Cardiovascular disease and chronic renal disease: A new paradigm

doi:10.1016/S0272-6386(00)70239-3

American Journal of Kidney Diseases

Volume 35, Issue 4, Supplement, April 2000, Pages S117-S131

https://doi.org/10.1016/S0272-6386(00)70239-3 Get rights and content

Abstract

Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with chronic renal disease (CRD). Despite improvement in treatment for CVD over the past 30 years, CVD mortality is approximately 15 times higher in dialysis patients than in the general population. The high prevalence of CVD among incident dialysis patients suggests that CVD begins in earlier stages of CRD, and that implementation of risk factor reduction strategies earlier in the course of CRD may provide an opportunity to prevent CVD in CRD. Based on parallels between CVD and renal disease progression, we have proposed a paradigm that CVD and CRD are outcomes of the same underlying disorders. We propose that risk factor reduction strategies used to prevent CVD in the general population also be applied to patients with CRD, with the hope of preventing progression of renal disease, as well as preventing CVD.

Section snippets

End stage

End-stage renal disease (ESRD), defined as a life-threatening reduction in renal function, requiring dialysis or transplantation to survive, is the most visible consequence of CRD (Table 1). Data from the US Renal Data System (USRDS) from 1998 indicate 335,000 patients with ESRD.³ From 40% to 75% of patients starting dialysis already have manifestations of CVD, and CVD accounts for 40% of deaths.3, 4 Patients treated by dialysis suffer a high burden of comorbid conditions, reduced quality of

CVD in ESRD

CVD mortality is approximately 10 to 30 times higher in patients treated by dialysis compared with patients in the general population, despite stratifying for gender, race, and the presence of diabetes (Table 2).⁴After stratifying for age, CVD mortality remains 10-fold higher in dialysis patients than in the general population, even at the extremes of age (Fig 1).

. Cardiovascular mortality in the general population (NCHS) and in ESRD treated by dialysis. Cardiovascular mortality defined by death

Epidemiology of CVD risk factors in CRD

CVD risk factors in CRD can be divided into traditional and uremia-related factors (Table 4). For convenience, we define traditional coronary risk factors as those derived from studies of the Framingham population, such as older age, diabetes, male gender, family history of coronary disease, hypertension, high low-density lipoprotein (LDL) cholesterol, low HDL cholesterol, history of smoking, physical inactivity, menopause, and psychosocial stress. We define uremia-related risk factors as other

Pathogenesis

The similarities between the pathogenesis of atherosclerosis and glomerulosclerosis have been reviewed by various investigators.⁶³ The histologic features common to both conditions include influx of monocytes, production of lipid-laden macrophages, presence of cholesterol and cholesterol esters, proliferation of contractile cells (either vascular smooth muscle cells or glomerular mesangial cells), and expansion of both collagenous and noncollagenous matrix expansion resulting in fibrosis. The

Lessons from CVD prevention in the general population

Over the past decade, there has been increasing recognition of the importance of systematic retrieval, assembly, and synthesis of evidence from the medical literature to develop guidelines for clinical practice. Evidence models are often used to facilitate this process. An evidence model is a flowchart that defines the relationships between stages of disease, as well as consequences of interventions. Evaluation of the benefits and harms of interventions is based on a review of evidence linking

References (76)

AS Levey et al.
Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here?
Am J Kidney Dis
(1998)
RN Foley et al.
The clinical epidemiology of cardiovascular disease in chronic renal disease
Am J Kidney Dis
(1998)
CA Jones et al.
Serum creatinine levels in the US population: Third National Health and Nutrition Examination Survey
Am J Kidney Dis
(1998)
WF Keane et al.
Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): A position paper of the National Kidney Foundation
Am J Kidney Dis
(1999)
RP Donahue et al.
The influence of sex and diabetes mellitus on survival following acute myocardial infarction: A community-wide perspective
J Clin Epidemiol
(1993)
JD Harnett et al.
Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors
Kidney Int
(1995)
WM Bennett et al.
Natural history of a asymptomatic coronary arteriographic lesions in diabetic patients with end-stage renal disease
Am J Med
(1978)
RN Foley et al.
Clinical and echocardiographic disease in patients starting end-stage renal disease therapy
Kidney Int
(1995)
A Levin et al.
Prevalent left ventricular hypertrophy in the predialysis population: Identifying opportunities for intervention
Am J Kidney Dis
(1996)
A Levin et al.
Left ventricular mass index increase in early renal disease: Impact of decline in hemoglobin
Am J Kidney Dis
(1999)

US Renal Data System

1998 Annual Data Report

(1998)

BF Culleton et al.

