Low cholesterol linked with enhanced risk of death

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I saw a patient this week who occasionally feels light-headed, particularly when he stands up quickly. This symptom – referred to as ‘postural hypotension’ in medicine – usually signals that someone’s blood pressure is on the low side, and drops even lower on standing. Sure enough, his blood pressure was low (100/70 mmHg). Most doctors here in the UK like to see a low blood pressure, and often remark that this means the person has likely immunity from raised blood pressure.

I, personally, don’t have so much of a relaxed attitude to low blood pressure. First of all, pressure is required to ‘force’ blood into the organs and tissues including the brain. If blood pressure is too low, vital organs may be effectively starved of blood and therefore not function optimally. Everything in the body, be it blood pressure, sodium levels or temperature, has an ‘optimal range’. Too much of something is, by definition, a problem, but by the same token so is little (if blood pressure gets low enough we lose consciousness and can die).

Could the same be true for cholesterol? I know there’s a vogue among members of the medical profession and certain scientists to urge us to drive our levels to ever-lower levels (‘lower is better’), but does this actually make sense? Cholesterol is, after all, an essential constituent of several important entities in the body including the brain, vitamin D and ‘steroid’ hormones such as cortisol and testosterone. If blood cholesterol levels get low enough, could this starve the body of essential element and therefore jeopardise health?

While ‘raised’ levels of cholesterol are associated with an increased risk of heart disease, lower levels of cholesterol are also associated with an increased risk of cancer as well as ‘haemorrhagic stroke’ (strokes caused by bleeding in the brain). These observations do not mean that low cholesterol causes cancer or stroke (neither do they mean that cholesterol causes heart disease either).

In order to get a best overall picture of the relationship between any factor and health, it makes sense to assess its relationship with overall risk of death – also known as overall mortality.

Previous evidence has revealed that while higher cholesterol levels may be associated with increased overall mortality in younger individuals, this trend reverses as people age. The relevance of this is that most individuals die when they are advanced in years, and therefore the relationship cholesterol has with overall mortality in the elderly is, generally, much more relevant and important than this relationship in the young.

A recent study illustrates this [1]. In it, researchers examined the relationship between overall mortality and individuals aged 60-85 (average age 71) over a period stretching 12 years. Initial analysis revealed that higher total cholesterol levels (> 200 mg/dl/5.2 mmol/l) were associated with a 24 per cent reduced risk of mortality over the study period. And lower cholesterol levels (< 170 mg/dl/4.4 mmol/l) were associated with a 60 per cent increased risk of death.

Some claim that the association between lower cholesterol levels and increased risk of death is due to the fact that when individuals are ill or frail their cholesterol levels tend to be low. In other words, the heightened risk of death is due to the illness and/or frailty associated with low cholesterol, not the low cholesterol per se.

To adjust for these so-called ‘confounding factors’ the data was reanalysed, this time after removing individuals who were low in weight (BMI < 20) and/or who died within 2 years of the analysis starting. Once these adjustments had been made, the relationship between raised cholesterol and lower risk of mortality was no longer statistically significant. However, the relationship between lower cholesterol levels and increased risk of death remained (36 per cent increased risk).

Again, epidemiological studies of this nature do not tell us if the relationship between lower cholesterol levels and reduced survival is ‘causal’. However, this sort of evidence should at least cause us to pause before we recommend that individuals, especially elderly ones, drive their cholesterol levels to ever-lower levels (like some would have them do).

References:

1. Sarria Cabrera MA, et al. Lipids and all-cause mortality among older adults: a 12-year follow-up study. Scientific World Journal Epub 1 May 2012

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