bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relative importance of particle count, type, and size of ApoB-containing lipoproteins in risk of myocardial infarction
Authors: Morze J , Melloni G E , Rynkiewicz A , Gruchala M , Guasch-Ferre M , Ruff C T , Hu F B , Sabatine M S , Marston N A 
Published: October 2022

Abstract

Background
An accumulating body of evidence suggests that the number of apolipoprotein B-containing particles (ApoB-P) is more predictive of cardiovascular risk than their lipid content. However, it is unclear if this association is consistent across different lipoprotein types and sizes.

Purpose
We aimed to evaluate if particle type and size are associated with incident myocardial infarction (MI) beyond ApoB-P count. Moreover, we aimed to determine if the risk associated with lipoprotein(a) is additive to that of ApoB-P.

Methods
This prospective cohort study included 96,126 participants without prior history of stroke, coronary or peripheral artery disease or use of lipid-lowering medication from the UK Biobank. Count and size of VLDL, IDL, LDL, and HDL, as well as ApoB level and total ApoB-P count were measured in non-fasting plasma samples by nuclear magnetic resonance platform. Lipoprotein(a) was measured by immunoturbidimetric assay. We explored associations between these lipoprotein markers and incident MI using Cox proportional hazard models adjusted sequentially for clinical covariates, HDL count and size, and ApoB-P.

Results
Over a median follow-up of 12.1 years, 1702 participants had incident MI. In unadjusted models, 1-SD increases in ApoB-P count, ratio of VLDL to (LDL+IDL) particle counts, VLDL size and lipoprotein(a) were associated with a higher risk of MI, while LDL size was associated with a lower risk of MI (Table 1). When adjusting for clinical covariates and lipid parameters, only ApoB-P and lipoprotein(a) remained significantly associated with a higher risk of MI (HR: 1.40 [1.32; 1.48] and 1.20 [1.14; 1.27], respectively). Adjusted restricted cubic splines confirmed findings from linear trend Cox models (Figure 1). ApoB-P count was highly correlated with ApoB level (r=0.99), and replication of analyses replacing one for another revealed no change in results.

Conclusion
The risk of MI is independently associated with the total particle count of all ApoB-P, and not the size or type of these lipoproteins. ApoB level can be used as a very accurate surrogate of ApoB-P count in the clinical setting. Lipoprotein(a) is associated with MI risk independently of total particle count, and therefore, the combination of ApoB and lipoprotein(a) may provide the optimal clinical evaluation of lipid-mediated MI risk.

Funding Acknowledgement
Type of funding sources: None.
Investigation of type 1 collagen a1 chain in plasma as a potential novel biomarker for prediction of coronary heart disease
Authors: Hammareus F , Nilsson L , Ong K L , Kristenson M , Festin K , Lundberg A , Chung R W S , Swahn E , Alfredsson J , Holm Nielsen S , Jonasson L 
Published: October 2022

Abstract

Background
Remodeling of the extracellular matrix (ECM) plays a crucial role in development and progression of atherosclerosis. Collagens, in particular type I collagen, are the most abundant ECM proteins in an atherosclerotic plaque. Recently, type I collagen α1 chain (COL1α1) in plasma was identified as a potential predictor of coronary heart disease (CHD).

Aim
The aim was to further confirm the predictive value of COL1α1 and also to investigate its correlates in a population-based cohort as well as changes over time in patients with manifest CHD in Sweden.

Methods
In a total of 1007 well-characterized individuals (50% women), 86 CHD cases and 184 sex- and age-matched controls were identified at 13 years follow-up. CHD at follow-up was defined as first-time event of myocardial infarction (MI) or invasive coronary intervention. Plasma levels of COL1α1 was quantified by the Luminex assay while PRO-C1 and C1M, two markers of type I collagen synthesis and degradation, respectively, were quantified by ELISA. In Cox proportional hazard analysis, log2 values of biomarker levels were used. In addition, temporal change of COL1α1 levels was also examined in a cohort of 125 patients with acute MI followed for 6 months.

