-); LGE at baseline, unchanged at follow-up (LGE+/-); LGE at follow-up, appeared or increased compared to baseline (LGE+/+). T2m was measured in the infero-lateral basal segment in all scans; in LGE+ scans only, LGE was also manually contoured (ROI_LGE), and the ROI_LGE copied and pasted on the matching T2m image (T2m_ROI_LGE). See Figure 1. Troponin I (TnI) was also dosed at each scan. A univariate repeated measures analysis of variance was used to compare the groups and Tukey-Kramer correction was applied.

Results

As expected, the presence of LGE was strongly associated with older age, higher global and regional T2m, left ventricular (LV) mass and TnI values. As a novelty, in the LGE+/+ scans (scar appearance/progression) T2m in the ROI_LGE was higher than in the LGE+/- scans (scar unchanged) (p value 0.02). None of the other parameters, such as LV mass, TnI and global T2m values, differ between the the LGE+/+ compared to the LGE +/- group. See Table 1.

Conclusions

In our AFD patients’ cohort, scar progression was associated with focal increase in T2m values, i.e. T2m may identify patients with active myocardial injury. The potential implication on management/disease progression monitoring needs to be tested in future research, with longer follow-up. The role of sex, with females known to have higher average T2m values, will also need to be explored in a wider patient’s cohort.
Interplay between family History and polygenic risk for coronary heart disease: a cohort study among over 60 thousand individuals
Authors: Iribarren C , Lu M , Gulati M , Wong N D , Rana J S
Published: October 2024

Background

The degree to which background genetic risk adds to self-report of family history of coronary heart disease (CHD) remains an important question.

Methods

We utilized data from the multiethnic Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort of 60,070 Kaiser Permanente of Northern California (KPNC) members (mean ± SD age=59 ± 9 years; 67% female; 18% non-white). We characterized the cohort at baseline in 2003-2007. Excluding those with missing self-report of family history of CHD (n=1,718) resulted in a final sample of 61,352. We stratified the cohort into not having (n=42,866; 70%) and having (n=18,486; 30%) self-reported family history of CHD and then (within stratum of family history of CHD) by three groups of CHD polygenic risk (low: quintile 1; intermediate: quintiles 2, 3 and 4 combined; and high: quintile 5) using a validated 12-SNP polygenic risk score (PRS) for CHD (CARDIO inCode-Score®). Incident CHD was based on ICD-9/10 codes for angina pectoris, myocardial infarction, revascularization procedures or CHD death (n=3,040) through 12/31/2022; mean follow-up was 14.5 years.

Results

Age-adjusted CHD incidence rates per 10,000 person years were estimated using Poisson regression (accounting for death and health plan disenrollment) by absence/presence of family history of CHD and polygenic risk groups. As shown in the Figure, polygenic risk provided additional risk stratification within categories of family history. The hazard ratio of high PRS (vs low PRS) adjusted for age, sex, 10 principal components of ancestry, smoking, body mass index, diabetes, hypertension, total cholesterol/HDL ratio and cholesterol lowering therapy was 1.62 (95% CI, 1.39-1.87; p<0.001) in those with no family history of CHD, and 1.66 (95% CI, 1.37-2.00; p<0.001) in those with family history of CHD (p-interaction PRS continuous*family history of CHD=0.93).

Conclusions

Our results show that polygenic risk predicts future CHD regardless of the presence of family history of CHD. Thus, it is not enough to rely of family history to fully characterize potential genetic burden. These data are therefore important for the future of precision medicine.
Residual risk post acute coronary syndroms after 1 year of cardiac rehabilitation. Can we improve it?
Authors: Gascuena R , De Blas C , Gomez Diego J , Jimenez Azzaoui B , Ruesgas R , Morales T , Molina M
Published: October 2024

How much do we reduce residual risk with a cardiac rehabilitation program? What is left to do? Which would be the impact of a lower cholesterol threshold for the use of more potent lipid lowering drugs on residual risk? We explored these issues.

Methods

We retrospectively analyzed clinical and biochemical data from patients after 1 year of cardiac rehabilitation following an acute coronary event. Changes in residual risk of combined myocardial infarction, stroke and cardiovascular death, and its modification with optimization of treatment in patients with suboptimal lipid control, and with the use of PCSK9 inhibitors in those with a LDL-cholesterol over 70 mg/dl, were estimated using the SMART-REACH model calculator. Wilcoson and McNemar tests for paired-samples were used in the statistical análisis.

