Does a raised inflammatory marker in primary care predict one-year mortality? A prospective cohort study using CPRD
Inflammatory markers such as C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and plasma viscosity (PV) have been implicated in predicting future mortality, particularly from cardiovascular disease. The relevance in primary care settings, and over the shorter term, is unclear. The aim of this study was to examine one-year all-cause mortality in a cohort of primary care patients in whom inflammatory marker bloods had been tested.
This was a prospective cohort study of 160,000 patients from Clinical Practice Research Datalink (CPRD) with inflammatory marker blood testing in 2014, with linkage to ONS mortality data. The primary outcome was one-year mortality in those with raised versus normal inflammatory marker. A comparison cohort of 40,000 age, sex and practice matched patients without inflammatory marker testing in 2014 was identified, to compare mortality in tested versus untested patients.
Of the tested cohort; 73% had a CRP test, 59% had an ESR test, and 10% had PV test; of these 29% had at least one raised inflammatory marker. One-year mortality in patients of any age with a raised inflammatory marker (n=47,797) was 6.89%, compared to 1.41% in those with normal inflammatory markers (p<0.001). In the untested comparison cohort, one-year mortality was 1.62%. The association between raised inflammatory markers and one-year mortality was seen in all age groups. In older age groups the absolute risk was considerable; a raised inflammatory marker in the over 80s was associated with a one-year mortality of 21.8%, compared to 8.4% in the over 80s with normal inflammatory markers. A dose response relationship was found with CRP >100mg/L and ESR >100mm/hr at any age both associated with >20% one-year mortality. The area under the receiver operator curve (AUC) was 0.77 for CRP, 0.75 for ESR and 0.65 for PV. The main cause of death in those with raised inflammatory markers was cancer (37%), followed by cardiovascular disease (24%) and respiratory disease (14%).
With an aging population and increasing multimorbidity, identification of frailty has become a high priority, with the aim of facilitating the planning and delivery of services. A range of frailty indexes have been developed, using various symptoms, signs, diseases and test results; these do not currently include the use of inflammatory markers. A single raised CRP has a similar AUC to several previously developed frailty indices, and could therefore be a useful and simple indicator to improve prediction of life-expectancy in primary care. Inflammatory marker test results must be interpreted within the overall clinical context; however in the absence of obvious, reversible causes of inflammation, clinicians should consider whether older patients with a raised inflammatory marker are reaching the end of life. Evidence-based interventions for frailty are needed alongside predictive tools.