Heart Attack, the Diabetes Equivalent

We all know that diabetes has often been call a CAD equivalent, obviously because diabetes cause many of their morbidity and mortality by their micro-vascular and macro-vascular effects. In the good (or not so good) old days, diabetics died from hyperglycemic effects. With insulin and many of the aggressive medical regimes, ketosis and acidotic comas are rare now. So many diabetics now die from CVS disease, heart attacks, strokes and the like.

A recent study by the Italians and reported in the 25th August issue of Lancet, showed that many patients after having suffered from a heart attacks, develop frank diabetes or IFG (impaired fasting glucose).Over a five-year period, Mozaffarian and colleagues tracked new-onset diabetes or the development of impaired fasting glucose (IFG) in a cohort of more than 8000 nondiabetic men and women who had experienced a recent AMI at baseline. Study participants were were part of the GISSI-Prevenzione trial, one of the first studies to establish the benefits of a Mediterranean diet, high in n-3 polyunsaturated fatty acids. The investigators also collected information on body-mass index (BMI), cardiovascular risk factors, diet, lifestyle, and medication use at baseline and over the follow-up period. Mozaffarian and colleagues showed that after an average followup of 3.2 years, 33% of the study cohort developed frank diabetes, and 62% of them had fasting blood glucose in excess of 5.6Mmols/L, against a rate of 3.7% and 27.5% respectively, in the general study cohort. The comparative annual diabetic rates for the general population is 1.8% and 1.6% respectively. The data shows clearly that after you have a heart attacks, you are obviously at risk of developing diabetes.

I suppose the next question that clinicians will ask is, "Is there a good explanation?". I am not sure. Obviously, more work needs to be done. I suppose, a heart attack is a great stress, and stress may precipitate a diabetic state in those likely to develop diabetes. What is even more interesting is that those on a mediterranean diet and a diet also lower in saturated fats and carbohydrates, have a lower risk of diabetes. The study did not study the effects of ACE-I or ARBs in this setting. Perhaps ACE-I and ARBs in this setting will show an even more diabetes protective effect. How interesting, Diabetes is a CAD equivalent and now it seems likely that CAD maybe a diabetes equivalent.

More Evidence on Abdominal Adiposity and CAD

The lastest issue of the Journal of the American College of Cardiology carry a study by the University of Texas, which again found an association between abdominal adiposity and CAD. They define abdominal adiposity as a abdominal girth in excess of 32 inches in females and 37 inches in males. They use calcium score on MSCT as an early index of CAD.

Instead of just measuring abdominal girth, they found that waist to hip ratio (WHR) was an even better index. This is of course not new news, as we have had many studies before which have taught us that WHR was a better predictor of CAD than just weight, or BMI alone. The Japanese have gone further that abdominal adiposity is associated with a lack of adiponectin and an increase in inflammatory markers, suggesting that the abdominal adiposites are actively promoting inflammation and lowering the protective effect of adiponectin.

Of course we are not forgetting that abdominal adiposity is also strongly associated with the metabolic syndrome, which is strongly predictive of CAD. Looks like the evidence here is very strong and fairly well worked out. What is even more encouraging is that reversing the abdominal girth also lessens the CAD risk, giving all us us with large abdominal girth, hope to better ourselves. There is also a follow-up study in UK which showed that if we walk briskly, for 15-30 mins daily can help lose our abdominal girth, lose our weight and also lessens our CAD risk.

Of course, it looks like the Italians will top us again. In the small Italian town of Varallo Sesia, a town of about 7,500 people, the Mayor has offered to reward any obese citizens of the town 50 euros for every 3 Kgs lost in a month and if you can maintain this lost for 5 months, you get another 100 euros. How about that. Needless to say, that many lined up to register. You must be medical certified, of course, before you can collect your money. Well there you are, obesity and shedding obesity, has its rewards, and not just CAD protection.

Pollution and CAD - An Inconvenient Truth

Traffic jams are a way of life here. I meet it everyday. Thank God that we face in in our cars. In that sense, we are part of the pollution process. For a long time, we have been wondering about the impact of traffic jams on CAD. It is obvious that one of the problem with traffic jams is stress and hypertension. Emotional stress is a part of modern day living. Perhaps that is why there is more heart disease in this modern generation, despite all our effective primary prevention programs.

