bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global molecular calcium score: is there a link between sodium fluoride uptake and cardiovascular risk burden?
Authors: Borges-Rosa J , Oliveira-Santos M , Silva R , Gomes A , Campos G O , Gomes A R , Abrunhosa A , Castelo-Branco M , Goncalves L , Ferreira M J 
Published: November 2023

Abstract

Background
Sodium fluoride (18F-NaF) uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification both in atherosclerotic plaques and the aortic valve.

Purpose
We aimed to evaluate global cardiac microcalcification activity with 18F-NaF, as a measure of the microcalcification burden, in high cardiovascular (CV) risk patients. Additionally, as an exploratory endpoint, we evaluated the association between global cardiac microcalcification and diastolic dysfunction.

Methods
High CV-risk individuals without previous CV events from a single centre were prospectively scanned with 18F-NaF PET-CT. Total cardiac 18F-NaF uptake was measured as global molecular calcium score (GMCS), which was calculated by summing the product of mean standardized uptake value and volume of the region of interest on every slice within the borders of the heart. The result was then divided by the number of slices to adjust for the volume.

Results
We included sixty-five patients with a mean age of 64.0 ± 9.0 years and 38.5% females. There was a high rate of CV risk factors, including hypertension (95.4%), diabetes (84.6%), dyslipidemia (78.5%), obesity (58.5%), smoking (26.2%) chronic kidney disease (18.5%), and family history of premature coronary disease (9.2%). The mean 10-year risk of fatal and nonfatal cardiovascular events predicted by ASCVD risk score was 30.54 ± 18.4. Median GMCS was 221.42 [IQR 144.55-317.58]. Individuals with &gt; 5 CV risk factors (46.2%) had increased overall GMCS compared to those with a lower number of CV risk factors (295.29, IQR 159.37-356.87 vs 186.16, IQR 122.57-281.78; p=0.03). Thirty-three patients underwent diastolic dysfunction evaluation by echocardiography. All patients had normal left ventricle ejection fraction, mean of 62.86 ± 3.58%. Mean E/A was 0.88 ± 0.27, mean septal e’ velocity 0.07 ± 0.02 m/s, mean lateral e’ velocity 0.08 ± 0.02 m/s, and mean average E/e’ 10.7 ± 3.3. The mean peak tricuspid regurgitation velocity was 2.14 ± 0.59 m/s and the median indexed left atrium volume was 37, IQR 29-44mL/m2. After applying the algorithm for diagnosis of diastolic dysfunction in subjects with normal ejection fraction, 21.2% had diastolic dysfunction and 36.4% had a normal diastolic function, while 42.4% were indeterminate. There was no correlation between echocardiographic variables of diastolic function and GMCS, except for indexed left atrium volume (r = 0.83, p&lt;0.01). There was no association between GMCS and diastolic function categories.

Conclusions
In a high CV risk cohort, the global cardiac microcalcification assessed by GMCS was associated with the burden of CV risk factors. Additionally, despite a strong positive correlation between GMCS and indexed left atrium volume, we found no association between GMCS and echocardiographic variables of diastolic function.
Three-dimensional printer guided new morphological classification of left atrial appendage -rock, paper and scissors-
Authors: Ryuzaki S , Kondo Y , Nakano M , Nakano M , Kajiyama T , Ito R , Kitagawa M , Sugawara M , Chiba T , Yoshino Y , Komai Y , Takanashi Y , Kobayashi Y 
Published: November 2023

Abstract

Background
Cardiogenic embolism by left atrial thrombi is one of the most important atrial fibrillation (AF)-related clinical problems. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). The WATCHMAN device was developed as a permanent implantable device to seal off the LAA to prevent cardiogenic embolism. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in JAPAN. It is known that the LAA diameter of Asians is larger than that of non-Asians. Furthermore, the LAA of the Japanese are more complicated, compared to the Western. Whereas the four classifications from previous reports are widely used in the world, the classification differs with different physicians in the real-world practice.

Purpose
We aimed to identify the relationship between morphological features of LAA and clinical events such as ischemic stroke in Japanese patients.

Methods
The LAAC database of our institution was respectively analyzed. All LAAC cases were performed between February 2020 and February 2022. The three-dimensional printing of LAA was generated from cardiovascular computed tomography imaging data. The shapes of the LAA were classified into 3 morphological types: (1) The LAA with bi lobe was defined as "Scissors" type; (2) The one with complicated erasing branches was "Paper" type; (3) The simple one was "Rock" type. We retrospectively examined the relationship between the risk of ischemic stroke and the morphological features of the LAA.

