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From Systolic Blood Pressure -- Change the EmphasisMarvin Moser, MD; Michael Weber, MD; Ray Townsend, MD |
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This round table was presented following a meeting on hypertension sponsored by the National Heart, Lung, and Blood Institute in Brooklyn, NY, on February 16, 2000. Several of the symposia speakers convened to discuss the importance of elevated systolic blood pressure as a risk factor for cardiovascular disease. The moderator was Dr. Marvin Moser of Yale University School of Medicine. Dr. Michael Weber, of Downstate College of Medicine in New York City, and Dr. Ray Townsend, of the University of Pennsylvania, were other panelists. The first topic addressed was why diastolic blood pressure (DBP) has been traditionally used to define cardiovascular risk, and why it has been used in all clinical trials designed to determine treatment benefit. In addition, the panelists explored the relative importance of elevated systolic blood pressure (SBP), and whether or not risk and benefit estimates would be more accurately discerned if SBP, or perhaps even pulse pressure, were considered the guideposts for outcome. [J Clin Hypertens 2(6):399-405, 2000. © 2000 Le Jacq Communications, Inc.] |
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Dr. Moser: Dr. Weber, in the early 1900s, the Journal of Johns Hopkins Medical School noted that too much attention was focused on SBP, and that it may be time to look more carefully at the diastolic level to determine risk. DBP levels do indeed predict cardiovascular diseases, but did we go too far? What are the relative risks of various levels of diastolic and systolic pressures, or indeed, different levels of pulse pressure? Should we forget about DBP and limit our concerns to systolic pressure?
Dr. Weber: I suspect that the original recommendation, early in the 20th century, to use DBP as a marker of risk was based on the belief that this might better reflect the state of the small arterial vessels. However, for many years, it has been quite apparent that SBP is a much better predictor of cardiovascular prognosis than DBP. Anyone who does physiologic studies on animal models finds that it is the SBP that best correlates with changes in the size of the heart wall, renal function, and arterial compliance.
Dr. Moser: Is a SBP of 150-155 mm Hg, for example, more of a risk for cardiovascular disease than a DBP of 95 or 100 mm Hg?
Dr. Weber: Yes, it is. Compared with an optimal SBP of about 110-120 mm Hg, even a SBP in the 140-150 mm Hg range is already associated with close to a tripling of risk. Levels of systolic pressure that, in the past, were regarded as normal, are now known to be associated with an increase in cardiovascular events. DBP is not always a faithful indicator of risk, especially after the age of 50.
Dr. Moser: Therefore, in younger individuals, more attention might be paid to the DBP level, and as patients become older, more attention should be paid to the SBP. Is that correct?
Dr. Weber: Up to the age of 50, DBP is acceptable, but probably not superior to systolic. Even in young people, SBP is a useful predictor of outcome. Over the age of 50, we know that for any level of SBP, the risk of a cardiovascular event actually is inversely related to the DBP. For example, for patients 25 or 30 years old, a high DBP is worrisome. For those 65 or 70 years old, a low DBP is cause for concern, particularly if it is coupled with a high SBP and a resulting high pulse pressure.
Dr. Moser: That is a result of a decreasing arterial compliance. Most older people have high SBP and relatively low DBP.
Dr. Townsend: One of the reasons DBP was the focus is that vessels are exposed to pressure in diastole for a longer period of time than they are in systole. In particular, physicians have concentrated on DBP because that is what reflects the coronary circulation. The heart contracts so hard that there is not much coronary flow at peak systole; instead coronary flow occurs during diastole. Many physicians have therefore subscribed to the idea that since coronary disease is the number one killer and high blood pressure is one of its major risk factors, then DBP must be important in determining the integrity of the coronary arteries.
Part of the problem is that we limited our vision to the numbers and may not have focused enough attention on endothelial function, lipids, and fibrinolysis, all of which are important factors in coronary disease and protection of flow to vital organs.
Dr. Moser: Do you believe that elevated SBP has a greater effect on endothelial dysfunction and carotid thickening, for example, than elevated DBP?
