>>DR. DAVID McCARRON I would like to welcome you today to a discussion about salt and health, and specifically to address the question: are the 2005 Dietary Guidelines, as they relate to salt intake recommendations, supported by the best science? I am Dr. David McCarron. I am a visiting professor at the University of California Davis and president of Academic Network in Portland, Oregon. In introducing this webcast, I would like to draw on the quote from Dr. Sandy Miller who in the mid-1980's was a deputy commissioner for the FDA and specifically the food section of the FDA. Sandy was there at the beginning of the government's policy of recommending broader universal sodium restriction, but 15 years later in a article that was published in the journal Science, Sandy was quoted as saying "the salt controversy is the number one perfect example of why science is a destabilizing force in public policy." I am joined today in our discussion by Suzanne Oparil, a professor of medicine at the University of Alabama Birmingham. Suzanne will discuss the salt and hypertension policy, the history behind it. Sandy Logan, professor of medicine at the University of Toronto will discuss the efficacy and safety of salt restriction as we know it from the randomized trials that have been carried out over the last 20 years. I will then come back and discuss the important issue of diet quality and how it relates to salt sensitivity, that is if we improve the quality of diet, will salt's effects on blood pressure be modified. And then finally Dr. Mickey Alderman, professor of medicine at Einstein Medical College, will discuss the evidence relating sodium intake or salt intake to cardiovascular disease outcomes. Ultimately the most important question: if we lower salt intake, will we live longer and will we live better? Now I would like to turn the discussion over to our first panelist Dr. Suzanne Oparil from the University of Alabama Birmingham. >>DR. SUZANNE OPARIL The salt and hypertension policy that we have in hand has a very interesting history in that over the course of time the evidence has become weaker but the policy has become progressively stronger. This was very well described in Science magazine in 1998 with the statement from a very thoughtful review by Gary Taubes and I will read it to you. "If ever there was a controversy over the interpretation of scientific data this (meaning salt's role in the pathogenesis of hypertension) is it." I could not say it that well myself. Another concept that we need to keep in mind is that "the obstacle to discovery is the illusion of knowledge," and if we have a policy that assumes knowledge that is not there or not in evidence, then we are headed for trouble. The nature of the controversy is this. Basically the hypothesis on which our salt policy, our salt and hypertension policy, is based is very old, based on data from animal models done 60+ years ago and in these animal models in fact there were issues that do not apply well to humans. They were models of kidney disease; these were inbred animals, generally rats, steroids were used in some of the animals, excessive levels of salt, up to 8% of the diet in salt was used to provoke cardiovascular changes that really are not relevant to humans, and in fact in these animals blood pressure did go up on these very high salt diets. Based on this, the policy was set in the year 1980, but human studies at that time were very limited and the critical ones in fact were initiated after, not before, after the policy was already established. Among those you have the first short-term randomized trials of salt restriction, which were published in 1982, the first US government survey NHANES in 1984, we have the first US-sponsored international survey Intersalt published in 1988, the first NIH large scale trial of salt restriction TOHP II in 1997, and then the first NIH trial using actual foods that assured adequate nutrition in 2001. All these came after the policy was established. The nature of the controversy is that once the findings from these human studies came out, it was very clear that they failed to provide convincing support for the policy. Specifically, these studies documented that for many persons salt had no adverse effect on blood pressure and, as Dr. Logan will discuss with you later, actually in some persons increasing salt intake lowers blood pressure. Previously unrecognized concerns in policy incompatibilities raised their ugly heads in the process of this in that summary analysis or meta-analysis of these trials indicated minimal benefit with respect to blood pressure in the general population by restricting dietary salt. And to make the problem deeper, in 1995 our colleague Dr. Alderman first reported that excessive cardiovascular disease might result from dietary salt restriction. In spite of the data from these human studies which provided contradictory evidence the policy has continued to expand instead of being more limited in scope. If we look at TOHP II, which was a study conducted by the National Heart, Lung, and Blood Institute, very well designed with very large numbers of subjects, we see that by 36 months of the trial, the ability to reduce blood pressure by lifestyle modification - including weight loss, sodium restriction and the combination - was very limited and in fact sodium restriction reduced systolic blood pressure by less than 1 mm Hg, and combining sodium restriction with weight loss attenuated the benefits of the weight loss. Hard to explain, but it is a finding that was clearly documented. Now if we look at the short term randomized trials of salt restriction, it is clear that there was a problem with these, which clouds the interpretation. In all cases, as you can see from the four studies cited here, the background potassium content of the diet on which salt restriction was superimposed was quite low, ranging from 49 to about 80 mEq per day. We now know that the official recommendation from the National Academy of Sciences, the Institute of Medicine, is 120 mEq per day and the DASH-Sodium diet which is highly touted as the best way, as the best dietary way, lifestyle way to reduce blood pressure, had a potassium content of 80-120 mEq per day. So, in conclusion, these salt restriction studies have all been done, up until we encounter DASH, on a poor quality diet and this virtually assures that salt