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Journal articleZhang J, Whitwell HJ, Emanueli C, et al., 2026,
Severe hypoxia drives loss of ST6GAL1-mediated α2,6-sialylation in the epicardial secretome impairing angiogenic activity.
, Biol Open, Vol: 15The epicardium contributes to cardiac development and regeneration, primarily through paracrine signalling. However, the impact of severe hypoxic stress, such as occurs immediately following myocardial infarction, on the activity of the epicardial secretome remains poorly defined. Here we investigated the angiogenic potential of the epicardial secretome under normoxic and hypoxic conditions. In contrast to expectation, the results demonstrate that the angiogenic effect of epicardial cells on vascular endothelium is hampered under severe hypoxia. Mechanistically, we found that hypoxia-mediated sialylation remodels the epicardial secretome altering its angiogenic potential. Severe hypoxia suppresses St6gal1 gene expression decreasing the level of α2,6-sialylation, as measured by comprehensive lectin profiling and sialyltransferase analysis. Functional studies revealed that both global and α2,6-specific sialylation inhibition markedly compromised the pro-angiogenic capacity of the epicardial secretome, reducing the in vitro tube formation. Our findings indicate that ST6GAL1-dependent α2,6-sialylation is required to activate the pro-angiogenic potential of the epicardial secretome. These data also suggest that glycosylation is a modifiable response to ischemic injury, offering a new therapeutic target for enhancing tissue repair.
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Journal articleRothman AMK, Toshner M, Wilkins MR, 2026,
Target engagement and drug delivery in PAH: lessons from inhaled imatinib.
, Am J Respir Crit Care Med, Vol: 212, Pages: 714-715 -
Journal articleFuenderich MT, Yogeswaran A, Janetzko P, et al., 2026,
PVRI-GoDeep-A Global Meta-Registry at the Crossroads of Heart and Lung.
, Compr Physiol, Vol: 16Pulmonary hypertension (PH) is a complex disease characterized by increased pressure in the pulmonary arteries. It encompasses a heterogeneous group of entities that increase right heart afterload and often lead to right heart failure and premature death. Advancing diagnosis, risk stratification, and treatment across the diverse PH spectrum requires large, high-quality, longitudinal datasets that exceed the scope of individual national or regional registries. To address this need, PVRI GoDeep was founded under the umbrella of the Pulmonary Vascular Research Institute (PVRI). This global meta registry harmonizes and integrates anonymized patient-level data from existing PH registries at expert centers worldwide. PVRI GoDeep enables the reuse of locally collected real-world data by mapping heterogeneous datasets to a predefined data dictionary, thorough quality checks, and regular updates. This approach supports phenotyping across all PH groups, enables international comparisons, and allows in-depth analysis of rare subtypes, disease progression, treatment responses, and survival rates. Importantly, GoDeep makes clinically relevant research possible that cannot be conducted at the level of a single center, such as validating risk-stratification tools across PH subgroups, evaluating off-label therapies, and investigating newly recognized entities, such as mild PH. By January 2026, data from more than 45,000 individuals worldwide were integrated into GoDeep, making it one of the largest and most diverse PH registries. Offering a scalable, governed, and disease-independent framework for harmonized real-world evidence generation, PVRI GoDeep is a powerful platform to deepen the understanding of PH and support the development of clinical guidelines for the diagnosis and treatment of PH.
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Journal articleDucker CB, Preece MV, Pericleous C, et al., 2026,
Revisiting antiphospholipid syndrome: A thrombo-inflammatory disorder beyond clotting.
