Relationship between heart rate variability traits and stroke: A Mendelian randomization study.

Area of Science:

• Cardiovascular Epidemiology
• Genetics
• Neurology

Background:

• Observational studies suggest a link between heart rate variability (HRV) and cerebrovascular disease.
• A causal relationship between HRV and stroke remains to be definitively established.

Purpose of the Study:

• To investigate the causal relationship between HRV and stroke using a two-sample Mendelian randomization analysis.
• To explore potential causal links between specific HRV measures and various stroke subtypes.

Main Methods:

• Utilized genome-wide association study data for HRV traits (SDNN, RMSSD, pvRSA/HF) and stroke subtypes (IS, LAS, LS, etc.).
• Employed two-sample Mendelian randomization with inverse-variance weighted (IVW) as the primary method.
• Conducted sensitivity analyses including Cochran's Q-test, MR-Egger's intercept, MR-PRESSO, and leave-one-out methods to ensure result reliability.

Main Results:

• Heart rate variability (SDNN) showed a causal association with ischemic stroke (IS) and large artery stroke (LAS).
• Peak-valley respiratory sinus arrhythmia/high-frequency power (pvRSA/HF) was causally linked to IS, LAS, and lacunar stroke (LS).
• The root mean square of successive differences (RMSSD) was not significantly associated with any stroke subtypes.

Conclusions:

• Provides genetic evidence for a causal effect of HRV (SDNN) on IS and LAS.
• Suggests a causal role for HRV (pvRSA/HF) in IS, LAS, and LS.
• Highlights specific HRV metrics as potential causal factors in different types of stroke.