In the last 10 years the number of people with type 2 diabetes in England has increased by a million. by 2013 in England 1 in 20 people were diabetic. That is over five and a half million people or put another way the same as all the people who work in the public sector in the UK or the population of Manchester and the West Midlands combined. Diabetes is a serious condition associated with an increased risk of heart and vascular disease, blindness and kidney failure. To put it in perspective your risk of having a heart attack if you are diabetic is the same as the risk of a person who has already had one heart attack having another one. We take diabetes seriously and spend a lot of time trying to prevent complications from condition. We also try to prevent diabetes by telling people about the lifestyle changes which will reduce their risk. In England every adult aged 40 to 74 is offered a NHS Health check designed to detect obesity, diabetes, high blood pressure and raised cholesterol. Doctors are told to calculate a patients cardiovascular risk and decide whether to prescribe statins. Originally the threshold of risk for statin prescription was 30%, then a few years later, when branded statins came off patent, it was lowered to 20% and soon, if new draft NICE guidelines go through, it will be lowered to 10%. As the prescription of statins has moved from people with established medical problems to those simply at risk concerns have been raised about the threat of medicalising the population. With this there has been growing worry about the unintended effects of statins. What has emerged is that statins definitely cause muscle problems and abnormalities of liver function tests but more worryingly there is growing evidence that statins cause diabetes. Randomized controlled trials prove that statins reduce risk of cardiovascular disease by 30%. This is an impressive number but remember the absolute benefit for an individual patient is absolutely determined by their actual risk of heart disease. If this number is low then the absolute benefit will also be low, 30% of a very small number is still a very small number. So in lower risk people the clinical benefit may be balanced or even outweighed by potential harm from unintended effects. A recent meta-analysis suggested that statins are associated with a 9% increased relative risk of diabetes and a systematic review reported an odds ratio of 1.31 for the development of diabetes. Another analysis of 5 statin trials with 32,752 participants without diabetes at baseline showed that 2749 developed diabetes (2.0 extra cases/1000 patient-years) with an odds ratio of 1.12 for new-onset diabetes. In women where the beneficial effects of statins are less clear, the Women’s Health Initiative study reported evidence of increased risk of diabetes with a number needed to harm of 44 patients for an additional case of diabetes over three years of treatment. We think the diabetes epidemic is related to the rising tide of obesity and slothfulness but could it be that the increase is being driven by the prescription of statins which have reached epidemic proportions over the last 10 years. In 2013 doctors wrote 63 million prescriptions for over 2.13 billion statins tablets in England. If being on a statin increases the risk of diabetes and we use the conservative estimate of 2 cases per 1000 patient year then because the number of people statins are prescribed to is so large (5.84 million people taking statins) we could expect at least 12,000 extra cases of diabetes to occur as a direct result of the statin treatment. A more pessimistic scenario based on the Women's Health Initiative number needed to harm of 44 would predict an extra 133,000 cases of diabetes as a direct result of statin treatment. The number of people with diabetes is rising by about 140,000 per year. Now association does not prove causation but the trend rise in diabetes and statin prescribing is worrying and should make doctors thick twice when recommending statin treatment to people at lower cardiovascular risk where the potential for harm from the treatment might outweigh the potential for benefit. Diabetes is now very common so doctors will never be surprised when new cases occur especially in people who are taking statins, after all these are the people at risk of cardiovascular disease in whom diabetes is likely to be prevalent anyway. Individual doctors will miss the association between diabetes and statins because the background level of the diabetes is very high. It is much easier to identify unwanted effects of a drug if it causes a rare or unusual effect because these events stand out. So we need to think carefully about the balance of risk and benefit when we prescribe statins, after all we need to ensure that overall the patient is likely to benefit from the treatment rather than be harmed by it especially if their underling cardiovascular risk is low.
