Cholesterol reduction and stroke

Clinical bottom line

In randomised trials, cholesterol reduction reduces the risk of stroke.

Reference

MR Law et al. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ 2003 326: 1423-1429.

Background

Reduction in serum cholesterol is associated with stroke risk being reduced. Here that risk reduction is quantified in randomised trials.

Systematic review

Randomised trials of cholesterol reduction by any means were sought, excluding those in which risk factors other than cholesterol were changed, fewer than five ischaemic heart disease events occurred, or in which there was no untreated control group. IHD events were IHD death or non-fatal myocardial infarction (and excluding silent infarcts).

Results

There were 58 trials with 76,000 treated patients and 72,000 controls, with 5,440 and 7,102 respective events, with treatments including fibrates, resins, niacin, statins or dietary change). Results from trials were standardised to a 1 mmol/L reduction in LDL cholesterol by raising the observed odds ratio to the power of 1.0 divided by the observed LDL cholesterol reduction.

Table 1 shows the calculated effects of a 1 mmol/L reduction in LDL cholesterol on risk of stroke, according to type of stroke and whether patients were known to have vascular disease or were not known to have vascular disease.

Table 1: Effect of cholesterol reduction on all stroke, by risk factors and stroke type

Category	Trials	Events	Percent change in risk (95% CI)
All stroke	41	3319	-20 (-14 to -26)
All stroke in people with known vascular disease	32	2311	-22 (-28 to -16)
All stroke in people without known vascular disease	7	752	-6 (-22 to 14)
Thromboembolic stroke	8	1204	-28 (-35 to -20)
Haemorrhagic stroke	8	149	-3 (-35 to 47)
Fatal stroke	56	678	-2 (-17 to 16)
Non-fatal stroke	40	2519	-23 (-29 to -16)

Comment

From cohort studies, reduction in LDL cholesterol is known to reduce thromboembolic, but not haemorrhagic stroke (and elegantly explained in the paper). Most non-fatal strokes are thromboembolic, which explains the significant effect of cholesterol reduction on non-fatal, but not fatal strokes.