Chronic kidney disease and risk of atrial fibrillation and heart failure in general population-based cohorts – the BiomarCaRE project

Abstract Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This study was conducted as part of the BiomarCaRE project using harmonised data from 12 population-based cohorts (n=40,212) from Europe. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and with competing mortality risk after adjusting for covariates. Results Mean age at baseline was 51.1 (standard deviation 11.9) years, and 49.3% were men. Overall, 3.5% had CKD at baseline. The rate for incident AF was 3.9 per 1000 person-years during follow-up. The HR for AF for those with CKD compared with those without was 1.23 (95% CI 1.00–1.52, p=0.0465) after adjustment for covariates. The rate for incident HF was 3.9 per 1000 person-years and the associated risk in the presence of CKD was HR 1.67 (95% CI 1.39–2.01). In subjects with CKD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed an association with AF, while NT-proBNP and C-reactive protein (CRP) showed an association with HF. Conclusion CKD is an independent risk factor for subsequent AF and even more so for HF. In patients with CKD, NT-proBNP was clearly associated with subsequent risk of AF. In addition to this marker, hs-CRP was also associated with risk of subsequent HF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011_278913. Atrial Fibrillation and HF in CKD

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Chronic kidney disease and risk of atrial fibrillation and heart failure in general population‐based cohorts: the BiomarCaRE project

ESC Heart Failure ◽

10.1002/ehf2.13699 ◽

2021 ◽

Author(s):

Martin Rehm ◽

Dietrich Rothenbacher ◽

Licia Iacoviello ◽

Simona Costanzo ◽

Hugh Tunstall‐Pedoe ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

General Population ◽

Population Based

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Functional vitamin K status and risk of incident chronic kidney disease and microalbuminuria: a prospective general population-based cohort study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa304 ◽

2020 ◽

Author(s):

Dion Groothof ◽

Adrian Post ◽

Camilo G Sotomayor ◽

Charlotte A Keyzer ◽

Jose L Flores-Guerero ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

General Population ◽

Vitamin K ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Serum Cystatin C ◽

Incident Chronic Kidney Disease

Abstract Background Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD. Methods We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population–based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders. Results Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219–532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59–2.16; P < 0.001] and 1.19 (95% CI 1.07–1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88–1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94–1.14; P = 0.50)], respectively. Conclusions The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.

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Abstract MP012: Plasma Galectin-3 Levels and Subsequent Risk of Incident Chronic Kidney Disease

Circulation ◽

10.1161/circ.135.suppl_1.mp012 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Casey M Rebholz ◽

Elizabeth Selvin ◽

Menglu Liang ◽

Christie M Ballantyne ◽

Ron C Hoogeveen ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Disease Risk ◽

Positive Association ◽

Cox Proportional Hazards ◽

Diabetes Status ◽

Incident Chronic Kidney Disease ◽

Galectin 3

Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend <0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend <0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.

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Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽

10.1161/circ.133.suppl_1.p005 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Faye L Norby ◽

Lindsay G Bengtson ◽

Lin Y Chen ◽

Richard F MacLehose ◽

Pamela L Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Real World ◽

Proportional Hazards ◽

Large Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Cox Proportional Hazards Models ◽

The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

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Hyperlipidemia and Statins Use for the Risk of New Diagnosed Sarcopenia in Patients with Chronic Kidney: A Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17051494 ◽

2020 ◽

Vol 17 (5) ◽

pp. 1494 ◽

Cited By ~ 2

Author(s):

Min-Hua Lin ◽

She-Yu Chiu ◽

Pei-Hsuan Chang ◽

Yu-Liang Lai ◽

Pau-Chung Chen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Research Database ◽

Newly Diagnosed ◽

Hazards Model

Background: Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease.

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Physical activity types and atrial fibrillation risk in the middle-aged and elderly: The Rotterdam Study

European Journal of Preventive Cardiology ◽

10.1177/2047487318780031 ◽

2018 ◽

Vol 25 (12) ◽

pp. 1316-1323 ◽

Cited By ~ 7

Author(s):

Marijn Albrecht ◽

Chantal M Koolhaas ◽

Josje D Schoufour ◽

Frank JA van Rooij ◽

M Kavousi ◽

...

