Chronotype as an Independent Predictor of Cardiovascular Risk in Euthymic Bipolar Patients
I. Uysal, I. Keleş AltunIntroduction
Patients with bipolar disorder (BD) have an increased risk of cardiovascular morbidity and mortality compared to the general population. While metabolic and pharmacological factors are well-documented contributors, the role of circadian rhythm and chronotype in cardiovascular vulnerability remains underexplored.
Objectives
To examine whether chronotype differences influence cardiovascular risk in euthymic bipolar patients and whether this effect remains independent of medication dose, mood stabilizer levels, illness duration, and other clinical variables.
Methods
Sixty euthymic BD patients (30 morning-type, 30 evening-type) were evaluated. Euthymia was confirmed using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Chronotype was assessed with the Morningness–Eveningness Questionnaire (MEQ). Cardiovascular risk was calculated using the QRISK3 algorithm, which integrates variables such as age, sex, blood pressure, smoking, diabetes, lipid profile, and BMI. The algorithm provides 10-year cardiovascular risk (%QRISK3), relative risk (RR), and heart age. The difference between heart and biological age was defined as the Heart–Biological Age Gap. Two multiple linear regression models were performed: a hierarchical regression for Relative Risk (RR), including MEQ score, illness duration, chlorpromazine-equivalent dose, and age at onset; and another model for the Heart–Biological Age Gap, including MEQ score, illness duration, chlorpromazine-equivalent dose, age at onset, and serum lithium and valproate levels.
Results
Both QRISK3 and Relative Risk (RR) scores were elevated compared to population norms, indicating increased cardiovascular vulnerability among euthymic bipolar patients. Evening-type individuals had significantly higher RR (Z = –2.43, p = 0.015) and greater Heart–Biological Age Gap (Z = –2.39, p = 0.017) than morning-types.
In the regression model predicting RR, lower MEQ scores (reflecting greater eveningness) significantly predicted higher RR (β = –0.009, p = 0.003; F = 5.00, p = 0.003), while other clinical and pharmacological variables were not significant.
In the model predicting the Heart–Biological Age Gap, both lower MEQ scores (β = –0.156, p = 0.001; F = 5.63, p < 0.001) and higher chlorpromazine-equivalent doses (β = 0.012, p = 0.003) were associated with greater cardiovascular aging.
Image 1: Long description.