Objective Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Resting heart rate (RHR), which may be modifiable through lifestyle changes, has been shown to be associated with cardiovascular disease risk and with inflammatory markers that have been predictive of VTE incidence.
Methods We examined whether RHR is also associated with VTE incidence independent of these risk factors. We studied 6479 Multi-Ethnic Study of Atherosclerosis participants free from clinical VTE at baseline who had baseline RHR ascertained by 12-lead ECG. VTE events were recorded from hospital records and death certificates using International Classification of Diseases (ICD)-9 and ICD-10 codes. We categorised RHR as <60, 60–69, 70–79 and ≥80 bpm. We used Cox hazard models to determine the association of incident VTE by RHR.
Results Participants had mean (SD) age of 62 (10) years and RHR of 63 (10) bpm. RHR was cross-sectionally correlated with multiple inflammatory and coagulation factors. There were 236 VTE cases after a median follow-up of 14 years. Compared with those with RHR<60 bpm, the HR (95% CI) for incident VTE for RHR≥80 bpm was 2.08 (1.31 to 3.30), after adjusting for demographics, physical activity, smoking, diabetes and use of atrioventricular (AV)-nodal blockers, aspirin and anticoagulants, and remained significant after further adjustment for inflammatory markers (2.05 (1.29 to 3.26)). Results were similar after excluding those taking AV-nodal blocker medications. There was no effect modification of these associations by sex or age.
Conclusion Elevated RHR was positively associated with VTE incidence after a median of 14 years; this association was independent of several traditional VTE and inflammatory markers.
- deep vein thrombosis
- venous thromboembol
- heart rate variability
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JA and OEF contributed equally.
Contributors The concept of this research study was designed by JA, OEF and EDM. OEF performed the statistical analyses under the guidance of DZ. JA and EDM wrote the initial draft. OEF, PLL, DZ and WTO contributed significant intellectual content. All authors approved of the final draft of the manuscript.
Funding EDM and DZ were supported by the Blumenthal Scholars Fund for Preventive Cardiology Research at Johns Hopkins University. This MESA study was supported by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169 from the National Heart, Lung and Blood Institute (NHLBI), and by grants UL1-TR-000040, UL1-TR-001079 and UL1-TR-001420 from NCATS.
Competing interests None declared.
Patient consent for publication The MESA study was approved by the Institutional Review Boards at each study site, and participants provided written informed consent.
Ethics approval Johns Hopkins School of Medicine Institutional Review Board (IRB) Multi-Ethnic Study of Atherosclerosis NA_00030361/CR00010390.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available. The MESA study participates in data sharing through the National Heart, Lung, Blood Institute (NHLBI) Biologic Specimen and Data Repository Coordinating Center (BioLINCC). Requests for access to the data can be made through their website: https://biolincc.nhlbi.nih.gov/studies/mesa/.
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