Published Online
on August 13, 2007

A more recent version of this article appeared on August 28, 2007

This Article Full Text (PDF) CME: Take the course for this article: Circulation: August 28, 2007, Volume 116, Number 9 All Versions of this Article: 116/9/984    most recent CIRCULATIONAHA.107.708537v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ingelsson, E. Articles by Vasan, R. S. Search for Related Content PubMed PubMed Citation Articles by Ingelsson, E. Articles by Vasan, R. S. Related Collections Epidemiology Pathophysiology Risk Factors

Submitted on April 10, 2007
Accepted on June 15, 2007

Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors. The Framingham Offspring Study

Erik Ingelsson MD, PhD, Michael J. Pencina PhD, Geoffrey H. Tofler MD, Emelia J. Benjamin MD, ScM, Katherine J. Lanier MA, Paul F. Jacques MD, Caroline S. Fox MD, MPH, James B. Meigs MD, MPH, Daniel Levy MD, Martin G. Larson ScD, Jacob Selhub PhD, Ralph B. D’Agostino Sr PhD, Thomas J. Wang MD, and Ramachandran S. Vasan MD^*

From the Framingham Heart Study, Boston University School of Medicine, Framingham, Mass (E.I., M.J.P., E.J.B., C.S.F., D.L., M.G.L., R.B.D., T.J.W., R.S.V.); Department of Mathematics (M.J.P., K.J.L., R.B.D.), and Cardiology Division and Preventive Medicine (E.J.B., R.S.V.), Boston University School of Medicine, Boston, Mass; Royal North Shore Hospital, Sydney, Australia (G.H.T.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, Mass (P.F.J., J.S.); Division of Endocrinology, Brigham and Women’s Hospital, Boston, Mass (C.S.F.); Department of Medicine (J.B.M.) and Cardiology Division (T.J.W.), Massachusetts General Hospital, Boston (T.J.W.); and National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.).

^* To whom correspondence should be addressed. E-mail: vasan{at}bu.edu.

Background—The metabolic syndrome (MetS) is associated with increased cardiovascular risk. We evaluated the relative contributions of circulating biomarkers representing distinct biological pathways to the incidence of MetS and to longitudinal changes of its constituent risk factors.

Methods and Results—We measured 8 circulating biomarkers reflecting inflammation (C-reactive protein), hemostasis (plasminogen activator inhibitor-1, fibrinogen), neurohormonal activity (aldosterone, renin, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide), and endothelial dysfunction (homocysteine) in 2292 Framingham Offspring Study participants (mean age, 57 years; 56% women). We related the biomarker panel to incidence of MetS on follow-up initially and then related biomarkers associated with incident MetS to longitudinal change in its components. On follow-up (mean, 2.9 years), 282 participants (of 1473 participants without prevalent MetS at baseline) developed MetS. After adjustment for clinical risk factors, the biomarker panel was associated with incident MetS (P=0.008). On backward elimination, plasminogen activator inhibitor-1 and aldosterone remained associated with incident MetS (multivariable-adjusted odds ratio per 1-SD increment log marker, 1.31 [P=0.004] and 1.21 [P=0.015], respectively). In multivariable analyses evaluating longitudinal change in MetS components (analyzed as continuous variables), plasminogen activator inhibitor-1 was significantly and positively associated with changes in fasting glucose, systolic blood pressure, and triglycerides (all P<0.05). Serum aldosterone was associated positively with change in systolic blood pressure (P=0.023) and inversely with change in high-density lipoprotein cholesterol (P=0.001).

Conclusions—Higher circulating plasminogen activator inhibitor-1 and aldosterone levels are associated with the development of MetS and with longitudinal change of its components, suggesting that these biomarkers and related pathways play a key role in mediating metabolic risk.

Key words: aldosterone • epidemiology • metabolic syndrome X • plasminogen activator inhibitor 1 • risk factors

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