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خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده: مورد

Chronic kidney disease and coronary heart disease

Chronic kidney disease and coronary heart disease
Authors:
Mark Sarnak, MD
C Michael Gibson, MS, MD
Section Editors:
Gary C Curhan, MD, ScD
Bernard J Gersh, MB, ChB, DPhil, FRCP, MACC
Deputy Editor:
John P Forman, MD, MSc
Literature review current through: May 2025. | This topic last updated: Jun 12, 2025.

INTRODUCTION — 

Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease, and for more severe coronary heart disease (CHD) [1-5]. CKD is also associated with adverse outcomes in those with existing cardiovascular disease [6-8]. This includes increased mortality after an acute coronary syndrome, after percutaneous coronary intervention (PCI) with or without stenting [9-16], and after coronary artery bypass. In addition, patients with CKD are more likely to present with atypical symptoms, which may delay diagnosis and adversely affect outcomes [17,18].

An overview of CKD and CHD is presented in this topic review. Issues related to CHD in patients with end-stage kidney disease (ESKD) and general discussions of risk factors for cardiovascular disease and interventions for secondary prevention are presented separately:

●(See "Clinical manifestations and diagnosis of coronary artery disease in end-stage kidney disease (dialysis)".)

●(See "Risk factors and epidemiology of coronary heart disease in end-stage kidney disease (dialysis)".)

●(See "Overview of established risk factors for cardiovascular disease".)

●(See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)

CHRONIC KIDNEY DISEASE AS AN INDEPENDENT RISK FACTOR FOR CHD — 

Both decreased glomerular filtration rate (GFR) and increased proteinuria increase the risk of cardiovascular disease. These associations have been shown in both community-based populations (ie, cohorts that were not selected specifically to enroll individuals with CKD or cardiovascular disease), and in populations of patients at high cardiovascular risk (ie, cohorts in which patients with preexisting cardiovascular disease or cardiovascular disease risk factors were specifically recruited).

Association between CKD and CHD in community-based populations — Numerous observational studies have shown that a reduced GFR and proteinuria are both independently associated with an increased risk of cardiovascular events in community-based populations of patients who were not selected based upon the presence of known kidney or cardiovascular disease [1,6,19-56]. In addition, the association between CKD and cardiovascular events may be stronger among Black individuals as compared with White individuals [19,34,38,55].

A meta-analysis of general population cohorts that included 105,872 participants with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants with urine protein dipstick measurements; all had documented baseline estimated GFR [23]. Compared with participants whose estimated GFR was 95 mL/min/1.73 m2, hazard ratios (HR) for all-cause mortality during 7.9 years of follow-up were 1.18 (95% CI 1.05-1.32), 1.57 (95% CI 1.39-1.78), and 3.14 (95% CI 2.39-4.13) for estimated GFRs of 60, 45, and 15 mL/min per 1.73 m2, respectively. Similar outcomes were observed for cardiovascular mortality, and similar results were obtained in older and younger individuals (age greater than 65 years versus 65 years or less). A higher risk for all-cause mortality was observed at estimated GFRs greater than 105 mL/min per 1.73 m2; however, this association may reflect either reduced muscle mass from ill health leading to a lower creatinine value, or a high prevalence of individuals with diabetes or obesity causing hyperfiltration and a low creatinine [57].

Albuminuria was independently associated with increased all-cause and cardiovascular mortality in this study [23]. Compared with an albumin-to-creatinine ratio (ACR) of 0.6 mg/mmol (6 mg/g), the adjusted hazard ratio for all-cause mortality was 1.20 (95% CI 1.15-1.26); 1.63 (95% CI 1.50-1.77); and 2.20 (95% CI 1.97-2.51) for ACRs of 1.1 (10 mg/g); 3.4 (30 mg/g); and 33.9 mg/mmol (300 mg/g), respectively. Similar findings were observed for cardiovascular mortality. An ACR greater than 3.4 mg/mmol (30 mg/g) was associated with a greater than twofold mortality risk for all levels of estimated GFR except the lowest (<30 mL/min per 1.73 m2). Among participants with dipstick determination of proteinuria, a trace urine positive dipstick was also associated with increased all-cause and cardiovascular mortality for all levels of kidney function, although large heterogeneity was present between studies that provided only dipstick measurement of protein.

Given that CKD alone appears to increase the risk of CHD in the general population, it is not surprising that methods of analyzing future cardiovascular risk among individuals without CKD provide poor overall accuracy in predicting cardiovascular events in patients with CKD [58,59]. Estimation of cardiovascular risk, including methods that incorporate measures of kidney function, is presented elsewhere. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults" and "Cardiovascular disease risk assessment for primary prevention: Risk calculators".)

Association between CKD and CHD among those at high cardiovascular risk — Numerous secondary analyses of studies that enrolled patients with known risk factors for cardiovascular disease (such as hypertension and diabetes), or preexisting cardiovascular disease, have shown that the presence or development of various degrees of kidney dysfunction is independently associated with cardiovascular events [21,53,54,60-71]. In addition, accounting for estimated GFR and ACR in conjunction with traditional risk factors improves the ability to predict cardiovascular events in patients at high cardiovascular risk [60].

The magnitude of the association of kidney function, albuminuria, and outcomes was illustrated in a collaborative meta-analysis of 10 cohorts with 266,975 patients who had hypertension, diabetes, cardiovascular disease, or a combination of these disorders [61]. Compared with a reference estimated GFR of 95 mL/min per 1.73 m2, the hazard ratios for cardiovascular mortality were 1.11 for an estimated GFR of 60 mL/min per 1.73 m2, 1.73 for an estimated GFR of 45 mL/min per 1.73 m2, and 3.08 for an estimated GFR of 15 mL/min per 1.73 m2. Similar findings were noted for all-cause mortality, and the associations were similar in younger and older patients. A monotonic association between higher ACR and risk of both cardiovascular and all-cause mortality was also noted.

CKD as a CHD risk equivalent — The above evidence that mild to moderate CKD is associated with an adverse cardiovascular prognosis led both the National Kidney Foundation and the American College of Cardiology/American Heart Association to recommend in older guidelines that CKD be considered a CHD risk equivalent [1,72-75]. Consistent with this, the number of cardiovascular events attributable to CKD in the Alberta Kidney Disease Network and Atherosclerosis Risk In Communities (ARIC) studies were comparable to the number of events attributable to diabetes, another factor considered to be a CHD risk equivalent [38,76].

