Novel Plasma Biomarkers Associated with Future Peripheral Atherosclerotic Disease and Abdominal Aortic Aneurysm—Insights from Contemporary Prospective Studies from the Malmö Diet and Cancer Study

Abstract

Introduction: The potential utility of inflammatory and hemodynamic plasma biomarkers for the prediction of incident lower extremity arterial disease (LEAD), carotid artery stenosis (CAS), isolated atherosclerotic disease without concomitant abdominal aortic aneurysm (AAA), and isolated AAA without concomitant atherosclerotic disease has not yet been integrated in clinical practice. The main objective of this prospective study was to find predictive plasma biomarkers for cardiovascular disease and to evaluate differences in plasma biomarker profiles between asymptomatic and symptomatic CAS, as well as between isolated atherosclerotic disease and isolated AAA. Methods: Blood samples collected at baseline from participants in the prospective Malmö Diet and Cancer study (MDCS) cardiovascular cohort (n = 5550 middle-aged individuals; baseline 1991–1994) were used for plasma biomarker analysis. Validation of each incident cardiovascular diagnosis was performed by random sampling. Cox regression analysis was used to calculate hazard ratios (HRs) per one standard deviation increment of each respective log-transformed plasma biomarker with 95% confidence intervals (CI). Results: Adjusted lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (HR 1.33; CI 1.17–1.52) and mass (HR 1.20; CI 1.05–1.37), C-reactive protein (CRP) (HR 1.55; CI 1.36–1.76), copeptin (HR 1.46; CI 1.19–1.80), N-terminal pro-B-type natriuretic peptide (N-BNP) (HR 1.28; 1.11–1.48), and cystatin C (HR 1.19; 95% 1.10–1.29) were associated with incident symptomatic LEAD. Adjusted N-BNP (HR 1.59; CI 1.20–2.11), mid-regional proadrenomedullin (HR 1.40; CI 1.13–1.73), cystatin C (HR 1.21; CI 1.02–1.43), and CRP (HR 1.53; CI 1.13–1.73) were associated with incident symptomatic but not asymptomatic CAS. Adjusted HR was higher for Lp-PLA2 (mass) for incident isolated AAA compared to for isolated atherosclerotic disease. Conclusions: Plasma biomarker profile data support that subclinical vascular inflammation and cardiovascular stress seem to be relevant for the development of atherosclerotic disease and AAA.