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Wednesday, April 13, 2016

Kidney disease and heart disease: five questions to unravel the link

A frequent conundrum that I see patients run into almost everyday, is understanding the link between chronic kidney disease (CKD) and coronary heart disease (CHD). They are surprised when I tell them that most CKD patients are more likely to die from heart disease, than from kidney disease (or require renal replacement therapy/dialysis).

Why is that so, and is there a link between kidney and heart disease? Lets explore.

Kidney disease has been well established as an independent risk factor for coronary disease. In other words, even if a person does not have the other traditional well recognized risk factors to develop heart disease (like smoking, diabetes, hypertension, abnormal cholesterol, older age), he/she is still at a high risk of developing coronary heart disease if they have preexisting kidney disease. This association has been known for quite some time now; however, what a recent study demonstrated was very surprising to me. Researchers found that in 3,938 participants studied over about 4 years, the incidence of recurrent CHD events (like heart attacks) was almost twice in patients who had CKD alone (35), compared to patients who had the high risk factors alone (18.9)! Does that mean that kidney disease is an equal, if not bigger, risk factor for development of heart disease? Possibly. This should perhaps then spur the average nephrologist to include cardiovascular care as a routine part of the treatment regimen of the CKD patient. Lets try to understand this link a little bit more and what can we do about it. To make it a little more digestible, I am going to break it down in to five pertinent questions.  


HOW COMMON IS HEART DISEASE IN PATIENTS WITH KIDNEY DISEASE?


Adjusted rates of hospitalization for cardiovascular disease (by dataset & CKD diagnosis code)
USRDS 2009 Annual Data Report


Patients with kidney disease are more likely to be hospitalized for heart disease.  Even though we have established that CKD is a risk factor for CHD; epidemiologically,  it can be hard to specifically delineate the incidence of CHD in patients with vs without CKD, since many patients with CKD will also have other traditional risk factors that cause heart disease. However, a quick look at the above graph from the US Renal Data System (USRDS) shows that hospitalization rates for heart disease in patients with CKD are much higher that in patients with no CKD, across all age groups. The rates tend to be especially higher in patients with more advanced CKD. Assuming hospitalization could be a rough surrogate for prevalence, it would seem that patients with kidney disease are more likely to have heart disease.


WHY DO PATIENTS WITH KIDNEY DISEASE TEND TO DEVELOP HEART DISEASE? WHAT ARE THEIR RISK FACTORS?

Even if a kidney disease patient lacks the above mentioned traditional risk factors for CHD, she/he is still at risk for heart disease. This is because of the presence of "non-traditional" risk factors. These so called non-traditional risk factors become even more influential in advanced kidney disease, and are unique to patients with CKD. 

One such risk factor that has receive a tremendous amount of attention lately has been disordered bone and mineral metabolism that occurs in patients with CKD, now called CKD-MBD (CKD related mineral and bone disorder). As kidney disease progresses, dietary phosphorus tends to build up in the blood since the kidneys are unable to get rid of it as well as normal kidneys do. This sets of a complicated cascade that includes increased production of parathyroid hormone from the parathyroid gland, and increased production of a hormone called FGF-23, as the body attempts to force the excess phosphorus out of the system. Other changes include fall in vitamin D levels (since vitamin D is activated in the kidneys, and diseased kidneys cannot do that efficiently), calcium loss from the bones and subsequent calcium deposition in the coronary arteries, and genetic changes. These events collude and cause harm that goes beyond changes in the bones, and leads to a higher risk of  heart disease.   

Other factors that have been postulated to cause heart disease in patients with kidney disease include accumulation of toxins in advanced kidney disease (uremic toxins), oxidative stressinflammation, and anemia of kidney disease. If you are interested in the deeper technical details about how these two organs talk to and influence each other, here is an article. 


WHAT CAN PATIENTS WITH KIDNEY AND HEART DISEASE EXPECT?

Most patients with kidney disease dread the thought of going on dialysis. However, statistically speaking, in older patients the risk of dying from heart disease far exceeds the risk of requiring renal replacement/dialysis, regardless of the stage of CKD that patients may have! This conclusion might not apply to younger people with CKD, who are more likely to require renal replacement/dialysis than dying. However, looking at CKD patients as a whole, since older patients form the overwhelming majority of CKD population, death, before dialysis ever becomes a possibility, is more likely. 


Image courtesy of dream designs/ FreeDigitalPhotos.net


HOW CAN PATIENTS WITH KIDNEY DISEASE REDUCE THEIR RISK OF HEART DISEASE?

Now that we know that there are factors unique to kidney disease patients as far as there heart disease risk goes, active steps need to be taken to minimize CHD risk. This should ideally be a team based approach between your primary doctor, nephrologist, and cardiologist. It goes without saying that an important part of prevention is optimal treatment of kidney disease and its complications like CKD-MBD, anemia, etc. In patients who also have high protein level in the urine, blood pressure should be controlled to a goal of <130/80, and medications called ACE inhibitors (eg. lisinopril, enalapril) or ARBs (eg. losartan, valsartan) should be used. 

Two issues that are often a cause of confusion among patients and physicians are (a) the use of aspirin (to prevent blood clots) and (b) statins (to lower cholesterol). Aspirin use (frequently recommended for the general population to prevent CHD) has been a mixed bag in CKD patients. As per one of the latest and biggest analysis that pooled data from multiple studies, that I have had a chance to look over, aspirin use has been demonstrated to reduce the risk of heart attacks, but not strokes or the risk of death, in patients with CKD. In addition, aspirin use in CKD patients is also associated with a significantly higher risk of major bleeding episodes. Given these findings, it is hard to make a universal recommendation regarding aspirin for all patients with CKD. It is best that you talk to your physician about the risks vs benefits and individualize treatment. 

There is also some evidence that use of cholesterol lowering statin medications (eg. simvastatin, lovastatin) might reduce CHD risk in patients with CKD. Again, this recommendation does come with some caveats that you should discuss with your physician. 

We, as patients and even as physicians, often tend to look at organs in isolation. There are not. They talk to each other and affect each other's function inside the microcosm that is the human body. Care of an organ like the kidney is incomplete without watching over the heart (and vice versa) as well. To do otherwise is a disservice to the patient. 

Veeraish Chauhan, MD, FACP, FASN

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