THE JOURNAL OF CLINICAL HYPERTENSION VOL. 8 NO. 2 FEBRUARY 2006142

A n a l y s i s o f R e c e n t P a p e r s i n H y p e r t e n s i o nJ a n B a s i l e , M D , S e n i o r E d i t o r

Michael J. Bloch, MD;1,2 Jan Basile, MD3

THE AMERICAN HEART ASSOCIATION/NATIONAL HEART LUNG AND BLOOD INSTITUTE UPDATED RECOMMENDATIONS FOR THE DIAGNOSIS AND TREATMENT OF THE METABOLIC SYNDROMEWhile the metabolic syndrome has attracted tre-mendous attention in the past few years, its utility as a clinical and research tool remains limited by a lack of consistency in its definition and a failure to be fully integrated into current risk stratification and treatment guidelines such as those proposed by the National Cholesterol Education Program (NCEP) in the 2001 Adult Treatment Panel III (ATP III). A recently updated executive summary scientific statement issued jointly by the American Heart Association and the National Heart, Lung, and Blood Institute (AHA/NHLBI) seeks to pro-vide up-to-date guidance for the diagnosis and management of the metabolic syndrome.

According to this statement, the metabolic syndrome is a constellation of at least three inter-related metabolic risk factors (elevated waist cir-cumference, elevated triglycerides, reduced HDL cholesterol, increased blood pressure [BP], and elevated fasting glucose) that tend to cluster in individual patients. It is present in as many as 25% of adult Americans. Importantly, this clustering of risk factors has been associated with an increased risk for developing both atherosclerotic cardiovas-

cular disease (ASCVD) and type 2 diabetes mellitus (T2DM). The risk of ASCVD and T2DM also appears to be directly correlated with the number of metabolic syndrome risk factors present; the more risk factors present, the greater the risk. In the opinion of the authors, it should be considered a “clinical syndrome” rather than a specific disease entity; the Framingham risk score should continue to be used to assess 10-year risk in people with the metabolic syndrome without established ASCVD or T2DM.

The presence of the metabolic syndrome is strongly related to both abdominal obesity and insulin resistance, but the exact relative contribu-tion of each is unclear. It appears that in some patients, insulin resistance predominates (Asian Americans, for example) while in others abdomi-nal obesity is the principle driving factor. The metabolic syndrome is characterized by athero-genic dyslipidemia with elevated serum triglycer-ides (>150 mg/dL) and apolipoprotein B, increased small LDL cholesterol particles, and reduced lev-els of HDL cholesterol (<50 mg/dL in women, <40 mg/dL in men). It has also been associated with both a prothrombotic state (as measured by an increase in plasminogen activator inhibitor-1) and a proinflammatory state (as measured by an increased high-sensitivity C-reactive protein).

This AHA/NHLBI statement clarifies and makes subtle changes to the diagnostic criteria for meta-bolic syndrome outlined in the previous NCEP guidelines: 1) the threshold for impaired fasting glucose is reduced from 110 to 100 mg/dL to correspond with the recently published American Diabetes Association (ADA) criteria; 2) a lower waist circumference cut point is included for indi-viduals with a strong genetic predisposition to insulin resistance, i.e., Americans of South Asian descent; and 3) any patient on drug therapy for either elevated fasting glucose, elevated BP, low HDL cholesterol, or high triglycerides is now presumed to have that risk criterion for diagnosis.

From the Division of General Internal Medicine, Division of Cardiology, University of Nevada School of Medicine, Reno, NV;1 Risk Reduction Center, Saint Mary’s Heart and Vascular Institute, Reno, NV;2 and the Division of General Internal Medicine/Geriatrics, Ralph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, SC3

Address for correspondence: Michael J. Bloch, MD, Risk Reduction Center, Saint Mary’s Regional Medical Center, 343 Elm Street, #308, Reno, NV 89503E-mail: mbloch@aol.com

www.lejacq.com ID: 5128

The Journal of Clinical Hypertension® (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.