Results
COL1α1 levels were significantly associated with incident CHD, both unadjusted (HR = 0.69, 95% CI 0.56–0.87, p=0.001) and after multiple adjustment (HR = 0.55, 95% CI 0.41–0.75, p&lt;0.001). PRO-C1 was similarly associated with CHD, unadjusted (HR = 0.62, 95% CI 0.47–0.82, p=0.001) as well as adjusted (HR = 0.61, 95% CI 0.43–0.86, p=0.005), while C1M was not. In patients with acute MI, COL1α1 levels remained stable over 6 months. COL1α1 was significantly correlated to PRO-C1 (r=0.73, p&lt;0.001), while there were no correlations to C1M, markers of inflammation (C-reactive protein, interleukin-6, matrix metalloproteinase-9) or myocardial injury (troponin T).

Conclusions
Circulating COL1α1 in plasma was independently and inversely associated with incident CHD. Furthermore, COL1α1 levels appeared to be relatively stable after an acute MI. COL1α1 levels seem to reflect collagen synthesis rather than collagen degradation and inflammation. Future studies are needed to confirm whether COL1α1 is a clinically useful marker and/or predictor of CHD.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): This research was in part financed by a grant from the Region of Östergötland, Sweden, aimed towards scientists early in their career. We would like to thank the people behind this grant for contributing to this research.This research was also partly supported by Futurum - the academy for healthcare in Region Jönköping County.
Plasma amyloid-beta levels and risk of new-onset atrial fibrillation in the general population
Authors: Lu Z , Tilly M , Wolters F , De Groot N M S , Ikram M A , Kavousi M 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) is a major health burden worldwide, with significant sex differences in epidemiology and risk factors. Amyloid-β40 (Aβ40) and Amyloid-β42 (Aβ42), the hallmark of cerebral amyloid angiopathy, have recently been linked to prevalence and prognosis of several cardiovascular outcomes including stroke and coronary heart disease. However, whether these biomarkers are associated with incident AF remains largely unknown.

Purpose
To investigate the associations between plasma concentrations of Aβ40 and Aβ42 with new-onset AF.

Methods
4,134 participants without a history of AF at baseline (from 2002 to 2005) with qualified plasma samples in the Rotterdam Study were included in this study. AF was diagnosed by electrocardiograms, general practitioners' and hospital records. Cox proportional hazards regression models with natural cubic splines were used to assess the linear/nonlinear association between biomarkers and risk of new-onset AF. All models were adjusted for traditional cardiovascular risk factors.

Results
Mean age was 71.3±7.2 years and 2,383 (57.6%) were women. Median follow-up time was 9.2 years. In the fully adjusted model, higher levels of Aβ40 [hazard ratio, 95% confidence interval: 1.16 (1.05–1.28)] and Aβ42 [1.19 (1.09–1.31)], as well as Amyloid-β42 to β40 ratio (Aβ42/40) [1.09 (1.02–1.17)] were significantly associated with incident AF. The observed association between Aβ40 and AF attenuated after mutual adjustment for Aβ42 [1.05 (0.92–1.19)]. In addition, a J-shaped association was found between Aβ40 and AF with the lowest AF risk at Aβ40 values of 212.5 pg/ml.

Conclusions
Both Aβ40 and Aβ42 were independently significantly associated with new-onset AF in the general population independent of cardiovascular risk factors. Findings also suggest a stronger association between AF onset and Aβ42 and AF onset, compared to Aβ40. A nonlinear association was found between Aβ40 and AF, reflecting a substantially increased AF risk among participants with severely increased Aβ40 values.

Funding Acknowledgement
Type of funding sources: None.
Decreasing albumin within normal range is associated with increased likelihood of ischemic heart disease
Authors: Coster D , Kodesh A , Fardman A , Tiosano S , Moshkovits Y , Bernstein D , Kaplan A , Shamir R , Maor E 
Published: October 2022

Abstract

Background
Albumin (ALB) is a known biomarker of frailty, and cardiovascular disease and frailty are interdependent. Epidemiological evidence demonstrates that low serum albumin levels are linked to events of ischemic heart disease (IHD), venous thromboembolism, heart failure, atrial fibrillation, and stroke.

Purpose
We aimed to investigate the association of variations in ALB levels that are within normal range with IHD events among apparently healthy adults.

Methods
A case-control retrospective study of self-referred adults participating in an executive screening program between 2002 and 2017. All subjects were free of IHD and diabetes at baseline and had their ALB documented in each visit. Only subjects with at least two ALB measurements and whose ALB levels were within the normal range at all visits were included. Relationships between ALB trend and occurrence of IHD (acute coronary syndrome or percutaneous coronary intervention) within 2 years from the last visit were investigated.

