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Research Article: 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

Date Published: 2023-09-15

Abstract:
Objectives To investigate the association between type I collagen ?1 chain (COL1?1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1?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. 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. Primary and secondary outcome measures Primary outcome was the association between baseline COL1?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?1 after acute MI up to 6 months and lastly, correlates between COL1?1 and patient characteristics along with circulating markers of collagen metabolism. Results COL1?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?1 remained unchanged up to 6 months. COL1?1 was correlated to PRO-C1, but not to C1M. Conclusions Plasma COL1?1 was independently and inversely associated with CAD. Furthermore, COL1?1 appeared to reflect collagen synthesis but not degradation. Future studies are needed to confirm whether COL1?1 is a clinically useful biomarker of CAD.

Introduction:
Cardiovascular disease is the leading cause of death and source of disease burden worldwide. Most clinical manifestations, such as coronary artery disease (CAD), are caused by atherosclerosis. 1 Atherosclerosis is a complex and long-lasting process in which multiple factors such as lipid profile, inflammation and extracellular matrix (ECM) remodelling contribute to the phenotype of the atherosclerotic plaque. Whether a plaque develops into a vulnerable one, with increased risk of atherothrombotic complications,…

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