Dr. Townsend: I think that for any target effect of blood pressure, the SBP will typically be the more important.
Dr. Moser: We classify normal as 120/80 mm Hg, high normal as 130-139/85-90 mm Hg, and hypertensive as >140/90 mm Hg. Is this a reasonable classification for all people? Clearly, these are artificial cut-off points. A recently published paper suggested that in older people the levels should be higher, on the basis of a statistical review by a group of nonphysicians who used mathematical models. Are they correct? Should we revert to the earlier consensus that a 70-year-old man can have a SBP of 165-170 and not be at risk?
Dr. Weber: No. I am not a statistician, but I believe that the analysis was misleading and it reflected some misunderstanding about relative and absolute cardiovascular risks. The fact is that anyone with a SBP >140 mm Hg, regardless of age, has a level of risk that is higher than if the SBP were 120 mm Hg or below.
Dr. Moser: You suggest, then, that the cut-off points that have been used for years are valid, whether one is 75 or 45 years of age.
Dr. Weber: I do believe that. An ongoing trial, OPERA, is examining possible benefits of lowering mildly elevated (Stage I) SBP, which is >140 mm Hg but <160 mm Hg, in older people who have normal DBP (<90 mm Hg).
Dr. Moser: This is the only group for whom there is no definitive proof of the benefit of lowering blood pressure.
Dr. Townsend: If we ignored the DBP completely, would we misclassify a great number of people as hypertensives?
There is a phenomenon called up-classifying or upstaging, which relates to using 140 or 90 mm Hg. A blood pressure of 142/88 mm Hg is classified as stage I hypertension, on the basis of the SBP alone. The diastolic BP would have been classified as "high normal," the systolic BP upstage this to "stage 1 hypertension." Evaluation of the reliability of this classification system shows that about 90% of the time the classification is correct if the SBP alone is used, especially in the elderly.
One of the lessons from clinical trials is that treatment of blood pressure prevents the change in stage that occurs with time. Blood pressure, especially systolic, tends to rise with age. Antihypertensive drug therapy frequently arrests the rise in blood pressure associated with age, which is why I believe that 140 mm Hg is a valid cut-off point. The line must be drawn somewhere, and this seems realistic.
Dr. Weber: If we use 140/90 mm Hg in older people, an individual at 142/92 mm Hg would qualify for hypertension by both criteria. On the other hand, a person at 142/72 mm Hg is hypertensive only by the systolic criterion, but might nevertheless be at risk.
Dr. Moser: The point is well taken; about 90% of people over the age of 55 or 60 will be correctly classified as stage 1 or 2 hypertensive, based on the SBP alone.
Dr. Weber: I agree completely with that approach. A recent editorial made the argument that life would be a lot simpler if we measured only SBP. We would probably misdiagnose or hurt only a small minority of patients if we followed that rule.
Dr. Moser: I will take exception to that, to some extent. Haven't we all seen patients in their 30s, 40s, and 50s with SBP of 135 or 140 mm Hg, but DBP of 95, 100, or even 105 mm Hg, who already have evidence of renal disease? If only SBP is considered, these are people who would not be treated. They certainly need treatment.
Dr. Weber: Some patients would be missed. However, what is the state of the artery of someone who is 135/100 mm Hg?
Dr. Townsend: If it is 135/100 mm Hg, it is the narrow pulse pressure individual who counterintuitively is at the least risk at that level of SBP, at any age.
Dr. Moser: I am reluctant to dismiss the DBP elevations. Years ago, we followed a group of patients with DBPs of about 100 mm Hg and relatively low SBP of 130-140 mm Hg who had proteinuria; they were certainly at increased risk, and I believe that these patients should be treated. I agree that in elderly patients it probably does not make a difference, since SBP tends to rise and DBP to fall; as we age, pulse pressure increases. But perhaps it is a mistake to ignore DBP elevation in younger patients.
There are some investigators who are strong advocates of pulse pressure rather than systolic or diastolic, and of basing prognosis and treatment on this measurement. May I have opinions on this?
