Pre-existing cardiovascular diseases in large b-cell lymphoma
T M Nicolaescu, K D Abalo, C Morth, I Glimelius, J Sundstrom, C Smedby, G EnbladAbstract
Background
Chronic inflammation is central to both cardiovascular disease (CVD) and large B-cell lymphoma (LBCL), yet whether CVD precedes and contributes to LBCL risk—or merely co-occurs due to age and healthcare contact—remains unclear.
Objectives
To examine the association between pre-diagnosis CVD and subsequent risk of LBCL, with particular attention to temporality and age-specific effects.
Methods
Using nationwide Swedish registry data (2000–2021), we conducted a matched case–control study including 11,258 patients with LBCL and 112,218 population controls. CVD occurring within 10 years prior to diagnosis was ascertained from inpatient, outpatient, and prescription registries; a 3-month lag period was applied to reduce reverse causation; sensitivity analyses used alternative lag periods (0 and 12 months). Conditional logistic regression adjusted for sociodemographic factors and comorbidities was performed in the overall study population, with prespecified analyses stratified by age at diagnosis (≤65 vs >65 years).
Results
Overall, prior CVD was not associated with LBCL risk (OR 1.03, 95% CI 0.98–1.08). However, age-related heterogeneity was observed in the primary lagged analysis: among individuals diagnosed at ≤65 years, prior CVD was associated with increased LBCL risk (OR 1.15, 95% CI 1.06–1.25), whereas no association was seen in older individuals (OR 0.98, 95% CI 0.93–1.03; P for interaction <0.001). The age-specific association was driven by arterial hypertension, the only CVD subtype consistently associated with increased risk in younger patients. Findings were consistent in sensitivity analyses using alternative lag periods (0 and 12 months).
Conclusion
In this population-based analysis, we found no evidence of a broad association between pre-existing CVD and LBCL risk after accounting for diagnostic timing. Nonetheless, the age-specific signal observed among individuals diagnosed at ≤65 years—driven primarily by arterial hypertension—suggests meaningful heterogeneity in the CVD–LBCL association across the lifespan. These findings underscore the importance of temporality and age context in reverse cardio-oncology research.