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Friday 25th April 2014- The Times, front page news, above the crease. The story must be important. It is they have discovered the "Secret of longer life". Here is the skill of the journalist. Take a study just published. Read it and Identify one fact from all the results which makes the hook for the story. In this case Japanese women have the highest life expectancy. Then find a plausible association. What do we know about Japan? Ah well Sushi? - that's raw fish and Green Tea? Well that must be the cause of the long survival and there it is you have your story and your headline and your front page. So what lies behind this news and is there any credibility in the conclusion. The Office for National Statistics published an international Compendium of Data on population statistics today. Much of the report will fuel the current debate around UK immigration as there is a substantial amount of data on population migration and enough material in the report to satisfy the needs of the pro as well as the anti-European debate and to prove either groups case! The life expectancy data comes later and leads to the headline. Well I'm sorry to have to disappoint but I am afraid that the secret of longer life isn't about raw fish or green tea. Sadly the journalists haven't been entirely transparent with the facts. It is true that Japanese females do have the highest life expectancy at birth (86.4 years) but the country with the highest male life expectancy at birth at 80.8 years was Iceland. Now it is true they eat a lot of fish in Iceland. In fact a recent FAO report indicates that the annual fish consumption in Iceland is 80.5kg/year compared to just 55.2 in Japan. So you could ask if fish in the diet was so important why didn't the Icelandic women top the Japanese. Well perhaps it's the type of fish, or the way it's cooked or not cooked. More likely perhaps this is simply an association which tells you nothing about causation. It could be the play of chance or any number of other factors which confound the association between the diet and life expectancy. its almost as bizarre as thinking that the amount of chocolate you eat determines the chance of winning a Nobel prize.
The old saying goes you should breakfast like a King, lunch like a Prince and dine like a pauper. Breakfast may be the most important meal of the day but now it turns out that it's effects reach far beyond the breakfast table. What you eat for breakfast influences not only how full you feel at the time but how much food you eat for lunch and dinner. So what's the best breakfast? A poached egg, a bowel of cereal and a slice of toast or something more continental - a croissant with butter and jam perhaps? Researchers at the University of Surrey have been looking at whether what you eat at breakfast alters how hungry you feel later in the day. They randomly assigned three groups of students to different breakfasts all containing 330 kilocalories. The breakfasts were either two poached eggs on a slice of white toast or a bowl of cornflakes with semi-skimmed milk, a slice of white toast or a croissant with butter and jam and orange juice. For lunch the students were offered a buffet of cheese sandwiches, plain crisps and water. For dinner they were offered a buffet of pasta and a tomato sauce and cheese and water. The amount of lunch and dinner they took from the buffet was recorded as were scores of hunger and fullness during the day. Their results showed that the egg breakfast made people feel significantly fuller for longer and reduced the amount of lunch and dinner taken from the buffet. The proportion of fat and protein in the egg breakfast was higher and the carbohydrate content lower than the other breakfasts. It is known that high-protein foods make you feel fuller than high fat or carbohydrate ones and show the importance of food choice at breakfast. But hold on I hear you say can a cardiologist really be recommending that people eat eggs. In the 1960's the Egg Marketing Board ran a highly successful campaign called "Go to work on an Egg" but with the demonization of saturated fat in the 1970's and 80's, eggs with their high cholesterol content were rejected in favour of high carbohydrate breakfast cereals. Well it turns out that your more likely to raise your cholesterol by eating butter on your toast than from the cholesterol in an egg. In a large meta-analysis published in the BMJ looking at 17 reports on data from 4 million people there was no evidence of an association between egg consumption and risk of coronary heart disease or stroke and now even the British Heart Foundation is now promoting the consumption of eggs. So this means you can go to work on an egg if you want to and it might well help you lose weight by reducing the size of your lunch and dinner. Which one would you choose? The healthy option or the chocolate bar? Perhaps your head says apple but your stomach says chocolate. If I told you the apple has 59 kilocalories and the Twix has 246, 18% of you would choose the apple. If I told you the apple has 247 kilojoules and the Twix has 1,029, 41% of you would choose the apple. When people are faced with healthy versus unhealthy choices the way in which nutritional information is presented influences that choice. If you test this in people with a low prior interest in energy information the probability of choosing the apple increases from 3% to 59%.