In addition, the nine-year rates of cardiovascular death among 1899 individuals in the Cardiovascular Health Study (CHS) were as follows (CKD was defined as an estimated GFR less than 60 mL/min per 1.73 m2) [77]:

●History of myocardial infarction, but no diabetes or CKD: 15.7 percent

●History of diabetes, but no myocardial infarction or CKD: 15.8 percent

●History of CKD, but no myocardial infarction or diabetes: 13 percent

Although CKD was a powerful risk factor for cardiovascular disease in these and other studies, the generalization that CKD is a CHD risk equivalent for all persons with CKD may not be warranted for several reasons:

●Some studies contradict the concept that CKD is a CHD risk equivalent. In the Alberta Kidney Disease Network cohort, for example, the four-year incidence of myocardial infarction was nearly threefold higher among those who had a prior history of myocardial infarction (7.7 percent) compared with those without a prior history of myocardial infarction but who had CKD (2.8 percent) [76]. The incidence of myocardial infarction among those who had a prior history of myocardial infarction but no diabetes and no CKD was more than twice the incidence among those with CKD but not prior myocardial infarction. Similarly, a secondary analysis from the ARIC study suggested that the risk associated with CKD was not comparable to the risk associated with a prior myocardial infarction [78].

●The risk of heart disease in those with CKD appears to vary based upon absolute level of kidney function and degree of proteinuria, as well as the rate at which these factors change. The simultaneous presence of both decreased kidney function and increased proteinuria further enhance the risk for cardiovascular disease compared with the risk associated with either problem alone [22-24,61,76]. In addition, the rate of decline of kidney function and the rate of increase of proteinuria also correlate with varying risks of adverse cardiovascular events [79-81].

●Even patients with the same degree of kidney dysfunction may not have the same risk of cardiovascular disease since the risk of cardiovascular disease in a patient with CKD is in part related to the presence and extent of significant comorbidities. As an example, the overall risk for a 25-year-old nonsmoking man with moderate CKD due to IgA nephropathy is not the same as that of a 65-year-old man with a similar degree of CKD but with a long history of smoking, hypertension, and elevated serum cholesterol levels. Thus, the proper assessment of overall cardiovascular risk in patients with CKD requires an adequate assessment for the presence and severity of the other major risk factors for cardiovascular disease. (See "Overview of established risk factors for cardiovascular disease".)

The concept of CHD risk equivalency was developed by expert panels as a means to help clinicians make decisions about how aggressively to treat their patients to prevent CHD [82]. As an example, while it is fairly simple to identify a patient who has diabetes or CKD, and thus institute aggressive therapy for secondary prevention of CHD, it is more cumbersome to calculate every patient's 10-year cardiovascular risk. Approximately half of adults in the United States with CKD have another CHD risk equivalent, specifically a prior history of myocardial infarction or stroke, diabetes, angina, or a calculated Framingham 10-year CHD risk greater than 20 percent [83]. Thus, the question of whether CKD is a CHD risk equivalent is germane to whether millions of additional patients with CKD should receive aggressive therapy to lower their LDL cholesterol and blood pressure, and whether they should receive antiplatelet therapy. In general, many expert panels are moving away from the concept of "risk equivalency" and are, instead, basing their recommendations for preventative therapies upon the predicted 10-year CHD risk. These issues are discussed in detail below. (See 'Reduction of CHD risk in patients with CKD' below.)

Limitations of the data — One possible limitation in nearly all of the above reports is that kidney function was indirectly estimated. Since the various estimates provide results that may differ from each other, the association between kidney function and cardiovascular risk is affected by the method selected to estimate kidney function. The association may be further compromised because some of the formulas utilized are based directly upon variables linked with cardiovascular risk, such as age, weight, and body mass index.

Another potential limitation of kidney function estimates in the vast majority of studies mentioned above is that level of GFR may not be accurately assessed using creatinine-based equations, particularly in those with estimated GFR values greater than 60 mL/min/1.73 m2. Estimation of kidney function is presented separately. (See "Assessment of kidney function".)

PRESENCE OF TRADITIONAL AND NONTRADITIONAL CARDIOVASCULAR RISK FACTORS IN CKD — 

Patients with CKD often have numerous traditional and nontraditional risk factors for the development of cardiovascular disease. Traditional risk factors appear to be associated with much larger absolute increases in risk in comparison with nontraditional risk factors in the earlier stages of CKD [84].

Traditional risk factors — Traditional cardiovascular risk factors, such as hypertension (which may be accompanied by left ventricular hypertrophy), smoking, diabetes, dyslipidemia and older age, are highly prevalent in CKD populations [1,85,86]. The number of cardiovascular risk factors appears to correlate with the severity of kidney dysfunction [86]. These are discussed in greater detail elsewhere. (See "Overview of hypertension in acute and chronic kidney disease" and "Overview of established risk factors for cardiovascular disease".)

Patients with CKD are also more likely to have the metabolic syndrome, which could contribute to the increase in cardiovascular risk [3,87]. This syndrome is defined as some combination of insulin resistance, dyslipidemia, elevated serum glucose, abdominal obesity, and hypertension. (See "Metabolic syndrome (insulin resistance syndrome or syndrome X)".)

Nontraditional risk factors — Possible risk factors that are relatively unique to patients with moderate to severe CKD include retention of uremic toxins, anemia, elevated levels of certain cytokines, positive calcium balance, abnormalities in bone mineral metabolism, and/or an "increased inflammatory-poor nutrition" state [4,88]. How these risk factors may lead to cardiovascular disease is unclear. As an example, disorders of bone mineral metabolism in patients with CKD have often been linked to coronary artery calcification. However, while there is a consistent association between CKD and a higher burden of coronary artery calcification [89-91], the associations among phosphorus, calcium, and parathyroid hormone with coronary artery calcification in these patients is inconsistent [92-94]. (See "Risk factors and epidemiology of coronary heart disease in end-stage kidney disease (dialysis)" and "Inflammation in patients with kidney function impairment" and "Coronary artery calcium (CAC) scoring: Overview and clinical utilization".)

Elevated levels of C-reactive protein (CRP) and asymmetric dimethylarginine, both of which are typically found in patients with CKD, were both independently associated with an increased risk of all-cause and cardiovascular mortality in the Modification of Diet in Renal Disease (MRDR) study [95,96], although a similar relation between CRP and cardiovascular disease was not observed in the Irbesartan for Diabetic Nephropathy trial [97]. Hyperhomocysteinemia has also been inconsistently associated with increased cardiovascular risk [98-100].

