bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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.
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

Abstract

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

Abstract

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&lt;0.001) in those with no family history of CHD, and 1.66 (95% CI, 1.37-2.00; p&lt;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

Abstract
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&lt;0.001). LDL-cholesterol was &gt;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&lt;0.001). LDL-cholesterol remained &gt; 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 &gt;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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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

Abstract

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&gt; 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&lt;0.001) and 135.0±26.1 vs 153.0±23.3 mg/dl (p&lt;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.