Loss of Y Chromosome and Major Cardiovascular Events in a Prospective Study of Older Men

Why it matters

Losing the Y chromosome from some blood cells is the most common acquired chromosome change in men and rises steeply with age. It is a large-scale form of somatic genomic instability. Earlier studies linked it to heart disease, but mostly in men who were already ill. This study follows healthy older men forward in time, which makes the link more convincing. Because loss of Y can be measured from standard genetic data, it could become an easy marker of how much somatic genomic damage a man has built up.

What they did

The researchers studied 5,131 men aged 65 or older from the ASPREE trial who had no cardiovascular disease at the start. They measured the percentage of blood cells missing the Y chromosome using microarrays and recorded heart attacks and ischaemic strokes during the trial and afterwards. They analysed loss of Y both as a continuous measure and in groups (none, moderate, substantial), and checked the result in 191,340 men aged 40 to 70 in the UK Biobank.

What they found

Over a median of 8.4 years, 9.8% of the men had a major cardiovascular event: 5% had a heart attack and 4% an ischaemic stroke. Each standard-deviation increase in loss of Y was linked to a 14% higher risk of heart attack (hazard ratio 1.14). Men with substantial loss (the top tenth) had a 68% higher heart-attack risk than men with none. No link was seen with stroke, and the results held up in sensitivity analyses. In the UK Biobank, loss of Y was also linked to heart attack, more weakly (hazard ratio 1.03 per standard deviation).

Limits

This is an observational study, so it cannot prove that losing the Y chromosome causes heart attacks. The ASPREE men were healthy volunteers and may not represent all older men. The effect in the younger UK Biobank men was much smaller, and the abstract does not explain the mechanism.

Key terms

Loss of Y (LOY)

Some blood cells losing the Y chromosome during life, common in older men.

Somatic mosaicism

Different cells in one body carrying different DNA.

Major adverse cardiovascular event (MACE)

A combined outcome including heart attack and stroke.

Microarray

A chip that measures DNA at many points at once.

Prospective study

A study that follows people forward from a starting point.

Standard deviation

A measure of spread; one standard deviation is a typical step up or down from the average.

Ischaemic stroke

A stroke caused by a blocked artery in the brain.