The CVD-CKD Connection: A Double-Edged Sword

Link Is Greater than Previously Thought

By Laura Brasseur

Chronic kidney disease (CKD) has been well-documented as an independent risk factor for cardiovascular disease (CVD). Convincing data from 2 new studies have now demonstrated that this connection ≥ says Thomas D. DuBose, Jr, MD.

In the first study (Arch Intern Med. 2007;167:1130-1136), investigators analyzed information from 15,792 participants (aged 45-64 years) in the Atherosclerosis Risk in Communities (ARIC) study and from 5201 participants (aged ≥65 years) in the Cardiovascular Health Study (CHS). At baseline, 1787 persons (12.9%) had CVD, which was defined by a history of myocardial infarction (MI), angioplasty, or bypass; angina; previous stroke; or claudication.

Thomas D. DuBose,Jr,MD

Over a mean follow-up of 9.3 years, baseline CVD was shown to increase the risk for all patient outcomes, including a decline in kidney function and the development of kidney disease—an association that remained significant after accounting for demographic and clinical variables.

The second study, published in the same issue (pages 1122-1129), included analysis of 37,153 individuals (mean age, 52.9 years; 69% female) who were at high risk for subclinical nephropathy, based on personal or family history of diabetes or hypertension, or family history of kidney disease.

After controlling for age, multivariate analysis confirmed the usual suspects as independent risk factors for CVD—diabetes, smoking, high body mass index, lower estimated glomerular filtration rate (eGFR), and increased albumin concentration.

The novel finding, however, was that the presence of 3 CKD measures&#8212;low eGFR (<60 mL/min/1.73 m²), microalbuminuria, and anemia&#8212;had a significant impact on patient survival.

Among those who had neither CKD nor CVD, survival was >98% at 30 months. When all 3 CKD measures were present, survival fell to 93%.

"It's been known for a while thatCKD seems to be a unique risk factor forthe development of CVD," Dr DuBose,coauthor of an accompanying editorial(pages 1113-1115), tells IMWR.

"These 2 studies help to point outthat patients with CVD are at risk forindependently developing CKD. One ofthe things we tried to do in the editorialis point out that this microvascularmilieu is the crux of the disease, in otherwords, the pivotal issue that unites theheart and the kidney," Dr DuBose says.

One of the major challenges now forprimary care physicians is, "Whomshould we screen, and how should wescreen?," says Dr DuBose, the TinsleyR. Harrison Professor and chair ofinternal medicine, professor of physiologyand pharmacology, Wake ForestUniversity School of Medicine,Winston-Salem, NC.

The answer to the first part of thequestion, he says, is to screen at-riskpopulations: "The diabetic, the hypertensive,the older patient, the patientwith a first-degree relative on dialysisbecause there certainly is a genetic basisfor developing this form of microvasculardisease."

In addition, "Because we know thatthe risk for CKD is much higher inAfrican Americans and in AmericanIndians and in Hispanics, I think primarycare physicians should pull thetrigger on the screen in those populationsmuch earlier."

One of the problems in answeringthe second part of the question ("Howdo you screen?"), Dr DuBose says, isthat "the reporting of the eGFR is notas widely applied as would be necessaryto really appreciate the prevalence ofkidney disease."

Primary care physicians need tounderstand "that we can't just focuson replacing kidney function whenit's lost. If we intervene earlier,progression can certainly be slowed,"using angiotensin-converting-enzymeinhibitors and angiotensin receptorblockers. Treating CVD and loweringcholesterol, he adds, are also extremelyimportant, "just as lowering the glucosein a diabetic is important, but in isolationmay not be sufficient."

Quick Questionnaire Can Predict CKD

Studies spanning the last 2 decades have documented a lack of screening in populations at increased risk for chronic kidney disease (CKD). A first patient tool has now been developed and has been shown to help identify at-risk individuals (Arch Intern Med. 2007;167:374-381).

This cross-sectional analysis included 8350 adult men and women (aged ≥20 years) from the Screening for Occult Renal Disease trial. After assessing a variety of potential risk factors and different variables, 7 factors were found to have significant associations with CKD:

• Age ≥50 years
• Anemia
• Cardiovascular disease
• Diabetes
• Female gender
• Hypertension
• Proteinuria.

Using these characteristics, the investigators created a user-friendly questionnaire to identify persons who are at risk for this disease.

"Many patients do not find out that they have CKD until it has progressed to end-stage kidney disease," says coinvestigator Abhijit V. Kshirsagar, MD, MPH, of the Kidney Center and Division of Nephrology, University of North Carolina School of Medicine.

For patients with a total score of ≥4, a confirmatory test for creatinine concentration and/or glomerular filtration rate is recommended.