, Blood Rev, Vol: 76The dysregulation of protective immunothrombosis is termed thrombo-inflammation. Antiphospholipid syndrome (APS) is an antibody mediated autoimmune, inflammatory and prothrombotic disease. APS is an archetypal disease for thrombo-inflammation, in which a proinflammatory/prothrombotic state is caused by antiphospholipid antibodies (aPL). These antibodies directly or indirectly exert effects on monocytes and neutrophils, as well as platelets and endothelium, through binding of phospholipid binding proteins. In addition, aPL are linked with activation of coagulation and complement, leading to thrombosis. Although APS is an autoimmune antibody-mediated prothrombotic disease, its main treatment strategy at present is anticoagulation. Anticoagulation does not modulate endothelial cells or inflammation. This could explain the high risk of recurrent thrombosis, despite patients being on adequate anticoagulation. This review examines endothelial dysfunction and thrombo-inflammation in thrombotic APS as understanding the role of thrombo-inflammation in the pathogenesis of APS may help to develop new treatments or repurpose existing treatments.
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Journal articleSchmidt LE, Burnap SA, Singh B, et al., 2026,
Integrative Proteomic and Lipidomic Analysis of Patients With Acute Myocardial Infarction Treated With PCSK9 Antibodies and Statins.
, Circ Genom Precis Med, Vol: 19BACKGROUND: PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition is a potent cholesterol-lowering strategy. This study examined the effects of PCSK9 monoclonal antibodies (mAbs) and high-intensity statins beyond low-density lipoprotein cholesterol reduction, which are not fully defined, particularly in patients with acute myocardial infarction (MI). METHODS: Proteomic and lipidomic analyses were conducted on plasma from 265 patients with acute MI from the PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) randomized, placebo-controlled PCSK9 mAb trial and 34 patients without MI with hyperlipidemia from the Vienna Lipid Clinic registry, also receiving PCSK9 mAbs. RESULTS: Discovery proteomics revealed changes in apolipoproteins and increased PCOLCE (procollagen C-endopeptidase enhancer 1) levels in both the PCSK9 mAb and placebo groups after MI. UK Biobank data confirmed PCOLCE and PCSK9 upregulation as associated with statin use. Hepatoma cell experiments demonstrated a dose-dependent PCOLCE induction on statin treatment. Compared with placebo (statins only), PCSK9 mAb therapy resulted in greater reductions in APOB (apolipoprotein B), APOE (apolipoprotein E), APOC2 (apolipoprotein C2), and APOC3 (apolipoprotein C3), as shown by targeted proteomics. Mediation analysis indicated that these changes were largely explained by low-density lipoprotein cholesterol lowering. Lipidomics identified more pronounced reductions in cholesteryl esters, ceramides, sphingomyelins, phosphatidylcholines, triglycerides, and diglycerides in PCSK9 mAb-treated patients with MI. Results were largely consistent in patients without MI. However, levels of LPA (apolipoprotein[a]), the characteristic protein component of lipoprotein(a), remained unchanged in PCSK9 mAb-treated patients with MI, since a rise of LPA was observed in the placebo group post-MI. CONCLUSIONS: Most apolipoprotein changes after PCSK9 m
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Journal articleHarbaum L, Klose H, Lund J, et al., 2026,
Metabolomic signature of right ventricular-pulmonary arterial coupling differentiates hemodynamic response to imatinib therapy in pulmonary arterial hypertension.
, J Heart Lung Transplant, Vol: 45, Pages: 647-656BACKGROUND: Right ventricular (RV) dysfunction is the leading cause of mortality in pulmonary arterial hypertension (PAH). Although RV metabolic remodeling in chronic pressure overload is recognized, the circulating metabolic signatures of RV-pulmonary arterial (PA) coupling and their clinical relevance remain poorly defined. METHODS: We first integrated pressure-volume-derived RV/PA metrics with untargeted plasma metabolomics in 33 PAH patients, using both network-based and single-metabolite analyses. Findings were replicated in 14 patients using echocardiographic surrogates. In 16 participants from the phase 2 PIPAH trial of imatinib, we examined longitudinal metabolite changes in relation to hemodynamic responses obtained from implanted devices. RESULTS: The end-systolic to arterial elastance ratio (Ees/Ea), a load-independent measure of RV contractility and RV-PA coupling, emerged as a central node in the metabolic network, while metrics related to afterload and RV stiffness were more peripherally located. In individual metabolite analyses, 9 metabolites were significantly associated with Ees/Ea and its echocardiographic surrogate, independent of potential confounders, including kidney and liver function. Pathway enrichment analysis confirmed a predominance of fatty acid metabolism, particularly acylcarnitines. In the PIPAH study cohort, individual-level analyses showed that reductions in acylcarnitine levels at 4 and 24 weeks of imatinib therapy discriminated patients with improved cardiac output (area under the curves 0.89 and 0.84). CONCLUSIONS: We identify a distinct circulating metabolomic signature, enriched in fatty acid metabolites, associated with RV-PA coupling in PAH. These metabolites may inform on the risk and trajectory of RV maladaptation during treatment and guide therapeutic decisions to optimize the benefit-harm ratio.