Results
The cohort consisted of 63 consecutive patients (age, 73±8 years; male gender, 73%; BMI, 24±4 kg/m²; the size of WATCHMAN device, 29±42 mm). Of those, 14 (22%), 21 (33%) and 28 (44%) patients were divided into the Scissors, Paper and Rock types, respectively. All groups were identically matched for comorbidities. Table shows the patient characteristics and the results of univariate and multivariate analysis. There were 35 (56%) patients who had a history of ischemic stroke (4 vs. 9 vs. 22; Rock vs. Scissors vs. Paper types, p-value=0.01). In the multivariate analysis, the Paper type is the potential risk factor of ischemic stroke (p-value&lt;0.01, respectively).

Conclusions
The morphological features of LAA by three-dimensional printing may be related to cardioembolic stroke. Patients with Paper type LAA were significantly more likely to have had a history of ischemic stroke. These results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic and bleeding events and, moreover, LAAC could be the best option for these patients.Table 1Table 2
Myocardial fibrosis activity following ST-segment elevation myocardial infarction
Authors: Barton A K , Tzolos E , Waight C , Loganath K , Joshi S , Singh T , Williams M C , Van Beek E J R , Brian D , Fletcher A , Clark T , Slomka P , Dey D , Newby D E 
Published: November 2023

Abstract

Background
Myocardial fibrosis following myocardial infarction (MI) is a key healing mechanism and involves widespread fibroblast activation. Once activated, fibroblasts express fibroblast activation protein (FAP) (1). Hybrid positron emission tomography (PET) imaging of radiolabelled fibroblast activation protein inhibitor (FAPI) fused with cardiovascular magnetic resonance (68Ga-FAPI PET/MR) is an emerging method for assessing myocardial fibrosis activity that may provide additional insights into the recovery of the heart following MI.

Methods
Forty patients with acute (&lt;4 weeks), 19 with recent (12 weeks), and 19 with prior established ST-segment elevation MI (&gt;12 months), and 20 healthy volunteer participants underwent 68Ga-FAPI PET/MR. Participants were imaged 30 min after administration of 100-200 MBq 68Ga-FAPI-04. Image analysis was performed using FusionQuant (Cedars Sinai, Los Angeles, California). 68Ga-FAPI uptake was quantified by maximum standardised uptake value (SUVmax) and tissue-to-background ratio (TBRmax) correcting for blood-pool activity in the left ventricle. Comparisons between were assessed with one-way ANOVA with Tukey-Kramer post-hoc testing where significant differences were detected. A 2-sided p-value of &lt;0.05 denoted statistical significance.

Results
Participants were predominantly middle-aged men with similar sized infarcts (peak plasma cardiac troponin concentrations and post-MI left ventricular ejection fraction) (Table). Blood pool tracer activity was also similar between groups. Focal myocardial 68Ga-FAPI uptake localised to areas of the infarct and peri-infarct zones on magnetic resonance late gadolinium enhancement imaging (Figure). Both myocardial SUVmax and TBRmax varied between infarcts of different ages, being highest in acute (TBRmax 4.1±1.2) and lowest in those with prior established MI (2.1±0.7, Table and Figure).

Conclusions
Fibrosis activity is greatest in the immediate aftermath of acute MI with a step-wise reduction in the weeks and years that follow. Fibrosis activity continues for many months and years after acute infarction.FigureTable
Increased Lipoprotein (a) and familial hypercholesterolemia: a dangerous combination.Data from a 12-year follow-up study
Authors: Andrikou I , Grigoriou K , Dima I , Skoumas I , Tsioufis K , Vlachopoulos C 
Published: November 2023

Abstract

Background
Lipoprotein (a)[Lp(a)] is a molecule characterized by very increased atherogenicity. Mounting evidence support the causal link between high Lp(a) concentration and atherosclerotic cardiovascular (CV) disease in the general population.

Purpose
The role of Lp (a) in specific categories of patients at high CV risk, such as patients with familial hypercholesterolaemia (FH), is also of special importance. The aim of our study was to investigate the prognostic role of Lp (a) regarding major adverse CV outcomes in subjects with heterozygous FH.

