Highlights
- •Patients with chronic kidney disease are at increased risk of cardiovascular events following coronary catheterization. Preceding coronary catheterization is an ideal time to measure biomarkers and estimate risk for future cardiovascular events.
- •Using a machine learning algorithm and targeted proteomics, we demonstrated that measuring four biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) can individualize cardiovascular events risk assessment among patients with chronic kidney disease
- •Future clinical trials may assess the efficacy of implementing the HART CVE model in lowering cardiovascular events compared to the standard of care
Abstract
Background
Patients with chronic kidney disease (CKD) undergoing coronary catheterization are
at increased risk of cardiovascular events (CVE). Measuring biomarkers before the
procedure may guide clinicians in identifying patients at higher risk of future cardiovascular
events.
Methods
In this sub-study the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA),
927 patients underwent coronary catheterization and were followed up for two years.
Using machine learning algorithm and targeted proteomics from samples of patients
with CKD, 4 biomarkers (kidney injury molecule-1, N-terminal pro B-type natriuretic
peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) were integrated
into a prognostic algorithm to predict CVE. Results from the panel are expressed in
a graded fashion (CVE higher risk and lower risk) using a data-driven cutoff optimized
for balanced sensitivity and specificity.
Results
During the 2-year follow-up, 74 CVE were ascertained. 51 (rate: 51/378 = 13.5%) events
occurred in stage 1–2 CKD and 23 (rate: 23/68 = 33.8%) events occurred in stage 3–5
CKD. The C-statistic for predicting 2-years cardiovascular events in all 446 patients
was 0.77 (0.72, 0.82). The model was well-calibrated (Hosmer-Lemeshow test p-value >0.40). Considering patients at CVE lower-risk within each CKD staging group
as a reference, the hazard ratio (95% confidence interval) of cardiovascular events
was 2.82 (1.53, 5.22) for CKD stage 1–2/CVE higher-risk, and 8.32 (1.12, 61.76) for
CKD stage 3–5/CVE higher-risk.
Conclusion
Measuring biomarker panel prior to coronary catheterization may be useful to individualize
CVE risk assessment among patients with CKD.
Graphical abstract

Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to International Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Impact of chronic kidney disease on the associations of cardiovascular biomarkers with adverse outcomes in patients with suspected or known coronary artery disease: The EXCEED-J Study.J. Am. Heart Assoc. 2022; 11e023464
- Long-term clinical impact of contrast-associated acute kidney injury following PCI: an ADAPT-DES substudy.JACC Cardiovasc. Interv. 2022; 15: 753-766
- Atherosclerosis in chronic kidney disease: more, less, or just different?.Arterioscler. Thromb. Vasc. Biol. 2019; 39: 1938-1966
- Incident type 2 myocardial infarction in a cohort of patients undergoing coronary or peripheral arterial angiography.Circulation. 2017; 135: 116-127
- The value of kidney injury molecule 1 in predicting acute kidney injury in adult patients: a systematic review and Bayesian meta-analysis.J. Transl. Med. 2021; 19: 105
- Relation of baseline neutrophil gelatinase-associated lipocalin (NGAL) levels and contrast-induced nephropathy following percutaneous coronary intervention among chronic kidney disease patients.J. Clin. Med. 2021; 10
- Blood kidney injury molecule-1 predicts short and longer term kidney outcomes in patients undergoing diagnostic coronary and/or peripheral angiography-Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study.Am. Heart J. 2019; 209: 36-46
- Osteopontin in vascular disease.Arterioscler. Thromb. Vasc. Biol. 2019; 39: 613-622
- Osteopontin: role in extracellular matrix deposition and myocardial remodeling post-MI.J. Mol. Cell. Cardiol. 2010; 48: 538-543
- Increased cardiac expression of tissue inhibitor of metalloproteinase-1 and tissue inhibitor of metalloproteinase-2 is related to cardiac fibrosis and dysfunction in the chronic pressure-overloaded human heart.Circulation. 2005; 112: 1136-1144
- Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction.Am. Heart J. 2006; 151 (e1-8): 1101
- N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy.Circulation. 2003; 108: 275-281
Article info
Publication history
Published online: October 03, 2022
Accepted:
September 29,
2022
Received in revised form:
September 24,
2022
Received:
August 25,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Inflammation in chronic kidney disease – Something old, something newInternational Journal of CardiologyVol. 370
- PreviewChronic kidney disease (CKD) is a highly prevalent condition associated with significant levels of morbidity and mortality. Cardiovascular disease represents the single largest cause of mortality in chronic renal failure patients. In patients with renal disease, specific cardiovascular risk factors include secondary hyperparathyroidism, increased sympathetic-nerve activity, elevated levels of oxidized low-density lipoprotein and endothelial dysfunction characterized by elevated endothelin levels and diminished vascular nitric oxide production [1,2].
- Full-Text
- Preview