Combining serum biomarkers: the association of C-reactive protein, insulin sensitivity, and homocysteine with cardiovascular disease history in the general US population.
BACKGROUND
Elevated levels of serum biomarkers such as C-reactive protein (CRP) and homocysteine have been independently associated with cardiovascular risk. However, the prevalence of concurrent elevations of these biomarkers in the general population is unknown, as is their association with cardiovascular disease (CVD).


METHODS
Data from adults (n = 4900) in the National Health and Nutrition Examination Survey were used to investigate the relationship between combinations of serum biomarkers of inflammation (CRP), atherosclerosis (homocysteine), and insulin sensitivity [homeostatic model assessment (HOMA) fasting insulin] and CVD. Using SUDAAN, logistic regression models were constructed to examine the relationships between elevated serum biomarkers (CRP, homocysteine, HOMA, or insulin), singly or in combination, and having a history of heart failure, myocardial infarction (MI), stroke, or any CVD, while controlling for age, race, sex, obesity, smoking, cholesterol level, diabetes history, hypertension history, exercise level, and dietary fiber intake.


RESULTS
After adjustment for covariates, there was a significant relationship between concomitant elevations of CRP plus homocysteine and a history of MI [odds ratio (OR) 2.21], heart failure (OR 2.14), and any CVD (OR 1.87) that was stronger than the relationship between individual biomarkers alone and a history of CVD. In addition, combinations of elevated CRP plus HOMA and CRP plus insulin, remained significantly related to having a history of any CVD.


CONCLUSIONS
Recent scientific evidence and the present findings demonstrate the possibility for improving cardiovascular risk stratification through the concurrent evaluation of multiple biomarkers. In particular, these findings demonstrate the need to evaluate the combination of CRP and homocysteine prospectively as predictors of CVD.
Brody School of Medicine, Department of Family Medicine, Greenville, North Carolina 27834, USA. cummingsd@mail.ecu.edu
Doyle M
DM
Cummings
Dana E
DE
King
Arch G
AG
Mainous
Mark E
ME
Geesey
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D005215:Fasting; D005260:Female; D006306:Health Surveys; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D016017:Odds Ratio; D012044:Regression Analysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D007328:Insulin; D006710:Homocysteine; D002097:C-Reactive Protein