Raising the Bar on Reducing Cardiometabolic Risk

Peter L. Salgo, MD: What are the risk factors for developing macrovascular complications in the setting of diabetes which magnifies these things?

Karol E. Watson, MD, PhD, FACC: I’m only a pathologist, but, obviously, there’s a multitude of risk factors that are important. If you look at it in a step-wise fashion, dyslipidemia is probably one of the most important. As a risk factor (there are a lot of different risk factors), you can develop atherosclerosis even if you have normal blood pressure, even if you have diabetes, and even if you don’t smoke. But unless you have an abnormal lipid particle that can get into the artery wall and start atherosclerosis, you’re not going to get ...

Peter L. Salgo, MD: So, if I were to follow that to its logical conclusion, I’ll take a step. I’ll take my LDL [low-density lipoprotein] way down or I’ll take some of these newer drugs and drop my LDL down to 20 mg/dL. Am I safe being a diabetic?

Karol E. Watson, MD, PhD, FACC: No. Patients with diabetes are still at risk because there are other risk factors.

Peter L. Salgo, MD: What are the other risk factors?

Karol E. Watson, MD, PhD, FACC: Hypertension, obesity, insulin resistance. As we mentioned, dysthymia.

Peter L. Salgo, MD: Is there something that’s more important? You’re a lipidologist. Does that mean lipids first and everything else second, or not?

Karol E. Watson, MD, PhD, FACC: Again, I agree with what you say, but I reject to the bet. I’m not going to prioritize. But you’re saying we have to go in a stepwise fashion, and I say, “No.” If you have a newly diagnosed patient with diabetes, I’m going to say, “Let’s have a nice discussion about what your various risk factors are.” And “I’d like you to start your statin. I want you to get your blood pressure down.” And “I’d like to start a glucose control agent.”

Stephen A. Brunton, MD, FAAFP: Karol, I don’t disagree with that. I think the problem is that we tend to overwhelm the patients. And as you know, most patients will stop their therapy within 3 months because they’re overwhelmed. So, I think I would rather work with the patient, the whole patient, and find out what they’re willing to do and give them some successes—some wins. In our effort to overwhelm the patient by getting all their risk factors under control, we do overwhelm them, and it’s hard to do it. I think some patients will really go with that, but I try to consider the patient’s understanding and work with that and do it on a grading basis. As a lipidologist, I think part of the problem is that we’ve become LDL-focused. We aren’t really measuring some subfractions of LDL.

Karol E. Watson, MD, PhD, FACC: Why would we?

Stephen A. Brunton, MD, FAAFP: Well, that’s an interesting question because the thing is, they say, “Well, the LDL is normal” and you have a lot of patients with “a normal LDL.” Is that giving us enough information?

Karol E. Watson, MD, PhD, FACC: I was one of the authors of the 2013 ACC/AHA [American College of Cardiology/American Heart Association] Treatment of Blood Cholesterol Guidelines, and we stopped focusing only on the LDL. We focused on the risk. So, if your LDL is 40 mg/dL, I kind of don’t care. If your risk is high, I’m going to treat that.

Stephen A. Brunton, MD, FAAFP: You would treat an LDL of 40 mg/dL with what?

Karol E. Watson, MD, PhD, FACC: A statin.

Stephen A. Brunton, MD, FAAFP: Really?

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

Peter L. Salgo, MD: It depends on the context?

Karol E. Watson, MD, PhD, FACC: If the risk is high, yes.

Peter L. Salgo, MD: If you’re in a high-risk group and that LDL is 40 mg/dL, you can do better and that will lower your risk. Is that what you’re saying?

Rosemarie Lajara, MD, FACE: Yes.

Karol E. Watson, MD, PhD, FACC: Right. No matter what it is, it’s too high for them.

Peter L. Salgo, MD: OK.

Christian T. Ruff, MD, MPH: And we know, even with patients who have established cardiovascular disease, if you do reduce their LDL even further, patients do tend to do better. And so, I don’t think there’s a threshold where we say, “There’s a patient that we’re worried about for cardiovascular disease.” We need to be aggressive in those patients regardless of what their number is—their LDL.

Peter L. Salgo, MD: In the early days with the statins, what I recall (and I think it was pointed out, at least in his studies) was that there was no threshold below which you could not further lower risk.

Rosemarie Lajara, MD, FACE: Right.

Karol E. Watson, MD, PhD, FACC: We’ve not seen the floor—the LDL floor with statins. I assume there is one because there is with everything, but we haven’t found it, yet.

Peter L. Salgo, MD: If we’re looking at diabetics as a group, and we’re looking at their cardiovascular risk, are we, as physicians, doing enough to really interest this risk? All-comers. Are we entering an era where we really need to reexamine what we’re doing and how we’re approaching this?

Rosemarie Lajara, MD, FACE: I believe so. If you look at recent data (in 2010, at least), 81.1% of individuals with type 2 diabetes were not hitting the ABCs in terms of A1C, blood pressure, and lipid control.

Peter L. Salgo, MD: Not hitting all these critical markers?

Rosemarie Lajara, MD, FACE: All 3 markers. And they have residual risk, even under the best circumstances. So, I do think that, obviously, we can and should do more.

Peter L. Salgo, MD: What about the medications we’ve got? Should we be asking more from the medications we’ve been using, traditionally, to treat diabetes?

Christian T. Ruff, MD, MPH: Yes. And I think you know, as Steven had mentioned, the focus on diabetes management had really been around glycemic targets. And not that that’s not important, but we realize, especially when we’re talking about cardiovascular disease and macrovascular disease, that there’s a relationship with hyperglycemia (and that’s also important), but we know most of the events that occur in diabetics actually occur at [a] reasonable hemoglobin A1C. The majority of first-time MIs [myocardial infarctions], if you look at a population level, actually occur in patients who have hemoglobin A1C around 7%. Clearly there’s something happening (and Karol mentioned this), in the process of insulin resistance of diabetes that’s happening for decades. They are having an atherosclerotic burden that’s progressing over many, many years before they even get diagnosed with diabetes and well before they have their first heart attack or stroke.

Peter L. Salgo, MD: We should be asking of our medications, “Don’t just control my sugar, but somehow or another, please help me with my cardiovascular disease.”

Christian T. Ruff, MD, MPH: Especially now with emerging medicines, where these diabetic medications also may have beneficial cardiovascular effects.

Transcript edited for clarity.