Dr. Weber: The pulse pressure should not be considered alone, but should be regarded in the context of the systolic pressure. In the end, both the systolic and diastolic values must be taken into account. It is hard to imagine that a person with a blood pressure of 100/50 mm Hg is at the same level of risk as someone with a blood pressure of 150/100 mm Hg. The pulse pressures but clearly different situations. It is necessary to anchor a pulse pressure to a systolic pressure in order to interpret it. That is why most of the time SBP is an adequate reflection of risk. The pulse pressure amplifies its importance, but in a context of considerable confusion and controversy, unnecessary complexity should be avoided.
Dr. Moser: I completely agree. Dr. Townsend, do you agree?
Dr. Townsend: To take this one step further, part of the issue with pulse pressure is that it is the current epidemiologic darling in hypertension because everything seems to correlate with pulse pressure. Treating the pulse pressure has never really been addressed in long-term clinical trials. We have always examined changes in DBP, with the exception of the isolated systolic hypertension (ISH) trials. We do not have a good understanding -- at least, I do not -- of specifically how to manage the pulse pressure.
If the blood pressure is 180/70 mm Hg, a diuretic is often used, and it works, but what is the likelihood that other drugs will not only reduce the SBP but also decrease the pulse pressure, which would be even more beneficial? However, I am unable to provide data regarding the value of other therapies.
Dr. Moser: We will discuss treatment in a moment; however, my reading of our own data as well as the literature sussest that most of the antihypertensive agents including diuretics decrease SBP proportionally more than DBP. Dr. Weber is correct: most experts feel that pulse pressure is a predictor, but not substantially better than SBP in estimating risk and, as noted, we have had enough difficulty in trying to simplify definitions. Let us emphasize SBP but not address pulse pressure at the present time, despite data that with the same SBP (for example, 150 mm Hg) the risk is lower if the pulse pressure is 60 than if it is 80 (i.e., 150/90 mm Hg compared to 150/70 mm Hg). These data, as you know, have been disseminated widely.
I believe we all agree that we should pay more attention to SBP, and at the moment we should not embrace pulse pressure as the gold standard, either in classification or as an index of when and how to treat.
Dr. Moser: Why have doctors ignored this kind of information? Is it because we were taught, years ago, that elderly people must have increased blood pressure to perfuse the brain or kidney, and that 170 or 180 mm Hg was normal in a 70- or 80-year-old person?
Some of the leading cardiologists in the U.S. believed this and, as late as 1978, the British medical establishment was advising physicians not to treat elderly people unless their blood pressures were above 200/110-120 mm Hg. I hope that most physicians now accept the definition of high blood pressure as >140/>90 mm Hg, regardless of age.
Dr. Weber: I think that is the case. Our battle will be to convince physicians, government regulatory agencies, and the pharmaceutical industry to also embrace SBP as a primary indicator of risk. To this day, DBP is still the most commonly used criterion.
The FDA acknowledges the importance of SBP, but for some reason drugs are still largely evaluated by diastolic criteria. Fortunately, this is starting to change.
Dr. Moser: I have a question. Drs. Weber and Townsend, you both have participated in many clinical trials. The reason I believe DBP was used as the main criterion is that it is easier to monitor DBP. Is that true?
Dr. Townsend: It is absolutely true. The variability is much less with DBP than with SBP.
Dr. Moser: I predict that at some point the FDA is going to examine SBP changes with new drugs much more carefully, rather than concentrating only on DBP changes.
Dr. Weber: I agree. However, I question the premise that the diastolic is in some way a more consistent or reliable measure. Even though SBP is more likely to change with emotional or physical stress, it is often easier to obtain an accurate SBP reading.
We must teach health care professionals who measure blood pressure to seat their patients quietly for 5 minutes before taking blood pressure. We can probably obtain systolic pressures that are both technically accurate and also physiologically relevant.
Dr. Moser: Is elevated SBP a big problem in the U.S.?
Dr. Townsend: Absolutely. Between 50% and 70% of the elderly population have a SBP >140 mm Hg.