reduction would show some benefit in blood pressure. Now we need to think about the objectives of a national nutrition policy. Number one clearly should be designed to extend life expectancy in the population, to improve quality of life, to impact on multiple risks, multiple cardiovascular risks at least. Recommendations should be feasible, if people do not do things then the things have very little benefit, and then finally they should be, these recommendations should be based on reproducible science, and the scientific evidence supporting the salt policy simply did not exist in 1980. The current national nutrition policy with respect to salt does not satisfy these criteria. >>DR. ALEXANDER LOGAN My name is Sandy Logan and I want to talk about the relationship between sodium and blood pressure. There is a wealth of information documenting the relationship between dietary sodium intake and blood pressure. In normal healthy subjects which this slide shows there is no relationship between dietary sodium intake and blood pressure. This has been documented in several other studies. Indeed, in this particular study the individuals on a low sodium diet had a higher blood pressure than when they were on a high salt diet. There is considerable variation in the blood pressure response of normotensive individuals to changes in dietary sodium intake. In this particular study when salt intake was restricted, up to 25% of the individuals had an increase in their blood pressure. From a blood pressure perspective, this increase puts these individuals at increased risk. There have been several studies summarizing the information on sodium trials. Our particular study published in 1996 cobbled together 28 studies in normotensive individuals. The duration of the trials ranged from 4 days to over 36 months and the average reduction in sodium intake was 125 mmol per day. This led to a small but significant reduction in systolic blood pressure, but no changes in diastolic blood pressure. A more recent analysis of the data looked only at the longer trials, ranging from 18 months to 36 months, and the results are very similar to what we found although the dietary salt reduction was significantly less than what we found. The DASH-Sodium trial was a single study published to look at the effects of dietary sodium restriction in individuals who were consuming the recommended typical North American diet. With a reduction of 77 mmol of sodium, this led to a 5.6 mm Hg reduction in systolic blood pressure and a 2.8 mm Hg reduction in diastolic blood pressure. These changes are dramatically different from all the other studies that have been published before. One possible explanation for the difference in response of this single study compared to all the other evidence is the background diet that the individuals were consuming. They were placed on a low quality diet which represents about the diet 25% of Americans consume, and as one can see here, that when you dietary salt-restrict individuals on a poor quality diet, there is a dramatic reduction in both systolic and diastolic blood pressure. In contrast and in the same study when they placed individuals on a high quality diet, the reduction in blood pressure with dietary salt restriction was markedly attenuated and the values were almost half of those found on the low quality diet. When one looks at the salt restriction on the recommended sodium diet, one can see again that a low quality diet leads to more significant reduction in blood pressure than individuals on a high quality diet. Indeed, if you look at the data on the high quality diet, the reduction in systolic blood pressure and the reduction in diastolic blood pressure were very similar to what we found in our meta-analysis and what Hooper found in his meta-analysis, with the systolic blood pressure being significant and no significant change in the diastolic blood pressure. When we look at the metabolic effects of dietary salt intake we see a number of different changes. First of all, atrial natruretic factor goes up as you go on a high salt diet and there is an increase, but on the other hand there is a reduction in aldosterone level, renin, and norepinephrine. It has been suggested that on a low sodium diet that the elevation of these biochemical parameters may have adverse effects. A particular issue that our group has been studying has been the change in insulin resistance as a result of being placed on a low sodium diet. In this particular study individuals were placed initially on a high salt diet and subsequently on a low salt diet. The reduction in the glucose-insulin ratio, meaning increase in insulin resistance, was highly significant and this was a systemic effect. When we looked at the vascular effects of going on a low sodium diet, there was a decrease in the ability of nitroglycerin, a major vasodilator to dilating the blood vessels indicating an element of venal constriction as a result of being on a low sodium diet. There are also other biochemical changes associated with being on a high salt diet, the most prominent of which is an increase in urinary calcium excretion, and this has been used as evidence to put forward the hypothesis that an increase in salt intake leads to osteoporosis or at least increases your risk of osteoporosis. What is failed to be understood is that when there is an increase in urinary calcium excretion there is a reduction in serum calcium leading to an increase in parathormone, which has multiple effects. On the kidney, it increases calcium reabsorption; on the gut it facilitates calcium absorption. The sum effect is a neutral effect on calcium, so therefore, until there is better evidence, there is low evidence showing any relationship between dietary sodium intake and bone disease. >>DR. DAVID McCARRON I would like to now move on to the issue of diet quality and salt sensitivity, a topic that has already been introduced by our prior speakers. I would like to just to state from the outset that there is a wonderful public policy opportunity here if we just stick with the science, because if we improve the diet quality of the American diet, then I would argue that sodium restriction becomes a moot issue - that for the vast majority of Americans, being concerned about the salt shaker is a nonissue, and I would like to give you a sense of the science that backs that. Dr. Oparil mentioned