Haemodynamic Gain Index Is Associated with Risk of Sudden Cardiac Death and Improves Risk Prediction: A Cohort Study

Jari A Laukkanen; Nzechukwu M Isiozor; Peter Willeit; Setor K Kunutsor

doi:10.1159/000530637

Haemodynamic Gain Index Is Associated with Risk of Sudden Cardiac Death and Improves Risk Prediction: A Cohort Study

Cardiology. 2023;148(3):246-256. doi: 10.1159/000530637. Epub 2023 Apr 13.

Authors

Jari A Laukkanen^{1

2

3}, Nzechukwu M Isiozor², Peter Willeit^{4

5}, Setor K Kunutsor^{6

7}

Affiliations

¹ Department of Medicine, Wellbeing Services County of Central Finland, Jyväskylä, Finland.
² Institute of Clinical Medicine, Department of Medicine, University of Eastern Finland, Kuopio, Finland.
³ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
⁴ Clinical Epidemiology Team, Medical University of Innsbruck, Innsbruck, Austria.
⁵ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁶ Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK.
⁷ Translational Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Bristol, UK.

Abstract

Introduction: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study.

Methods: HGI was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1897 men aged 42–61 years during CPX from rest to peak exercise. Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for SCD.

Results: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p value for non-linearity = 0.63). A unit (bpm/mm Hg) higher HGI was associated with a decreased risk of SCD (HR: 0.84; 95% CI: 0.71-0.99), which was attenuated following adjustment for CRF. CRF was inversely associated with SCD, which remained after further adjustment for HGI (HR: 0.85; 95% CI: 0.77-0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change = 0.0096; p = 0.017) and reclassification (net reclassification improvement [NRI] = 39.40%, p = 0.001). The corresponding values for CRF were (C-index change = 0.0178; p = 0.007) and (NRI = 43.79%, p = 0.001).

Conclusion: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.

Keywords: Cardiopulmonary exercise testing; Cohort study; Haemodynamic gain index; Sudden cardiac death.

MeSH terms

Cohort Studies
Death, Sudden, Cardiac* / etiology
Hemodynamics*
Humans
Male
Prospective Studies
Risk Factors

Grants and funding

This work has been supported in part by grants from the Finnish Foundation for Cardiovascular Research, Helsinki, Finland. S.K.K. is funded by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and Leicester NIHR Biomedical Research Centre (BRC). The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.