Blog entry by Meguid El Nahas
In this week (September 1-7, 2012: http://www.ncbi.nlm.nih.gov/pubmed/22717317) issue of the Lancet, Tonelli and colleagues from Alberta explored whether CKD was a coronary artery disease (CAD) risk equivalent. Risk equivalent would imply that the 10 year CAD risk associated with CKD (eGFR<60) is 20% similar to that affecting sufferers of myocardial infarction. They studied a local cohort of 1,268,029 individual over a 4-5 year period.
They concluded that: "Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events"
However, reading the paper I come to different conclusions:
1. The rate of myocardial infarction (the primary end point) was higher in people with previous myocardial infarction than in those with CKD.
2. It is true than unadjusted risk rate in CKD was higher than that of people with diabetes (illustrated in the Figure, for maximal impact....).
3. When risk is adjusted for age (older in CKD compared to those with DM) as well as CVD co-morbidities the adjusted risk no longer exceeds that of DM. In other words, the increased risk associated with CKD was to a large extent the reflection of older AGE but also of CV CO-MORBIDITIES associated with older age...
So, as stated on numerous previous occasions on OLA, CKD is a CVD risk marker for the simple reason that:
a. Individuals with CKD and a eGFR<60 are older and have been exposed in their lifetime to CVD risks such as hypertension, obesity/DM, and dyslipidemia. Not to mention the presence of anemia which in a previous study seemd to explain most of the CVD risk associated with CKD (Vlagopoulos et al, 2005). None of these confounders has been explored in the Tonelli analysis.
b. Individuals with CKD have underlying overt or subclinical CVD including CAD, thus making them at obvious CVD risk as they already suffer from CVD....(Park et al, 2012: http://www.ncbi.nlm.nih.gov/pubmed/22935481).
Also, as previously shown in a number of studies reviewed by Chang and Kramer in 2011 (http://www.ncbi.nlm.nih.gov/pubmed/21811078), adding eGFR or albuminuria to standard CVD risk scores, such as the Framingham Risk Score, adds little to the predictive value of established CVD scoring system.
Had Tonelli and colleagues checked conventional CVD risk factors such as Hypertension, Smoking and dyslipidemia in the community studied, they would have found that CKD patients with eGFR <60 or worse still <45 have been exposed to most of these confounders or CVD risk...and that CKD merely reflects in th eelderly such lifetime exposure, leading to CVD and consequently to CKD!
Finally, the authors and the accompanying review make the point that CKD patients should therefore be put on statins in view of their high CVD risk. This is true intuitively, but unproven clinically as the SHARP study they both refer to FAILED to show any benefit of statin + Ezetemibe treatment in CKD as far as prevention of CAD or reduction of overall mortality. So there is NO EVIDENCE that statins reduce the coronary events risk the authors are focusing on in CKD or even in those with ESRD with DM (4D study) (http://www.ncbi.nlm.nih.gov/pubmed/19332456).
Altogether, it is high time that the Nephrology community comes to realise that CKD is a CVD risk equivalent because CKD = CVD in the ageing general population where age, hypertension, obesity, DM, dyslipidemia and smoking are prevalent and individuals often have overt (but undiagnosed) or subclinical (not tested for...) CVD. Of note, the Baltimore Longitudinal Study of Ageing showed many years ago that age related decline in kidney function was prominent in those with co-morbidities.
Chicken and Egg situation where the chicken is CVD and th eegg is CKD...!!!