that in 1984, the first US government survey was released looking at the American diet and its relationship to blood pressure. My laboratory was the source of that publication and I was the senior author on that paper, and in that paper there was this graph which shows the relationship between the daily intake of calcium from foods and systolic blood pressure in the US population and, as you can see, if you did not know this was food you would think this was a drug that Americans were taking because the more calcium the individuals in America reported in their diet, the lower their blood pressure. Now at that time the study talked about calcium, it talked potassium, but in reality when you discussed dietary calcium or dietary potassium or even dietary magnesium you are really discussing the quality of the diet. We now know that individuals who tend to have richer mineral intake in their diet overall have a better quality diet. And in fact, in that same paper in 1984 in Science, we did what is called a multivariate regression analysis; what we did was we asked the computer, go look at this large database from the US government with 10,600 people in it and tell us, based upon the data, what foods you would introduce to the American diet to get blood pressure as low as possible. Here is the table taken directly from that Science paper in 1984, and as you can see the first group that enters is dairy foods, and that is probably because they are the major source of minerals in the diet and they are also tied to a higher quality diet. Now there is some debate whether it should be low fat, no fat, or, you know, normal fat dairy foods, but the bottom line here was dairy foods were the first food group that would enter the diet that would be a high quality diet to lower blood pressure. Then the second group is fruits and vegetables and juices, and of course we now know and will talk about this a little bit further and Dr. Logan already mentioned this, the DASH diet which is all through the Dietary Guidelines and at the base of the new food pyramid is a diet rich in dairy foods, fruits, and vegetables. Colleagues from Canada looked at data about 10 years later from over 40 trials or studies that were similar to our Science paper in 1984, and they noted in their analysis of the randomized trials that were done that there was an effect of increasing calcium in a diet. Again the effect was small, sort of what like what we say about salt restriction, but then they noted that if you looked at people who were African American, if you looked at older subjects, if you considered the state of pregnancy, and we will hear about that from Dr. Alderman later, or salt sensitive subjects, that the effect of a high quality high calcium diet might have been much greater. The evidence still was not there, but they felt that if we did a study that fixed the baseline intake and looked at populations that appeared to be particularly salt sensitive, we would see a greater effect. In fact, a year after that summary analysis in JAMA in 1997, the first DASH trial was reported, and here is a summary figure from that National Heart, Lung, and Blood Institute study, which by the way was the first trial looking at foods in a dietary pattern to lower blood pressure rather than looking at single nutrients or a single issue like sodium restriction. And keep in mind this is reported in 1997, just eight years ago, and yet our policy had been set 13 years before this study was reported. The important message from this slide is if you look at the bars under fruits and vegetables, low fat dairy, the DASH diet, during the intervention which is the solid blue bar, people with high blood pressure in this National Institutes of Health trial accomplished an 11.6 mm reduction in their systolic blood pressure and you can compare that to the findings from the TOHP study that Dr. Oparil just showed in a simple bar graph where the effect of salt restriction was about 1 mm Hg. So the effect of the DASH diet appeared to be at least 5-10 times as great. And in fact the DASH investigators subsequently noted that when you started the DASH diet - fruits and vegetables and low fat dairy - you had an immediate and sustainable effect. It was independent of weight and sodium intake because those were fixed in the study and were not a factor, and they stated in the New England Journal paper that reported the results that the effects were comparable to single drug therapy. They also stated because the study was structured to look at subgroups that the effect was generalizible across the entire population, that means everybody, whether you had a normal blood pressure or high blood pressure, whether you were African American or Caucasian, whether you were older or younger, improving the quality of your diet, adding fruits and vegetables and low fat dairy lowered your blood pressure risk. They then went on to note in a subsequent paper that 70% of the people who entered the original DASH study would not have needed medications had they been on a DASH diet, and that 78% of the older people in the trial who had systolic, or primary elevation of the upper number, would not have needed medications either if they had simply changed their diet to fruits and vegetables and low fat dairy. This of course would lead to a dramatic reduction in medication use. There is a second study that was reported several years after the DASH trial and it is called DASHSodium. Dr. Logan has shown you some of the results and I want to show them in a slightly different way. This figure is taken directly from a report last summer from the DASHSodium investigators, and what I want to point out is the DASH-Sodium trial really I think nailed down the notion of salt sensitivity being a surrogate marker for a poor quality diet, and if you improve the quality of the diet, modifying salt intake really has no impact on your blood pressure at all. And that is shown in the upper line here, these are the people in the DASH sodium trial who were Caucasian and did not have high blood pressure, so this is still the largest portion of the US population representative of that. If they were on a lousy diet, or the control diet which was mineral poor, high in fat, low in fiber, as you progressively, moving from left to right, lowered the salt intake you saw a reduction in blood pressure. But if these same individuals