This review summarizes evidence that higher IL-6 levels are associated with a higher risk of cardiovascular death, major adverse cardiovascular events, myocardial infarction, stroke, peripheral artery disease, and heart failure. It cites the 2006 cohort by Suuronen et al. and notes that IL-6 has been studied as a prognostic marker after myocardial infarction and acute coronary syndromes.

In HFpEF patients, higher IL-6 was associated with worse outcomes, including subsequent heart failure hospitalization in continuous analyses. However, the article also states that the association between IL-6 tertile and subsequent heart failure hospitalization was not apparent after adjustment, showing that tertile-based results can differ from continuous-model results.

Patients were followed for a median of 2.5 years for major adverse cardiovascular events and cardiovascular death or heart failure hospitalization. For every SD increase in IL-6, there was a 22% higher risk of cardiovascular death or heart failure (adjusted hazard ratio 1.22, 95% CI 1.11-1.34).

This is the cohort study most likely matching the claim: 382 adults younger than 60 years were assessed 3 months after a first myocardial infarction and followed for long-term outcomes. The study reported that higher interleukin-6 predicted later heart-failure hospitalization, with the highest tertile having a substantially higher risk than the lowest tertile.

Secondary reporting and later reviews describe the same post-myocardial-infarction cohort as showing that interleukin-6 predicted long-term adverse outcomes, including heart-failure hospitalization, in adults under 60 years old followed for many years after their first MI.

In a large heart failure cohort, IL-6 independently predicted the primary outcome of all-cause mortality and heart failure hospitalization during 2 years of follow-up.[5] The hazard ratio per doubling of IL-6 for the combined endpoint of all-cause mortality and HF hospitalization was 1.16 (95% confidence interval 1.11–1.21, P < 0.001), and for all-cause mortality alone was 1.22 (1.16–1.29, P < 0.001).[5] IL-6 also predicted cardiovascular and non-cardiovascular mortality, and higher IL-6 was associated with worse functional capacity.[5]

"Compared to tercile 1, participants with IL-6 tercile 3 had a higher adjusted risk of all-cause mortality (HR: 1.98 [95% CI: 1.67–2.36]), CV mortality (HR: 1.55 [95% CI: 1.05–2.30]), non-CV mortality (HR: 2.05 [95% CI: 1.65–2.56]), and heart failure (HR: 1.48 [95% CI: 0.99–2.19])." "Individuals in IL-6 tercile 3 had a similar risk of incident HF compared to individuals in tercile 1 (adjusted HR: 0.80 [95% CI: 0.45–1.45])." "High levels of circulating IL-6 were found to be associated with worse CVD outcomes and all-cause mortality in this ethnically diverse cohort."

The review discusses systemic inflammatory biomarkers and notes that when studies reported odds ratios, they were treated as approximations of hazard ratios because event rates were low and follow-up was short. This is relevant context for comparing reported effect sizes across IL-6 studies.

High levels of circulating IL-6 are associated with worse cardiovascular outcomes and increased all-cause mortality consistently across all racial and ethnic groups. Individuals in IL-6 tercile 3 had a higher risk of all-cause mortality compared to individuals in tercile 1 (adjusted HR: 1.98 [95% CI: 1.67–2.36]). For incident heart failure, individuals in IL-6 tercile 3 had a numerically higher but not statistically significant risk compared with tercile 1 (adjusted HR: 1.48 [95% CI: 0.99–2.19]).

In the DAPA-HF trial of patients with chronic heart failure with reduced ejection fraction, elevated IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels were each associated with the risk of worsening heart failure or cardiovascular death.[4] The primary outcome was a composite of heart failure hospitalization or urgent visit for heart failure requiring intravenous therapy, or cardiovascular death.[4] A doubling of IL-6 between baseline and 12 months was associated with a hazard ratio of 1.34 (95% CI 1.19–1.50) for the primary composite outcome, whereas a halving of IL-6 was associated with a hazard ratio of 0.75 (95% CI 0.67–0.84).[4]