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Journal articleMoscarelli M, Skeffington KL, Fudulu D, et al., 2026,
Left and right myocardial ventricular energetics during cardioplegic ischemic arrest and reperfusion in patients undergoing cardiac surgery.
, J Mol Cell Cardiol, Vol: 213, Pages: 84-92BACKGROUND: Effective myocardial protection during cardiac surgery is essential, yet the differential metabolic stress of the left (LV) and right ventricles (RV) to ischemia-reperfusion remains poorly characterized. METHODS: This predefined substudy of a multicenter randomized trial conducted in the United Kingdom (ISRCTN33084113) evaluated remote ischemic preconditioning in patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). Paired LV and RV biopsies were obtained before ischemia and after reperfusion. High-performance liquid chromatography was used to quantify metabolite concentrations and calculate markers of energetics. Cross-clamp time and postoperative troponin levels were recorded. RESULTS: Eighty-nine patients were included (CABG: n = 49; AVR: n = 40). Following ischemia-reperfusion, LV exhibited greater decline in metabolites than the RV. In CABG, this included larger sustained fall in ATP (-0.90 vs -0.13 μmol/mg, p = 0.0032) and glutamate (-4.22 vs -1.33 μmol/mg, p = 0.0009), alongside ADP (-0.53 vs -0.20 μmol/mg, p = 0.0196), GTP (-0.04 vs -0.01 μmol/mg, p = 0.0160), and B-NAD (-0.15 vs -0.04 μmol/mg, p = 0.0137). Computed energy charge decreased significantly in both ventricles (LV: p = 0.0002; RV: p = 0.010), but remained stable in AVR. ATP/AMP and ATP/ADP ratios declined more in the LV, suggesting impaired energy buffering. There was no significant correlation between cross-clamp time and changes in energy charge in either the LV or RV. Troponin release correlated with ischemic time in CABG, but EC decline did not. CONCLUSIONS: The LV shows greater depletion of myocardial metabolites than the RV following ischemia-reperfusion, particularly in CABG patients. These findings support ventricle-specific strategies to optimize myocardial protection.
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Journal articleDelgado-SanMartin JA, Keles M, Errington N, et al., 2026,
Assessing the feasibility of using smartphone data to identify risk of idiopathic pulmonary arterial hypertension
, npj Cardiovascular Health, Vol: 3, ISSN: 2948-2836Idiopathic pulmonary arterial hypertension (IPAH) is a progressive, life-limiting condition often diagnosed late due to non-specific symptoms and requirement of invasive right heart catheterisation. This pilot study explores the feasibility of using real-world physical activity data from wearable devices and a smartphone app (My Heart Counts) to aid earlier detection. We analysed up to eight years of retrospective data from 109 UK participants, including patients with IPAH, disease controls, and healthy individuals. A classifier trained on pre-diagnostic activity and heart rate, distinguished individuals with IPAH from healthy and disease controls with an ROC AUC of 0.87, improving to 0.94 with in-app questionnaire input. Validation in a matched US cohort yielded an ROC AUC of 0.74. Wearable-derived metrics correlated with clinical 6MWD supporting their potential to complement traditional risk assessment. These pilot findings suggest that digital health tools may support earlier detection and remote monitoring of IPAH warranting larger scale studies.
