Last updated December 18, 2021

Primary Prevention of ASCVD and T2DM in Patients at Metabolic Risk

Recommendations

Definitions and diagnosis

In individuals aged 40 to 75 years in the office setting, we suggest providers screen for all five components of metabolic risk at the clinical visit. The finding of at least three components should specifically alert the clinician to a patient at metabolic risk (at higher risk for atherosclerotic cardiovascular disease and type 2 diabetes mellitus). (2-VL)
Technical remark: The main components of metabolic risk as defined in this guideline are (i) elevated blood pressure, (ii) increased waist circumference, (iii) elevated fasting triglycerides, (iv) low high-density lipoprotein cholesterol, and (v) elevated glycemia. Elevated glycemia should be determined either by HbA1c, fasting glucose, or 2-hour glucose with a second test for confirmation using a new blood sample. Testing for additional biological markers (e.g., high-sensitivity C-reactive protein) associated with metabolic risk should be limited to subpopulations. This recommendation is specifically for adults aged 40 to 75 years, those for whom the interventions have the greatest impact and evidence for efficacy. This does not restrict screening for appropriate individuals outside of this age range, especially those who are younger.
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In individuals aged 40 to 75 years in the office setting who do not yet have atherosclerotic cardiovascular disease or type 2 diabetes mellitus and already have at least one risk factor, we advise screening every 3 years for all five components of metabolic risk as part of the routine clinical examination. (UGPS)
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To establish metabolic risk in the general population, we recommend that clinicians measure waist circumference as a routine part of the clinical examination. (1-M)
Technical remark: This measurement does not replace the routine measurement of weight or calculation of body mass index but can provide more focused information regarding risk for atherosclerotic cardiovascular disease and type 2 diabetes mellitus. The Writing Committee agrees that the cutoffs for elevated waist circumference should be ≥102 cm for men and ≥88 cm for women in white, African, Hispanic, and Native American populations. The Writing Committee agrees that the cutoffs for waist circumference in Asian populations (both East Asian and South Asian) should be ≥90 cm for men and ≥80 cm for women.
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In individuals previously diagnosed with prediabetes, we suggest testing at least annually for the presence of overt type 2 diabetes mellitus. (2-M)
Technical remark: Prediabetes is defined in a variety of ways (fasting plasma glucose, 2-hour plasma glucose following a 75-g oral glucose tolerance test, or HbA1c) by different organizations in different countries, and the Writing Committee does not endorse preferential use of one definition over another.
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We recommend that all individuals at metabolic risk in the office setting have their blood pressure measured annually and, if elevated, at each subsequent visit. (1-H)
Technical remark: Blood pressure should be measured after 5 minutes of rest. Ambulatory and/or home blood pressure monitoring, when performed correctly, is recommended to confirm a diagnosis of hypertension after initial screening.
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For individuals with elevated blood pressure >130 mm Hg systolic and/or >80 mm Hg diastolic who are not documented as having a history of hypertension, we recommend confirmation of elevated blood pressure on a separate day within a few weeks or with a home blood pressure monitor. (1-H)
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Lifestyle and behavioral therapy

In individuals at metabolic risk, we recommend that lifestyle modification be first-line therapy. (1-H)
Technical remark: The Writing Committee believes that primary care providers, endocrinologists, geriatricians, and cardiologists should initiate discussions about the importance of adopting a healthy lifestyle with all individuals at metabolic risk. These and other relevant providers should encourage individuals to join comprehensive programs led by trained health professionals that support the adoption of healthy lifestyles, including diet and physical activity, aiming for moderate but sustained weight loss.
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For individuals at metabolic risk with excess weight (defined by body mass index and/or waist circumference), we recommend that comprehensive programs to support the adoption of a healthy lifestyle should aim to achieve a weight loss of ≥5% of initial body weight during the first year. (1-H)
Technical remark: Maintenance of weight loss by adoption of sustainable healthy behaviors should be encouraged with continuing support of primary providers and/or extended programs.
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In individuals at metabolic risk, we recommend prescribing a cardiovascular-healthy diet. (1-M)
Technical remark: Providers can offer dietary recommendations based on common components of healthy cardiovascular dietary patterns to all individuals at metabolic risk. Specific dietary changes according to individual risk profiles could be supported with the help of a nutrition specialist in addition to the primary care provider.
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In individuals at metabolic risk, we recommend prescribing daily physical activity, such as brisk walking, and reduction in sedentary time. (1-M)

Technical remark: Providers should encourage all individuals at metabolic risk to adopt an active lifestyle by walking and reducing the amount of time in sedentary activities. Structured activity programs may be added with the help of an exercise specialist for appropriate individuals.

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Medical and pharmacological therapy

Risk assessment and evaluation

In individuals identified as having metabolic risk, we recommend global assessment of 10-year risk for either coronary heart disease or atherosclerotic cardiovascular disease to guide the use of medical or pharmacological therapy. (1-M)
Technical remark: Global risk assessment includes the use of one of the established cardiovascular risk equations. Elevated low-density lipoprotein is indicative of cardiovascular risk.
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In individuals with low-density lipoprotein cholesterol ≥190 mg/dL (4.9 mmol/L) or triglycerides ≥500 mg/dL (<5.6 mmol/L), we recommend that, before considering the diagnosis of primary hyperlipidemia, practitioners should rule out secondary causes of hyperlipidemia. If a secondary cause can be excluded, primary hyperlipidemia should be suspected. (1-M)

Technical remark: Examples of secondary causes of hyperlipidemia include untreated hypothyroidism, nephrotic syndrome, renal failure, cholestasis, acute pancreatitis, pregnancy, polycystic ovarian disease, excess alcohol use, treatment with estrogens/oral contraceptives, antipsychotic agents, glucocorticoids, cyclosporine, protease inhibitors, retinoids, and beta blockers.

