Cardiovascular

Differential associations of resting heart rate and heart rate variability indices with cardiovascular and coronary heart disease mortality risk: the prospective KORA study.

Oluwagbemigun K, Ziegler D, et al. • Scientific reports • 2026

PubMed 42618690 DOI 10.1038/s41598-026-66516-y

TL;DR

RHR and HRV indices provide differential and complementary insights into long-term CVD mortality risk in the general population, with RHR directly associated with CVD and CHD mortality overall, and specific HRV indices showing glucose tolerance status-specific associations.

Key Findings

Results

Resting heart rate (RHR) was independently and directly associated with CVD mortality in the overall study sample.

HR per 1-SD increment: 1.20 (95% CI: 1.04, 1.39), P = 0.013
Association was independent of covariates
Sample included 1390 adults from the KORA S4 study (1999–2001)
CVD mortality was ascertained over a 22-year follow-up period

Results

Resting heart rate was independently and directly associated with CHD mortality in the overall study sample.

HR per 1-SD increment: 1.32 (95% CI: 1.08, 1.62), P = 0.007
Association was independent of covariates
This was a stronger association than that observed for CVD mortality (HR 1.32 vs. 1.20)
RHR was measured from five-minute electrocardiograms performed at baseline

Results

Very-low frequency power (VLF) was directly associated with CVD mortality specifically in individuals with normal glucose tolerance (NGT).

HR per 1-SD increment: 1.17 (95% CI: 1.01, 1.37), P = 0.038
This association was specific to the NGT subgroup and not observed overall
66 HRV indices were examined in total using Cox models
Both linear and non-linear associations were assessed

Results

RMSSD showed a non-linear association with CVD mortality specifically in individuals with type 2 diabetes.

RMSSD is defined as the square root of the mean squared differences of successive NN intervals
The non-linear association was specific to the type 2 diabetes subgroup
No statistically significant linear association of RMSSD with CVD mortality was reported in the overall sample
Cox models were used to determine both linear and non-linear associations across glucose tolerance subgroups

Results

SPPA_c_8 (number of data points in the 8th column of a 12×12 matrix, a nonlinear HRV index) was inversely associated with CVD mortality in individuals with prediabetes.

HR per 1-SD increment: 0.54 (95% CI: 0.32, 0.93), P = 0.025
This association was specific to the prediabetes subgroup
SPPA_c_8 is a symbolic dynamics-based nonlinear HRV measure
The inverse association suggests higher SPPA_c_8 values were associated with lower CVD mortality risk in prediabetes

Methods

The study examined RHR and 66 HRV indices in 1390 adults followed prospectively for 22 years for CVD and CHD mortality outcomes.

Data from the KORA S4 study conducted in 1999–2001 in the Augsburg region of Germany
HRV indices were derived from five-minute resting ECG recordings at baseline
Participants were stratified by glucose tolerance status: normal glucose tolerance (NGT), prediabetes, and type 2 diabetes
Cox proportional hazards models were used for both overall and subgroup analyses
Both linear and non-linear associations were examined

What This Means

This research suggests that a faster resting heart rate is linked to a higher risk of dying from cardiovascular disease (CVD) or coronary heart disease (CHD) over a 22-year period in the general population. The study followed nearly 1,400 adults in Germany, measuring their heart rate and a wide range of heart rate variability (HRV) indices — measures of the tiny fluctuations in time between heartbeats — using short ECG recordings. After accounting for other health and lifestyle factors, people with higher resting heart rates had roughly 20% higher CVD mortality risk and 32% higher CHD mortality risk compared to those with lower resting heart rates. Beyond resting heart rate, the study found that certain HRV measures were associated with CVD mortality risk in ways that differed depending on whether a person had normal blood sugar regulation, prediabetes, or type 2 diabetes. For example, a specific frequency-based HRV measure (very-low frequency power) was linked to higher CVD mortality risk only in people with normal glucose tolerance, while a nonlinear HRV measure (SPPA_c_8) was associated with lower CVD mortality risk only in people with prediabetes. In people with type 2 diabetes, a common HRV measure called RMSSD showed a more complex, non-linear relationship with CVD mortality risk. This research suggests that resting heart rate and HRV measures capture different and complementary information about long-term heart disease mortality risk, and that the relevance of specific HRV measures may vary depending on a person's metabolic health status. These findings highlight the potential value of using multiple heart rhythm measures together — rather than any single metric alone — to better understand cardiovascular risk, particularly in populations with varying degrees of blood sugar regulation.

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Citation

Oluwagbemigun K, Ziegler D, Strom A, Heier M, B&#xf6;nhof G, Roden M, et al.. (2026). Differential associations of resting heart rate and heart rate variability indices with cardiovascular and coronary heart disease mortality risk: the prospective KORA study.. Scientific reports. https://doi.org/10.1038/s41598-026-66516-y

Key Findings

What This Means

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