Correlation among soluble markers and severity of disease in non-diabetic subjects with pre-mature coronary artery disease Nitin Mahajan Namita Malik Ajay Bahl Yashpaul Sharma Veena Dhawan Received: 26 January 2009 / Accepted: 16 April 2009 / Published online: 2 May 2009 Ó Springer Science+Business Media, LLC. 2009 Abstract Studies are lacking in literature, which dem- onstrate the cumulative impact of certain soluble markers in predicting the severity of CAD. Serum hsCRP, MMP-9, TIMP-1 and sRAGE levels were measured in non-diabetic 100 angiographically proven CAD patients (Group I) and 40 non-diabetic subjects with coronary risk factors and without any lesions (Group II). Increased levels of serum hsCRP, MMP-9, TIMP-1 and decreased levels of sRAGE were observed in Group I as compared to Group II. Gensini score, a measure for severity of CAD was found to be positively correlated with serum hsCRP, MMP-9, TIMP-1 and negatively with sRAGE. Multivariate analysis revealed serum MMP-9, hsCRP, sRAGE and family history as predictors of severity of CAD with a cumulative sensitivity and specificity of 92% and 82%, respectively. Cumulative impact of these soluble markers, in addition to the estab- lished markers will contribute to improve the predictive value for the assessment of disease severity. Keywords Pre-mature CAD Á sRAGE Á MMP-9 Á TIMP-1 Á Gensini score Introduction Cardiovascular diseases (CVD) are major causes of mor- tality and disease in the Indian subcontinent, causing more than 25% of deaths. It has been predicted that these dis- eases will increase rapidly in India and the country will be host to more than half the cases of heart disease in the world within the next 15 years [1]. It usually involves the middle and older age group [2]. Evaluation of major cor- onary risk factors in Indian patients undergoing angiogra- phy has shown that in about one-third of the patients, the disease occurs in absence of any major risk factors [3]. The increasing incidence of CAD in young Indian population ( \ 55 years) is attributed to global industrialization, stres- sed life, lack of exercise and increasing incidence of smoking and alcohol consumption and other nutritional and lifestyle factors [4]. C-reactive protein (CRP) is an acute-phase reactant, which is a marker for underlying systemic inflammation. There are two different tests for CRP. The standard test measures a much wider range of CRP levels but is less sensitive in the lower ranges. The hs-CRP test can more accurately detect lower concentrations of the protein (as it is more sensitive), which makes it more useful than the CRP test in predicting a healthy person’s risk for cardio- vascular disease [5]. hsCRP has a useful prognostic utility in patients with myocardial infarction (MI) and unstable angina [6, 7]. Further, several prospective studies have shown that CRP is a predictor of increased risk for MI, stroke or peripheral vascular disease in asymptomatic individuals with no known coronary artery disease [8, 9]. Evidence in literature indicates that serum level of matrix metalloproteinase-9 (MMP-9) levels might be a sensitive inflammatory marker for prediction of cardio- vascular mortality in patients with CAD [10, 11], and is N. Mahajan Á N. Malik Á V. Dhawan (&) Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education & Research (PGIMER), Research Block ‘B’, Chandigarh 160012, India e-mail: veenad2001@yahoo.com A. Bahl Á Y. Sharma Department of Cardiology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh 160012, India 123 Mol Cell Biochem (2009) 330:201–209 DOI 10.1007/s11010-009-0134-1