Results

262 consecutive patients were included. Median age was 63.5 years, 80.5% men, 89.3% stented. Baseline use of high intensity statins was 90.8%. After 1 year, the use of Ezetimibe was doubled to 77.1%, empaglifozin to 26%, and PCSK inhibitors were used only in 5%, with a residual use of colchicine.

Blood pressure and Cholesterol profile improved after 1 year, with no change in HbA1c. Absolute 10- years and life-long residual risk were reduced 4.8% (95%CI:3.6-5.9) and 6% (95%IC: 4.5-7.5) respectively (both p<0.001). LDL-cholesterol was >55 mg/dl with a suboptimal lipid lowering treatment in 29.8% of patients: an optimization to higher dose of rosuvastatin/atorvastatin plus ezetimibe would decrease absolute 10-years and life-long residual risk in 7.2% (95%CI: 4.9-9.4) and 9.9% (95%CI: 6.4-13.5%) respectively (both p<0.001). LDL-cholesterol remained > 70 mg/dl after higher dose of statin plus ezetimibe in 13.7% of patients: use of PCSK9 inhibitors in this group would reduce absolute 10-year and life-long residual risk in an additional 5.4% (95%CI:2.4-7,6;p=0,018) and 7% (95%CI: 3,8-10,1) compared to maximal dose of statins plus ezetimibe.

Conclusions

Cardiac rehabilitation programs reduce cardiac risk 1 year after an acute coronary event. Residual risk remain very high, and a significant proportion of patients do not reach recommended targets and optimal lipid lowering treatment. Optimization of lipid lowering drugs, and a lower LDL-cholesterol threshold for the use of PCSK9 inhibitors, would have a significant impact on residual risk.Changes in residual riskPCSK9-inhibitors in LDLchol >70 mg/dl
Metabolomic profiling of the entire UK Biobank enables interpretation of familial hypercholesterolemia mutations and prediction of severe cardiovascular outcomes
Authors: Barrett J , Jostins-Dean L , Schut K , Kerminen S , Wurtz P
Published: October 2024

Background

Familial hypercholesterolemia (FH) is an inherited disorder resulting in high levels of LDL-C from birth. Premeature coronary heart disease occurs in half of affected men by age 50 years(1). While many genetic variants that cause FH are well understood, there are also many variants in FH genes that are of uncertain clinical significance. Furthermore, the variability in residual cardiovascular risk of FH carriers after statin treatment is not fully understood. We here investigate whether metabolomic and genomic data from the 500,000 person UK Biobank cohort can aid in interpretation of candidate pathogenic variants for FH, and characterise future risk of severe cardiac events in the carriers of such variants.

Methods

We have quantified 249 metabolomic parameters in 490,830 blood samples from UK Biobank cohort. Among 186,483 participants with exome sequence data we identified 896 who carried known pathogenic FH variants and 405 who carried variants of unknown significance in an established FH gene. We fitted a logistic predictive model to identify pathogenic mutations using LDL levels, statin use and 17 principal components of the metabolomic parameters. We further tested whether metabolomic and genomic scores for predicting future risk of myocardial infarction (MI), that were trained in the general population (i.e. individuals without FH), could predict risk in FH carriers.

Results

A model including all metabolites had a higher accuracy at identifying known pathogenic FH variants (36/56 at FDR < 0.05), compared to LDL and statin use alone (30/56). Our model also identified 8 FH variants marked as uncertain significance in ClinVar with significant (FDR < 0.05) evidence of predicted pathogenicity. We found that our metabolomic risk score predicted 10-year risk of MI among FH carriers (HR=1.96 per SD, p = 0.0011). This was indeed stronger than the effect in the general population (HR = 1.64 per SD, p = 2.5e-168). A combined metabolomic and polygenic risk score had an even larger effect at predicting MI in FH carriers (HR = 3.06 per SD, p = 2.0e-6), and this score was significantly better at predicting MI in FH carriers than in non-carriers (HR = 3.06 vs 1.88 per SD, interaction p = 0.042).

Conclusion

Familial hypercholesterolemia is an important source of risk for early cardiovascular disease. Population-scale metabolomics can help distinguish pathogenic from benign variants that have not yet been characterised. Metabolomic and genomic scores can also identify individuals at most elevated risk, and provide even more information to FH individuals than in the general population.
Quality of life and clusters of patient characteristics in individuals with statin intolerance
Authors: Stuerzebecher P E , Gouni-Berthold I , Mateev C , Frenzel O , Erbe S , Boeckel J N , Scholz M , Schatz U , Weingaertner O , Kassner U , Laufs U
Published: October 2024

Background

Statin intolerance (SI) is associated with increased risk for cardiovascular events and mortality. The characteristics and symptoms of patients with SI are incompletely known.

