Chronic Kidney Disease Is Associated With the Incidence of Atrial Fibrillation

Background - Several traditional cardiovascular risk factors, including hypertension, diabetes, and obesity have been associated with the risk of atrial fibrillation (AF). Literature on non-traditional risk predictors for AF is scarce, but high phosphorus, which has been linked with calcification and higher cardiovascular morbidity and mortality both in those with and without kidney dysfunction, may be one such marker. We assessed whether serum phosphorus levels were associated with AF incidence in a large community-based cohort in the US. Methods - Our analysis included 14,693 participants (25% African-American, 45% men) free of AF at baseline (1987-89), and with measurements of fasting serum phosphorus from the Atherosclerosis Risk in Communities (ARIC) study. Incidence of AF was ascertained through the end of 2008 from study visit ECGs, hospitalizations and death certificates. Cox proportional hazard models were used to estimate the hazards ratios (HR) of AF by serum phosphorous levels, adjusting for potential confounders. Results - During a median follow-up of 19.7 years, we identified 1659 incident AF cases. Higher serum phosphorus was associated with higher AF risk: multivariable HR: 1.20, 95% confidence interval (CI) 1.02-1.42 comparing extreme quintiles, p for trend=0.009 ( table ). The HR (95% CI) of AF with a 1 mg/dL increase in serum phosphorus was 1.15 (1.04-1.28). No significant interaction was seen by race (p=0.92) or gender (p=0.62). A possible interaction was seen between eGFR and phosphorus quintiles (p=0.05), with an increased risk of AF associated with higher serum phosphorus in those with eGFR =>90 mL/min/1.72m² but not among those with eGFR<90 ( table ). Conclusion - In this large population-based study, higher levels of serum phosphorus were associated with a higher incidence of AF. The association was seen only in those with normal kidney function. Table. Multivariable hazard ratio (95% confidence interval) of atrial fibrillation by quintiles of serum phosphorus levels, ARIC, 1987-2008 Serum Phosphorus Quintiles (mg/dL) P for trend ≤3.0 3.1-3.3 3.4-3.5 3.6-3.8 ≥3.9 Total population N (14,693) 3201 3287 2483 3048 2674 AF cases 380 373 260 360 286 Hazard Ratio (95% CI) * 1 (Ref.) 1.09 (0.94-1.26) 1.06 (0.90-1.25) 1.22 (1.05-1.42) 1.20 (1.02-1.42) 0.009 eGFR = > 90 mL/min/1.72m² N (10,149) 2143 2279 1723 2160 1844 AF cases 226 223 155 229 189 Hazard Ratio (95% CI) * 1 (Ref.) 1.06 (0.88-1.28) 1.01 (0.82-1.25) 1.26 (1.04-1.52) 1.37 (1.11-1.69) 0.001 eGFR <90 mL/min/1.72m² N (4544) 1058 1008 760 888 830 AF cases 154 150 105 131 97 Hazard Ratio (95% CI) * 1 (Ref.) 1.11 (0.88-1.39) 1.14 (0.88-1.39) 1.17 (0.91-1.49) 1.01 (0.77-1.32) 0.69 * Cox proportional hazard models adjusted for baseline age, gender, race, education, ARIC center, height, income, smoking status, drinking status, BMI, systolic blood pressure, diastolic blood pressure, antihypertensive medications, diabetes, serum calcium, estimated glomerular filtration rate (eGFR), prevalent stroke, prevalent heart failure and prevalent coronary heart disease Funding(This research has received full or partial funding support from the American Heart Association, National Center)