There is also a relationship between cardiovascular disease and moderately increased albuminuria (formerly called "microalbuminuria") among patients without diabetes with normal estimated GFR. However, some disagree with the KDOQI and KDIGO working groups that isolated moderately increased albuminuria (ie, without a reduction in GFR or some other kidney abnormality) necessarily reflects kidney disease among patients without diabetes [72]. It correlates best with generalized endothelial dysfunction and is associated with an increase in cardiovascular risk. (See "Overview of the management of chronic kidney disease in adults", section on 'Definition and classification' and "Moderately increased albuminuria (microalbuminuria) and cardiovascular disease".)

COMPETING RISKS OF CARDIOVASCULAR AND END-STAGE KIDNEY DISEASE — 

Morbidity and mortality from cardiovascular disease among those with CKD is high. The risk of death, particularly due to cardiovascular disease, is typically higher than the risk of eventually requiring kidney replacement therapy. However, this risk varies with age and other factors. In many studies, older patients with less severe CKD and lower levels of proteinuria are more likely to die (usually due to cardiovascular disease) before needing kidney replacement therapy, while younger patients with proteinuria and diseases localized to the kidney are more likely to ultimately need kidney replacement therapy [21,56,68,101-105]. This is illustrated by the following examples:

●The following three studies largely include older patients identified through Medicare participation or through the Veteran's Affairs Network:

•In a study of over 1,000,000 individuals enrolled in the Medicare program in the United States, outcomes were reported for several groups, including those with CKD but no diabetes (2.2 percent) and both CKD and diabetes (1.6 percent) [21]. After two years of follow-up, the rates for requiring kidney replacement therapy were 1.6 and 3.4 per 100 patient-years for patients with CKD alone and those with both disorders, respectively; by comparison, the death rates were 17.7 and 19.9 per 100 patient-years. In addition, rates for atherosclerotic vascular disease for these two groups were 35.7 and 49.1, while heart failure rates were 30.7 and 52.3, respectively.

•A longitudinal follow-up of nearly 30,000 older patients with estimated glomerular filtration rates (GFR) of less than 90 mL/min per 1.73 m2 reported the rate of kidney replacement and death at five years [101]. The rate of kidney replacement therapy in those with stage 2, 3, or 4 disease was 1.1, 1.3, and 19.9 percent, respectively; by comparison, the mortality rate was 19.5, 24.3, and 45.7 percent. A higher incidence of coronary artery disease, heart failure, diabetes mellitus, and anemia was noted in those who died.

•In a report of over 12,000 older patients with diabetes, 48 percent had CKD defined as GFR less than 60 mL/min per 1.73 m2, or proteinuria [102]. After three years of follow-up, mortality rates were 6, 10, 20 and 30 percent for patients with CKD stages 2, 3, 4 and 5, respectively, compared to 5 percent for those with preserved kidney function at baseline. Rates of progression to end-stage kidney disease (ESKD) were much lower, less than 1 percent for stages 2 and 3, and 14 percent for stage 4.

●The patients without diabetes in the MDRD study included a broad range of ages, causes of kidney disease, baseline GFR, and baseline protein excretion. After nearly 12 years of follow-up, 936 patients (56 percent) developed ESKD, and 369 (22 percent) died [106]. Death prior to ESKD was more likely to occur in older as compared with younger individuals. In those patients older than 65 years, for example, 42 percent developed ESKD and 22 percent died before developing ESKD. However, in those 45 years or younger, 65 percent developed ESKD and less than 1 percent died before developing ESKD.

●The following are two studies with long-term observations from two cohorts of younger individuals with type 1 diabetes and nephropathy:

•The rate of ESKD incidence was substantially greater than the mortality rate (35.5 versus 9.5 percent) in a cohort of 592 young (median age 42 years) patients with type 1 diabetes followed for 10 years [103]. All patients in this study had at least 300 mg/day of proteinuria, and 60 percent of patients had an estimated GFR less than 60 mL/min per 1.73 m2.

•Similar results were observed in a cohort of 423 young (median age 39 years) patients with type 1 diabetes, at least 300 mg/day of proteinuria, and a median baseline estimated GFR of 66 mL/min per 1.73 m2 [104]. During 15 years of follow-up, 41 percent of patients developed ESKD, while 7 percent died without developing ESKD.

Although these data suggest that age differences determine whether or not patients with CKD will develop ESKD before dying, this observation may be biased by study design. Patients enrolled into studies of cardiovascular disease tend to be older and have less severe kidney disease than patients enrolled into studies of kidney disease. In addition, older patients with severe kidney dysfunction are more likely to develop ESKD before dying, as was observed in 3228 older individuals with type 2 diabetes and nephropathy (mean age 59 years, estimated GFR 44 mL/min per 1.73 m2, and mean urine albumin-to-creatinine ratio 1.37 g/g) [107].

REDUCTION OF CHD RISK IN PATIENTS WITH CKD — 

In patients without CKD, risk factor modification and beneficial lifestyle changes can substantially decrease morbidity and mortality in those with coronary, cerebrovascular, or peripheral artery disease. These modalities, and the supporting evidence, are discuss elsewhere:

●Lifestyle modification (see "Prevention of cardiovascular disease events in those with established disease (secondary prevention)")

●Blood pressure control (see "Goal blood pressure in adults with hypertension", section on 'Patients with chronic kidney disease' and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of hypertension in patients with diabetes mellitus" and "Hypertension in adults: Initial drug therapy" and "Hypertension in adults: Antihypertensive medication titration")

●Statins (see "Lipid management in patients with nondialysis chronic kidney disease")

●Aspirin (see "Aspirin for the secondary prevention of atherosclerotic cardiovascular disease")

TREATMENT OF CORONARY HEART DISEASE — 

Patients with CKD require drug dose adjustments and have a higher risk of drug-related adverse effects. Despite the increased risk of adverse effects, the treatments used for established CHD and acute coronary syndrome that are used in patients with normal kidney function (eg, revascularization, medical therapy) usually have similar benefits in patients with CKD [108,109]. (See "Chronic coronary syndrome: Indications for revascularization" and "Chronic coronary syndrome: Overview of care" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction" and "Non-ST-elevation acute coronary syndromes: Selecting a management strategy" and "Coronary artery bypass graft surgery in patients with acute ST-elevation myocardial infarction".)