In patients with first-time ST-elevation myocardial infarction (STEMI) treated with primary PCI, high levels of IL-6 at all sampling points during hospitalization were significantly associated with increased infarct size, reduced left ventricular ejection fraction (LVEF), and an increased risk of experiencing a composite endpoint during the first 12 months after STEMI.[1] Patients with sustained high levels of IL-6 4 months after STEMI, indicating residual inflammatory risk, had increased risk of death during a median 70 months of follow-up, with a hazard ratio of 13.4 (95% CI 4.4–40.5; p<0.001) for patients in the upper quartile of IL-6 compared with lower levels.[1] IL-6 measured acutely and at 4 months was thus associated with larger infarct size, reduced LVEF, and increased long-term all-cause mortality.[1]

In acute coronary syndrome patients, elevated IL-6 was an independent predictor of long-term cardiovascular mortality. The study found that higher IL-6 values were strongly associated with worse prognosis, supporting IL-6 as a prognostic inflammatory marker after myocardial infarction-related events.

In patients recently hospitalized with acute decompensated heart failure with preserved ejection fraction, IL-6 is predictive of all-cause mortality, cardiovascular death, and heart failure hospitalization after adjustment for clinical risk factors including BNP. Each 1-unit log increase in IL-6 was associated with a 24% increased risk of subsequent heart failure hospitalization (hazard ratio, 1.24 [95% CI, 1.01–1.51]). The adjusted risk of all-cause mortality and cardiovascular death was higher in IL-6 tertile 3 when compared with tertile 1 (adjusted HR for all-cause mortality, 2.47 [95% CI, 1.49–4.11]; cardiovascular death 2.46 [95% CI, 1.43–4.22]).

In hospitalized patients with coronary artery disease, serum IL-6 is significantly associated with all-cause and cardiovascular mortality. Patients in the highest serum IL-6 tertile versus the lowest tertile were at higher risk of all-cause and cardiovascular mortality, with hazard ratios of 17.12 (95% CI 3.11–71.76) and 8.68 (95% CI 1.88–37.51), respectively. During 1,663 person-years of follow-up, all-cause and cardiovascular mortality increased progressively across IL-6 tertiles.

"Conclusions—In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers." "Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adjusted hazard ratio [Q4:Q1] 1.57, 95% CI 1.22–2.03) and cardiovascular death or heart failure (adjusted hazard ratio 2.29, 95% CI 1.60–3.29)." "After further adjustment for biomarkers (hs-CRP, lipoprotein-associated phospholipase A2 activity, hs-troponin I, and BNP), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adjusted hazard ratio 1.43, 95% CI 1.09–1.88) and cardiovascular death or heart failure (adjusted hazard ratio 1.79, 95% CI 1.22–2.63)."

Among women with prevalent cardiovascular disease, those with high IL-6 levels had greater than 4-fold risk of death (relative risk 4.6; 95% CI 2.0 to 10.5) compared with women in the lowest tertile. In the unadjusted analysis, women in the highest tertile of IL-6 had an almost 4-fold risk of mortality (RR 3.8; 95% CI 2.2 to 6.6) compared with women in the lowest tertile. In a fully adjusted model, women in the middle and highest tertiles had a relative risk of death of 1.8 (95% CI 0.6 to 4.9) and 2.8 (95% CI 1.01 to 7.03), respectively, compared with those in the lowest tertile.

Patients after acute coronary syndrome (ACS) were followed for a median of 2.5 years for major adverse cardiovascular events and for cardiovascular death or heart failure hospitalization.[9] For each standard deviation increase in IL-6, the adjusted hazard ratio for cardiovascular death or heart failure hospitalization was 1.22 (95% CI 1.11–1.34).[9] When IL-6 was categorized in quartiles, patients in the highest IL-6 quartile had a higher risk of cardiovascular death or heart failure (adjusted hazard ratio 2.29, 95% CI 1.60–3.29) compared with those in the lowest quartile, and this association persisted after further adjustment for multiple biomarkers.[9]

"Increased serum IL-6 is predictive of long-term cardiovascular events and mortality in patients undergoing coronary angiography." "Patients were followed for a median of 10.7 years." "Pre-procedure IL-6 above 1.5 pg/mL was associated with an increased risk of long-term composite cardiovascular events (HR 2.94, 95% CI 1.56–5.54) and all-cause mortality (HR 3.68, 95% CI 1.77–7.67)."

