Patterns of Circadian Variation in 24-Hour Ambulatory Blood Pressure, Heart Rate, and Sympathetic Tone Correlate with Cardiovascular Disease Risk: A Cluster Analysis

To investigate whether specific time series patterns for blood pressure (BP), heart rate (HR), and sympathetic tone are associated with metabolic factors and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). A total of 989 patients who underwent simultaneous 24-hour ambulatory BP and Holter electrocardiogram monitoring were enrolled. The patients were categorized into sixteen groups according to their circadian patterns using the consensus clustering analysis method. Metabolic factors, including cholesterol profiles and apolipoprotein, were compared. The 10-year ASCVD risk was estimated based on the Framingham risk model. Overall, 16 significant associations were found between the clinical variables and cluster groups. Age was commonly associated with all clusters in systolic BP (SBP), diastolic BP (DBP), HR, and sympathetic tone. Metabolic indicators, including diabetes, body mass index, total cholesterol, high-density lipoprotein, and apolipoprotein, were associated with the four sympathetic tone clusters. In the crude analysis, the ASCVD risk increased incrementally from clusters 1 to 4 across SBP, DBP, HR, and sympathetic tone. After adjustment for multiple variables, however, only sympathetic tone clusters 3 and 4 showed a significantly high proportion of patients at high risk (≥7.5%) of 10-year ASCVD (odds ratio OR=5.90, 95% confidential interval CI=1.27-27.46, and P value = 0.024 and OR=15.28, 95% CI=3.59-65.11, and P value < 0.001, respectively). Time series patterns of BP, HR, and sympathetic tone can serve as an indicator of aging. Circadian variations in sympathetic tone can provide prognostic information about patient metabolic profiles and indicate future ASCVD risk.