Objectives: Embolic stroke is a major complication of atrial fibrillation (AF). Mechanisms that lead to elevated stroke risk in AF are also likely to increase risk of extracranial systemic embolic events (SEE). However, little is known about the magnitude of the association of AF with SEE, needed to fully characterize the impact of AF on cardiovascular outcomes. We evaluated the association of AF with SEE and the prediction of SEE among persons with AF in a community-based cohort. Methods: We included 14,941 participants of the ARIC study (mean age, 54 ± 6, 55% women, 74% white) without AF at baseline (1987-89) and followed through 2017. AF was identified from study electrocardiograms, hospital discharges, and death certificates. SEE was defined as the presence of hospitalization discharge codes ICD-9-CM 444.xx or ICD-10-CM I74.x (Arterial embolism and thrombosis) in any position. CHA2DS2-VASc score, a predictor of stroke risk in AF, was calculated at the time of AF diagnosis. Cox models adjusting for fixed and time-varying covariates were used to estimate associations of incident AF with SEE risk and between CHA2DS2-VASc score and SEE risk in those with incident AF. Results: Among eligible participants, 3,114 developed AF and 270 had a SEE event. Incident AF was associated with increased risk of SEE [hazard ratio (HR) = 3.6, 95% confidence interval (CI) 2.6 - 5.0], after adjusting for baseline and time-dependent covariates (Table). The association of incident AF with SEE was stronger in women (HR 5.3, 95% CI 3.3 - 8.4) than in men (HR 2.7, 95% CI 1.7 - 4.3) (p for interaction = 0.002). In participants with incident AF, we identified 59 SEE events. Higher CHA 2 DS 2 -VASc score was associated with increased SEE risk (HR per 1-point increase = 1.2, 95% CI 1.1 - 1.5). Conclusions: AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA 2 DS 2 -VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict outcomes and guide treatments in persons with AF.

BackgroundIncreased concentrations of circulating fibroblast growth factor 23 (FGF‐23) have been associated with higher risk of cardiovascular disease. The association between FGF‐23 and the risk of atrial fibrillation (AF), a common arrhythmia, is less defined. Thus, we explored whether FGF‐23 concentration was associated with AF incidence in a large community‐based cohort.Methods and ResultsWe studied 12 349 men and women enrolled in the Atherosclerosis Risk in Communities (ARIC) study, without prevalent AF at baseline in 1990–1992. Serum intact FGF‐23 concentration was measured with the Kainos 2‐site ELISA. Incident AF through 2010 was ascertained from study ECGs and hospital discharge codes. Cox proportional hazards models adjusted for potential confounding factors, including kidney function, were used to estimate the association between FGF‐23 and AF risk. We identified 1572 AF events during a mean follow‐up of 17 years. In multivariable analysis, a difference of 1 SD (16 pg/mL) in baseline FGF‐23 was not associated with the risk of AF (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.99, 1.09). Results were similar when FGF‐23 was modeled in quartiles (HR, 1.09; 95% CI, 0.94, 1.26, comparing extreme quartiles). Reduced kidney function was associated with increased AF risk across quartiles of FGF‐23 levels.ConclusionIn this large community‐based cohort, baseline FGF‐23 levels were not associated with AF risk independently of kidney function. Our results do not support a major role for FGF‐23 as a risk factor for AF or as a mediator of the association between chronic kidney disease and AF.

POSTER PRESENTATIONS

BackgroundEarly evidence suggests proteinuria is independently associated with incident atrial fibrillation (AF). We sought to investigate whether the association of proteinuria with incident AF is altered by kidney function.Methods and ResultsRetrospective cohort study using administrative healthcare databases in Ontario, Canada (2002–2015). A total of 736 666 patients aged ≥40 years not receiving dialysis and with no previous history of AF were included. Proteinuria was defined using the urine albumin‐to‐creatinine ratio (ACR) and kidney function by the estimated glomerular filtration rate (eGFR). The primary outcome was time to AF. Cox proportional models were used to determine the hazard ratio for AF censored for death, dialysis, kidney transplant, or end of follow‐up. Fine and Grey models were used to determine the subdistribution hazard ratio for AF, with death as a competing event. Median follow‐up was 6 years and 44 809 patients developed AF. In adjusted models, ACR and eGFR were associated with AF (P<0.0001). The association of proteinuria with AF differed based on kidney function (ACR × eGFR interaction, P<0.0001). Overt proteinuria (ACR, 120 mg/mmol) was associated with greater AF risk in patients with intact (eGFR, 120) versus reduced (eGFR, 30) kidney function (adjusted hazard ratios, 4.5 [95% CI, 4.0–5.1] and 2.6 [95% CI, 2.4–2.8], respectively; referent ACR 0 and eGFR 120). Results were similar in competing risk analyses.ConclusionsProteinuria increases the risk of incident AF markedly in patients with intact kidney function compared with those with decreased kidney function. Screening and preventative strategies should consider proteinuria as an independent risk factor for AF.

