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To define the natural history of patients with isolated metabolic syndrome (MS).Metabolic syndrome is associated with increased risk of cardiovascular mortality. Patients with isolated MS are a subset of patients with MS who do not meet the diagnostic criteria of hypertension (HTN) and diabetes mellitus (DM). Data were collected prospectively on a population-based random sample of 1042 Olmsted County, Minnesota, residents aged 45 years or older who underwent clinical evaluation, medical record abstraction, and echocardiography (visit 1: January 1,1997, to December 31, 2000). The cohort was subdivided into healthy controls, those with isolated MS, and those with MS with HTN and/or DM groups. After 4 years, patients returned for visit 2 (September 1, 2001, to December 30, 2004). After visit 2, we have a median of 8.3 years of follow-up.There was a higher incidence of HTN, DM, and obesity in the isolated MS group at visit 2 (P<.001) than in healthy controls. Patients with isolated MS did not have significantly higher rates of cardiovascular mortality (hazard ratio [HR], 0.85; 95% CI, 0.23–3.13; P=.80) or development of heart failure (HR, 1.29; 95% CI, 0.58–2.73; P=.53) compared with healthy controls over 8 years of follow-up after visit 2. However, patients with MS with HTN and/or DM had higher rates of cardiovascular mortality (HR, 2.40; 95% CI, 1.00–5.83; P=.02) and heart failure (HR, 2.24; 95% CI, 1.16–4.32; P=.02) compared with healthy controls over 8 years of follow-up after visit 2.Isolated MS was associated with increased risk for the development of HTN, DM, and obesity, but not increased mortality or heart failure over an 8-year period compared with healthy controls. Future studies should determine whether aggressive management of risk factors in isolated MS will prevent progression to MS.