High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy

Haj-Yehia, Elias; Mincu, Raluca I.; Korste, Sebastian; Lampe, Lena; Margraf, Simone M.; Michel, Lars; Mahabadi, Amir A.; Ferdinandy, Péter; Rassaf, Tienush; Totzeck, Matthias

doi:10.1007/s00392-023-02327-9

Cited by 3 publications

(2 citation statements)

References 64 publications

(64 reference statements)

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“…showed a correlation with NLR and the length of hospital stay in myocarditis patients. Previous studies have shown that NLR increased in patients with ICI‐induced myocarditis and that elevated NLR is associated with major adverse cardiovascular events related to ICI therapy 20–22 . Our results further confirm the association between NLR and cardiovascular events as reported in previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have shown that NLR increased in patients with ICI‐induced myocarditis and that elevated NLR is associated with major adverse cardiovascular events related to ICI therapy. 20 , 21 , 22 Our results further confirm the association between NLR and cardiovascular events as reported in previous studies. NLR reflects inflammatory activity, which may be as a possible mediator for severe myocarditis in cancer patients receiving ICIs.…”

Section: Discussionsupporting

confidence: 91%

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Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

Zheng,

Chen,

Song

et al. 2024

Cancer Medicine

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BackgroundOver the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune‐related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate.MethodsWe conducted a multicenter retrospective study to characterize ICI‐associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer–Lemeshow test.ResultsForty‐four patients were identified, including thirty‐five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin‐I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme‐MB (CK‐MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty‐one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N‐terminal pro‐B‐type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK‐MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non‐severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK‐MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055–2.984, p = 0.031) was the independent risk factor of the development of ICI‐associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002–1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026–3.483, p = 0.041) were the independent risk factors of ICI‐associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK‐MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016).ConclusionsElevated CK‐MB after ICI treatment is the independent risk factor for the incidence of ICI‐associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI‐associated severe myocarditis. CK‐MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI‐associated myocarditis and severe myocarditis.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

Zheng,

Chen,

Song

et al. 2024

Cancer Medicine

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Aortic regurgitation is associated with African American and Asian race, smoking, renal disease, and numerous autoimmune diseases in addition to traditional cardiovascular risk factors but has lower risk with alcohol intake

Timmerman,

Hashemzadeh,

Movahed

2024

Clin Res Cardiol

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Nomograms based on ratio indexes to predict severity and prognosis in immune checkpoint inhibitors-related myocarditis: a retrospective analysis

Li,

Yao,

Liu

et al. 2024

J Cancer Res Clin Oncol

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Purpose Immune checkpoint inhibitors-related myocarditis (ICI-M) is one of the immune-related adverse events (irAEs), which is rare and highly lethal. This study aimed to establish nomograms based on ratio biomarkers to predict the severity and prognosis of ICI-M. Methods We retrospectively examined patients with advanced cancers who were also diagnosed with ICI-M at the Fourth Hospital of Hebei Medical University. The patients of ICI-M were divided into mild and severe groups and a 40-day following up was carried out. The major adverse cardiovascular events(MACEs) were regarded as the endpoint. Nomogram-based models were established and validated. Results Seventy-seven patients were involved, including 31 severe cases(40.3%). Lactate dehydrogenase-to-albumin ratio(LAR) combined with the change rate from baseline to onset of LAR($$\triangle$$ ▵ LAR) which performed best to diagnose the severe ICI-M was identified to establish the nomogram-based model. The bootstrap-corrected concordance index [0.752 95% confidence interval (CI): 0.635$$-$$ - 0.866] and calibration plot with good degree of fitting confirmed this diagnostic model. Neutrophil-to-high-density lipoprotein cholesterol ratio(NHR) and LAR were also screened into the nomogram-based model for 40-day MACEs after ICI-M, which performed well by validating for concordance index(0.779 95% CI: 0.677$$-$$ - 0.865)and calibration plots after being bootstrap-corrected. Moreover, a $$\ge$$ ≥ 101% increase in LAR significantly separated patients in MACE-free survival. Conclusion Ratio indexes at onset and their change rates from baseline showed good diagnostic value for the severity of ICI-M and prognostic value for subsequent MACEs, particularly LAR, NHR and their change rates. The nomogram-based models of ratio indexes could provide a potential choice for early detection and monitor of the severe ICI-M and subsequent MACEs. Graphical abstract

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High neutrophil-to-lymphocyte ratio is associated with cancer therapy-related cardiovascular toxicity in high-risk cancer patients under immune checkpoint inhibitor therapy

Cited by 3 publications

References 64 publications

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study

Aortic regurgitation is associated with African American and Asian race, smoking, renal disease, and numerous autoimmune diseases in addition to traditional cardiovascular risk factors but has lower risk with alcohol intake

Nomograms based on ratio indexes to predict severity and prognosis in immune checkpoint inhibitors-related myocarditis: a retrospective analysis

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