Metabolic Syndrome and CVD Risk

Scott Solomon, MD: We call them “metabolic syndrome.” It’s really a consultation of things. It’s hypertension, it’s dysglycemia, and it’s obesity, kind of all rolled up into 1 condition. And this puts patients at increased risk. What do we do to treat these patients? Well, we treat their risk factors just like everything else. We want to make sure that they’re not doing other things that are going to increase their risk—like smoking. We want to make sure that their blood pressure is well controlled. We want to make sure that their lipids are appropriate, that they’re low, and that they’re being treated appropriately for LDL (low-density lipoprotein) management. We can’t do a lot, these days, about raising HDL (high-density lipoprotein), other than use statins, and certainly reduce the ratio of LDL to HDL. Diet is also important, so we refer our patients to nutritionists as well.

Robert A. Gabbay, MD, PhD: If we look at the cardiometabolic syndrome, it really is a constellation of risk factors that are brought together to increase the risk of cardiovascular disease. If you look at the progression of the development of diabetes, it seems to start with becoming insulin-resistant. That insulin resistance really is the core defect that mediates a lot of the risk factors associated with cardiometabolic disease. People become resistant to insulin, and most are able to make extra to compensate for that. When they can’t make that extra insulin, that’s where their blood sugars start to rise and we diagnose them as having diabetes. It’s really a continuum from becoming insulin-resistant, increasing your risk for cardiovascular disease, and then when the beta cell is unable to make enough insulin to compensate, then to developing diabetes, and all of those factors increase the risk of cardiovascular disease.

It’s been an exciting decade or 2 in the understanding of cardiometabolic disease and its relationship with cardiovascular disease. This started with the realization that people with diabetes were at much higher risk for cardiovascular events than those without diabetes. It then progressed from epidemiologic data to be able to state that people with diabetes had the same risk of a cardiovascular event as someone without diabetes that has already had a cardiovascular event. In other words, it’s a cardiovascular risk equivalent—your risk is the same as if you already had a myocardial infarction.

Once that was well understood, the mechanism through which this is mediated was identified. There are a number of risk factors that are much more prevalent in people with diabetes than those without. And that constellation of findings became what we talk about when we speak of the metabolic syndrome. They seem to be largely mediated by insulin resistance and a specific lipid profile, a high triglyceride, low HDL, small dense LDL, and the presence of hypertension. Obesity is another risk factor. And you bring all of these together, and now you have a much higher risk of heart disease.

The good news has been that we have a lot of understanding, now, about how to treat the metabolic syndrome and lower the risk of cardiovascular disease. The widespread use of statins has dramatically improved cardiovascular outcomes. Better blood pressure control has been key, as well as realizing that glucose control is not the only factor in people with diabetes in terms of reducing cardiovascular risk. In fact, it’s probably only a small factor. It’s really blood pressure and cholesterol that are the dominant ones. Then, of course, a healthy weight through lifestyle changes related to diet and exercise are important as well. So, we’ve come a long way in our understanding. We have better tools to be able to manage metabolic disease, but we still have more to go because people are still, sadly, dying from cardiovascular disease, and that’s still the number 1 killer in the US.

Scott Solomon, MD: We’ve certainly evolved in our understanding of the metabolic syndrome over the last decade. And part of this is really understanding the relationship between the components that make up the metabolic syndrome and the risk. And these components, again, are obesity, hypertension, and dysglycemia. We have ways to control all these things. Unfortunately, what we don’t know is that control of blood sugar, for example, reduces cardiovascular risk. We do know that, in general, control of blood sugar does reduce microvascular complications. Whether this affects macrovascular complications is a little more controversial.

There’s some recent evidence with GLP-1 (glucagon-like peptide-1) inhibitors that there may be a benefit in terms of overall cardiovascular risk with these drugs. It’s one of the first suggestions that you can lower atherosclerotic risk with an antidiabetic medication. The SGLT2 (sodium-glucose co-transporter-2) inhibitors also appear to reduce cardiovascular risk. We’re not sure, exactly, what that’s due to, but it doesn’t appear to be related to the degree of glucose lowering.

Transcript edited for clarity.