Back to Basics: Latest European Guidelines on CVD Prevention
Medscape: In some fundamental ways, these new ESC CVD prevention guidelines differ a lot from the previous version published in 2007. What was the background to making these changes?
Prof. Perk: When I took the chairmanship of this Fifth JTF, I looked back at the previous 4 versions of the guidelines and I drew a line between those and the ones that we were going to produce. I tried to find out in what way the guidelines have been growing in size, and I discovered that if we continued this line of growth, we would end up with a text book, not a guidelines document. It was simply becoming too big, and we felt that we needed to find a completely different formula, a different way of working, and we actually did. The 26 people from the JTF came together in a small château outside Paris, and we said, "We are not going to leave here until we have agreed on a new format."
I based our discussion on 5 basic questions set out by the Greek philosopher Plato: What is the thing? Why is it needed? To whom do you do it? How do you do it? And where do you do it? I got the group to agree on a consensus for a new document where we tried to answer these 5 important basic questions for clinical practice: What is CVD prevention? Why is it needed? Who should benefit from it? How can CVD prevention be applied? And where should prevention programs be provided? So that was a completely different format that gave us a chance to reduce the amount of text, and that is what this document is all about. This is a document in which we try to provide people in clinical practice with the rationale and the toolbox for the practice of CVD prevention.
Other new aspects of the guidelines are the use not only of the American College of Cardiology/American Heart Association/ESC grading system, which awards recommendations for different classes (I, IIa, IIb, or III) according to the type of trial evidence, but also the British Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, which allows more evidence-based recommendations to be adapted to the needs of clinical practice. That was important for us because with prevention you have only large population studies. You cannot do randomized controlled trials, for example assigning smoking to a couple of thousand people and not smoking to another couple of thousand and then following them for 20 years. Randomized controlled studies can never be done, so we've had a problem with the scientific weight of population studies. GRADE takes these population studies into account. It makes recommendations even easier, especially for general practice, because it gives only a strong or a weak recommendation. "Strong" means "Do it," and "Weak" means "You could do it, but you might well wish to put your effort or your money somewhere else." With this approach, we tried to make the recommendations as understandable and as easy as possible.
Another new feature of the new guidelines is the use of 4 different levels of cardiovascular risk: very high, high, moderate, and low. These correlate to a calculated risk measured according to the Systematic Coronary Risk Evaluation Project (SCORE) system of > 10% (very high), ≥ 5% to < 10% (high), ≥ 1 to < 5% (moderate), and < 1% (low). For these 4 different groups there are different levels of recommendations for prevention. They are also compatible with the joint European Atherosclerosis Society/ESC lipid guidelines, which offer further advice on lipid interventions based specifically on these risk categories.
Our patient population knows about blood pressure and lipids, but they don't get the message about lifestyle. So in the new guidelines, we have put much more emphasis on behavioral factors such as adherence to treatment, how to help patients follow recommendations, and how to address psychosocial problems.
An element of these guidelines that is completely new is the last chapter on where to deliver CVD prevention. I felt that we needed to address the role of the general practitioner, the cardiologist, the nurse, the patient, and nongovernmental organizations in CVD prevention. It also describes how health professionals can influence politicians. That is completely new, and I feel strongly about this because it gives very practical suggestions about lobbying activities by people in clinical practice.
The sections of the guidelines on smoking, diet and physical exercise, blood pressure, and lipids have been updated, but these updates are not very revolutionary. What might be revolutionary in hypertension is that any drug in the 4 major groups -- diuretics, beta-blockers, calcium channel blockers, and renin-angiotensin system inhibitors -- can be used for blood pressure control. We do not see any major differences among these groups. Some pharmaceutical companies have told us that they are not happy about this, but we state it nonetheless. We do not want to say use only angiotensin-converting enzyme inhibitors or beta-blockers or diuretics, and so forth; we leave that up to the individual prescribing clinician. It is more important that the patient reaches the target values, and there are different solutions for that. However, we have seen in the EURIKA and EUROASPIRE studies that although there are guidelines to follow, only one third of the population is at target for blood pressure or lipid levels. So we make it easy; we say the target levels are important, you know how to reach them, just see to it that you do it.
