1/6/2021 Annual Data Report | USRDS

End Stage Renal Disease: Chapter 8

Cardiovascular Disease in Patients with ESRD

Highlights
The prevalence of cardiovascular disease (CVD) in 2018 was 76.5% in patients receiving hemodialysis
(HD), 65.0% in patients receiving peritoneal dialysis (PD), and 53.7% in patients with a functioning
kidney transplant (Figure 8.1). The most common manifestations of CVD were heart failure (HF) (HD,
44.2%; PD, 31.1%; kidney transplant, 18.3%), CAD (43.9%, 36.4%, and 26.1%, respectively), and
peripheral arterial disease (PAD) (41.5%, 27.7%, and 21.9%, respectively).

Key cardiovascular procedures (Table 8.1) occurred more commonly in patients receiving PD than HD
in 2018, including percutaneous coronary intervention (PCI) (4.0% in patients receiving PD versus
3.4% in patients receiving HD), coronary artery bypass grafting (CABG) (1.4% versus 0.7%), and
carotid artery stenting or carotid endarterectomy (CAS/CEA) (0.24% versus 0.21%).
Kidney transplant recipients with CVD had longer adjusted survival than patients receiving dialysis
without CVD (Figure 8.2).

The unadjusted survival probability following a first cardiovascular procedure in 2016-2018 was highest
among patients with a kidney transplant and lowest among patients receiving PD. In the case of CABG,
the two-year adjusted survival probability of patients with a functioning kidney transplant (0.75) was
comparable to the 12-month survival probability of a patient receiving HD and the 10-month survival
probability of a patient receiving PD (Figure 8.3).
The percentage of patients receiving dialysis with HF increased from 39.2% to 43.0% between 2014
and 2018 (Figure 8.5). Diagnosis of HF with reduced ejection fraction (HFrEF) and HF with preserved
ejection fraction (HFpEF) increased in patients receiving HD or PD by approximately 50% over this
period, while the percentage of patients with unspecified HF decreased. In 2018, more patients
receiving HD than patients receiving PD had HFrEF (17.5% versus 13.2%) and HFpEF (13.9% versus
8.8%).
The unadjusted cumulative incidence of HF was substantially higher among those initiating HD than
among those initiating PD or those with a first kidney transplant. For example, 20% of patients initiating
HD received a diagnosis of HF within 2 months, whereas it took 8 months for patients initiating PD to
reach this benchmark and 2 years for those with a first kidney transplant (Figure 8.6).

Introduction
This chapter focuses on CVD in patients with end stage renal disease (ESRD). In the U.S., CVD is the
leading cause of death (https://www.cdc.gov/heartdisease/facts.htm). As discussed in Chapter 4 of Volume
1 (CVD in patients with CKD), CVD in patients with kidney disease is related to both “traditional” and
“nontraditional” risk factors. In addition, many patients receiving dialysis, and HD in particular, suffer from
chronic volume overload – itself a risk factor for CVD.

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In this chapter, we first examine the prevalence of cardiovascular disease by ESRD treatment modality. As
we do throughout the Annual Data Report (ADR), we stratify by age, sex, race, but also, in this case, by
diabetes status, since patients with diabetes are at exceptionally high risk of CVD compared with patients
without diabetes. We then display the use of cardiovascular procedures in patients with ESRD by treatment
modality. Following this, we analyze survival probabilities by cardiovascular disease status and ESRD
treatment modality and survival after a cardiovascular procedure by treatment modality. We next explore
pharmacologic therapies for key CVD manifestations, examining medications that are most relevant to the
CVD conditions of interest.

Finally, we examine HF. We show trends in HF between 2014 and 2018 for patients receiving dialysis,
displayed by HF type (HFrEF or “systolic dysfunction”, HFpEF or “diastolic dysfunction”, or unspecified HF).
We then show unadjusted cumulative probabilities of incident HF among patients receiving HD or PD,
contrasting these patients to those with a functioning kidney transplant.

Methods
In this chapter, we utilize data from the Centers for Medicare & Medicaid Services and the Organ
Procurement and Transplantation Network (OPTN), which we use to construct the ESRD Database. For
details of data sources and the construction of the ESRD database, see the section on Data Sources in the
ESRD Analytical Methods.