We are exposed to this type of unit effect all the time. When we buy something for £9.99 we focus on the £9. When you are told a product costs just £1 a day rather than £30 a month and when a waiting time for treatment is 18 weeks rather than 4 and a half months. The way we present information has a significant effect on the choices people make so we should consider that when giving health promotion advice. How to Make a 29% Increase Look Bigger: The Unit Effect in Option Comparisons Stop smoking, lose weight, and change your diet! As doctors we are constantly giving advice to people how to improve their health. We think these messages are clear. You are overweight, your blood pressure is too high and obesity increases blood pressure so lose weight. But much of this advice goes unheeded. How can we make it more effective. One way is to use the concept of appealing to Social Norms. We've all seen those signs in hotel bathrooms asking us to reuse the towels. Its good for the environment and after all you don't change your towel everyday at home? But only about a third of people actually reuse the towels. How can we increase that and does the way the message is conveyed alter the likelihood the towels are reused? A study published in the Journal of Consumer Research looked at this question and the results are interesting. They had 2 messages for the hotel guests. A standard one focused on environmental protection "HELP SAVE THE ENVIRONMENT. You can show your respect for nature and help save the environment by reusing your towels during your stay." The other message had a descriptive norm informing people that a majority of other guests reused their towels: “JOIN YOUR FELLOW GUESTS IN HELPING TO SAVE THE ENVIRONMENT. Almost 75% of guests who are asked to participate in our new resource savings program do help by using their towels more than once. You can join your fellow guests in this program to help save the environment by reusing your towels during your stay." The messages were randomly assigned to different hotel rooms. Towel reuse went up from about 30% in the standard message to 44% with the descriptive norm message. With further adjustment to the wording “JOIN YOUR FELLOW GUESTS IN HELPING TO SAVE THE ENVIRONMENT. In a study conducted in Fall 2003, 75% of the guests who stayed in this room participated in our new resource savings program by using their towels more than once. You can join your fellow guests in this program to help save the environment by reusing your towels during your stay", they increase towel reuse to 50%. Descriptive norms improve towel reuse at least in hotel bathrooms but does this work in other areas. The Behavioural Insights Team, the so called Nudge Unit of the Cabinet Office, looked at charitable donations in wills. The average donation was £3,300. When people rang to book a will-writing appointment they were randomly assigned to one of two groups of will-writers. The first took their details and then asked "Would you like to leave any money to charity in your will?". The second said "many of our customers like to leave money to charity in their will. Are there any causes you’re passionate about?” The first or "Plain Ask" method had no effect on donations but the second social normative doubled the average donation to £6,661. The results are important for hoteliers and charities but also have implications for doctors and nurses trying to improve the uptake of health promotion programs. If we can introduce social norms into our recommendations this is likely to improve the chance that our advice is followed. Assessment of patients with CT scans of the heart is becoming more common. A CT scan can detect the earliest signs of coronary artery disease which manifest itself as calcification and remodelling of the arteries before any stenosis or symptom develops and way before it can be detected by exercise treadmill or other functional tests. When patients are found to have moderate coronary artery disease or coronary calcification detected on a CT they are offered treatment with intensive risk factor modification with aspirin, statins and ACE inhibitors. Usually they ask two questions. First will these treatments reverse the coronary artery disease and second how can they monitor the situation going forward to find out if the treatment is working beyond simple measures like the absence of symptoms or change in cholesterol levels. Traditionally repeating the CT scan after a time interval has not been recommended however a recent paper from the MESA study group has questioned this. They looked at the value of repeat cardiac CT scanning to detect changes in coronary artery calcification (CAC) and to see if this was associated with increased risk of cardiac events such as heart attack. They studied 5,682 people with a baseline and follow-up CAC 2.5 years later. The results showed an annual increase in CAC score of about 25. In people with a CAC of 0 at baseline a 5-unit annual increase was associated with a 1.5 fold increase in risk of heart attack. In those people with a raised calcium score at baseline, for every 100 annual increase there was a 1.3 fold increase in risk. In those people with an annual progression of more than 300 there was a 6.3 fold increase in risk. So progression of CAC is associated with an increase risk of adverse outcomes for patients and monitoring progression of disease with a CT scan after an interval of about 2.5 years is a reasonable strategy. If progression is <100 then the patient can be reassured that their treatment is working and there risk is not increasing. If there is progression of >300 then they might benefit from a more intense treatment program. When patients come to a hospital outpatient clinic it is common for them to be asked about the medication they are taking. As a physician, medicines are your main weapon against disease and even as an interventional cardiologist I spend most of my time intervening with my pen rather than with catheters. It is essential for the doctor to know which medication the patient is taking and in what dose. Some patient with angina, high blood