Methods

The statin intolerance registry (SIR) is an observational, prospective, multicenter study that included n = 1111 patients between 2021 and 2023 in Germany. SI was defined as the inability to tolerate at least two different statins due to symptoms that resolved after statin-discontinuation. SIR baseline data were compared with the population-based LIFE-Adult-Study (n = 9983).

Results

The mean age was 66.1 years. Patients with SI had impaired quality of life with a mean EQ VAS score of 64.9 (SD 18.1) (Figure 1). The problems related to pain/discomfort (55.0%), mobility (32.3%), usual activity (23.9%), and anxiety/depression (20.4%). Diagnosis of depression was frequent (10.3%). 95.9% of patients with SI reported muscle symptoms that were associated with high severity of pain in 43.2% of patients. A higher percentage of SI patients was female in comparison to patients on statin in LIFE-Adult (57.6 vs. 38.2%). Women reported more depressive symptoms and lower quality of life in all domains compared to men. The symptoms increased with age.

A data-driven k-means analysis based on variables predicting severity of pain while on statin therapy identified 5 clusters of SI patients (Figure 1). The clusters differed in sex, premature ASCVD, depression, quality of life, comorbidities, and expectations to tolerate statin therapy.

Conclusion

Overall, patients with SI have a highly impaired quality of life. Women are more frequently and more severely affected. The identified clusters may help identify patients at risk for SI and to develop individualized strategies to improve patient trajectories.
Real-world evaluation of a lipid transformation project in primary care settings
Authors: Zambelli Z , Watson R , Jenkins R , Beaumont A , Williams H , Wierzbicki T , Howatson R
Published: October 2024

Background

The National Health Service England Long-Term Plan (2019) highlights the need to optimise lipid management to reduce cardiovascular disease (CVD) risk. A collaborative project was funded between a local health service and an industry partner to review current practice and improve outcomes in a UK region through introduction of lipid management pathways, primary care education and patient-focused reviews to optimise lipid-lowering therapies among high-risk patient groups.

Purpose

The project aimed to increase prescribing of CVD risk reduction therapies such as high-intensity statins (HIST), escalation of therapy to achieve lipid-lowering treatment targets, to improve clinician knowledge and confidence in lipid management and provide benefits for local populations in reducing CVD risk.

Methods

Systematic patient searches across six Primary Care Networks (PCNs) prioritised high-risk patients for review. Community of Practice sessions were held to facilitate shared learning and problem-solving.

A pragmatic, real-world evaluation was conducted to explore the impact of the new pathways and tools on prescribing outcomes and optimisation of lipid-lowering therapies. To examine the changes in HIST prescriptions, a statistical analysis of open-source prescribing data was undertaken between baseline (December 2021) and follow-up (December 2022) on over 39,000 eligible patient records. Qualitative interviews with clinicians from all participating PCNs and a thematic analysis of emerging themes was conducted in 2023.

Results

A paired sample t-test demonstrated a significant increase in the percentage of HIST prescribed, of the total number of statins prescribed, across the six PCNs between baseline and follow-up t(5) = -3.38, p = 0.01. Table 1 illustrates the changes at individual PCN level. Four of the six PCNs reached the National Institute for Health and Care Excellence minimum threshold of 65% target for HIST prescribing in statin prescriptions and three of these PCNs exceeded the optimal target of 75% HIST. An additional 600 patients were prescribed Ezetimibe (as therapy escalation or for statin intolerance).

Through qualitative data, clinicians reported development of new skills and knowledge, leading to increased confidence in optimising lipid management with medication and lifestyle interventions.

Conclusion

The lipid transformation project demonstrated significant improvements in prescribing of lipid-lowering therapies and improved clinician competence in lipid management pathways and guidance. This has enabled sustainable improvements in lipid management and cardiovascular disease reduction in local populations.
Effects of Chios Mastiha essential oil on cholesterol levels of healthy volunteers: a prospective, randomized, placebo-controlled study
Authors: Afendoulis D , Ampeliotis M , Moutafi M , Voutas P , Papagiannis N , Kartalis N , Toutouzas K , Didagelos M , Kartalis A
Published: October 2024

Introduction

Chios Mastiha essential oil (CMO) is a natural product extracted from the resin of Mastiha, possessing antioxidant, anti-microbial, anti-ulcer, anti-neoplasmatic and cholesterol lowering capabilities in vitro, and its hypolipidemic effect was confirmed in animal studies. Yet, there are no randomized, placebo-controlled clinical studies in the literature regarding CMO’s hypolipidemic effects in humans. A prospective, randomized, placebo-controlled study was designed to study the hypolipidemic effect of CMO capsules on healthy volunteers with elevated cholesterol.

