Risk Factors for Enhanced CV Mortality in ESRD Patients

Cardiovascular mortality in the general ESRD population is between 10- and 20-fold higher than that of the general population, and is an astounding 65-fold higher in ESRD individuals in the 45-54-year-old subgroup of the Framingham study.  A recent review lists some of the risk factors which have been targeted as being contributers to this enhanced cardiovascular mortality, which include:

1.  Disordered Mineral Metabolism--there has been an increased awareness that calcium-phosphate deposition within the walls of blood vessels could play a role in cardiovascular mortality.

2.  Existence of a pro-inflammatory state--there is good epidemiologic evidence linking hsCRP to mortality in the general population, which appears to also hold true in a dialysis population as well.  

3.  Anemia--it is postulated that anemia drive left ventricular hypertrophy, which is correlated with a worsened cardiovascular mortality.

4.  Dyslipidemia--this is controversial, as LDL levels are often normal in dialysis patients, and treatment of LDL levels with a statin in ESRD patients does not seem to have the same beneficial effect as in the general population.  Perhaps a different altered lipid profile--for example, low HDL and high triglycerides--are responsible for some of the increased cardiovascular disease in ESRD patients.

5.  Endothelial dysfunction--there is some evidence that the endothelium of ESRD patients is less able to synthesize nitric oxide (NO), an inhibitor of vascular smooth muscle cell proliferation and important regulator of blood flow based via its actions as a vasodilator.  

6.  Other biomarkers under investigation--lipoprotein A, hyperhomocysteinemia, and whatever the biomarker-du-jour happens to be--are being investigated into their link between ESRD and cardiovascular mortality.

The difficulty in ascribing any of these risk factors as the predominant cause of the elevated mortality rate seen in ESRD patients is that they are all pretty common in this population.  What dialysis patient doesn't have an elevated hsCRP or anemia at some point?  My guess is, this is a complex problem which is not likely to yield a single answer.