Risk of atrial fibrillation in persons with type 2 diabetes and the excess risk in relation to glycaemic control and renal function: a Swedish cohort study

Background There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF). Methods This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan–Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM. Results In total 1109 AF patients were included, of whom 373 (33.6%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR = 1.40 95% confidence intervals [CI] 1.11–1.75), CV mortality (aHR = 1.39, 95% CI 1.07–1.81), sudden cardiac death (aHR = 1.73, 95% CI 1.19–2.52), stroke (aHR = 1.87, 95% CI 1.01–3.45) and the composite outcome of hospitalization or CV death (aHR = 1.27, 95% CI 1.06–1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6–8.2% being independent predictors of increased all-cause mortality, and values < 6.2% predicting significantly decreased all-cause and CV mortality. Conclusions The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.

Section: Discussionsupporting

confidence: 92%

Prognostic significance of diabetes mellitus in patients with atrial fibrillation

Papazoglou

Κάρτας

Samaras

et al. 2021

“…The presence of DM has been implicated to explain the coexistence of CKD, HF, and AF [ 3 , 4 ]. Compared to the general population, individuals with DM and stage 5 CKD have a threefold increased risk to develop AF, [ 5 ] in which comorbid DM increases the risk of bleeding in patients with AF [ 57 ]. DM has also been found to increase the risk of suboptimal response to cardiac resynchronization therapy with defibrillator in patients with HF [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes mellitus (DM) and related comorbidities including heart failure (HF), obesity, hypertension, and chronic kidney disease (CKD) are closely linked to atrial fibrillation (AF) [ 1 – 5 ]. These conditions are associated with myocardial fibrosis and remodeling, neurohormonal activation, autonomic dysfunction, and electrical remodeling, predisposing to the development of AF and cardiac arrhythmias [ 2 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis

Lip

Feng

et al. 2021

115

Background Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD. Methods MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. Results Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70–0.96), embolic stroke (RR 0.32, 95% CI 0.12–0.85), AF/AFL (RR 0.82, 95% CI 0.71–0.95), and VT (RR 0.73, 95% CI 0.53–0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58–1.17) and cardiac arrest (RR 0.83, 95% CI 0.61–1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used. Conclusions SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.

“…In a meta-analysis which included 7 prospective studies and 4 case–control studies on 1.7 million subjects, diabetes was associated with about 40% higher risk of AF; however, after adjustment, the effect was more limited with an increased risk of only 24% [ 3 ]. The risk of type 2 diabetes on incident AF was 28% greater vs controls in a recent Swedish cohort study [ 21 ]. The results in our large adjusted analysis in almost 3 million subjects indicates that the adjusted excess risk was lower, around 15% (10% for men and 17% for women with type 2 diabetes).…”

Section: Discussionmentioning

confidence: 99%

Sex, age, type of diabetes and incidence of atrial fibrillation in patients with diabetes mellitus: a nationwide analysis

Bisson

Bodin

Fauchier

et al. 2021

Background There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. Methods All patients aged ≥ 18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). Results In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27–1.37) in women vs. 1.12(1.08–1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16–1.19) in women vs. 1.10(1.09–1.12) in men for type 2 diabetes. Conclusion Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.