A score of low-grade inflammation and risk of mortality: prospective findings from the Moli-sani study

Abstract

Low-grade inflammation is associated with an increased risk of chronic degenerative disease, but its relationship with mortality is less well explored. We aimed at evaluating, at a large epidemiological level, the possible association of low-grade inflammation, as measured by a composite score, with overall mortality risk. We conducted a population-based prospective investigation on 20,337 adult subjects free from major hematological disease and acute inflammatory status, randomly recruited from the general population of the Moli-sani study. A low-grade inflammation score was obtained from the sum of 10-tiles of plasmatic (C-reactive protein) and cellular (leukocyte and platelet counts, granulocyte/lymphocyte ratio) biomarkers of low-grade inflammation; higher levels indicated increased low-grade inflammation. Hazard ratios were calculated using multivariable Cox proportional hazard models with 95% confidence intervals. At the end of follow-up (median 7.6 years), 837 all-cause deaths were recorded. As compared to subjects in the lowest quartile of the low-grade inflammation score, those in the highest category had a significantly increased risk in overall mortality (HR=1.44; 1.17-1.77), independently of possible confounders, including the presence of chronic diseases and a number of health-related behaviors. The magnitude of the association of low-grade inflammation with mortality was relatively higher in type 2 diabetic patients (HR=2.90; 1.74-4.84) and in individuals with a history of cardiovascular disease (HR=2.48; 1.50-4.11) as compared to their counterparts who were free from the disease. In conclusion, an elevated degree of low-grade inflammation, as measured by a composite score of inflammatory biomarkers, is an independent risk factor for total mortality in an apparently healthy adult general population.

Figure 1.

Relative risk of all-cause death for each quartile of low-grade inflammation score according to the presence of diabetes at baseline. The reference group is the lowest quartile for each subgroup. Hazard ratios are adjusted for age, sex, cardiovascular disease, heart failure, cancer, hypercholesterolemia, systolic and diastolic BP, leisure-time PA, waist to hip ratio, fruit and vegetables intake, energy intake, smoking, education. Vertical bars indicate 95% confidence intervals. PA: physical activity; BP: blood pressure.