- Email: [email protected]
Controversies in cardiology
Correspondence
Lionel Opie and colleagues (Jan 7, p 69)1 pose the question “In view of the survival benefit shown for coronary-artery bypass grafting, the real controversy is why patients with symptoms and anatomy known to benefit from the procedure are still submitted to percutaneous coronary intervention.” The simple answer is that clinical practice has been distorted by the misunderstanding and inappropriate widespread application of the results of randomised clinical trials, done in highly select populations, to a much wider population.2 There have been 15 randomised trials of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG) for multivessel coronaryartery disease, which reported a fourfold reduction in the need for repeat intervention with CABG but little difference in survival between the two interventions.2 This apparent lack of survival benefit with CABG was, however, “manufactured” by largely populating the trials with patients with one-vessel or two-vessel coronaryartery disease and normal ventricular function—a population in whom it had already been established that there is little prognostic benefit from surgery.3 This was achieved by excluding around 95% of the screened population from the trials and, in particular, patients known to have prognostic benefit from CABG (those with left mainstem, real triple-vessel disease, severe and complex coronary-artery disease including occluded vessels, and those with impaired ventricular function). Because the patients in the trials were therefore much different from those who actually undergo CABG in the real world, the trials were inherently biased against the survival benefits of CABG. Nevertheless, there is consistently strong evidence of survival advantage with CABG in the real world.4 For example, in the New York Registry of www.thelancet.com Vol 367 April 22, 2006
almost 60 000 risk-matched patients with severe coronary disease, within 3 years of treatment there was an absolute reduction in mortality by around a third and a sevenfold reduction in the need for reintervention in patients undergoing CABG rather than PCI. The survival advantage of CABG is probably because, by contrast with PCI, surgery deals not only with the immediate culprit lesion but also future culprit lesions by placing the graft to the midcoronary vessel, well beyond diseased segments. The current tendency of some cardiologists to abandon the traditional multidisciplinary approach to multivessel coronary-artery disease effectively denies some patients the option of surgery and consequently falls far short of best practice.
modest increases in potassium intake are associated with blood pressure reductions in the order of 4–8 mm Hg systolic and 2–5 mm Hg diastolic in hypertensive individuals.3-5 Furthermore, the antihypertensive effects of increased potassium intake seem to be greatest in those with high dietary salt intake and in blacks.4 Therefore, potassium supplementation, particularly through dietary modification (eg, by increasing intake of fruits and vegetables) is a cheap, easy, effective, and safe means to reduce blood pressure in hypertensive patients with preserved renal function. I declare that I have no conflict of interest.
Steven G Coca [email protected] Yale University School of Medicine, New Haven, CT 06520, USA 1
I declare that I have no conflict of interest.
David P Taggart
2
[email protected] Department of Cardiac Surgery, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK 1
2
3
4
Opie LH, Commerford PJ, Gersh BJ. Controversies in cardiology 1: controversies in stable coronary artery disease. Lancet 2006; 367: 69–78. Taggart DP. Surgery is the best intervention for severe coronary artery disease. BMJ 2005; 330: 785–86. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994; 344: 563–70. Hannan EL, Racz MJ, Walford G, et al. Longterm outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005; 352: 2174–83.
The article on controversies in hypertension by Norman Kaplan and Lionel Opie (Jan 14, p 168)1 was thorough and insightful. However, Kaplan and Opie did not mention one key, additional strategy for blood pressure reduction—ie, an increase in potassium intake. Potassium intake is inadequate in a large proportion of the general population and is generally the lowest in blacks.2 Several clinical trials and three meta-analyses have shown that
e-mail submissions to [email protected]
3
4
5
Kaplan NM, Opie LH. Controversies in cardiology 2: controversies in hypertension. Lancet 2006; 367: 168–76. Institute of Medicine. Dietary reference intakes: water, potassium, sodium chloride, and sulfate, 1st edn. Washington, DC: National Academy Press, 2004. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. J Hypertens 1991; 9: 465–73. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure: metaanalysis of randomized controlled clinical trials. JAMA 1997; 277: 1624–32. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hypertens 2003; 17: 471–80.
