Setting Targets for Lowering Cardiometabolic Risk

Peter L. Salgo, MD: Let’s talk about some of these targets. Clearly, we would like the blood pressure and the glucose to be normal. We’d like the lipids to be normal. What does the AHA [American Heart Association] and the AACE [American Association of Clinical Endocrinologists] say about targets? What are we shooting for? Let’s talk about glycemic control, first.

Karol E. Watson, MD, PhD, FACC: I think the AHA and AACE will have different perspectives on glycemic targets. What we are interested in is the cardiovascular milieu, and we know that hypoglycemia is terrible for the cardiovascular system. You start to activate all the same systems that we try to block all the time, like the sympathetic nervous system.

Peter L. Salgo, MD: But, I heard, when I was in medical school, high blood sugar, bad; heart, bad; lots of things, bad.

Karol E. Watson, MD, PhD, FACC: Right.

Peter L. Salgo, MD: What’s new?

Karol E. Watson, MD, PhD, FACC: There has been less focus on glycemia and more on things like lipids and blood pressure. But you can give me your perspective.

Rosemarie Lajara, MD, FACE: Well, again, it’s individualizing the patient, and, obviously, risk stratification. But AACE does use hard targets in terms of blood pressure—ideal blood pressure within that framework of individualizing.

Peter L. Salgo, MD: All right. But let’s focus, first, on sugar. Then, I want to transition to blood pressure. How tight do you keep glycemic controls?

Karol E. Watson, MD, PhD, FACC: I’m happy at 7%.

Peter L. Salgo, MD: You’re looking at an A1C of 7%?

Karol E. Watson, MD, PhD, FACC: A 7% level.

Peter L. Salgo, MD: What about blood sugar? What do you want it at? How tight should you be?

Stephen A. Brunton, MD, FAAFP: That’s a very good point, because A1C is a very crude measure of actual blood sugar. What ends up happening is you can have 2 people with an A1C of 7%. One has vast fluctuations that causes oxidative stress that results in significant hypoglycemia. So, you’re recognizing that an A1C of 7% isn’t really “normal.” A person who is a nondiabetic has an A1C between 4.5% and 5.5%. So, they’re more aggressive targets for younger people. For older people, I think we are not quite as aggressive because hypoglycemia becomes a greater risk. I might be comfortable with a 7.5% level.

Christian T. Ruff, MD, MPH: This is very much like lipids. We know that a lot of the atherosclerosis is probably occurring in these diabetic patients at hemoglobin A1Cs before 7%, even when they’re at a prediabetic phase. And so, we know that’s abnormal glucose metabolism. And certainly, being aggressive in getting the best glucose management you can would help these patients, long term. The problem is, what is their risk of hypoglycemia? So, I think being aggressive to less than 7%, whether you’re targeting 6.5%, if you can get away with that in a patient who’s at low risk of hypoglycemia, great.

With lipids, because the medications are relatively safe, we’re finding that by stacking therapy, we can be very aggressive in lipid management—that helps patients. The same thing is probably true in diabetes. It’s just that you’re going to pay a cost if you try to push too hard for patients who are at risk for hypoglycemia because, as you said, if they’re then having a serious hypoglycemic event, that’s probably worse than allowing them to ride a 7% level or above.

Rosemarie Lajara, MD, FACE: And associate it with MACE [major adverse cardiac events].

Karol E. Watson, MD, PhD, FACC: We have to acknowledge that the pivotal clinical trial showing that an A1C of less than 7% reduces mortality or cardiovascular events hasn’t been done yet.

Peter L. Salgo, MD: Every time I hear this, I am shocked that it hasn’t been done yet.

Karol E. Watson, MD, PhD, FACC: Well, it has been done, and it hasn’t worked.

Rosemarie Lajara, MD, FACE: There have been landmark studies intending to bring down the A1C below 7%, 6.5%, or even 6%. But the results have not proven that.

Peter L. Salgo, MD: We’re going to get to that. Younger patients versus older ones with multiple comorbidities, if I understood you correctly, wouldn’t “looser” be better in the older patients than in the younger ones?

Rosemarie Lajara, MD, FACE: Absolutely.

Stephen A. Brunton, MD, FAAFP: Yes. The ADA [American Diabetes Association] guidelines really talk about individualizing the approach. In patients who are elderly, particularly if they have comorbidities where they’re at risk for hypoglycemia or heart problems, in that situation, you don’t need to be at 7% because those patients may be more at risk from the hypoglycemia.

Rosemarie Lajara, MD, FACE: Right.

Peter L. Salgo, MD: Blood pressure goals, where do we want to be? Is everybody going to be 120/80 mm Hg or better, or even lower?

Karol E. Watson, MD, PhD, FACC: Again, I think we have to remember exactly what everyone on this panel has said. There’s always a price to pay—there’s no free lunch. You can shoot to lower and lower targets, but you’re going to pay a penalty in hypoglycemia, or hypotension, or falling, or whatever. So, you have to individualize this as well. And I know, from the SPRINT data that excluded patients with diabetes, that in certain high-risk individuals, getting to a blood pressure of less than 120 is better than less than 140. But, again, the SPRINT trial excluded patients with diabetes.