Dr. Moser: Therefore, the expectation is that if we live long enough, two thirds of us will probably have systolic hypertension.
Dr. Townsend: Two thirds to three quarters. Those are the data as I understand them.
Dr. Moser: What about the treatment of systolic hypertension? Let us consider nonpharmacologic treatment first. Do we have any data on how nondrug treatment or lifestyle changes affect SBP?
Dr. Townsend: My clinical impression, from patients placed on a reasonable exercise regimen, is that it results in an approximate 5% reduction in SBP. If the SBP is 160 mm Hg, a reduction of approximately 8 mm Hg can be expected. The decrease is proportional rather than absolute, in my experience, and the reduction is not dramatic. Also, the benefit seems to be maximal about 20-30 minutes after an exercise session. When patients need encouragement, I tell them to check their blood pressure just after exercise.
The other issue with exercise is that the benefits are quickly dissipated. When an exercise program is stopped, blood pressure benefits are lost, usually within a few weeks.
Dr. Moser: What about the benefits of weight loss and low sodium diets? In many of the studies that report an 8-9/8-9 mm Hg decrease in blood pressures, either all the food was supplied, or extensive support was provided (e.g., nutritionists). Most patients are treated not in specialized clinics, but in doctors' offices, and dieticians are usually not available. What is your guess on how many people with SBP elevations in the >50 age group can be controlled at blood pressure levels of _140 mm Hg with lifestyle interventions. Dr. Townsend is correct; even moderate exercise, such as brisk walking four to five times a week, will decrease blood pressure but, over time, the benefit may not be large unless the patient stays on a program. We know that weight loss is highly effective, and that in some patients moderate sodium restriction is helpful.
Dr. Weber: The reality is that very few patients can maintain a meaningful weight loss. This is disappointing, because weight loss is the single most consistently effective way of reducing blood pressure. Exercise is more likely to work long-term, and there are some people who start exercise programs and stay with them.
Dr. Moser: As well as watch their weight and diet.
Dr. Weber: The exercisers, of course, are a self-selected group. Most patients, if they are not already doing exercise, will not begin a regimen and continue it simply because the doctor recommends it.
Dr. Townsend: In general, nonpharmacologic therapy is interesting to conceptualize and discuss, but very difficult to apply in clinical practice, to other than highly motivated patients. I would like to believe that weight loss would really make a big difference. The problem is that the data on weight loss actually show considerable variability. In some cases, blood pressure decreases; in others, the blood pressure barely changes.
Furthermore, maintaining a weight loss program is almost as hard as the initial weight reduction because the required changes in eating behavior also entail profound lifestyle changes, particularly in activities that are associated with eating, such as watching television.
Dr. Moser: Let us be specific. In the case of a 74-year-old male patient who is mildly obese but very motivated, has blood pressures of 158/86 mm Hg, no left ventricular hypertrophy, no macro- or microproteinuria, and no diabetes, for how long should nonpharmacologic interventions be applied?
Dr. Townsend: I would treat that patient with medication from the start, and I would offer the potential of discontinuing medication if the patient were to lose weight, exercise, and reduce his sodium intake. The problem with many patients with systolic hypertension is that they are difficult to treat. Part of the reason for the difficulty is that they have been hypertensive for years, but they have not been treated because their DBP has been normal.
Dr. Moser: Sounds reasonable, but that is not in accordance with the Joint National Committee VI recommendations, which are that relatively low risk patients should first undergo nonpharmacologic therapy for 3-6 months. The World Health Organization recommendations go even further: In patients with SBP of 140-159 mm Hg and no other risk factors, they suggest follow-up for 1 year or longer, without medication.
Dr. Townsend: However, this hypothetical patient is 74 years of age, and although he appears to be at low risk, one lesson we have learned from clinical trials is that the older a person is, the more benefit there is in reducing blood pressure with medication; that is why I would not hesitate to treat him.
Dr. Moser: Dr. Weber, would you start this patient on medication right away, along with lifestyle interventions?
Dr. Weber: Yes, under the circumstances described, and after confirming the blood pressure level.
