Relations of biomarkers representing distinct biological pathways to left ventricular geometry

Abstract

Background: Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear.

Methods and results: We evaluated 2119 Framingham Offspring Study participants (mean age, 57 years; 57% women) who underwent measurements of biomarkers of inflammation (C-reactive protein), hemostasis (fibrinogen and plasminogen activator inhibitor-1), neurohormonal activation (B-type natriuretic peptide), and renin-angiotensin-aldosterone system (aldosterone and renin modeled as a ratio [ARR]) and echocardiography at a routine examination. LV geometry was defined on the basis of sex-specific distributions of LV mass (LVM) and relative wall thickness (RWT): normal (LVM and RWT <80th percentile), concentric remodeling (LVM <80th percentile but RWT >or=80th percentile), eccentric hypertrophy (LVM >or=80th percentile but RWT <80th percentile), and concentric hypertrophy (LVM and RWT >or=80th percentile). We related the biomarker panel to LV geometry using polytomous logistic regression adjusting for clinical covariates and used backwards elimination to identify a parsimonious set of biomarkers associated with LV geometry. Modeled individually, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, and ARR were related to LV geometry (P<0.01). In multivariable analyses, the biomarker panel was significantly related to altered LV geometry (P<0.0001). On backwards elimination, logARR alone was significantly and positively associated with eccentric (odds ratio per SD increment, 1.20; 95% confidence interval, 1.05 to 1.37) and concentric LV hypertrophy (odds ratio per SD increment, 1.29; 95% confidence interval, 1.06 to 1.58).

Conclusions: Our cross-sectional observations on a large community-based sample identified ARR as a key correlate of concentric and eccentric LV hypertrophy, consistent with a major role for the renin-angiotensin-aldosterone system in LV remodeling.