SAN DIEGO – Among patients with chronic kidney disease, LDL cholesterol level was positively associated with risk of atherosclerotic vascular events, regardless of baseline inflammation, according to a large, randomized study.
In addition, lowering LDL cholesterol with ezetimibe/simvastatin was similarly effective in the presence or absence of inflammation.
Dr. Ben Storey
“There has been substantial interest in the relationship between LDL cholesterol and outcomes in the general population, and in particular among people with kidney disease,” study author Dr. Richard Haynes of the Nuffield Department of Population Health at the University of Oxford (England) said in an interview in advance of the meeting.
“Previous studies have found a paradoxical increased risk of death at low cholesterol levels, which may be due to another disease process – such as inflammation – both lowering cholesterol and increasing the risk of death, thereby creating a false association,” he explained.
Dr. Haynes and his associates set out to determine the relevance of LDL cholesterol and C-reactive protein (CRP) to cardiovascular risk among 9,270 patients with chronic kidney disease who were enrolled in the Study of Heart and Renal Protection (SHARP), in which they received either ezetimibe/simvastatin or placebo.
The researchers used Cox regression to analyze the hazard ratio for all atherosclerotic vascular events over a period of 4.9 years. The effect of ezetimibe/simvastatin on major atherosclerotic events was estimated in the presence and absence of inflammation, which was defined as a CRP of 3 mg/L. The mean age of SHARP participants was 62 years, and 63% were men.
Dr. Ben Storey, a colleague of Dr. Haynes at Oxford, reported the study results at the meeting sponsored by the American Society of Nephrology.
Among all patients, usual LDL was positively associated with the risk of atherosclerotic vascular events (hazard ratio, 1.34). Compared with patients who had low CRP, those with high CRP were at higher risk, but the relationship between LDL-C and atherosclerotic vascular event risk was similar in both groups (HR, 1.32 and 1.41, respectively).
Ezetimibe/simvastatin was similarly effective at reducing major atherosclerotic events in patients with low and high CRP (risk ratio, 0.84 and 0.83, respectively). Sensitivity analyses yielded similar results.
“The observational data from SHARP show that LDL cholesterol is positively associated with the risk of atherosclerotic vascular events, irrespective of baseline inflammation,” Dr. Storey concluded. “The randomized evidence showed that lowering LDL cholesterol was similarly effective in the presence or absence of inflammation, but CRP is associated with vascular risk in [chronic kidney disease].”
The findings’ clinical implications are that inflammation, “while it is relevant to patients’ outcomes, does not modify the beneficial effects of lowering LDL cholesterol,” according to Dr. Haynes, “So, clinicians should not be put off from prescribing statin-based, cholesterol-lowering therapy by the presence – or absence – of inflammation.”
Merck funded SHARP, but the University of Oxford conducted and analyzed the study independently. The Australian National Health and Medical Research Council, the British Heart Foundation, Cancer Research UK, and the UK Medical Research Council provided additional support.