Ranking the effect of early-life social and lifestyle risk factors on biological functioning and premature mortality to prioritize prevention strategies
Description: RATIONALE: Chronic diseases (CDs) contribute to poor population health and are the major cause of death world-wide. To mitigate this, the World Health Organization set the goal to reduce mortality from CDs by 25% before 2025 through reducing modifiable risk factors, such as unhealthy lifestyle behaviours. However, not considered in this goal are upstream social determinants of health, such as low income or education, which affect a large portion of the society, alter biological functioning, e.g. through physiological and epigenetic mechanisms, and eventually reduce longevity. Actually, prevention strategies addressing social disadvantage or unhealthy lifestyles can reduce the burden on healthcare systems, and work towards the elimination of socioeconomic inequalities in health, hence improving population health. Evidence is growing that prevention has the greatest impact early in life. However, it is not known which early-life risk factors, social or lifestyle, need prioritization to mitigate health inequalities and improve population health in adult life. AIMS: Our overarching aim is to assess and rank the effects of several early-life risk factors, spanning socioeconomic conditions and lifestyle behaviours, on CDs-related biological functioning and mortality by mid-life. Specifically, in aim 1, we will assess mechanisms underlying the early-life determinants of socioeconomic inequalities in CDs-related markers of physiological and epigenetic functioning by mid-life. In aim II, we will assess mechanisms underlying the early-life determinants of socioeconomic inequalities in CDs-related mortality by mid-life. In aim III, we will simulate population interventions on the early-life risk factors, such as reducing early-life socioeconomic disadvantage, or lowering the prevalence of one or multiple unhealthy lifestyle behaviours, and rank their impact for improving the biological functioning and premature mortality outcomes.METHODS: Data comes from four large prospective population-based cohort studies, the Add Health study from the US and the Young Finns study from Finland (aim I and III), and the 1958 and 1970 birth cohort studies from the UK (aim II and III), including approximately 50,000 individuals followed from early- to mid-life with repeated assessments over more than 25 years. We will measure inequalities in health outcomes driven by different levels of parental education and income during early-life. We will consider unhealthy lifestyle behaviours (smoking, poor diet, high alcohol intake, physical inactivity) in adolescence as intermediate risk factors. We will measure biological functioning via multiple physiological outcomes of cardiometabolic- and inflammation-related health, which are the leading risk factors of CDs, and via epigenetic signatures predicting CDs. We will assess whether a mechanism of differential susceptibility – whereby the social risk factor exacerbates the effect of unhealthy lifestyle on health – underlies the inequalities. We will apply g-methods to estimate potential outcomes models assessing the impact on the health outcomes of “what if” scenarios for the early-life factors, such as the reduction of CD-related mortality risk when lowering the prevalence of socioeconomic or lifestyle risk factors. IMPACT: Our results will provide strong empirical evidence across many relevant public health outcomes from three countries about early-life mechanisms underlying socioeconomic inequalities in biological functioning and premature mortality by mid-life. Specifically, increased susceptibility to specific lifestyle risk factors among those having experienced disadvantaged socioeconomic conditions will imply a prioritization of preventive policies targeting these susceptible population groups in order to mitigate health inequalities. Findings will also inform public health about the impact of addressing early-life risk factors to improve population health at mid-life. Specifically, as these data are observational, but by using potential outcomes models results may aid in decision-making about what type of interventions, i.e. either on social or one or multiple lifestyle risk factors, should be prioritized in real-world preventive strategies.
Amount: CHF 464,900
Funding type: research
Funder scheme: Project funding
Start date: 2022-10-01
End date: 2026-09-30
Investigator: Carmeli, Cristian
Institution: University of Fribourg – FR
Funded outputs count: 7
Funder award ID: 208205
OpenAlex ID: G3620985298