A prospective evaluation of the long-term clinical associations of neurocardiovascular instability in older people

Abstract

Introduction Neurocardiovascular instability (NCVI) describes a group of disorders characterised by orthostatic hypotension (OH), carotid sinus hypersensitivity (CSH) and autonomic dysfunction. In cross-sectional studies, NCVI has been associated with cognitive impairment, depression and falls. It is suggested that episodic hypotension causes cerebral hypoperfusion, which in turn causes anoxic brain damage. White matter hyperintensities (WMH) on MRI are thought to represent ischaemic damage due to hypoperfusion and are also associated with cognitive impairment, depression, and falls. Despite these observations, the long-term clinical significance of NCVI remains unclear, particularly in asymptomatic individuals Aims  To examine the associations between NCVI and cognition, depression and falls over a ten-year follow-up  To examine the association between NCVI and WMH volume on MRI  To examine the association between NCVI and ten-year all-cause mortality. Methods Participants were recruited from an established cohort of people aged ≥65 years in 2002. Baseline evaluation of neurocardiovascular function in 2002 included heart rate variability, autonomic function tests and carotid sinus massage. Neuropsychological assessment was performed at baseline and at follow-up. MRI was performed at follow-up (but not at baseline). WMH volume was calculated using FLAIR MRI. Cox regression analysis was used to examine the association between NCVI and mortality. Results In 2002 1000 individuals aged ≥65 years were selected at random from a single GP practice and invited to participate in the study. 353 consented to enrolment in the baseline study. Of whom 104 individuals [median age 79 years (range 74-92)] participated in the year 10 follow-up. Asymptomatic NCVI was not associated with cognition, depression, falls or WMH volume at follow-up. Symptomatic OH was associated with greater decline in CAMCOG memory score [B =1.19, P<0.05] and symptomatic CSH was independently associated with increased WMH volume [P<0.01]. NCVI defined according to standard criteria was not associated with ten-year mortality. However, at baseline it had been identified that the 95th percentile for systolic vasodepression was 76.6 mmHg and the 95th percentile for RR interval post CSM was 7.3 seconds. These thresholds were used to define CSH modified criteria. CSH defined according to modified criteria, derived from the baseline populations’ response to CSM, was associated with increased mortality [HR2.37, P=0.02]. Conclusions NCVI is not associated with adverse outcomes at ten years in asymptomatic older people but symptomatic NCVI is associated with decline in memory and greater WMH volume, suggesting symptoms are of prognostic significance. Modified CSH criteria are better predictors of ten-year mortality than current criteria.