Abstract
BACKGROUND: Standard modifiable risk factors (SMuRFs) are important causative factors leading to coronary atherosclerosis. However, a significant number of individuals develop coronary atherosclerosis despite the absence of SMuRFs. Inflammation is another major cause of atherosclerosis, and this study aims to investigate the association of the novel inflammatory markers systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) with mortality in patients with coronary heart disease (CHD) with and without SMuRFs. METHODS: In this study, we included 1708 CHD participants from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Patients were categorized into ≥ 1SMuRF and SMuRF-less groups by questionnaire and serologic testing. SII and SIRI were categorized into four groups according to quartiles. Multivariate weighted Cox regression was used to explore the risk factors associated with mortality in patients with or without SMuRFs. Restricted cubic spline (RCS) curve was used to assess their nonlinear correlation. RESULTS: In patients with ≥1 SMuRF, all-cause mortality (SII:hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.18-1.84, p < 0.001; SIRI:HR 1.66, 95%CI 1.31-2.10, p < 0.001) and cardiovascular mortality (SII:HR 1.52, 95%CI 1.07-2.17, p = 0.020; SIRI:HR 1.63, 95%CI 1.11-2.38, p = 0.011) were significantly higher in the SII Q4 and SIRI Q4 group compared to the SII Q1 and SIRI Q1 group, respectively. In patients with SMuRF-less, the incidence of all-cause mortality was also significantly higher in the group with higher levels of SII, SIRI (SII:HR 3.32, 95%CI 1.45-7.59, p = 0.004; SIRI:HR 4.25, 95%CI 1.67-10.80, p = 0.002), but no significant difference was observed in cardiovascular mortality for SII (SII:HR 2.21, 95%CI 0.54-8.97, p = 0.272), while a significant association was found for SIRI (SIRI:HR 11.69, 95%CI 1.43-95.21, p = 0.028). The RCS analysis showed a linear trend between high levels of SII, SIRI, and elevated all-cause mortality, and cardiovascular mortality in patients with ≥1 SMurRF. In contrast, a positive linear trend between SII, SIRI, and all-cause mortality, but no significant association with cardiovascular mortality was observed in the group with SMuRF-less. CONCLUSIONS: The findings showed that SII and SIRI were positively associated with all-cause mortality in a population with CHD irrespective of the presence or absence of SMuRFs. The present study suggests that inflammation may be an important factor in the poor prognosis of patients with no specific cardiovascular risk factors, which needs to be further argued by more prospective studies.