Medscape: Many patients with hypertension have other risk factors that need to be taken into consideration when choosing antihypertensive treatment. Presumably you couldn't list all the compelling indications for specific drugs.
Prof. Perk: That is right. My first problem was to keep the guidelines under 50,000 words, so we would not be able to give detailed guidelines on hypertension, lipids, diabetes, and so on. In that way, it is a compromise solution, and we refer to the other guidelines if someone wants more depth. But the basic idea is to use the drugs that you feel are OK for your patients. I would point out that guidelines are just guiding doctors -- this is not a law book. Your clinical engagement, judgment, enthusiasm -- those are the most important factors. Of course, in many cases multiple drug treatment is needed, but it is clearly stated in the guidelines that if you do not get your patient's blood pressure below 140/90 mm Hg, you have not done what you are supposed to do. That is the same for low-density lipoprotein cholesterol (LDL-C) levels. We say that in the high-risk groups you need to get people down to 1.8 mmol/L (about 70 mg/dL), and because this is not always possible, we say at least try to get it down to half of what it was at the beginning.
Medscape: For lipids, is the target simply focused on LDL-C rather than on high-density lipoprotein cholesterol (HDL-C) or triglycerides?
Prof. Perk: That is correct. We have added an HDL-C correcting factor to the HeartSCORE algorithm, the digital format of the SCORE risk charts, because HDL-C does play a part as a risk marker, but according to experts there is not sufficient science to use HDL-C as a target value for treatment. As for triglycerides, if you get your LDL-C and your blood pressure down properly, triglycerides suddenly lose strength as a risk marker. So even there we said no, let's make it as simple as possible: only LDL-C. There has been some pressure to use the apolipoproteins, such as the apolipoprotein (apo) B/apoA1 ratio, and we have values for those, but LDL-C is what we are aiming for, in general, to allow for variations among laboratories and among countries.
Medscape: I believe that one of your new recommendations is not to use aspirin in primary prevention.
Prof. Perk: That is right.
Medscape: The 2007 ESC guidelines recommended lifelong aspirin (75-150 mg daily) in diabetics.
Prof. Perk: Yes, we have removed that recommendation in diabetes, but we do recommend statins for all patients with diabetes.
Medscape: There has been some controversy lately about statins causing new-onset diabetes. Did that affect your recommendations about statins?
Prof. Perk: That came just before we closed the book, and after a lot of discussions we drew a line and said that to our knowledge at this moment the benefits of statins fully outweigh the limited chance of developing diabetes.
Speaking of diabetes, another interesting aspect of the guidelines is that we also made the diabetes treatment recommendations even more straightforward. We say that any patient with diabetes, monitored to whatever level, with 1 or more risk factors and/or target organ damage, is already at very high risk, and that all other diabetics without other risk factors or target organ damage are in the high-risk group. We took away the age limits and other factors to make it as clear as possible that patients with diabetes who have target organ damage are at very high risk and patients without organ damage are still at high risk. That makes things more practical.
Medscape: I think the treatment target for glycated hemoglobin has been increased from < 6.5% to < 7%. Is getting everyone down to < 7% good enough?
Prof. Perk: Yes, or < 53 mmol/mol, which is the measurement we use more often in the Scandinavian countries. We say keep it below that level for preventive purposes.
Medscape: The guidelines also contain some recommendations about antiplatelet drugs in acute coronary syndromes. Is this for primary or secondary prevention?
Prof. Perk: Actually in the guidelines we are trying to get rid of the idea of primary and secondary prevention. We put the patients who have already had a cardiovascular event in the very-high-risk group; for example, people who have had a myocardial infarction. However, we no longer differentiate between primary and secondary prevention. With modern techniques we can demonstrate coronary calcification so much earlier --- before the disease even starts -- so it seems there is no cutoff point at all for prevention; it is a continuous line. There is just cardiovascular prevention in general. It is just a question of which methods you use.