We use three basic analytical approaches to cohort construction in this chapter. First, when determining
prevalence of a condition or incidence of a CVD procedure or drug utilization in a given calendar year or
survival by presence of CVD and treatment modality, we utilize a point-prevalent cohort of patients on
January 1 of that year with their first ESRD service date at least 90 days prior to the point-prevalent date.
Second, when evaluating survival after a cardiovascular procedure, we create cohorts consisting of all
ESRD patients with a first cardiovascular procedure in 2016-2018; follow-up begins on the day that a claim
for the procedure of interest appears and treatment modality is identified on the day of the procedure. Third,
when examining the cumulative incidence of HF, we utilize an incident cohort of ESRD patients receiving
HD or PD 90 days after their first ESRD service date plus a cohort of incident kidney transplant patients
from 2016-2018 (combined). For time-to-event analyses, censoring definitions vary based on the outcomes
assessed; specific details of each analysis can be found in the section on Chapter 8 within the ESRD
Analytical Methods.

There are several specific analytical details to note. Only adult patients (those aged ≥18 years of age) are
analyzed in this chapter. For most analyses, we divide patients receiving dialysis for ESRD into those
utilizing HD or PD, but for some analyses, we study all patients receiving dialysis as one group. For HF
analyses, type of HF is now termed HFrEF (heart failure with reduced ejection fraction, or “systolic
dysfunction”) or HFpEF (heart failure with preserved ejection fraction, or “diastolic dysfunction”); the specific
hierarchy of the assignment of HF type can be found in the section on Chapter 8 within the ESRD Analytical
Methods. The approach used for sudden cardiac arrest (SCA) differs this year, mainly because the current
definition considers only “lethal” arrhythmias (cardiac arrest, ventricular fibrillation, and ventricular flutter -
arrhythmias which, in the absence of resuscitation, would be fatal); unlike in some previous ADRs, we do
not include reentry ventricular arrhythmia, paroxysmal ventricular tachycardia, and other premature beats.
We consider only nonvalvular atrial fibrillation when reporting survival in patients with CVD diagnoses and
pharmacologic treatments for CVD. When examining use of cardiovascular medications, we focus only on

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the medications most germane to the specific CVD condition under consideration. For the denominator of
this medication analysis, we used Medicare beneficiaries with Parts A, B, and D coverage, leading to
somewhat higher percentages of medication use than have been reported in years past.

Figure 8.1 Unadjusted prevalence of common cardiovascular diseases in adult patients with ESRD, by treatment modality, 2018

Overall By Age (Years) By Race By Sex By Diabetic Status

Overall
100

75
Percentage

50

25

0
Any CVD HF CAD AMI VHD PAD CVA/TIA AF SCA VTE/PE
Cardiovascular disease

- HD - PD - KTx

Data source: USRDS ESRD Database. January 1, 2018 point prevalent patients with ESRD aged 18 and older with Medicare Parts A and B coverage. Abbreviations:
SCA, sudden cardiac arrest; VHD, valvular heart disease; VTE/PE, venous thromboembolism and pulmonary embolism.

Percentages of patients with key CVD diagnoses in 2018 are shown in Figure 8.1, overall and by ESRD
treatment modality. Results are stratified by basic demographic factors and by diabetes status. The
prevalence of CVD was 76.5% in patients receiving HD, 65.0% in patients receiving PD, and 53.7% in
patients with a functioning kidney transplant. The most common CVD diagnoses were HF (HD, 44.2%; PD,
31.1%; kidney transplant, 18.3%), CAD (43.8%, 36.4%, and 26.1%, respectively), and PAD (41.5%, 27.7%,
and 21.9%, respectively). SCA occurred in 1.1% of patients receiving HD and 0.7% of those receiving PD.
As might be expected, CVD diagnoses were more common with advancing age, but even among patients
aged 18-44, 61.4% of patients receiving HD and 50.0% of those receiving PD had some form of CVD.
Women receiving HD had a higher prevalence of most CVD diagnoses than did men, but the opposite was
observed for those receiving PD. Across all modalities, White patients generally had a higher prevalence of
CVD diagnoses than did Black individuals. Patients with diabetes had substantially higher prevalence of
CVD diagnoses than did patients without diabetes.