were put on a DASH diet, fruits and vegetables, low fat dairy, and you then lowered their salt intake you can see the line is essentially straight. There was no benefit of salt restriction once the diet was improved. This is another graph taken from the DASH sodium investigators' report last summer, in July of 2004. Here are the people who are less than 45 years of age and also are normotensive, again a large a segment of the US population, and you see the same trend. Once these individuals are on the DASH diet, essentially nothing happened to their blood pressure when they had their salt intake progressively restricted. And it turns out that there were reports from the observational literature 10 years before that predicted precisely the outcome of the DASH sodium trial. Here is one example done by Dr. Pavel Hamet, past president of the International Society of Hypertension, reported in 1991 in the American Journal of Hypertension, and what I want to point out is the fact that in this study done in Montreal in about 700 individuals, you could have the highest blood pressure in Montreal on a high salt diet, shown by the salt quartiles in the high purple bar, as long as your calcium intake or the quality of your diet was poor, but you could be on that same higher salt intake in Montreal and have the lowest blood pressure provided you were on a high mineral intake as measured by a high calcium intake. This in not the only study that has noted this; there are essentially four or five papers like this in the observational literature. So in summary, improving diet quality, i.e. following the DASH diet rather than restricting salt, appears to be the most effective nutritional strategy to lower blood pressure and, in fact, the JNC guidelines that Dr. Oparil alluded to does rank the DASH diet above salt restriction. It is also associated with improvements in cardiovascular risk factors. There is some data that says your weight comes down, there is data that some of those listening today have recently heard about improving the risk of diabetes, and we also know from several longitudinal studies that the DASH dietary pattern is associated with a reduction in all-cause mortality and specifically cardiovascular events, myocardial infarctions or heart attacks, and strokes. And my colleagues and I have reported in the medical literature using US government healthcare cost that the introduction of the DASH diet across the US population would lead to dramatic reductions in healthcare costs in this country. Thank you. >>DR. MICHAEL ALDERMAN I became interested in the relationship of sodium intake to cardiovascular outcomes as a result of the work that our group was doing then at Cornell University and Medical Center in New York on the renin-angiotensin system. It is well known that the renin-angiotensin system plays an important role in modulating the relationship between vasoconstriction and volume in the determination of blood pressure levels in all of us, normals and hypertensives as well. But in addition to the effects of the renin-angiotensin system on blood pressure control, the business end of the renin-angiotensin system, which is angiotensin II, has adverse effects on blood vessels and various target organs that influence the occurrence of strokes and heart attacks, which of course are the primary outcomes, adverse outcomes, associated with high blood pressure. We found during the evaluation of a large population of persons with high blood pressure that the measurement of plasma renin and the division of persons with high blood pressure into categories of renin - low and normal and high - added to our capacity to predict who was likely to have a heart attack or stroke among our treated hypertensive patients. You know, the fact of the matter is that even when we treat hypertension successfully we reduce events by 30% or so, strokes and heart attacks, but the fact of the matter is that most of the events that were going to occur happen anyway and what renin did was give us an additional tool to identify persons at higher risk of having a cardiovascular event. Indeed, we feel that these elevated levels of angiotensin II, which are inappropriate in persons with high blood pressure, actually participate in the causality of these strokes and heart attacks. We also found, as did others, that there was an inverse relationship between dietary sodium intake and the level of blood pressure, but more importantly in our view, the relationship between sodium and plasma renin activity. Those who ate the least amount of salt had the highest levels of plasma renin. And that of course raised the question as to whether or not folks who ate less salt might they be at higher risk of experiencing a cardiovascular event, which led us to undertake a study in our hypertensive population. We knew not only that reduced sodium intake was associated with elevated plasma renin activity but there were other adverse consequences of a low sodium diet, for example, decreased sensitivity to insulin and increased sympathetic nerve activity. This slide depicts the association of sodium intake to insulin sensitivity. So for a variety of reasons this seemed to us a reasonable hypothesis: that folks who ate less sodium might have more cardiovascular events in the face of successful antihypertensive therapy. We therefore, at the initiation of antihypertensive therapy, determined plasma renin activity and urinary sodium intake, and divided our population into quartiles of sodium intake. The first quartile here is the lowest sodium intake and the fourth is the highest. And what we found over almost a five year study was that the likelihood of cardiovascular events, particularly myocardial infarction was significantly greater in those who had less sodium intake. Indeed, there was about a 50% gradient in the likelihood of myocardial infarction comparing the first to the fourth quartile. Clearly in this population of successfully treated hypertensive patients, a low sodium diet was not associated with superior outcomes. Well, this was the first data published linking sodium intake to ultimate cardiovascular outcomes and since then, since 1995, there have been 7 or 8 other studies published with various amounts of data. Overall I think it is clear from this slide that depicts the outcomes presented in several of the studies in which data is presented, the results