Another term that you will not find in these guidelines is "metabolic syndrome." Our diabetes colleagues have completely abandoned this idea. We discussed this issue widely, but in the end we had to take out the metabolic syndrome as an entity. We describe the different risk factors and so on, but to call it a disease, no, it is gone.
Medscape: Among the other new recommendations in the guidelines is to treat periodontitis to improve endothelial dysfunction.
Prof. Perk: Yes. Although evidence is not very strong, quite a few studies on periodontitis indicate that a chronic inflammatory process might also enhance inflammation of the vascular walls. So now we strongly recommend that people keep their gums in good shape. There is very strong scientific evidence, however, for other diseases such as sleep apnea and erectile dysfunction as markers for CVD.
Medscape: You mentioned psychosocial risk factors already, and the guidelines mention that anxiety and certain personality traits increase CVD risk. How did you decide what kind of recommendations you could include about this in CVD prevention guidelines?
Prof. Perk: That was a problem. The interventional studies that have been done using drugs or cognitive behavioral therapy have not shown consistent positive results. However, there is now a desire to recognize cognitive behavioral support for people with severe anxiety or depression. We do not include anything about drugs because we still lack evidence there. Another issue that we have not been able to assess is the enormous differences in psychosocial elements among different European countries and people in Eastern vs the rest of Europe.
Medscape: Reports on the previous guidelines, which, as you said, were much longer than the new ones, have noted the difficulties encountered in implementing them in different countries. Is there any new advice in the political section or the section on healthcare settings that would make implementation less difficult?
Prof. Perk: Life expectancy in Eastern Europe is 16 years shorter than in Western Europe, and this is based on socioeconomic level, but although we have this observation, we do not know what to do about it.
We have national versions of the SCORE diagram and we have divided Europe into low-risk, higher-risk, and very-high-risk countries. There are special tables for these different countries but they are only used for clinical practice. I would love to come out with guidance on a more political level: what to do with society in order to reduce the enormous differences between European countries, which have to do with poverty and unrest. As doctors, we cannot address these factors. Nonetheless, in the last chapter we have said that even the medical profession should stand up and make their voices heard because these disparities are not justified.
Now that I have finished this work, I will be in charge of the prevention implementation committee. The different societies that have come together will try to provide guidance to get things really working. That is what I see as my task with my group for the coming 3 years: to see that this document really takes roots in different countries. We have already identified national coordinators for prevention in each country, and we are going to work with them and try to help them develop documents to use nationally in clinical practice. This is a great challenge and it will be very gratifying to see our writing work become dirt under the nails, as we say.
Medscape: Obviously research and drug development are ongoing, so is there any provision for updating these guidelines before another 5 years is up? For instance, many new drugs are likely to become available in the next few years for lipid lowering, treating hyperglycemia in diabetes, and weight loss.
Prof. Perk: We have been discussing this intensively, but our behavioral scientists say, "don't force too much information upon people in a short period of time." The world will not go under if you wait 1 or 2 or 3 years. Let it settle, see to it that we get it working, and when it works, then we can take the next step. Of course, if there is extremely important new scientific information it will leak out anyhow, but we should not tire people with too many documents because they will get "guideline lethargy" and the guidelines won’t have any effect any longer.
Medscape: At the launch you mentioned that in addition to the conventional pocket version, a 1-page summary version of the guidelines would be available. Is that out yet?
Prof. Perk: Our team of general practitioner experts is working on it at the moment. What we are doing was inspired by Ingvar Kamprad, who founded the big Swedish furniture retail company IKEA. He comes from my state in Sweden, by the way, and one of his main statements was that if you cannot get a message across on half a piece of A4 paper, nobody will read it. So at this year's ESC Congress in Munich we are going to present the IKEA-style recommendations -- the core points of prevention -- on one piece of paper. It is intended to be placed on the desk but it should not take up the top surface of the desk, so it is a challenge.
Medscape: Will the pocket guidelines be released in English and other languages?
Prof. Perk: The pocket guidelines will be launched in English, and it will be up to other countries to translate it. We will see to it with the people from our national cardiology societies that they make this 1-page summary available for general practitioners everywhere in the world. I think we have got to make a lot of noise about it -- that is what is going to happen.
