CANCER RISKS THAT CARDIOLOGIST MUST BE AWARE OF

The month of September 2011, may be noted as the month with new data on cancer risk. That dreaded disease with much morbidity and mortality. Avoiding cancers become and important part of adult life.

Firstly, The Sept 19th issue of the American Journal of Transplantation, carried a piece of work by the workers in Heidelberg University, Germany. Led by Dr Gerhard Opelz, they looked into the Collaborative Transplant registry. This is a prospective transplant registry involving 400 international transplant centers. This registry, across 400 centers, involving 24,000 patients, was tracking patients since 1998. They looked at the patients who were transplanted, who were using either ACE-I or ARB, and who smoked. Of course, transplanted patients, because of the immunosuppressives that they are on, are at higher risk of cancers. Dr Opelz and colleagues, found that there was a correlation between the use of ACE-I and ARB, smoking and lung cancers. Those who were on ACE-I or ARB but who do not smoke had no such association.
This study then join the growing list of studies which showed that there may be a correlation between ACE-I / ARB and cancers.
It looks like on this issue, there are now two camps. The pro ACE-I / ARB cancer risk camp would include this study, the Sapahi study, the DIRECT study. The anti ACE-I / ARB cancer risk camp would include the FDA announce earlier this year, the Bangalore study, and the ARB Collaboration Trialist. I do not think we have heard the end of this story yet.

The second was a presentation at the 2011 European Multi-discipline Cancer Congress. This was held recently at Stockholm. At this meeting, Dr Mieke Van Hemelrijck and colleague from the King's College, London, reviewed, the records of about 560,000 patients from the Me-Can project ( Metabolic Syndrome - Cancer project ). This project collects data from cancer patients across Europe, from Norway, Sweden and Austria. They studied patients who have a record of two or more BP readings to see who has hypertension. After 12 years of follow-up, they found that those patients who fulfilled the criteria of hypertension, had a correlation with cancers, amongst the males. With the females, there was correlation was not statistically significant. Hypertension, in this cohort, was associated with cancers, in males, like ca lung, colorectal ca, oral ca, bladder ca. There was no correlation with one type of cancer.
They concluded that in males, a history of hypertension may put you at risk of cancers. This study again is an observational data, but because it involved half a million patients followed up for 12 years, it must carry some message for us. Unfortunately, this study, does not record the drugs that those hypertensives were on. I am not sure if the King's College workers will look into that issue now. Perhaps they can throw some light into the issue of ACE-I / ARB and cancers, as it is very lightly that many of those hypertensives in their cohort, could be on ACE-I / ARB.

I suppose, the take home message would be to keep a healthy lifestyle ( as if we do not know that ), and take drugs only if you really have to. Good drugs ( presently ), may later be shown to be harmful ( in 10 years time ). One never knows.

AIR POLLUTION TRIGGERS HEART ATTACKS.

With rising concern about the environment, and in particular air-pollution, there are now more and more studies highlighting the harmful effects of air pollution and the heart. I have written on this before.
In the latest issue of the British Medical Journal, Dr Krishnan Baskharan and colleague from the London School of Hygiene and Tropical Medicine, studied the records of 80,000 heart attack survivors in England and Wales. They then plot the hourly pollution index of that locale and found that there seem to be a correlation between heart attacks and pollution index, up to six hours. Meaning that exposure to pollution could trigger a heart attack, within 6 hours. They were quite clear in saying that pollution, did not cause the heart attack, but it may have triggered the heart attack. There seemed to be some statistical correlation.
The how is much more difficult to answer. It is lightly that petrol fumes and pollution increase the viscosity of the blood, or may have produce coronary vasospasm, thus triggering the coronary thrombosis.
It is noted that this is a retrospective study from case records, and thus cannot be conformatory, it would be good advice for patients with coronary artery disease to avoid polluted areas, if at all possible, otherwise, there is an immediate danger ( within 6 hours ) that the pollution may trigger a heart attack.
I would like to see the same study carried out in China, or even Malaysia, seeing that before this round of rain, the air was quite obviously polluted and smell of the haze.

