The regulatory effects of the autonomic nervous system (ANS) concern almost all organs which permanently feed information back to this global biological vigilance system controlling allostasis. Heart rate fluctuations are highly dependent on ANS control, making the heart one of the best indicators of ANS activity.

Low ANS activity level is associated with severe cardiac and cerebral events, as well as to death from any cause in the general population.

This PROOF study was hence designed to evaluate ANS activity levels among a healthy retired population, but should these levels decline overtime, to use this as a predictor of cardiovascular and cerebrovascular events, taking into account established cardiovascular risk factors.

The main goal of this PROOF study is to evaluate, on a selected prospective cohort of subjects aged 65 years upon study entry, the prognostic values of ANS activity levels measured at preset times, and more specifically, of its decline over the follow-up period, for fatal and non-fatal cardiovascular and cerebrovascular events.

Inclusion Criteria:

• 65 years old
• informed consent signed

Exclusion Criteria:

• prior myocardiac infarction
• prior stroke
• hearth failure
• atrial fibrillation
• insulin-treated diabetes mellitus
• cardiac pacemaker
• disease limiting life expectancy to < 5 years
• contraindication to brain MRI
• living in an institution

Subjects were recruited amongst the inhabitants of the city of Saint-Etienne, France, and were eligible if aged 65 at the inclusion date.