The Interview With Professor Joep Perk
Medscape: In some fundamental ways, these new ESC CVD prevention guidelines differ a lot from the previous version published in 2007. What was the background to making these changes?
Prof. Perk: When I took the chairmanship of this Fifth JTF, I looked back at the previous 4 versions of the guidelines and I drew a line between those and the ones that we were going to produce. I tried to find out in what way the guidelines have been growing in size, and I discovered that if we continued this line of growth, we would end up with a text book, not a guidelines document. It was simply becoming too big, and we felt that we needed to find a completely different formula, a different way of working, and we actually did. The 26 people from the JTF came together in a small château outside Paris, and we said, "We are not going to leave here until we have agreed on a new format."
I based our discussion on 5 basic questions set out by the Greek philosopher Plato: What is the thing? Why is it needed? To whom do you do it? How do you do it? And where do you do it? I got the group to agree on a consensus for a new document where we tried to answer these 5 important basic questions for clinical practice: What is CVD prevention? Why is it needed? Who should benefit from it? How can CVD prevention be applied? And where should prevention programs be provided? So that was a completely different format that gave us a chance to reduce the amount of text, and that is what this document is all about. This is a document in which we try to provide people in clinical practice with the rationale and the toolbox for the practice of CVD prevention.
Other new aspects of the guidelines are the use not only of the American College of Cardiology/American Heart Association/ESC grading system, which awards recommendations for different classes (I, IIa, IIb, or III) according to the type of trial evidence, but also the British Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, which allows more evidence-based recommendations to be adapted to the needs of clinical practice. That was important for us because with prevention you have only large population studies. You cannot do randomized controlled trials, for example assigning smoking to a couple of thousand people and not smoking to another couple of thousand and then following them for 20 years. Randomized controlled studies can never be done, so we've had a problem with the scientific weight of population studies. GRADE takes these population studies into account. It makes recommendations even easier, especially for general practice, because it gives only a strong or a weak recommendation. "Strong" means "Do it," and "Weak" means "You could do it, but you might well wish to put your effort or your money somewhere else." With this approach, we tried to make the recommendations as understandable and as easy as possible.
Another new feature of the new guidelines is the use of 4 different levels of cardiovascular risk: very high, high, moderate, and low. These correlate to a calculated risk measured according to the Systematic Coronary Risk Evaluation Project (SCORE) system of > 10% (very high), ≥ 5% to < 10% (high), ≥ 1 to < 5% (moderate), and < 1% (low). For these 4 different groups there are different levels of recommendations for prevention. They are also compatible with the joint European Atherosclerosis Society/ESC lipid guidelines, which offer further advice on lipid interventions based specifically on these risk categories.
Our patient population knows about blood pressure and lipids, but they don't get the message about lifestyle. So in the new guidelines, we have put much more emphasis on behavioral factors such as adherence to treatment, how to help patients follow recommendations, and how to address psychosocial problems.
An element of these guidelines that is completely new is the last chapter on where to deliver CVD prevention. I felt that we needed to address the role of the general practitioner, the cardiologist, the nurse, the patient, and nongovernmental organizations in CVD prevention. It also describes how health professionals can influence politicians. That is completely new, and I feel strongly about this because it gives very practical suggestions about lobbying activities by people in clinical practice.
The sections of the guidelines on smoking, diet and physical exercise, blood pressure, and lipids have been updated, but these updates are not very revolutionary. What might be revolutionary in hypertension is that any drug in the 4 major groups -- diuretics, beta-blockers, calcium channel blockers, and renin-angiotensin system inhibitors -- can be used for blood pressure control. We do not see any major differences among these groups. Some pharmaceutical companies have told us that they are not happy about this, but we state it nonetheless. We do not want to say use only angiotensin-converting enzyme inhibitors or beta-blockers or diuretics, and so forth; we leave that up to the individual prescribing clinician. It is more important that the patient reaches the target values, and there are different solutions for that. However, we have seen in the EURIKA and EUROASPIRE studies that although there are guidelines to follow, only one third of the population is at target for blood pressure or lipid levels. So we make it easy; we say the target levels are important, you know how to reach them, just see to it that you do it.
