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High levels of cholesterol are a major risk factor for stroke according to new research published today in Nature Medicine. The study suggests that more widespread use of statin therapy could prevent a large number of strokes as well as heart disease in the Chinese population and others with high stroke rates.

There are two major types of stroke, one caused by a blockage of blood supply to the brain (ischaemic stroke) and the other caused by bleeding into the brain (haemorrhagic stroke). While high cholesterol is a well-established risk factor for heart disease, there is little reliable evidence about its association with risk of the different stroke types.  

The China Kadoorie Biobank (CKB) contains data on half a million middle-aged adults in ten areas of China and has recorded over 33,000 ischaemic stroke cases and 8,000 haemorrhagic stroke cases after nine years of follow-up. Researchers from the University of Oxford, the Chinese Academy of Medical Sciences and Peking University examined the associations of blood levels of cholesterol with risk of the two main stroke types. They studied a subset of CKB participants with no prior history of cardiovascular disease to compare blood cholesterol levels in over 5,000 ischaemic stroke cases, nearly 5,000 haemorrhagic stroke cases and over 6,000 controls.

The researchers found that higher levels of LDL-cholesterol ─ so-called ‘bad cholesterol’ ─ were positively associated with risk of ischaemic stroke and inversely associated with haemorrhagic stroke. Assessment of the net benefits of lowering LDL-cholesterol using statin therapy showed that the number of ischaemic strokes and major cardiovascular events that might be avoided with statin therapy greatly exceeded the likely numbers of haemorrhagic strokes.

Study author, Professor Zhengming Chen from the Nuffield Department of Population Health, University of Oxford, and Principal Investigator of the China Kadoorie Biobank said ‘Stroke is the second most common cause of death worldwide. The results provide important new evidence of the link between LDL-cholesterol and ischaemic stroke and the overall benefits of LDL-cholesterol lowering therapy in China.’

A 1 mmol/L lower blood level of LDL-cholesterol (a reduction typically achieved by treatment with statins) was associated with approximately 15% lower risk of ischaemic stroke, but 15% higher risk of haemorrhagic stroke. These findings were confirmed by analyses using genetic markers for lifelong differences in LDL-cholesterol levels in the same population, and are consistent with findings from smaller cholesterol-lowering trials conducted in Western populations.

Although ischaemic strokes and haemorrhagic strokes account for similar numbers of deaths, the incidence of ischaemic stroke is about four times higher than haemorrhagic stroke. The researchers applied risk estimates to all 500,000 CKB participants to predict the likely net effects of statin treatment in the Chinese population. The results showed that the beneficial effects of lowering LDL-cholesterol on ischaemic stroke and major heart disease events exceeded the adverse effects on haemorrhagic stroke by about five-fold. The benefits were even greater in people with a prior history of vascular disease. 

Study author, Professor Robert Clarke, from the Nuffield Department of Population Health, University of Oxford, said ‘The results highlight the need for more widespread use of statins for prevention of stroke and other cardiovascular diseases in high-risk individuals not only in high-income countries, but also in middle-income countries such as China and low-income populations.’

In China, long-term routine use of cholesterol lowering agents such as statins is very low, even among those with a prior history of vascular disease. This is partly because of lower LDL-cholesterol levels found in the Chinese population, partly because of concerns about a higher risk of haemorrhagic stroke associated with LDL-lowering drug treatment, and partly because of the higher rates of haemorrhagic stroke typically found in the Chinese population.

In this Chinese population, the average LDL-cholesterol level was 2.3 mmol/L, which was much lower than that typically reported in Western populations (~3 mmol/L) and the incidence of haemorrhagic stroke (as well as ischaemic stroke) was much higher than that reported in Western populations. Despite this, the study demonstrated a definite net benefit of LDL-lowering on total stroke and major heart disease events among adults at both low- and high-risk in China.

Study author, Professor Liming Li from Peking University Health Science Centre, and Principal Investigator of the China Kadoorie Biobank, said ‘Our research showed that even in populations with low mean LDL-cholesterol levels, there are still significant benefits from using LDL-lowering drug treatment. In China, the mean levels of cholesterol have been increasing steadily in recent decades. The net benefits of lowering LDL-cholesterol levels are likely to be even greater if cholesterol levels continue to rise and the incidence of cardiovascular diseases continues to increase.’