Dr. Moser: Let us turn to the clinical trials. Most were focused on outcomes dependent on DBP change. However, in the clinical trials there was an average placebo-corrected decrease of SBP of 10-12 mm Hg (it was higher in the Swedish Trial in Old Patients with hypertension study, or STOP, but the initial pressures were higher). Is this magnitude of decrease enough to reduce myocardial infarctions, strokes, and heart failure?
Dr. Weber: In some studies, the active treatment was not dramatically more effective than placebo in reducing blood pressure, yet there was a statistically significant reduction in strokes, heart failure, and even myocardial infarctions. Therefore, in trials it does not take large blood pressure reductions to show benefits.
Dr. Moser: This is an important point for clinicians. For example, in a patient with blood pressures of 175/80 mm Hg, the goal is to reduce SBP to <140 mm Hg because that is what a national committee suggested. However, if it decreases to only 160 or 155 mm Hg, even with use of two different medications, the physician and patient may be discouraged. Physicians should be assured that benefit may accrue with a decrease of only 10 or 15 mm Hg, and that in some patients with ISH, an ideal goal pressure may not be reached.
Dr. Weber: That is a critical point. Doctors often ask what they should do when patients faithfully and reliably take two or three different kinds of antihypertensive drugs yet do not have blood pressure reduction to goal levels. Patients should be reassured that the most important hurdle has already been crossed; they are taking medication and are at lower risk because of it.
Dr. Moser: Several trials have examined isolated sysolic hypertension, or ISH. The Systolic Hypertension in the Elderly Program (SHEP) study used diuretics and, in some cases, ß blockers. The Systolic Hypertension-Europe (Syst-Eur) trial employed a calcium channel blocker, nitrendipine, along with other drugs. There are cohorts of patients with ISH in the Medical Research Council trial in the elderly. All of these trials have shown marked benefits of treatment, especially the SHEP and trial where CHF, strokes, and all CV events were reduced and the SYSt-Eur trial the reductions in stroke and congestive heart failure alone are sufficient reason to treat patients with ISH.
Dr. Townsend: Absolutely correct. A point often made, in reference to SHEP, is that among all of the things that can happen to elderly persons, in their own minds the most devastating possibility is a stroke, because it leaves them dependent. If a trial produces solid data on stroke reduction, treatment is warranted.
Dr. Moser: In the Syst-Eur trial, the reduction in coronary artery events was not significant at 2 years, but strokes were significantly decreased.
Well, how are we doing in the U.S.? We have effective and safe medications and, unlike 25-35 years ago, when the available antihypertensive agents were difficult to tolerate, most patients tolerate currently available medications fairly well. But what kind of response rates are we seeing in elderly patients with systolic hypertension?
Dr. Weber: Unfortunately, we are not doing as well as we should be doing. We know from the NHANES data, that only about one half of U.S. patients under treatment for hypertension have adequate blood pressure control. Moreover, one half of hypertensive persons are untreated. The main reason for failure to achieve control is that many clinicians are satisfied when the DBP decreases to about 90 mm Hg, and they do not pay enough attention to the systolic side of the problem.
Dr. Moser: The data indicate that about 70% of patients with diastolic hypertension are treated successfully, but for systolic hypertension, the figure is fewer than 30%.
Dr. Townsend: That is correct.
Dr. Moser: We reported a 10-year follow up many years ago on our isolated systolic hypertensives over 65 years of age, and despite the fact that we thought we were doing very well, fewer than 40% were controlled at below 140 mm Hg. More than 80% of patients with systolic/diastolic hypertension were controlled at goal levels of <140/90 mm Hg. Thus, it is difficult to control elderly patients with elevated SBP to a goal of 140 mm Hg. It is simple to advocate that all doctors reduce all their patients' SBP to less than 140 mm Hg but, in reality, even with careful attention to blood pressure, we may not achieve that goal. What is the solution?
