Background The ageing population and prevalence of long-term disorders with multimorbidity is a major health challenge worldwide. Patients with multimorbidity account for a disproportionately high share of healthcare workload and costs and experience reduced wellbeing and quality of life. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospitalisations with multimorbidity. Our study examines the independent associations for a range demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity using a prospective community-based cohort of middle-aged and older men and women resident in Norfolk, UK. We explore demographic, lifestyle and physiological exposures including age and sex, body mass index, cigarette smoking, alcohol intake, educational attainment, occupational social class, physical activity, plasma vitamin C, total cholesterol, systolic blood pressure and common prevalent diseases.

Methods Incident hospital admissions with multimorbidity were examined in 25014 men and women aged 40–79 in EPIC-Norfolk, a British prospective population-based study initially recruited in 1993–1997 and followed-up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥2, were examined in multivariable models for the 10-year period 1999–2009 and repeated with independent measurements in a second 10-year period 2009–2019.

Results Between 1999–2009 18179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidity were observed in 11% and 21% of participants respectively. Age per 10-year increase OR 2.13 (95% CI 2.03–2.23) and male sex OR 1.28 (95% CI 1.17–1.39) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking OR 1.71 (95% CI 1.53–1.91), BMI >30 kg/m² OR 1.37 (95% CI 1.24–1.51) and physical inactivity OR 1.09 (95% CI 1.00–1.18) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase OR 0.88 (95% CI 0.84–0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period 2009–2019.

Conclusion Age, male sex and potentially modifiable lifestyle behaviours including smoking, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.