James Rosenzweig, MD, on the New Guideline for Preventing ASCVD, T2D in Patients With Metabolic Risk

In July 2019, the Endocrine Society released an update to its 2008 clinical practice guideline for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes in patients with metabolic risk.

Endocrinology Consultant discussed key points and updates in the guideline with James Rosenzweig, MD, chair of the task force that developed the new guideline and endocrinologist at Hebrew Rehabilitation Hospital in Boston, Massachusetts.

Endocrinology Consultant: Why was it important to develop this guideline?

Dr Rosenzweig: Developing this guideline was important because a large number of people currently fall into the category of having metabolic risk, defined as an increased risk for both type 2 diabetes and cardiovascular disease (CVD). In the new guideline, we decided to focus on metabolic risk instead of what we previously called “metabolic syndrome,” meaning we now focus on those people who do not yet have type 2 diabetes or CVD. It is important to take steps to prevent these conditions from occurring in patients with metabolic risk, which represent a significant portion of the US population.

The new guideline is especially beneficial for patients aged 40 to 75 years, for whom there is much higher quality of evidence, and the recommendations we make have the greatest impact. However, this does not necessarily mean our recommendations should not be used for younger or older age groups. For instance, many patients who are older than 75 years are very functional and still would be candidates to continue measures such as blood pressure (BP) control, cholesterol control, proper diet, and so forth. However, the impact of these interventions among very elderly patients is less clear.

Conversely, there are also patients under age 40 years with very high risk for CVD and diabetes, but there is currently some debate regarding the situations in which one would use some of the pharmacologic therapies that we recommend in our guideline.

Endocrinology Consultant: Could you discuss the key conclusions made in the new guideline?

Dr Rosenzweig: In the office setting, we suggest that providers screen patients aged 40 to 75 years for 5 components of metabolic risk at their clinical visit, including increased waist circumference, elevated blood glucose, elevated fasting triglycerides, increased BP, and increased low-density lipoprotein cholesterol. For elevated blood glucose, we suggest the use of either hemoglobin A1c (HbA1c), fasting plasma glucose, or 2-hour oral glucose tolerance test. Then, we recommend a second test for confirmation using a blood sample. The finding of 3 positive components for these 5 categories should alert the clinician to a patient at metabolic risk.

We recommend that clinicians monitor patients with metabolic risk and treat them with lifestyle modifications and behavioral therapy, specifically with attention to weight loss, exercise, and proper diet, as the first-line approach. If these measures are not successful, perhaps medication can be considered. In the new guideline, we decided to emphasize the use of waist circumference at the patient’s initial visit, which is not commonly done in the office setting, because it provides a more specific estimate of risk for these conditions.

There are a few things that are different from the previous guideline. First, for patients aged 40 to 75 years, we advocate that HbA1c can be used, and this has become much more commonplace. As for the definition of prediabetes, or the category between normal and overt diabetes, we recommend screening for diabetes more frequently. Since the publication of the 2008 guideline, the American Heart Association and American College of Cardiology published new guidelines of their own with a tool to estimate cardiovascular risk, which we recommend for calculating 10-year ASCVD risk. There was some controversy after the AHA and ACC’s guideline came out as to what extent one should use lipid-lowering agents to treat to a specific target. This was not emphasized in those guidelines, but the guidelines were very specific about recommendations for the amount of statins that should be used.

The 2008 guideline also had numerous recommendations for behavioral or lifestyle modifications that needed to be adapted or changed in light of new data that have emerged since then. Although we recommended the use of daily small doses of aspirin for primary prevention in the 2008 guideline, subsequent data have shown that the benefits are outweighed by the risks in terms of gastrointestinal bleeding and similar issues, so this is no longer recommended.

Endocrinology Consultant: Were there any notable limitations in the evidence assessed in the guideline that could ultimately inform future research endeavors?

Dr Rosenzweig: There are currently a number of issues regarding the pathogenesis related to metabolic syndrome, or risk of ASCVD and type 2 diabetes. More needs to be known about the relationship between inflammation and the liver and blood vessels, as well as the connection between blood vessels and insulin resistance and atherosclerosis in β cells. More needs to be known about the relationship between metabolic risk, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and how this relationship might affect new medical therapies for these conditions. Other biomarkers need to be discovered to see which ones may aid in calculating risk more specifically for these conditions in the future. More research also needs to be done for genetic markers, risk estimation, and how genetic markers may help personalize care and determine which interventions are best for each patient.

More research is also needed on how the various categories of metabolic risk should be weighted, as some may be more important than others for specific interventions. We recognize that the term prediabetes is not exactly separate from diabetes, and that treating this condition is part of a continuum. Many new agents for the treatment of diabetes have emerged, and these agents need to be studied further to see if their use can be beneficial before diabetes occurs. Some of these agents have been quite helpful in reducing the risk of CV complications as well. Ultimately, we need to learn more about how these agents might affect people who do not yet have these conditions, and how prevention can be accomplished.

We also recognize that larger changes will often have to be done via public health measures. Improving diet, exercise, weight loss, etc, are not fully accomplished in the office setting, so more public health approaches are needed for these issues.

Endocrinology Consultant: What take-home message would you like to leave with endocrinologists and other clinicians treating these conditions?

Dr Rosenzweig: The take-home message of the guideline is that prevention is a very important part of how clinicians should care for their patients. We need to be able to attack these issues earlier before the overt diseases actually occur. Approaches include behavioral and lifestyle modifications, as well as earlier use of certain medications, to decrease severe metabolic risk.

—Christina Vogt

Reference:
Rosenzweig JL, Bakris GL, Berglund LF, et al. Primary prevention of ASCVD and T2DM in patients at metabolic risk: An Endocrine Society* clinical practice guideline. J Clin Endocrinol Metab. 2019;104(9):3939-3985. https://doi.org/10.1210/jc.2019-01338