Shorter leukocyte telomere length is associated with higher risk of infections: a prospective study of 75,309 individuals from the general population

Abstract

In the general population, older age is associated with short leukocyte telomere length and with high risk of infections. In a recent study of allogeneic hematopoietic cell transplantation for severe aplastic anemia, long donor leukocyte telomere length was associated with improved survival in the recipients. These findings suggest that leukocyte telomere length could possibly be a marker of immune competence. Therefore, we tested the hypothesis that shorter leukocyte telomere length is associated with higher risk of infectious disease hospitalization and infection-related death. Relative peripheral blood leukocyte telomere length was measured using quantitative polymerase chain reaction in 75,309 individuals from the general population and the individuals were followed for up to 23 years. During follow up, 9228 individuals were hospitalized with infections and infection-related death occurred in 1508 individuals. Shorter telomere length was associated with higher risk of any infection (hazard ratio 1.05 per standard deviation shorter leukocyte telomere length; 95% confidence interval 1.03-1.07) and pneumonia (1.07; 1.03-1.10) after adjustment for conventional infectious disease risk factors. Corresponding hazard ratios for infection-related death were 1.10 (1.04-1.16) for any infection and 1.11 (1.04-1.19) for pneumonia. Telomere length was not associated with risk of skin infection, urinary tract infection, sepsis, diarrheal disease, endocarditis, meningitis or other infections. In conclusion, our findings indicate that leukocyte telomere length may be a marker of immune competence. Further studies are needed to determine whether risk of infections in allogeneic hematopoietic cell transplantation recipients can be reduced by considering donor leukocyte telomere length when selecting donors.

Figure 1.

Risk of first hospitalization for any infection and specific infections in the general population per standard deviation shorter telomere length. The sum of specific infections exceeds the number of any infection since some individuals had more than one type of infection. Multivariable models were adjusted for values at study enrollment of age, sex, smoking status, cumulative smoking in pack-years, alcohol consumption, body mass index, plasma C-reactive protein level, Charlson comorbidity index, number of non-infectious disease hospitalizations within ten years before study enrollment, and study cohort. CI: confidence interval

Figure 2.

Risk of first hospitalization for any infection and pneumonia in the general population according to age-adjusted quartiles of telomere length. Multivariable models were adjusted for values at study enrollment of age, sex, smoking status, cumulative smoking in pack-years, alcohol consumption, body mass index, plasma C-reactive protein level, Charlson comorbidity index, number of non-infectious disease hospitalizations within ten years before study enrollment, and study cohort. CI: confidence interval.

Figure 3.

Risk of first hospitalization for any infection and pneumonia in the general population per standard deviation shorter telomere length stratified according to follow-up interval. Multivariable models were adjusted for values at study enrollment of age, sex, smoking status, cumulative smoking in pack-years, alcohol consumption, body mass index, plasma C-reactive protein level, Charlson comorbidity index, number of non-infectious disease hospitalizations within ten years before study enrollment, and study cohort. P for interaction was calculated using a likelihood ratio test, comparing models with and without an interaction term. CI: confidence interval.

Figure 4.

Stratified analyses for risk of first hospitalization for any infection per standard deviation shorter telomere length. Number of individuals at risk and number of infections vary slightly among the stratifications due to varying numbers of individuals with missing data on each of the covariates. Multivariable models were adjusted for values at study enrollment of age, sex, smoking status, cumulative smoking in pack-years, alcohol consumption, body mass index, plasma C-reactive protein level, Charlson comorbidity index, number of non-infectious disease hospitalizations within ten years before study enrollment, and study cohort. P for interaction was calculated using a likelihood ratio test, comparing models with and without an interaction term. CI: confidence interval. ^#Ever smokers only. ^†>168 g/week for men and >84 g/week for women. ^§As defined by the Charlson comorbidity index. ^‡Defined as any inpatient hospitalization within ten years before study enrollment for any cause other than infections. ^¶Includes measurements of white blood cell differential count, platelet count, blood hemoglobin, plasma alanine aminotransferase, plasma creatinine, and non-fasting plasma glucose.

Figure 5.

Risk of death related to any infection and death related to specific infections in the general population per standard deviation shorter telomere length. The sum of deaths related to specific infections exceeds the number of deaths related to any infection since some individuals had more than one type of infection listed on the death certificate. For meningitis, exact calculations of risk estimates were not possible since there were only 2 meningitis-related deaths. Multivariable models were adjusted for values at study enrollment of age, sex, smoking status, cumulative smoking in pack-years, alcohol consumption, body mass index, plasma C-reactive protein level, Charlson comorbidity index, number of non-infectious disease hospitalizations within ten years before study enrollment, and study cohort. CI: confidence interval.