Addition of 24-Hour Heart Rate Variability Parameters to the Cardiovascular Health Study Stroke Risk Score and Prediction of Incident Stroke: The Cardiovascular Health Study

Rohan K Bodapati, Jorge R Kizer, Willem J Kop, Hooman Kamel, Phyllis K Stein, Rohan K Bodapati, Jorge R Kizer, Willem J Kop, Hooman Kamel, Phyllis K Stein

Abstract

Background: Heart rate variability (HRV) characterizes cardiac autonomic functioning. The association of HRV with stroke is uncertain. We examined whether 24-hour HRV added predictive value to the Cardiovascular Health Study clinical stroke risk score (CHS-SCORE), previously developed at the baseline examination.

Methods and results: N=884 stroke-free CHS participants (age 75.3±4.6), with 24-hour Holters adequate for HRV analysis at the 1994-1995 examination, had 68 strokes over ≤8 year follow-up (median 7.3 [interquartile range 7.1-7.6] years). The value of adding HRV to the CHS-SCORE was assessed with stepwise Cox regression analysis. The CHS-SCORE predicted incident stroke (HR=1.06 per unit increment, P=0.005). Two HRV parameters, decreased coefficient of variance of NN intervals (CV%, P=0.031) and decreased power law slope (SLOPE, P=0.033) also entered the model, but these did not significantly improve the c-statistic (P=0.47). In a secondary analysis, dichotomization of CV% (LOWCV% ≤12.8%) was found to maximally stratify higher-risk participants after adjustment for CHS-SCORE. Similarly, dichotomizing SLOPE (LOWSLOPE <-1.4) maximally stratified higher-risk participants. When these HRV categories were combined (eg, HIGHCV% with HIGHSLOPE), the c-statistic for the model with the CHS-SCORE and combined HRV categories was 0.68, significantly higher than 0.61 for the CHS-SCORE alone (P=0.02).

Conclusions: In this sample of older adults, 2 HRV parameters, CV% and power law slope, emerged as significantly associated with incident stroke when added to a validated clinical risk score. After each parameter was dichotomized based on its optimal cut point in this sample, their composite significantly improved prediction of incident stroke during ≤8-year follow-up. These findings will require validation in separate, larger cohorts.

Keywords: autonomic nervous system; clinical stroke risk model; heart rate variability; prediction; predictors; risk prediction; risk stratification; stroke.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Survival curves for incident stroke based on combined categories of higher and lower coefficient of variance (CV%) and power law slope (SLOPE) after adjustment for continuous CHS‐SCORE. Reference category is HIGHCV%‐HIGHSLOPE. HIGHCV%‐LOWSLOPE: HR=1.3 (95% CI=0.6–2.8, P=0.59); LOWCV%‐HIGHSLOPE: HR=1.6 (95% CI=0.8–3.4, P=0.19); LOWCV%‐LOWSLOPE: HR=3.5 (95% CI=1.8–6.8, P<0.001) where LOWCV%=CV% ≤12.8%, HIGHCV%=CV% >12.8%, LOWSLOPE=SLOPE <−1.4, HIGHSLOPE=SLOPE ≥−1.4. CHS‐SCORE indicates Cardiovascular Health Study stroke risk score; HR, hazard ratio.

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