are at best inconsistent. There is one study recently published from a Japanese population, for example, in which a low sodium diet was associated with a favorable outcome, but I think it is important to note that in the Japanese population the general sodium intake is two or three times that in the United States. In Western communities with diets like our own there has mostly been an inverse association between sodium intake and ultimate outcomes. A single exception to that generalization is a sub group of the NHANES trial, the National Health and Nutrition Examination Survey. In that study of a representative sample of the United States population, for the whole group there was an inverse association between sodium and outcome, less sodium, more cardiovascular events. However, in an obese subset, 28% of that population, the reverse was found. Well, in short, it seems to me that the evidence is at best inconclusive and to my mind suggests that there is, that the association is least, the association between salt intake and health outcomes suggests that there is no particular advantage to a low sodium diet. It seems to me what we really need to address is the answer to that hard question. It is important to know what the intermediate effects of dietary manipulation might be. But most importantly, we want to know what the health outcomes are. How long is the life and what is the quality of that life? We need to do, I think first, a more expertly and precisely designed prospective study to associate salt intake to ultimate outcomes. If, when the results of these studies are available and there is a strong body of evidence that suggests that a low sodium diet would be advantageous, that would justify in my mind a randomized prospective trial to address the question in the most scientifically rigorous fashion. The questions we want to ask are: does sodium restriction reduce the likelihood of strokes and heart attacks and kidney failure, and finally, of course most importantly, would salt restriction reduce all-cause mortality? >>DR. DAVID McCARRON Well I would like to thank our panel members, Drs. Suzanne Oparil, Sandy Logan, and Mickey Alderman for joining me today in what I think is an important session to bring out issues about whether or not the current Dietary Guidelines of the year 2005, as they are articulated for salt and blood pressure reduction, are really based upon science. I would like to just summarize a few points that came out today. What we need to resolve the salt restriction safety issue is the same level of efficacy and safety trial data that would be required of a new drug therapy. We should expect no less of our nutrition policy recommendations, and as we have heard from Dr. Oparil and from Dr. Alderman, we're not there and we need to get there. A long-term prospective study that enrolls a sufficiently large enough population, involves multiple international sites, and has a period of observation that is probably greater than five years, and it monitors at some regular interval urinaary sodium excretion, which is an absolute marker of your dietary intake, blood pressure, and health status including the rest of your diet and cardiovascular events is what is needed. Well, you have seen this slide earlier; Dr. Oparil pointed out what some of the critical purposes of a national nutrition policy are and the question now is do the salt data pass the test, do they meet these requirements, and I think the information we have shared with you today would argue that they do not. Specifically, as we have heard, we do not have the data that says salt restriction extends life expectancy, i.e. reduces cardiovascular morbidity and mortality and all-cause mortality. We have essentially no evidence that going a low salt diet improves the quality of your life, and that is important because if you are asking a population to do something that adversely impacts the quality of their life they are not likely to incorporate that in their lifestyle. We have little evidence that a lower salt diet improves multiple risk factors, which is in contrast to what we now know about the DASH diet, i.e. a mineral rich diet from dairy foods and fruits and vegetables, where we now have evidence that multiple risk factors are improved, and we need to know that these are feasible recommendations. Can people incorporate the low sodium diet into their lifestyle and do it for a long period of time and again the evidence is lacking to support that notion. A lot of times we hear some experts say "well, this is just because the food industry has not produced the low sodium diets or low sodium foods that we need for a low sodium diet." That is not true. We have had low sodium products available in this country and in Canada and Europe and Japan for a long time, and the facts are that patients are not able to incorporate these foods into their diet in a meaningful way. But we need to document this and know, if we are going to move forward with this policy, that this is do-able. And finally, as we have repeated several times over, the science is really not reproducible to support the current policy as articulated in the 2005 Dietary Guidelines, and if the science is not there, then we need to look at what the policy should be based upon the science that is in the medical literature. In summary, we have a current policy that was set before science had verified it as safe and efficacious. There are clinical trials that demonstrate only a modest benefit of salt reduction in certain subgroups, not everybody. And a variety of potentially adverse outcomes have been identified and noted in many of the trials. We need to follow up on that and make sure this is a safe intervention for the general population. Thus, we need properly designed clinical trials, conducted to establish the safety and efficacy of salt reduction and specifically determine whether it reduces morbidity and mortality. It would appear, as our current guidelines in other areas indicate, that if we will improve diet quality by adding minerals back into our diet, primarily through fruits and vegetables and dairy foods, this will negate salt's effects on blood pressure in most individuals, and it has been associated with a reduction in all-cause mortality, including specifically cardiovascular events. The current policy of salt restriction for the general population is not