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Table 8.1 Incidence of cardiovascular procedures in adult patients with ESRD, by treatment modality and stratified by age, race, and sex,
2018

Percentage of patients

Overall 18-44 45-64 65-74 75+ White Blk/Af Am AI/AN Asian Other Male Female

PCI

Hemodialysis 3.41 1.36 3.69 4.09 3.09 3.97 2.59 3.64 3.72 3.51 3.69 3.03

Peritoneal dialysis 4.02 1.61 4.23 5.12 4.51 4.39 3.17 4.38 3.63 3.92 4.44 3.51

Transplant 1.24 0.35 1.21 1.49 1.64 1.40 0.83 0.95 1.01 1.06 1.45 0.94

CABG

Hemodialysis 0.74 0.42 0.93 0.86 0.34 0.86 0.57 0.90 0.69 0.83 0.92 0.50

Peritoneal dialysis 1.35 0.57 1.62 1.75 0.82 1.53 0.76 1.20 1.81 2.29 1.79 0.82

Transplant 0.29 0.07 0.29 0.37 0.26 0.33 0.18 0.27 0.29 0.11 0.35 0.20

ICD/CRT-D

Hemodialysis 0.30 0.19 0.29 0.37 0.28 0.34 0.25 0.27 0.23 0.25 0.36 0.21

Peritoneal dialysis 0.25 0.22 0.26 0.30 0.20 0.26 0.26 0.00 0.15 0.33 0.32 0.18

Transplant 0.09 0.03 0.07 0.12 0.14 0.10 0.08 0.14 0.00 0.00 0.12 0.04

CAS/CEA

Hemodialysis 0.21 0.03 0.16 0.29 0.33 0.27 0.14 0.15 0.16 0.19 0.20 0.22

Peritoneal dialysis 0.24 0.07 0.29 0.31 0.13 0.31 0.10 0.00 0.15 0.00 0.27 0.20

Transplant 0.14 0.02 0.07 0.23 0.26 0.17 0.06 0.00 0.12 0.21 0.18 0.09
Data source: USRDS ESRD Database. January 1, 2018 point prevalent patients with ESRD aged 18 and older with Medicare Parts A and B coverage. Abbreviations: CAS/CEA, carotid
artery stenting and carotid endarterectomy; ICD/CRT-D, implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator; PCI, percutaneous coronary interventions.

Table 8.1 shows the incidence of PCI, CABG, implantable cardioverter defibrillator/cardiac
resynchronization therapy defibrillator (ICD/CRT-D), and carotid artery stenting and carotid endarterectomy
(CAS/CEA) for prevalent patients with ESRD in 2018. Relative to patients receiving HD, a higher
percentage of patients receiving PD underwent PCI (4.0% versus 3.4%) and CABG (1.4% versus 0.7%).
Among patients receiving HD or PD, patients aged ≥75 years were less likely to receive procedure than
those aged 65-74. White patients generally underwent more procedures than Blacks. For example, the
percentage of Whites receiving HD who underwent a CABG (0.86%) was higher than Blacks (0.57%); this
White-Black difference was approximately 2-fold among patients receiving PD. Similarly, the percentage of
patients receiving CAS/CEA was 2- to 3-fold greater among White, as compared with Black, patients
receiving dialysis. Procedures generally occurred more often among men than among women.

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Figure 8.2 Adjusted survival probability in adult patients with ESRD by cardiovascular disease status and treatment modality, 2017-2018

By CAD By AMI By HF By VHD By CVA/TIA By PAD By NVAF By SCA By VTE/PE

Adjusted Unadjusted

By CAD
1.0

0.8
Probability of survival

0.6

0.4

0.2

0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Months

- Dialysis, CAD - Dialysis, non-CAD - Transplant, CAD - Transplant, non-CAD

Data source: USRDS ESRD Database. January 1, 2017 point prevalent patients with ESRD aged 18 and older with Medicare Parts A and B coverage. Adjustments
were for age, race, and sex. Abbreviations: SCA, sudden cardiac arrest; VHD, valvular heart disease; VTE/PE, venous thromboembolism and pulmonary embolism;
NVAF, nonvalvular atrial brillation.