Norman Kaplan and Lionel Opie’s article on hypertension1 is timely, but its halfhearted approach to this pandemic is most disappointing. They rightly point out the importance of lowering population blood pressure by public health approaches, but then pour cold water on diet and lifestyle changes, casting doubt that, in populations, such measures can be applied. They ignore the fact that, in most developed countries, much of the salt, saturated fat, and sugar in the diet is hidden in processed foods, meaning that the changes required to lower blood pressure are largely in the hands of the food industry and
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
1313
Science Photo Library
Controversies in cardiology
Science Photo Library
Correspondence
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
not of individuals. For instance, about 80% of salt intake comes from salt added to processed, restaurant, fast, and takeaway foods. A reduction in salt intake can easily be achieved by a gradual reduction in the amount of salt added to food by the food industry. A strategy of small reductions (10–20%), which are not detected by the human salt taste receptors, and repeated every 1–2 years, is being achieved in the UK. Within 5 years, salt intake should be reduced from the current daily level of 10–12 g to 5–6 g. In the interest of customers, the food industries of other countries should follow this example. It is surprising that Kaplan and Opie brush aside the important role of fruit and vegetables in lowering blood pressure. Randomised trials have shown that increasing fruit and vegetable consumption lowers blood pressure2 via the increase in potassium intake. The combination of a low-salt diet with an increased consumption of fruit and vegetables has a greater effect on blood pressure than either intervention alone. Furthermore, evidence suggests that a higher consumption of fruit and vegetables might have other beneficial effects on health, independent of and in addition to its effect on blood pressure.3 Prospective cohort studies have shown that increased fruit and vegetable intake is related to a reduction in the risk of stroke4 and coronary heart disease.5 A comprehensive nationally promoted public health approach, preferably government led, is needed to reduce salt, saturated fat, and sugar in the diet; to increase the intake of fruit and vegetables; to stop smoking and reduce alcohol consumption; and to reduce bodyweight and increase exercise. Such an approach will reduce the appalling burden of cardiovascular disease worldwide, particularly in less developed countries. We declare that we have no conflict of interest.
Feng J He, Hugh E de Wardener, *Graham A MacGregor [email protected] 1314
Blood Pressure Unit, St George’s University of London, Cranmer Terrace, London SW17 0RE, UK. 1
2
3 4
5
Kaplan NM, Opie LH. Controversies in cardiology 2: controversies in hypertension. Lancet 2006; 367: 168–76. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336: 1117–24. He FJ, MacGregor GA. Beneficial effects of potassium. BMJ 2001; 323: 497–501. He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: metaanalysis of cohort studies. Lancet 2006; 367: 320–26. Law MR, Morris JK. By how much does fruit and vegetable consumption reduce the risk of Ischaemic heart disease? Eur J Clin Nutr 1998; 52: 549–56.
In their article on controversies in hypertension,1 Norman Kaplan and Lionel Opie contradict our hypothesis that an increase in the concentration of the antioxidant uric acid in plasma provoked by diuretics, even at low doses devoid of effects on potassium, might benefit the heart and vessels.2 We believe that, by implication, it is apposite to theorise that other increases in plasma uric acid that result from reduced renal excretion, such as those that accompany curtailment of sodium intake or those that might be caused by low-dose acetylsalicylic acid,2 could partly explain the salutary cardiovascular actions of their causative factors. Kaplan and Opie support their stance by quoting studies in which it was found that: (1) plasma uric acid and mean blood pressure rose in parallel in men with normotension; (2) hyperuricaemia predicted the development of hypertension; and (3) mounting levels of plasma uric acid predicted increased target organ damage. They also mention that mild hyperuricaemia has been found to promote renal vascular and interstitial alterations and hypertension in rats. In their conclusion, they subscribe to the hypothesis that high concentrations of uric acid in plasma convey disadvantages that outweigh the slight antioxidant benefit that they might confer. First, we wish to emphasise that our hypothesis does not refer to raised
concentrations of plasma uric acid but to the increases caused by diuretics— ie, to specific changes in the variable and not its absolute values. Increases in plasma uric acid could stem from increased synthesis mediated by xanthine dehydrogenase or xanthine oxidase, from reduced renal excretion, or from combinations thereof, as seems to happen in heart failure.3 Thus, considering increases or decreases in plasma uric acid indiscriminately is not heuristically valuable.4 The results of the studies in human beings quoted by Kaplan and Opie do not necessarily mean that increasing plasma uric acid concentrations harm cardiovascular structures, since such rises could be inconsequential epiphenomena of processes that bring about hypertension or its complications, or they could constitute a compensatory reaction, triggered by unknown signals, aimed at countering oxidative stress. The authors of the Atherosclerosis Risk in Communities Study5 found that plasma uric acid and the occurrence of ischaemic stroke were positively associated in participants who did not take a diuretic, but not in those who did; our hypothesis is congruent with these results. Second, it has never been proven that lowering plasma uric acid or counterbalancing the increases in this variable caused by diuretics or by diminutions in sodium intake benefits human cardiovascular structures or function independently of the possible effect of attendant changes in other variables that matter. Third, the rat is hardly an adequate animal model in which to study uric acid, which is enzymatically transformed into allantoin in rodents but not in man. Lastly, we think that our hypothesis warrants testing and do not aim to impinge on practice before the results of purposive research, scientific reasoning, and clinical considerations justify applied conclusions. We declare that we have no conflict of interest.