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Cholesterol reduction

In individuals 40 to 75 years of age with low-density lipoprotein cholesterol ≥190 mg/dL (≥5.9 mmol/L), we recommend high-intensity statin therapy to achieve a low-density lipoprotein cholesterol reduction of ≥50%. (1-M)
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In individuals 40 to 75 years of age with low-density lipoprotein cholesterol 70 to 189 mg/dL (1.8 to 4.9 mmol/L), we recommend a 10-year risk for atherosclerotic cardiovascular disease should be calculated. (1-M)
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  • In individuals 40 to 75 years of age without diabetes and a 10-year risk ≥7.5%, we recommend high-intensity statin therapy either to achieve a low-density lipoprotein cholesterol goal <100 mg/dL (<2.6 mmol/L) or a low-density lipoprotein cholesterol reduction of ≥50%.
(1-M)
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  • In individuals 40 to 75 years of age without diabetes and a 10-year risk of 5% to 7.5%, we recommend moderate statin therapy as an option after consideration of risk reduction, adverse events, drug interactions, and individual preferences, to achieve either a low-density lipoprotein cholesterol goal <130 mg/dL (<3.4 mmol/L) or a low-density lipoprotein cholesterol reduction of 30% to 50%.
(1-M)
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  • In individuals with metabolic risk, without diabetes, on statin therapy, we suggest monitoring glycemia at least annually to detect new-onset diabetes mellitus.
(2-M)
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  • In individuals aged >75 years without diabetes and a 10-year risk ≥7.5%, we recommend discussing the benefits of statin therapy with the patient based on expected benefits vs possible risks/side effects.
(1-M)
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Technical remark: Decisions should be made on a case-by-case basis depending on estimates of likely benefits vs risks in individual patients. Statin therapy should be calibrated to reach the recommended low-density lipoprotein targets.

In individuals at metabolic risk who are taking statins with adequate low-density lipoprotein cholesterol reduction, elevated triglyceride levels [≥200 mg/dL (2.3 mmol/L)], and reduced high-density lipoprotein levels [≤50 mg/dL (1.3 mmol/L) in females, or ≤40 mg/dL (1.0 mmol/L) in males], we suggest considering fenofibrate adjunct therapy. (2-M)

Technical remark: Avoid gemfibrozil in this situation.

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In individuals ≥40 years of age at metabolic risk with low-density lipoprotein cholesterol at target, an estimated 10-year atherosclerotic cardiovascular disease risk of >7.5%, and without clinical atherosclerotic cardiovascular disease or other atherosclerotic cardiovascular disease risk factors, we suggest treatment with a moderate-intensity statin. (2-M)
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Blood pressure reduction

In individuals with blood pressure >130/80 mm Hg and a 10-year cardiovascular risk ≤10%, we suggest lifestyle management to lower blood pressure to <130/80 mm Hg and to reduce the risk for atherosclerotic cardiovascular disease. (2-M)
Technical remark: Because the 10-year risk is ≤10%, lifestyle intervention is appropriate and preferable to use of medications. Interventions include weight loss, healthy diet, sodium restriction, enhanced potassium intake, increased physical activity, and moderation of alcohol use.
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In individuals without a history of atherosclerotic cardiovascular disease with metabolic risk who have a 10-year cardiovascular risk of >10% and blood pressure of >130/80 mm Hg, we suggest the use of blood pressure–lowering medication in addition to lifestyle modifications for primary prevention of atherosclerotic cardiovascular disease only when lifestyle modification alone has failed. (2-M)
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Reducing progression to type 2 diabetes

In individuals with prediabetes, we recommend prescribing lifestyle modification before drug therapy to reduce plasma glucose levels. (1-H)
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In individuals with prediabetes who have limitations to physical activity or are not responding to lifestyle modifications, we recommend metformin as a first pharmacologic approach to reduce plasma glucose levels. (1-M)
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Recommendation Grading

Overview

Title

Primary Prevention of ASCVD and T2DM in Patients at Metabolic Risk

Authoring Organization

Publication Month/Year

July 31, 2019

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory

Scope

Counseling, Assessment and screening, Prevention, Treatment

Diseases/Conditions (MeSH)

D003920 - Diabetes Mellitus, D002318 - Cardiovascular Diseases, D003924 - Diabetes Mellitus, Type 2, D050356 - Lipid Metabolism, D008660 - Metabolism

Keywords

diabetes, cardiovascular disease, primary prevention

Source Citation

James L Rosenzweig, George L Bakris, Lars F Berglund, Marie-France Hivert, Edward S Horton, Rita R Kalyani, M Hassan Murad, Bruno L Vergès, Primary Prevention of ASCVD and T2DM in Patients at Metabolic Risk: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 9, September 2019, Pages 3939–3985, https://doi.org/10.1210/jc.2019-01338