Peter L. Salgo, MD: The question is, is there any reason to believe diabetics are different? And probably, the answer is, there’s a lot of reasons to believe that they’re different.

Karol E. Watson, MD, PhD, FACC: Right. And the ACCORD blood pressure trial was the same thing—it did not show benefit. But it was a much smaller study and they did a 2-by-2 factorial, so there were a lot of reasons why, maybe, it didn’t show benefit.

Peter L. Salgo, MD: Is there any agreement on lipid goals? Where do you want the lipids levels to be? Where do you want LDLs [low-density lipoproteins]?

Christian T. Ruff, MD, MPH: There’s not agreement about lipid goals. Forget about diabetics.

Karol E. Watson, MD, PhD, FACC: Interestingly though, the 2013 ACC/AHA [American College of Cardiology/American Heart Association] Treatment of Blood Cholesterol Guidelines and the ADA looked at those very differently. If you look at a standard middle-aged, intermediate- to high-risk patient, they end up at the same place: high-intensity statins. Where you get differences are if you end up or start with a lower-risk patient.

Peter L. Salgo, MD: I know that there’s no agreement. Let’s see if we can find some agreement, if you will? LDL cholesterol of 190 mg/dL, bad?

Karol E. Watson, MD, PhD, FACC: Terrible.

Rosemarie Lajara, MD, FACE: Absolutely.

Peter L. Salgo, MD: Terrible. How about 120 mg/dL in a diabetic? Not so great. Now, we’re getting down to 80 mg/dL on a statin.

Christian T. Ruff, MD, MPH: But to Karol’s point: you shouldn’t measure a LDL level in a diabetic patient to trigger your decision about managing. You should say, “They’re a diabetic. I’m going to give them a high-intensity statin.” And then, if you want to add on other therapies, then I think it’s reasonable to say what your LDL is. But don’t ever say, “Well, their LDL is 69 mg/dL. They’re a diabetic. I’m not going to prescribe them with that.”

Stephen A. Brunton, MD, FAAFP: But see, that’s where the confusion exists. Because you’re giving a statin for an LDL of 40 mg/dL, which is fine, I’ll accept that, but the biggest question is about a target. When do you add something like acetamide, or something like that, if the patient is at 69 mg/dL and Karol wants to get them down to 0 mg/dL?

Karol E. Watson, MD, PhD, FACC: No.

Peter L. Salgo, MD: Wait. If I can summarize what you said (because I found that to be really profound), you’re not giving a statin to a number.

Christian T. Ruff, MD, MPH: Right.

Peter L. Salgo, MD: You’re giving the statin to a person at risk.

Christian T. Ruff, MD, MPH: You’re exactly right.

Peter L. Salgo, MD: So, your diagnosis of diabetes, a priori, statin—that’s it?

Karol E. Watson, MD, PhD, FACC: Yes.

Christian T. Ruff, MD, MPH: Right.

Peter L. Salgo, MD: Now we’ll argue about a number.

Rosemarie Lajara, MD, FACE: Right.

Rosemarie Lajara, MD, FACE: Even though, at face value, it looks like we disagree, we don’t.

Karol E. Watson, MD, PhD, FACC: Yes, I agree.

Rosemarie Lajara, MD, FACE: We do believe that you have to stratify risk. However, we do, at AACE, like to see some numbers attached to that goal. Again, do we know how low?

Karol E. Watson, MD, PhD, FACC: We don’t. We can make up a number, but, again, we don’t know.

Peter L. Salgo, MD: If I were to put you into a clinical situation where you could not get LDL readings (LDL numbers), but you could know you had diabetic patients, you’d start them on statins?

Karol E. Watson, MD, PhD, FACC: Absolutely. No question.

Rosemarie Lajara, MD, FACE: Sure.

Peter L. Salgo, MD: Period.

Christian T. Ruff, MD, MPH: Although there’s never been a trial to target a number for cholesterol, alone, if you look at any trial, whether it’s statin trials, PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor trials, if you look at the lower LDL achieved, those patients did better. And so, if you end up with an LDL of 30 mg/dL, you do better than someone who ended up with an LDL of 50 mg/dL. It’s not randomized, but we know diabetes is such a potent cardiovascular risk factor that they need to be on a statin. And if their LDL is 40 mg/dL after a high-intensity statin, great. They’re going to do better than a patient whose LDL is still at 120 mg/dL, 130 mg/dL, and we might want to do additional therapies. But they need to be on a statin. Regardless of what their LDL is, they’re at increased risk.

Stephen A. Brunton, MD, FAAFP: The other point, though, is, you’ve got the person on a high-intensity statin and their LDL (even though we accidentally measured it) was 105 mg/dL. Do you then add something else? You do, in a way, have a target. You want to get below 70 mg/dL, potentially, in a patient. Karol doesn’t agree.

Karol E. Watson, MD, PhD, FACC: I totally agree. We actually wrote a scientific statement (from the ACC) on this because, in the cholesterol guidelines, we were intentionally vague about add-on therapy. At the time that we published them, there were no trials that showed any improvements by adding additional therapy.

Transcript edited for clarity.