www.thelancet.com Vol 367 April 22, 2006
Lionel Opie and colleagues (Jan 7, p 69)1 pose the question “In view of the survival benefit shown for coronary-artery bypass grafting, the real controversy is why patients with symptoms and anatomy known to benefit from the procedure are still submitted to percutaneous coronary intervention.” The simple answer is that clinical practice has been distorted by the misunderstanding and inappropriate widespread application of the results of randomised clinical trials, done in highly select populations, to a much wider population.2 There have been 15 randomised trials of percutaneous coronary intervention (PCI) and coronary-artery bypass grafting (CABG) for multivessel coronaryartery disease, which reported a fourfold reduction in the need for repeat intervention with CABG but little difference in survival between the two interventions.2 This apparent lack of survival benefit with CABG was, however, “manufactured” by largely populating the trials with patients with one-vessel or two-vessel coronaryartery disease and normal ventricular function—a population in whom it had already been established that there is little prognostic benefit from surgery.3 This was achieved by excluding around 95% of the screened population from the trials and, in particular, patients known to have prognostic benefit from CABG (those with left mainstem, real triple-vessel disease, severe and complex coronary-artery disease including occluded vessels, and those with impaired ventricular function). Because the patients in the trials were therefore much different from those who actually undergo CABG in the real world, the trials were inherently biased against the survival benefits of CABG. Nevertheless, there is consistently strong evidence of survival advantage with CABG in the real world.4 For example, in the New York Registry of www.thelancet.com Vol 367 April 22, 2006
almost 60 000 risk-matched patients with severe coronary disease, within 3 years of treatment there was an absolute reduction in mortality by around a third and a sevenfold reduction in the need for reintervention in patients undergoing CABG rather than PCI. The survival advantage of CABG is probably because, by contrast with PCI, surgery deals not only with the immediate culprit lesion but also future culprit lesions by placing the graft to the midcoronary vessel, well beyond diseased segments. The current tendency of some cardiologists to abandon the traditional multidisciplinary approach to multivessel coronary-artery disease effectively denies some patients the option of surgery and consequently falls far short of best practice.
modest increases in potassium intake are associated with blood pressure reductions in the order of 4–8 mm Hg systolic and 2–5 mm Hg diastolic in hypertensive individuals.3-5 Furthermore, the antihypertensive effects of increased potassium intake seem to be greatest in those with high dietary salt intake and in blacks.4 Therefore, potassium supplementation, particularly through dietary modification (eg, by increasing intake of fruits and vegetables) is a cheap, easy, effective, and safe means to reduce blood pressure in hypertensive patients with preserved renal function. I declare that I have no conflict of interest.
Steven G Coca [email protected] Yale University School of Medicine, New Haven, CT 06520, USA 1
I declare that I have no conflict of interest.
David P Taggart
2
[email protected] Department of Cardiac Surgery, Oxford Heart Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK 1
2
3
4
Opie LH, Commerford PJ, Gersh BJ. Controversies in cardiology 1: controversies in stable coronary artery disease. Lancet 2006; 367: 69–78. Taggart DP. Surgery is the best intervention for severe coronary artery disease. BMJ 2005; 330: 785–86. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994; 344: 563–70. Hannan EL, Racz MJ, Walford G, et al. Longterm outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005; 352: 2174–83.
The article on controversies in hypertension by Norman Kaplan and Lionel Opie (Jan 14, p 168)1 was thorough and insightful. However, Kaplan and Opie did not mention one key, additional strategy for blood pressure reduction—ie, an increase in potassium intake. Potassium intake is inadequate in a large proportion of the general population and is generally the lowest in blacks.2 Several clinical trials and three meta-analyses have shown that
e-mail submissions to [email protected]
3
4
5
Kaplan NM, Opie LH. Controversies in cardiology 2: controversies in hypertension. Lancet 2006; 367: 168–76. Institute of Medicine. Dietary reference intakes: water, potassium, sodium chloride, and sulfate, 1st edn. Washington, DC: National Academy Press, 2004. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. J Hypertens 1991; 9: 465–73. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure: metaanalysis of randomized controlled clinical trials. JAMA 1997; 277: 1624–32. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hypertens 2003; 17: 471–80.