Multiple studies have reported that medical therapy commonly used in patients without CKD is employed significantly less frequently in patients with CKD [13,14,110-116]. As an example, a study of 889 patients with an acute coronary syndrome (ACS) evaluated the association between kidney dysfunction, defined as an estimated glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2, and in-hospital management and outcomes [14]. Kidney dysfunction was associated with a lower likelihood of receiving percutaneous coronary intervention, and a reduction in the use of a GP IIb/IIIa inhibitor, although the frequency of coronary artery bypass grafting was similar in those with and without kidney dysfunction. Less frequent utilization of angiography, revascularization, and standard medical therapy (eg, angiotensin-converting enzyme inhibitors, beta blockers) in patients with CKD after ACS has also been observed in other studies [110,115,116].

However, not all of the usual treatments used in patients with normal kidney function should be universally applied in patients with CKD. As an example, a meta-analysis of 9969 patients with CKD who were having an ACS or percutaneous coronary intervention found that the use of glycoprotein IIb/IIIa inhibitors or clopidogrel increased major bleeding episodes without preventing cardiovascular events or death [117]. In addition, automated implantable defibrillators may not provide a survival advantage in patients with CKD [118-120].

PROGNOSIS OF CORONARY HEART DISEASE IN PATIENTS WITH CKD — 

A pervasive finding among patients who suffer coronary events or who have coronary interventions is that those with impaired kidney function have a worse prognosis. The mechanisms which underlie the poor prognosis in patients with CKD are not entirely clear.

One possibility is that patients who have a coronary event and abnormal kidney function are more likely to have other predictors of adverse outcomes such as older age, hypotension, and lower body weight; these factors may confound the associations observed in the various studies despite statistical adjustment. A second potential explanation is that the adverse outcome (eg, death, recurrent vascular event) ascribed to worse kidney function may instead reflect a more severe acute coronary syndrome (ACS). Because only baseline creatinine values (at the time of presentation with an ACS) were used in most studies to define the presence of CKD, patients with hemodynamic compromise would have been more likely to be defined as having CKD. The formulas used to estimate glomerular filtration rate (GFR) based upon serum creatinine are predicated on there being a stable creatinine concentration. (See "Assessment of kidney function".)

Prognosis after acute coronary syndrome — An adverse association between mild to moderate kidney dysfunction and cardiovascular prognosis in patients with ACS has been reported, both in patients with ST elevation myocardial infarction and non-ST elevation ACS. This is discussed in detail elsewhere. (See "Risk factors for adverse outcomes after non-ST elevation acute coronary syndromes", section on 'Chronic kidney disease' and "Risk factors for adverse outcomes after ST-elevation myocardial infarction", section on 'Chronic kidney disease'.)

Prognosis after CABG — Although there are some reports of equivalent outcomes [121], most studies demonstrate that decreased kidney function at the time of coronary artery bypass grafting (CABG) is associated with higher risk of adverse outcomes [111,122]. As a consequence, kidney function is included in a commonly used risk prediction algorithm for cardiac surgical mortality (table 1). (See "Operative mortality after coronary artery bypass graft surgery", section on 'Chronic kidney disease'.)

In-hospital complication rates and in-hospital as well as long-term mortality are highest among patients on dialysis [123-126].

Patients with CKD who develop acute kidney injury after CABG may require temporary or permanent dialysis. This issue is discussed elsewhere. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Acute kidney injury'.)

Prognosis after PCI — The presence of even mild CKD appears to predict an adverse prognosis after percutaneous coronary intervention (PCI) with or without stenting [15,16,127-130], and kidney function is incorporated into a commonly used risk score that predicts one-year mortality following PCI in patients with acute myocardial infarction (table 2). (See "Intracoronary stent restenosis", section on 'Clinical factors'.)

The observation that revascularization for restenosis is required less frequently when stents are deployed has been made in patients with CKD as it has in patients with normal kidney function [131]. In addition, CKD does not appear to mitigate the angiographic benefits observed with drug-eluting stents [132,133]. (See "Percutaneous coronary intervention with intracoronary stents: Overview".)

A separate issue is whether the presence of CKD is associated with higher rates of restenosis. While some studies have found an increased risk of restenosis in patients with CKD [130,134], other studies have reported that CKD is not associated with increased restenosis [127,132].

PCI versus CABG in patients with CKD — The choice of revascularization approach in patients with stable coronary disease is discussed elsewhere. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

INCREASED SERUM CARDIAC ENZYMES AND ACUTE CORONARY EVENTS — 

Cardiac troponins are the preferred marker for the diagnosis of myocardial injury among patients with normal kidney function because of their increased specificity compared with CK-MB and other markers. (See "Troponin testing: Clinical use".)

Cardiac troponins are also used in the diagnosis of myocardial infarction in patients with CKD and a suspected acute coronary syndrome, although minor chronic elevations in serum troponins are commonly observed in patients with CKD who do not have clinical evidence of a myocardial infarction. These issues are discussed in detail separately. (See "Cardiac troponins in patients with kidney disease".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)

SUMMARY

●Chronic kidney disease (CKD) as a risk factor for coronary heart disease (CHD) – Both decreased glomerular filtration rate (GFR) and increased proteinuria increase the risk of cardiovascular disease. These associations have been shown in both community-based populations (ie, cohorts that were not selected specifically to enroll individuals with CKD or cardiovascular disease) and in populations of patients at high cardiovascular risk (ie, cohorts in which patients with preexisting cardiovascular disease or cardiovascular disease risk factors were specifically recruited). (See 'Chronic kidney disease as an independent risk factor for CHD' above.)

Patients with CKD often have numerous traditional and nontraditional risk factors for the development of cardiovascular disease. Traditional risk factors (hypertension, smoking, diabetes, dyslipidemia, and older age) appear to be more important risk factors during the earlier stages of CKD. Nontraditional risk factors include uremic toxins, anemia, elevated levels of certain cytokines, an increased calcium load, abnormalities in bone mineral metabolism, and/or an increased inflammatory-poor nutrition state. (See 'Presence of traditional and nontraditional cardiovascular risk factors in CKD' above.)