Dr. Townsend: First, if therapy is unsuccessful within 1 or 2 years, there should be no delay in referring the patient to a hypertensive specialist. In patients whose blood pressure is difficult to control, the chance of successful treatment is greater if the diagnosis is relatively recent than if decades have passed and the vessels are very stiff.
Dr. Moser: Let us say that a patient has been treated for 6 months, starting with a low dose of a diuretic, which is what the JNC VI recommended on the basis of strong data. Then an ACE inhibitor or ß blocker, or perhaps a long acting calcium channel blocker is added. The patient is very reliable, and is taking 25 mg of hydrochlorothiazide plus 50 mg of atenolol, 5 mg of bisoprolol, or 10 mg of enalapril or lisinopril. Baseline blood pressures were 180/85 mm Hg and now are 160/80 mm Hg. The patient feels fine so far. What should be done now?
Dr. Townsend: I would consider the use of amiloride in this patient. I have had success in reducing blood pressure further on an already established regimen.
Dr. Moser: So you would use a K sparer in some patients?
Dr. Townsend: I use a K sparer because many of these patients have low renin activity and retain salt.
Dr. Moser: Do you increase the thiazide dosage?
Dr. Townsend: I sometimes increase the thiazide to 50 mg per day. Sometimes I add a loop diuretic as well, if I strongly suspect that a "drug resistant" hypertensive has a sodium problem.
Dr. Moser: Dr. Weber, what would be your approach?
Dr. Weber: I am not always as aggressive because the SHEP trial showed that an alternative goal in patients who are not easily reduced to 140 mm Hg is a reduction in SBP of 20 mm Hg. A patient who begins at about 180 mm Hg and is lowered to the 150-160 mm Hg range probably has already benefited substantially. The hope is that these drugs work on the stiff arteries to induce enough remodeling that a further reduction in blood pressure will occur over the next 1 or 2 years.
Dr. Townsend: At what level of SBP would you be uncomfortable with that approach?
Dr. Weber: I am concerned with a SBP of >160 mm Hg, and I will keep trying to reduce it. One of the failures in treating older people is prescribing an inadequate dose of a diuretic. Many doctors believe that 6.25 or 12.5 mg of hydrochlorothiazide or its equivalent will be effective. n combination with a ß blocker, an ACE inhibitor, or an ARB, this dosage is probably adequate. However, a higher dosage is often required. In the SHEP trial, chlorthalidone was used, and it may be more effective than hydrochlorothiazide.
Dr. Moser: That is a good point. Let us say the physician is determined to reduce the SBP to 140 mm Hg, and the patient is on a diuretic and a ß blocker, or a diuretic and an ACE inhibitor, and is definitely taking the medicine. The SBP has decreased from 180 mm Hg to 160 mm Hg and the patient reacts to the doctor's latest suggestion with, "I am not going to take another one of these darn pills. I'm going to feel lousy." Does that ever happen?
Dr. Townsend: All the time.
Dr. Moser: What do you do?
Dr. Townsend: There has to be a balance. We must weigh the quality of life issue against the potential benefits of further blood pressure reduction. Sometimes a point is reached where the patient is very reluctant to have the regimen changed or is miserable on medication, and the physician must consider these feelings and settle for less than an ideal result. In such cases I monitor for emerging target organ effects.
Dr. Moser: That is an important point. Sometimes we are glib about insisting that goal blood pressure be achieved. But all clinicians know that that is not always possible. We have safe, effective, and generally well accepted medications, but some patients simply cannot tolerate them. We are not sure why; it may not be a decrease in cerebral perfusion, since blood pressure should decrease over period of a few weeks and there is usually time for vascular autoregulation. Renal function may not be adversely affected, cardiac output may not be reduced, and yet it happens. It may be that arterial compliance is so compromised that SBP cannot be reduced very much without causing symptoms, and the least desirable outcome in an elderly person is an adverse impact on the quality of life.
Dr. Weber: What about the "white coat effect" and the possibility that blood pressures are lower at home than in in the physician's office?