MORE PROBLEMS FOR SANOFI ADVENTIS. THE ISSUE OF DRONEDARONE

I have just read the announcement by the European Medicine Agency ( EMA ), that they will be recommending restricting the use of dronedarone. This is of course, following the release of the PALLAS data, which showed that the use of Dronedarone in patients with permanent atrial fibrillation was associated with a higher incidence of cardiovascular events. There were several small studies which seem to suggest that Dronedarone may also be associated with liver and lung damage ( sounds like amiodarone !! ).
Dronedarone is an anti-arrhythmic manufactured by Sanofi Adventis, for the use in patients with paroxysmal atrial fibrillation or persistent, but non-permanent atrial fibrillation, to try and chemo-revert them and also to maintain sinus rhythm. It was launch by Sanofi Adventis in the early part of this year in Malaysia, with some pomp and fanfare, all staff dressed up in Greek attire to reflect the ATHENA study, which promote the use of Dronedarone.
I do have a few patients on Dronedarone. In two of them, with paroxsymal atrial fibrillation, it failed to convert and failed to maintain. One of them had severe gastric upset and refused to take the drug. There is only one patient left on dronedarone. I must inform him, when he next comes for checkup, that there are problems with this drug.
The US FDA never approved its use, so this is not an issue in USA.

UN INITIATIVE ON NCDs

It is laudable, for the United Nations to take up the subject of non-communicable diseases, amongst the many important items in the UN General assembly, going on in New York, at the moment. calling it the United nations ( UN ) High Level Meeting on Prevention and Control of Non-Communicable Diseases ( NCD ). By non-communicable diseases, they mean Cardiovascular Disease, Diabetes, Cancers and chronic Respiratory diseases.
The UN secretary general Ban Ki-moon, noted that NCD kills about 25% of the population in the prime of their working lives. WHO projects that NCD will rise by 17% over the next decade and by about 24% in the African countries. If this trend continues, it will cost the world economy trillions of dollars to control. We can see the spread of this non-communicable diseases from the first world nations, now to the third world nations, driven mainly by the globalisation of unhealthy lifestyles.
However, besides centering on tobacco, the UN initiative is short on details, as to how to carry out a co-ordinated preventive program. Some mention was made about the negative impact on food advertisement to entice children, but not much is said as to how to stop it. I suppose this is mainly due to the strong fast food lobby.
Well, at least it is a start, I suppose. The world is waking up to the fact that we could be losing trillions of dollars if we do not control this NCD epidermic.
Well, the gong has been sounded. Lets see what happens next. Will it be back to life as usual, or will we as a global community, begin healthy lifestyle programs, of exercise, eating less salt, food calorie labelling. stop smoking, preventive check-ups for all adults, ban fast food advertisement, reward slimmers, etc.
I am afraid that I am not so optimistic. Remember, Malaysia uses her many unhealthy foods as a tourism promotion strong point., .............. so.
Well, at least it is a good initiative.

WHAT SHALL WE EAT. MORE NEWS FROM EASD

The Atkin's diet was a rather popular diet to lose weight, when Dr Atkins was alive. Books were written and some proponents swear by it. It did certainly lose weight in the short term, but is it good for the body in the long term. No, I am not going to discuss Atkin's diet per se, but I am relating to a paper presented at the just concluded EASD ( European association for the study of Diabetes ) 2011, Lisbon, Portugal.
Dr Ulrika Ericson and colleagues from the Lund University at Malmo, Sweden, presented a paper on the association of a high protein diet with diabetes.
Dr Ericson and colleagues looked into the Malmo Diet and Cancer Cohort. Picked out 27,140 patients who had no diabetes, and followed them up over 15 years. More than half the cohort were females. They took a detailed diet history from each of the patients, including a 7 day diet diary, have them fill up a 168 items questionaire, and also interviewed them for 45 mins.
After a follow up of 15 years , they found that those on a high protein diet had a 37% increase in the incidence of diabetes. So also those on a diet, high in process meats, poultry and eggs. Surprisingly, those on a high carbohydrate, did not show such a trend. What was good was that those on a diet high in high fibre cereals and breads showed a 30% decline in the incidence of diabetes.
Well this is not a study on the Atkins diet, but the study criteria is almost that of an Atkins.
It is important to note that this is just registry data, on retrospective recall and diary keeping. It is not the most accurate way of studying diet and disease. However, it is cheap and does allow us to see a trend and guide us in what is good and bad for us.
I just wanted to share that a high protein, high process meat diet is bad. Looks like low fat, high cereals and bread diet is good.
But then some us like to eat, in fact some live to eat. We are all different. But then health is wealth too.
Too each his own and all in moderation. That cannot be wrong.