Among those with CKD, the risk of death, particularly due to cardiovascular disease, is typically higher than the risk of eventually requiring kidney replacement therapy. However, this risk varies with age and other factors. In many studies, older patients with less severe CKD and lower levels of proteinuria are more likely to die (usually due to cardiovascular disease) before needing kidney replacement therapy, while younger patients with proteinuria and diseases localized to the kidney are more likely to ultimately need kidney replacement therapy. (See 'Competing risks of cardiovascular and end-stage kidney disease' above.)

●CHD risk reduction in CKD – Our general approach to reduce the risk of atherosclerotic cardiovascular disease in most patients with CKD not requiring dialysis includes lifestyle modification, blood pressure control, lipid management and, in some patients, antiplatelet therapy. (See 'Reduction of CHD risk in patients with CKD' above.)

●Treatment of CHD in CKD – Patients with CKD require drug dose adjustments and have a higher risk of drug-related adverse effects. Despite the increased risk of adverse effects, the treatments used for established CHD and acute coronary syndrome that are used in patients with normal kidney function (eg, revascularization) may have similar benefits in patients with CKD. (See 'Treatment of coronary heart disease' above.)

●Prognosis of CHD in CKD – Patients with CKD who suffer an acute coronary syndrome or who have coronary interventions (ie, coronary artery bypass grafting, percutaneous coronary intervention [PCI]) have a worse prognosis than patients with normal kidney function who have similar events or procedures (table 1 and table 2). The mechanisms which underlie the poor prognosis in patients with CKD are not entirely clear. (See 'Prognosis of coronary heart disease in patients with CKD' above.)

ACKNOWLEDGMENT — 

We are saddened by the death of William Henrich, MD, MACP, who passed away in July 2024. UpToDate acknowledges Dr. Henrich's past work as an author of this topic.

