RT Journal Article
SR Electronic
T1 Interleukin 6 trans-signalling and the risk of future cardiovascular events in men and women
JF Open Heart
JO Open Heart
FD British Cardiovascular Society
SP e001694
DO 10.1136/openhrt-2021-001694
VO 8
IS 2
A1 Yasmin Miri
A1 Karin Leander
A1 Per Eriksson
A1 Bruna Gigante
A1 Louise Ziegler
YR 2021
UL http://openheart.bmj.com/content/8/2/e001694.abstract
AB Objective Pro-inflammatory interleukin 6 (IL6) trans-signalling is associated with increased risk of cardiovascular events (CVEs). Whether this association exists for both sexes is, however, uncertain. Hence, we analysed the risk of CVE associated with IL6 trans-signalling in men and women and investigated if potential interaction between IL6 trans-signalling and sex affects the risk.Methods In a prospective cohort of 60-year-old men and women without cardiovascular disease (men=2039, women=2193), subjects were followed for 20 years. To assess the IL6 trans-signalling activity, the proportion between the active binary and inactive ternary IL6 complexes, the binary/ternary ratio (B/T ratio), was estimated. CVE (myocardial infarction, angina pectoris and ischaemic stroke, n=629) risk was analysed with Cox regression, presented as HRs with 95% CIs. B/T ratio was dichotomised, with levels >median representing IL6 trans-signalling. Interaction was analysed on the additive scale and expressed as the synergy index (S). Analyses were adjusted for cardiovascular risk factors.Results B/T ratio >median was associated with increased CVE risk in men (HR 1.63; 95% CI 1.32 to 2.01), but not in women (HR 1.21; 95% CI 0.93 to 1.57). There was a significant synergistic interaction (S=1.98; 95% CI 1.15 to 3.42) between the B/T ratio and male sex, the combination increasing the risk by 88%.Conclusions Our results suggest differential susceptibility to inflammation mediated by IL6 trans-signalling and subsequent CVE in men and women. The B/T ratio could be considered as a novel biomarker for cardiovascular risk in men, but not in women.Data are available on reasonable request. Data are stored at Karolinska Institutet. Due to legal restrictions imposed by the Swedish Secrecy Act, requests for access individual data can be sent to BG (bruna.gigante@ki.se).