Complement component 7 is associated with total- and cardiac death in chest-pain patients with suspected acute coronary syndrome

Reidun Aarsetøy, Thor Ueland, Pål Aukrust, Annika E Michelsen, Ricardo Leon de la Fuente, Heidi Grundt, Harry Staines, Ottar Nygaard, Dennis W T Nilsen, Reidun Aarsetøy, Thor Ueland, Pål Aukrust, Annika E Michelsen, Ricardo Leon de la Fuente, Heidi Grundt, Harry Staines, Ottar Nygaard, Dennis W T Nilsen

Abstract

Background: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease.

Aim: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information.

Methods: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death.

Results: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population.

Conclusions: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976.

Keywords: Acute coronary syndrome; All-cause mortality; Cardiac death; Complement component 7; High-sensitivity C-reactive protein; Prognostic biomarkers.

Conflict of interest statement

The authors declare that they have no competing interests. There are no relationships with industry.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Survival curves by CC7 quartiles for 60-months follow-up in the Argentinean population. a all-cause mortality, b cardiac death and c SCD
Fig. 2
Fig. 2
Forest plot of the HR from univariate- and multivariable analysis for CC7 in the Argentinean and Norwegian population, respectively. In multivariable analysis, we adjusted for age, gender, a medical history of previous coronary heart disease (i.e. angina pectoris, myocardial infarction, coronary artery bypass grafting or percutaneous coronary intervention), a history of heart failure, diabetes mellitus, hypercholesterolemia (total cholesterol > 6.5 mmol/L), smoking status, use of angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers, statins and beta blockers, index diagnosis acute myocardial infarction and laboratory parameters (high-sensitivity C-reactive protein (hsCRP), Troponin T, estimated glomerular filtration rate (eGFR) and B-type natriuretic peptide (BNP). CC7, loge-transformed value of complement component 7; HR, Hazard Ratio; 95% CI, 95% confidence interval, Unadjusted; univariate analysis, Adjusted; multivariable analysis
Fig. 3
Fig. 3
Survival curves by CC7 quartiles for 60-months all-cause mortality in the Norwegian population
Fig. 4
Fig. 4
Forest plot of the multivariable analysis for CC7, hsCRP, BNP, TnT and eGFR in the a Argentinean population and the b Norwegian population. CC7; loge-transformed value of complement component 7 divided by its standard deviation, CRP; loge-transformed value of high-sensitivity C-reactive protein divided by its standard deviation, BNP; loge-transformed value of B-type natriuretic peptide divided by its standard deviation, TnT; Troponin T, eGFR, loge-transformed value of estimated glomerular filtration rate divided by its standard deviation

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