Is the association between visit- to- visit heart rate variability and cardiovascular disease mediated by arteriopathy as measured by carotid intima- media thickness?

BACKGROUND: Visit-to-visit heart rate variation (HRV-VV) is associated with mortality and cardiovascular events. Mechanisms of the interaction between HRV-VV and vascular disease are not clearly understood. Our study aimed to evaluate the association between HRV-VV and carotid intima-media thickness (IMT) and their potential impact on cardiovascular disease development. METHODS: The study population is derived from a cohort of elderly patients enrolled in the primary-care-based INtervention project on cerebroVAscular diseases and Dementia in the community of Ebersberg (INVADE). We included all patients with a follow-up of eight years and five follow-up visits in regular two-year intervals. HRV-VV was defined by the standard deviation of between-visit measurements (SD). Uni- and multivariable regression models were used to identify associations between HRV-VV, IMT, and a combined cardiovascular endpoint of new onset stroke and myocardial infarction. RESULTS: 2815 patients were included in the study. HRV-VV was positively associated with IMT in multivariable analysis (p = 0.026). Every SD HRV-VV of 10 bpm was associated with a change of IMT of 18 ± 8 µm. Furthermore, HRV-VV showed a numerical and positive association with the combined cardiovascular endpoint (p = 0.07), while a simultaneous increase in HRV-VV and IMT increased the likelihood more than either factor alone (p = 0.009). CONCLUSION: HRV-VV showed a positive association with IMT, a surrogate marker for early arteriopathy. Both parameters furtherly demonstrated a synergistic impact on the likelihood of cardiovascular disease development. Given its widespread availability by continuous monitoring with wearables, HRV-VV may provide a potentially modifiable medical target for personalized cardiovascular risk stratification.