Plasma type I collagen 1 chain in relation to coronary artery disease: findings from a prospective population-based cohort and an acute myocardial infarction prospective cohort in Sweden

Objectives To investigate the association between type I collagen alpha 1 chain (COL1 alpha 1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1 alpha 1 to clinical characteristics and circulating markers of collagen metabolism.Design Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design. Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.Design Life conditions, Stress and Health (LSH) study: prospective cohort study, here with a nested case-control design. Assessing Platelet Activity in Coronary Heart Disease (APACHE) study: prospective cohort study.Setting LSH: primary care setting, southeast Sweden. APACHE: cardiology department, university hospital, southeast Sweden.Setting LSH: primary care setting, southeast Sweden. APACHE: cardiology department, university hospital, southeast Sweden.Participants LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls. APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI. Exclusion criteria: Intervention study participation, warfarin treatment and short life expectancy.Participants LSH: 1007 randomly recruited individuals aged 45-69 (50% women). Exclusion criteria was serious disease. After 13 years of follow-up, 86 cases with primary endpoint were identified and sex-matched/age-matched to 184 controls. APACHE: 125 patients with myocardial infarction (MI), 73 with ST-elevation MI and 52 with non-ST-elevation MI. Exclusion criteria: Intervention study participation, warfarin treatment and short life expectancy.Primary and secondary outcome measures Primary outcome was the association between baseline COL1 alpha 1 and first-time major event of CAD, defined as fatal/non-fatal MI or coronary revascularisation after 13 years. Secondary outcomes were the association between the collagen biomarkers PRO-C1 (N-terminal pro-peptide of type I collagen)/C1M (matrix metalloproteinase-mediated degradation of type I collagen) and CAD; temporal change of COL1 alpha 1 after acute MI up to 6 months and lastly, correlates between COL1 alpha 1 and patient characteristics along with circulating markers of collagen metabolism.Results COL1 alpha 1 levels were associated with CAD, both unadjusted (HR=0.69, 95% CI=0.56 to 0.87) and adjusted (HR=0.55, 95% CI=0.41 to 0.75). PRO-C1 was associated with CAD, unadjusted (HR=0.62, 95% CI=0.47 to 0.82) and adjusted (HR=0.61, 95% CI=0.43 to 0.86), while C1M was not. In patients with MI, COL1 alpha 1 remained unchanged up to 6 months. COL1 alpha 1 was correlated to PRO-C1, but not to C1M.Conclusions Plasma COL1 alpha 1 was independently and inversely associated with CAD. Furthermore, COL1 alpha 1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1 alpha 1 is a clinically useful biomarker of CAD.