The Management of Hypertension in Diabetic Patients

CARLOS R. HAMILTON, JR., MD, FACE: Hello, I'm Dr. Carlos Hamilton. Welcome to the AACE Clinical Conversations. In this program, we will discuss the management of hypertension in diabetic patients.

Joining me today to discuss this topic are Dr. Joe Torre, Senior Endocrinologist at the Buffalo Medical Group and Assistant Clinical Professor at the State University of New York at Buffalo, and also with us, Dr. Addison Taylor, Professor of Medicine and Chief of the hypertension and clinical pharmacology section in the Department of Medicine at the Baylor College of Medicine in Houston. Thanks to both of you for being with us today.

Dr. Torre, what do you consider to be the role of hypertension in the macro- and microvascular complications of diabetic patients?

JOSEPH J. TORRE, MD, FACP, FACE: Carlos, I believe we now feel that while hyperglycemia may initiate nephropathy, it's predominantly hypertension that's the most important risk factor in the development of macrovascular disease.

The -- there are a variety of mechanisms involved, and this certainly may involve the accumulation of glycosylation end products in the glomerular basement (?) membrane.

But primarily hyperglycemia, hypertension, insulin resistance itself, seem to be involved with the production of inflammatory cytokines, which may be involved with then endothelial dysfunction, which in turn can affect vasodilatation, vasoconstriction within the kidney.

CARLOS R. HAMILTON, JR., MD, FACE: Addison, what should be the goals of blood pressure control in diabetic patients and in diabetic patients that have nephropathy, if they should be different?

ADDISON TAYLOR, MD, PHD: The current recommendations are that diabetics have their blood pressure lowered to 130 systolic and 80 diastolic with a particular emphasis, I think, on the systolic values.

People with diabetes and nephropathy in addition to hypertension probably ought to have their blood pressures lowered to values -- the current recommendation is 125/75, but I think I speak for all of us in saying those are arbitrary. Probably lower is better, as long as you can get away from orthostatic hypotensive complications, and we just don't have the information to tell us how low might continue to...

CARLOS R. HAMILTON, JR., MD, FACE: So there doesn't seem to be a threshold at which protection of the kidneys is found. It's whatever degree of reduction of the blood pressure you can achieve seems to be beneficial.

ADDISON TAYLOR, MD, PHD: I think the threshold may be if you get below the threshold for renal autoregulation, then you start getting into problems with progressive rises in serum creatinine, progressive deterioration in renal function. But those are values that are usually less than 100 and usually are less than 90.

So if we can get patients that low, I think we would have to be more cautious. But it's not common for us to be able to achieve those kind of values.

CARLOS R. HAMILTON, JR., MD, FACE: When I first started out in this business, to lower somebody's blood pressure to the degrees that we've been talking about would be number one, very, very difficult if not impossible, and number two, if you did it, they would be so symptomatic from orthostatic hypotension that they wouldn't be able to tolerate it.

So the availability of well-tolerated drugs, such as ACE inhibitors and ARBs and other combinations of these drugs has really made it possible to do the things that you're mentioning in terms of getting the blood pressure down to these levels.

I just can't imagine having been able to do that back in the 1960s when I first started doing this.

ADDISON TAYLOR, MD, PHD: There were a number of agents that you could -- you could almost dose, dependent upon how much orthostatic hypotension you created.

CARLOS R. HAMILTON, JR., MD, FACE: That's exactly right.

ADDISON TAYLOR, MD, PHD: Clearly, blood pressure is a continuous variable. It's not a discrete variable, and we arbitrarily have defined hypertension, and as we've accumulated more information, we've been able to reduce the recommended goal values because we know that there is additional improvement in cardiovascular outcomes.

CARLOS R. HAMILTON, JR., MD, FACE: The availability of effective drugs with minimal side effects has really been a major step forward in this. To go back even before my time, when there was nothing but phenobarbital and reserpine, you know it's -- we've come a long way.

JOSEPH J. TORRE, MD, FACP, FACE: Our challenge is now to get doctors to use these because despite this armamentarium that we have, we have not been that effective in lowering blood pressures anywhere near the 130/80 target.

CARLOS R. HAMILTON, JR., MD, FACE: Well, that's a very good point. Well taken.

ADDISON TAYLOR, MD, PHD: Even in clinical trials where conditions are thought to be optimal, we still have trouble achieving those goals, so it's going to be interesting to see with some of the new combination studies that are now looking at initial therapy with at least two drugs and achieving blood pressures of less than 140/90 on a regular basis, whether we benefit outcomes or not.

I think we all hope that we will see a positive benefit, but we'll have to wait for those study results to find out.

CARLOS R. HAMILTON, JR., MD, FACE: Joe, when do you think treatment for hypertension should be started in patients with diabetes?

JOSEPH J. TORRE, MD, FACP, FACE: Carlos, I take a very aggressive approach, and I believe that we should start even before a patient is hypertensive, certainly with the angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

And there are some -- you read sometimes that blood pressure should be more than 140/90 before pharmacologic therapy is initiated. I don't see why there should be any difference between the goal -- the target goal blood pressure and when you start treating.