Medscape: Many patients with hypertension have other risk factors that need to be taken into consideration when choosing antihypertensive treatment. Presumably you couldn't list all the compelling indications for specific drugs.
Prof. Perk: That is right. My first problem was to keep the guidelines under 50,000 words, so we would not be able to give detailed guidelines on hypertension, lipids, diabetes, and so on. In that way, it is a compromise solution, and we refer to the other guidelines if someone wants more depth. But the basic idea is to use the drugs that you feel are OK for your patients. I would point out that guidelines are just guiding doctors -- this is not a law book. Your clinical engagement, judgment, enthusiasm -- those are the most important factors. Of course, in many cases multiple drug treatment is needed, but it is clearly stated in the guidelines that if you do not get your patient's blood pressure below 140/90 mm Hg, you have not done what you are supposed to do. That is the same for low-density lipoprotein cholesterol (LDL-C) levels. We say that in the high-risk groups you need to get people down to 1.8 mmol/L (about 70 mg/dL), and because this is not always possible, we say at least try to get it down to half of what it was at the beginning.
Medscape: For lipids, is the target simply focused on LDL-C rather than on high-density lipoprotein cholesterol (HDL-C) or triglycerides?
Prof. Perk: That is correct. We have added an HDL-C correcting factor to the HeartSCORE algorithm, the digital format of the SCORE risk charts, because HDL-C does play a part as a risk marker, but according to experts there is not sufficient science to use HDL-C as a target value for treatment. As for triglycerides, if you get your LDL-C and your blood pressure down properly, triglycerides suddenly lose strength as a risk marker. So even there we said no, let's make it as simple as possible: only LDL-C. There has been some pressure to use the apolipoproteins, such as the apolipoprotein (apo) B/apoA1 ratio, and we have values for those, but LDL-C is what we are aiming for, in general, to allow for variations among laboratories and among countries.
Medscape: I believe that one of your new recommendations is not to use aspirin in primary prevention.
Prof. Perk: That is right.
Medscape: The 2007 ESC guidelines recommended lifelong aspirin (75-150 mg daily) in diabetics.
Prof. Perk: Yes, we have removed that recommendation in diabetes, but we do recommend statins for all patients with diabetes.
Medscape: There has been some controversy lately about statins causing new-onset diabetes. Did that affect your recommendations about statins?
Prof. Perk: That came just before we closed the book, and after a lot of discussions we drew a line and said that to our knowledge at this moment the benefits of statins fully outweigh the limited chance of developing diabetes.
Speaking of diabetes, another interesting aspect of the guidelines is that we also made the diabetes treatment recommendations even more straightforward. We say that any patient with diabetes, monitored to whatever level, with 1 or more risk factors and/or target organ damage, is already at very high risk, and that all other diabetics without other risk factors or target organ damage are in the high-risk group. We took away the age limits and other factors to make it as clear as possible that patients with diabetes who have target organ damage are at very high risk and patients without organ damage are still at high risk. That makes things more practical.
Medscape: I think the treatment target for glycated hemoglobin has been increased from < 6.5% to < 7%. Is getting everyone down to < 7% good enough?
Prof. Perk: Yes, or < 53 mmol/mol, which is the measurement we use more often in the Scandinavian countries. We say keep it below that level for preventive purposes.
Medscape: The guidelines also contain some recommendations about antiplatelet drugs in acute coronary syndromes. Is this for primary or secondary prevention?
Prof. Perk: Actually in the guidelines we are trying to get rid of the idea of primary and secondary prevention. We put the patients who have already had a cardiovascular event in the very-high-risk group; for example, people who have had a myocardial infarction. However, we no longer differentiate between primary and secondary prevention. With modern techniques we can demonstrate coronary calcification so much earlier --- before the disease even starts -- so it seems there is no cutoff point at all for prevention; it is a continuous line. There is just cardiovascular prevention in general. It is just a question of which methods you use.
