Oxymorons and unintended consequences

I receive a daily digest of articles from the HSJ, or Health Service Journal in full. Today there are two headlines:

More trusts considered for ‘financial special measures’

All trusts given new targets to achieve provider sector surplus

Now Trusts considered for special measures are, basically, in financial trouble, in other words in deficit.  Many such Trusts have been unable to solve their deficit problem, and have had a succession of managers who have come and gone as the impossibility of balancing the books and maintaining safe clinical services becomes apparent.  As I have commented before, reducing deficits means cutting services, while maintaining these with adequate staff means increasing the deficits; there is a limit to how long the pips can squeak for.  The disastrous failure of clinical safety in Stafford will almost certainly be accepted to have been due to the cutting of corners, but the Care Quality Commission can put a Trust into special measures if its finances are wrong (even if its clinical services are fine) or if its clinical services are wrong (but its finances are fine). Heads I win, tails you lose.

To achieve a provider sector surplus requires Trusts to save more money still.  If they cannot do it now, how will they possible do it tomorrow? And what will be the effect on their clinical services if they succeed?

So these two juxtaposed headlines are, effectively, mutually exclusive.  The irony of the juxtaposition appears to have escaped the HSJ.  However there is another ingredient to this toxic mix. Jeremy Hunt,  the Rachman landlord of the NHS, has spoken at the Conservative party conference to announce that he intends to force trainees to stay in the country after qualification for four years, because too many are leaving and abandoning patients to foreign doctors who can’t speak good English.  He also intends to increase medical school entry to make it less necessary to recruit NHS medics from abroad, but also fill the unfilled posts currently washing around the system.

But herein lies a problem.  If Trusts are bust then how will they be able to employ more doctors?  It won’t help the provider sector surplus, will it? Cutting deficits means shedding staff, not employing more.

Of course what Mr head-in-the-sand Hunt has failed to realise, or chooses to ignore if he has realised, is that doctors are voting with their feet because life as an NHS doctor employee is becoming intolerable.  He won’t fill medical school places when all the prospective students are being put off by their medical friends, parents and relatives.  So before trying to induct more people into this uncomfortable and failing system he should first address the concerns of doctors over workloads, continuing education, regulation and bullying (viz the attempt to enforce a new contract).  Then we might get somewhere.  But he will never produce results from a sullen and rebellious workforce.

 

Cardiovascular risk, Cholesterol and NSAIDs

The complexity of the inflammatory response continues to puzzle the medical world.  Arterial plaque in the coronary vessels predisposes to heart disease, but why does it develop? Is it due to high cholesterol levels (seeing as cholesterol is present in them) or primarily due to intimal inflammation? Non-steroidal anti-inflammatory drugs (NSAIDs) reduce inflammation but increase cardiac risk.  Treating an “inflammatory” disease such as rheumatoid arthritis (RA) with a disease-modifying drug – and RA has a high cardiac risk – appears to diminish that risk, but using an NSAID increases it.  If inflammation is a single entity these facts conflict.

The answer to what causes the increased cardiovascular (CV) risk from NSAIDs appears to lie in the cyclooxygenase pathway and I am grateful to Fred Kummerow of THINCS for my Damascene moment[1].  The enzymes COX-1 and COX-2 (primarily COX-2) are principal agents in the genesis of prostacyclin, which is a vasodilator, and of platelet aggregation inhibition.  Thus suppressing them leads to a reduction of prostacyclin and an increase in platelet aggregation, and suppression of COX-2 will produce a greater effect than suppression of COX-1.  Arterial plaque is irregular and platelets will stick to it – which will trigger aggregation.  So although the COX enzyme by-products are inflammatory, inhibiting them will increase the risk of platelets sticking to plaque, and the reduction of prostacyclin will mean the vessels, plaque or no, will be narrower than they would otherwise.

That explains not only the increased risk, but also the reason why COX-2 inhibitors have a worse effect on cardiovascular disease than COX-1 inhibitors.  Of course, research into RA has shown that the inflammatory cascade is unbelievably complex, with the interaction of T- and B-lymphocytes, tumour necrosis factor, interleukins (and we number them in dozens), complement, autoantibodies, immunoglobulins and other immune mediators.  Of interest is that nitric oxide, which plays a part in vascular integrity, may also be important in RA.

There does not appear to be any evidence supporting a hypothesis that cholesterol plays any part in altering COX enzyme levels.  There is, however, evidence that exposure to trans fats does.  These are found in partially hydrogenated oils, and ingestion of these produces substantial reductions in prostacyclin release.  The belief that trans fats were no different from other fats has been upset both by this finding and by the chemical analysis of them showing that there are subtle differences in molecular structure with the production of isomers that do not occur in nature. These are recognised as foreign by the body and provoke an inflammatory reaction. There is also good evidence to show that the increase in CV mortality during the last years of the 20th century has a direct relationship with trans fat intake, and likewise the removal of trans fat from consumables has been mirrored by a reduction in mortality.

Plaque generation per se is not related to lipid levels either.  The fact that cholesterol is found in plaques is simply an expression of what happens when intimal damage is followed by an attempted repair process.  Reducing cholesterol will not reduce the risk of plaque formation, as it is not the cause of the initial intimal damage.  Neither will reduction alter vascular calibre or interfere with surface platelet aggregation on an arterial plaque. There is now too much evidence and too many “Black Swans” that contradict a direct link between cholesterol and vascular disease for this link to be acceptable.  There is plenty of evidence to explain both the causes and mechanisms of vascular disease, but I hope to see an understanding that statins are, population-wise, a costly mistake.  There is good reason to suppose that aspirin, which is a potent inhibitor of platelet aggregation, is of more use in CV protection that cholesterol-lowering drugs.  I have a personal reason to suppose this is true.  I have suffered from migraine from the age of 12 (when it might reasonably be supposed that my blood vessels were clear of cholesterol-laden plaque despite my high blood levels).  Migraine is a condition in which an aura, is followed by a typical headache.  It was hypothesised many years ago in an article in “The Lancet” that the cause of the aura was ischaemia as a result of localised platelet aggregation, which with the subsequent release of prostacyclin as a response resulted in vasodilatation which caused the headache.  I began taking aspirin and my attacks, which were severe and occurring monthly or more often, stopped completely.  After five or six years of symptom-free life I stopped the aspirin without ill effect, but after a decade the attacks re-started, interestingly with the same intensity of aura but a much reduced subsequent headache.  I began taking aspirin once more and my auras vanished again.  While I accept that I am treating a condition on the basis of a hypothesis I have been unable to find another sensible explanation of the aspirin effect.

[1] Kummerow FA. In Fat and Cholesterol Don’t Cause Heart Attacks and Statins are Not the Solution (Ed Paul J Rosch) 2016: Chapter 4, pp65-71.