Assessment of Relative Utility of Underlying vs Contributory Causes of Death

In etiological research, investigators using death certificate data have traditionally extracted underlying cause of mortality alone. With multimorbidity being increasingly common, more than one condition is often compatible with the manner of death. Using contributory cause plus underlying cause would also have some analytical advantages, but their combined utility is largely untested.

To compare the relative utility of cause of death data extracted from the underlying cause field vs any location on the death certificate (underlying and contributing combined).

This study compares the association of 3 known risk factors (cigarette smoking, low educational attainment, and hypertension) with health outcomes based on where cause of death data appears on the death certificate in 2 prospective cohort study collaborations (UK Biobank [N = 502 655] and the Health Survey for England [15 studies] and the Scottish Health Surveys [3 studies] [HSE-SHS; N = 193 873]). Data were collected in UK Biobank from March 2006 to October 2010 and in HSE-SHS from January 1994 to December 2008. Data analysis began in June 2018 and concluded in June 2019.

Death from cardiovascular disease, cancer, dementia, and injury. For each risk factor-mortality end point combination, a ratio of hazard ratios (RHR) was computed by dividing the effect estimate for the underlying cause by the effect estimate for any mention.

In UK Biobank, there were 14 421 deaths (2.9%) during a mean (SD) of 6.99 (1.03) years of follow up; in HSE-SHS, there were 21 314 deaths (11.0%) during a mean (SD) of 9.61 (4.44) years of mortality surveillance. Established associations of risk factors with death outcomes were essentially the same irrespective of placement of cause on the death certificate. Results from each study were mutually supportive. For having ever smoked cigarettes (vs never having smoked) in the UK Biobank, the RHR for cardiovascular disease was 0.98 (95% CI, 0.87-1.10; P value for difference = .69); for cancer, the RHR was 0.99 (95% CI, 0.93-1.05; P value for difference = .69). In the HSE-SHS, the RHR for cardiovascular disease was 0.94 (95% CI, 0.87-1.01; P value for difference = .09); for cancer, it was 1.01 (95% CI, 0.94-1.10; P value for difference = .75).

Risk factor-end point associations were not sensitive to the placement of data on the death certificate. This has implications for the examination of the association of risk factors with causes of death where there may be too few events to compute reliable effect estimates based on the underlying field alone.