Inflammation more likely to predict cardiovascular death than high cholesterol in people on statins, research suggests.
Inflammation is a better predictor of cardiovascular mortality than cholesterol in people taking statins, a new study suggests.
The study adds to growing evidence that inflammation plays a role in cardiovascular disease, researchers say.
A recent meta-analysis including over 31,000 people taking statins for dyslipidaemia found that participants with the most elevated high-sensitivity C-reactive protein (hs-CRP) levels were 2.7 times more likely to die from a cardiovascular cause after five years than people with the lowest CRP.
By contrast, there was no clinically significant difference in the risk of cardiovascular death between people with the highest LDL-C level compared with those with the lowest levels of LDL-C (1.27 vs 1.16).
In addition, high CRP levels were associated with a 30% increased risk of cardiovascular events, whereas high LDL-C levels were associated with only a 7% increased risk.
“Among patients receiving contemporary statins, inflammation assessed by high-sensitivity CRP was a stronger predictor for risk of future cardiovascular events and death than cholesterol assessed by LDL-C,” the US authors wrote in The Lancet.
A combination of aggressive lipid-lowering and anti-inflammatory therapies might become standard of care for atherosclerotic disease in the future, they said.
“Although the current data must not be construed to diminish the crucial role of adjunctive lipid lowering beyond statins for patients with persistent or refractory hypercholesterolaemia, they do suggest that targeting LDL-C alone is unlikely to completely reduce atherosclerotic risk and that inflammatory pathways have yet to be fully exploited to reduce fatal and non-fatal cardiovascular event rates.”
Professor Stephen Nicholls, president of the Cardiac Society of Australia and New Zealand, told TMR that the study reinforced emerging evidence that there were other factors apart from cholesterol that drove cardiovascular risk, and inflammation may be a therapeutic target.
“These are important findings, because they reinforce the importance of inflammation and suggest that inflammation might be a target,” said Professor Nicholls, who is also program director of the Victorian Heart Hospital and director of the Victorian Heart Institute.
“It doesn’t diminish the importance of targeting LDL cholesterol because the data is pretty convincing that if you lower LDL cholesterol, patients do better.
“But we also know that even when we do treat patients well from a cholesterol perspective, that plenty of patients still have events.”
Professor Nicholls said there was some evidence that colchicine, normally used to treat gout, had some cardiovascular benefits.
“It’s a cheap drug but it’s also a medication that has been demonstrated to have clinical benefit in a number of clinical trials.”
Professor Nicholls said an IL-1 inhibitor had already been shown to have some cardiovascular benefit, and a clinical trial was underway with an IL-6 inhibitor.
“We’re seeing increasing activity in this space because there’s a recognition that inflammation is an important driver of ongoing risk, and this data supports that.”
Professor Nicholls said inflammatory markers tended to be high after a myocardial infarct but usually came down in the following six to eight weeks.
But he said for some people, inflammatory markers still remained higher than normal after that period even when other risk factors were well controlled through blood pressure, cholesterol and anti-platelet therapies.
Whether those patients would then benefit from an anti-inflammatory drug was a credible theory but was still being tested in clinical trials, he said.
“If we are able to develop better therapies that target inflammation, and we can then do trials that show that identifying somebody with this kind of inflammatory residual risk does benefit. Then perhaps that would lead to more routine monitoring.”
