Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and for the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
1. Definitions and Diagnosis
There is growing evidence that many patients who develop cardiovascular disease (CVD) or type 2 diabetes mellitus (T2DM) have common antecedents of metabolic origin. Although the pathophysiology underlying these antecedents is not fully understood, there is a strong overlap between cardiovascular risk factors and prediabetes (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]). For this reason, it is reasonable to identify a general condition called metabolic risk.
The Task Force decided to define metabolic risk as reflecting an individual's risk for CVD and T2DM (see the appendix in the original guideline document for a full discussion of this choice of terminology). Individuals at high metabolic risk often have:
- Elevations of apolipoprotein B (apo B)-containing lipoproteins (low-density lipoprotein [LDL] and very-low-density lipoprotein [VLDL]) with elevated triglycerides
- Reduced levels of high-density lipoprotein cholesterol (HDL-C)
- Increased plasma glucose levels
- Hypertension
- Enlarged waist circumference
- A prothrombotic state
- A proinflammatory state
1.1. The Task Force did not attempt to reach consensus on endorsement of a specific definition of the metabolic syndrome. The two currently used definitions describe closely overlapping but not identical populations (see Table 1 below.) Of the most commonly used definitions of the metabolic syndrome, the Task Force suggests that physicians screen for the components of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition at the clinical visit, because of its ease of use and convenience of implementation in the office setting. The finding of at least three components especially should alert the clinician to a patient at metabolic risk (at higher risk for CVD and T2DM] (2 | +000).
Table 1: Criteria Proposed for Clinical Diagnosis of the Metabolic Syndrome
| Clinical Measure |
AHA/NHLBI: any 3 of the following 5 features |
IDF |
| Waist circumference |
>102 cm in men or >88 cm in women (non-Asian origin); >90 cm in men or >80 cm in (both East Asians and South Asians) |
>94 cm in men or >80 cm in women (Europids, Sub-Saharan Africans, and Middle Eastern); >90 cm in men or >80 cm in women (both East Asians and South Asians; South and Central Americans); >85 cm in men or >90 cm in women (Japanese), plus any 2 of the following: |
| Triglycerides (fasting) |
>150 mg/dl or on drug therapy for high triglycerides |
>150 mg/dl or on drug therapy for high triglycerides |
| HDL-C |
<40 mg/dl in men or <50 mg/dl in women or on drug therapy for low HDL-C |
<40 mg/dl in men or <50 mg/dl in women or on drug therapy for low HDL-C |
| Blood pressure |
>130 mm Hg systolic or >85 mm Hg diastolic or on drug therapy for hypertension |
>130 mm Hg systolic or >85 mm Hg diastolic or on drug therapy for hypertension |
| Glucose (fasting) |
>100 mg/dl or drug therapy for elevated glucose |
>100 mg/dl (includes diabetes) |
AHA/NHLBI: American Heart Association/National Heart, Lung, and Blood Institute; IDF: International Diabetes Foundation
1.2. The Task Force recommends that providers screen for the main components of the metabolic syndrome at regular intervals (1 | +++0). The Task Force suggests that this should be done at least every 3 yr (2 | +000) in those individuals who have one or more risk factors but do not meet the established definitions of the syndrome. These components include measurement of blood pressure, waist circumference, fasting lipid profile, and fasting glucose.
1.3. The Task Force recommends that waist circumference be measured by clinicians as a routine part of the clinical examination. This measurement does not replace the routine measurement of weight or calculation of body mass index (BMI) but can provide more focused information regarding risk for CVD and T2DM (1 | +000).
The Task Force recommends that the cutoffs for elevated waist circumference be at least 102 cm for men and at least 88 cm for women in Caucasian, African-American, Hispanic, and Native American populations. The Task Force recommends that the cutoffs for waist circumference in Asian populations (both East Asian and South Asian) be at least 90 cm for men and at least 80 cm for women (1 | +000).
1.4. The Task Force suggests that individuals previously diagnosed with prediabetes (IGT or IFG) be screened for the presence of overt T2DM at 1- to 2-year intervals (2 | +000). This can be done with fasting plasma glucose (FPG) and, wherever possible, with an oral glucose tolerance test (OGTT). For individuals at metabolic risk without IFG, there is less consensus on the recommended interval of screening.
1.5. A number of additional biological markers have been associated with metabolic risk: apo B, adiponectin, leptin, fasting insulin or proinsulin, free fatty acids, homocysteine, plasminogen activator inhibitor-1 (PAI-1), fibrinogen, alanine transferase (ALT) as a marker of liver fat, C-reactive protein (CRP), inflammatory cytokines (e.g., IL-6), liver or myocellular fat content by magnetic resonance (MR) spectroscopy, and microalbuminuria (in patients without diabetes). Evidence that these markers provide an indication of metabolic risk beyond routine measurements is limited. Their measurement is not recommended for routine evaluation of metabolic risk in clinical practice. (2 | +000).
