Comparative prognostic value of glomerular filtration rate estimating formulas in ischaemic heart disease

Coceani et al.
European Journal of Cardiovascular Prevention & Rehabilitation

Special Introduction by the Authors 

Chronic kidney disease (CKD) is a major risk factor for cardiovascular death, with incidence of cardiovascular disease in dialysis patients even 1000 times greater than that of the general population. Renal function is typically assessed through serum creatinine, which is limited by dependency on age, gender, and body mass. Creatinine clearance qualifies CKD more accurately, but requires a carefully collected urine sample over 24 hours, thus conditioning its use in routine clinical practice. For this reason, various formulas have been developed to estimate glomerular filtration rate (GFR). The Modification of Diet in Renal Disease (MDRD) formula, for example, has been identified by the American Heart Association as a means to screen for CKD in patients with cardiovascular disease. However, the role of the formula has not been verified in this particular setting. In the present study, the impact on prognosis of CKD defined by the simplified MDRD formula in comparison with GFR calculated with the Cockcroft-Gault (CG) formula corrected for body surface area was examined in a large population of patients with ischaemic heart disease (IHD) and long-term follow-up.

Renal function was analysed in 2066 patients (mean age 55 ± 9.5 years, 79% male) that had been hospitalized for IHD and that had undergone coronary angiography. Ten-year mortality was 21% and had as predictors CKD (GFR<60 ml/min/1.73 m²) diagnosed with either the MDRD or CG formula (p<0.0001 for each). Using Cox regression analysis, significant coronary atherosclerosis, defined as a greater than 50% stenosis in at least one major vessel, turned out to be the factor most closely linked to increased mortality (HR 4.40, 95% CI 2.78-6.97, p<0.001), followed by reduced CG GFR (HR 2.08, 95% CI 1.55-2.79, p<0.001) and left bundle branch block (HR 2.00, 95% CI 1.10-3.61, p<0.001). Serum creatinine and MDRD GFR, as well as markers of cardiovascular disease, such as left ventricular hypertrophy, atrial fibrillation, and proteinuria, did not show any relationship with survival at multivariate analysis.

The observation of a better performance of the CG formula, corrected for body surface area, over the simplified MDRD formula is of interest. One may hypothesize that the simplified MDRD formula, taking into account only age, gender, and race, lacks accuracy in patients with IHD. The extended version of the MDRD formula, on the other hand, is difficult to apply to routine clinical practice due to its dependency on serum albumin and blood urea nitrogen. The CG formula corrected for body surface area, therefore, presents itself as an attractive choice for estimating GFR in IHD. An alternative explanation is that the value of GFR estimating formulas varies according to clinical context, a hypothesis that has already emerged from previous studies. Because GFR estimating formulas have been validated primarily in young populations and in subjects with chronic renal disease, further studies are necessary to establish which formula - CG corrected for body surface area, simplified MDRD, or extended MDRD - should be used in patients with IHD.

In conclusion, CKD is an important prognostic determinant in patients with suspected IHD and should always be calculated in this clinical setting. The predictive value of GFR when estimated with the CG formula corrected for body surface area, is superior to other measures of renal function, traditional coronary risk factors, and markers of cardiovascular disease. GFR should always be calculated in patients with suspected IHD, preferably with the CG formula.

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