Preventing Metabolic Risk Requires Assessing 5 Clinical Factors

Clinical Practice Guidance refocuses attention to visceral fat vs BMI, and lipid fractions beyond LDL, among other key risk factors. Also, even older patients need to continue statin therapy to avoid cardiac events.

with James L. Rosenzweig, MD, and Joel Coste, MD, PhD

An updated Clinical Practice Guideline—Primary Prevention of Atherosclerotic Cardiovascular Disease (ASCVD) and Type 2 Diabetes (T2D) in Patients at Metabolic Risk—was published today by Endocrine Society,1 to reflect the significant research, particularly on lipids and hypertension that has been amassed over the past decade with the aim of assuring diagnosis of these comorbid conditions sooner.

Focus on waist circumference and triglycerides are key to warding off CVD and diabetes.Senior over age 75 still need to take a statin to keep their risk of heart disease down and avoid cardiac events, in addition to regular monitoring of metabolic risk factors. Photo: 123rf

Preventing Diabetes and Heart Disease Require Increased Vigilance

“Metabolic syndrome and metabolic risk have been used to describe a set of risk factors for both cardiovascular disease and diabetes that tend to be clustered together in many individuals,” said writing committee chair, James L. Rosenzweig, MD, associate professor of medicine at Boston University School of Medicine in Massachusetts.

Published online in the Journal of Clinical Endocrinology & Metabolism, this Clinical Practice Guideline, was co-sponsored by American Diabetes Association and the European Society of Endocrinology.

“Singling out patients with metabolic risk—We define this as risk for cardiovascular disease and diabetes in those people who have not yet developed either condition. This is a prevention guideline and does not address treatment of existing CVD or DM,” Dr. Rosenzweig told EndocrineWeb.

The recommendation places great emphasis on the need for routine assessment of classic CVD risk factors (ie, low density lipoprotein-cholesterol, (LDL-C), cigarette smoking, physical inactivity, and family medical history of cardiovascular disease, with particular attention to diagnostic screening of five significant risks associated with ASCVD and T2D,1 namely:

  • Excessive accumulation of abdominal fat (measured by waist circumference)
  • Low serum high density lipoprotein (HDL) level
  • Elevated serum triglyceride level
  • Hypertension
  • High blood glucose levels

There is an urgency to identifying at-risk patients earlier—as reflected in the guidance—to capture patients with an irregular presentation of three or more of these risk factors so they are monitored at least once annually and in patients with at least one risk factor, they should be checked every three years.1

Individualizing Lifestyle Patterns Is Best Strategy to Lessen Disease Risks

With regard next steps, since this guidance is focused on prevention, the writing committee emphasized lifestyle, dietary, and behavioral interventions as well as the much-expanded array of pharmacotherapies that have been approved since the guideline was first issued in 2008.2

The revised guideline addresses the specific needs of adults, 40 to 75 years of age. “We focus on individuals between 40 and 75 years of age, for whom there is a higher quality of evidence and [in whom] the recommendations will have the greatest impact. This doesn’t mean that our recommendations should not be used in those who are in younger or older age groups,” said Dr. Rosenzweig.

In addition to the specific age range featured,1 Dr. Rosenzweig highlighted six other notable changes from the previous version of this clinical practice guideline:

  • “We don’t define the Metabolic Syndrome as a distinct disease but rather emphasize its components as risk factors for cardiovascular disease and diabetes; 
  • We use hemoglobin A1c (HbA1c) measurement as one of the tests that can define prediabetes, the intermediate category between normal blood glucose and diabetes. Prediabetes is described more broadly and in a variety of ways to include definitions from different organizations in different countries. For individuals who have been diagnosed with prediabetes, we recommend screening for diabetes more frequently than previously;
  • We recommend using a tool to calculate 10-year heart disease risk that was developed from American Heart Association and American College of Cardiology;
  • We recommend somewhat more intensive use of lipid-lowering agents;
  • The target levels for blood pressure treatment are lower;
  • We no longer recommend use of low-dose aspirin given less evidence of its benefit and it is countered by potential adverse effects like bleeding; and
  • Updates to the dietary and exercise recommendations.”

How Should Patients Over Age 75 Be Managed?