Figure 8.2 displays the survival probability, by the presence or absence of key CVD diagnoses, for patients
receiving dialysis or with a functioning kidney transplant. For most diagnoses, the survival benefit of
transplantation outweighed the disadvantage of CVD, particularly over the second year. With the exception
of SCA, transplanted patients with each CVD diagnosis had similar adjusted survival probability over the
first year and better survival in the second year than patients receiving dialysis who did not have that
diagnosis. For example, the adjusted 2-year survival probability of patient with a kidney transplant with HF
(81%) was comparable to the probability of surviving 20 months for a patient receiving dialysis who did not
have HF.

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Table 8.2 Unadjusted and adjusted 2-year survival probability in adult patients with ESRD by cardiovascular disease status and treatment
modality, 2017-2018

Unadjusted Adjusted

Dialysis Transplant

Survival when Survival when not Survival when Survival when not
Cardiovascular disease present (%) present (%) present (%) present (%)

CAD 60.2 75.5 83.6 91.5

AMI 52.6 71.2 77.2 89.9

HF 60.3 76.8 81.1 91.8

VHD 54.9 71.3 81.1 90.2

CVA/TIA 58.6 71.0 80.9 90.2

PAD 61.7 74.2 83.0 91.1

NVAF 55.1 72.1 79.5 90.8

SCA 39.6 68.8 67.4 89.2

VTE/PE 56.3 69.4 80.8 89.6

Data source: USRDS ESRD Database. January 1, 2017 point prevalent patients with ESRD aged 18 and older with Medicare Parts A and B coverage. Adjustments were for age, race,
and sex. Abbreviations: SCA, sudden cardiac arrest; VHD, valvular heart disease; VTE/PE, venous thromboembolism and pulmonary embolism; NVAF, nonvalvular atrial fibrillation.

Table 8.2 lists the 2-year survival probabilities, by the presence or absence of key CVD diagnoses, for
patients receiving dialysis or with a functioning kidney transplant. In absolute terms, the difference in
survival probability between patients with and without a given CVD diagnosis was greater among patients
receiving dialysis than among kidney transplant recipients. For most CVD diagnoses, the survival benefit of
transplantation was larger than the disadvantage of CVD. At two years, adjusted survival probability of
kidney transplant recipients with each CVD diagnosis was greater than that of patients receiving dialysis
without each CVD manifestation; the only exception was SCA, where the adjusted survival probabilities
were approximately equal.

Age and race were also strongly associated with survival. Older patients had higher mortality regardless of
CVD status. Similarly, Black patients with CVD had better survival than White patients with CVD, and Black
patients without CVD had better survival than White patients without CVD.

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Figure 8.3 Unadjusted survival probability in adult patients with ESRD following a first cardiovascular procedure, by treatment modality,
2016-2018

PCI CABG ICD/CRT-D CAS/CEA

PCI
1.0

0.8
Probability of survival

0.6

0.4

0.2

0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Months

- HD - PD - KTx

Data source: USRDS ESRD Database. ESRD patients with a rst cardiovascular procedure in 2016-2018 aged 18 and older with Medicare Parts A and B coverage.
Adjustments were for age, race, and sex. Abbreviations: CAS/CEA, carotid artery stenting and carotid endarterectomy; ICD/CRT-D, implantable cardioverter
de brillator/cardiac resynchronization therapy de brillator; PCI, percutaneous coronary interventions.

The unadjusted survival probability following a first cardiovascular procedure in 2016-2018 is shown in
Figure 8.3 for patients receiving HD, PD, or with a functioning kidney transplant. Unadjusted survival
probability after each procedure was highest among patients with a kidney transplant and lowest among
patients receiving PD. In the case of CABG, for example, the 2-year survival probability of a patients with
kidney transplant (75%) was comparable to the 12-month survival probability of a patient receiving HD and
the 10-month survival of probability of a patient receiving PD.

