Why do men have more heart attacks?

26 April 2016

Interview with

Dr Vicky MacRae, University of Edinburgh

Heart disease affects one in three deaths worldwide. It's caused when arteries Heart Attackthat supply blood to the heart become narrowed and stiffened and men seem to be particularly vulnerable to this. Now new research suggests that the male hormone testosterone might be partly to blame by transforming the muscle cells found normally in the walls of arteries into bone cells, which build up calcium and stiffen the tissue. Vicky MacRae explains more about the study, which was carried at the University of Edinburgh, to Chris Smith...

Vicky - So this study shows that testosterone, which is one of the main hormones in men, can act on blood vessels and valves in the heart to increase the hardening of this tissue, and this is important because the hardening of the tissue can be linked to increased likelihood of a patient getting heart disease.

Chris - So, is it fair to say that this goes some way towards explaining why men might be more at risk of heart disease, which they are, than women?

Vicky - Definitely.  The hardening of blood vessels has been previously been correlated with increased risk of heart disease and it's been shown that men are more susceptible to heart disease, so I think this really fits well with this theory.

Chris - So how did you show that the androgen, the testosterone, that men have, makes the vessels harder?  What did you actually do?

Vicky - We used samples from patients who have hardened valves and hardened blood vessels and we studied these. We also looked at cells that we'd taken from the walls of arteries and we put these into dishes in the laboratory and studied these by adding testosterone and other agents that cause the cells to harden in a similar way to that that happens in the patients.

Chris - Do we understand what actually causes the hardening? Why are things getting hard in the first place?

Vicky - Well the main difference is you've got your cells in your arteries becoming more bone-like.  So they're undergoing this transformation to become more like bone tissues and you actually see molecules that are associated with normal bone development and bone growth turning on in these diseased tissues.  So it's the process of the blood vessels actually almost becoming like another tissue which is enabling this process to happen.

Chris - And the calcium we associate with the skeleton, does that build up there as well?

Vicky - Yes, so you get formation of little crystals which are a mixture of calcium and phosphate in the blood vessels and in the valves so calcium plays a very important part in this.

Chris - And your experiments using the cells in the dish that you then add the testosterone to them, that's making those cells become more bone cell-like, is it - that's how they respond?

Vicky - That's right.  So when we culture ourselves in a dish, we add phosphate which mimics the conditions often seen in chronic kidney disease where the patients have higher levels of phosphate which causes these cells to change into a more bone-like structure and then, on top of this when we add the testosterone, this accelerates this effect.

Chris - But do you understand or have any insights into why the lining of a blood vessel needs to pretend it's a bone?  Why should it respond to testosterone in that way?

Vicky - In general, one idea actually is it's a protective mechanism.  The tissue is becoming very damaged, the cells are dying and the tissue actually calcifies to almost stop any more degradation happening and to kind of stabilize the area.  But, at the moment, it's a very understudied area - there's a lot more to find out, and a lot more research to do.

Chris - What are the implications of this Vicky because, obviously, half the population are male so they're going to have high levels of testosterone? Also, a proportion of the population, probably illegally, are using anabolic steroids. These are forms of testosterone that are there to bulk up muscles, but are they going to have the same sorts of effect?

Vicky - This research certainly highlights the potential dangers of abusing steroids and the fact that adverse effects of steroids on your cardiovascular health.  In terms of preventing this obviously, at the moment, there's no real way to prevent vascular calcification or hardening of your arteries.  There's no drug to stop this at the moment so the best way forward would be to have a healthier lifestyle, taking regular exercise, have a good diet. At the moment, research is still ongoing to try and understand the pathways behind the process and ways that we might be able to stop it from happening.

Chris - And can you reverse it?

Vicky - That's really the gold standard of the kind of research field that we're into at the moment.  At the moment a lot of studies focus on can you prevent it from happening in a model where you know where it'll develop but once it's actually developed, to reverse it is very difficult. And so I think a lot more research needs to be done and a lot more understanding of the pathways, to make the bone go away is a very difficult thing indeed but, hopefully, in the future that would be the aim.

Chris - And could we use it as a screening test?  For instance, are there markers that we could use which tell us: ah, this persons at a higher risk of this happening, they're at higher risk of hardening of their arteries and having a heart attack - we need to intervene with other heart sparing procedures?

Vicky - Definitely. I think it could be brought in with a whole range of other potential risk factors that you could study. It's possible to image calcification at really high resolution now as well, so you could see tiny specks that might then develop into areas of calcification which, to the naked eye, you wouldn't be able to detect.  As imaging techniques become more and more sophisticated this could definitely become part of that profile.

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