Cardiovascular and Noncardiovascular Mortality Among Patients Starting Dialysis

Title: Cardiovascular and Noncardiovascular Mortality Among Patients Starting Dialysis
Topic: General Cardiology
Date Posted: 11/20/2009
Author(s): de Jager DJ, Grootendorst DC, Jager KJ, et al.
Citation: JAMA 2009;302:1782-1789.
Clinical Trial: No

Study Question: Cardiovascular (CV) mortality is considered the main cause of death in patients receiving dialysis and is 10 to 20 times higher in such patients than in the general population. Is the high overall mortality in patients with end-stage renal disease (ESRD) starting dialysis a consequence of increased CV mortality risk only, or is non-CV mortality equally increased?

Methods: Using data from between January 1, 1994 and January 1, 2007, the authors age-stratified mortality in a European cohort of 123,407 adults starting dialysis and receiving follow-up for a mean of 1.8 (standard deviation, 1.1) years. The outcome measure of death was compared with the European general population. Standardized CV and non-CV mortality rates, their ratio, difference, and relative excess of CV over non-CV mortality were calculated.

Results: Mean age of the patients at start of dialysis was 63.2 years, and 61.2% were men. During follow-up, 25,084 patients (20.3%) were censored because of kidney transplantation, and 42,643 (34.6%) died. Overall all-cause mortality rates in patients and the general population were 192 per 1,000 person-years (95% confidence interval [CI], 190-193) and 12.06 per 1,000 person-years (95% CI, 12.05-12.06), respectively. Cause of death was known for 90% of the patients and 99% of the general population. In patients, 16,654 deaths (39%) were CV and 21,654 (51%) were nonCV, which was very similar to the general population. CV and non-CV mortality rates in patients were respectively 38.1 per 1,000 person-years (95% CI, 37.2-39.0) and 50.1 per 1,000 person-years (95% CI, 48.9-51.2) higher than in the general population. On a relative scale, standardized CV and non-CV mortality were respectively 8.8 (95% CI, 8.6-9.0) and 8.1 (95% CI, 7.9-8.3) times higher than in the general population. The ratio of these rates, i.e., relative excess of CV over non-CV mortality in patients starting dialysis compared with the general population, was 1.09 (95% CI, 1.06-1.12).

Conclusions: The authors concluded that patients starting dialysis have an increased risk of death that is not specifically caused by excess CV mortality.

Perspective: The mortality rate of 35% in 3 years was distributed similarly between CV disease (CVD) and non-CVD as in the general population in Europe and the United States (45% CVD and 55% non-CVD). Infection and malignancies are the dominant causes for the increase in non-CVD deaths. The increase in CVD deaths in ESRD is attributable to several factors among which the most important are an increase in hypertension, diabetes, inflammatory milieu, and the effects of uremia and possibly dialysis on vascular calcification. The failure of high-dose statins to lower the CV mortality in patients on dialysis was a major surprise.

--Melvyn Rubenfire, M.D., F.A.C.C.