“We did not want to make a blanket application to all people over age 75 because the quality of evidence is less, and there are more extenuating circumstances related to frailty, cognitive decline, comorbidities and life-expectancy,” Dr. Rosenzweig said. 

“Clearly, a significant percentage of those over age 75 would benefit from our guideline recommendations; there might be adjustments, in some cases, to the intensity of treatment, however.  We do not say that our treatment recommendations should be stopped when a person reaches the age of 75,” he said.

As timing would have it, a team of French researchers published results of a retrospective, population-based primary prevention study looking at the effect of discontinuing statin therapy in patients who reach 75 years and older.3  The investigators captured medical information on 120,173 individuals who were taking a statin but had no prior history of cardiovascular disease and who turned age 75 between 2012-2014 in the national healthcare database.

Continuing Statin Therapy Suggests Least Risk of Future Cardiac Events

Among these patients, followed for an average of 2.4 years, 14.3% discontinued statins (defined as not taking the medication for at least three consecutive months) and 5,396 of them (4.5%) were hospitalized for a cardiac event, according to senior author, Joel Coste, MD, PhD, professor of studies in public health at the France Assistance Public University Hospital of  Paris, France.

The adjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18–1.50] for any cardiovascular event), 1.46 (95% CI 1.21–1.75 for a coronary event), 1.26 (95% CI 1.05–1.51 for a cerebrovascular event), and 1.02 (95% CI 0.74–1.40 for other vascular events).3

Reasons for discontinuation of stain therapy included:

  • Hospitalization during follow-up
  • Admission to a skilled nursing home (
  • Diagnosis of a metastatic solid tumor
  • Initiation of enteral or oral feeding  

In addition, an interesting pattern was detected among patients who stopped statin therapy—they were more likely to have also discontinued other medication, including ace inhibitors, angiotensin II receptor blockers, or the direct renin inhibitor, aliskiren.

Conversely, continuation of use or a new prescription of any of the blood pressure meds during follow-up led to a greater probability that the statin would be taken, the authors wrote. A similar pattern was seen with many other cardiovascular medications including: if other heart meds were prescribed or taken ongoing, the patient was more likely to take the statin, too.3

While the authors assessed the type and dosages of statins taken, “however, the intensity of statin therapy had little influence on the estimated effect of statin discontinuation,” Dr. Coste said.

Medication Adherence Among Seniors Offers Clues to Long-Term Outcomes

Important factors related to subsequent resumption of statin therapy were use of antiplatelet agents other than aspirin, use of oral antidiabetic agents, use of insulin, metastatic solid tumor during the previous two years, and residence in a skilled nursing home.

Dr. Coste and his team reported a 33% increase in the risk of admission to the hospital for treatment of a CVD event in this senior population, suggesting the importance of encouraging older patients to maintain their preventive regimen of statin therapy to reduce their risk of future cardiovascular events.3

“The presence of major cardiovascular risk factors, indicated by cardiovascular drug use, comorbidities and frailty indicators, was investigated both at baseline and continuously during follow-up and their association with treatment discontinuation was taken into account by the analytical method adopted,” Dr. Coste told EndocrineWeb.

“In particular, discontinuation of other cardiovascular drug therapies was corrected for. However, due to the real life observational nature of this study, residual confounding cannot be excluded,” he said.

As such, the investigators acknowledged that the results of cohort study need corroboration from randomized controlled trials, including specific individualized information on lifestyle behaviors; in the meantime, clinicians may choose to reinforce the likely benefit of maintaining their medication regimen as the best means possible to lessening their risks of cardiovascular events.3

Other members of the Endocrine Society guidance writing committee were: George L. Bakris, MD, at the University of Chicago Medicine in Chicago, Ill.; Lars F. Berglund, MD, PhD, at the University of California/Davis in Sacramento, California; Marie-France Hivert, MD, and Edward S. Horton, MD, both of Harvard Medical School in Boston, Massachusetts.; Rita R. Kalyani, MD, MHS, at Johns Hopkins University School of Medicine in Baltimore, Maryand; Mohammad H. Murad at the Mayo Clinic in Rochester, Minnesota; and Bruno L. Vergès, MD, PhD, at the University Hospital in Dijon, France. Financial Disclosures for all members are available in the practice document.


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