Observed and hidden factors underlying the accumulation of chronic diseases across eight major organ systems: a longitudinal birth cohort study

Abstract

Summary

Background: Although individual risk factors have been linked to specific diseases, the cumulative effect of life-course factors on the accumulation of multiple chronic diseases remains unclear. This study aimed to quantify the extent to which measured and unmeasured factors explain disease burden across eight major organ systems.

Methods: We did a longitudinal analysis of a population-based birth cohort of individuals born at Helsinki University Central Hospital (Helsinki, Finland) between 1934 and 1944, who attended child welfare clinics in the city, were living in Finland in 1971, and were included in the random subsample undergoing clinical investigations between 2001 and 2004. We tracked chronic disease accumulation across eight organ systems for 30 years from hospital inpatient and outpatient records. Measured life-course factors (including age, sex, early life factors, adult lifestyle, clinical characteristics, biomarkers, and socioeconomic status) were assessed from birth until late midlife. Unmeasured factors were estimated to capture influences beyond measured factors. Multidimensional linear mixed models assessed the contribution of measured and unmeasured factors to organ-specific disease accumulation (the main outcome for this study), accounting for interdependence across organ systems.

Findings: We included data from 2003 people, collected from Jan 1, 1934, to Dec 31, 2017, in this analysis. The upper limit in disease accumulation explained by measured and unmeasured life-course factors ranged from 24·5–86·3% across eight organ systems, and was 48·3% for the total number of all diseases. Most (20·1–82·0%) of this variance was attributable to unmeasured factors. Of measured factors, clinical characteristics and biomarkers explained the largest proportion of disease accumulation (mean 30·3%; SD 15·3%; range 13·6–55·1%), followed by age (22·2%; 22·9%; 0·2–75·7%), early life factors (20·8%; 11·6%; 2·0–38·2%), lifestyle (15·8%; 10·2%; 6·8–35·6%), socioeconomic factors (8·5%; 7·1%; 0·8–17·4%), and sex (2·4%; 3·4%; 0·01–9·2%). Age, BMI, fasting blood glucose, and systolic blood pressure accelerated disease accumulation across multiple organ systems. Each decade of ageing increased disease accumulation 1·28–2·06 times. A 1-SD increase in BMI predicted a 1·28–1·72-times increase in cardiovascular, gastrointestinal, metabolic, musculoskeletal, and respiratory diseases. A 1-SD increase in fasting blood glucose predicted a 1·14–1·35-times increase in cardiovascular, metabolic, neurological, and sensory diseases; a 1-SD increase in systolic blood pressure predicted a 1·16-times increase in cardiovascular diseases and a 1·39-times increase in metabolic diseases.

Interpretation: Measured and unmeasured life-course factors explain up to three-quarters of chronic disease accumulation across systems, with the remainder probably influenced by chance. Key modifiable drivers include BMI, blood glucose, and systolic blood pressure, but substantial unexplained variance calls for further research into additional determinants.

Funding: Finska Läkaresällskapet.