The latest online journal of Genome Biology reported an article by Dr Andre Nel, a nanomedicine expert, on the effects of diesel and LDL-C on CAD. In an elegant piece of basic science work, he cultured endothelial cells with diesel pollutants and LDL-C, and noted that these cells express more inflammatory molecules, then those cells cultured with either molecule alone. This gives rise to the interesting theory that diesel pollutants and LDL-C excites oxidative stress and this in turn, initiates atherosclerosis. Interesting.

So when we are walking in a space full of smog and pollution, our arterial wall is bombarded with these pollutant/LDL-C molecules, that begins to clog our arteries. Can you imagine what is happening when September comes and the yearly haze begins. Alas, we have no clinical studies here to see if there is an increase incidence of heart attacks, during the "haze months". Perhaps, Malaysia would be a good country for Dr Andre to test his hypothesis in humans.

COURAGE from ACC 2007

The biggest news from from ACC 2007, New Orleans (at least if the normal talking heads on the internet are to be believed) is the "Courage" trial.

Courage stands for "Clinical Outcomes Utilising Revascularisation and Aggressive Drug Evaluation". This trial was originally scheduled for 27th March (last day of the ACC) but had to be brought forward because a speaker (Dr Martin Leon) at the earlier weekend symposium seemed to have broken the embargo not to discuss the trial before it was formally presented. Once the results were leaked the press honed in like hungry sharks, nothing leads better than bad news and this one bled all the way to the columns above the fold, the ones with big big fonts. The organizers felt that they had to bring forward the presentation by one day.

Make no mistake. COURAGE is an important landmark because it will influence the practice of interventional cardiology. COURAGE enrolled 2287 patients from 1999 to 2004, and had mean followup of 4.8 years. The PI is Dr William Boden of Buffalo GH. They compared patients with CAD treated with PCI + optimal medical therapy against patients who only received optimal medical therapy. After a mean followup of 4.6 years, they showed that there was no difference in death, heart attacks and strokes. There was a difference in chest pain control (more of the PCI group had less chest pains).

This study findings is not really surprising. Angioplasty has never been shown to reduce death or MI especially in the assymptomatic population. PCI does reduce death and MI in certain subsets like unstable angina (currently called acute coronary syndrome). This trial is not without flaws. Remember the physicians were not blinded. How can you blind against angioplasty. It could be that more severely ill patients received PCI.

Anyway "COURAGE" is interesting. What are the implications of this trial results (if you believe in evidence based medicine).

1. Checking out assymptomatic individuals, diagnosing CAD by MSCT and reacting to it with angiogram and angioplasty, is not supported by this trial result. You need chest pains or inducible ischemia, to justify intervention. Assymptomatic patients with high calcium scores, should receive optimal medical therapy.

2. That after coronary angiogram in assymptomatic patients, interventionist will have no basis to go on to PCI (oculo-stenotic reflex), without giving a period of optimal medical therapy.

3. Those who treat assymptomatic patients aggressively with medical therapy know that they are supported by the "COURAGE" study. They are medico-legally protected.

4. Maybe MSCT company shares and interventional company shares will fall. Clinical guidelines, will have to be amended. I am sure that non-interventionist will accuse interventionist of "dilating for bread" . Perhaps they are right. I am sure that more is to come, on this subject.

Folic Acid And The Heart

Preventing CAD is very important. This is the primary strategy in our fight against CAD. Indentifying coronary risk factors (CRF) is something that any rookie doctor should be able to rattle off without much ado. Hypertension, diabetes, cigaratte smoking, hyperlipidemia, obesity should pop right off the top of the head. However homocysteinemia is the odd one.

I always had trouble understanding homocysteinemia as an important CRF. Even the pathogenesis of homocysteine promoting CAD is difficulty to work out. However, many considered the use of folic acid for lowering serum homocysteine as innocuous enough to accept it without close scrutiny of data, for a long time. Recently much meta-analysis and clinical trials has been undertaken to see if folic acid actually help, indirectly asking if homocysteinemia is actually a CRF?

Dr Lydia A Bazzano, et al. published an article entitled "Effect of folic acid supplementation on risk of cardiovascular diseases. A meta-analysis of randomized controlled trials". JAMA 2006; 296: 2720-2726, which found no diference between those given folic acid and those not on folic acid, again underlining the fact that homocysteinemia is a very controversial CRF.