Relations of proteinuria to cardiovascular disease events and mortality in older persons

J Am Soc Nephrol

(1998)

K Iskeki et al.

Risk of developing end-stage renal disease in a cohort of mass screening

Kidney Int

(1996)

MI Harris

Diabetes in America

TJ Thom et al.

Incidence, prevalence, and mortality of cardiovascular diseases in the United States

CA Herzog et al.

Poor long-term survival after myocardial infarction among patients on long-term dialysis

N Engl J Med

(1998)

D Levy et al.

Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study

N Engl J Med

(1990)

Cited by (497)

Association between systolic blood pressure and target organ damage in naturally occurring cases of systemic hypertension in the dog
2024, Topics in Companion Animal Medicine
Chronic elevation in the systolic blood pressure (SBP) adversely affects the lifespan in the dog by causing injury to the eye, heart, kidney and brain. Understanding the association between SBP and target organ damage (TOD) helps in risk categorization and treatment planning. Therefore, a prospective study was undertaken to find the association between SBP and renal resistive index (RI) in naturally occurring cases of canine systemic hypertension. Based on the ACVIM guidelines 2018, dogs (n=135) were categorized into four risk groups of SBP, viz., A (minimal), B (low), C (moderate), and D (high). Ophthalmoscopy and echocardiography were used to assess ocular and cardiac changes, respectively. Nephrosonography, urinalysis, and RI were used to assess kidney damage. Odds ratio (OR) was used to quantify the risk of TOD for different categories of SBP. One-way Anova with Tukey's post-hoc test was used to test the effect of different SBP risk groups on urine protein creatinine ratio (UPC) and RI as well as the effect of number of TOD on the RI. Pearson's correlation test was done to see the relation of SBP with UPC and RI. Tortuous retinal vessels were common in group B with an OR of 11 (95% CI: 0.59-207). Retinal hemorrhage and left ventricular hypertrophy were common in group D with an OR of 13 (95% CI: 0.67-234) and 11 (95% CI: 0.61-207), respectively. A significant strong positive correlation of SBP with UPC (R²=0.65) and RI (R²=0.58) was observed. The renal RI significantly increased when the number of TOD was ≥ 2. It was concluded that SBP and RI are associated with the number and severity of TOD and might be valuable in risk classification in hypertensive dogs.
Trends of medication used in patients with pre-ESKD from 2010 to 2018 in Taiwan
2022, Journal of the Formosan Medical Association
The burden of end-stage kidney disease (ESKD) continues to grow globally. Information on medication prescribed to advanced chronic kidney disease (CKD) patients can help formulate further CKD prevention policies. This study aimed to review and assess several major medications routinely prescribed to pre-ESKD patients.
Medication information of advanced CKD patients one year before regular dialysis was collected from the National Health Insurance Research Database from 2000 to 2018 in Taiwan. Usages of major medication were comprehensively analyzed.
During 2000–2018, trends in medication usage evolved gradually in the pre-ESKD population in Taiwan. The use of erythropoietin had increased (48.3% in 2000 to 71.0% in 2018) with decreased blood transfusion rate (70.9% in 2003 to 52.1% in 2018). The use of non-steroidal anti-inflammatory drugs had also dropped (43.5% in 2004 to 25.5% in 2018). These changes were more evident for patients enrolled in the pre-ESKD prevention program. The most frequently used blood pressure-lowering and glucose-lowering agents were calcium channel blockers (90.6%) and insulin (78.1%), but usage of metformin was unexpectedly high (38.4% in 2018). The most frequently used blood thinner was aspirin (49.5%), with considerably increased use of direct oral anticoagulant (16.5% in 2018).
An overview of the trends of major medication usage and blood transfusion represented the continuously improving care quality in pre-ESKD patients in Taiwan. These trends were especially evident in patients enrolled in the pre-ESKD prevention program. This report also indirectly indicated the potential and long-term benefits of implementing CKD and pre-ESKD prevention programs.
Arterial stiffness and pulsatile hemodynamics in renal disease
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
Of the three main target organs vulnerable to damage from hypertension in humans, the kidneys, unlike the brain or heart reside below the diaphragms, thus, in the upright position they are exposed to higher ambient pressure loads compared to the cerebral or the coronary arteries. Moreover, the unique excretory function of the kidneys requires the ability to receive, filter, and process many liters of blood each hour. Sandwiched in between the afferent and efferent arterioles are more than a million glomeruli in each kidney, composed of a delicate set of capillaries which are responsible for the initial filtration that leads to urine formation. The kidneys, like the brain, are a marvel of low resistance vascular beds. Despite accounting for less than 2% of the body weight, they receive about 22% of the cardiac output. An intricate system of neural and myogenic reflexes which dampen the vagaries of pulsatile flow and the large artery stiffness that accompanies aging, and a variety of co-morbidities like diabetes. These reflexes are progressively lost as kidney fail, resulting in a vicious cycle of increasing kidney function loss. In this chapter we discuss the nature of the kidney circulation, the consequences on the kidney circulation of large artery stiffening, pathogenic pulsatile hemodynamics, and the associations of large artery stiffness with kidney function loss and cardiovascular diseases in chronic kidney disease.
Renal-Cerebral Pathophysiology: The Interplay Between Chronic Kidney Disease and Cerebrovascular Disease
2021, Journal of Stroke and Cerebrovascular Diseases
Cerebrovascular disease has increasingly been linked to overall vascular health. Pathologic conditions like diabetes, hypertension, and kidney disease have been shown to affect brain health and cerebrovascular and nervous systems. Acute kidney injury (AKI) and chronic Kidney Disease (CKD) represent a variety of vascular insults that can adversely affect cerebral health. Hypertension, fluctuations in blood pressure, and diabetic vasculopathy are known risk factors for cerebrovascular disease associated with CKD. Other emerging areas of interest include endothelial dysfunction, vascular calcification due to calcium and phosphorus metabolism dysregulation, and uremic neuropathy present the next frontier of investigation in CKD and cerebrovascular health.
It has become apparent that the interrelation of AKI and CKD with vascular health, chemical homeostasis, and hormonal regulation upset many aspects of cerebral health and functioning. Stroke is an obvious connection, with CKD patients demonstrating a higher proclivity for cerebrovascular accidents. Cerebral bleeding risk, uremic neuropathies, sodium dysregulation with impacts on nervous system, vascular calcification, and endothelial dysfunction are the next salient areas of research that are likely to reveal key breakthroughs in renal-cerebral pathophysiology.
In this review nephrological definition are discussed in a neuro-centric manner, and the areas of key overlap between CKD and cerebrovascular pathology are discussed. The multifaceted effects of renal function on the health of the brain are also examined.
This review article aims to create the background for ongoing and future neurological-nephrological collaboration on understanding the special challenges in caring for patients with cerebrovascular disease who also have CKD.
Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective
2024, Inflammopharmacology
Donor-Derived Engineered Microvessels for Cardiovascular Risk Stratification of Patients with Kidney Failure
2024, Small