supported by the available scientific evidence. I will conclude by just showing you a picture of the new food guide pyramid released last month by the US Department of Agriculture and the Department of Health and Human Services and point out to you that if you look along the base of the pyramid, the center of that pyramid is the DASH diet: vegetables, fruits, and milk, combined with some exercise, which is important. As I saw in another publication recently with an individual standing by this pyramid asking where the elevator is, is not going to get this done. So I would encourage all of you to rethink what you are consuming in terms of cardiovascular health and well being, and think first about fruits and vegetables, low fat dairy, the DASH diet, the current recommendation of the National Heart, Lung, and Blood institute is the first nutritional recommendation to lower blood pressure. And on that note, we will finish our presentations and we will take questions and answers. For those of you interested in submitting a question, please follow the guidelines that are available on the website and your questions will be taken. Thank you. QUESTION AND ANSWER SESSION >>DR. DAVID McCARRON I would like to thank all the panel members for the presentation today, and we've opened the forum up to question from the internet audience. And I would like to start with a question that came in asking what is the relationship of small changes--I take the questioner's intent there to mean a one or two millimeter reduction in blood pressure--with cardiovascular disease outcomes? Mickey, you might like to address that. >>DR. MICHAEL ALDERMAN Thanks, Dave. Well, that's a good question that's got two answers. One is if we could lower the blood pressure of the entire population, 250 million Americans, for example, by one or two millimeters of mercury, that would have a--and it could be done at no cost, no downside associated with the technique for lowering blood pressure--that would produce a measurable benefit for the whole population. The second part of that answer is that for an individual patient, a blood pressure change of one or two millimeters of mercury has no important measurable impact. Our blood pressure as individuals varies much more widely than that in the normal routine of our daily lives. So as a public health issue, if we had a technique that was absolutely cost-free that could lower the whole population's blood pressure, it would be a highly desirable objective. Unfortunately, we don't have such a tool. >>DR. DAVID McCARRON Thank you, Mickey. We have a second question here, asking the U.S. government guidelines--I suspect that means the recently released dietary guidelines from earlier this year--if we were to believe they are the ultimate authority on diet and health, how do you account for the fact that they use the Dash sodium trial to support recommending a lower salt intake, and yet in our presentations we have used the same study to suggest that lower sodium intake does not really improve blood pressure as long as the quality of the diet is greater. And what would be the reason for the government to flip the use of that study, if you will? And I will take a first shot here if Mickey, Sandy, or Suzanne you would like to jump in, please do. I think this is a classic situation. It depends how you look at data from the Dash sodium trial and what data is presented. Unfortunately in the original publications of the Dash sodium trial, critical pieces of information were removed from the presentation in the New England journal of medicine, and had all of the data been available at the time, it would have been evident that the interpretation that we've gone over today is correct. Now, it was published in 2001 in the New England journal of medicine. It was actually only in July of last year in the American journal of cardiology that the Dash sodium investigators actually published the graphs that I showed in my presentation that clearly show once you're on the Dash diet, sodium restriction, for the vast majority of the subjects in that trial, had no impact on their blood pressure at all. Curiously, and I can't account for it, but curiously at a minimum, those graphs were never made available to the dietary guidelines committee and were only published after the guidelines had been set in motion. Now, any additional thoughts from colleagues? >>DR. MICHAEL ALDERMAN Dave, I would like to take a slightly different tact in response to that question. The Dash diet was a feeding study in about 400 subjects a month on one diet--and then a month on another diet--and the end points were blood pressure and several other, what I would describe as intermediate variables. That, in my mind, is not a basis on which recommendations for dietary intake of 250 million Americans can be made. What we really need to know, and is very difficult to find out but it's what we need to know, is whether this diet will affect our health, and Dash doesn't tell us anything about that. We can quibble about the numbers of millimeters of mercury change that was accomplished for a very short period of time in that small group of people, but it seems to me what we've heard from Sandy Logan is that there are perhaps 100 good studies of the effect of sodium restriction on blood pressure, and that's a known fact. It does affect the blood pressure of some people by a very modest amount. The question is--the question that we care about as doctors and patients is does this translate into a longer and better life? And until we get the answer to that question, it seems to me it is a hazardous undertaking to tell a whole population what to eat. >>DR. DAVID McCARRON Agreed. I think from some National Institute's of Health trials that have observed people over 5 to 10, in one case almost 15 years now, at least the dietary pattern that has been described as the Dash diet and is now at the base of the food pyramid has been associated with improvements in cardiovascular mortality--in fact, all cause mortality. I believe at least one of those references may be on the reference list that is at the website for those that are interested. We have another question here and I'm going to ask Dr. Logan to respond to it. If a higher mineral intake and a diet is healthful to you and can improve your blood pressure, is it just as well achieved with mineral supplements as with food, or