Understanding the link between high cholesterol and kidney disease

It has been known for a very long time that people with chronic kidney disease (CKD) have a very much higher than normal incidences of cardiovascular diseases, such as strokes and heart attacks. We’ve asked consultant nephrologist Dr Christopher Lawrence to explain just when the link between high cholesterol and renal disease was first discovered and how the conditions relate to one another.

What does research tell us about cardiovascular disease and CKD?

One often-quoted study from America showed the risk of dying of cardiovascular causes in patients receiving dialysis as strikingly higher compared to the ‘healthy’ or the general population. The relative risk adjustment varied depending on the age group but, for example, a middle-aged patient receiving dialysis is approximately 20 times more likely to die from cardiovascular causes than an age-matched member of the general population.¹

In a population of patients who were not yet on dialysis but had advanced (CKD stage 4 and 5) kidney impairment, one study showed that in high-risk patients the incidence of flow-limiting coronary artery narrowing was 30%. 2 This was in those who met at least one of the following three criteria: over 50 years of age; diabetic; or with symptoms or signs of heart disease.

It would seem then that the effect of high cholesterol on kidneys or at least people with kidney problems is obvious, however it is not as straightforward as all that!

What’s the role of statins in lowering cholesterol?

In the general population, cholesterol-lowering therapy with statins is thought to provide benefit in two ways. Firstly, conferring nearly immediate benefit by stabilising cholesterol plaques and making them less likely to rupture (resulting in blockage of the coronary artery). Secondly, by lowering cholesterol with time and therefore reducing the deposition of cholesterol plaques in the coronary arteries.

In the 1990s statins were shown to be effective at primary prevention, such as preventing heart attacks in people at risk of a heart attack but who had not yet had a heart attack.3 They also proved to be effective in secondary prevention, 4 preventing further heart attacks in people who had already experienced one heart attack.

Are statins beneficial for CKD?

It followed, therefore, that as people with kidney disease are more prone to cardiovascular events, such as stroke and heart attacks, and that cholesterol-lowering drugs, like statins, prevent heart attacks (and strokes), it meant that people with kidney disease should take statins. Or did it?

In heart disease, as in many other things, it is rather more complicated for people with kidney disease than without.

Cholesterol causes atherosclerosis (fatty plaques in the blood vessels) but people with kidney disease also have accelerated arteriosclerosis (calcification of the arteries) as well as being more likely to have high blood pressure (due to salt and water overload, or the kidney disease itself) and a heart that pumps less well. It wasn’t therefore obvious that cholesterol-lowering drugs were of definite benefit to people with kidney disease.

Finally, in 2011 the SHARP study was published showing that cholesterol-lowering (using a combination of simvastatin and ezetimibe) did reduce the need for coronary revascularisation (angioplasties and bypass grafts); non-fatal heart attacks and ischaemic strokes. (The 85% of strokes that aren't bleeding.)5 

The effect was bigger in patients with no history of vascular disease (surprisingly); diabetics, those aged over 50, non-smokers, those with a starting total cholesterol of more than 5.5 or an LDL more than 3, a body mass index of over 28, an eGFR of less than 60 ml/min but not yet on dialysis; and at least moderate albuminuria.
 

What are the risk factors for cardiovascular-related CKD?

Whilst there is statistically robust evidence from the SHARP study that cholesterol-lowering can benefit many people with kidney disease preventing vascular events, it is worth remembering that age, being diabetic and being a current smoker are all more important risk factors than cholesterol for cardiovascular disease.

Do not hesitate to book an appointment with Dr Lawrence for a first consultation.

____________________________________________________________________

References:

¹Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32[Suppl 3}:S115,1998

² Kumar N et al. Effect of elective coronary angiography on glomerular filtration rate in patients with advanced chronic kidney disease. Clin J Am Soc Nephrol 4(12):1907-1913.

³ Pedersen TR for the Scandinavian Simvastatin Survival Study (4S) Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study  (4S) Group. The Lancet 344(8934):1383-1389.

⁴ Sacks FM et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. NEJM 335(14):1001-1009.

⁵ Baigent C et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. The Lancet 377(9784):2181-2192.