Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study

doi:10.1016/j.ahj.2016.07.004

American Heart Journal

Volume 180, October 2016, Pages 46-53

https://doi.org/10.1016/j.ahj.2016.07.004 Get rights and content

Background

Individuals with chronic kidney disease, particularly those requiring dialysis, are at high risk of sudden cardiac death (SCD). However, comprehensive data for the full spectrum of kidney function and SCD risk in the community are sparse. Furthermore, newly developed equations for estimated glomerular filtration rate (eGFR) and novel filtration markers might add further insight to the role of kidney function in SCD.

Methods

We investigated the associations of baseline eGFRs using serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, and eGFRcr-cys); cystatin C itself; and β₂-microglobulin (B2M) with SCD (205 cases through 2001) among 13,070 black and white ARIC participants at baseline during 1990-1992 using Cox regression models accounting for potential confounders.

Results

Low eGFR was independently associated with SCD risk: for example, hazard ratio for eGFR <45 versus ≥90 mL/(min 1.73m²) was 3.71 (95% CI 1.74-7.90) with eGFRcr, 5.40 (2.97-9.83) with eGFRcr-cys, and 5.24 (3.01-9.11) with eGFRcys. When eGFRcr and eGFRcys were included together in a single model, the association was only significant for eGFRcys. When three eGFRs, cystatin C, and B2M were divided into quartiles, B2M demonstrated the strongest association with SCD (hazard ratio for fourth quartile vs first quartile 3.48 (2.03-5.96) vs ≤2.7 for the other kidney markers).

Conclusions

Kidney function was independently and robustly associated with SCD in the community, particularly when cystatin C or B2M was used. These results suggest the potential value of kidney function as a risk factor for SCD and the advantage of novel filtration markers over eGFRcr in this context.

Section snippets

Study participants

The ARIC Study consists of 15,792 individuals aged 45 to 64 years at baseline (1987-1989) from 4 US communities in North Carolina, Mississippi, Minnesota, and Maryland. Details of the ARIC Study have been described elsewhere.²⁰ The current study used visit 2 (1990-92) as baseline, at which 14,348 participants attended and B2M and cystatin C were measured along with serum creatinine. Participants were excluded from the study if they did not have records of B2M (n = 975), cystatin C (n = 88), or

Results

Among 13,070 blacks and whites at the second visit (1990-1992) of the ARIC Study, 205 participants developed SCD during a median of 11.2 years of follow-up (incidence rate: 1.4 per 1000 person-years). Basic characteristics of the cohort are shown in Table I based on incidence of SCD during the follow-up. Those who developed SCD were more likely to be older, male, African American, and smokers and to have diabetes, hypertension, dyslipidemia, history of CHD and HF, and higher Cornell voltage

Discussion

In this community-based study, reduced kidney function, as assessed by 3 eGFR equations and each of cystatin C, B2M, and BTP, was associated with increased risk of SCD independently of traditional risk factors at baseline and incident CHD and HF during follow-up. eGFR <60 mL/(min 1.73m²) was consistently associated with higher SCD risk compared with eGFR ≥90 mL/(min 1.73m²). The association was more evident when kidney dysfunction was assessed with the novel filtration markers cystatin C and B2M

Disclosures

Dr Sotoodehnia was supported by HL111089, HL116747, and the Laughlin Family. Dr Selvin reports grants from National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study and personal fees from Roche Diagnostics outside the submitted work. Dr Calkins reports personal fees from Medtronic, St Jude Medical, Atricure, Abbott, and Boerringer Inglheim outside the submitted work. Dr. Matsushita reports unrestricted research funding

Acknowledgements

The authors thank the staff and participants of the ARIC Study for their important contributions. The authors also thank Ms. Lucia Kwak for technical support to produce Figure 2. Reagents for the B2M assays at visit 2 were donated by the manufacturer (Roche Diagnostics).

