Metabolic Syndrome

Table 1.

Risk Factor	Cutpoint
Abdominal obesity
Men	Waist circumference ≥ 40 inches
Women	Waist circumference ≥ 35 inches
Elevated triglycerides	≥ 150 mg/dL
Low HDL cholesterol:
Men	< 40 mg /dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130 / ≥ 85 mm Hg
Elevated fasting glucose	≥ 110 mg/dL

Table 1. ATP III Diagnostic Criteria for Metabolic Syndrome^[37]

Table 1.

Risk Factor	Cutpoint
Abdominal obesity
Men	Waist circumference ≥ 40 inches
Women	Waist circumference ≥ 35 inches
Elevated triglycerides	≥ 150 mg/dL
Low HDL cholesterol:
Men	< 40 mg /dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130 / ≥ 85 mm Hg
Elevated fasting glucose	≥ 110 mg/dL

Table 1. ATP III Diagnostic Criteria for Metabolic Syndrome^[37]

Table 2.

Risk Factor Component	Cutpoint for Abnormality
Overweight/obesity	BMI ≥ 25 kg/m²
Elevated triglycerides	≥ 150 mg/dL
Low HDL-C
Men	< 40 mg/dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130/85 mm Hg
2-hour postglucose challenge
Other risk factors	Family history of type 2 diabetes, hypertension, or cardiovascular disease
	Polycystic ovary syndrome
	Sedentary lifestyle
	Advancing age
	Ethnic groups having high risk for type 2 diabetes or cardiovascular disease

Table 2. AACE Diagnostic Criteria for the Insulin Resistance Syndrome*^[37]

AACE = American Association of Clinical Endocrinologists; BMI = body mass index
*Diagnosis depends on clinical judgment, which is based on risk factors.

Table 3.

Parameter	Mean (SD)
Parameter	Metabolic Syndrome (n = 194)	No Metabolic Syndrome (n = 382)
LDL-C, mg/dL
Baseline	187 (20)	186 (18)
Week 12	99 (31)	96 (25)
% change	-47 (15)	-48 (12)
HDL-C, mg/dL
Baseline	44 (9)	54 (13)
Week 12	49 (11)	58 (14)
% change	+10 (13)	+9 (12)
Triglycerides (mg/dL)
Baseline	216 (60)	155 (57)
Week 12	167 (64)	122 (50)
% change	-23 (20)	-19 (24)
Non-HDL-C (mg/dL)
Baseline	230 (23)	217 (21)
Week 12	132 (35)	120 (27)
% change	-43 (14)	-45 (12)
Non-HDL-C/HDL-C ratio
Baseline	5.4 (1.2)	4.2 (1.0)
Week 12	2.8 (1.1)	2.2 (0.8)
Δ %	-47 (15)	-48 (13)
ApoB (mg/dL)
Baseline	182 (22)	173 (20)
Week 12	115 (26)	106 (21)
% change	-37 (14)	-38 (12)
ApoA-I (mg/dL)
Baseline	141 (23)	155 (25)
Week 12	150 (25)	164 (27)
% change	+7 (13)	+6 (12)
ApoB/ApoA-1 ratio
Baseline	1.3 (0.3)	1.1 (0.2)
Week 12	0.8 (0.2)	0.7 (0.2)
% change	-40 (15)	-41 (13)

Table 3. Baseline and Week 12 Lipid Levels and Percent Change From Baseline in Patients With Hypercholesterolemia Treated With Rosuvastatin 10 mg

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Diagnosis

The current report issued by the National Heart, Lung, and Blood Institute on the definition of metabolic syndrome summarizes diagnostic criteria issued by the Adult Treatment Panel (ATP) III, World Health Organization (WHO), and American Association of Clinical Endocrinologists (AACE).^[37]

ATP III [45]

