In 2012, a population study was published by the Mayo Clinic (Rochester, Minnesota) that utilised sera collected between 1995 and 2003 from Olmsted County residents over the age of 50 
. After excluding subjects with abnormal κ/λ sFLC ratios or other evidence of a monoclonal process, the population comprised >15,000 individuals, with a median follow-up of 12.7 years. In this population, the sum of κ and λ sFLC concentrations (ΣFLC) was found to be a significant predictor of reduced overall survival. This was particularly noticeable for subjects in the top decile (>47.2 mg/L) and remained so even after correction for age, sex and serum creatinine (Figure 35.17
). Increased mortality was associated with many causes of death, with “Circulatory”, “Neoplasms” and “Respiratory” being the most frequent. The authors concluded that their data added to the body of literature connecting inflammation, aging and chronic disease, but acknowledged that information on other inflammatory markers was lacking. Similar findings have been reported in another study, conducted in Germany, which analysed sera from 4350 subjects who had been monitored as part of an investigation of cardiac risk factors 
. CRP data was also available for these patients, and elevated ΣFLC was found to be associated with increased mortality independently of sex, age, renal function and CRP concentrations. Further follow-up of this population is continuing.
Anandram and colleagues  analysed mortality in a population referred for haematological investigation. The population was smaller than those discussed above (n=723) but more diagnostic information was available. Again, elevated ΣFLCs was associated with increased mortality and this was independent of other risk factors, including decreased serum albumin, reduced renal function, increased erythrocyte sedimentation rate (ESR) and elevated CRP concentrations. This cohort forms the basis of a pilot study for a large prospective study, which is currently in progress .