pressure or diabetes are prescribed over 10 different medications, but how many of them are being taken? Compliance is understood to mean acting in accordance with advice of the prescriber. The word is linked with an old-fashioned paternalistic attitudes towards the patient by the prescriber and so instead the idea of concordance, implying that prescriber and patient were in general agreement about the drug regimen is preferred. Some people prefer the term adherence which implies a steady observance or maintenance. So in the clinic how do we really know whether our patients are adhering to their medications as prescribed? A study just published in Heart looked at this question in 208 patients referred their secondary care hypertension clinic. Using an HPLC assay to detect 40 of the most commonly prescribed antihypertensive medications they ran samples of the patient's urine to see if the drugs on prescription chart were present in the urine. Shockingly in 25% of patients only some of the blood pressure medications were found and in 10% none were found. This follows on from a study in Germany that looked at 108 patients with resistant hypertension. Of these 15 patients had secondary causes of hypertension and 17 achieved blood pressure control by the addition another drug. In the remaining 76 patients, using the same type of HPLC analysis of the urine, 53% of patients were non-adherent to the prescribed medication and 30% were not taking any blood pressure medication at all. Patients with resistant hypertension are often sent for expensive investigations such as MRIs, blood and urine tests looking for secondary hypertension often with normal results. Apart from higher BP levels and elevated heart rate, adherent and non-adherent patients are indistinguishable which supports the idea that a doctors impression, patient's interviews or pill counts are not reliable markers of adherence. With the results from these studies in mind a formal check of adherence to treatment using a urine analysis would be helpful. Of course this can't give the whole picture since it is also recognised that patients adherence to treatments increases around the time of clinic appointments. In the future it is likely that we will be able to monitor medication adherence. New smart pills containing a silicon chip the size of a grain of sand are already a reality. Composed of trace amounts of magnesium and copper, when swallowed, they react with stomach acid generating a tiny voltage which can be detected by a special skin patch and relayed to a smartphone. These can be built into a medication and would allow doctors to know if medication has been taken and also act as a remind to the patient who might have forgotten to take their tablets. With some medicines such as the new oral anticoagulants addition of this technology could be very cost effective as improved adherence is very likely to improve patient outcomes. On Sunday about 35,000 people will line up to run the London Marathon. Along the route there will be 1,500 St John first aiders and 150 doctors, physiotherapists and podiatrists. The majority of runner's medical problems involve blisters and muscle cramps however what always makes a headline is if a runner dies or has a cardiac arrest during the marathon. Fortunately cardiac death during a marathon occurs very rarely (1 in 80,000 runners). Since 1981, when the London Marathon started, there have been eight cardiac deaths. Five of them were from coronary heart disease, two from hypertrophic cardiomyopathy and one from arrhythmogenic right ventricular cardiomyopathy. So far all the cardiac deaths have been in men. As the race day gets closer some runners seek advice as they are concerned about the risk of having a cardiac problem during the marathon. So how should a prospective marathon runner be assessed? I divide runners into two groups. In men aged more than 40 years the main cause of cardiac problems in an marathon is due to coronary artery disease. In women and younger men it is usually due to undiagnosed structural heart disease, usually hypertrophic cardiomyopathy. Assessment involves taking a detailed clinical history looking for symptoms of chest pain, shortness of breath, dizziness or blackouts associated with exercise. We document any cardiovascular risk factors and family history of sudden cardiac death or cardiac diseases. A cardiovascular examination is performed looking for murmurs, measurement of blood pressure and pulses. The cardiologist will usually do an electrocardiogram and often an echocardiogram to rule out structural heart disease In men over 40 or those with risk factors for ischaemic heart disease an exercise treadmill test is helpful to look for any evidence of coronary artery disease. Running a marathon is a gruelling event which places huge stresses on the heart and musculoskeletal systems but fortunately the risk of a cardiac problems is very low and the majority of patients will compete the marathon without problem. When discussing revascularisation procedures (coronary artery bypass grafting (CABG) or stents), patients often ask: How long will my bypass/stent last? There is no easy answer to this question. I have patients with stents implanted 20 years ago which are still working perfectly and also known people who had a CABG in the 1980’s where all the grafts are in excellent condition. Conversely patients may return rapidly after surgery with graft failure or develop critical in-stent restenosis within months of angioplasty. Results from randomised clinical trials of stents versus surgery such as the SOS and SYNTAX favour CABG as superior treatment compared to stenting. CABG appears to be associated with a lower likelihood of repeat revascularisation. But there is a problem with these trials. Inherent clinician bias usually favours repeating angiograms in patients treated with stents who develop symptoms after the procedure compared to those patients who have received treatment with CABG. Since the clinician and the patients are not blinded to the original treatment this belief that surgery is a more robust and reliable method