is there a difference? >>DR. ALEXANDER LOGAN Thanks, David, for the question. With regard to taking in calcium supplementation as opposed to taking in a diet that is rich in dairy products, I think the answer is quite clear that taking in supplements has very little or no effect on blood pressure whatsoever. It seems that it is important to take in calcium in the form of dairy products. Now, whether it is calcium per se or what travels with calcium in dairy products or the combination seems to be more important than just taking calcium per day as a tablet. On the other hand, the issue of potassium supplementation is not as clear-cut. There is evidence, at least from studies where they have given potassium supplements to people who are potassium deficient, this does, in and of itself, lower blood pressure. So there seems to be some difference between potassium supplementation on the one hand and calcium supplementation on the other hand. >>DR. SUZANNE OPERIL This is [indistinct]. I would like to agree with and emphasize that there are many important nutrients in food such as milk and dairy products--many vitamins, minerals other than calcium that are beneficial. And also cultivating a so-called healthy diet with low-fat dairy products and fruits and vegetables will have the positive effect of excluding some other foods that may be less nutritious and may have not as good health consequences. Not only with respect to blood pressure, which we have isolated here, but other risk factors like blood lipids, influence sensitivity, and so on. >>DR. DAVID McCARRON We have another question here that is a common one, particularly in this day and age, as to whether or not the evidence we're citing has really been supported by industry, and I presume that implies the Salt Institute and the food industry, and therefore of questionable bias. Any of you can jump in here, but I think it is fair to say that virtually every study that we've presented and is noted in the slides was funded by the federal government--the United States government and/or an independent agency, and not any of these studies were supported by the food industry or specifically the Salt Institute. And I think that is a fair question. But the data that you have seen is essentially U.S. government data. We have another question here, and let me paraphrase it. It says that salt in a diet has been present for a long time. Has it substantially increased over the last 100 years? Sandy, what's your impression of whether our salt intake has really increased over the last 100 years, as we typically hear? >>DR. ALEXANDER LOGAN As far as I'm aware of trends in dietary salt intake, there has been a somewhat modest increase in dietary salt intake in the younger population--the population that tends to be more salt resistant--with over the past 10 to 15 years probably as a consequence of an increase in calorie intake, which is well documented over this period of time. What is particularly striking, though, if we look at dietary trends in salt intake as one ages, one's dietary salt intake falls and falls quite dramatically. Yet after the age of 50 or 60, hypertension, which is relatively low in its prevalence up to that point, takes off so that by the age of 70 or 80 years of age the prevalence of hypertension approaches greater than 50% to 60%, and this occurs at a time that dietary salt intake is falling dramatically. So I don't think that there is much of a relationship between blood pressure and dietary salt intake. >>DR. DAVID McCARRON I think that's absolutely correct. We have almost 100 years of urinary sodium-excretion measurements from clinical trials and it is a fairly solid marker of your salt intake the day before. And what is actually quite striking is you can reach back into the medical literature almost 100 years ago, and even for studies that weren't done for blood pressure where urine sodium is reported, it is virtually identical to what it is today. So there may be higher salt food products out there, but it would appear that people compensate in their diet and make the adjustments. And I think that there is a physiologic basis for that and it hasn't substantively changed, in spite of a call from policy makers to make it happen. Another question that has come in relates to our society and every society's concern with a rapid increase in overweight or obesity--now not only in our adults but children also--and diabetes. In listening to both Dr. Logan and Dr. Alderman comment on the possibility of some impact of sodium restriction on the effect of insulin on the body. Mickey, would you like to clarify what the data seems to suggest about insulin's effects and whether there is any relationship of salt intake to weight gain? >>DR. MICHAEL ALDERMAN Well, that is an interesting and important question. The interaction of sodium re-absorption and insulin sensitivity has been an issue that has been sort of part of the whole diabetes/obesity story. What we know is that people who consume less sodium tend to be more resistant to insulin and have higher insulin levels, and this is associated with increased fat deposition and conversation of sodium by the kidney. So there is the theoretical possibility that a low-sodium diet might contribute to obesity, but I'm not sufficiently familiar with the details of that argument to know whether it has clinical relevance or not. >>DR. DAVID McCARRON Dr. Logan, would you like to...? >>DR. ALEXANDER LOGAN A related issue is a very well done observational study suggesting that individuals who consume a poor quality diet, and one not necessarily high or low in sodium per se but deficient in dairy products, leads to the development of insulin resistance with time, and this becomes an increasing problem as metabolic syndrome becomes an issue for the general population. >>DR. MICHAEL ALDERMAN Another question that in part is related to one that Dr. Alderman answered earlier. Do we have other examples where blood pressure has been reduced and there has not necessarily been a positive health outcome? I guess that means an improvement in cardiovascular reduction--a reduction in cardiovascular events. Mickey, what do you think about that? >>DR. MICHAEL ALDERMAN The one that comes to mind--there are diuretic drugs that have proved to be harmful that have not been marketed that did lower blood pressure but had other adverse consequences. But