Table 1.
Clinical studies that revealed the association between inflammatory and proteostasis biomarkers and the development of atrial fibrillation
| Biomarkers | Study Design | Conclusion |
|---|---|---|
| CRP | cross-sectional & longitudinal | CRP is not only associated with the presence of AF but also associated with the increased risk for future development of AF.151 |
| prospective | CRP levels were higher in pAF group. CRP levels were significantly associated with successful cardioversion to sinus rhythm.152 | |
| prospective | High-sensitive (hs)-CRP predicts the risk of occurrence of new-onset AF in patients with CAD.153 | |
| prospective | A rise in the CRP level is associated with the incidence of AF.154 | |
| case-control | Serum level of hsCRP was significantly higher in AF patients compared to control patients, and the increase is more prominent in perAF patients than pAF patients.155 | |
| retrospective | CRP levels were increased in AF patients, and CRP levels were higher in perAF than pAF.156 | |
| IL-6 | case control | Serum level of IL-6 was significantly higher in AF patients than in non-AF controls, and the increase is more prominent in perAF than in pAF patients.157 |
| prospective | −174G/C polymorphism of the IL-6 promoter modulates the inflammatory response and the GG genotype is an independent predictor of postoperative atrial AF.158 | |
| prospective | Circulating IL-6 level positively correlates with the prolongation and dispersion of P-waves, and negatively correlates with the circulation connexin protein. Incubation of the atrial myocyte-like cell line (HL-1 cells) with IL-6 reduced the expression of connexins, which is also reversible by removing IL-6.159 | |
| prospective | Dataset from the Chronic Renal Insufficiency Cohort (CRIC) study revealed that plasma IL-6 level was not only associated with the presence of AF at baseline, but also new onset of AF in patients with chronic kidney disease.160 | |
| prospective | The decreased serum level of IL-6 is associated with the free of recurrent AF within 6-months follow-up post ablation.161 | |
| IL-1β | case-control | Microvesicle-bound IL-1β was significantly increased in perAF patients compared to controls.162 |
| IL-2 | prospective | Higher serum level of IL-2 is an independent predictor of AF recurrence in pAF patients post ablation.163 |
| IL-10 | case-control | The plasma level of IL-17A was significantly increased in AF patients. IL-17A level was positively correlated with left atrial diameter.164 |
| case-control | IL-10 promoter polymorphism (−592A/C) have an impact on POAF development in north Indian patients. AA genotype increases AF risk in post-surgery.165 | |
| IL-18 | case-control | The serum level of IL-18 was significantly higher in AF patients than in controls. Among AF subgroups, IL-18 was significantly higher in perAF patients than in pAF patients. IL-18 also correlates with the left atrial diameter, a risk factor of AF.27 |
| IL-17A | case-control | Plasma level of IL-17A was significantly increased in patients with AF compared to controls. There was no significant difference in the level of IL-17A between different types of AF. 164, 166 |
| IL-37 | case-control | The serum level of the anti-inflammatory cytokine IL-37 and the expression of IL-37 mRNA in the peripheral blood mononuclear cells were increased in AF patients compared to non-AF controls.167 |
| TNFα | case-control | The serum level of TNFα was significantly higher in AF patients (including both pAF and perAF patients) compared to control patients.155 |
| case-control | The serum level of TNFα positively correlates with the severity of AF.29 | |
| MPO | case-control | Serum level of MPO was increased in AF patients regardless of the stage.168 |
| prospective | Increased serum level of MPO correlates with the risk of AF recurrence post ablation.169 | |
| HSPB1 (HSP27) | case-control | Serum HSPB1 levels predicted AF recurrence after catheter ablation. HSP27 also correlated with left atrial diameter, left atrial voltage and fractionated intervals.170 |
| case-control | Elevated HSPB1 levels in atrial tissue from patients with pAF compared to perAF or sinus rhythm controls.66, 171, Also, an inverse correlation was observed between HSPB1 levels and the duration of AF and the extent of structural damage (myolysis) was observed.66 | |
| HSPA1A (HSP70) | case-control | Higher HSPA1A levels in atrial tissue of patients in sinus rhythm undergoing cardiac bypass surgery are correlated with a lower incidence of POAF.172, 173 |
| prospective | Mutation in HSPA1A-Hom gene (Met439Thr substitution) is associated with higher levels of serum HSPA1A and incidence of POAF after cardiac bypass surgery.174 | |
| HSPD1/E1 (HSP60/10) | prospective | HSPD1 levels were lower in both atrial tissue and plasma of AF patients undergoing mitral valve replacement and spontaneously restored to sinus rhythm. HSPD1 and was positively correlated with apoptosis, interstitial fibrosis, and inflammation.175 |
| prospective | Pre- and post- operative circulating anti-HSPD1 antibodies are associated with POAF in patients undergoing cardiac bypass surgery.176 | |
| case-control | Higher levels of mitochondrial HSPD1 and HSPE1 in are found in right atrial tissue of patients with peAF compared to controls.177 | |
| cohort study | However, the Multi-Ethnic Study of Atherosclerosis (MESA) reveals no association between HSPD1 levels in blood and occurrence of AF was found.178 | |
AF, atrial fibrillation; CAD, coronary artery disease; CRP, C-reactive protein; IL-1β, interleukin-1β; IL-18, interleukin-18; pAF, paroxysmal atrial fibrillation; perAF, persistent atrial fibrillation; POAF, post-operative atrial fibrillation.