Elsevier

The Lancet

Volume 382, Issue 9889, 27 July–2 August 2013, Pages 339-352
The Lancet

Series
Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention

https://doi.org/10.1016/S0140-6736(13)60595-4Get rights and content

Summary

Since the first description of the association between chronic kidney disease and heart disease, many epidemiological studies have confirmed and extended this finding. As chronic kidney disease progresses, kidney-specific risk factors for cardiovascular events and disease come into play. As a result, the risk for cardiovascular disease is notably increased in individuals with chronic kidney disease. When adjusted for traditional cardiovascular risk factors, impaired kidney function and raised concentrations of albumin in urine increase the risk of cardiovascular disease by two to four times. Yet, cardiovascular disease is frequently underdiagnosed and undertreated in patients with chronic kidney disease. This group of patients should, therefore, be acknowledged as having high cardiovascular risk that needs particular medical attention at an individual level. This view should be incorporated in the development of guidelines and when defining research priorities. Here, we discuss the epidemiology and pathophysiological mechanisms of cardiovascular risk in patients with chronic kidney disease, and discuss methods of prevention.

Introduction

Bright1 wrote in 1836, “The obvious structural changes in the heart have consisted chiefly of hypertrophy...and what is most striking, out of fifty-two cases…no valvular disease could be detected in thirty-four…This naturally leads us to look for some less local cause”, and “It is observable, that the hypertrophy of the heart seems, in some degree, to have kept pace with the advance of disease in the kidneys; for in by far the majority of cases, when the heart was increased, the hardness and contraction of the kidney bespoke the probability of long continuance of the disease.” Bright was the first to report the association between chronic kidney disease and cardiovascular abnormalities. He suggested that the altered quality of the blood in patients with renal disease affected the peripheral vasculature, particularly the capillaries, in a way that required increased force to propel the blood around the body.2 By taking the view that renal disease is the primary disorder and cardiovascular changes are secondary, Bright established the concept of the renal origin of cardiovascular disease. Many studies have since confirmed and extended this association, and explanations have been sought. As part of this Series on global kidney disease, we discuss the relation between chronic kidney disease and cardiovascular risk. We present available information on the epidemiology, pathophysiological mechanisms, and prevention of chronic kidney disease and aim to provide guidance for future research.

Section snippets

Cardiovascular risk

As discussed by Eckardt and colleagues3 in this Series, chronic kidney disease is defined as impaired kidney function or raised proteinuria that are confirmed on two or more occasions at least 3 months apart. The estimated glomerular filtration rate is the recommended method of assessment. The preferred equation to calculate estimated glomerular filtration rate is that of the Chronic Kidney Disease Epidemiology Collaboration (commonly known as the CKD-EPI), which takes into account sex, age,

Pathophysiological mechanisms

Increased cardiovascular risk in individuals with chronic kidney disease is due partly to the high prevalence of traditional risk factors, such as hypertension and diabetes. The associations of kidney function and albuminuria with cardiovascular risk are, however, independent of these traditional cardiovascular risk factors. Thus, non-traditional kidney-specific mechanisms make notable contributions to cardiovascular risk. Elucidation of these mechanisms could reveal ways to lessen the

Prevention of cardiovascular disease

Cardiovascular disease can be prevented by lifestyle and pharmacological interventions. In low-income countries lifestyle modifications might be particularly useful. The prevention of cardiovascular disease in patients with chronic kidney disease is generally focused on achieving the best possible control of traditional cardiovascular risk factors (Table 1, Table 2). In view of the progressive increase in cardiovascular risk as kidney function declines, however, prevention of loss of kidney

Diagnosis and treatment of established cardiovascular disease

Patients with recognised symptoms of acute coronary syndromes are generally referred to hospital, where the diagnostic work-up routinely consists of electrocardiography, measurement of cardiac damage biomarkers, and, sometimes, coronary angiography. In cases of confirmed acute coronary syndrome, percutaneous thrombolysis or coronary artery bypass grafting are used, followed by medical treatment and lifestyle advice to prevent recurrence. Patients with chronic kidney disease are disadvantaged at

Future challenges and goals

Recommendations for prevention and treatment in patients with chronic kidney disease (Table 1, Table 2) are, unfortunately, based on only a small number of trials that have investigated cardiovascular disease specifically in populations of patients with chronic kidney disease. Most of these trials were underpowered to assess hard endpoints for clinical outcomes. Analyses of subpopulations of patients with chronic kidney disease in large cardiovascular randomised, controlled trials are sparse,

Conclusions

Since Bright's first description of the association between chronic kidney disease and cardiovascular disease, we have come a long way. Many epidemiological studies have confirmed this association and established that it is not only due to the fact that these two diseases share common risk factors, such as smoking, obesity, hypertension, hypercholesterolaemia, and diabetes. Mechanisms specific to chronic kidney disease promote vascular disease and, therefore, substantially increase the burden

Search strategy and selection criteria

We searched PubMed and Medline in April, 2012, with search terms that included but were not restricted to “chronic kidney disease”, “chronic kidney failure”, “glomerular filtration rate”, or “albuminuria”, in combination with “cardiovascular morbidity”, “cardiovascular mortality”, “cardiovascular risk”, “myocardial infarction”, or “heart failure”. Further publications were identified from references cited in relevant articles. We also relied on our own familiarity with the scientific

References (115)

  • A Levin et al.

