Relevance of renal impairment as a risk factor for cardiovascular disease

1 - Renal damage and CV risk

The presence of renal damage is associated with an increased risk of future development of cardiovascular (CV) events and death. The enhanced risk is already present when microalbuminuria is detected in the presence of a totally preserved glomerular filtration rate (GFR). Since then and until the development of end-stage renal disease (ESRD), CV risk rises continuously to attain a maximum level 20 to 30 times above that of the general population (1).

2 - The evolution of Chronic Kidney Disease (CKD)

Four stages have been defined before the development of ESRD (stage 5) in the evolution of Chronic Kidney Disease (CKD) as defined in the Kidney Disease Outcomes Quality Initiative (K-DOQI)(2).
They are based on the level of estimated glomerular filtration rate (eGFR), obtained using the MDRD formula (3), or of estimated creatinine clearance using the Cockroft-Gault formula (4), and on the presence of albuminuria either micro (30-300 mg/g of creatinine) or macro (> 300 mg/g). The presence of albuminuria is more frequent with diminished values of eGFR and their simultaneous finding is accompanied by an additive effect on risk prediction.

3 - CKD and the level of renal function in the Prevention of CV disease

The relevance of CKD for the prediction of CV disease has been demonstrated in the general (5) and hypertensive populations (6), as well as in patients with established cardiac disease in particular coronary artery disease (7), post-MI patients (8), and heart failure (9). The level of renal function has also been shown to be a good predictor of outcome after coronary interventions (10) and cardiac catheterization (11).
The development of CKD is associated with the presence of classical CV risk factors in particular age, arterial hypertension, and hyperlipidemia (12) and recently it has been shown to be associated with the presence of metabolic syndrome (13). 

- In hypertensive patients longitudinal data have shown that the progressive decay of eGFR from normal or mildly diminished levels to values below 60 ml/min/m2 is accompanied by a significant increase in CV events and death during that evolution (14). CKD and CV disease can then develop in parallel being the consequence of the activity of similar risk factors (15) and both contribute independently to increase the risk prediction (16). Once CKD has progressed and eGFR are below the figure of 60 ml/min/m2, other factors specifically dependent on the level of renal insufficiency appear and contribute to enhance the level of CV risk. These are the presence of changes in calcium/phosphate homeostasis and the ulterior development of secondary hyperparathyroidism (17) and anemia due to a diminished renal production of erythropoietin (18).

 - In patients presenting with heart failure, it has been shown that renal function is independently associated with a heightened risk for death, CV death and hospitalisation from heart failure in patients with both preserved and reduced left ventricular ejection fraction (9). 
 Interestingly, in heart failure the finding of a diminished level of eGFR could be, not the consequence of established renal disease but a direct reflection of an impaired hemodynamic status related to the severity of the underlying cardiac disease causing a functional derangement in renal function (19).
Data from the CHARM study have shown that eGFR and cardiac function had effects that were independent in terms of predicting the primary end-point of the study (9).

The factors explaining the increased risk of CV events and death in the presence of any manifestation of CKD are the presence of advanced atherosclerosis and very frequently hypertensive vascular disease. This fact contributes to explain the frequent association of renal insufficiency and established CV disease and explains the need for an early integral CV intervention in an attempt to control all the different CV risk factors usually present in these patients (20)(Table 1). It also must be stressed that patients with renal insufficiency are less likely to be prescribed efficacious therapies in particular when situations like heart failure or established coronary artery disease are present (21). The prescription of the adequate medications is accompanied by better survival rates across the full spectrum of renal function (21).  

Table 1. Therapeutic attitudes in patients with renal damage and high cardiovascular risk.

LIFE-STYLE CHANGES : Salt intake, body weight, and smoking
STRICT BLOOD PRESSURE CONTROL : Goal BP control <130/80 mmHg, (<125/75 mmHg if proteinuria>1g/d ).
Combination therapy required in most cases
Blockade of angiotensin II effects is required
CONTROL OF ASSOCIATED RISK FACTORS :Lipids: Statins, fibrates
Insulin resistance: Insulin sensitizers (metformin, glitazones)
Platelet aggregation: Aspirins, others

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.