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CLINICAL RESEARCH: GENETICS

Heritability and correlates of intercellular adhesion molecule-1 in the Framingham Offspring Study

John F. Keaney, Jr, MD, FACC^*,*, Joseph M. Massaro, PhD^||, Martin G. Larson, ScD^||, Ramachandran S. Vasan, MD, FACC^*||, Peter W. F. Wilson, MD, FACC^*||, Izabella Lipinska, PhD, Diane Corey, BS^||, Patrice Sutherland, BS^||, Joseph A. Vita, MD, FACC^* and Emelia J. Benjamin, MD, ScM, FACC^*||

^* Evans Memorial Department of Medicine, Boston, Massachusetts, USA
Whitaker Cardiovascular Institute, Boston, Massachusetts, USA
Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
^|| National Heart, Lung, and Blood Institute's Framingham Study, Framingham, Massachusetts, USA

Manuscript received December 4, 2003; revised manuscript received February 10, 2004, accepted March 16, 2004.

^* Reprint requests and correspondence: Dr. John F. Keaney, Jr., Boston University School of Medicine, Whitaker Cardiovascular Institute, 715 Albany Street, Room W507, Boston, Massachusetts 02118, USA.
jkeaney{at}bu.edu

OBJECTIVES: We sought to determine the clinical factors and heritability associated with inflammation measured as circulating levels of soluble-intercellular adhesion molecule-1 (sICAM-1) in a community-based cohort.

BACKGROUND: Several prospective studies indicate that circulating sICAM-1 is predictive of future cardiovascular events. However, in some studies this predictive value is lost after multivariable adjustment for traditional cardiovascular disease (CVD) risk factors. We addressed the heritability of sICAM-1 and its relation to CVD risk factors in a community-based cohort.

METHODS: We examined 3,295 subjects from the Framingham Heart Study and measured sICAM-1 levels. We then used linear and stepwise multivariable regression to determine predictors or sICAM-1 levels.

RESULTS: In age- and gender-adjusted regression models, increased sICAM-1 levels were positively associated with age, total/high-density lipoprotein cholesterol, systolic blood pressure, body mass index (BMI), blood glucose, diabetes, smoking, and prevalent CVD. In stepwise multivariable regression models, sICAM-1 levels remained associated with age, female gender, total/high-density lipoprotein cholesterol ratio, BMI, blood glucose, smoking, and prevalent CVD. The residual heritability of sICAM-1 was 24%.

CONCLUSIONS: In addition to prevalent CVD, established CVD risk factors and non-traditional ones such as BMI were associated with systemic inflammation as determined by sICAM-1 levels. There also is significant heritability of sICAM-1, which suggests a genetic component to systemic inflammation.

Abbreviations and Acronyms   BMI = body mass index   BP = blood pressure   CHD = coronary heart disease   CHF = congestive heart failure   CVD = cardiovascular disease   MI = myocardial infarction   sICAM-1 = soluble intracellular adhesion molecule-1

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