Methods

192 healthy volunteers were screened and 160 of them with total cholesterol> 200 mg/dl participated in the study. They were randomized with a 2:1 ratio of receiving CMO capsules (200 mg mastiha-oil/capsule) and placebo for 8 weeks respectively. 113 patients received CMO and 47 were randomized in the control group, and all of them completed the follow-up period.

Results

After 8 weeks of CMO administration, total and LDL cholesterol were significantly lower in the CMO compared to the placebo group 215.2±27.5 vs 237.0±27.9 mg/dl (p<0.001) and 135.0±26.1 vs 153.0±23.3 mg/dl (p<0.001) respectively. No gastrointestinal adverse events, liver or renal toxicity were reported. Additionally, in the CMO group total cholesterol was significantly decreased by 20.6 mg/dl (9%) and LDL by 18.1 mg/dl (12%), triglycerides by 21.8 mg/dl (15%) and glucose by 4.6 mg/dl (5%) and HDL was increased by 2.4 mg/dl (5%), compared to their baseline values.

Conclusion

MASTIHA-OIL study showed the efficacy and safety of CMO in reduction of Total and LDL-cholesterol after 8 weeks of administration in healthy volunteers with elevated cholesterol levels. Multicenter clinical studies are needed to further study its hypolipidemic effect and establish CMO as a treatment choice for patients with dyslipidemia, given its safety, efficacy and multiple beneficial biologic effects.
Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort
Authors: Van Den Bogaart M , Snaterse M , Van Trier T J , Martens F M A C , Boekholdt S M , Jorstad H T
Published: October 2024

Background

Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up.

Methods

We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking.

Results

We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1).

Conclusion

After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.
Mean body mass index during 20 years of follow-up and cardiovascular disease incidence: results from the ATTICA cohort study (2002-2022)
Authors: Damigou E , Chrysohoou C , Barkas F , Vlachopoulou E , Vafia C , Dalmyras D , Anastasiou G , Koutsogianni A D , Mentzantonakis G , Kravvariti E , Tsioufis C , Pitsavos C , Liberopoulos E , Sfikakis P P , Panagiotakos D B
Published: October 2024

Background/Introduction

The Global Burden of Disease study has estimated that the burden of increased body mass index (BMI) (i.e., approximately >2.000.000 deaths and >70.000.000 disability-adjusted life years) was predominantly dominated by cardiovascular disease (CVD) during 1990–2017. However, the lifelong body weight (BW) status and its relation to CVD risk remains poorly elucidated.

Purpose

The purpose of this study was to evaluate the relationship between mean BMI during a 20-year period and CVD incidence.

Methods

Participants initially free-of-CVD from the ATTICA cohort study were used (n=1,348). At baseline and the 10- and 20-year follow-up, CVD events were assessed, according to WHO-ICD-10. Based on three measurements of weight and height, BMI for each measurement was calculated, and, afterwards, the mean BMI during the whole 20-year period was computed.

Results

During the whole 20-year period, 41% (n=552) of participants consistently had a normal BW, 48% (n=651) had overweight and 11% (n=145) had obesity. The 20-year CVD incidence was: 8.0% (n=44), 14.9% (n=97) and 19.3% (n=28) in those who consistently had a normal BW, overweight and obesity, respectively (p-value<0.001). In multi-adjusted Cox proportional hazards models, adjusted for age, sex, clinical and lifestyle characteristics, compared to participants who consistently had a normal BW, those who had overweight as well as those who had obesity had almost 2 times higher risk to develop CVD during the 20-year period [Hazard Ratio-HR: 1.73, 95%Confidence Interval-CI: 1.13-2.66 and HR: 2.04, 95%CI: 1.11-3.76, for participants with overweight and obesity, respectively].