Norman Kaplan and Lionel Opie’s article on hypertension1 is timely, but its halfhearted approach to this pandemic is most disappointing. They rightly point out the importance of lowering population blood pressure by public health approaches, but then pour cold water on diet and lifestyle changes, casting doubt that, in populations, such measures can be applied. They ignore the fact that, in most developed countries, much of the salt, saturated fat, and sugar in the diet is hidden in processed foods, meaning that the changes required to lower blood pressure are largely in the hands of the food industry and
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
1313
Science Photo Library
Controversies in cardiology
Science Photo Library
Correspondence
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
not of individuals. For instance, about 80% of salt intake comes from salt added to processed, restaurant, fast, and takeaway foods. A reduction in salt intake can easily be achieved by a gradual reduction in the amount of salt added to food by the food industry. A strategy of small reductions (10–20%), which are not detected by the human salt taste receptors, and repeated every 1–2 years, is being achieved in the UK. Within 5 years, salt intake should be reduced from the current daily level of 10–12 g to 5–6 g. In the interest of customers, the food industries of other countries should follow this example. It is surprising that Kaplan and Opie brush aside the important role of fruit and vegetables in lowering blood pressure. Randomised trials have shown that increasing fruit and vegetable consumption lowers blood pressure2 via the increase in potassium intake. The combination of a low-salt diet with an increased consumption of fruit and vegetables has a greater effect on blood pressure than either intervention alone. Furthermore, evidence suggests that a higher consumption of fruit and vegetables might have other beneficial effects on health, independent of and in addition to its effect on blood pressure.3 Prospective cohort studies have shown that increased fruit and vegetable intake is related to a reduction in the risk of stroke4 and coronary heart disease.5 A comprehensive nationally promoted public health approach, preferably government led, is needed to reduce salt, saturated fat, and sugar in the diet; to increase the intake of fruit and vegetables; to stop smoking and reduce alcohol consumption; and to reduce bodyweight and increase exercise. Such an approach will reduce the appalling burden of cardiovascular disease worldwide, particularly in less developed countries. We declare that we have no conflict of interest.
Feng J He, Hugh E de Wardener, *Graham A MacGregor [email protected] 1314
Blood Pressure Unit, St George’s University of London, Cranmer Terrace, London SW17 0RE, UK. 1
2
3 4
5
Kaplan NM, Opie LH. Controversies in cardiology 2: controversies in hypertension. Lancet 2006; 367: 168–76. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336: 1117–24. He FJ, MacGregor GA. Beneficial effects of potassium. BMJ 2001; 323: 497–501. He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: metaanalysis of cohort studies. Lancet 2006; 367: 320–26. Law MR, Morris JK. By how much does fruit and vegetable consumption reduce the risk of Ischaemic heart disease? Eur J Clin Nutr 1998; 52: 549–56.
In their article on controversies in hypertension,1 Norman Kaplan and Lionel Opie contradict our hypothesis that an increase in the concentration of the antioxidant uric acid in plasma provoked by diuretics, even at low doses devoid of effects on potassium, might benefit the heart and vessels.2 We believe that, by implication, it is apposite to theorise that other increases in plasma uric acid that result from reduced renal excretion, such as those that accompany curtailment of sodium intake or those that might be caused by low-dose acetylsalicylic acid,2 could partly explain the salutary cardiovascular actions of their causative factors. Kaplan and Opie support their stance by quoting studies in which it was found that: (1) plasma uric acid and mean blood pressure rose in parallel in men with normotension; (2) hyperuricaemia predicted the development of hypertension; and (3) mounting levels of plasma uric acid predicted increased target organ damage. They also mention that mild hyperuricaemia has been found to promote renal vascular and interstitial alterations and hypertension in rats. In their conclusion, they subscribe to the hypothesis that high concentrations of uric acid in plasma convey disadvantages that outweigh the slight antioxidant benefit that they might confer. First, we wish to emphasise that our hypothesis does not refer to raised
concentrations of plasma uric acid but to the increases caused by diuretics— ie, to specific changes in the variable and not its absolute values. Increases in plasma uric acid could stem from increased synthesis mediated by xanthine dehydrogenase or xanthine oxidase, from reduced renal excretion, or from combinations thereof, as seems to happen in heart failure.3 Thus, considering increases or decreases in plasma uric acid indiscriminately is not heuristically valuable.4 The results of the studies in human beings quoted by Kaplan and Opie do not necessarily mean that increasing plasma uric acid concentrations harm cardiovascular structures, since such rises could be inconsequential epiphenomena of processes that bring about hypertension or its complications, or they could constitute a compensatory reaction, triggered by unknown signals, aimed at countering oxidative stress. The authors of the Atherosclerosis Risk in Communities Study5 found that plasma uric acid and the occurrence of ischaemic stroke were positively associated in participants who did not take a diuretic, but not in those who did; our hypothesis is congruent with these results. Second, it has never been proven that lowering plasma uric acid or counterbalancing the increases in this variable caused by diuretics or by diminutions in sodium intake benefits human cardiovascular structures or function independently of the possible effect of attendant changes in other variables that matter. Third, the rat is hardly an adequate animal model in which to study uric acid, which is enzymatically transformed into allantoin in rodents but not in man. Lastly, we think that our hypothesis warrants testing and do not aim to impinge on practice before the results of purposive research, scientific reasoning, and clinical considerations justify applied conclusions. We declare that we have no conflict of interest.
www.thelancet.com Vol 367 April 22, 2006