JMIR Publications

ABSTRACT

Background:

The rest-activity rhythm amplitude (RARA), as a fundamental human behavior, has been linked to various health conditions. However, its causality with ischemic heart disease (IHD), along with the potential modification by genetic predisposition, remains unclear.

Objective:

We aimed to investigate the causality between RARA and IHD using a triangulation approach and whether genetic predisposition modifies it.

Methods:

On the one hand, a prospective cohort analysis was conducted on individuals from the UK Biobank. Disrupted RARA was established as the first quintile of accelerometer-derived amplitude. Incident IHD was identified through medical records. Genetic predisposition is assessed with polygenic risk scores for IHD(IHD-PRS). Cox proportional hazards models were used to assess the association between RARA with incident IHD, as well as the modification effects of IHD-PRS. On the other hand, a two-sample Mendelian randomization by Inverse variance weighted methods was performed to examine the causality about them.

Results:

84,095 participants were followed up for a median of 7.90 years with 3,870 (4.60%) incident IHD. Disrupted RARA was significantly associated with a higher risk of IHD (HR: 1.20, 95% CI: 1.12–1.30). No significant modification effects of genetic predisposition on this association were found (interaction term: 0.92(0.76 to 1.11), 0.91(0.74 to 1.12), all P > 0.05). Mendelian randomization results supported the observational findings (OR: 1.13, 95% CI: 1.04–1.23).

Conclusions:

The study supports a likely causal relationship between RARA and IHD, independent from genetic predisposition, highlighting the significance of rest-activity rhythm amplitude for IHD prevention.