Results
The final study cohort included 16,386 subjects. Median age was 53 (IQR 45–60), 11,461 (70%) were men. Analysis included a total of 99,127 visits. Median number of visits per subject was 5 (IQR 3–9, median inter-visit time 1.02 years) and median ALB level was 4.4 (IQR 4.2–4.6). IHD within 2 years was diagnosed in 545 (3%) subjects. Of those, only 36 were female and they tended to have lower variations in ALB throughout the years. Hence, we conducted an analysis of the 509 males only, and created an equal-size age-matched cohort of IHD-free subjects. Our analysis demonstrated a progressive and significant decrease in ALB levels among IHD cases, but not among controls (mean decrease of 0.021 g/DL vs. 0.004 g/DL per year, p&lt;0.01; OR [CI] = 0.82 [0.72–0.93]; Figure 1). Similar results were found among subjects with at least 3 or 4 visits (0.015 g/DL vs. 0.006 g/DL per year, p=0.027, and 0.009 g/DL vs. 0.003 g/DL per year, p=0.045, respectively).

Conclusions
Kinetics of ALB within the normal range can identify men at risk for IHD in preventive healthcare screening programs.

Funding Acknowledgement
Type of funding sources: None.
Characteristics of patients with lipoprotein(a) assessment: a health insurance claims database analysis
Authors: Stuerzebecher P E , Schorr J , Klebs S , Laufs U 
Published: October 2022

Abstract

Background
Elevated lipoprotein(a) (Lp(a)) is an inherited risk factor for cardiovascular disease. Testing for Lp(a) in primary care is recommended by current ESC guidelines to identify persons at risk. We aimed to report contemporary trends in Lp(a) testing in Germany and subsequent changes in treatment strategies and patient's outcome over time.

Methods and results
An observational, retrospective, anonymized claims data analysis was performed on a database with 4 million patients, representative of the German population in the years 2015 to 2018. Patients were eligible when no Lp(a) test was documented in the year prior to the index date/quarter (time point of the first documented Lp(a) test) and if the patient data was available for at least 1 year before and after the Lp(a) test or until death, whichever came first. In a cross-sectional analysis, Lp(a) test rates in the selected database population increased from 0.25% (n=7,432) in 2015 to 0.34% (n=10,257) in 2018. About 57.8% of the tested population was female. Higher test rates were observed in women especially in younger age groups. A subgroup analysis of patients with previous atherosclerotic cardiovascular disease (ASCVD) revealed overall higher Lp(a) test rates (0.43% in 2015, 0.60% in 2018). In a longitudinal analysis, patients tested for Lp(a) and respective controls matched for age, gender and region, were followed for a maximum of four years. Out of 3,139,410 eligible patients, 36,609 (1.17%) were tested for Lp(a) over the study period at a mean age of 51.91 years and were meeting the inclusion criteria. In comparison to matched controls without Lp(a) test, patients tested for Lp(a) had more comorbidities and higher ASCVD risk. The Lp(a)-tested cohort and the control group had similar mortality rates (0.88 vs. 0.94 per 100 person-years (PY), p=0.21). However, total mortality was lower in patients with prior ASCVD and Lp(a) test compared to matched patients with prior ASCVD but no Lp(a) test (Rates: 2.30 vs. 3.64 per 100 PY, p&lt;0.001). Importantly, the patients with Lp(a) test were treated with a higher number of cardiovascular medications, underwent more laboratory examinations, and had more frequent consultations by specialized physicians after the test.

Conclusion
Lp(a) testing is an indicator of more intensive diagnostic work-up and treatment. Less than 1% of the patients have been newly tested for Lp(a) in 2018. The data identify an opportunity to better characterize ASCVD risk by testing for Lp(a).

Funding Acknowledgement
Type of funding sources: None.
Quantitative cardiovascular magnetic resonance perfusion mapping as a guide for diagnosis
Authors: Androulakis E , Azzu A , Surkova E , Bakula A , Papagkikas P , De Silva R , Kellman P , Pennell D , Alpendurada F 
Published: October 2022

Abstract

Background
There is a lack of gold-standard non-invasive clinical markers derived from quantitative cardiovascular magnetic resonance (CMR) stress perfusion.