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Figure 8.4 Percentage of adult patients with ESRD receiving pharmacologic treatments for cardiovascular disease, by treatment modality,
2018

CAD AMI HF CVA/TIA PAD NVAF

CAD, All Dialysis (n=83,738)

Lipid-
Beta
lowering
blockers
agents

ACEI/ARBs

● None: 7.0

CAD, Transplant (n=14,439)

Lipid-
Beta
lowering
blockers
agents

ACEI/ARBs

● None: 4.1
Data source: USRDS ESRD Database. January 1, 2018 point prevalent patients with ESRD aged 18 and older with Medicare Parts A, B, and D coverage and the CVD condition of interest
in 2018. Abbreviations: ARNIs, angiotensin receptor neprilysin inhibitors; DOACs, direct oral anticoagulants; MRAs, mineralocorticoid receptor antagonists; NVAF, nonvalvular atrial
fibrillation.

The percentage of adult patients with ESRD receiving pharmacologic therapies for key CVD diagnoses in
2018 is shown in Figure 8.4. Patients are divided into those receiving dialysis and those with a functioning
kidney transplant. Medications were specifically selected for their relevance to the CVD condition of interest.
Generally, patients with a kidney transplant were more likely to have received medications than were
patients receiving dialysis. Among patients with AMI, 85.1% of kidney transplant recipients received beta-
blockers, compared with 82.2% of patients receiving dialysis. Among kidney transplant recipients with PAD,
76.0% were receiving lipid-lowering agents, compared with only 66.8% of patients receiving dialysis. Among

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patients with nonvalvular atrial fibrillation, 65.9% of kidney transplant recipients were receiving warfarin or a
direct-acting oral anticoagulant, compared with 52.1% of patients receiving dialysis. Notably, among
patients with HF, only 43.7% of patients with a kidney transplant and 44.5% of patients receiving dialysis
received angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor
neprilysin inhibitors.

Figure 8.5 Percentage of adult patients receiving dialysis with heart failure, by heart failure type, stratified by dialysis modality, 2014-2018

HFrEF HFpEF Unspecified HF All HF

HFrEF
30

25

20
Percentage

15

10

0
2014 2015 2016 2017 2018
Year

- HD - PD - All dialysis

Data source: USRDS ESRD Database. January 1 point prevalent patients receiving dialysis aged 18 and older with Medicare Parts A and B coverage, 2014-2018.
Abbreviations: HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction.

Figure 8.5 displays trends in HF prevalence between 2014 and 2018 among patients receiving HD, PD, and
all dialysis (including uncertain dialysis type). HF is classified as HFrEF (heart failure with reduced ejection
fraction, or “systolic dysfunction”), HFpEF (heart failure with preserved ejection fraction, or “diastolic
dysfunction”), or unspecified HF. The percentage of all patients receiving dialysis with HF of any type
increased from 39.2% to 43.0% over 4 years. Diagnosed HFrEF and HFpEF increased in patients receiving
either of the dialysis modalities over time by approximately 50%, while the percentage of patients with
unspecified HF decreased, perhaps due to efforts to improve diagnosis coding specificity. Regardless of HF
type, over the period of 2014-2018, prevalence of HF was consistently higher in patients receiving HD than
in patients receiving PD. In 2018, a higher percentage of patients receiving HD than patients receiving PD
had both HFrEF (17.5% versus 13.2%) and HFpEF (13.9% versus 8.8%). Since patients receiving HD
vastly outnumber those receiving PD, the overall results are similar to those of the HD subset.

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Figure 8.6 Unadjusted cumulative probability of incident heart failure among adult patients with incident dialysis or kidney transplant, by
treatment modality, 2016-2018
0.6

0.5

0.4
Probability

0.3

0.2

0.1

0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Months

- HD - PD - KTx

Data source: USRDS ESRD Database. Patients with incident dialysis or kidney transplant aged 18 and older with Medicare Parts A and B coverage, 2016-2018
combined.

Figure 8.6 displays the unadjusted cumulative incidence of HF among patients receiving HD or PD or with a
functioning kidney transplant. Beyond month 4, cumulative incidence was highest in patients receiving HD
and lowest in patients with a kidney transplant. The 2-year cumulative probability of developing HF among
patients with a kidney transplant was approximately 20%. Onset of HF was much more common among
patients receiving HD: those receiving HD reached a 20% cumulative probability of incident HF after less
than 2 months.