Another term that you will not find in these guidelines is "metabolic syndrome." Our diabetes colleagues have completely abandoned this idea. We discussed this issue widely, but in the end we had to take out the metabolic syndrome as an entity. We describe the different risk factors and so on, but to call it a disease, no, it is gone.
Medscape: Among the other new recommendations in the guidelines is to treat periodontitis to improve endothelial dysfunction.
Prof. Perk: Yes. Although evidence is not very strong, quite a few studies on periodontitis indicate that a chronic inflammatory process might also enhance inflammation of the vascular walls. So now we strongly recommend that people keep their gums in good shape. There is very strong scientific evidence, however, for other diseases such as sleep apnea and erectile dysfunction as markers for CVD.
Medscape: You mentioned psychosocial risk factors already, and the guidelines mention that anxiety and certain personality traits increase CVD risk. How did you decide what kind of recommendations you could include about this in CVD prevention guidelines?
Prof. Perk: That was a problem. The interventional studies that have been done using drugs or cognitive behavioral therapy have not shown consistent positive results. However, there is now a desire to recognize cognitive behavioral support for people with severe anxiety or depression. We do not include anything about drugs because we still lack evidence there. Another issue that we have not been able to assess is the enormous differences in psychosocial elements among different European countries and people in Eastern vs the rest of Europe.
Medscape: Reports on the previous guidelines, which, as you said, were much longer than the new ones, have noted the difficulties encountered in implementing them in different countries. Is there any new advice in the political section or the section on healthcare settings that would make implementation less difficult?
Prof. Perk: Life expectancy in Eastern Europe is 16 years shorter than in Western Europe, and this is based on socioeconomic level, but although we have this observation, we do not know what to do about it.
We have national versions of the SCORE diagram and we have divided Europe into low-risk, higher-risk, and very-high-risk countries. There are special tables for these different countries but they are only used for clinical practice. I would love to come out with guidance on a more political level: what to do with society in order to reduce the enormous differences between European countries, which have to do with poverty and unrest. As doctors, we cannot address these factors. Nonetheless, in the last chapter we have said that even the medical profession should stand up and make their voices heard because these disparities are not justified.
Now that I have finished this work, I will be in charge of the prevention implementation committee. The different societies that have come together will try to provide guidance to get things really working. That is what I see as my task with my group for the coming 3 years: to see that this document really takes roots in different countries. We have already identified national coordinators for prevention in each country, and we are going to work with them and try to help them develop documents to use nationally in clinical practice. This is a great challenge and it will be very gratifying to see our writing work become dirt under the nails, as we say.
Medscape: Obviously research and drug development are ongoing, so is there any provision for updating these guidelines before another 5 years is up? For instance, many new drugs are likely to become available in the next few years for lipid lowering, treating hyperglycemia in diabetes, and weight loss.
Prof. Perk: We have been discussing this intensively, but our behavioral scientists say, "don't force too much information upon people in a short period of time." The world will not go under if you wait 1 or 2 or 3 years. Let it settle, see to it that we get it working, and when it works, then we can take the next step. Of course, if there is extremely important new scientific information it will leak out anyhow, but we should not tire people with too many documents because they will get "guideline lethargy" and the guidelines won’t have any effect any longer.
Medscape: At the launch you mentioned that in addition to the conventional pocket version, a 1-page summary version of the guidelines would be available. Is that out yet?
Prof. Perk: Our team of general practitioner experts is working on it at the moment. What we are doing was inspired by Ingvar Kamprad, who founded the big Swedish furniture retail company IKEA. He comes from my state in Sweden, by the way, and one of his main statements was that if you cannot get a message across on half a piece of A4 paper, nobody will read it. So at this year's ESC Congress in Munich we are going to present the IKEA-style recommendations -- the core points of prevention -- on one piece of paper. It is intended to be placed on the desk but it should not take up the top surface of the desk, so it is a challenge.
Medscape: Will the pocket guidelines be released in English and other languages?
Prof. Perk: The pocket guidelines will be launched in English, and it will be up to other countries to translate it. We will see to it with the people from our national cardiology societies that they make this 1-page summary available for general practitioners everywhere in the world. I think we have got to make a lot of noise about it -- that is what is going to happen.