A MET a Day Keeps Arrhythmia at Bay: The Association Between Exercise or Cardiorespiratory Fitness and Atrial Fibrillation

Serum 25-hydroxyvitamin D and the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study

Background— Recent studies show that lower levels of low density lipoprotein cholesterol (LDLc) and total cholesterol are associated with incident atrial fibrillation (AF), whereas AF is not associated with high density lipoprotein cholesterol (HDLc) and triglycerides. To test a potential causal association between lipid levels and AF risk, we assessed whether previously developed lipid gene scores are associated with the incidence of AF in a large community-based cohort. Methods— Our analysis included 8849 white participants free of AF at baseline (1987-1989) and with lipid gene scores from the ARIC study. We used previously developed phenotype-specific lipid gene scores, based on loci significantly associated with lipid levels. Incidence of AF was ascertained through 2009 from study visit ECGs, and ICD codes from hospitalizations and death certificates. Cox proportional hazards models were used to estimate the hazard ratio (HR) of AF by each respective lipid gene score quintile and per 1 standard deviation (SD) increase of each effect-size weighted lipid gene score. Results— During a median follow-up of 20.7 years, we identified 1207 incident AF cases. The HDLc gene score, the total cholesterol score, and the triglyceride score were not associated with incidence of AF. The continuous LDLc score was not associated with AF overall, but had a significant interaction with gender (p=0.03). A higher LDLc score was associated with a lower incidence of AF in females but not in males (table): multivariable HR and 95% confidence interval (CI) per 1-SD increase: 0.90 (0.83-0.98) vs. 1.03 (0.95-1.11). When the LDLc gene score was split into quintiles, a higher LDLc score for females was associated with a lower AF risk: HR (95% CI) = 0.74 (0.56-0.98) when comparing extreme quintiles (table). Conclusion— In this large population-based study, a higher LDLc score in females was associated with a lower incidence of AF. No association with AF was observed in the LDLc score in males or with the gene scores for HDLc, total cholesterol or triglycerides.

There is limited knowledge on the relationship between kidney function and incidence of atrial fibrillation. Thus, this prospective study was designed to evaluate whether various biomarkers of kidney function are associated to the risk of atrial fibrillation. The study population consisted of 1840 subjects (615 women and 1225 men) aged 61-82 years. Cystatin C- and creatinine-based estimation of glomerular filtration rate (eGFRcys and eGRFcreat , respectively) and urinary albumin/creatinine ratio (ACR) were assessed to investigate their relationship with the risk of atrial fibrillation. During a median follow-up of 3.7 years, a total of 159 incident atrial fibrillation cases occurred. After adjustment for potential confounders, the risk of atrial fibrillation was increased (hazard ratio 2.74, 95% confidence interval (CI) 1.56-4.81, P < 0.001) in subjects with reduced kidney function (eGFRcys , 15-59 mL/min per 1.73 m(2) ) compared to subjects with normal kidney function (≥90 mL/min per 1.73 m(2) ). Similar results were also found when comparing the respective groups of subjects defined by their eGRFcreat levels (hazard ratio 2.41, CI 1.09-5.30, P = 0.029). Consistently, subjects with ACR ≥300 mg/g had an increased risk of incident atrial fibrillation (hazard ratio 2.16, CI 1.35-2.82, P < 0.001) compared to those with ACR <30 mg/g. Reduced eGFR and albuminuria were associated with an increased risk of atrial fibrillation.

Effect of Dietary Fish Oil on Atrial Fibrillation After Cardiac Surgery

Background: Both chronic kidney disease (CKD) measures, estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR), are associated with incident heart failure (HF). Anemia is thought to play an important role in this association, particularly when eGFR is reduced, but this concept has not been rigorously evaluated. Methods: Using data from 5,539 participants in the Atherosclerosis Risk in Communities (ARIC) study at the fourth visit (1996-98), we first assessed the prevalence ratio (PrR) of anemia for eGFR and ACR using cross-sectional Poisson models, and then prospectively quantified the associations of eGFR, ACR, and anemia with incident HF using Cox proportional hazard models. Results: Based on the WHO definition, 477 (8.6%) participants had anemia at baseline. Both CKD measures were associated with increased prevalence of anemia independently of each other and other potential confounders (PrR, 1.22 [95% confidence interval, 1.11-1.34] with every 1SD decrease in eGFR; and 1.12 [1.03-1.23] with every 1SD increase in log 10 ACR). There were 724 (13.1%) cases of incident HF over median follow-up of 14.8 years. Lower eGFR and higher ACR were independently associated with increased risk of HF regardless of anemia status (Figure A for eGFR, and B for ACR). The association between anemia and HF risk was generally consistent in the range of eGFR below 90 ml/min/1.73m 2 and ACR between 5 and 300 mg/g, without significant interaction between both CKD measures and anemic status (e.g., hazard ratio for anemia vs. no anemia: 1.40 [0.81-2.41] at eGFR 60 ml/min/1.73m 2 and 1.37 [0.67-2.80] at ACR 30 mg/g). Conclusions: Reduced eGFR and elevated ACR were independently associated with higher prevalence of anemia and HF risk. The contribution of anemia to HF risk was overall consistent across CKD ranges of eGFR and ACR. Our results suggest the need of clinical attention on anemia and related HF risk in persons with low eGFR as well as those with high ACR.