Summary
Cardiovascular disease remains extraordinarily common in patients with ESRD. This is likely because CVD
and ESRD are interwoven processes: underlying conditions such as diabetes, hypertension, and
atherosclerosis cause both CVD and kidney disease. Furthermore, CVD contributes to the development of
kidney disease and kidney disease to the development of CVD.

The prevalence of CVD among patients with ESRD varies considerably by modality of kidney replacement
therapy, with more than three-quarters of patients receiving HD, nearly two-thirds of patients receiving PD,
and over half of patients with a kidney transplant having a CVD diagnosis. This variability likely reflects a
selection process among the treatment options available for kidney replacement therapy. The healthiest
patients are most likely to receive a kidney transplant, whereas those with the greatest burden of CVD may
be excluded from transplantation and “channeled” into HD rather than PD. It is intriguing to consider the
implications of reducing CVD burden in patients with non-dialysis-dependent CKD: in addition to slowing the
progression to ESRD, it is possible that utilization of PD, relative to that of HD, might increase.
Consideration of survival probability according to the presence of CVD (Figure 8.2) serves to highlight the
likely contributions of patient selection and comorbid CVD to the differences in survival among patients
receiving dialysis and those who receive a kidney transplant. In other words, the survival benefit we ascribe
to kidney transplantation likely reflects not only an effect of transplantation itself, but also underlying health
status, which determines, in part, whether a patient is likely to be a suitable kidney transplant candidate.

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Concerning the issue of race, most CVD diagnoses and CVD procedures were more common in White
patients than in Black patients. It is possible that CVD is truly more common in Whites than in Blacks,
leading to more diagnostic procedures in the former than in the latter. However, higher utilization of
procedures in Whites than in Blacks could also represent a racial disparity wherein fewer CVD procedures
in Blacks leads to underdiagnosis of CVD. Better survival of Black patients with and without CVD may
support the former possibility, but elucidation of this question will require further study. Specifically, analyses
with risk adjustment for important differences in the Black and White ESRD populations (e.g., older age
among White patients) will be needed.

HF is a CVD condition of particular interest to the nephrology community. We report an increase in HF of

approximately 10% over a mere 4 years. Greater attention to HFpEF, or “diastolic dysfunction”, as a clinical
entity may be one reason for the increase. Perhaps patients who had previously been diagnosed as
unspecified HF are now increasingly labelled as having HFpEF. However, this would not explain why HFrEF,
or traditional “systolic dysfunction,” is also increasing. The finding of an increase in HF must be considered
with caution because there are substantial challenges to HF classification and measurement when using
administrative claims. First, in patients receiving dialysis, particularly hemodialysis, the distinction between
true heart failure and “mere” volume overload (typically due to inadequate ultrafiltration) can be difficult to
make clinically (Herzog, 2019). Indeed, traditional taxonomies used for classification for HF may be
inadequate in patients with ESRD and likely require a unique classification system (Chawla et al., 2014).
Second, coding practices can change over time, particularly when subject to reimbursement pressures.
These, and possibly other, factors make statements about HF epidemiology difficult. Whatever the
explanation for this finding, novel approaches to fluid removal during dialysis may be required before
progress in reducing the population-wide burden of HF becomes evident.

References
Herzog, C. (2019). Congestive Heart Failure and Chronic Kidney Disease: The
CardioRenal/Nephrocardiology Connection. J Am Coll Cardiol, 73(21),2701-2704.
https://www.sciencedirect.com/science/article/pii/S073510971934690X?via%3Dihub
Chawla, L., Herzog, C., Costanzo, M., Tumlin, J., Kellum, J., McCullough, P., Ronco, C., ADQI XI
Workgroup (2014). Proposal for a Functional Classification System of Heart Failure in Patients with
End-Stage Renal Disease: Proceedings of the Acute Dialysis Quality Initiative (ADQI) XI Workgroup. J
Am Coll Cardiol, 63(13),1246-1252.
https://www.sciencedirect.com/science/article/pii/S0735109714003313?via%3Dihub

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