Dataset Information

Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial.

ABSTRACT:

Background

Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based biomarkers for determining the complexity and severity of CAD, as it is assessed via the SYNTAX score.

Methods

Corlipid is a prospective, non-interventional cohort trial empowered to enroll 1065 patients with no previous coronary intervention history, who undergo coronary angiography in University Hospital AHEPA, Thessaloniki. Venous blood samples are collected before coronary angiography. State-of the-art analytical methods are performed to calculate the serum levels of novel biomarkers: ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and the ratio of apolipoprotein B/apolipoprotein A1. Furthermore, all patients will be categorized based on the indication for coronary angiography (acute coronary syndrome, chronic coronary syndrome, preoperative coronary angiography) and on the severity of CAD using the SYNTAX score. Follow-up of 12 months after enrollment will be performed to record the occurrence of major adverse cardiovascular events. A risk prediction algorithm will be developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD based on their metabolite signatures. The first patient was enrolled in July 2019 and completion of enrollment is expected until May 2021.

Discussion

CorLipid is an ongoing trial aiming to investigate the correlation between metabolic profile and complexity of coronary artery disease in a cohort of patients undergoing coronary angiography with the potential to suggest a decision-making tool with high discriminative power for patients with CAD. To our knowledge, Corlipid is the first study aspiring to create an integrative metabolomic biomarkers-based algorithm by combining metabolites from multiple classes, involved in a wide range of pathways with well-established biochemical markers. Trial registration CorLipid trial registration: ClinicalTrials.gov number: NCT04580173. Registered 8 October 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04580173 .

SUBMITTER: Karagiannidis E

PROVIDER: S-EPMC7869241 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial.

Karagiannidis Efstratios E Sofidis Georgios G Papazoglou Andreas S AS Deda Olga O Panteris Eleftherios E Moysidis Dimitrios V DV Stalikas Nikolaos N Kartas Anastasios A Papadopoulos Anastasios A Stefanopoulos Leandros L Karvounis Haralambos H Gika Helen H Theodoridis Georgios G Sianos Georgios G

BMC cardiovascular disorders 20210208 1

<h4>Background</h4>Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based b ...[more]

PMID: 33557756

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Project description:BackgroundDespite major advances in prevention and treatment, coronary artery disease (CAD) remains the leading cause of death worldwide. Whereas many sources of data are available on the epidemiology of acute coronary syndromes, fewer datasets reflect the contemporary management and outcomes of stable CAD patients.HypothesisA worldwide contemporary registry would improve our knowledge about stable CAD. The main objectives are to describe the demographics, clinical profile, contemporary management and outcomes of outpatients with stable CAD; to identify gaps between evidence and treatment; and to investigate long-term prognostic determinants.MethodsCLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an ongoing international observational longitudinal registry. Stable CAD patients from 45 countries in Europe, Asia, America, Middle East, Australia and Africa were enrolled between November 2009 and June 2010. The inclusion criteria were previous myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischemia or prior revascularization procedure. The main exclusion criteria were serious non-cardiovascular disease, conditions interfering with life expectancy or severe other cardiovascular disease (including advanced heart failure). Follow-up visits were planned annually for up to 5 years, interspersed with 6-month telephone calls.ResultsOf the 32,703 patients enrolled, most (77.6%) were male, age (mean ± SD) was 64.2 ± 10.5 years, and 71.0% were receiving treatment for hypertension; mean ± SD resting heart rate was 68.2 ± 10.6 bpm. Patients were enrolled based on a history of myocardial infarction >3 months earlier (57.7%), having at least one stenosis >50% on coronary angiography (61.1%), proven symptomatic myocardial ischemia on non-invasive testing (23.1%), or history of percutaneous coronary intervention or coronary artery bypass graft (69.8%). Baseline characteristics were similar across the four subgroups identified by the four inclusion criteria.ConclusionCLARIFY will provide a useful resource for understanding the current epidemiology of stable CAD.