Dr. Moser: The patient is miserable and complaining. He was happy with blood pressures of 160/80 mm Hg; the doctor added therapy and reduced it to 145/78 mm Hg, but the patient feels awful. He had been taking his blood pressures at home and they were consistently 145-150/75-80 mm Hg. Do we back off because of symptoms, even though BPs are not too low?
Dr. Weber: In an elderly patient, I will be guided by what is practical. If the readings at home are lower, that reassures me.
Dr. Moser: And it is comforting to know that the patient's annoying symptoms are not due to excessively low pressures. But, in some cases, even if home BPs aren't too low, therapy might have to be adjusted because of symptoms.
Dr. Weber: That is right; it is helpful in both respects.
Dr. Moser: An important issue is DBP and coronary flow. One of the reasons physicians have not vigorously pursued the treatment of isolated systolic hypertension is fear of the J curve phenomenon. A patient presents with blood pressures of 170/85 mm Hg and the physician is concerned that if the systolic is decreased from 170 mm Hg to 150 mm Hg, the diastolic might be decreased to <80 mm Hg, thereby reducing coronary blood flow, which might at least theoretically precipitate an ischemic heart disease event in a susceptible elderly subject. I truly believe this is one reason why doctors do not pursue systolic reduction in older patients.
Dr. Townsend: I agree that it is an excuse for not treating. The data from SHEP showed that a SBP decrease of about 3-4 mm Hg will result in a DBP reduction of only 1 mm Hg. The DBP fall in patients with wide pulse pressure is actually small compared to the systolic drop achieved with drug therapy. The J curve has been overemphasized, based upon a limited number of patients who experienced a little more chest pain after blood pressure reduction.
Dr. Weber: I agree with that. In fact, even if some reduction in backfilling of the coronary circulation occurs during diastole, we should remember that the substantial concomitant fall in SBP reduces the amount of work required of the left ventricle. A modest reduction in the supply of oxygenated blood to the myocardium is tolerable when there is a disproportionately large reduction in heart work.
Dr. Moser: In the SHEP trial it appears that a decrease in DBP to <55 mm Hg or 60 mm Hg may increase risk of ischemic heart disease events, but this level is not often achieved in clinical practice. In the Hypertension Optimal Treatment trial, there was no evidence, even in patients with pretherapy ischemic heart disease, that lowering DBP to <80 mm Hg increased events. As Dr. Weber noted, lowering SBP is beneficial and may negate the effects of low DBP.
Dr. Townsend: There are patients whose DBP is 70 mm Hg, with a SBP of 180-200 mm Hg. One risk must be balanced against another, but in my experience, the SBP has always been the primary issue, and I have rarely decreased the diastolic to as low as 50 mm Hg in the interest of reducing the systolic to a reasonable range.
Dr. Moser: Perhaps, if the diastolic decreases to <60 mm Hg, we should be careful about further reductions in blood pressure.
Dr. Townsend: I agree with that.
Dr. Moser: Among newer treatment modalities, is there anything on the horizon that might be more useful than diuretics in reducing SBP? Are there any calcium channel blockers that also are effective in reducing SBP? ACE inhibitors, ARBs, and ß blockers, although not as effective in the elderly, are extremely effective when given with small doses of a diuretic.
Dr. Weber: Currently there is considerable interest in a new class of drugs called the vasopeptidase inhibitors, which have a dual mode of action. These molecules not only inhibit ACE and produce effects that are typical of ACE inhibitors, but also increase availability of endogenous vasodilatory peptides (the so-called natriuretic peptides) by neutral endopeptides, which are enzymes necessary for their breakdown. These actions result in a marked fall in blood pressure. These drugs, of which omipatrilat is an example, may be useful in treating both systolic and diastolic hypertension. Studies of ompatrilatat have demonstrated that it has greater efficacy, particularly in reducing SBP, than several of the currently available agents.
Dr. Moser: We await data on outcome, as well as shorter-term data, comparing it to other drugs. To summarize, the main issues discussed today are as follows:
Many, but not all, patients will respond to the use of one or several of the available medications. There are medications and approaches to therapy that may improve on this effort and increase the number of patients who respond. We await the results of ongoing trials.