References (39)

MH Kong et al.
Systematic review of the incidence of sudden cardiac death in the United States
J Am Coll Cardiol
(2011)
M Tonelli et al.
Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study
Lancet
(2012)
H Hreybe et al.
Renal insufficiency predicts the time to first appropriate defibrillator shock
Am Heart J
(2006)
I Goldenberg et al.
Relations among renal function, risk of sudden cardiac death, and benefit of the implanted cardiac defibrillator in patients with ischemic left ventricular dysfunction
Am J Cardiol
(2006)
PH Pun et al.
Chronic kidney disease is associated with increased risk of sudden cardiac death among patients with coronary artery disease
Kidney Int
(2009)
D Green et al.
Sudden cardiac death in hemodialysis patients: an in-depth review
Am J Kidney Dis
(2011)
BC Astor et al.
Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population
Am J Kidney Dis
(2012)
AR Folsom et al.
Community prevalence of ideal cardiovascular health, by the American Heart Association definition, and relationship with cardiovascular disease incidence
J Am Coll Cardiol
(2011)
LR Loehr et al.
Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study)
Am J Cardiol
(2008)
JM Peacock et al.
Serum magnesium and risk of sudden cardiac death in the Atherosclerosis Risk in Communities (ARIC) Study
Am Heart J
(2010)

JA Karnik et al.

Cardiac arrest and sudden death in dialysis units

Kidney Int

(2001)

RS Parekh et al.

The association of sudden cardiac death with inflammation and other traditional risk factors

Kidney Int

(2008)

K Reinier et al.

Increased left ventricular mass and decreased left ventricular systolic function have independent pathways to ventricular arrhythmogenesis in coronary artery disease

Heart Rhythm

(2011)

E Selvin et al.

Within-person variability in kidney measures

Am J Kidney Dis

(2013)

RA Kyle et al.

Review of 1027 patients with newly diagnosed multiple myeloma

Mayo Clin Proc

(2003)

P Morel et al.

International prognostic scoring system for Waldenstrom macroglobulinemia

Blood

(2009)

PH Pun et al.

Implantable cardioverter-defibrillators for primary prevention of sudden cardiac death in CKD: a meta-analysis of patient-level data from 3 randomized trials

Am J Kidney Dis

(2014)

GI Fishman et al.

Sudden cardiac death prediction and prevention: report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop

Circulation

(2010)

D Mozaffarian et al.

Heart disease and stroke statistics—2015 update: a report from the American Heart Association

Circulation

(2015)

Cited by (22)

KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease
2024, Kidney International
Structured Moderate Exercise and Biomarkers of Kidney Health in Sedentary Older Adults: The Lifestyle Interventions and Independence for Elders Randomized Clinical Trial
2023, Kidney Medicine
In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect.
Randomized controlled trial.
A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial.
Structured, 2-year, moderate-intensity exercise intervention versus health education.
Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure.
Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs <1,568 steps/day) had significant improvement in urine albumin (mean, −0.22 mg albumin/g urine creatinine [interquartile range (IQR), −0.37 to −0.06]), alpha-1-microglobulin (−0.18 mg/L [−0.28 to −0.08]), trefoil factor-3 (−0.24 pg/mL [−0.35 to −0.13]), epidermal growth factor (0.19 pg/mL [0.06-0.32]), uromodulin (0.06 pg/mL [0.00-0.12]), interleukin 18 (−0.09 pg/mL [−0.15 to −0.03]), neutrophil gelatinase-associated lipocalin (−0.16 pg/mL [−0.24 to −0.07]), monocyte chemoattractant protein-1 (−0.25 pg/mL [−0.36 to −0.14]), clusterin (-0.16 pg/mL [−0.30 to −0.02]), serum tumor necrosis factor receptor-1 (−0.25 mg/dL [−0.39 to −0.11]) and tumor necrosis factor receptor-2 (−0.30 mg/dL [−0.44 to −0.16]). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin 18 and serum tumor necrosis factor-1.
The original study was not designed to assess the impact on kidney health. Non-white individuals and patients with advanced chronic kidney disease are underrepresented.
Randomization to structured exercise did not improve kidney health at a group level. However, higher exercise was associated with concurrent improvements in biomarkers of glomerular injury, tubular function/repair, tubular injury, generalized inflammation, and tubulointerstitial repair/fibrosis.
In the Lifestyle Interventions For Elders (LIFE) study, randomization to an exercise and physical activity intervention improved the slope of estimated glomerular filtration rate over 2 years compared with health education among older adults. In this study, we sought to determine whether there were specific biomarkers of kidney health that were affected by the exercise and physical activity intervention to investigate potential mechanisms for this positive impact on kidney decline. We found that randomization to the intervention did not improve any of the 14 measures of kidney tubule health. However, in observational analyses, higher activity was independently associated with improvements in several domains, especially tubular injury and generalized inflammation. These results help to clarify the impact of physical activity on kidney health.
Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes
2022, Mayo Clinic Proceedings
Citation Excerpt :
Diabetes is independently associated with increased SCA risk.1-5,25 However, patients with diabetes also have a significantly increased prevalence of other SCA risk factors including obesity,26 hypertension,27 renal disease,28 and coronary disease.29 In our analysis, the prevalence of these risk factors were higher in SCA cases compared with controls, but were similar among T1D and T2D SCA cases, despite the T1D patients being younger on average at the time of the event.
To investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).
In a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.
Patients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.
Type 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.
A Comparison of Hemodialysis and Peritoneal Dialysis in Patients with Cardiovascular Disease
2021, Cardiology Clinics
Citation Excerpt :
The risk of SCD in dialysis patients is approximately 100-fold greater than the nondialysis population. This is comparable with the risk of SCD post–myocardial infarction or in patients with HF and reduced ejection fraction.46 Foley and colleagues47 found that all-cause-mortality, mortality from cardiac arrest, infection-related mortality, and mortality from myocardial infarction were higher on the day after the long interdialytic interval than any other day.
Arterial Stiffness in CKD: A Review
2019, American Journal of Kidney Diseases
Citation Excerpt :
Calcified aortas are stiffer, but there is little we can do about decalcification and we have no evidence to say that decalcification will be beneficial. One of the most important consequences of CKD and ESRD is the alarming incidence of sudden cardiac death.51-53 Although not formally analyzed in the CRIC Study (yet), it may be that arterial stiffness is a predictor of sudden cardiac death, possibly because the long-term consequences of arterial stiffness predispose to left ventricular hypertrophy, jeopardizing the endocardium to arrhythmia because it is vulnerable to the effects of increased afterload,54 or because of the effects of arterial stiffness on baroreceptor dysfunction.55
This narrative review summarizes a decade of experience examining the cross-sectional and longitudinal relationships of arterial stiffness, as assessed using carotid-femoral pulse wave velocity, with outcomes in patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort. Our goal is to review the importance of the pulse wave contour and pulse wave velocity and present data on the reproducibility of pulse wave velocity measurements, determinants of pulse wave velocity, and the relationship that velocity measurements have with longitudinal kidney and cardiovascular outcomes. Measures of arterial stiffness have contributed substantially to our understanding of mechanisms of cardiovascular disease, kidney disease progression, and all-cause mortality. Given the independent relationship of arterial stiffness to a variety of outcomes, it is our hope that future developments in behavioral, nutritional, and pharmacologic approaches to vascular destiffening will provide interventions that benefit patients with chronic kidney diseases.
Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD
2024, Journal of the American Society of Nephrology

View all citing articles on Scopus

: Funding sources: The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). This research was also supported by an unrestricted research fund from Kyowa Hakko Kirin to Dr. Matsushita and NIH/NIDDK grants K24DK106414andR01DK089174 to Dr Selvin.

View full text

Clinical InvestigationKidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study

Background

Methods

Results

Conclusions

Section snippets

Study participants

Results

Discussion

Disclosures

Acknowledgements

J Am Coll Cardiol

Lancet

Am Heart J

Am J Cardiol

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

J Am Coll Cardiol

Am J Cardiol

Am Heart J

Kidney Int

Kidney Int

Heart Rhythm

Am J Kidney Dis

Mayo Clin Proc

Blood

Am J Kidney Dis

Sudden cardiac death prediction and prevention: report from a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop

Circulation

Heart disease and stroke statistics—2015 update: a report from the American Heart Association

Circulation

Clinical Investigation
Kidney function and sudden cardiac death in the community: The Atherosclerosis Risk in Communities (ARIC) Study