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Total Physical Activity ◽

Rotterdam Study ◽

Cox Proportional Hazards Models ◽

Activity Types ◽

Study Population

Background The association between physical activity and atrial fibrillation remains controversial. Physical activity has been associated with a higher and lower atrial fibrillation risk. These inconsistent results might be related to the type of physical activity. We aimed to investigate the association of total and types of physical activity, including walking, cycling, domestic work, gardening and sports, with atrial fibrillation. Design Prospective cohort study. Methods Our study was performed in the Rotterdam Study, a prospective population-based cohort. We included 7018 participants aged 55 years and older with information on physical activity between 1997–2001. Cox proportional hazards models were used to examine the association of physical activity with atrial fibrillation risk. Models were adjusted for biological and behavioural risk factors and the remaining physical activity types. Physical activity was categorised in tertiles and the low group was used as reference. Results During 16.8 years of follow-up (median: 12.3 years, interquartile range: 8.7–15.9 years), 800 atrial fibrillation events occurred (11.4% of the study population). We observed no association between total physical activity and atrial fibrillation risk in any model. After adjustment for confounders, the hazard ratio and 95% confidence interval for the high physical activity category compared to the low physical activity category was: 0.71 (0.80–1.14) for total physical activity. We did not observe a significant association between any of the physical activity types with atrial fibrillation risk. Conclusion Our results suggest that physical activity is not associated with higher or lower risk of atrial fibrillation in older adults. Neither total physical activity nor any of the included physical activity types was associated with atrial fibrillation risk.

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Association of Arterial Stiffness With Kidney Function Among Adults Without Chronic Kidney Disease

American Journal of Hypertension ◽

10.1093/ajh/hpaa097 ◽

2020 ◽

Vol 33 (11) ◽

pp. 1003-1010

Author(s):

Seiji Itano ◽

Yuichiro Yano ◽

Hajime Nagasu ◽

Hirofumi Tomiyama ◽

Hiroshi Kanegae ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Arterial Stiffness ◽

Kidney Function ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Kidney Dysfunction ◽

Cox Proportional Hazards Models ◽

Egfr Decline

Abstract BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. We compared 2 groups of CAVI measurements—the highest quartile (≧8.1) and the combined lower 3 quartiles (<8.1). We used Cox proportional hazards models to assess associations between these 2 groups and subsequent CKD events, proteinuria, eGFR <60 ml/min/1.73 m2, and rapid eGFR decline (greater than or equal to −3 ml/min/1.73 m2 per year). RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR <60 ml/min/1.73 m2, and the odds ratio with 95% CI was 1.3 (1.1, 1.4) for rapid eGFR decline. CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements <8.1. Greater arterial stiffness among adults without CKD may be associated with kidney dysfunction.

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Association between Sleep Duration and Incident Chronic Kidney Disease: A Population-Based Cohort Analysis of the NAGALA Study

Kidney & Blood Pressure Research ◽

10.1159/000504545 ◽

2020 ◽

Vol 45 (2) ◽

pp. 339-349

Author(s):

Hanako Nakajima ◽

Yoshitaka Hashimoto ◽

Takuro Okamura ◽

Akihiro Obora ◽

Takao Kojima ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Sleep Duration ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cohort Analysis ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Incident Chronic Kidney Disease

Background: The duration of sleep might be a risk factor for chronic kidney disease (CKD). We investigated the relationship between sleep duration and incident CKD. Methods: In this retrospective cohort study of 7,752 men and 6,722 women, we divided the subjects into 4 groups according to sleep duration, i.e., those whose reported regular sleep duration was <6 h (the “<6 h group”), those whose sleep duration was >6 but <7 h (the “6 to <7 h group”), those with a sleep duration of 7 to <8 h (the “7 to <8 h group”), and those with ≥8 h sleep (the “≥8 h group”). CKD was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The HR of the 4 groups for incident CKD were calculated with a Cox proportional hazards model, with the 7 to <8 h group set as the reference. Results: Incident CKD was detected in 1,513 (19.5%) men and 688 (10.2%) women over the median follow-up period of 7.0 (3.3–11.9) years in the men and 6.7 (3.1–10.8) years in the women. There was no association between sleep duration and incident CKD in the women. In the men, the HR of incident CKD was 0.54 (95% CI 0.45–0.64, p < 0.001) in the <6 h group, 0.73 (95% CI 0.66–0.82, p < 0.001) in the 6 to <7 h group, and 0.93 (95% CI 0.78–1.11, p = 0.433) in the ≥8 h group. Conclusion: The risk of incident CKD is lowest in those who sleep <6 h. We revealed that the risk of incident CKD is lowest in those who sleep <6 h among apparently healthy men.