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Journal articleRajakulasingam R, Alaour B, McGrath S, et al., 2026,
Cardiac myosin-binding protein C in ST-elevation myocardial infarction
, European Heart Journal: Acute Cardiovascular Care, ISSN: 2048-8726AimsCardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, rising and falling more rapidly than cardiac troponins in myocardial infarction (MI), potentially enabling earlier diagnosis. Its performance has not been assessed in reperfused acute ST-segment elevation myocardial infarction (STEMI), against gold-standard biochemical (high-sensitivity cardiac troponin I, hs-cTnI) or imaging (cardiovascular magnetic resonance, CMR) biomarkers. This study tested the hypotheses that: i) cMyC correlates with acute and final MI size by late gadolinium enhancement (LGE) CMR and ii) cMyC is related to the presence of acute microvascular obstruction (MVO) by CMR.Methods and resultsBlood samples were obtained at 6 ± 2 hourly intervals for 24 hours (hrs) for measurement of hs-cTnI and cMyC concentrations in patients with reperfused acute STEMI. Patients underwent 3T LGE-CMR at ∼3–5 days (n = 69) and ∼4 months (n = 65) after reperfusion. Acute cMyC at all timepoints significantly correlated with acute and final MI size on LGE-CMR, most strongly at 6-hrs post reperfusion (r = 0.7, P < 0.001). cMyC at 6-, 12-, 18− and 24-hrs demonstrated significant discriminatory power in identifying patients with acute MVO, with the 6-hr level having the highest discriminative power. Hs-cTnI correlated more strongly with acute and final MI size compared with cMyC and had significantly higher discriminatory ability in identifying MVO at 12−, 18− and 24-hrs.ConclusioncMyC is a quantitative biochemical biomarker of myocardial injury in reperfused STEMI. Further studies, using optimised high-sensitivity assays, are warranted to evaluate its potential as a novel biomarker after acute MI.
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Journal articleFicany A, Del Alamo M, Bernabeu C, et al., 2026,
Correction: Ficany et al. Epistaxis Prevention, Treatment, and Future Perspectives for Hereditary Hemorrhagic Telangiectasia. J. Clin. Med. 2025, 14, 7724.
, J Clin Med, Vol: 15, ISSN: 2077-0383In the original publication [...].
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Journal articleAjjan RA, Huckstepp RTR, Akbar N, et al., 2026,
Senescence-related myocardial dysfunction: keeping a young heart.
, Eur Heart JThe heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium's regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myo
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Journal articleRoumelioti G, Montoya A, Fisher GLM, et al., 2026,
High-throughput proteomics sample preparation using a 96-channel pipettor and magnetic pin device
, Journal of Proteome Research, Vol: 25, Pages: 1647-1661, ISSN: 1535-3893High-throughput proteomics requires efficient and highly reproducible sample processing, yet workflows─particularly for PTM profiling─remain complex and costly to fully automate. Here, we present a practical intermediate solution using manually operated 96-channel devices: the Gilson Platemaster P220 pipettor and VP Scientific 96-well magnetic pin device. Using this setup, we achieved robust and reproducible phosphoproteomics in a 96-well format, completing protein aggregation capture (PAC/SP3) digestion, desalting, phosphopeptide enrichment, and a second desalting step within 2 days while minimizing operator workload and variability. Several innovations enable this workflow. First, we describe a cost-efficient method to generate 96-well solid-phase extraction plates by directly packing the Oasis HLB sorbent into tapered filter plates. We extensively characterize these plates in terms of loading capacity, lipid removal efficiency, and suitability for high-pH fractionation. Second, we demonstrate that efficient PAC digestion does not require continuous bead suspension; instead, digestion can be achieved by briefly aspirating beads in protease solution, eliminating the need for orbital shaking and simplifying automation. The presented workflow familiarizes users with 96-channel devices and hence serves as a good step toward full automation.
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Journal articleKeles M, Wilkins MR, Lawrie A, 2026,
A blood biomarker to specifically identify idiopathic pulmonary arterial hypertension.
