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Heart Rhythm

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Inflammation and SCD in older adults

A greater burden of inflammation in older adults (>65 years), assessed by interleukin-6 (IL6) levels, is associated with sudden cardiac death (SCD) risk beyond traditional risk factors, incident myocardial infarction, and heart failure, according to a study1 published recently in Heart Rhythm.

In the Cardiovascular Health Study, 5,806 and 5,382 participants had measurements of C-reactive protein (CRP) and IL6, respectively, and were followed for up to 17 years. SCD risk as a function of baseline IL6 and CRP was assessed in the overall population and in a group of participants without known prevalent cardiac disease.

In univariate analyses, both IL6 and CRP were associated with SCD risk. In covariate-adjusted analyses, accounting for baseline risk factors, incident myocardial infarction, and heart failure, the association with SCD risk persisted for IL-6 but was significantly attenuated for CRP. Similar findings were observed in participants without prevalent cardiac disease.

Gershlick

Prof Tony Gershlick (University Hospitals of Leicester)

Inflammation is linked to adverse cardiovascular events, but its association with sudden cardiac death (SCD) has been controversial. Older subjects, who are at particular risk for SCD, were underrepresented in previous studies addressing this issue.

A note of caution was voiced by Professor Tony Gershlick (Professor of Interventional Cardiology, University Hospitals of Leicester), who commented to BJC Arrhythmia Watch: “The authors have set out to investigate the importance of inflammation in sudden cardiac death, focussing on the elderly who they rightly state are under-represented in most other studies…The paper is well written and the statistical methods section appears robust,  albeit somewhat densely incomprehensible for most I suspect. Taken at face value there appears to be an association between one of the markers of inflammation (IL-6) and sudden cardiac death.”

“This raises the question of whether we should now be trying to suppress inflammation in the elderly population to prevent sudden cardiac death, over and above controlling for the standard recognised risks associated with this clinical outcome (such as myocardial infarction (MI) and heart failure). The answer is probably ‘no’ for a number of reasons. Firstly the hypothesis, in the absence of clear understanding of potential pathology, is weak. The authors are unclear of the mechanism,” he added.

“The authors’ insightful limitations paragraph highlighting uncontrolled aspects of the study (especially the presence or not of defibrillators) needs to be read when considering the robustness of the findings. Other issues include: changes in treatments over time (these data were collected in the early 1990s); the mechanism that could ever possibly underlie a raised inflammatory biomarker at source influencing sudden cardiac death so late (at median of 13 years); the weakness of the association together with the lack of detailed consideration of the impact of other co-morbidities; the fact that many had sudden cardiac death without a raised biomarker and there were those with a raised biomarker who did not suffer sudden cardiac death. Such factors make this a difficult and treacherous area to be researching, and add to the potential weakness of the finding,” Professor Gershlick continued.

“Therefore, based on what we have, I do not think there is enough here to warrant investing resources in – not least since primary prevention has a poor cost efficacy balance. However there is something going on and a relationship between inflammation and acute changes in atheromatous plaques has been established in many other publications. Whether it is truly of real, causal significance (as opposed to merely an association) and of sufficient impact to be worth doing something about, requires further investigation. Population studies such as the one by Hussein et al are vital, but difficult to perform and difficult to interpret. The introduction of and clinical study cytokine inhibitors (for example Anakinra an IL-1 receptor antagonist) may help focus the studies,” he concluded.

References

1. Hussein AA, Gottdiener JS, Bartz TM, et al. Inflammation and sudden cardiac death in a community-based population of older adults: The Cardiovascular Health Study. Heart Rhythm 2013. http://dx.doi.org/10.1016/j.hrthm.2013.07.004

Published on: October 30, 2013

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