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Sarcopenia is an independent predictor of hospitalization in chronic kidney disease outpatients

10.1101/516096 ◽

2019 ◽

Author(s):

Hye Yun Jeong ◽

Wooyeol Ahn ◽

Jun Chul Kim ◽

Yu Bum Choi ◽

Jinkwon Kim ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Muscle Strength ◽

Proportional Hazards ◽

Handgrip Strength ◽

Cox Proportional Hazards ◽

Chronic Illnesses ◽

Free Survival ◽

Cox Proportional Hazards Models ◽

Appendicular Skeletal Muscle

AbstractBackgroundPatients with chronic kidney disease (CKD) experience much more marked and earlier muscle wasting than subjects who do not have chronic illnesses. However, a few studies that have examined sarcopenia have been reported in CKD patients. We investigated the prevalence of sarcopenia in predialysis and dialysis outpatients with CKD and explored its relationship with the clinical outcomes.MeasurementsSarcopenia was defined as reduced muscle strength accompanied by decreased adjusted appendicular skeletal muscle (ASM), while those patients who exhibited only one of these characteristics were categorized as presarcopenic patients. ASM was measured by bioimpedence analysis, and muscle strength was evaluated by handgrips. ASM was adjusted by weight (ASM/wt). Patients were prospectively followed for up to 2 years.ResultsOne hundred seventy-nine patients were recruited (114 male and 65 female patients who were classified into 103 predialysis patients and 76 dialysis patients, with 44.7% having diabetes). Their mean age was 60.6 ± 13.5 years old. The prevalence of sarcopenia was 9.5%, while 55.9% of the patients were categorized as presarcopenic. The ASM/wt index showed significant correlations with age, handgrip strength, HOMA-IR and frailty scores. Multivariate Cox proportional hazards models demonstrated that the risk of hospitalization was significantly higher for patients with presarcopenia [hazard ratio (HR), 2.48; 95% confidence interval (CI), 1.180–5.230], and the risk of hospitalization was much higher for patients with sarcopenia than for patients in the nonsarcopenic group (HR, 9.11; 95% CI, 2.295–25.182)ConclusionsSarcopenia and presarcopenia, which were defined using the ASM/wt index and handgrip strength, predicted a poorer, hospitalization-free survival in CKD patients

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Taking Sleeping Pills and the Risk of Chronic Kidney Disease: A Nationwide Population-Based Retrospective Cohort Study

Frontiers in Pharmacology ◽

10.3389/fphar.2020.524113 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chen-Yi Liao ◽

Chi-Hsiang Chung ◽

Kuo-Cheng Lu ◽

Cheng-Yi Cheng ◽

Sung-Sen Yang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Sleeping Pills ◽

Potential Association ◽

Increased Risk ◽

Stage Renal Disease ◽

End Stage

Background: Sleeping disorder has been associated with chronic kidney disease (CKD); however, the correlation between sleeping pills use and CKD has not been investigated in-depth yet. This study elucidated the potential association of sleeping pill use with the risk of CKD and CKD progression to end-stage renal disease (ESRD) requiring dialysis.Methods: This study was based on a population-based cohort that included 209,755 sleeping pill users among 989,753 individuals. After applying the exclusion criteria, 186,654 sleeping pill users and 373,308 nonusers were enrolled to monitor the occurrence of CKD. Using a cumulative daily dose, we analyzed the types of sleeping pills related to the risk of CKD and ESRD. Propensity score matching and analysis using Cox proportional hazards regression were performed with adjustments for sex, age, and comorbidities.Results: Sleeping pill use was related to increased CKD risk after adjusting for underlying comorbidities (adjusted hazard ratio [aHR] = 1.806, 95% confidence interval [CI]: 1.617–2.105, p < 0.001). With the exception of hyperlipidemia, most comorbidities correlated with an increased risk of CKD. Persistent use of sleeping pills after CKD diagnosis increased the risk of concurrent ESRD (aHR = 7.542; 95% CI: 4.267–10.156; p < 0.001). After the subgroup analysis for sleeping pill use, brotizolam (p = 0.046), chlordiazepoxide (p < 0.001), clonazepam (p < 0.001), diazepam (p < 0.001), dormicum (p < 0.001), estazolam (p < 0.001), fludiazepam (p < 0.001), flunitrazepam (p < 0.001), nitrazepam (p < 0.001), trazodone (p < 0.001), zolpidem (p < 0.001), and zopiclone (p < 0.001) were found to have significant correlation with increased CKD risk.Conclusion: Sleeping pill use was related to an increased risk of CKD and ESRD. Further studies are necessary to corroborate these findings.

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