J-CURVE FOR DIABETIC CONTROL. NEWS FROM EASD

The European Association for the Study of Diabetes, have just concluded their annual meeting in Lisbon, Portugal. Amongst, the many interesting paper presented, was one presented by Dr Carl Ostgren ( Lingkoping University, Sweden ) dealing with the issue of a J-curve phenomenon, in diabetic control. Is there a J-curve in Diabetes control ?.
A J-curve phenomenon, is an observation that the better the control of a disease, the better the outcome, up to a certain point. Thereafter, better control, seem to result in more MACE. We have observed this in the control of BP in hypertension. It is well known that when BP control is good, below 130/80mmHg, there is reduction in MACCE. But when diastolic BP lowers below 70 mmHg, there seem to be an increase in MACE especially in patients with a history of CAD. So we are all taught not to lower the BP too much, and also too fast.
Dr Carl Ostgren and colleagues, went through the records of about 33,000 diabetics in the Swedish registry, to analyse HbA1c levels, against registry data of hospital admissions, drug dosages, AMIs, deaths. etc. They also studied the educational levels of their patient cohort.
What they found was that when diabetic control ( using HbA1c levels as a guide ), was between 6-7%, the MACE rates were the lowest. HbA1c levels below 6% and above 7% had higher MACEs, thereby showing that there may be a J-curve phenomenon is diabetic control More intensive control of diabetes, may be associated with more major adverse cardiac events.
Of course, this controversial observation was met wit ( it is reported ) a very heated question time, almost to the point of scolding Dr Ostgren. It is true that observational data is often not confirmatory, and may be more hypothesis generating. Some were calling Dr Ostgren irresponsible to have these reports. Anyway, I believe that as physician scientists, we can see the truth from the facts, and make out our own minds. we must forget that we saw something like this in the large ACCORD syudy, where people rationalised that it was not the level of low HbA1c that was the culprit, but the rapidity at which those levels were reached.
Certainly, like some of my patients, more intensive control means more hypoglycemic episodes. I have a patient ( now 75years ) who insist on insulin and who self increase his insulin dose to achieve a level below 6. He things that he must normalise his blood sugar. No amount of counselling by me and his daughter, will persuade him otherwise. so of course, he has been fainting. I just saw him last week. I hope that he can understand.
To a certain degree, I would agree that there seem to be a J-curve phenomenon is hypertension control and also in Diabetic control
It is only fair to say that the ultimate proof must be large randomised controlled trials, and I do not see any in the horizon.
The controversies continue, and we await more data.

