BACKGROUND: It is unknown if incidental lymphopenia detected in the general population is associated with higher all-cause and cause-specific mortality. We aimed to identify the associations between lymphopenia and all-cause and cause specific mortality.

METHODS: In a prospective cohort study, we examined and followed participants enrolled in the Copenhagen General Population Study between November 2003 and April 2015. In our analysis, we modelled risks using Cox proportional hazards regression for 3 groups: participants with a lymphocyte count below the 2.5th percentile; those with a lymphocyte count at or between the 2.5th and 97.5th percentiles (reference category); and those with a lymphocyte count above the 97.5th percentile.

RESULTS: The cohort included 108 135 participants with a median age of 68 years. During a median follow-up of 9 (interquartile range [IQR] 0-14) years, 10 372 participants died. We found that participants with lymphopenia (lymphocyte count < 1.1 × 109/L) compared with those with a lymphocyte count in the reference range (1.1-3.7 × 109/L) had higher mortality with multivariable adjusted hazard ratios (HRs) of 1.63 (95% confidence interval [CI] 1.51-1.76) for all causes, 1.67 (95% CI 1.42-1.97) for nonhematologic cancers, 2.79 (95% CI 1.82-4.28) for hematologic cancers, 1.88 (95% CI 1.61-2.20) for cardiovascular diseases, 1.88 (95% CI 1.55-2.29) for respiratory diseases, 1.86 (95% CI 1.53-2.25) for infectious diseases, and 1.50 (95% CI 1.19-1.88) for other causes. For all-cause mortality, the highest absolute 2-year risks of death were observed in women (61%) and men (75%) who smoked and were aged 80 years or older with lymphocyte counts less than 0.5 × 109/L. Participants with a lymphocyte count higher than the reference category had increased mortality (adjusted HR 1.17, 95% CI 1.04-1.31).

INTERPRETATION: We found that lymphopenia was associated with an increased risk of all-cause and cause-specific mortality.