    Prevalent LVH in the predialysis population: Identifying opportunities for intervention

    Am J Kidney Dis

    (1996)
  • A Levin et al.

    Cardiovascular disease in chronic renal insufficiency

    Am J Kidney Dis

    (2000)
  • C Drechsler et al.

    Changes in adiponectin and risk of sudden death, stroke, myocardial infarction, and mortality in hemodialysis patients

    Kidney Int

    (2009)
  • D Green et al.

    Sudden cardiac death in hemodialysis patients: an in-depth review

    Am J Kidney Dis

    (2011)
  • JT Kielstein et al.

    Asymmetric dimethylarginine: a cardiovascular risk factor and a uremic toxin coming of age?

    Am J Kidney Dis

    (2005)
  • C Zoccali et al.

    Left ventricular hypertrophy, cardiac remodeling and asymmetric dimethylarginine (ADMA) in hemodialysis patients

    Kidney Int

    (2002)
  • C Ronco et al.

    Cardiorenal syndrome

    J Am Coll Cardiol

    (2008)
  • AJ Bleyer et al.

    Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population

    Kidney Int

    (2000)
  • JE Heeg et al.

    Efficacy and variability of the antiproteinuric effect of ACE inhibition by lisinopril

    Kidney Int

    (1989)
  • CP Wen et al.

    Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study

    Lancet

    (2011)
  • D De Zeeuw et al.

    CKD treatment: time to alter the focus to albuminuria?

    Adv Chronic Kidney Dis

    (2011)
  • C Baigent et al.

    The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial

    Lancet

    (2011)
  • D De Zeeuw et al.

    Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial

    Lancet

    (2010)
  • K Yamagata et al.

    Risk factors for chronic kidney disease in a community-based population: a 10-year follow-up study

    Kidney Int

    (2007)
  • SI Hallan et al.

    Smoking is a risk factor in the progression to kidney failure

    Kidney Int

    (2011)
  • FJ He et al.

    Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials

    Lancet

    (2011)
  • M Postorino et al.

    Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease

    J Am Coll Cardiol

    (2009)
  • B Cianciaruso et al.

    Effect of a low- versus moderate-protein diet on progression of CKD: follow-up of a randomized controlled trial

    Am J Kidney Dis

    (2009)
  • AG Stack et al.

    Association of physical activity with mortality in the US dialysis population

    Am J Kidney Dis

    (2005)
  • AL Weigert et al.

    Uremic bleeding: pathogenesis and therapy

    Am J Med Sci

    (1998)
  • P DasMahapatra et al.

    Subclinical atherosclerotic changes related to chronic kidney disease in asymptomatic black and white young adults: the Bogalusa Heart Study

    Ann Epidemiol

    (2011)
  • DM Charytan et al.

    Clinical presentation of myocardial infarction contributes to lower use of coronary angiography in patients with chronic kidney disease

    Kidney Int

    (2007)
  • AJ Saltzman et al.

    Long-term impact of chronic kidney disease in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: the HORIZONS-AMI trial

    JACC Cardiovasc Interv

    (2011)
  • R Bright

    Cases and observations illustrative of renal disease accompanied with the secretion of albuminous urine

    Guy's Hospital Trans

    (1836)
  • J Harlos et al.

    Hypertension as cause and consequence of renal disease in the 19th century

    Am J Nephrol

    (1994)
  • K-U Eckardt et al.

    Evolving importance of kidney disease: from subspecialty to global health burden

    Lancet

    (2013)
  • KDIGO clinical practice guideline for evaluation and management of chronic kidney disease

    Kidney Int Suppl

    (2013)
  • K Matsushita et al.

    Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis

    Lancet

    (2010)
  • A Kottgen et al.

    Reduced kidney function as a risk factor for incident heart failure: the Atherosclerosis Risk In Communities (ARIC) study

    J Am Soc Nephrol

    (2007)
  • K Wattanakit et al.

    Kidney function and risk of peripheral arterial disease: results from the Atherosclerosis Risk In Communities (ARIC) study

    J Am Soc Nephrol

    (2007)
  • A Alonso et al.

    Chronic kidney disease is associated with the incidence of atrial fibrillation: the Atherosclerosis Risk In Communities (ARIC) study

    Circulation

    (2011)
  • MI Aguilar et al.

    Albuminuria and the risk of incident stroke and stroke types in older adults

    Neurology

    (2010)
  • SI Hallan et al.

    Age and association of kidney measures with mortality and end-stage renal disease

    JAMA

    (2012)
  • D Nitsch et al.

    Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

    BMJ

    (2013)
  • AS Go et al.

    Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

    N Engl J Med

    (2004)
  • SI Hallan et al.

    Association of kidney function and albuminuria with cardiovascular mortality in older versus younger individuals; the HUNT II study

    Arch Intern Med

    (2007)
  • Mahmoodi BK, Matsushita K, Woodward M, et al, for the Chronic Kidney Disease Prognosis Consortium, Associations of...
  • BR Hemmelgarn et al.

    Overview of the Alberta Kidney Disease Network

    BMC Nephrol

    (2009)
  • TC Turin et al.

    Chronic kidney disease and life expectancy

    Nephrol Dial Transplant

    (2012)
  • TC Turin et al.

    Proteinuria and life expectancy

    Am J Kidney Dis

    (2013)
  • Cited by (1532)

    View all citing articles on Scopus
    View full text