Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study.
BACKGROUND
Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations.


METHODS
We measured sST2 using a highly sensitive ELISA in 3450 Framingham Heart Study participants who attended a routine examination. We used multivariable linear regression models to identify covariates associated with sST2 in the general sample. We obtained a reference sample (n = 1136) by excluding individuals with prevalent coronary disease, heart failure, atrial fibrillation, diabetes, hypertension, obesity, valvular disease, left ventricular systolic dysfunction, and pulmonary and renal dysfunction. We used empiric and quantile regression techniques to estimate the 2.5th, 50th, 97.5th, and 99th quantiles.


RESULTS
In the general sample (mean age 59 years, 55% women), systolic blood pressure (P = 0.006), antihypertensive medication use (P = 0.03), and diabetes (P < 0.001) were associated with sST2 concentrations. In the reference sample (mean age 55, 59% women), male sex (P < 0.0001) and older age (P = 0.004) were predictive of higher sST2 concentrations. Quantile and empirical methods were used to define the reference intervals. Using the empirical approach, upper 99% percentile values in different age groups ranged from 46.6 to 64.4 μg/L in men and 36.7 to 53.0 μg/L in women.


CONCLUSIONS
In a well-characterized, community-based cohort, values for sST2 differ between men and women, increase with age, and are associated with diabetes and hypertension.
Division of Cardiology, Loyola University Health System, Maywood, IL, USA.
Erin E
EE
Coglianese
Martin G
MG
Larson
Ramachandran S
RS
Vasan
Jennifer E
JE
Ho
Anahita
A
Ghorbani
Elizabeth L
EL
McCabe
Susan
S
Cheng
Michael G
MG
Fradley
Dana
D
Kretschman
Wei
W
Gao
George
G
O'Connor
Thomas J
TJ
Wang
James L
JL
Januzzi
D000328:Adult; D000367:Age Factors; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood*; D012016:Reference Values; D012737:Sex Factors
D000959:Antihypertensive Agents; D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface