Chronic Kidney Disease as a Risk Factor for Cardiovascular Disease and All-Cause Mortality

Study design:

This particular research activity was conducted using the secondary evaluation of four community-based, longitudinal public-use data sets in order to determine the relationship of baseline kidney function and long-term risk of cardiovascular disease (CVD) and all-cause mortality. As such, the researchers included the AtherosclerosisRisk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the Framingham Heart Study (FHS), and the Framingham Offspring Study (Offspring) as data pool that were analysed accordingly as studies that have meticulous ascertainment of CVD events during theirfollow-up periods.

Background/Objectives:

The completion of the research activity was grounded on the attainment of the following research objectives that likewise state the purpose of the study:

To pool the findings fromseveral large community-based cohort studies.

To evaluate moresystematically whether chronic kidney disease (CKD), as quantified by estimated GFR,is a risk factor for CVD.

To investigate the effect of moderate and severeCKD outcomes in subjects without CVD at baseline.

To identify high-risk subgroups particularly the differences between blackand white subjects as a trend toward a differing impact of CKD.

Population number and social demographic parameters:

Since the study was completed based on previously conducted research activities, the sampling population was directly sampled from the techniques used by the cohorts. The population included the following:

Between 1987 and 1989, ARIC enrolled 15,792 participants aged45 to 64 yr from Jackson, Mississippi; Forsyth County, NorthCarolina; the northwestern suburbs of Minneapolis, Minnesota;and Washington County, Maryland. (The Mississippi cohort is entirelyblack and composes >80% of the black individuals in ARIC.)

CHS is a population-based study of 5201 subjects 65 yr and olderrandomly selected from Medicare eligibility files during 1989and 1990 from four different communities: Sacramento County,California; Washington County, Maryland; Forsyth County, NorthCarolina; and Pittsburgh, Pennsylvania. (An additional 687 blackswere recruited in 1992 and 1993. )

FHS began in 1948 with 5209 residents of Framingham, Massachusetts, aged 28 to 62 yr. Serum creatinine levels were initially assessed at the 15th biennial examination (1977–1979; n = 2632) in FHS.

Offspring recruited5124 of the children and the spouses of children of FHS participantsin 1971, and serum creatinine was assessed at the second examination (1979–1983; n = 3863).

The 15th examinationin FHS and the second examination in Offspring were consideredto be the baseline period for our current analysis.

Sampling frame and sampling strategy:

The researchers excluded 575 subjects who had data missing on age, race,gender, or creatinine or were of nonwhite/nonblack race; 36subjects with glomerular filtration rate (GFR) <15 ml/min per 1.73 m2; 93 subjects whodid not provide permission to release data; three subjects withoutfollow-up data; 556 subjects with missing baseline CVD data;and 4278 subjects with preexisting CVD. The final study population consisted of 22,634 subjects. Since a totalof 602 subjects had missing single data points, such as systolicBP and total cholesterol, single imputationwas performed on the basis of age, gender, and race stratifiedmeans. Although analyses were performed using both the imputed and non-imputeddata, the final models were based on the imputed results.

Inclusion criteria and exclusion criteria:

Baseline characteristics included the following criteria:

demographics

gender

race

education level

lifestyle

smoking

]alcohol intake

medical history

baseline CVD

diabetes

hypertension

medication use

antihypertensive agents

lipid-lowering agents

diabetes medications

physical examination findings

height

weight

body mass index (BMI)

systolic and diastolic BP

left ventricular hypertrophy (LVH) by electrocardiogram

laboratory variables

total cholesterol

HDL cholesterol

creatinine

glucose

Screening tests, clinical parameters and laboratory parameters:

In order to meet the criteria set by the researchers to the selected population representatives and participants of the study, the following screening tests, clinical parameters and laboratory parameters were utilized:

BMI was calculated using the formula weight (kg)/height2 (m).

Total cholesterol and HDL cholesterol were measured in all studies.

Urinalysis results were not available for all studies; therefore,proteinuria was not included as a variable.

LVH was derivedfrom electrocardiographic criteria.

Baseline CVD included a history of both recognized and silentmyocardial infarction (MI), angina, stroke, transient ischemicattack, and intermittent claudication as defined by consensuscommittees for the respective studies.

BaselineCVD included a history of congestive heart failure in CHS, FHS,and Offspring (not coded in ARIC) and a history of angioplastyand coronary bypass procedures in ARIC and CHS (not availablein the Framingham cohorts).

Results:

Upon careful analyses and evaluation of the data that were utilized in the research activity, the following information was presented as results and findings of the study:

· The mean serum creatinine for both whites and blacks was 0.9mg/dl. The mean estimated GFR was 88.6 ml/min per 1.73 m2 forwhites and 99.9 ml/min per 1.73 m2 for blacks.

· CKD was presentin 1664 subjects. The CKD group was composed of 1505 (8.1%)white and 159 (3.8%) black subjects; 19% of patients with CKDwere from ARIC, 47% were from CHS, 25% were from FHS, and 9%were from Offspring.

· In patients with CKD, the mean estimatedGFR was 51.9 ml/min per 1.73 m2 for whites and 49.6 ml/min per1.73 m2 for blacks. But because of the large study sample, all studyvariables were significantly different between the white andblack subgroups.

· The prevalence of traditional CVD risk factors was higher inpatients with CKD as compared with those without CKD.

· Patientswith CKD were older and more likely to include those with ahistory of hypertension and diabetes.

Conclusion and discussion:

The study suggested that the presence of CKD isan independent risk factor for adverse outcomes in a large, pooled, community-based cohort of patients without CVD. Therisk associated with CKD appears to be stronger in blacks thanin whites. Moreover, evidence that patientswith CKD should be considered at high risk for CVD and mortalityoutcomes. Lastly, patients with CKD are potential candidatesfor aggressive risk factor reduction.

Limitations:

Because the public-use databasedoes not provide center information in ARIC and CHS due confidentiality concerns, the researchers were not able to adjust for differencesor clustering of outcomes as a result of center effects. As such theyseveral socioeconomic variables (education, race, smoking, andalcohol use) were used to control for such centrality effects.

Moreover, the definition of CKD in the study was singularly based on serum creatinine assessment which could have likely introduced misclassificationbias. It should also be taken into consideration that these studies evaluated subjects when they were at their baseline and presumably free of acute illnesses that mayaffect serum creatinine.

Despite the large study population, there were relativelyfew blacks with CKD which were selected as samples. However, the relationship betweenblacks with CKD and adverse outcomes was highly significant.

Furthermore, the study likewise lack data on several more recently identified risk factorsfor CVD that may be especially prominent in patients with kidneydisease such as C-reactive protein, homocysteine,and albuminuri.

Finally, the researchers were not able to adjust forchanges in medication use during follow-up or to assess theimpact that several newer therapies like statins and renin-angiotensin-aldosteronesystem blockade, which may have had on CVD outcomes indicated in the cohorts.

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