Chronobiological Patterns and Risk of Acute Aortic Dissection: A Clinical Retrospective and Two-Sample Mendelian Randomisation Study

Aim: Acute aortic dissection (AAD) represents a cardiovascular ailment characterised by a notable mortality rate. Chronobiological patterns can offer a predictive framework for anticipating the onset of AAD.

Method: Data were gathered from 1,151 patients diagnosed with AAD at Changhai Hospital in Shanghai, China, spanning 2000-2023. The χ² test was used to assess whether specific periods exhibited significantly different seasonal/weekly distributions compared with others. Fourier models were utilised for the analysis of rhythmicity in monthly/circadian distribution. Publicly available genome-wide association studies datasets were used to establish the causal relationship between chronotype and AAD. Two sets of genetics instruments were used for analysis, derived from publicly available genetic summary data: 75 single-nucleotide polymorphisms (SNPs) significantly associated with chronotype; and SNPs associated with AAD in the FinnGen consortium.

Results: The mean age was 51.5±13.8 years, with 665 patients (57.8%) aged <55 years. Among the 1,151 patients, 80.9% were male. The distribution of DeBakey types was 73.2% (843) for DeBakey I, 21% (242) for DeBakey II, and 5.7% (66) for DeBakey III. Comorbidities included hypertension in 58.5% (673 cases) and diabetes in 7.8% (90 cases). A peak occurred during colder periods (winter/December), and a trough was noted in warmer periods (summer/June). Weekly distribution exhibited no significant variation. Fourier analysis revealed a statistically significant circadian variation (p<0.0001) with a trough between 23:00 and 00:00, a prominent peak from 07:00 to 08:00, and a minor peak between 20:00 and 21:00. Subgroup analyses identified circadian rhythmicity in all subgroups, except for the DeBakey III group and the female group. Using the 75 chronotype-related SNPs, evidence was found of a potential causal effect of chronotype on the risk of AAD, as the inverse-variance weighting analysis showed that self-report chronotype of morningness was associated with a decreased risk of AAD.

Conclusion: The findings substantiate that the initiation of AAD displays noteworthy seasonal, monthly, and circadian patterns. The Mendelian randomisation analysis also indicated that the onset of acute aortic dissection is related to circadian rhythm. These findings offer a fresh perspective, facilitating the identification of triggering factors for AAD and bolstering preventive measures for this catastrophic event.