Struthers, Allan

Professor Struthers has repeatedly spotted new therapeutic opportunities and conducted the initial “proof of concept” studies which, led to confirmation in larger trials. For example, he was the first to ever show that aldosterone blockade had beneficial cardiac effects in man on top of ACE inhibitors (Am J Card 1995, 76: 1259): those effects were to reduce both ventricular arrhythmias and cardiac sympathetic activity. The discovery helped lead to the RALES trial where spironolactone reduced mortality in heart failure (HF) by 30%. He also discovered other mechanisms contributing to aldosterone’s ability to increase cardiac deaths, i.e. it decreases endothelial nitric oxide, it decreases cardiac autonomic function and it increases plasma collagen markers (which are a good surrogate for myocardial fibrosis).

A second area where he made important original discoveries is B-type natriuretic peptide (BNP). He wrote one of the two original studies published together in the Lancet (1993) which led to the use of plasma BNP levels to identify heart failure (HF). A later paper by him, also in the Lancet, confirmed this. BNP is now an integral part of all HF guidelines. Professor Struthers has now moved on to make original observations about BNP in a completely new (non HF) area. He has recently discovered that if an apparently healthy individual has a high BNP level, this often signifies that they have silent coronary artery disease (Heart 2006, 92: 487 and 916). This is a major finding as BNP screening could now be used to help identify those many apparently healthy middle aged individuals whose first ever manifestation of their previously silent coronary disease is sudden cardiac death.

A whole other area pioneered by him is allopurinol. He developed the novel idea that allopurinol could be “oxygen in a pill” because it inhibits an oxidase enzyme which normally “wastes” oxygen in ischaemic tissue. A recent Lancet paper (2010, 375: 2161 – 7) showing this could lead eventually to the use of allopurinol as an oxygen sparing agent in all ischaemic diseases. He had already unravelled the exact mechanism whereby allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not at all by decreasing uric acid. This was a much debated issue before his elegant paper in Circulation settled the issue.

Lastly, he had the original idea behind another paper of major therapeutic importance. In conjunction with Professor McMurdo, he showed that ACE inhibitors improve mobility in elderly, disabled, immobile patients, which should greatly improve the quality of life of many elderly patients. In fact, this paper won the Bruce P Squires award as one of the best in the year. If confirmed, ACE inhibitors could become the equivalent of “exercise in a pill” to the many elderly with limited mobility.