In 2001, the National Cholesterol Education Program (NCEP) introduced the concept of metabolic syndrome into its guidelines to improve cardiovascular risk reduction beyond that achievable with LDL-C lowering alone.^[45] Unlike type 2 diabetes, metabolic syndrome in the absence of type 2 diabetes was not accorded the status of "risk equivalent" (high risk) warranting aggressive treatment to an LDL-C goal of < 100 mg/dL. According to Framingham equations, most men with type 2 diabetes exceed the ATP III's 10-year absolute coronary risk threshold of 20%, whereas most men with metabolic syndrome alone are considered at intermediate risk, with 10-year risks between 10% and 20%.^[45] Many women with the metabolic syndrome are still at lower risk, but as they age, risk for both diabetes and cardiovascular disease increases. Appropriate risk assessment to guide cholesterol-lowering therapy is made with Framingham risk assessment for CHD, which determines the combined risk of 5 measures: smoking status, blood pressure, age, total cholesterol, and HDL-C. Non-HDL-C (total cholesterol minus HDL-C) was considered a secondary treatment target beyond LDL-C in patients with elevated triglyceride levels.

The metabolic syndrome is identified by a different but overlapping set of risk factors: waist circumference, triglyceride level, HDL-C, blood pressure, and glucose. Metabolic syndrome is diagnosed when 3 of 5 signs listed in Table 1 are present. The ranking of abdominal adiposity as the first risk factor in Table 1 reflects its priority as a contributor to the pathogenesis of metabolic syndrome. Even a modest increase in waist circumference, with the final circumference being < 40 inches in men (or < 35 inches in women), may be associated with the development of multiple metabolic risk factors, particularly in racial or ethnic groups who may be genetically predisposed to insulin resistance (eg, South Asians). According to ATP III, it is not necessary to demonstrate insulin resistance per se in order to diagnose the metabolic syndrome; increased fasting blood glucose (FBG) suffices.

WHO [46]

Guidelines from the WHO differ from ATP III guidelines chiefly in that they require the presence of insulin resistance in order for a diagnosis of metabolic syndrome to be made.

The WHO diagnostic criteria for metabolic syndrome^[37] include:

Insulin resistance as identified by 1 of the following:
- Type 2 diabetes
- Impaired fasting glucose
- Impaired glucose tolerance
- Glucose uptake below the lowest quartile for background population under investigation under hyperinsulinemic, euglycemic conditions (in patients with normal fasting glucose levels < 110 mg/dL)

Plus any 2 of the following:
- Antihypertensive medication and/or systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg
- Plasma triglycerides ≥ 150 mg/dL;
- HDL cholesterol < 35 mg/dL in men or < 39 mg/dL in women;
- Body mass index > 30 kg/m² or waist-hip ratio* > 0.9 in men or > 0.85 in women
- Urinary albumin excretion rate ≥ 20 mcg/min or albumin/creatinine ratio ≥ 30 mg/g

*Waist circumference at the umbilicus divided by hips' circumference at their widest point.

Demonstrating insulin resistance in a patient without type 2 diabetes usually involves oral glucose tolerance testing (OGTT) or hyperinsulinemic/euglycemic clamp testing. Such testing is often considered to be costly or inconvenient in many clinical practices.

The WHO also uses different blood pressure and HDL-C cutpoints from those set forth in ATP III; includes both overweight (body mass index [BMI] > 30 kg/m²) and central adiposity (waist-hip ratio > 0.9 in men or >0.85 in women) as criteria; and identifies proteinuria as a risk factor.

AACE [10]

Largely a combination of the ATP III and WHO guidelines, the AACE guidelines do not specify the number of risk factors needed to meet the definition of metabolic syndrome but rather relegate this matter to individual clinician judgment (Table 2).

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Page 4 of 7

Treatment

References

Table 1.

Table 1.

Table 2.

Table 3.

Metabolic Syndrome: A Growing Clinical Challenge: Diagnosis

Diagnosis

ATP III [45]

WHO [46]

AACE [10]

Table of Contents

Table 1.

Table 1.

Table 2.

Table 3.

References

Faculty and Disclosures

Metabolic Syndrome: A Growing Clinical Challenge: Diagnosis

Diagnosis

ATP III [45]

WHO [46]

AACE [10]

Table of Contents