Novel prognostic inflammatory markers of cancer survival and cardiovascular disease are; the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammation index (SII). As normal values for these markers are unknown, our objective was to obtain reference values in the general population. We obtained data from a population-based prospective cohort study of individuals aged 45 years and over between 2002 and 2014. Absolute blood counts were used to calculate the NLR, PLR and SII. All inflammatory indices followed a log-normal distribution. We calculated the mean and 95% reference intervals in an unselected population. Furthermore we studied whether the inflammatory markers differed between age categories and gender. In total 8,711 participants (57.1% female; mean age 65.9 years, standard deviation 10.5 years) were included. Mean values and corresponding 95% reference intervals for the NLR were: 1.76 (0.83–3.92), for PLR: 120 (61–239) and for SII: 459 (189–1168). The inflammatory markers increased with age. The PLR and SII were higher in females, whilst the NLR was higher in males. In conclusion, we provided reference values for new inflammatory markers. All increase with age and vary with gender. This provides context that allows for proper interpretation of their potential value in future clinical practice and research.

Several studies found that the systemic immune‐inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population‐based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow‐up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow‐up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 [95% CI; 1.11–1.53]), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10‐year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p‐value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow‐up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.

Inflammation is a risk factor for morbidity and mortality in the elderly. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that integrates the information of the leukocyte differentials into one variable. We aimed to assess whether the NLR is a risk indicator for overall and cause-specific mortality in the general population. We analyzed data (2002–2014) from the Rotterdam Study, a long-standing, population-based, prospective cohort study in a community-dwelling ageing population. The association between the NLR and time to all-cause mortality was assessed with Cox proportional hazard models. We additionally assessed cardiovascular, cancer and other mortality. The multivariable analyses were adjusted for age, gender, socio-economic status (SES), smoking status, body mass index, type 2 diabetes, and history of cancer and cardiovascular disease (CVD). Data of 8715 individuals were included. The mean age was 65.9 years (SD 10.5) and the majority were women (57.1%). The NLR was higher in men, higher age categories, smokers and among individuals with lower SES, prevalent diabetes, or a history of cancer or CVD. During the 11.7 years follow-up period, 1641 individuals died. Survival among individuals in the 3rd, 4th, and 5th quintile of the NLR was significantly poorer than that of those in the 1st quintile ( P < 0.001). In the multivariable analysis, NLR levels were independently and significantly associated with an increased risk of all-cause mortality (HR 1.64; 95% CI 1.44–1.86), cardiovascular mortality (HR 1.92; 95% CI 1.49–2.48), and other mortality (HR 1.86; 95% CI 1.54–2.24). No significant association was found for cancer mortality (HR 1.20; 95% CI 0.95–1.51). The NLR is a strong and independent risk indicator for mortality in the elderly population. Its clinical value needs to be established in further studies. Electronic supplementary material The online version of this article (10.1007/s10654-018-0472-y) contains supplementary material, which is available to authorized users.

Background Immunity has been suggested to be important in the pathogenesis of dementia. However, the contribution of innate versus adaptive immunity in the development of dementia is not clear. In this study, we aimed to investigate (1) the association between components of innate immunity (granulocytes and platelets) and adaptive immunity (lymphocytes) with risk of dementia and (2) the association between their derived ratios (granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII]), reflecting the balance between innate and adaptive immunity, with risk of dementia. Methods Blood cell counts were measured repeatedly between 2002 and 2015 in dementia-free participants of the prospective population-based Rotterdam Study. Participants were followed-up for dementia until 1 January 2016. Joint models were used to determine the association between granulocyte, platelets, and lymphocyte counts, and their derived ratios with risk of dementia. Results Of the 8313 participants (mean [standard deviation] age 61.1 [7.4] years, 56.9% women), 664 (8.0%) developed dementia during a median follow-up of 8.6 years. Doubling of granulocyte and platelet counts tended to be associated with an increased risk of dementia (HR [95%CI] 1.22 [0.89–1.67] and 1.45 [1.07–1.95], respectively). Doubling of the derived ratios GLR, PLR, and SII were all associated with an increased dementia risk (HR [95%CI] 1.26 [1.03–1.53], 1.27 [1.05–1.53], and 1.15 [0.98–1.34], respectively). Conclusions GLR, PLR, and SII are associated with an increased risk of dementia in the general population. This supports the role of an imbalance in the immune system towards innate immunity in the pathogenesis of dementia. Electronic supplementary material The online version of this article (10.1186/s12974-019-1454-z) contains supplementary material, which is available to authorized users.

No abstract