Nighttime Heart Rate Variability and The Risk of Stroke in Apparently Healthy Subjects

Transcription

1 Nighttime Heart Rate Variability and The Risk of Stroke in Apparently Healthy Subjects Zeynep Binici 1,2, Mette Rauhe Mouridsen 2, Lars Køber 3, Ahmad Sajadieh 1,2 (No potential conflict of interest regarding the following presentation) 1. Department of Cardiology, Copenhagen University Hospital of Amager, Denmark 2. Department of Cardiology, Copenhagen University Hospital of Bispebjerg, Denmark 3. Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Denmark

2 Background - 1 STROKE Stroke is the third leading cause of death in the Europe, United States, and many countries in the world. Incidences of stroke-related deaths and disability are expected to rise even higher as the population ages. One year after an index stroke: One third has died, One third still need help from other, Only one third are resourceful. 30% of all stroke cases are believed to be cardioembolic.

3 Background - 2 HEART RATE VARIABILITY Heart rate is controlled by the autonomic system. Heart rate variability (HRV) reflects the influence of the sympathetic and parasympathetic activity. Heart rate variability predicts mortality and cardiovascular diseases. The association between HRVand stroke is not well studied Koukam C, Guédon-Moreau L, Lucas C, Zghal N, Mahe I, Klug D, Jarwe M, Lacroix D, leys D, Kacet S. Long-term evaluation of autonomic tone in patients below 50 years of age with unexplained cerebral infarction: relation to atrial vulnerability. Europace 2000; 2:

4 Background - 3 NIGHTTIME HEART RATE VARIABILITY Nighttime HRV may be more free from incidental influences like physical activity and mental stress. Nighttime HRV may be more reproduceable.

5 Hypothesis 1. Reduced HRV is predictive of stroke 2. Nighttime HRV is a better predictive tool than 24-h HRV Nighttime HRV 24-h HRV Stroke Mortality

6 Definitions - 1 Heart rate variability: reflects fluctuations in heart rate over time (from beat to beat and over longer time periods) SDNN: the standard deviation of normal to normal (NN) QRS intervals over a defined periode of time. Nighttime SDNN: a period of 15 min from 02:00 am to 02:15 am. 24-h SDNN: calculated for a 24-h period

7 Definitions - 2 Heart rate MeanNN: the mean value for the time between normal complexes. Nighttime MeanNN: a sequence of between 2:00 am and 2:15 am. 24-h MeanNN: calculated for an entire 24-h period. MeanNN for each period reflects the mean heart rate during that period ( / MeanNN = heart rate in beat/ sec).

8 Methods Copenhagen Holter study: An epidemiological survey From two districts of Copenhagen: Men aged 55, 60, 65, 70, 75 and women aged 60, 65, 70, 75 were identified and contacted by a questionnaire Interview Physical examination Fasting laboratory testing 48-h Holter study 7-year follow-up

9 Results Follow-up Median follow-up: 76 months (interquartile range 73-78) Endpoints Death or Stroke: 98 Stroke: 26 Death: 80

10 Baseline Variables ALL N=653 with Sinus Rhythm Age, y Female sex, n (%) 276 (42%) Current smoking, n (%) 305 (46.7%) Diabetes mellitus, n (%) 71 (10.9%) SBP, mmhg DBP, mmhg Total Cholesterol, mmol/l Triglyceride, (mmol/l) Glucose, (mmol/l) HbA1c ( ) C-Reactive Protein (µl/ml) 3 (3-5) Low level of physical activity, n (%) 169 (25.9%) BMI, (kg/m 2 ) Nighttime SDNN 38 (27-55) SDNN Nighttime MeanNN MeanNN

11 Correlations Multivariable Regression analysis Nighttime HRV was associated with: Triglyceride hs-c-reactive Protein Gender Diabetes 24-h HRV was associated with: Age Plasma glucose Diabetes Gender Smoking Low level of physical activity

12 All-cause mortality or stroke Nighttime SDNN Nighttime MeanNN 24-h SDNN 24-h MeanNN Hazard Ratio (95% Confidence Intervals) per 10 ms change p-value Univariate 0.84 ( ) ( ) ( ) ( ) Age and gender adjusted 0.83 ( ) ( ) < ( ) < ( ) < Multivariable* 0.86 ( ) ( ) ( ) ( ) * age, gender, smoker, diabetes mellitus, systolic blood pressure, total cholesterol

13 Stroke Nighttime SDNN Nighttime MeanNN 24-h SDNN 24-h MeanNN Hazard Ratio (95% Confidence Intervals) per 10 ms change p-value Univariate 0.67 ( ) ( ) ( ) ( ) Age and gender adjusted 0.66 ( ) ( ) ( ) ( ) Multivariable* 0.67 ( ) ( ) ( ) ( ) * age, gender, smoker, diabetes mellitus, systolic blood pressure, total cholesterol

14 All-cause mortality Nighttime SDNN Nighttime MeanNN 24-h SDNN 24-h MeanNN Hazard Ratio (95% Confidence Intervals) per 10 ms change p-value Univariate 0.88 ( ) ( ) ( ) ( ) Age and gender adjusted 0.87 ( ) ( ) < ( ) < ( ) Multivariable* 0.91 ( ) ( ) ( ) ( ) * age, gender, smoker, diabetes mellitus, systolic blood pressure, total cholesterol

15 Kaplan-Meier survival curve showing time course of events (death or stroke) according to the quartiles of nighttime heart rate variability. Kaplan-Meier survival estimates P< Time (months) 4. quartile 3. quartile 2. quartile 1. quartile

16 Events per 1000 patient-year Incidence of stroke admissions per 1000 patientyear in relation to nighttime SDNN ,5 11, ,96 2 1,05 0 n=156 n=167 n=163 n=166 Study subjects with nighttime SDNN Quartile:

17 Conclusions Nighttime heart rate variability (HRV) is strongly associated with stroke. 24-h HRV, 24-h heart rate and nighttime heart rate were not significantly associated with stroke but with all-cause mortality. The risk of stroke increases with 33% for every decrease of 10 ms of nighttime heart rate variability. Clinical perspective: Nighttime HRV provides additional information on the risk of stroke.