Purpose
This study aimed to compare quantification indices testing the hypothesis that they can discriminate possible normal from abnormal groups including microvascular dysfunction (MVD), coronary artery disease (CAD), and non-diagnostic tests due inappropriate response to the stressor agent.

Methods
Four-hundred and thirty-six consecutive patients (n=436, mean age 59.5 yrs) with typical angina and/or risk factors for CAD underwent stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse protocol to estimate quantitative markers on a 1.5 T scanner. Anatomical coronary information, risk factors, and myocardial infarct were evaluated. Myocardial perfusion reserve values (MPR) were adjusted for rate-pressure product. For each perfusion assessment 3 short axis slice locations were imaged per heartbeat over a 60-heartbeat acquisition during an IV bolus of 0.05 mmol/kg of gadolinium contrast. Patients were divided into 4 groups: A) normal perfusion study; B) positive perfusion study due to epicardial coronary artery disease; C) positive perfusion study due to microvascular coronary artery disease; and D) non-diagnostic perfusion study due to inappropriate response to pharmacological stress.

Results
Stress myocardial blood flow (SMBF) and mean adjusted MPR differed between patients with no ischaemia and those clinically diagnosed with MVD (2.41±0.75 vs 1.81±0.52 mL/g/min, p&lt;0.001, 2.78±0.94 vs 2.39±1.02, p=0.009, respectively). Patients deemed to have inadequate hyperaemia as opposed to inducible ischaemia had the lowest mean SBF of 1.25±0.32 vs 1.80±0.61 mL/g/min (p&lt;0.001); a cut-off value of &lt;1.34 mL/g/min had the best predictive diagnostic accuracy for inadequate stress (area under curve [AUC] 0.875). Of note, comparing MVD vs CAD (single, 2-vessels, multivessel disease) without infarction stress pulmonary transit time (PTT) (centroid 6.9±0.72 vs 5.95±0.58, p=0.026), SMBF (1.80 vs 2.10 mL/g/min, p=0.0075), stress endo (1.60 vs 1.94 mL/g/min, p=0.0013), and stress epi (1.94 vs 2.21 mL/g/min, p=0.021) differed significantly between the two groups. The presence of infarction was shown also to be a significant discriminator between the two groups in logistic regression analysis (OR: 8.3, p=0.030).

Conclusions
This study showed fully quantitative stress markers may be useful in discriminating MVD and CAD patients as well as excluding patients with inadequate hyperaemia.

Funding Acknowledgement
Type of funding sources: None.
Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients
Authors: Mavraganis G , Georgiopoulos G , Delialis D , Aivalioti E , Patras R , Petropoulos I , Dimopoulou A M , Angelidakis L , Sianis A , Bampatsias D , Dimoula A , Maneta E , Kosmopoulos M , Stellos K , Stamatelopoulos K 
Published: October 2022

Abstract

Background
The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established.

Purpose
In the present study we aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients.

Methods
We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n=751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n=2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology (ESC) guidelines (clinical ESCrisk). Intima-media thickness (IMT) excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As endpoint of the study was defined the composite of CV death, acute myocardial infarction (MI) and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort.

Results
MaxWT &gt;2.00mm and avg.maxWT &gt;1.39mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (p&lt;0.05 for net reclassification index, integrated discrimination index and Delta Harrell's C index). MaxWT &lt;0.9mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort.

Conclusion
Integration of carotid ultrasonography in guidelines-defined risk stratification may identify very high risk patients in need for further residual risk reduction or at very low probability

Funding Acknowledgement
Type of funding sources: None.
Effects of canagliflozin on cardiovascular and kidney outcomes and mortality in primary and secondary cardiovascular prevention: pooled analysis from the CANVAS program and CREDENCE trial
Authors: Ang F , Rapattoni W , Bajaj H S , Mancini G B J , Poirier P , Sharma A , Wong N C , Slee A , Levin A , Mahaffey K W 
Published: October 2022

Abstract

Background/Introduction
Individuals with type 2 diabetes mellitus (T2DM) are at a greater risk for experiencing cardiovascular (CV) and kidney events. Canagliflozin is a sodium glucose co-transporter 2 inhibitor that has demonstrated reduction of these events in participants with T2DM with or without a history of CV disease (CVD) in both the CANVAS Program and CREDENCE trial.

Purpose
To determine the pooled effects of canagliflozin on CV outcomes, kidney outcomes, and all-cause mortality in trial participants with and without a history of CVD (secondary and primary prevention, respectively).