Project description:BackgroundAlthough coronary artery calcium (CAC) has been investigated for over two decades, there is very limited data on the association of CAC with cause of death. The CAC Consortium is a large ongoing multi-center observational cohort of individuals who underwent non-contrast cardiac-gated CAC testing and systematic, prospective, long-term follow-up for mortality with ascertainment of cause of death.MethodsFour participating institutions from three states within the US (California, Minnesota, and Ohio) have contributed individual-level patient data to the CAC Consortium (spanning years 1991-2010). All CAC scans were clinically indicated and physician-referred in patients without a known history of coronary heart disease. Using strict inclusion and exclusion criteria to minimize missing data and to eliminate non-dedicated CAC scans (i.e. concomitant CT angiography), a sharply defined and well-characterized cohort of 66,636 patients was assembled. Mortality status was ascertained using the Social Security Administration Death Master File and a validated algorithm. In addition, death certificates were obtained from the National Death Index and categorized using ICD (International Classification of Diseases) codes into common causes of death.ResultsMean patient age was 54 ± 11 years and the majority were male (67%). Prevalence of CVD risk factors was similar across sites and 55% had a <5% estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Approximately 45% had a Calcium score of 0 and 11% had an Agatston Score ≥400. Over a mean follow-up of 12 ± 4 years, there were 3158 deaths (4.15 per 1000 person-years). The majority of deaths were due to cancer (37%) and CVD (32%). Most CVD deaths were due to CHD (54%) followed by stroke (17%). In general, CAC score distributions were similar across sites, and there were similar cause of death patterns.ConclusionsThe CAC Consortium is large and highly generalizable data set that is uniquely positioned to expand the understanding of CAC as a predictor of mortality risk across the spectrum of disease states, allowing innovative modeling of the competing risks of cardiovascular and non-cardiovascular death.

Project description:Recent studies support that acylcarnitines exert a significant role in cardiovascular disease development and progression. The aim of this metabolomics-based study was to investigate the association of serum acylcarnitine levels with coronary artery disease (CAD) severity, as assessed via SYNTAX Score. Within the context of the prospective CorLipid trial (NCT04580173), the levels of 13 circulating acylcarnitines were accurately determined through a newly developed HILIC-MS/MS method in 958 patients undergoing coronary angiography in the AHEPA University Hospital of Thessaloniki, Greece. Patients presenting with acute coronary syndrome had significantly lower median acylcarnitine C8, C10, C16, C18:1 and C18:2 values, compared to patients with chronic coronary syndrome (p = 0.012, 0.007, 0.018, 0.011 and <0.001, respectively). Among CAD subgroups, median C5 levels were significantly decreased in unstable angina compared to STEMI (p = 0.026), while median C10, C16, C18:1 and C18:2 levels were higher in stable angina compared to STEMI (p = 0.019 p = 0.012, p = 0.013 and p < 0.001, respectively). Moreover, median C2, C3, C4 and C8 levels were significantly elevated in patients with diabetes mellitus (p < 0.001, <0.001, 0.029 and 0.011, respectively). Moreover, short-chain acylcarnitine C2, C4, C5 and C6 levels were elevated in patients with heavier calcification and lower left ventricular ejection fraction (LVEF) % (all p-values less than 0.05). With regard to CAD severity, median C4 and C5 levels were elevated and C16 and C18:2 levels were reduced in the high CAD complexity group with SYNTAX Score > 22 (p = 0.002, 0.024, 0.044 and 0.012, respectively), indicating a potential prognostic capability of those metabolites and of the ratio C4/C18:2 for the prediction of CAD severity. In conclusion, serum acylcarnitines could serve as clinically useful biomarkers leading to a more individualized management of patients with CAD, once further clinically oriented metabolomics-based studies provide similar evidence.

Dataset Information

Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial.

Background

Methods

Discussion

Publications

Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial.

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