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  29. Wong TY, Coresh J, Klein R, et al. Retinal microvascular abnormalities and renal dysfunction: the atherosclerosis risk in communities study. J Am Soc Nephrol 2004; 15:2469.
  30. Hillege HL, Fidler V, Diercks GF, et al. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106:1777.
  31. Knight EL, Rimm EB, Pai JK, et al. Kidney dysfunction, inflammation, and coronary events: a prospective study. J Am Soc Nephrol 2004; 15:1897.
  32. Henry RM, Kostense PJ, Bos G, et al. Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int 2002; 62:1402.
  33. Fox CS, Larson MG, Keyes MJ, et al. Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: the Framingham Heart Study. Kidney Int 2004; 66:2017.
  34. Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004; 15:1307.
  35. Tonelli M, Wiebe N, Culleton B, et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 2006; 17:2034.
  36. Hallan SI, Dahl K, Oien CM, et al. Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey. BMJ 2006; 333:1047.
  37. Van Biesen W, De Bacquer D, Verbeke F, et al. The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years. Eur Heart J 2007; 28:478.
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  46. Fried LF, Katz R, Sarnak MJ, et al. Kidney function as a predictor of noncardiovascular mortality. J Am Soc Nephrol 2005; 16:3728.
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  52. Hemmelgarn BR, Manns BJ, Lloyd A, et al. Relation between kidney function, proteinuria, and adverse outcomes. JAMA 2010; 303:423.
  53. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 2012; 380:1662.
  54. Mahmoodi BK, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet 2012; 380:1649.
  55. Gutiérrez OM, Khodneva YA, Muntner P, et al. Association between urinary albumin excretion and coronary heart disease in black vs white adults. JAMA 2013; 310:706.
  56. Thomas B, Matsushita K, Abate KH, et al. Global Cardiovascular and Renal Outcomes of Reduced GFR. J Am Soc Nephrol 2017; 28:2167.
  57. Leoncini G, Viazzi F, Pontremoli R. Overall health assessment: a renal perspective. Lancet 2010; 375:2053.
  58. Weiner DE, Tighiouart H, Elsayed EF, et al. The Framingham predictive instrument in chronic kidney disease. J Am Coll Cardiol 2007; 50:217.
  59. Chang A, Kramer H. Should eGFR and albuminuria be added to the Framingham risk score? Chronic kidney disease and cardiovascular disease risk prediction. Nephron Clin Pract 2011; 119:c171.
  60. Matsushita K, Coresh J, Sang Y, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol 2015; 3:514.
  61. van der Velde M, Matsushita K, Coresh J, et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 2011; 79:1341.
  62. Mann JF, Gerstein HC, Pogue J, et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001; 134:629.
  63. Segura J, Campo C, Gil P, et al. Development of chronic kidney disease and cardiovascular prognosis in essential hypertensive patients. J Am Soc Nephrol 2004; 15:1616.
  64. Ruilope LM, Salvetti A, Jamerson K, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study. J Am Soc Nephrol 2001; 12:218.
  65. Beddhu S, Allen-Brady K, Cheung AK, et al. Impact of renal failure on the risk of myocardial infarction and death. Kidney Int 2002; 62:1776.
  66. Knobler H, Zornitzki T, Vered S, et al. Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria. J Am Coll Cardiol 2004; 44:2142.
  67. Kong AP, So WY, Szeto CC, et al. Assessment of glomerular filtration rate in addition to albuminuria is important in managing type II diabetes. Kidney Int 2006; 69:383.
  68. Rahman M, Pressel S, Davis BR, et al. Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate. Ann Intern Med 2006; 144:172.
  69. Perkovic V, Ninomiya T, Arima H, et al. Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study. J Am Soc Nephrol 2007; 18:2766.
  70. Schneider CA, Ferrannini E, Defronzo R, et al. Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. J Am Soc Nephrol 2008; 19:182.
  71. Weiner DE, Tighiouart H, Stark PC, et al. Kidney disease as a risk factor for recurrent cardiovascular disease and mortality. Am J Kidney Dis 2004; 44:198.
  72. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39:S1.
  73. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110:588.
  74. Levey AS, Beto JA, Coronado BE, 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? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 1998; 32:853.
  75. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003; 139:137.
  76. Tonelli M, Muntner P, Lloyd A, et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 2012; 380:807.
  77. Rashidi A, Sehgal AR, Rahman M, O'Connor AS. The case for chronic kidney disease, diabetes mellitus, and myocardial infarction being equivalent risk factors for cardiovascular mortality in patients older than 65 years. Am J Cardiol 2008; 102:1668.
  78. Wattanakit K, Coresh J, Muntner P, et al. Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction. J Am Coll Cardiol 2006; 48:1183.
  79. Matsushita K, Selvin E, Bash LD, et al. Change in estimated GFR associates with coronary heart disease and mortality. J Am Soc Nephrol 2009; 20:2617.
  80. Shlipak MG, Katz R, Kestenbaum B, et al. Rapid decline of kidney function increases cardiovascular risk in the elderly. J Am Soc Nephrol 2009; 20:2625.
  81. Schmieder RE, Mann JF, Schumacher H, et al. Changes in albuminuria predict mortality and morbidity in patients with vascular disease. J Am Soc Nephrol 2011; 22:1353.
  82. Tonelli M. Should CKD be a coronary heart disease risk equivalent? Am J Kidney Dis 2007; 49:8.
  83. Hyre AD, Fox CS, Astor BC, et al. The impact of reclassifying moderate CKD as a coronary heart disease risk equivalent on the number of US adults recommended lipid-lowering treatment. Am J Kidney Dis 2007; 49:37.
  84. Shlipak MG, Fried LF, Cushman M, et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA 2005; 293:1737.
  85. Muntner P, He J, Astor BC, et al. Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease: results from the atherosclerosis risk in communities study. J Am Soc Nephrol 2005; 16:529.
  86. Foley RN, Wang C, Collins AJ. Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES III study. Mayo Clin Proc 2005; 80:1270.
  87. Kobayashi S, Maesato K, Moriya H, et al. Insulin resistance in patients with chronic kidney disease. Am J Kidney Dis 2005; 45:275.
  88. Becker B, Kronenberg F, Kielstein JT, et al. Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study. J Am Soc Nephrol 2005; 16:1091.
  89. Schwarz U, Buzello M, Ritz E, et al. Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000; 15:218.
  90. Nakamura S, Ishibashi-Ueda H, Niizuma S, et al. Coronary calcification in patients with chronic kidney disease and coronary artery disease. Clin J Am Soc Nephrol 2009; 4:1892.
  91. Nakano T, Ninomiya T, Sumiyoshi S, et al. Association of kidney function with coronary atherosclerosis and calcification in autopsy samples from Japanese elders: the Hisayama study. Am J Kidney Dis 2010; 55:21.
  92. Russo D, Palmiero G, De Blasio AP, et al. Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 2004; 44:1024.
  93. Tomiyama C, Higa A, Dalboni MA, et al. The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients. Nephrol Dial Transplant 2006; 21:2464.
  94. Dellegrottaglie S, Saran R, Gillespie B, et al. Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study). Am J Cardiol 2006; 98:571.
  95. Menon V, Greene T, Wang X, et al. C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease. Kidney Int 2005; 68:766.
  96. Young JM, Terrin N, Wang X, et al. Asymmetric dimethylarginine and mortality in stages 3 to 4 chronic kidney disease. Clin J Am Soc Nephrol 2009; 4:1115.
  97. Friedman AN, Hunsicker LG, Selhub J, et al. C-reactive protein as a predictor of total arteriosclerotic outcomes in type 2 diabetic nephropathy. Kidney Int 2005; 68:773.
  98. Ducloux D, Motte G, Challier B, et al. Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study. J Am Soc Nephrol 2000; 11:134.
  99. Menon V, Sarnak MJ, Greene T, et al. Relationship between homocysteine and mortality in chronic kidney disease. Circulation 2006; 113:1572.
  100. Shishehbor MH, Oliveira LP, Lauer MS, et al. Emerging cardiovascular risk factors that account for a significant portion of attributable mortality risk in chronic kidney disease. Am J Cardiol 2008; 101:1741.
  101. Keith DS, Nichols GA, Gullion CM, et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164:659.
  102. Patel UD, Young EW, Ojo AO, Hayward RA. CKD progression and mortality among older patients with diabetes. Am J Kidney Dis 2005; 46:406.
  103. Forsblom C, Harjutsalo V, Thorn LM, et al. Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol 2011; 22:537.
  104. Rosolowsky ET, Skupien J, Smiles AM, et al. Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol 2011; 22:545.
  105. De Nicola L, Minutolo R, Chiodini P, et al. The effect of increasing age on the prognosis of non-dialysis patients with chronic kidney disease receiving stable nephrology care. Kidney Int 2012; 82:482.
  106. Menon V, Wang X, Sarnak MJ, et al. Long-term outcomes in nondiabetic chronic kidney disease. Kidney Int 2008; 73:1310.
  107. Packham DK, Alves TP, Dwyer JP, et al. Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. Am J Kidney Dis 2012; 59:75.
  108. Washam JB, Herzog CA, Beitelshees AL, et al. Pharmacotherapy in chronic kidney disease patients presenting with acute coronary syndrome: a scientific statement from the American Heart Association. Circulation 2015; 131:1123.
  109. Bangalore S, Maron DJ, O'Brien SM, et al. Management of Coronary Disease in Patients with Advanced Kidney Disease. N Engl J Med 2020; 382:1608.
  110. Weisbord SD, Mor MK, Hochheiser H, et al. Utilization and Outcomes of Clinically Indicated Invasive Cardiac Care in Veterans with Acute Coronary Syndrome and Chronic Kidney Disease. J Am Soc Nephrol 2023; 34:694.
  111. Gibney EM, Casebeer AW, Schooley LM, et al. Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: a national Veterans Administration study. Kidney Int 2005; 68:826.
  112. Newsome BB, Warnock DG, Kiefe CI, et al. Delay in time to receipt of thrombolytic medication among Medicare patients with kidney disease. Am J Kidney Dis 2005; 46:595.
  113. Han JH, Chandra A, Mulgund J, et al. Chronic kidney disease in patients with non-ST-segment elevation acute coronary syndromes. Am J Med 2006; 119:248.
  114. Patel UD, Ou FS, Ohman EM, et al. Hospital performance and differences by kidney function in the use of recommended therapies after non-ST-elevation acute coronary syndromes. Am J Kidney Dis 2009; 53:426.
  115. Charytan D, Mauri L, Agarwal A, et al. The use of invasive cardiac procedures after acute myocardial infarction in long-term dialysis patients. Am Heart J 2006; 152:558.
  116. Fox CS, Muntner P, Chen AY, et al. Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry. Circulation 2010; 121:357.
  117. Palmer SC, Di Micco L, Razavian M, et al. Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012; 156:445.
  118. Jukema JW, Timal RJ, Rotmans JI, et al. Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients. Circulation 2019; 139:2628.
  119. Bansal N, Szpiro A, Reynolds K, et al. Long-term Outcomes Associated With Implantable Cardioverter Defibrillator in Adults With Chronic Kidney Disease. JAMA Intern Med 2018; 178:390.
  120. Pun PH, Al-Khatib SM, Han JY, 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; 64:32.
  121. Tabata M, Takanashi S, Fukui T, et al. Off-pump coronary artery bypass grafting in patients with renal dysfunction. Ann Thorac Surg 2004; 78:2044.
  122. Zakeri R, Freemantle N, Barnett V, et al. Relation between mild renal dysfunction and outcomes after coronary artery bypass grafting. Circulation 2005; 112:I270.
  123. Anderson RJ, O'brien M, MaWhinney S, et al. Renal failure predisposes patients to adverse outcome after coronary artery bypass surgery. VA Cooperative Study #5. Kidney Int 1999; 55:1057.
  124. Dacey LJ, Liu JY, Braxton JH, et al. Long-term survival of dialysis patients after coronary bypass grafting. Ann Thorac Surg 2002; 74:458.
  125. Liu JY, Birkmeyer NJ, Sanders JH, et al. Risks of morbidity and mortality in dialysis patients undergoing coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group. Circulation 2000; 102:2973.
  126. Massad MG, Kpodonu J, Lee J, et al. Outcome of coronary artery bypass operations in patients with renal insufficiency with and without renal transplantation. Chest 2005; 128:855.
  127. Pinkau T, Mann JF, Ndrepepa G, et al. Coronary revascularization in patients with renal insufficiency: restenosis rate and cardiovascular outcomes. Am J Kidney Dis 2004; 44:627.
  128. Ix JH, Mercado N, Shlipak MG, et al. Association of chronic kidney disease with clinical outcomes after coronary revascularization: the Arterial Revascularization Therapies Study (ARTS). Am Heart J 2005; 149:512.
  129. Lemos PA, Arampatzis CA, Hoye A, et al. Impact of baseline renal function on mortality after percutaneous coronary intervention with sirolimus-eluting stents or bare metal stents. Am J Cardiol 2005; 95:167.
  130. Attallah N, Yassine L, Fisher K, Yee J. Risk of bleeding and restenosis among chronic kidney disease patients undergoing percutaneous coronary intervention. Clin Nephrol 2005; 64:412.
  131. Stigant C, Izadnegahdar M, Levin A, et al. Outcomes after percutaneous coronary interventions in patients with CKD: improved outcome in the stenting era. Am J Kidney Dis 2005; 45:1002.
  132. Halkin A, Mehran R, Casey CW, et al. Impact of moderate renal insufficiency on restenosis and adverse clinical events after paclitaxel-eluting and bare metal stent implantation: results from the TAXUS-IV Trial. Am Heart J 2005; 150:1163.
  133. Charytan DM, Varma MR, Silbaugh TS, et al. Long-term clinical outcomes following drug-eluting or bare-metal stent placement in patients with severely reduced GFR: Results of the Massachusetts Data Analysis Center (Mass-DAC) State Registry. Am J Kidney Dis 2011; 57:202.
  134. Charytan D, Forman JP, Cutlip DE. Risk of target lesion revascularization after coronary stenting in patients with and without chronic kidney disease. Nephrol Dial Transplant 2007; 22:2578.
Topic 7190 Version 38.0

References

1 : Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.

2 : USRDS 2009 Annual Data report: Atlas of end-stage renal disease in the United States

3 : The metabolic syndrome and chronic kidney disease in U.S. adults.

4 : The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction.

5 : Association between renal insufficiency and inducible ischemia in patients with coronary artery disease: the heart and soul study.

6 : Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States.

7 : A population-based study of the incidence and outcomes of diagnosed chronic kidney disease.

8 : Creatinine levels and cardiovascular events in women with heart disease: do small changes matter?

9 : Association of renal insufficiency with treatment and outcomes after myocardial infarction in elderly patients.

10 : Acute myocardial infarction and renal dysfunction: a high-risk combination.

11 : Prognostic implications of abnormalities in renal function in patients with acute coronary syndromes.

12 : Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality.

13 : Emergency evaluation of chest pain in patients with advanced kidney disease.

14 : Influence of concurrent renal dysfunction on outcomes of patients with acute coronary syndromes and implications of the use of glycoprotein IIb/IIIa inhibitors.

15 : The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.

16 : Grade of chronic renal failure, and acute and long-term outcome after percutaneous coronary interventions.

17 : Differential symptoms of acute myocardial infarction in patients with kidney disease: a community-wide perspective.

18 : Clinical characteristics of dialysis patients with acute myocardial infarction in the United States: a collaborative project of the United States Renal Data System and the National Registry of Myocardial Infarction.

19 : Association of Estimated GFR Calculated Using Race-Free Equations With Kidney Failure and Mortality by Black vs Non-Black Race.

20 : Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review.

21 : Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999.

22 : Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.

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

24 : Using proteinuria and estimated glomerular filtration rate to classify risk in patients with chronic kidney disease: a cohort study.

25 : How does minor renal dysfunction influence cardiovascular risk and the management of cardiovascular disease?

26 : Level of kidney function as a risk factor for cardiovascular outcomes in the elderly.

27 : Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.

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

29 : Retinal microvascular abnormalities and renal dysfunction: the atherosclerosis risk in communities study.

30 : Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.

31 : Kidney dysfunction, inflammation, and coronary events: a prospective study.

32 : Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study.

33 : Kidney function is inversely associated with coronary artery calcification in men and women free of cardiovascular disease: the Framingham Heart Study.

34 : Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies.

35 : Chronic kidney disease and mortality risk: a systematic review.

36 : Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey.

37 : The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years.

38 : Kidney disease, Framingham risk scores, and cardiac and mortality outcomes.

39 : Independent components of chronic kidney disease as a cardiovascular risk state: results from the Kidney Early Evaluation Program (KEEP).

40 : Renal insufficiency and mortality in patients with known or suspected coronary artery disease.

41 : Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons.

42 : The relationships of proteinuria, serum creatinine, glomerular filtration rate with cardiovascular disease mortality in Japanese general population.

43 : Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial.

44 : Cystatin C and the risk of death and cardiovascular events among elderly persons.

45 : Cystatin C concentration as a risk factor for heart failure in older adults.

46 : Kidney function as a predictor of noncardiovascular mortality.

47 : Cystatin C and subclinical brain infarction.

48 : Renal function and heart failure risk in older black and white individuals: the Health, Aging, and Body Composition Study.