View all citing articles on Scopus

^☆: Address reprint requests to Mark J. Sarnak, MD, Division of Nephrology, New England Medical Center, Box 391, 750 Washington St, Boston, MA 02111. E-mail: [email protected]

View full text

Research Issues Related to the Aims and Goals of the National Kidney FoundationCardiovascular disease and chronic renal disease: A new paradigm☆

Abstract

Section snippets

End stage

CVD in ESRD

Epidemiology of CVD risk factors in CRD

Pathogenesis

Lessons from CVD prevention in the general population

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

J Clin Epidemiol

Kidney Int

Am J Med

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Kidney Int

Kidney Int

Kidney Int

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Kidney Int

Kidney Int

J Clin Epidemiol

Am J Kidney Dis

Am J Med

Accelerated atherosclerosis in prolonged maintenance hemodialysis

N Engl J Med

1998 Annual Data Report

Relations of proteinuria to cardiovascular disease events and mortality in older persons

J Am Soc Nephrol

Risk of developing end-stage renal disease in a cohort of mass screening

Kidney Int

Diabetes in America

Incidence, prevalence, and mortality of cardiovascular diseases in the United States

Poor long-term survival after myocardial infarction among patients on long-term dialysis

N Engl J Med

Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study

N Engl J Med

Research Issues Related to the Aims and Goals of the National Kidney Foundation
Cardiovascular disease and chronic renal disease: A new paradigm☆