Lymphocyte-to–C-reactive-protein ratio is a strong predictor of mortality risk in cardiac transthyretin amyloidosis
V Cejka, M J Steinahrdt, A C Ruhemann, C Dolderer, L Kastenhuber, B Beer, N C Scholz, M Kortuem, H Einsele, S Frantz, S Stoerk, C MorbachAbstract
Background & Purpose
Cardiac transthyretin amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy characterized by transthyretin amyloid deposition in the myocardium, triggering interleukin release and recruitment of immune cells. The lymphocyte-to-C-reactive protein (CRP) ratio (LCR) reflects lymphocyte activation relative to systemic inflammation. LCR has been linked to mortality in malignant and cardiovascular conditions. Because this inflammatory association has not been studied in in ATTR-CM, we evaluated whether LCR is associated with all-cause death in ATTR-CM.
Methods
We investigated participants from the regional cohort study, including outpatients presenting at a tertiary care hospital. Diagnosis of ATTR-CM was ascertained by either myocardial biopsy or non-invasive algorithms incorporating bone scintigraphy and monoclonal protein testing. LCR was calculated as the absolute lymphocyte count per µl divided by high-sensitivity CRP in mg per dl. The outcome of interest was death from any cause during follow-up. Cox proportional hazards regression analyses with log(2)-transformed LCR as a continuous predictor were calculated. In a complementary analysis, LCR was examined in age- and sex-adjusted Cox regression as a binary variable using the previously published threshold of LCR >6000.
Results
We analyzed 208 patients with proven ATTR-CM enrolled between May 2023 and December 2024. Of these, 162 (78%) had wild-type ATTR-CM, 15 (7%) had variant ATTR-CM, 31 (15%) had unknown genetic status. Mean age was 79 (7.3) years, 177 (85%) were men. NAC (National Amyloidosis Center, London UK) stage was I in 110 (54%), II in 68 (33%), and III in 27 (13%) patients. Median LCR was 8222 (quartiles: 3200, 13833). During a median follow-up of 572 days (range: 55-730), 25 patients died. In univariable analysis, higher LCR was significantly associated with lower risk of death: HR 0.77 per log(2)-LCR (95%CI 0.64–0.93, p=0.006). After adjustment for age and sex, the predictive utility of LCR was not attenuated: HR 0.78 per log2-LCR (95%CI 0.64–0.96, p=0.016). Consistently, when modeled as a binary variable, LCR>6000 was significantly associated with a lower hazard of death: HR 0.28 (95%CI 0.12–0.65, p=0.003).
Conclusions
In this exploratory analysis, higher LCR was associated with better survival in ATTR-CM. Lymphocyte mobilization relative to CRP levels may reflect disease-specific inflammatory mechanisms. The inflammatory profile of a patient may help refine risk stratification and guide the use of an expanding range of disease-modifying treatment options. Future studies should confirm the incremental prognostic yield beyond established ATTR-CM risk markers.Survival curves by LCR cut-offs