Conclusion

The study findings highlight that, despite the observations of the J-shaped relationship between BMI and all-cause mortality observed in some studies, both overweight and obesity can be significant risk factors for CVD, when lifelong BW status is assessed. Therefore, currently, new lifelong measures are needed to prevent and manage the pervasive overweight and obesity.
The visceral adiposity index predicts cardiovascular events both in coronary artery disease patients with and in those without diabetes
Authors: Plattner T , Larcher B , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H
Published: October 2024

The Visceral Adiposity Index (VAI) is calculated based on waist circumference, BMI, triglyceride and HDL-cholesterol levels and is a validated measure of visceral adiposity. In the general population, the VAI has been shown to be an independent risk factor for premature mortality. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) with or without type 2 diabetes mellitus (T2DM) is not known and is addressed in the present study.

We prospectively investigated 927 patients with angiographically diagnosed CAD over a mean follow-up time of 8.2±4.3 years.

At baseline, the VAI was significantly higher in patients with T2DM (n=303) than in those who did not have diabetes (6.5±5.2 vs. 4.8±4.9; p<0.001). During follow-up, we recorded 385 cardiovascular events. The VAI significantly predicted the incidence of cardiovascular events both univariately (standardized HR 1.09 [1.02-1.16]; p=0.011) and after adjustment for age, gender, smoking, LDL cholesterol, hypertension and T2DM (standardized adjusted HR 1.11 [1.04- 1.18]; p=0.002); T2DM also significantly predicted cardiovascular events in this fully adjusted model (adjusted HR 1.26 [1.04-1.52]; p=0.018) independently from the VAI.

We conclude that the VAI and T2DM are mutually independent predictors of cardiovascular events in patients with CAD.
Impact of glucose metabolism status on the relationship between remnant cholesterol and ischemic risk after percutaneous coronary intervention: a large-scale long-term cohort study from real-world
Authors: Yan K , Li J , Zhang K , Li Y , Yuan J , Zhao X
Published: October 2024

Background

Elevated remnant cholesterol (RC) is considered a risk factor for ischemic events in patients with coronary artery disease (CAD). Recently evidence demonstrates a close connection between RC and cardiometabolic disorders, particularly diabetes mellitus (DM). However, it remains unclear whether different glucose metabolism statuses modify the association between RC and ischemic risk after percutaneous coronary intervention (PCI).

Purpose

This study aims to explore whether glucose metabolism statuses alter the relationship between RC and ischemic risk in CAD patients undergoing PCI.

Methods

This prospective study enrolled consecutive 10,724 CAD patients undergoing PCI throughout 2013. Patients were categorized into three groups: DM, pre-DM, and normal glucose regulation (NGR) group. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and was analyzed based on tertile levels (low, middle, and high). The clinical endpoint was major adverse cardiovascular and cerebrovascular events (MACCE, including cardiac mortality, revascularization and stroke).

Results

A total of 9,406 PCI patients were ultimately included, among whom the average age was 58.44 ± 10.26 years and 2,142 (22.80%) were female. During 5-year follow-up, 1,876 (19.9%) patients experienced MACCE. In the overall cohort, the highest RC tertile was associated with a higher risk of MACCE (hazard ratio [HR]: 1.129, 95% confidence interval [CI]: 1.006-1.267) compared to those in the lowest tertile (Figure 1). Importantly, a significant interaction was observed between RC levels and glucose metabolism statuses (P for interaction = 0.032). In the DM group, multivariate Cox regression analysis revealed that the highest tertile of RC significantly increased a 1.172-fold risk of MACCE (HR:1.172, 95% CI:1.004-1.369). However, neither the pre-DM nor NGR groups showed any significant association between RC and MACCE (both P > 0.05). Further subgroup analysis found that the correlation between the highest tertile of RC and an increased MACCE risk was only in the DM group, which was prominent among females (Figure 2).

Conclusions

In a large-scale 5-year follow-up study, we are the first to demonstrate that RC-related ischemic risk may be exacerbated by diabetes in CAD patients undergoing PCI, highlighting the potential benefits of intensifying RC-lowering treatments for PCI patients combined with DM.
Interleukin-6 and suPAR improves prediction of all-cause mortality in type 1 diabetes - the Thousand & 1 Study
Authors: Bahrami H , Jorgensen P G , Hove J D , Dixen U , Rasmussen L J H , Eugen-Olsen J , Rossing P , Jensen M T
Published: October 2024

Background

Cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (T1D). Inflammation frequently accompanies T1D and is suggested as an important contributor to the pathogenesis and progression of CVD. However, current risk prediction models for T1D lack biomarkers of inflammation.