Some of the above measurements may have utility for determining the pattern or severity of metabolic risk, but must be considered as optional based on clinical judgment. Although these measures are not recommended for routine measurement, one or more of them may be measured according to physician discretion to confirm or clarify estimates of metabolic risk.
2. Absolute Risk Assessment
2.1. The Task Force recommends that all patients identified as having metabolic risk undergo global risk assessment for 10-year risk for either coronary heart disease (CHD) or CVD. Framingham and Prospective Cardiovascular Munster (PROCAM) scoring assesses 10-year risk for CHD. The European systematic coronary risk evaluation (SCORE) algorithm predicts 10-year risk for total cardiovascular mortality. Risk factor scoring with these algorithms can be easily carried out. Global risk assessment for cardiovascular outcomes is recommended before starting preventative treatment (1 | +000).
3. Treatment to Prevent Atherosclerotic CVD (Especially CHD and Stroke)
3.1.1. The Task Force recommends that apo B-containing lipoproteins (LDL and VLDL) be lowered in patients at metabolic risk to reduce risk for CVD (1 | ++++).
3.1.2. The Task Force recommends that LDL cholesterol (LDL-C) be the primary target of lipoprotein-lowering therapy (1 | ++++) and that non-HDL-C (an indicator for all apo B-containing lipoproteins) be the secondary target (1 | +++0). Furthermore, if HDL-C remains reduced after treatment of non-HDL-C, consideration can be given to therapies designed to raise HDL-C (2 | ++00).
3.1.3. The Task Force recommends that intensity of lipoprotein lowering therapy be adjusted to the absolute 10-year risk for CVD. (1 | ++00) The Task Force suggests that intensity of lipoprotein-lowering therapy further be adjusted to the absolute lifetime risk for CVD (2 | +000).
3.2.1. The Task Force recommends that when blood pressure is elevated, it be lowered to reduce the risk for CVD (1 | ++++).
3.2.2. The Task Force recommends that type and intensities of blood pressure-lowering therapies be selected to optimize risk reduction, safety, and cost-effectiveness. The Task Force recommends that blood pressure be treated to a target of less than 140/90 mm Hg (or <130/80 in individuals with diabetes or chronic kidney disease). If weight loss or lifestyle modifications are not successful, then antihypertensive medications should be instituted and dose adjusted to treat to target (1 | +++0).
3.3 The Task Force recommends that lifestyle management be considered first-line therapy for patients at increased metabolic risk (1 | +000).
3.4.1. The Task Force recommends that the prothrombotic state be treated with lifestyle therapies to reduce risk for CVD (1 | +000).
3.4.2. In individuals at metabolic risk who are over age 40 and whose 10-yr risk is more than 10%, the Task Force recommends that lowdose aspirin prophylaxis for primary prevention of CVD (75–162 mg/d) be considered if there are no contraindications (1 | +++0).
There is no consensus on the specific recommended dose within this range.
4. Treatment to Prevent T2DM
4.1.1. For primary prevention of T2DM, the Task Force recommends that patients found to be at higher metabolic risk on the basis of multiple metabolic syndrome components be started on a clinical program of weight reduction (or weight maintenance if not overweight or obese) through an appropriate balance of physical activity, caloric intake, and formal behavior modification programs to achieve a lowering of body weight/waist circumference below the targets indicated (see recommendation 1.3. for waist circumference and 4.1.2. for weight) (1 | ++00).
Although it is important to aim for these targets, any lowering of body weight/waist circumference is beneficial, and the Task Force recommends use of lifestyle modification programs for this purpose (1 | ++00).
4.1.2. In individuals at metabolic risk who have abdominal obesity, the Task Force suggests that body weight be reduced by 5–10% during the first year of therapy (2 | +000). Efforts to continue weight loss or maintain the weight loss over the long term should be encouraged.
4.1.3. The Task Force recommends that patients at metabolic risk undergo a program of regular moderate-intensity physical activity (1 | ++00). This activity would be for at least 30 minutes, but preferably 45–60 minutes, at least 5 days/week. It could include brisk walking or more strenuous activity. It can be supplemented by an increase in physical exercise as part of daily lifestyle activities.
4.1.4. The Task Force recommends that all individuals at metabolic risk follow a diet that is low in total and saturated fat, is low in trans fatty acids, and includes adequate fiber (1 | ++00). The Task Forces suggest that saturated fat be less than 7% of total calories and dietary cholesterol less than 200 mg/dL (2 | +000). The Task Force recommends that trans fat in the diet should be avoided as much as possible (1 | +000). There is much controversy regarding the proportion of carbohydrates in the diet. The Task Forces were unable to reach consensus on the optimal ratio of carbohydrates to fats in the diet. The Task Force recommends that individuals at metabolic risk increase the proportion of fiber, unprocessed grains, and unsaturated fat in their diet. Avoiding foods with high glycemic index may help lower metabolic risk.
4.2. The Task Force recommends that priority be given to reducing risk for diabetes with lifestyle therapies rather than drug therapies (1 | +++0).
Definitions:
Strength of Recommendations
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."
Quality of the Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