CARLOS R. HAMILTON, JR., MD, FACE: Well, I'm glad to hear you say that because I certainly feel that an aggressive approach to this is clearly in order. You want to start treating this condition before it gets bad enough to where it's already had end-organ effects.

There is some concern about the effects of various antihypertensive drugs on two important parameters, namely blood sugar and lipids. How does this influence your choice of drugs in the treatment of these patients?

JOSEPH J. TORRE, MD, FACP, FACE: It doesn't have a lar -- a big effect on that. I would say certainly there is some concern about thiazide diuretics making blood sugar harder to control, perhaps increasing hyperuricemia. Beta blockers can increase triglycerides and lower HDL cholesterol, but used in the proper dosages, and particularly with the combined alpha/beta blockers, carvedilol, we don't see this much of a problem.

CARLOS R. HAMILTON, JR., MD, FACE: Do you agree with that Addison? Are there certain classes of drugs that you prefer in patients with diabetes or are there some that you avoid?

ADDISON TAYLOR, MD, PHD: I try to use those drugs that complement one another. Dr. Torre has already mentioned the adverse potential effects of thiazide diuretics. Fortunately, when they're combined with ACE inhibitors or ARBs, they frequently will complement the reduction in blood pressure and their adverse effects are offset in large part by the ARB or the ACE inhibitor.

The newer beta blockers, for example, seem to have fewer metabolic side effects than our older, more traditional beta blockers and perhaps better cardiovascular end-organ protection as well.

CARLOS R. HAMILTON, JR., MD, FACE: Do you have a certain procedure for adding these additional drugs to the regimen, say at a certain interval or a certain period of time?

ADDISON TAYLOR, MD, PHD: That's always a challenge for those of us seeing people in a primary care setting, and clearly you want to wait long enough to see maximum benefits from a particular drug at whatever starting dose you choose to use.

Generally, for most drugs, that's in the range of four to six weeks. And if you haven't achieved good blood pressure control in that period of time, I'm more often likely to add a second drug or maybe a third drug at that point, rather than trying to increase the dose of the agent I first started.

In addition to that, I think we're finding that adding drugs for people with already substantially elevated blood pressure in combination as initial therapy is something that I'm using more and more.

CARLOS R. HAMILTON, JR., MD, FACE: Is -- is simply the control of blood pressure the factor that we need to be aware of, or are there certain drugs that tend to have a beneficial effect on endothelial dysfunction over and above or beyond their effects on lowering the blood pressure?

ADDISON TAYLOR, MD, PHD: Well, in experimental animals, it's quite clear that if you activate the renin angiotensin system or the sympathetic nervous system, both of which feed in each other and cause this inflammatory cascade that we've already mentioned, you actually have the setup, if you will, for further vascular damage to any of our crucial end-organs like the kidney and the brain and the heart.

And so doing something to address those with either an antiangiotensin or an antialdosterone agent, perhaps in combination, is probably a reasonable place to start. And trying not to disrupt the system very much by adding additional agents that may have adverse consequences on insulin sensitivity and on vascular constriction is the way I usually try to approach that.

CARLOS R. HAMILTON, JR., MD, FACE: What sort of drugs particularly will affect insulin sensitivity that we're using in the treatment of hypertension?

ADDISON TAYLOR, MD, PHD: Well, there's a whole spectrum of changes in insulin sensitivity that are associated with different classes of drugs. The ACE inhibitors and the ARBs seem to improve insulin sensitivity and so in patients with pre-diabetes, the metabolic syndrome and diabetes, those agents would be particularly valuable.

Agents like thiazide diuretics do, indeed, have adverse consequences. The older beta blockers have adverse effects on insulin sensitivity. Those agents like both the dihydropyridine and the nondihydropyridine calcium channel blockers probably have neutral effects.

CARLOS R. HAMILTON, JR., MD, FACE: So the selection of these drugs may be important, but the critical factor seems to be primarily to get the blood pressure down to one of these levels that is really acceptable in terms of preventing progression of renal disease and perhaps preventing the progression or, if you will, of endothelial dysfunction.

ADDISON TAYLOR, MD, PHD: The World Health Organization clinical trialists group in hypertension have looked at this and -- in a very extensive series of studies in which they've looked at over 275,000 people with hypertension. It's very clear no matter what you use, if you get the blood pressure down, you improve cardiovascular outcomes. If you don't get the blood pressure down, you don't. So it doesn't seem to matter in that case what you use to do it.

CARLOS R. HAMILTON, JR., MD, FACE: Well, I think that for those of us that are charged with managing patients with diabetes, we have our marching orders here and we will benefit greatly from this conversation today. I think this has been very useful.

Dr. Torre, thank you very much. Dr. Taylor, thank you for being here. And thank you for watching. This is Dr. Carlos Hamilton.