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Funding Information: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is supported by Stichting Lijf en Leven. The sponsor had no role in study design, methods, subject recruitment, data collection or analysis, or preparation of the manuscript. Publisher Copyright: © The Author(s) 2023. Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947. publishersversion epub_ahead_of_print

Supplemental material, sj-pdf-3-vmj-10.1177_1358863X231181159 for Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm by Elke Bouwens, Alexander Vanmaele, Sanne E Hoeks, Hence JM Verhagen, Bram Fioole, Adriaan Moelker, Sander ten Raa, Burhan Hussain, José Oliveira-Pinto, Frederico Bastos Gonçalves, Arne S Ijpma, Imo E Hoefer, Felix van Lier, K Martijn Akkerhuis, Danielle F Majoor-Krakauer, Eric Boersma and Isabella Kardys in Vascular Medicine

Supplemental material, sj-pdf-2-vmj-10.1177_1358863X231181159 for Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm by Elke Bouwens, Alexander Vanmaele, Sanne E Hoeks, Hence JM Verhagen, Bram Fioole, Adriaan Moelker, Sander ten Raa, Burhan Hussain, José Oliveira-Pinto, Frederico Bastos Gonçalves, Arne S Ijpma, Imo E Hoefer, Felix van Lier, K Martijn Akkerhuis, Danielle F Majoor-Krakauer, Eric Boersma and Isabella Kardys in Vascular Medicine

Supplemental material, sj-pdf-3-vmj-10.1177_1358863X231181159 for Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm by Elke Bouwens, Alexander Vanmaele, Sanne E Hoeks, Hence JM Verhagen, Bram Fioole, Adriaan Moelker, Sander ten Raa, Burhan Hussain, José Oliveira-Pinto, Frederico Bastos Gonçalves, Arne S Ijpma, Imo E Hoefer, Felix van Lier, K Martijn Akkerhuis, Danielle F Majoor-Krakauer, Eric Boersma and Isabella Kardys in Vascular Medicine

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231181159 for Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm by Elke Bouwens, Alexander Vanmaele, Sanne E Hoeks, Hence JM Verhagen, Bram Fioole, Adriaan Moelker, Sander ten Raa, Burhan Hussain, José Oliveira-Pinto, Frederico Bastos Gonçalves, Arne S Ijpma, Imo E Hoefer, Felix van Lier, K Martijn Akkerhuis, Danielle F Majoor-Krakauer, Eric Boersma and Isabella Kardys in Vascular Medicine

Additional file 1. Supplemental materials.

Supplemental material, sj-pdf-2-vmj-10.1177_1358863X231181159 for Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm by Elke Bouwens, Alexander Vanmaele, Sanne E Hoeks, Hence JM Verhagen, Bram Fioole, Adriaan Moelker, Sander ten Raa, Burhan Hussain, José Oliveira-Pinto, Frederico Bastos Gonçalves, Arne S Ijpma, Imo E Hoefer, Felix van Lier, K Martijn Akkerhuis, Danielle F Majoor-Krakauer, Eric Boersma and Isabella Kardys in Vascular Medicine

Purpose: Higher soluble ST2 (sST2) levels at admission are associated with adverse outcome in acute coronary syndrome (ACS) patients. We studied the dynamics of sST2 over time in post-ACS patients prior to a recurrent ACS or cardiac death. Methods: We used the BIOMArCS case cohort, consisting of 187 patients who underwent serial blood sampling during one-year follow-up post-ACS. sST2 was batch-wise quantified after completion of follow-up in a median of 8 (IQR: 5–11) samples per patient. Joint modelling was used to investigate the association between longitudinally measured sST2 and the endpoint, adjusted for gender, GRACE risk score and history of cardiovascular diseases. Results: Median age was 64 years and 79% were men. The 36 endpoint patients had systematically higher sST2 levels than those that remained endpoint free (mean value 29.6 ng/ml versus 33.7 ng/ml, p-value 0.052). The adjusted hazard ratio for the endpoint per standard deviation increase of sST2 was 1.64 (95% confidence interval: 1.09–2.34; p = 0.019) at any time point. We could not identify a steady or sudden increase of sST2 in the run-up to the combined endpoint. Conclusion: Asymptomatic post-ACS patients with persistently higher sST2 levels are at higher risk of recurrent ACS or cardiac death during one-year follow-up.