49 : Cystatin C as a risk factor for outcomes in chronic kidney disease.

50 : Method of glomerular filtration rate estimation affects prediction of mortality risk.

51 : Cystatin C identifies chronic kidney disease patients at higher risk for complications.

52 : Relation between kidney function, proteinuria, and adverse outcomes.

53 : Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis.

54 : Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.

55 : Association between urinary albumin excretion and coronary heart disease in black vs white adults.

56 : Global Cardiovascular and Renal Outcomes of Reduced GFR.

57 : Overall health assessment: a renal perspective.

58 : The Framingham predictive instrument in chronic kidney disease.

59 : Should eGFR and albuminuria be added to the Framingham risk score? Chronic kidney disease and cardiovascular disease risk prediction.

60 : Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

61 : Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

62 : Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.

63 : Development of chronic kidney disease and cardiovascular prognosis in essential hypertensive patients.

64 : Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study.

65 : Impact of renal failure on the risk of myocardial infarction and death.

66 : Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria.

67 : Assessment of glomerular filtration rate in addition to albuminuria is important in managing type II diabetes.

68 : Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

69 : Chronic kidney disease, cardiovascular events, and the effects of perindopril-based blood pressure lowering: data from the PROGRESS study.

70 : Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease.

71 : Kidney disease as a risk factor for recurrent cardiovascular disease and mortality.

72 : K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

73 : ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).

74 : 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? National Kidney Foundation Task Force on Cardiovascular Disease.

75 : National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

76 : Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study.

77 : The case for chronic kidney disease, diabetes mellitus, and myocardial infarction being equivalent risk factors for cardiovascular mortality in patients older than 65 years.

78 : Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction.

79 : Change in estimated GFR associates with coronary heart disease and mortality.

80 : Rapid decline of kidney function increases cardiovascular risk in the elderly.

81 : Changes in albuminuria predict mortality and morbidity in patients with vascular disease.

82 : Should CKD be a coronary heart disease risk equivalent?

83 : The impact of reclassifying moderate CKD as a coronary heart disease risk equivalent on the number of US adults recommended lipid-lowering treatment.

84 : Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors.

85 : Traditional and nontraditional risk factors predict coronary heart disease in chronic kidney disease: results from the atherosclerosis risk in communities study.

86 : Cardiovascular risk factor profiles and kidney function stage in the US general population: the NHANES III study.

87 : Insulin resistance in patients with chronic kidney disease.

88 : Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study.

89 : Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.

90 : Coronary calcification in patients with chronic kidney disease and coronary artery disease.

91 : Association of kidney function with coronary atherosclerosis and calcification in autopsy samples from Japanese elders: the Hisayama study.

92 : Coronary artery calcification in patients with CRF not undergoing dialysis.

93 : The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients.

94 : Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study).

95 : C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.

96 : Asymmetric dimethylarginine and mortality in stages 3 to 4 chronic kidney disease.

97 : C-reactive protein as a predictor of total arteriosclerotic outcomes in type 2 diabetic nephropathy.

98 : Serum total homocysteine and cardiovascular disease occurrence in chronic, stable renal transplant recipients: a prospective study.

99 : Relationship between homocysteine and mortality in chronic kidney disease.

100 : Emerging cardiovascular risk factors that account for a significant portion of attributable mortality risk in chronic kidney disease.

101 : Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization.

102 : CKD progression and mortality among older patients with diabetes.

103 : Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria.

104 : Risk for ESRD in type 1 diabetes remains high despite renoprotection.

105 : The effect of increasing age on the prognosis of non-dialysis patients with chronic kidney disease receiving stable nephrology care.

106 : Long-term outcomes in nondiabetic chronic kidney disease.

107 : Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database.

108 : Pharmacotherapy in chronic kidney disease patients presenting with acute coronary syndrome: a scientific statement from the American Heart Association.

109 : Management of Coronary Disease in Patients with Advanced Kidney Disease.

110 : Utilization and Outcomes of Clinically Indicated Invasive Cardiac Care in Veterans with Acute Coronary Syndrome and Chronic Kidney Disease.

111 : Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: a national Veterans Administration study.

112 : Delay in time to receipt of thrombolytic medication among Medicare patients with kidney disease.

113 : Chronic kidney disease in patients with non-ST-segment elevation acute coronary syndromes.

114 : Hospital performance and differences by kidney function in the use of recommended therapies after non-ST-elevation acute coronary syndromes.

115 : The use of invasive cardiac procedures after acute myocardial infarction in long-term dialysis patients.

116 : Use of evidence-based therapies in short-term outcomes of ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction in patients with chronic kidney disease: a report from the National Cardiovascular Data Acute Coronary Treatment and Intervention Outcomes Network registry.

117 : Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis.

118 : Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients.

119 : Long-term Outcomes Associated With Implantable Cardioverter Defibrillator in Adults With Chronic Kidney Disease.

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

121 : Off-pump coronary artery bypass grafting in patients with renal dysfunction.

122 : Relation between mild renal dysfunction and outcomes after coronary artery bypass grafting.

123 : Renal failure predisposes patients to adverse outcome after coronary artery bypass surgery. VA Cooperative Study #5.

124 : Long-term survival of dialysis patients after coronary bypass grafting.

125 : Risks of morbidity and mortality in dialysis patients undergoing coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.

126 : Outcome of coronary artery bypass operations in patients with renal insufficiency with and without renal transplantation.

127 : Coronary revascularization in patients with renal insufficiency: restenosis rate and cardiovascular outcomes.

128 : Association of chronic kidney disease with clinical outcomes after coronary revascularization: the Arterial Revascularization Therapies Study (ARTS).

129 : Impact of baseline renal function on mortality after percutaneous coronary intervention with sirolimus-eluting stents or bare metal stents.

130 : Risk of bleeding and restenosis among chronic kidney disease patients undergoing percutaneous coronary intervention.

131 : Outcomes after percutaneous coronary interventions in patients with CKD: improved outcome in the stenting era.

132 : Impact of moderate renal insufficiency on restenosis and adverse clinical events after paclitaxel-eluting and bare metal stent implantation: results from the TAXUS-IV Trial.

133 : Long-term clinical outcomes following drug-eluting or bare-metal stent placement in patients with severely reduced GFR: Results of the Massachusetts Data Analysis Center (Mass-DAC) State Registry.

134 : Risk of target lesion revascularization after coronary stenting in patients with and without chronic kidney disease.

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