WHITE FRUITS, VEGES AND STROKE

The saying is true. "An apple a day, keeps the doctor away".
Dr Linda M Oude Griep and colleagues at the Wageningen Uni of the Netherlands did a study relating veges and fruits to the risk of strokes. This study is published in the latest online edition of strokes.
What they did was to enrol 20,069 subjects, both male and females, age 20-65 years, with no heart disease or strokes. Let them answer a 178 items fruits and veges questionaire ( the Dutch are very patient people ). Follow them up for 10 years, and not their incidence of chronic lifestyle diseases, especially strokes. In their questionaire, they divided veges and fruits into 4 colour category, namely green would comprise of broccoli, brussel sprouts, orange / yellow would comprise of cirus fruits like oranges, carrots, cantaloupe, red / purple would include grapes, cherries, red cabbage, tomatoes and white would include hard fruits like apple and pear, cauliflower and cucumber. Their theory was that different colour fruits and veges may contain different kinds of bio-active chemicals like carotenoids, anthocyanins, and flavonoids, and so confer different benefits on the human body. They are not the same.
Well, at the end of a 10 year follow-up, what they found ( after adjustments for all the confounding factors ), was that white fruits, the hard fruits confer a 9% reduction in risk of strokes for every 25gms consumes. If you consume 5 servings of white fruots and veges, it could mean a 45-50% reduction in the risk of strokes. If this is proven true by other collaborative studies, then taking 5 servings of fruits maybe better then aspirin, or plavix, or for that matter, BP reduction pills. ( I am talking only on stroke prevention, and only if this study is proven true by other studies ).
Very interesting.
We obviously need more studies, and more people to confirm this findings. This is the first study of this kind that I have come across. I do not see many such studies, because it would have to be public funded ( and the public has not much moeny now, with all the crisis ) and pharmas will not fund it as there is no money to make. I doubt that the fruit sellers and vege sellers will fund it.
As there is little downside, it would be good medical advice for all of us to try and take 5 servings of fruits a day, mainly white fruits if possible. The only good thing about white fruits is that it is hard, quite sweet and you can take it on the run.
So the saying is true. " an apple a day keeps the doctor away ".

FPMPAM weekend seminar in Cardiology for GPs 2011, KUANTAN

I spend the whole weekend in Kuantan conducting the above seminar.
The event went well. About 92 signed up before the event but only about 80 turned up. I am told that by Kuantan's standard, that is good. The whole program went well. We started at about 8.30am and finished at about 6.20pm. many stayed till the end. The program had lectures, questions and answers, ECG tutorials, and CPR lectures and demonstration. About 4 doctors from Kuantan and 6 doctors from Klang valley formed the faculty. About 15 facilitators ( looks like schoolboys from Kuantan ), help to conduct the CPR demonstration. I must say that the Kuantan doctors were quite interactive and question time was well taken up. My lecturers did have some problem with time keeping. Some of them obviously needed some more practice. That is also a part of our aim, conducting doctor's seminars. I am sure that just as the audience gain ( and I hope so ), the lecturers also gain from the exposure. The feedback from the delegates at the end of the seminar was good.
The whole event was held at the Zenith Hotel, Kuantan, a very new facility, with adequate conference facilities. It was new, with a big convention center, and an office block adjoining it. I worry for the marketing department, as they would have to work very very hard to get enough activities, in small, quiet Kuantan, to make ends meet. That would be their biggest challenge in the years ahead. I must say that the hotel food could be better, especially when there are no hawker centers nearby and you are totally dependent on the hotel for food and catering.
I hope that the GPs there gain something from the meeting.
The pharma support was good, and they even organise a lucky draw to attract doctors to their exhibit booth.
The drive to Kuantan was quite pleasant. I took my Lexus Hybrid out as the BMX5 was in the workshop with air-suspension problem ( they cannot find out why my air-suspension was not activated ). It took me 3 and half hours to get there, and it was raining. But the drive was pleasant.
All in all, another successful meeting.
The next meeting will be in Kuching, 7-9th Oct 2011, for the ICF 2011. This will be at the Pullman Hotel, Kuching.

STENTING FOR INTRACRANIAL STENOSIS DOES WORSE THAN AGGRESSIVE MEDICAL THERAPY IN STROKE PREVENTION.

Attention all neuro-interventionist and patients with strokes and TIAs.
The latest issue of New England Journal Of Medicine ( Sept 7th ) carries an article by Dr Marc Chimowitz on the results of SAMMPRIS ( Stenting and Aggressive Medical Management for Preventing Recurrent Strokes in Intracranial Stenosis trial. Dr Chimowitz is from the Medical University of South carolina, and the trial is sponsored by the national Institute of Neuro disorders and stroke ( a government funded institution ).
Dr Chimowitz and colleagues enrolled patients with history of TIA or stroke, with 70-99% intracranial vessel stenosis, randomised them into aggressive medical management only versus aggressive medical management with intracranial angioplasty with stenting using the Wingspan system.
They found that as they enrolled patients, enrollment has to be stopped in April 2011 ( 451 patients enrolled ), when the safety review committee discovered that the intervention arm ( after 30 days follow-up ) had significantly more events and complications than the aggressive medical arm. This trial was scheduled to enroll 750 patients with two years follow-up. Their primary endpoint was of course re-stroke or death, and secondary endpoint was recurrent stroke or TIA.
We learn a few lessons here. We learn that such important trials are better funded by National public bodies ( if they can afford it ) , and not by industry. We also learn that over the years, intensive medical therapy for atherosclerosis and athero-thrombosis, has progress by leaps and bounds. Intracranial intervention, is much more tricky then extracranial interventions and carries a higher risk and complications. The trial reported a 30% incidence of cerebral hemorrhage and vessel perforations.
This is the third such trial to show this result. The other two also had similar outcomes, telling us that intracranial stenosis should be left alone on intensive medical therapy.
But then, this means that the interventionist cannot " dilate for bread". Just too bad.