Having analysed 12 controlled clinical trials with a total of about 16,500 patients make this a very large meta-analysis. However, there is a yet bigger meta-analysis by Oxford on the way. For the moment, use folic acid supplements, if you wish. It is safe without side-effects, but whether you need to or not, is not so easy to answer. I rather suspect, maybe not. Suffice to know that I don't see another large RCT, perhaps only more meta-analysis, with all the shortcomings of meta-analysis.

Athelete's heart or early CAD

Is there such a thing as the athletes' heart? I am encouraging my patients to exercise as a means of primary protection against coronary heart disease. Some of my patients are quite serious about exercise and in fact are runing regularly with the hash harriers and pacemaker clubs. In fact a few of them are running 40 Km marathons regularly. Is this wise?

When we see "fit" well trained patients with a low heart rate and enlarged heart, we attribute all this to their fitness and regular exercise. The enlarged heart we call "athlete's heart". But is there such an entity and is it normal. We have written earlier, that marathon running can be associated with rises in CKMB and troponin T, suggesting myo-sacomere destruction with marathon running.

At the recent AHA annual scientific meeting in Chicago, Dt Stephan Mohlenkamp presented the Master Marathon Study. They studied about 100 marathon runners (run at least 20 marathons over the last 20 years), who had a low cardiac risk profile using the Framingham Scores. They subjected these runners to echocardiograms, the MSCT and the Calcium score, and found that many of them had enlarged heart with increase calcium score, suggesting that these marathon runners in fact may have subclinical CAD.

A week later, at the American Radiological Society Annual Scientific meeting, also held in Chicago, Dr Torleif Sandner of Munich also presented another study done in on the same population of now 110 marathon runners, now average years 57, to MRI scans of the heart in an attempt to measure their LV mass. They found that these marathon runners all had an increase LV mass of 150 grams or more. Obviously this second study was done in collaboration with the first study. When they compared their studies, they found that those runners with higher calcium score also had higher LV mass, suggesting that the increase LV mass may be related to early CAD as suggested by the increase calcium score. Interesting.

I have never been a firm believer in calcium score having a positive correlation with presence of CAD. I have always thought that zero calcium score is better correlated with lack of CAD. Anyway, I thought it interesting that fit marathon runners should be careful. You may have early CAD. If that is true, it further supports the earlier posting that the rise in CKMB and Troponin T may be due to some degree of heart muscle damage from micro-infarcts. Marathon runners beware.

Drug coated balloons

When DES (Drug eluting stent) was first announced to the world in 2001, it was touted as a revolutionary advancement in PCI. This advancement would solve all problems of percutaneous coronary intervention for CAD. At that time, little did we all realise that altthough DES did solve the problem of re-stenosis, it created a new problem of late stent thrombosis, first highlighted to us by the Swiss in the Late Basket Trial, and now openly announced and debated in ESC/WCC in September in Barcelona and later again debated in TCT/Washington in October. This is now widely seen as the inter-Atlantic Stent-war.

It looks like there is an issue, a problem of late stent thrombosis with DES (much as the Washington Americans would not agree). It does look like the fact the DES lessens and delays re-endothelialisation, this fact actually promotes stent thrombosis, making deployment technique and the role of plavix, absolutely vital. Of course the patient mix is also important.

With that long intro, the latest issue of the New England Journal of Medicine, had an article by a group of Germans interventionist (I must say that this are the lesser known Germans in our circle), who studied 52 patients with in-stent restenosis following bare metal stents, who received treatment witha paclitexal coated balloon. They compared their results with the control group who were tretaed with plain old balloon angioplasty (POBA). Lo and behold, the paclitaxel coated balloon group had restenosis of about 5% as compared with the POBA-treated group who had a restenosis rate of 43%. POBA is one of the ways of treating restenosis of bare metal stents in the days before DES.

What is amazing is that a drug coated balloon, inflated over a lesion for about 1 min, can affect tissue reaponse in such a significant manner. Of course, we are all holding our breathes to see if we can achieve this good result in native, virgin lesions. We must note that an in-stent restenosis lesion is not like a native, virgin atherosclerosis lesion.

This paper is very interesting and I am sure that other groups will begin to do the same and perhaps a large scale clinical trial will result, either confirming or disputing this findings. What was also intriging for me was that this work was not broadcast on the world stage of TCT Washington.

We should probably also take some time on this blog to comment on the industry news that JnJ Cordis has acquired Conors (the owners of the Costar technology).