Multimarker approach to evaluate the incidence of the metabolic syndrome and longitudinal changes in metabolic risk factors: the Framingham Offspring Study.
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.


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.
Ingelsson
Erik
E
Framingham Heart Study, Boston University School of Medicine, Framingham, MA 01702-5803, USA.
Pencina
Michael J
MJ
Tofler
Geoffrey H
GH
Benjamin
Emelia J
EJ
Lanier
Katherine J
KJ
Jacques
Paul F
PF
Fox
Caroline S
CS
Meigs
James B
JB
Levy
Daniel
D
Larson
Martin G
MG
Selhub
Jacob
J
D'Agostino
Ralph B
RB
Wang
Thomas J
TJ
Vasan
Ramachandran S
RS
D000450:Aldosterone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001775:Blood Circulation; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D002648:Child; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D008137:Longitudinal Studies; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D000450:Aldosterone; D002097:C-Reactive Protein