, Nat Cardiovasc Res, Vol: 5, Pages: 178-180 -
Journal articleKelshiker MA, Chhatwal K, Bachtiger P, et al., 2026,
Safety and effectiveness of remote monitoring and prioritization of patients awaiting transcatheter aortic valve implantation: a propensity-matched prospective observational cohort study.
, Eur Heart J Digit Health, Vol: 7AIMS: Health systems face increasing waiting times for transcatheter aortic valve implantation (TAVI), incurring excess deaths and morbidity. To determine whether remote patient monitoring (RPM) using connected technologies can mitigate these risks by prioritizing patients awaiting TAVI, we aimed to measure the clinical safety and effectiveness of an RPM-based prioritization programme. METHODS AND RESULTS: Prospective observational cohort study of all patients awaiting TAVI at Imperial College Healthcare NHS Trust, London, UK, between 24th April 2023 and 15th November 2023. An RPM pathway was implemented for all patients accepted for TAVI. These patients responded to a weekly symptom questionnaire via web, smartphone RPM platform or telephone monitoring; with rule-based clinical escalation. The primary endpoint was the rate of adverse events (defined as emergency department presentation, unplanned hospitalization, or death), compared with a propensity score-matched (PSM) historical control group. Secondary endpoints included pathway performance characteristics for detection of deterioration. 200 patients met inclusion criteria. Despite growth of the waiting list, responsible for longer waiting times experienced by the RPM group [median 104 days (IQR 61.00-176.00) vs. 75 days (IQR 38.75-118.00)], there was no difference in rates of adverse events between RPM-patients and historical controls (Log rank P = 0.9). The RPM pathway had high sensitivity for prediction of waiting list death (100%). Patients deemed at high-risk of deterioration experienced shorter waiting times to treatment. CONCLUSION: RPM for patients awaiting TAVI is feasible and may mitigate the adverse effects of longer waiting times through accurate detection of deterioration and by informing prioritization decisions.
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Journal articleSakkers TR, Mili E, Winter H, et al., 2026,
Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β.
, Circ Res, Vol: 138BACKGROUND: Sex and atherosclerotic plaque histology are intertwined, with fibrous plaques being more prevalent in women. Plaque erosion, a significant contributor to acute coronary syndromes, is linked to fibrous plaques and is more prevalent in women than men. We hypothesize that the molecular drivers of histologically determined fibrous plaques differ between men and women. METHODS: Human end-stage atherosclerotic plaques were isolated from carotid endarterectomy patients included in the Athero-Express Biobank. Fibrous plaques were histologically assessed, linked to clinical characteristics, and processed for protein, bulk RNA, single-cell RNA, and DNA methylation data. We leveraged sex-differential gene expression and deconvolution analyses to uncover sex-biased molecular and cellular mechanisms. Spatial transcriptomics localized gene expression patterns in plaques. Furthermore, we studied the female-biased processes in human plaque endothelial cells and vascular smooth muscle cells stimulated with TGF-β (transforming growth factor-β), with or without SMAD3 (SMAD family member 3) inhibition. RESULTS: Of 1889 atherosclerotic plaques (1309 male and 580 female), fibrous lesions were observed in 50% of female and 31% of male patients. Compared with patients with atheromatous plaques (n=494), women with fibrous plaques exhibited a high prevalence of smoking, while men with fibrous plaques presented more often with diabetes. Female fibrous plaques were characterized by smooth muscle cell-driven ECM (extracellular matrix) remodeling, TGF-β response, and endothelial-to-mesenchymal transition, localized to the fibrous cap. Conversely, male plaques were linked to macrophage-mediated inflammation proximal to the core, dependent on diabetes. Finally, we experimentally confirmed these female-biased mechanisms, showing that TGF-β induced endothelial-to-mesenchymal transition in endothelial cells and ECM remodeling in vascular smooth muscle cells, both part
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Journal articleOshima A, Serruys PW, Garg S, et al., 2026,
Adjunctive pharmacological strategies for residual risk reduction after myocardial revascularisation.