Methods
155 patients from the outpatient lipid clinic of our hospital (56 males,mean age 41.2±14.2 years, 26% smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FH criteria participated in the study. Participants were evaluated for a mean follow-up period of 12.4±7.1 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile and levels of Lp(a). All subjects were on lipid-lowering medication during the follow-up period. The endpoint of our study was the composite of major CV events (coronary artery disease events and stroke).

Results
The incidence of the composite endpoint of major CV events during the follow-up period was 9% (n=14). In the total population, the mean baseline Lp (a) levels were 34.9±33.7 mg/dl, while 42% had increased Lp (a) levels ≥30mg/dl. The group of FH patients with new-onset CV disease had higher levels of Lp(a) at baseline compared to those without new-onset CV disease (48.1±37.3 vs 33.6±33.1 mg/dl, p=0.01). Also, those with new-onset CV disease had higher percentage of increased Lp(a) levels (≥30mg/dl) at baseline compared to those without development of CV disease (71% vs 39%, p=0.02).Multiple Cox regression analysis revealed that during the follow-up period independent predictors of major adverse CV events were:increased baseline Lp(a) levels(≥30mg/dl)(HR 5.61, 95% CI 1.51-10.92, p=0.01), male sex (HR 8.11, 95% CI 2.02-12.48, p&lt;0.01), baseline low-density cholesterol levels (HR 1.01, 95% CI 1.00-1.02, p=0.04) and the presence of hypertension at baseline (HR 3.59, 95% CI 1.03-12.49, p=0.04), after adjustment for confounding factors.

Conclusions
In patients with FH, increased baseline Lp(a) is an independent predictor of adverse CV events, after a 12-year follow-up period. FH patients with Lp (a)levels ≥30mg/dl have an almost 5-fold greater CV risk compared to those with lower Lp (a) levels. It seems that Lp (a) reclassifies the already increased CV risk of FH subjects into an even higher level.
The Cycle study: a prospective study on cholesterol levels during the menstrual cycle
Authors: Mulder J , Balsrud P , Schreuder M , Van Vark-Van Der Zee L C , Mulder M T , Bogsrud M P , Narverud I , Retterstol K , Langslet G , Boersma E , Holven K B , Roeters Van Lennep J E 
Published: November 2023

Abstract

Background
Previous studies showed fluctuating lipid levels during the menstrual cycle in healthy women with normal cholesterol (nChol). Cycle-related variations in lipid levels in women with familial hypercholesterolemia (FH) have not been studied, while these might have important consequences for lipid management.

Purpose
To investigate menstrual cycle-related fluctuations in lipid levels in women with FH compared to those with nChol.

Methods
In the Netherlands and Norway, 20 women with clinical/genetic FH and 63 healthy women with nChol were included - details are presented in the figures. Participants had to have a regular cycle between 21-35 days, while pregnant women, and those using hormone-based contraceptives without hormone free interval (HFI) were excluded. Lipid levels were measured in the follicular (visit 1), ovulation (visit 2), and luteal (visit 3) phases. In women using oral contraceptives (OC) measurements were taken during day 12-14 of the pill period (visit 1) and during day 5-7 of the HFI (visit 2).

Results
Mean (sd) age of the included subjects was 33 (9) years, BMI 23.9 (4) kg/m2, and cycle duration 28 (2) days. These characteristics were similar in FH and nChol. Women with nChol showed slight, although statistically significant, cycle-related variations in cholesterol levels (mean maximum variation total Chol 0.53, LDL-Chol 0.39 and HDL-Chol 0.22 mmol/L; figure 1). FH women who did not receive statin therapy for various reasons showed largest mean variations (total Chol 0.80, LDL-Chol 0.59 and HDL-Chol 0.23 mmol/L), with the highest lipid levels during the ovulation phase.
The women with OC had an increase in total- and LDL-cholesterol (groups combined: mean difference 0.55 and 0.51 mmol/L, respectively) between the two visits (n=9) (figure 2).