AIMS: Previous studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF). METHODS AND RESULTS: RNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)-1306-5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time-points during the study's 1-year follow-up. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR-1306-5p were positively associated with risk for reaching the primary endpoint at the same time-point [hazard ratio (HR) 4.69, 95% confidence interval (CI) 2.18-10.06], independent of clinical characteristics and NT-proBNP. Baseline miR-1306-5p did not improve model discrimination/reclassification significantly compared with NT-proBNP. For miR-320a, miR-378a-3p, miR-423-5p and miR-1254, associations with the primary endpoint were present after adjustment for age and sex (HR 1.38, 95% CI 1.12-1.70; HR 1.35, 95% CI 1.04-1.74; HR 1.45, 95% CI 1.10-1.92; HR 1.22, 95% CI 1.00-1.50, respectively). Rates of detection of myomiRs miR-208a-3p and miR-499a-5p were very low. CONCLUSIONS: Repeatedly measured miR-1306-5p was positively associated with adverse clinical outcome in AHF, even after multivariable adjustment including NT-proBNP. However, baseline miR-1306-5p did not add significant discriminatory value to NT-proBNP. Low-abundance, heart-enriched myomiRs are often undetectable, which mandates the development of more sensitive assays.

Dyspnea is a common side effect of ticagrelor, leading to drug discontinuation in roughly one in every 20 treated patients. Studies have suggested that ticagrelor inhibits the sodium-independent equilibrative nucleoside transporter-1, which may increase adenosine plasma levels and explain drug-related dyspnea. However, the identification of a pattern of periodic breathing associated to increased chemosensitivity to hypercapnia in patients with ticagrelor-related dyspnea has reinforced the hypothesis that this side effect may result from direct inhibition of P2Y receptors on neurons leading to purinergic stimulation of the chemoreflex system. Simultaneous measurements of adenosine and ticagrelor plasma levels in patients with and without dyspnea while on treatment with ticagrelor may help unraveling the mechanism of this common and clinically relevant side effect.

BACKGROUND: Several clinical studies have evaluated the association between galectin-3 levels and outcome in patients with heart failure (HF). However, little is known about the predictive value of repeated galectin-3 measurements. This study evaluates the prognostic value of repeated time-dependent galectin-3 measurements in acute HF patients. METHODS AND RESULTS: In the TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients with Heart Failure) clinical cohort study, 496 acute HF patients were enrolled in 14 hospitals in The Netherlands, between 2009 and 2014. Repeated blood samples (7) were drawn during 1-year follow-up. Associations between repeated biomarker measurements and the primary end point were assessed using a joint model. Median age was 74 years and 37% were women. The primary end point, composite of all-cause mortality and HF rehospitalization, was reached in 188 patients (40%), during a median follow-up of 325 days (interquartile range 85-401). The median baseline galectin-3 level was 24 ng/mL (interquartile range 18-34). The mean number of galectin-3 measurements available per patient was 4.3. After adjustment for clinical factors and N-terminal pro-brain natriuretic peptide, there was a weak association between baseline galectin-3 and risk of the primary end point. When repeated measurements were taken into account, the adjusted hazard ratio per 1 SD increase of the galectin-3 level (on the log2 scale) at any time point increased to 1.67 (95% confidence interval, 1.24-2.23, P

Background It has been shown that intravascular ultrasound (IVUS) and radiofrequency (RF-)IVUS can detect high-risk coronary plaque characteristics. Objectives The authors studied the long-term prognostic value of (RF-)IVUS-derived plaque characteristics in patients with coronary artery disease (CAD) undergoing coronary angiography. Methods From 2008 to 2011, (RF-)IVUS was performed in 1 nonstenotic segment of a nonculprit coronary artery in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. The pre-defined primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, nonfatal ACS, or unplanned revascularization. Hazard ratios (HRs) were adjusted for age, sex, and clinical risk factors. Results During a median follow-up of 4.7 years, 152 patients (26.2%) had MACE. The presence of a lesion with a minimal luminal area ≤4.0 mm2 was independently associated with MACE (HR: 1.49; 95% CI: 1.07 to 2.08; p = 0.020), whereas the presence of a thin-cap fibroatheroma lesion or a lesion with a plaque burden ≥70% on its own were not. Results were comparable when the composite endpoint included cardiac death instead of all-cause death. The presence of a lesion with a plaque burden of ≥70% was independently associated with the composite endpoint of cardiac death, nonfatal ACS, or unplanned revascularization after exclusion of culprit lesion-related events (HR: 1.66; 95% CI: 1.06 to 2.58; p = 0.026). Likewise, each 10-U increase in segmental plaque burden was independently associated with a 26% increase in risk of this composite endpoint (HR: 1.26 per 10-U increase; 95% CI: 1.03 to 1.52; p = 0.022). Conclusions IVUS-derived small luminal area and large plaque burden, and not RF-IVUS–derived compositional plaque features on their own, predict adverse cardiovascular outcome during long-term follow-up in patients with CAD. (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis–Intravascular Ultrasound Study [AtheroRemoIVUS]; NCT01789411)