Methods
This post hoc analysis pooled individual participant data from the CANVAS Program and CREDENCE trial. The effects of canagliflozin versus placebo on time to first event for CV outcomes (major adverse cardiovascular events [MACE], which was defined as CV death, myocardial infarction [MI] or stroke; CV death; hospitalization for heart failure [HHF], and the composite of CV death or HHF), kidney outcomes (end-stage kidney disease [ESKD], doubling of serum creatinine [dSCr], and the composite of ESKD or dSCr), and all-cause mortality were assessed in participants with T2DM with or without a history of CVD.

Results
Among the 14,543 participants from the pooled CANVAS Program (N=10,142) and CREDENCE trial (N=4401), 5667 (39%; canagliflozin, n=3128; placebo, n=2539) were in the primary prevention group and 8876 (61%; canagliflozin, n=4869; placebo, n=4007) were in the secondary prevention group. Baseline characteristics of participants in each group were generally similar. Across both primary and secondary prevention participants, no heterogeneity in the relative risk reduction of CV outcomes, kidney outcomes, and all-cause mortality with canagliflozin versus placebo was observed (all P interaction &gt;0.624; Figures 1 and 2). The benefits of canagliflozin on MACE and the composite of CV death or HHF were observed as early as 6 months into treatment in both subgroups of participants and were sustained throughout the study.

Conclusions
In this pooled analysis of patient-level data from the CANVAS Program and CREDENCE trial, treatment with canagliflozin demonstrated early benefits and was associated with reduced risk of CV outcomes, kidney outcomes, and all-cause mortality, with similar results across primary and secondary prevention participants with T2DM.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Janssen, Inc.
Right ventricular function and outcome in patients undergoing transcatheter mitral valve repair
Authors: Koschutnik M , Dona C , Nitsche C , Dannenberg V , Koschatko S , Mascherbauer K , Beitzke D , Loewe C , Huelsmann M , Schneider M , Bartko P , Goliasch G , Hengstenberg C , Kammerlander A , Mascherbauer J 
Published: October 2022

Abstract

Objectives
This study sought to assess the impact of right ventricular dysfunction (RVD) on event-free survival after transcatheter mitral valve repair (TMVR) for severe mitral regurgitation.

Background
The prognostic value of left and RV global longitudinal strain (LV- and RV-GLS) on cardiovascular magnetic resonance feature tracking (CMR-FT) in patients undergoing TMVR is unknown.

Methods
Consecutive TMVR patients underwent pre-procedural and follow-up CMR-FT analysis. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization (HFH) and death.

Results
62 patients (78.3±7.0y/o, 45% female, EuroSCORE-II: 9.6±7.1%) underwent CMR-FT prior to TMVR, 24% had concomitant tricuspid edge-to-edge repair (TTVR). On presentation, 23 (37%) patients suffered RVD, defined as RV-GLS &gt;−20% on CMR-FT. RVD was associated with reduced LV and RV ejection fraction (LVEF: 39.2 vs. 48.7%, p=0.008, RVEF: 35.1 vs. 46.7%, p&lt;0.001), as well as impaired LV-GLS (−14.0 vs. −19.5%, p=0.012).
Eighteen events (12 deaths, 6 HFH) occurred during follow-up (11.4±9.1 months). On multivariable Cox-regression adjusted for baseline, procedural, imaging, and biomarker data, RV but not LV-GLS was significantly associated with outcome (adj.HR 2.50, 95% CI: 1.29–4.86, p=0.007 and 1.46, 95% CI: 0.50–4.28, p=0.491, respectively). Among various definitions of RVD on echocardiography and CMR, only RV-GLS on CMR-FT was significantly associated with outcome (RV-GLS &gt;−20%: adj.HR 7.53, 95% CI: 2.07–27.42, p=0.002), but not RVEF on CMR or echo-indices of RV function (Central Illustration).
Follow-up CMR-FT was performed in 21 (34%) patients and RV-GLS significantly improved after TMVR (−20.6 to −25.2%, p=0.016), irrespective of additional TTVR.

Conclusions
RV-GLS, as determined on CMR-FT, rather than LV-GLS or RVEF, is an independent predictor of outcome in patients undergoing TMVR.

Funding Acknowledgement
Type of funding sources: None.