The proteomic profile of leisure time physical activity across two decades: implications for future cardiovascular risk and mortality

Aim We aimed to 1) investigate associations between leisure time physical activity level cumulated over 20 years and multiple plasma proteins and 2) explore if proteins significantly associated with physical activity are also associated with risk of imminent myocardial infarction (MI), long-term MI and mortality. Methods In the cohort Uppsala Longitudinal Study of Adult Men (ULSAM), leisure time physical activity was self-reported at ages 50, 60, and 70. At age 70, 720 plasma proteins were analyzed in 782 participants with up to 19.3 years of follow-up for MI and 26.3 years follow-up for mortality. In the nested case-cohort study Markers of Imminent Myocardial Infarction (MIMI), plasma proteins were measured in disease-free individuals from six European cohorts. Cases (n=420) were those with acute MI within 6 months of a blood draw, with up to four cohort representatives per case (n=1,598). Results A higher level of leisure time physical activity level was inversely associated with 12 plasma proteins after adjusting for age, education, smoking and established cardiovascular risk factors (Bonferroni corrected p<0.000069). Of these 12 proteins, IL-6 was associated with increased incidence of imminent MI (HR 1.22 95%CI [1.09-1.37]), TNFRSF11A was associated with increased long-term MI incidence (HR 1.22 [1.01-1.48]) and 11 proteins were associated with increased mortality (HR 1.14-1.30 [1.01-1.42]). Conclusions These findings confirm and extend our understanding of how physical activity could assert its beneficial effect on cardiovascular health through proteins involved with modulating inflammatory, immune and metabolic pathways. Further research is needed to explore the causal mechanisms behind these associations.