Background— Evidence on the relationship of a wide range of alcohol consumption with risk of incident atrial fibrillation has been limited. Methods— Between 1991 and 1995, 8602 Japanese men and women aged 30 to 80 years and free of clinical atrial fibrillation took part in the first examination of the Circulatory Risk in Communities Study(CIRCS)- a population based cohort study of cardiovascular risk factors, cardiovascular disease incidence, and their trends in Japanese communities. In the first examination, we checked a detailed medical history, physical examination, blood and urine examination, and electrocardiogram (ECG). An interviewer obtained histories in detail for weekly alcohol intake. In the follow-up period, incident atrial fibrillations were ascertained by annual ECG record and medical history of treatment of atrial fibrillation. ECGs were coded with the Minnesota Code by trained physician-epidemiologists. Differences in baseline characteristics between atrial fibrillation cases and controls were compared using Student t-tests or chi-squared tests. The hazard ratios (HRs) of incidence of atrial fibrillation and 95% confidence interval (CI) relative to the never-drinking group were calculated with adjustment for age and other potential confounding factors using the Cox proportional hazard model. Results— During an average follow-up of 6.4 years, 290 incident atrial fibrillation occurred. The higher incidence rate of atrial fibrillation was observed among participants with more than 69 g of ethanol drinking per week, compared with less than 69 g of ethanol drinking per week. On the other hand, light to moderate alcohol consumption was not associated with risk of atrial fibrillation. Compared with the never drinking group, the multivariable-adjusted HRs of past, light (&lt;23 g), light moderate (23-46 g), moderate (46-69 g), and heavy (&gt;69 g) drinking groups were 1.20 (95% CI, 0.61-2.35), 0.85 (95% CI, 0.57-1.27), 1.05 (95% CI, 0.63-1.75), 1.34 (95% CI, 0.78-2.32), and 2.92 (95% CI, 1.61-5.28), respectively. Conclusions— Heavy alcohol consumption was associated with the higher risk of atrial fibrillation, whereas there was no association of less than moderate alcohol consumption and atrial fibrillation.

Different risk of atrial fibrillation according to the type of cancer: a nationwide population-based study

BackgroundAlthough inflammation is involved in the development of atrial fibrillation (AF), the association of white blood cell (WBC) count and differential with AF has not been thoroughly examined in large cohorts with extended follow-up.MethodsWe studied 14,500 men and women (25% blacks, 55% women, mean age 54) free of AF at baseline (1987–89) from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort in the United States. Incident AF cases through 2010 were identified from study electrocardiograms, hospital discharge records and death certificates. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for AF associated with WBC count and differential.ResultsOver a median follow-up time of 21.5 years for the entire cohort, 1928 participants had incident AF. Higher total WBC count was associated with higher AF risk independent of AF risk factors and potential confounders (HR 1.09, 95% CI 1.04–1.15 per 1-standard deviation [SD] increase). Higher neutrophil and monocyte counts were positively associated with AF risk, while an inverse association was identified between lymphocyte count and AF (multivariable adjusted HRs 1.16, 95% CI 1.09–1.23; 1.05, 95% CI 1.00–1.11; 0.91, 95% CI 0.86–0.97 per 1-SD, respectively). No significant association was identified between eosinophils or basophils and AF.ConclusionsHigh total WBC, neutrophil, and monocyte counts were each associated with higher AF risk while lymphocyte count was inversely associated with AF risk. Systemic inflammation may underlie this association and requires further investigation for strategies to prevent AF.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.