of revascularisation is likely to increases the rate of repeat angiography which leads to a high rate of repeat revascularisation. So what is the rate of CABG vein graft occlusion? A recent paper looked at this question in 1829 patients who had a coronary angiogram within 12-18 months after CABG and were then followed for a further 3 years. Within 18 months after CABG 43% of patients (770/1829) had at least one vein graft occlusion. The identification of this occlusion was associated with a 5-fold increase in repeat revascularisations procedures although it did not lead to a higher number of heart attacks or deaths compared to patients whose grafts were all patent. There rate of revascularization procedures within 14 days of angiography demonstrating a vein graft occlusion shows the power of the occlulostenotic reflex as discussed before in an earlier blog. Since the angiography was protocol, and not symptom, driven the identification of the stenosis on an angiogram was enough to result in a repeat revascularisation procedure with a stent. What is the reason for the graft occlusion? Surgical technique, quality of the vein graft and target vessels or is it perhaps that the stenosis didn’t need bypassing in the first place. The FAME study using pressure wire showed that 20% of coronary arteries with significant stenosis (70-90%) on an angiogram were not associated with ischemia and in such cases vein graft failure could easily ay occur without clinical consequence or symptoms. So when answering the question about the longevity of a bypass graft we should say that nearly half of patients will lose at least one graft within 18 months of surgery but the chance that it will cause harm to the patient is low unless someone discovers that it is occluded. Bergamot a member of the citrus family which is found in the Calabria region of southern Italy. The fruit is a source of essential oils which when added to Earl Grey tea result in the unique scented flavour of this drink. Yesterday national newspapers articles appeared suggesting that Earl Grey tea was as "effective as statins in the fight against heart disease." Is this too good to be true? The newspapers reported a study in rats published in the Journal of Functional Foods. The authors from Italy showed that extract of bergamot fruit reduced cholesterol levels in these animals and that it was as effective as simvastatin. Now if you want to write a story for the newspaper it's only a few steps of logic before you can claim that drinking Earl Grey tea is a possible substitute for a statin. This conclusion goes way beyond the experimental data but some patients I talked to yesterday were clearly ready to give up their statin and try the natural approach. Is there any evidence that bergamot can treat heart disease? Bergamot fruit contains high concentrations of polyphenols. This is usually thought of as a good thing but really we are not sure what these chemicals do. They are in a group called anti-oxidants and since oxidation is bad these chemicals are thought of as good. This is a vast over-simplification of a complex and poorly understood area of biology. The anti-oxidant potential of bergamot is found in other fruits such as pomegranates and blueberries. These are commonly referred to as super-foods in the pages of popular magazines and their beneficial properties are often promoted. There are several human studies reporting potent effects of bergamot extract on cholesterol levels. In one study LDL, or so called bad, cholesterol levels were reduced as much as in people taking 20mg of rosuvastatin. This is very interesting and if reproduced is quite an astounding effect. But wait, what of outcome trials, where is the data that these fruit extracts reduce heart attacks and save lives? Of course this is completely lacking and there will never be any large clinical trials to prove effectiveness in reducing cardiovascular disease. This is because such studies cost millions of pounds and at the end even if it proved effective there is no prospect of a patentable medicine. Doctors usually demand strong evidence before they prescribe drug treatment and this is true in the field of cholesterol lowering drugs or is it? Every year millions of doses of a cholesterol lowering drug called ezetimibe are prescribed for patients intolerant of statins or in whom cholesterol cannot be reduced enough by statins. Ezetimibe definitely lowers cholesterol but is there is scant evidence that it reduces heart attacks or deaths from heart disease. The IMPROVE-IT trial (simvastatin versus a combination of simvastatin/ezetimibe) started years ago and the results are still awaited. Meanwhile doctors continue to prescribe ezetimibe with enthusiasm. Apart from more evidence that it lowers cholesterol there isn’t too much difference between ezetimibe and bergamot fruit extract when it comes to outcome trials. Patients often favour a natural approach but is important to remember that fruit extracts simply contain chemicals and chemicals sometimes have unwanted effects. For example pomegranate juice can interact with drugs like warfarin leading to serious consequences as we previously reported. So where do we go from here? If you enjoy Earl Grey tea continue to enjoy it as a drink but not for its medicinal properties. If you don’t like Earl Grey tea, no problem because there is almost certainly no health benefit in drinking it. If your statin is working, keep taking it. If your statin isn’t working or you are getting unacceptable side effects such as severe muscle aches which have been proven to be due to the statin by a period of withdrawal and re-challenge then you might discuss taking an alternative with your doctor. Whether this involves the recommendation of bergamot extract or ezetimibe is a matter of opinion. |
Dr Richard BogleThe opinions expressed in this blog are strictly those of the author and should not be construed as the opinion or policy of my employers nor recommendations for your care or anyone else's. Always seek professional guidance instead. Archives
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