I think maybe an analogous situation would be that related to weight gain during pregnancy. It was noted in the 1940s and '50s that preeclampsia, a devastating complication of pregnancy, was associated with weight gain and increased blood pressure, and so there was a campaign in the '50s in this country to get all pregnant women to limit weight gain to less than 20 pounds. It seemed like a good idea and in fact it lowered blood pressure. The consequences of that rational intervention was increased fetal wastage--in other words, increased infant mortality. So the consequence of extrapolating from an intermediate variable, like in this case, blood pressure in pregnant women, can produce unintended consequences that are not very good. And that's why I think it is important to know what the health outcomes associated with this technique of lowering blood pressure might be. >>DR. ALEXANDER LOGAN David, just to add what Mickey has already stated, when you look at the data in people who have normal blood pressure, the vast majority of people with normal blood pressures who restrict their dietary salt intake either have no change in their blood pressure or at best a small fall in their blood pressure. However, up to 25% of these individuals have a significant increase in their blood pressure. And if we're recommending this to normal, healthy individuals, then we're putting at least a significant fraction of otherwise healthy individuals with normal blood pressure at increased risk, which I don't think is good public policy. >>DR. SUZANNE OPERIL I just would like to add that I think that Dr. Alderman's observations--observational studies, which are observational--still are quite convincing that it appears that large numbers of people who have lower salt intake have bad cardiovascular outcomes over the long term. People who are hypertension experts now--physicians and basic scientists--are now beginning to recognize and make recommendations that blood pressure is not the be all and end all of cardiovascular risk and that the other risk factors, like lipids, like insulin resistance, synthetic nervous system activity and what not, need to be assessed when making health recommendations, whether you're talking about lifestyle modification or medication. And I think this is something that also needs to be weighed, since we have said very little emphasis or focus on the adverse metabolic consequences of salt reduction in the diet, as well as the adverse metabolic consequences of diuretic use. >>DR. DAVID McCARRON I think we will take one more question that has come in and any of use can answer it. Is it really feasible to do this long-term study of safety and efficacy, Because don't we hear often that we know enough and we can't wait to get the answer? So the question is it possible to do the study, would it be too costly, too complicated? Mickey, your thoughts. >>DR. MICHAEL ALDERMAN I think it is a two-stage process. Number one is I think we need better observational studies. That is not an experiment--that is simply carefully measuring sodium and other factors of importance and then following a population over time and then relating those exposures, in this case salt, to the outcomes. The studies we have our all imperfect in one way or another, but they are inconsistent. Because they are inconsistent and because they raise the possibility that a low-sodium diet may be harmful, I don't think we are justified, as yet, in pursuing a randomized clinical trial. I think we need better consistent observational data to assure us that it is a reasonable thing to ask people to cut their sodium intake by 30% or 40%. But having said that, I must admit that the reality is that our natural guidelines in a sense are asking us to do an experiment; we have never done this sort of thing before and we are asking 250 million people to do it. I guess there are people out there who believe that this experiment is worth doing in a setting, I might add, in which cardiovascular health continues to improve in this country. There is a continuing decline in cardiovascular stroke and heart attacks and mortality, while we're eating more and more salt all the time and life expectancy in the United States is at an all-time high. I don't think that we are exactly confronting a public health emergency that would justify a universal experiment such as is proposed by the national guidelines in regard to salt. >>DR. DAVID McCARRON Well, that is a good lead-in to a last question that just came across the screen. So, what should the 2005 dietary guidelines [indistinct] for sodium intake or should the guidelines actually have been silent on the issue? Suzanne, What are your thoughts? >>DR. SUZANNE OPARIL My personal view is that the guidelines might well be silent on the issue and emphasize the high-quality diet of fruits, vegetables, and dairy products. >>DR. DAVID McCARRON Sandy? >>DR. ALEXANDER LOGAN I came to the same conclusion, and indeed the Canadian recommendations are simply that. For people who do have a blood pressure problem or at very high risk to developing a blood pressure problem we have recommended modification of dietary salt intake. But for the vast majority of individuals in Canada, we have been silent on making a recommendation one way or another with regard to sodium intake and at the same time are recommending a high-quality diet. >>DR. DAVID McCARRON Mickey, anything to add? >>DR. MICHAEL ALDERMAN No, I like the Canadians. >>DR. DAVID McCARRON Well, how they do seem to exercise prudence sometimes. And I would echo what Dr. Oparil said: the guidelines should have be silent. If this is a new issue being introduced for the first time before the committee, just like a new drug being introduced into the formulary of America, I do not think the data would have supported any recommendations in the guidelines. Well, we have gone a little bit over an hour. Those people who have stayed with us after the broadcast we would like to thank you. If there are further questions that come in as a result of this, they will be answered. We'll get back to you with responses to those questions. I'd like to thank my colleagues, Dr. Alderman from Einstein in New York City, Dr. Logan from Toronto and the University of Toronto, and Dr. Suzanne Oparil from Birmingham and the University of Alabama at Birmingham. Hope all of you have a good day. Thank you.