Methods

A prospective study of individuals with T1D without overt heart disease was evaluated. Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) were analysed. In Cox proportional hazards model, adjustments were made for variables in the Steno T1 Risk Engine: age, sex, duration of diabetes, HbA1c, systolic blood pressure, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity. The model included the biomarkers as continuous variables, and a "combination" category was defined as simultaneously elevated suPAR > 4 ng/mL and IL-6 > 3 pg/mL. The net reclassification improvement (NRI) and C-statistics were calculated.

Results

For included individuals (n=1,014, 52% male, mean age 50±15), follow-up was 100% after median of 12.2 years (interquartile range: 11.8 to 12.9).In the fully adjusted model, IL-6 and suPAR were both associated with all-cause mortality (IL-6 hazard ratio (HR): 1.6 (95% confidence interval: 1.04 to 2.4), suPAR HR: 1.9 (1.2 to 2.9). HsCRP was not associated with the outcome. The combination category showed even stronger association: HR 2.7 (1.4 to 5.1). When added to the Steno T1 Risk Engine, IL-6, suPAR, and their combination all added discriminatory power in predicting all-cause mortality assessed by NRI; IL-6: 38% (19 to 58), suPAR: 45% (25 to 65), combination 56% (36 to 76). C-statistics showed similar results for only suPAR. Area under the curve for suPAR: from 0.84 to 0.86 (P=0.049), IL-6: 0.84 to 0.85 (P=0.338), combination: 0.84 to 0.86 (P=0.066).

Conclusions

IL-6 and suPAR are independently associated with all-cause mortality in T1D without known heart disease. Assessment of IL-6 and suPAR in T1D may enhance risk prediction.Figure 1Figure 2
Effects of glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on mitochondrial-derived peptide-c and on markers of neurohumoral activation
Authors: Ikonomidis I , Pavlidis G , Pliouta L , Katogiannis K , Maratou E , Thymis J , Michalopoulou E , Prentza V , Katsanaki E , Vlachomitros D , Kountouri A , Korakas E , Parissis J , Andreadou I , Lambadiari V
Published: October 2024

Background/Introduction

Type-2 diabetes mellitus (T2DM) is associated with increased prevalence of cardiovascular disease.

Purpose

We investigated the effects of insulin, glucagon like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on mitochondrial-derived peptide-c (MOTS-c), N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, oxidant and antioxidant biomarkers and cardiovascular function of T2DM patients.

Methods

A total of 160 T2DM patients were randomized to insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40) or their combination (GLP-1RA+SGLT-2i) (n = 40) as add-on to metformin. We measured at baseline, at 4 and at 12 months of treatment: a) plasma levels of MOTS-c, NT-proBNP and GDF-15, b) thiobarbituric acid reactive substances (TBARS), as an oxidant biomarkers, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), as an antioxidant biomarker, and c) global left ventricular longitudinal strain (GLS) and global work index (GWI) using speckle-tracking imaging.

Results

Twelve months after treatment, treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c (14.89 ± 11.27 vs. 7.26 ± 4.21 ng/mL, p=0.009, 6.49 ± 3.91 vs. 5.6 ± 3.38 ng/mL, p=0.029, respectively), while treatment with insulin and GLP-1RA had a neutral effect on this biomarker (p > 0.05; Table). GLP-1RA, SGLT-2i and their combination showed a greater reduction of NT-proBNP (-43.1% vs. -54.2% vs. -56.9% vs. -14.7%; Figure) and GDF-15 (-14.8% vs. -15.2% vs. -16.1% vs. -0.9%) than insulin (p < 0.05 for all comparisons), despite the fact that all patient achieved adequate glycemic control. GLP-1RA or GLP-1RA+SGLT-2i provided a remarkable reduction of TBARS and increase of GLS and GWI compared to insulin or SGLT-2i (p < 0.05). In all patients, at 4 and at 12 months, the percentage reduction of NT-proBNP was associated with the improvement of TBARS, GLS and GWI (p < 0.05). The percentage reduction of GDF-15 was correlated with the increase of ABTS and with the improvement of GLS at 4 and 12 months (p < 0.05). In SGLT-2i group, the percentage increase of MOTS-c was related with the percentage reduction of GDF-15 (r = 0.81, p = 0.005) at 12 months.

Conclusions

Twelve-month treatment with GLP-1RA, SGLT-2i and their combination resulted in reduction of cardiac biomarkers in parallel with a greater decrease of oxidative stress than insulin in T2DM. SGLT-2i appears more effective in the improvement of MOTS-c and markers of neurohumoral activation.TableFigure