Conclusions
In women with untreated FH and normal cholesterol with a regular menstrual cycle, total- and HDL-cholesterol were highest at ovulation. These menstrual fluctuations were absent in women with FH who used statins. Women with OC showed an increase in total- and LDL-cholesterol from the contraceptive pill period to the HFI. Even though in most women the absolute variation in lipid levels during the menstrual cycle and OC are modest, the moment of measurement can be of clinical value in particular in women with untreated high lipid levels. In these women, it is recommended to measure lipid levels at a fixed time of the menstrual cycle.Figure 1Figure 2
Unrealized opportunities for cardiovascular risk reduction with optimized statin and ezetimibe in veterans with coronary artery disease
Authors: Kovach C , Mesenbring E , Gupta P , Glorioso T , Ho M , Waldo S , Schwartz G 
Published: November 2023

Abstract

Background
Many patients with coronary artery disease (CAD) do not achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals (1,2).

Purpose
To quantify unrealized opportunities to improve clinical outcomes of Veterans with CAD through optimized oral lipid-lowering therapy (LLT) with statins and ezetimibe within the United States Veterans Affairs healthcare system.

Methods
Veterans with CAD by coronary angiography between 2015 and 2020 were identified, the observed LLT and LDL-C were described, and the observed rates of death, myocardial infarction, stroke, and coronary revascularization were determined. Potential reductions in these events with optimized statin alone or with ezetimibe were modelled based on expected further LDL-C reductions (3).

Results
The analysis cohort comprised 111,954 Veterans (59.7% statin-treated at baseline angiography) observed for median 3.4 (IQR 2.1-4.0) years. At 6 months, statin prescription increased to 68.7%, but high-intensity statin regimens were prescribed in only 52.9%, ezetimibe use was low (1.1%), and LDL-C remained ≥70 mg/dL in 52.1% of patients. At 4 years, observed incidences (95% CI) of death, myocardial infarction, stroke, and coronary revascularization were 21.6% (21.3-21.8), 5.0% (4.9-5.2), 2.2% (2.1-2.3), and 15.4% (15.2-15.7), respectively (Figure 1). With optimized statin, projected absolute reductions in these incidences were 1.3% (0.9-1.7), 0.8% (0.7-1.0), 0.2% (0.1-0.3), and 2.3% (2.0-2.7). With optimized statin and ezetimibe, projected absolute reductions were 1.8% (1.2-2.4), 1.1% (0.9-1.3), 0.3% (0.2-0.4) and 3.1% (2.6-3.6).

Conclusions
Suboptimal LLT was prevalent among Veterans with CAD. Meaningful improvements in their cardiovascular outcomes could be achieved with optimized statin alone. Despite lesser lipid-lowering efficacy of ezetimibe, its widespread use on a population level could contribute substantially to cardiovascular risk reduction from intensified oral LLT.Figure 1Figure 2
Statins under-treatment and mortality in patients with atrial fibrillation. Insights from the nationwide START registry
Authors: Menichelli D , Antonucci E , Pignatelli P , Violi F , Palareti G , Pastori D 
Published: November 2023

Abstract

Background
Statins are mainstream drugs for cardiovascular (CV) prevention, but under-prescription is an important clinical challenge. Data on the use of single statins as the rate of under-prescription in atrial fibrillation (AF) are lacking. To evaluate the association of statin underuse with mortality risk in a large AF cohort.

Methods
5,477 patients from the nationwide START registry were included. The prevalence of different statins was reported and the association with all-cause and CV mortality investigated. Mortality risk of patients with an indication to but not taking statins was also analysed.

Results
Mean age was 80.2 years, 46.4% were women. Among 2,899 patients with a clinical indication to statin, only 1,578 (54.4%) were on treatment. In a mean follow-up of 22.5±17.1 months, 491 (4.7%/year) deaths occurred (106 CV deaths, 1.0%/year). Atorvastatin and Simvastatin inversely associated with all-cause (HR 0.692, 95%CI 0.519-0.923, p=0.012 and HR 0.598, 95%CI 0.428-0.836, p=0.003, respectively). and CV death (HR 0.372, 95%CI 0.178-0.776, p=0.008 and HR 0.306, 95%CI 0.123-0.758, p=0.010, respectively).
The 1,321 untreated patients were older, more frequently women and with a higher prevalence of diabetes, previous cerebrovascular disease, peripheral artery disease compared to those on treatment. Statin undertreatment was associated with higher risk of all-cause (HR 1.565, 95%CI 1.235-1.983, p&lt;0.001) and CV death (HR 2.057, 95%CI 1.188-3.561, p=0.010).

