Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401
infections and experienced 1,045
infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with
lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any
infection, 1.31 (1.14-1.52) for
pneumonia, 1.44 (1.15-1.79) for skin
infection, 1.26 (1.02-1.56) for
urinary tract infection, 1.51 (1.21-1.89) for
sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for
endocarditis, and 2.26 (1.21-4.24) for other
infections. The corresponding hazard ratio for
infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma
C-reactive protein, blood neutrophil count, recent
infection, Charlson comorbidity index,
autoimmune diseases, medication use, and immunodeficiency/
hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.
CONCLUSIONS: