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This study aims to transfer and extend the previous findings to two general population-based samples to explore the hypothesis that NIM-ratio is associated with all-cause mortality. Two large population studies (MIDUS 2: N\u2009=\u20091255 and Whitehall II wave 5: N\u2009=\u20097870) with complete data from a total of N\u2009=\u20093860 participants (36.1% females; average age\u2009=\u200956.3\u00a0years; 11.1% deaths, last exit 18.1\u00a0years post inclusion) were available. NIM indices were calculated using the vagally-mediated HRV measure RMSSD divided by measures of CRP (NIM<jats:sub>CRP<\/jats:sub>) or IL-6 (NIM<jats:sub>IL6<\/jats:sub>). The NIM-ratios were quartiled and entered into age, ethnicity and body mass index adjusted Cox proportional hazards models. For NIM<jats:sub>IL6<\/jats:sub> the lowest quartile was 45% more likely to die during the observed period (max. 18\u00a0years follow-up) compared to the highest quartile (HR\u2009=\u20090.55 CI 0.41\u20130.73; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). NIM<jats:sub>CRP<\/jats:sub> parallel these results. Here we show that an easily computable index of IL-6 inhibition is associated with all-cause mortality in two large general population samples. These results suggest that this index might be useful for risk stratification and warrant further examination.<\/jats:p>","DOI":"10.1038\/s41598-021-82168-6","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T11:04:39Z","timestamp":1611831879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lower values of a novel index of Vagal-Neuroimmunomodulation are associated to higher all-cause mortality in two large general population samples with 18\u00a0year follow up"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-385X","authenticated-orcid":false,"given":"Marc N.","family":"Jarczok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1009-9625","authenticated-orcid":false,"given":"Julian","family":"Koenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9385-3421","authenticated-orcid":false,"given":"Julian F.","family":"Thayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"82168_CR1","first-page":"1","volume":"10","author":"M Madjid","year":"2020","unstructured":"Madjid, M., Safavi-Naeini, P., Solomon, S. 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