, EuroIntervention, Vol: 22, Pages: 202-223Pharmacological treatment remains vital in the effective management of atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein (LDL) cholesterol-lowering therapies, such as statins, have consistently demonstrated robust efficacy in the primary and secondary prevention of cardiovascular events. The introduction of ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors have further strengthened the effectiveness of LDL cholesterol management, particularly in patients who are statin intolerant or who remain at high risk despite maximal tolerated statin therapy. In addition to managing LDL cholesterol, addressing residual lipid risk by targeting elevated triglyceride and lipoprotein(a) levels and low high-density lipoprotein cholesterol levels has emerged as a potentially important therapeutic consideration, as these are increasingly recognised as independent cardiovascular risk factors. Concurrently, inflammation is increasingly acknowledged as a significant contributor to atherogenesis and subsequent cardiovascular events. Clinical trials examining anti-inflammatory therapies, such as colchicine and interleukin-1β inhibitors (e.g., canakinumab), have demonstrated beneficial effects in reducing cardiovascular events independent of lipid modification. This narrative review provides an updated overview targeted specifically at physicians performing coronary artery bypass grafting or percutaneous coronary intervention. It summarises current evidence regarding established lipid-lowering therapies, emerging therapeutic approaches to address residual lipid risk, and the evolving role of anti-inflammatory interventions in the comprehensive management of ASCVD.
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Journal articleAnwar M, Sarkar M, Ford K, et al., 2026,
Human left ventricle circRNA-miRNA-mRNA network analyses reveal a novel proangiogenic role for circNPHP1 under ischemic conditions
, JACC: Basic to Translational Science, Vol: 11, ISSN: 2452-302XTherapies promoting microvascular flow and endothelial repair require effective identification of new targets in ischemic heart disease (IHD). The aim of this study was to unravel and functionally investigate circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) networks in endothelial cells in the context of IHD and Type 2 Diabetes Mellitus (T2DM). We performed RNA sequencing on left ventricle biopsies from patients with IHD, IHD and T2DM and non-IHD. Next, we created circRNA-miRNA-mRNA networks and mechanistically investigated the top circRNA-miRNA sponging interactions in endothelial cells (ECs). We found that circNPHP1 promotes angiogenesis via sponging of miR-221-3p and regulates its downstream target genes, VEGFA and BCL2 in IHD and T2DM.
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Journal articleSingh B, Karpov OA, Mayr M, 2026,
Clinical proteomics in cardiovascular medicine: Current capabilities, limitations, and future directions.
, Atherosclerosis, Vol: 413BACKGROUND AND AIMS: Commercial high-throughput proteomics platforms, such as Olink and SomaLogic, enable large-scale epidemiological studies with integrated multi-omics measurements. While these proteomics approaches have been widely applied in biobanks, issues of data quality remain underappreciated. In this review, we discuss these limitations and outline a way forward for realizing the clinical translation of proteomics as a comprehensive 'liquid health check'. METHODS: We reviewed the recent literature for artificial intelligence (AI) and multi-omics, particularly proteomics in atherosclerotic cardiovascular disease (ASCVD). RESULTS: AI-driven multi-omics analyses have the potential to advance our understanding of multifactorial causes of ASCVD, including aging. Emerging concepts such as "ageotypes" suggest the potential for personalized intervention to slow aging processes. Commercial proteomics platforms have accelerated biomarker discovery in ASCVD, but challenges remain in clinical translation. Limited correlation between Olink and SomaLogic necessitates orthogonal validation of findings. Platform-specific issues, such as epitope effects and cross-reactivity, can yield divergent protein quantitative trait loci for the same protein, complicating causal inference. While tissue proteomics provides complementary insights to plasma proteomics, reliance on autopsy samples raises concerns about protein degradation and measurement reliability. Increasingly, single-cell and spatial proteomics are being explored to better capture plaque heterogeneity, complementing bulk proteomics in larger cohorts. CONCLUSION: Beyond risk prediction, proteomics offers opportunities to elucidate disease mechanisms and enable drug repurposing. To realize the clinical potential of plasma proteomics, absolute or reliably recalibratable relative quantification will be required to guide patient care. Ultimately, the clinical value of proteomics will be determined by the quality