Conclusions
AF patients with an indication to statins but left untreated disclose a high risk of all-cause and CV mortality. Implementation of statin prescription in the AF population can help reducing the residual CV risk.
Body fat distribution, fat-free mass and cardiovascular function in the UK Biobank
Authors: Oguntade A S , Lacey B , Taylor H , Lewington S 
Published: November 2023

Abstract

Background
Excess adiposity and high body mass index have been associated with cardiac dysfunction and heart failure. However, the role of whole body imaging and independent associations of regional fat and fat-free mass on left ventricular and vascular function is unclear.

Purpose
This study determined the cross-sectional associations of regional fat depots and fat-free mass on left ventricular function and arterial stiffness to explain obesity-related cardiac dysfunction.

Methods
Participants who underwent whole body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA) in an ongoing imaging study of 100,000 individuals in the UK were included in this analysis. Analyses exclude individuals with major cardiac and vascular diseases at initial baseline assessment. Regional fat distribution was quantified using MRI while body fat-free mass was quantified with DXA. Cardiac MRI was used to measure left ventricular (LV) ejection fraction and LV mass while pulse wave velocity from finger photo-plethysmography was used to measure arterial stiffness index. Associations of body fat distribution (visceral fat, abdominal subcutaneous fat, other body fat) and fat-free mass with each of LV ejection fraction, LV mass and arterial stiffness index, after mutual adjustment for one another and potential confounders were determined using multivariable linear regression.

Results
We included 31,088 individuals (mean age 63.4 years, 53% women). Among regional body fat measures, higher visceral fat was associated with lower LVEF (β=-0.43; 95% CI: -0.55, -0.31 per SD) and higher arterial stiffness index (β=0.44; 95% CI: 0.34, 0.54 per SD) while none of the regional fat and fat-free mass showed significant association with LV function or arterial stiffness. None of the fat or fat-free mass measures showed significant association with LV mass. These associations were not explained by inflammatory markers, blood pressure or glycaemic profile.

Conclusion
Visceral fat is the main driver of obesity-related cardiac and vascular dysfunction. There is need for further studies to understand the biological causal pathways of obesity-heart disease.Figure 1Figure 2
The prognostic value of high-sensitivity cardiac troponin t in diabetes patients without coronary artery disease
Authors: Deng J , Guo Q , Tu J B , He Y B , Lu X Z , Li Q , Deng J Y , Zhang Z M , Zhang J L , Wu J L , Zhou Z Y , Liu J , Chen S Q , Chen J Y , Liu Y 
Published: November 2023

Abstract

Background
High-Sensitivity Cardiac Troponin T (hs-cTnT) is associated with poor prognosis in patients with Diabetes mellitus (DM). However, whether it remains a valuable index for risk stratification in DM patients without coronary artery disease (CAD) is not yet determined.

Objective
To assess the association between hs-cTnT and follow-up mortality among patients with DM but without CAD in different renal function status.

Methods
2,774 patients with DM but without CAD were enrolled from the Cardiorenal Improvement II (CIN-II) Study and were divided into three groups according to tertiles of hs-cTnT levels (low, intermediate and high). The associations between hs-cTnT and all-cause mortality and Cardiovascular mortality was detected by Cox regression and Fine-Gray models, respectively. Subgroup analysis was performed in patients with different renal function status.

Results
During a median follow-up of 3.96 (interquartile range: 2.45 to 5.79) years, 246 (8.9%) patients died and 134 (4.8%) died from cardiovascular disease (mean age: 62.6±9.5 years; 50.4% female) among 2,774 patients. Compared to the low tertile of hs-cTnT, the high tertile of hs-cTnT increased 2.19-fold risk of all-cause mortality in DM patients without CAD (HR: 3.19, 95% CI: 2.15-4.71; P &lt; 0.001) and increased 4.89-fold risk of cardiovascular mortality (HR: 5.89, 95% CI: 3.08-11.28; P &lt; 0.001). Consistent results were only found in patients with eGFR &gt;60 mL/min/1.73 m2 while the association between HS-TnI and mortality was insignificant in patients with eGFR≤60 mL/min/1.73 m2.

Conclusions
The present study demonstrates that for patients with eGFR &gt;60 mL/min/1.73 m2, the high level of hs-cTnT is still associated with an increased risk of follow-up mortality in patients with diabetes, even without CAD.Foreset plots