SLEEP AND HYPERTENSION. MORE EVIDENCE

Sleep, that part of our life cycle, when we lose contact with the world until we are awaken, and sometimes rudely. For a long time, many have felt that when we sleep, everything stops and we rest our body. Maybe some also think that our body stops functioning for us to rest. Well, the latter is certainly not true, and the formerly is only partly true. It appears that with more and more research, we now discover that when we sleep, part of the body rest, and whine down, but some other part of the body is still very active. This is almost like fat cells around our middle kingdom. It is not an inactive organ, but a very active metabolic, neuro-hormonal organ.
The latest online edition of Hypertension, carries an interesting article by Dr Maple Fung from San Diego, and Dr Susan Redline from Women and Bringham, Boston. It is an interesting study. They have a project called the Outcome of sleep disorders in Oldermen Study. They enrolled 784 men from 2003-2005. Measured their sleep duration, sleep breathing patterns and also their sleep architecture. These are all healthy oldermen with no heart disease or hypertension. They fill up a questionaire, or their health status. After 3.5 years, from 2007-2009, they fill in a second questionaire about their health status, and also undergo another sleep study, on their sleep duration, sleep breathing patterns and sleep architecture.
What they discover was that oldermen who had a shorten duration of "slow wave sleep ( SWS ), had a 2x increase incidence of hypertension after 3.5 years. Interesting. These men had no difference in their overall sleep duration, no difference in their sleep breathing patterns ( no sleep apnea ), and no difference in their REM ( Rapid eye movement ) sleep.
I suppose, I should have began by explaining that when we sleep, our sleep is divided into REM sleep and non-REM sleep. The non-REM sleep phase is further divided into the N1, N2, N3 phase. The N3 phase is also called the SWS phase. This is the phase when it is most difficult to arouse us ( commonly called deep sleep ). It appears that during this phase of SWS ( deep sleep ), the body rest and all our daily metabolic, neuro-hormonal processes wind down and goes to basal level. An inability to get enough SWS does not allow the body to wind down completely, and so the metabolic and neuro-hormonal reactions continue, the sympathetic system and the vagal system continues in overdrive, and these increases the incidence of diabetes and also hypertension.
So sleep like diet and physical activity is important for good health, particularly in oldermen.

STROKES ON THE RISE IN USA

The Annals of Neurology recently carried an article by the US Center for Disease Control, on the epidermiology of strokes. They dug into the records of all strokes reported,and there were about 8 million. They divided strokes presentation by age groups and revealed a few interesting points.
On the whole, stroke in in the increase, by about 30%, mainly in the younger age group. Hemorraghic strokes seem to be on the decrease. Of the increase in strokes, there was also a 30% increase in strokes in the 15-40 years age group. There seem to be an increase in stroke rates in the young. Strokes is no longer a disease of the 65 years and above.
UK also reported about 500 strokes a year in amongst their children admitted.
Of course, the interesting point is the why?? Why has stroke rates amongst the younger age group, increased?Is it the eating habits ( fast foods, MacDonalds, coca colas ), the remote control ( sit down no move ) culture? Lack of exercise? Obesity? Diabetes? I suppose we can all specculate. Along the way, almost 25% of the strokes were blood pressure related.
These data are coming to us at no cost, without any conflict of interset, and we should all take note of it.
The saying is true, the strokes are best prevented, and the large majority of them can be prevented.