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Journal articlePaul R, Rossios C, Hinken A, et al., 2026,
IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia
, PLoS ONE, Vol: 21, ISSN: 1932-6203Inflammation is thought to contribute to muscle loss in acute and chronic sarcopenia. Which inflammatory proteins contribute to sarcopenia in any condition is not clear. In a well-characterised cohort of patients experiencing acute sarcopenia following surgery, we used a proteomic screen of plasma to identify proteins associated with the change in strength. We compared change in handgrip strength over 7 days in surgery patients with plasma protein levels quantified by SOMAscan before and 24h after surgery. Surgery increased circulating concentrations of 295 proteins and decreased 301. Analysis of the day 1 protein levels showed that IL-18BP associated with maintenance of strength. To further investigate relationships between IL18BP and strength, IL-18BP as well as its ligands IL-18 and IL-37, were quantified by ELISA and in surgery patients and in 129 individuals (68 women) with age-related sarcopenia recruited to the Leucine and/or ACE inhibitor (LACE) trial. In LACE participants, the proteins were compared to grip strength, quadriceps maximal voluntary contraction (QMVC) and 6-minute walk distance (6MWD) and baseline SARC-F score. In the LACE cohort, IL-18BP was negatively associated with grip strength in men but not women, at baseline (r = −0.314, p = 0.014) and 12 months (r = −0.446, p = 0.001). QMVC and 6MWD showed similar associations. IL-18BP was associated with SARC-F in men (r = 0.389, p = 0.003) but not women. Investigation of SOMAscan data from surgery patients at baseline showed similar inverse associations of IL-18BP with strength. Comparison of circulating IL-18BP with the muscle transcriptome in these patients showed negative enrichment for mitochondrial genes. Analysis of the ligands showed that free IL-18 was proportional to 6MWD. After surgery high IL-18BP levels associate with maintenance of strength but circulating IL-18BP concentrations are associated
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Journal articleSimader FA, Rajkumar CA, Foley MJ, et al., 2026,
Association Between Age and PCI Effectiveness in Stable CAD: Secondary Analysis of ORBITA-2.
, J Am Coll Cardiol, Vol: 87, Pages: 253-265BACKGROUND: ORBITA-2 (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) was the first randomized placebo-controlled trial to show the efficacy of percutaneous coronary intervention (PCI) in patients with stable angina and single- or multivessel coronary artery disease without background antianginal medication. Whether the effect is consistent across age groups is unknown. OBJECTIVES: The authors sought to evaluate the interaction between age and symptom and stenosis severity, and the efficacy of PCI on the ORBITA-2 primary and secondary endpoints. METHODS: All patients from the primary ORBITA-2 trial contributed data to this post hoc analysis. For daily symptoms, a bayesian longitudinal Markov model was constructed. For treadmill exercise time, stress echocardiography, and questionnaires, a bayesian ordinal proportional odds model was used, including the prerandomization value and treatment arm, which were allowed to interact with age. RESULTS: The mean age was 64 ± 9 years, ranging from 40 to 82 years. There was little relationship between age and symptom and stenosis severity. In older patients, PCI was more effective for symptom relief (OR: 2.03; 95% CrI: 1.67-2.45; Pr > 0.99) than in younger patients (OR: 1.70; 95% CrI: 1.38-2.15; Pr > 0.99; Pr [interaction] = 0.99). In contrast, the effect of PCI on treadmill exercise time was far greater in younger than in older patients (50-year-old: +125 s [95% CrI: 35.8-215.0 s; Pr > 0.99]; 70-year-old: +31.9s [95% CrI: -12.6 to 78.3; Pr = 0.92]; Pr [interaction] = 0.96). CONCLUSIONS: PCI was effective across all ages in reducing angina frequency. Notably, there was limited improvement in treadmill exercise time in the elderly, challenging its role as a primary endpoint in many antianginal trials. These data should inform cardiovascular clinical trial design to ensure applicability across all ages. (Objective Randomized Blinded Investigation With Optimal
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