Patients with HFpEF and highest IL-6 levels were numerically more likely to have been hospitalized for heart failure in the preceding 12 months (35% vs 20% in the bottom tertile). Higher IL-6 levels were associated with increased risk of subsequent heart failure hospitalization and composite adverse outcomes during follow-up. IL-6 emerged as a marker of poor prognosis in HFpEF, independent of traditional risk factors.

A recent review notes that interleukin-6 (IL-6) is associated with the pathogenesis of heart failure and with an increased risk of heart failure in people without previous myocardial infarction.[7] In hospitalized patients with acute decompensated heart failure (ADHF), IL-6 remained independently associated with ADHF after adjustment (odds ratio 1.461, 95% CI 1.053–2.028, p = 0.023), and higher plasma IL-6 levels predicted higher mortality and worse outcomes.[7] Within a stable chronic heart failure group, IL-6 showed significant correlations with NT-proBNP, NYHA class, and LVEF, indicating that IL-6 correlates with heart failure severity across the disease spectrum.[7]

"IL-6 is a powerful independent predictor of future cardiovascular events in high-risk Japanese patients, suggesting its predictive value is superior to that of hs-CRP." "In multivariate Cox proportional hazards analysis, IL-6 levels were significantly associated with future cardiovascular events after adjustment for traditional risk factors and hs-CRP."

In a cohort of patients with acute heart failure, interleukin-6 (IL-6) was shown to play a role in predicting death and rehospitalization.[10] The study found that higher IL-6 levels on admission were associated with increased risk of all-cause mortality and heart failure re-hospitalization during follow-up, and IL-6 provided prognostic information beyond conventional risk markers.[10] The authors concluded that IL-6 has a differential prognostic impact in acute heart failure and could help stratify patients according to risk of adverse outcomes.[10]

"The landmark meta-analysis of 29 prospective studies published by Kaptoge et al. in 2014 showed a 25% increased risk of nonfatal myocardial infarction or coronary heart disease death per 1-SD higher level of IL-6." "Ridker et al. (2000) showed a 38% increase in risk of myocardial infarction per quartile increase in IL-6."

The main goal of this study is to evaluate the ability of a single administration of tocilizumab (an anti–IL-6 receptor monoclonal antibody) to reduce myocardial damage in patients presenting with an acute ST-elevation myocardial infarction. The primary endpoint will be the between-group difference in the myocardial salvage index as measured in the acute phase by cardiac magnetic resonance imaging with late gadolinium enhancement. This trial assesses whether IL-6 pathway inhibition around the time of myocardial infarction can modify cardiac injury and potentially downstream outcomes such as heart failure.

In patients presenting with acute myocardial infarction, high admission levels of interleukin-1 receptor antagonist (IL-1Ra) were associated with increased rates of all-cause mortality and heart failure hospitalization during follow-up.[8] The study reported that individuals in the highest IL-1Ra category had significantly higher risk of death and HF hospitalization compared with those with lower levels, suggesting that elevated inflammatory markers at admission are linked to adverse outcomes after myocardial infarction.[8] Although the focus was on IL-1Ra rather than IL-6, the findings support the broader concept that heightened inflammatory activation during acute MI is related to subsequent heart failure events.[8]

When researchers measure IL-6 in people, they find that increased levels independently predict who will get heart failure and who will suffer most from it. IL-6 is both a cause and an effect of heart failure. High IL-6 throughout the body can increase diseases that make heart failure worse, including frailty, kidney disease, atrial fibrillation, and iron imbalance; monoclonal antibody medications targeting IL-6 are in development to reduce chronically high levels.

This retrospective cohort study analyzed the association between the systemic inflammatory response index and 1-year all-cause mortality in intensive care unit patients with heart failure. The systemic inflammatory response index is based on neutrophil, lymphocyte, and platelet counts, reflecting systemic inflammation. Elevated systemic inflammatory response index was associated with higher 1-year mortality, supporting the role of inflammation in prognosis among heart failure patients.