Eat healthily, exercise regularly, keep your ideal weight ( BMI <24, Waistline <34 inches ). Plenty of greens veges, and fruits. No smoking and take to wine.
We all wish to live longer and better, not bedridden.

Take heed of the message please.

STATINS HEAD TO HEAD. ROSUVASTATIN DID NO BETTER THAN ATORVASTATIN

Yesterday, Astra Zeneca, the maker of rosuvastatin, put out a press release on the findings of the SATURN trial. This is a statin head to head trial, comparing high dose rosuvastatin ( 40mg ) against atorvastatin 80mg. It is sponsored by Astra Zeneca. The trial studied 1,300 patients with angiographically proven coronary artery disease, given the statins over 2 years. They all had baseline angiogram and IVUS, and a repeat IVUS at 2 years.
The endpoint was percentage reduction in atheroma volume by IVUS over a 40mm segment of disease, and the secondary endpoint was percentage change in atheroma volume.
After 2 years, there was no significant difference in the percentage atheroma volume in both treatment arms and also there was no significant difference in the change in atheroma volume.
Basically, high dose rosuvastatin was not any better then high dose atorvastatin .
The side effects risk was no different in both arms.
The full results, says the press release, will be announced at the annual scientific meeting of the American Heart Association in Nov 2011.
I was surprise that the FDA continued to allow the trial to continue, as we now know that high dose statins carries a significant risk of side effects. The other comments is obvious that we need clinical end-points. Obviously, the trial was over too short a period for clinical end-points. It was also not powered, and obviously, an IVUS trial over 2 years will be much, much cheaper then a 10,000 patient trial with clinical follow-up over 5 years. What more, if the trial is negative ( no significant difference ), then Astra will be paying for a trial that will benefit their generic competitor.
At the end, clinical trial is also all about money.

ESC IS OVER. NOTHING NEW TO DISCUSS.

Well, the European Society of Cardiology, Annual Scientific meeting 2011 has concluded in Paris. I had the look at what was presented, and my take is that nothing earth shuttering was revealed. Our last post was on the newer CETP inhibitors, and we need to keep a close watch on this knowing that it could be of great benefit to our patients and knowing also that we have failed once with Torcetrapid.
On the interventional end, I see that second generation DES role is firmly established and there is almost deafening silence on the ABSORB bio-degradeable DES stent.
1. On the 30th August, there were 32 papers on the Xience V ( everolimus eluting DES by Abbott ). My friend from Japan, Dr Kimura presented the findings of the RESET study. A 3,200 patient study, comparing the use of the Xience V DES ( just approved in Japan 1 year ago ) with the Cypher sirolimus eluting ( now removed from the market place ) by JnJ Cordis. Basically, the results showed that Xience V was as good as Cypher ( not surprising ). We have seen the same conclusion with ISAR Test 4 and SORT OUT 4. No surprises.
2. Paris also saw the presentation of longer term data from the SCARR registry ( this guy gave us a scare in 2006 remember ) and the Bern Rotterdam data ( this guy also gave us a scare in 2006 ), showing that out to 4 years, the Xience V DES is safer, have less late stent thrombosis ( almost non ) and also less TLR.

These two papers basically confirmed what we know. That second generation DES are safer and better, especially in the longer term. Looks like stent design, drug dosages, elution characteristics and refined polymer coatings have made a difference. We have learn our lessons well.
In fact, the second generation DES are so safe now, that we can advocate their use in AMI ( a high thrombus load millieu ). This was also highlighted in a paper by Dr Sabate ( Barcelona ), on the use of Xience V in acute STEMI. The EXAMINATION study. There was no difference in the primary end point, when comparing Xience V with Abbotts multilink bare metal stent. No difference in the stent thrombosis rates. There was significant difference in the secondary end points of TLR, and TVR. Of course the caveat here is that the dual anti-platelet compliance rate was 95%. That is important to note. basically, do not use a DES in Acute STEMI, if the patient cannot comply with DAPT.
Looks like there was alot of Xience V in Paris, and Paris also see the withdrawal of Cypher ( so sad ).
Looks like Interventional Cardiology has reached a plateau.