Relation of the Number of Metabolic Syndrome Risk Factors With All-Cause and Cardiovascular Mortality John S. Ho, MD a, *, John J. Cannaday, MD a , Carolyn E. Barlow, MS b , Tedd L. Mitchell, MD a , Kenneth H. Cooper, MD a , Shannon J. FitzGerald, PhD a The metabolic syndrome (MS) is a constellation of risk factors associated with diabetes and cardiovascular disease. This syndrome consists of at least 3 parameters assessing central obesity, hypertension, high-density lipoprotein cholesterol, triglycerides, and impaired glucose metabolism. Whether persons with 4 or 5 risk factors are at higher risk than those with 3 risk factors is unclear. Also unclear is whether those without the MS but with 1 or 2 risk factors warrant therapy. We assessed cardiovascular and all-cause mortality as a function of the number of these risk factors. We followed 30,365 men for a median follow-up of 13.6 years. During follow-up, 1,449 participants died, 527 from cardiovascular causes. All of the individual parameters defining the MS were significantly associated with both all-cause and cardiovascular mortality (p <0.001). After adjustment for age and the other MS variables, hypertension was the most potent risk factor whereas central obesity and hypertriglyceridemia remained associated with both all-cause and cardiovascular mortality. A highly significant trend was also noted between both all-cause or cardiovas- cular mortality and the number of risk factors (p <0.001 for trend). Risk increased incrementally, beginning at 1 risk factor for cardiovascular mortality and at 2 risk factors for all-cause mortality. In conclusion, there is a continuum of risk as the number of metabolic syndrome risk factors increases. These findings add to the growing evidence that central obesity can independently and adversely affect health. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:689 – 692) At present, whether the number of component risk factors is important in defining the metabolic syndrome (MS) is un- clear. Should persons with 1 or 2 of these risk factors be considered as not having the MS? Conversely, are persons with 4 or 5 risk factors at greater risk than those with MS with 3 risk factors? To answer these questions, we assessed cardiovascular and all-cause mortality as a function of the number of MS risk factors. Materials and Methods The study group included all eligible men from 1979 to 2004 who presented to our institution for a preventive med- ical examination. Participants gave informed consent before participation in the Aerobics Center Longitudinal Study, which was approved annually by The Cooper Institute In- stitutional Review Board. All study participants underwent questioning by a phy- sician regarding the presence of any of the traditional car- diovascular risk factors. Diabetes was defined as a previ- ously documented fasting blood glucose of 126 mg/dL or treatment with antidiabetic medications. Hypertension was either self-reported or defined as a previously documented systolic blood pressure 140 mm Hg or a diastolic blood pressure 90 mm Hg (or both). Hyperlipidemia was either self-reported or defined as a previously documented total cholesterol level of 200 mg/dL. Moreover, all participants were questioned regarding current tobacco or cigarette use. Participants also underwent objective assessments for each of the MS components. Each of these MS components was defined per the updated and most recent MS definition put forth by the American Heart Association (AHA) and National Heart, Lung, and Blood Institute (NHLBI) in 2005. 1 Per these guidelines, the metabolic syndrome is present when at least 3 of various metabolic abnormalities exist in an individual. These defining parameters include a) fasting plasma glucose 100 mg/dL; b) high-density li- poprotein (HDL) cholesterol 40 mg/dL in men or 50 mg/dL in women; c) triglycerides 150 mg/dL; d) waist circumference 102 cm in men or 88 cm in women; and e) systolic blood pressure 130 mm Hg or diastolic blood pressure 85 mm Hg or self-report of hypertension. This most recent MS definition mirrors the guidelines provided by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), 2 with the exception that the cut-off point for impaired fasting glucose was low- ered from 110 mg/dl to 100 mg/dl. Follow-up of the study participants continued either until their death or until December 31, 2004. Deaths were iden- tified from the National Center for Health Statistics’ Na- tional Death Index. Cardiovascular mortality was defined as a Cooper Clinic, Dallas, Texas; and b The Cooper Institute, Dallas, Texas. Manuscript received March 21, 2008; revised manuscript received and accepted May 1, 2008. The development of the Aerobics Center Longitudinal Study database was partially supported by Grants AG06945 and HL62508 and by the Communities Foundation of Texas on recommendation of Nancy Ann and Ray L. Hunt. *Corresponding author: Tel: 972-560-2741; fax: 972-560-2681. E-mail address: jsho@cooper-clinic.com (J.S. Ho). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. www.AJConline.org doi:10.1016/j.amjcard.2008.05.010