VOL. 8 NO. 2 FEBRUARY 2006 THE JOURNAL OF CLINICAL HYPERTENSION 143

According to this update, the metabolic syndrome can be diagnosed when three of the following five conditions are met:• Waist circumference ≥35 inches for women or ≥40

inches for men (or for patients with a strong genetic predisposition to insulin resistance ≥31 inches for women and ≥37 inches for men)

• Triglycerides ≥150 mg/dL (or on drug therapy for high triglycerides)

• HDL cholesterol <50 mg/dL for women and <40 mg/dL for men (or on drug therapy for low HDL cholesterol)

• Systolic BP ≥130 mm Hg and diastolic BP ≥85 mm Hg (or on antihypertensive medication)

• Fasting glucose ≥100 mg/dL (or on drug therapy for elevated glucose)The focus of treatment remains therapeutic

lifestyle change. Initial recommendations include a decline of about 7%–10% in total body weight from baseline over 6–12 months and at least 30 minutes of moderate intensity exercise on most days of the week. Low-dose aspirin can be recom-mended for patients with the metabolic syndrome who have a 10-year risk for coronary heart disease ≥10% as calculated from the Framingham risk score, but no specific drug therapies are recom-mended for treating the proinflammatory state. In addition, modification of individual risk factors for ASCVD, namely elevated LDL cholesterol and non-HDL cholesterol, hypertension, smoking, and diabetes is warranted. This statement emphasizes that the presence of the metabolic syndrome is not considered a coronary heart disease risk equivalent (in the absence of T2DM), and its recognition is meant to augment, not replace, global risk assess-ment.—Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syn-drome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752.

COMMENTThe term metabolic syndrome has become widely accepted since it was first described as “syndrome X” by Gerald Reaven in the late 1980s. At that time, Dr. Reaven proposed that insulin resistance was the underlying cause of the metabolic syn-drome because patients who had it were more susceptible to hypertension, hyperlipidemia, and diabetes. Reaven felt that abdominal obesity was an essential component of syndrome X.

The present updated executive summary sci-entific statement of the AHA/NHLBI expands on the previously issued ATP III definition from

2001. Obesity, which is not required for diagno-sis, remains a central characteristic for diagnosis. While maintaining that the syndrome is not a dis-tinct disease, the update reaffirms that diagnosing the metabolic syndrome helps practitioners identify people at high risk for heart disease and diabetes.

This well thought out summary, however, stands in stark contrast to another recent statement from the American Diabetes Association and the European Association for the Study of Diabetes (Kahn R, Buse J, Ferrannini E, et al., for the American Diabetes Association and the European Association for the Study of Diabetes. The meta-bolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289–2304). They questioned the value of diagnosing the meta-bolic syndrome because: 1) the risk of ASCVD associated with the metabolic syndrome appears to be no greater than the sum of the risks associated with its individual components; 2) the underlying pathophysiology (i.e., the relative contributions of insulin resistance and abdominal obesity) remains unknown; and 3) there is no evidence that treat-ment of the syndrome as a whole (i.e., treatment of the core defect) should vary from the treatment of its individual risk factors. These authors reaffirmed the importance of weight maintenance or reduc-tion, exercise, and a healthy diet regardless of the diagnosis of the metabolic syndrome and went on to state that clinicians should evaluate and treat all cardiovascular disease risk factors without regard to whether their patient meets the criteria for diag-nosis of the metabolic syndrome.

Given the conflicting information surrounding these two statements, how should the practicing clinician evaluate the metabolic syndrome when treating individual patients? It appears that the metabolic syndrome is a useful construct to convey the importance of intensive lifestyle modification as both a contributor to metabolic derangements and a potential target for intervention. The lack of a unified understanding of the pathophysiology of the metabolic syndrome should not be a bar-rier to its utilization as a clinical construct. For example, we use the term hypertension as a single concept, yet patients with elevated BP represent a heterogeneous group, with the exact pathophysi-ologic defect leading to hypertension remaining poorly understood and likely varying between indi-viduals. The presence of the metabolic syndrome should lead to a frank discussion with the patient about the associated increased risk of ASCVD and

The Journal of Clinical Hypertension® (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.