KDOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients

Section III. State of the science: novel and controversial topics in cardiovascular diseases

The following sections have been prepared to ensure that the state of the art and science related to CVD includes novel concepts, therapeutic strategies, and emerging areas of pathophysiological and practical importance to the care of dialysis patients.

The reader will notice that the format of this section is different, reflecting its different perspective: namely, the relative lack of evidence on which to base plausible guideline statements. The evidence that does exist, and is cited in this section, is either completely in nondialysis populations, or is purely associative information, with no intervention in any population yet tested. Thus, it would be a problem to include guideline statements or recommendations.

Nonetheless, this section describes the current status of knowledge with respect to risk factors and biomarkers, and represents an overview of key areas for future clinical trials. The reader is encouraged to review this section, and examine his or her current understanding and practice within the context of these highlights.

The literature review has been conducted using the same systematic strategy as for the previous guidelines in this document. The reviews presented here have been thoughtfully constructed so that clinicians can adopt different practices based on them. However, for reasons cited above, the ability to truly recommend or suggest changes in practice would be premature at this time.

Risk Stratification

Overview of risk stratification

Risk stratification is the categorization of patients with a special disease into risk strata that reflect the probability to develop a certain event or an exacerbation of the disease. The categorization is based on several factors, e.g., demographic variables, comorbidities, or conditions that are already known to be associated with an increased risk for the endpoints of interest. It is, therefore, the goal of risk stratification to identify those patients who have the highest risk to develop an endpoint. The most important task of risk stratification is to improve the health status by slowing or preventing complications through early detection or appropriate intervention before a fatal or nonfatal event occurs. One opportunity to do so is to offer the patients disease management programs.It is important to distinguish between two different kinds of stratifiers. The first kind includes those conditions that can be detected and changed by avoidance (e.g., smoking) or intervention (e.g., high blood pressure or hypercholesterolemia). Data from the general population show that these changes are associated with a lower incidence of cardiovascular events. In CKD patients, data are often rare and it is necessary to extrapolate results from the general population. On the other hand, many of these conditions are reported to show paradoxical associations in dialysis patients. For example, many studies show a higher BMI to be associated with a higher mortality risk in CKD patients, which is completely opposite to what is observed in the general population.668672 This association is even independent of serum albumin, clinical assessment of nutritional status, and comorbid conditions. Similar associations with mortality, which are opposite to those in the general population, were reported for cholesterol and homocysteine.181,562,673677 Studies that described associations opposite to what is known from the general population resulted in a discussion of a so-called reverse epidemiology in dialysis patients.678,679 In many cases, there is an explanation for this apparent paradox on further examination of the data, as was recently shown for the reverse association between cholesterol and mortality in dialysis patients.262

The second kind of risk stratifiers is that that is “fixed” and cannot usually be changed. Examples are age, gender, and—in particular—genetically determined conditions. Biomarkers also belong to this category, since they cannot be changed, but they point to an already damaged cardiovascular system or to a cardiovascular system which is at high risk of future damage. Typical examples discussed earlier include troponins411,412,414,419,680 or particular genetic variants of the apo(a) gene, the so-called LMW (or small) apo(a) isoforms.603605,613,617619,624,630 Although age, gender, or special genetic variants are fixed stratifiers, they should be considered in any decision regarding intervention. For example, patients with adverse conditions should be followed more closely by noninvasive tests (e.g., ultrasound of the carotid arteries) and in shorter time intervals, since cardiovascular changes often develop rapidly. If an invasive test (e.g., coronary angiography) is indicated, these adverse conditions might support its use. However, at present, no randomized controlled studies in CKD patients are available that have investigated whether risk stratification by these fixed stratifiers is beneficial, when it is either followed by a “forced” structured disease management program or by “routine” care.


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