Increased systemic myeloperoxidase (MPO) has been associated with both the presence and severity of heart failure (HF). This study tested the hypothesis that increased systemic MPO in apparently healthy elderly subjects may predict increased risk of developing HF. Systemic MPO was measured in all available samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS). After excluding subjects without available blood samples or with a history of prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were included. A total of 569 subjects developed incident HF during 7.2 ± 2.3 years of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher risk of developing incident HF after adjusting for MI, age, gender, systolic blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus, and any subclinical cardiovascular disease (hazard ratio 1.34, 95% confidence interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after censoring subjects with incident MI before incident HF, even when adjusted for C-reactive protein and cystatin C (hazard ratio 1.46, 95% confidence interval 1.08 to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation between increased MPO and HF risk was stronger in subjects without traditional cardiovascular risk factors (≤75 years old, systolic blood pressure ≤136 mm Hg, no subclinical cardiovascular disease, and no diabetes mellitus). In conclusion, an independent association between increased MPO and the development of HF in apparently healthy elderly subjects was observed, particularly beyond MI and traditional cardiac risk factors.
Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species and impacts on nitric oxide through complex mechanisms, including direct catalytic consumption resulting in endothelial dysfunction.1,2 Myeloperoxidase has been shown to provide prognostic value in the setting of chest pain and acute coronary syndromes.3–5 Recent studies of the community-based European Prospective Investigation of Cancer (EPIC)/Nolfork population also reported that systemic MPO independently predicted risk of the development of incident cardiovascular disease and death in apparently healthy middle-aged subjects.6 A potential pathogenic role of MPO in the development of left ventricular dysfunction and heart failure (HF) was also emerging.7–9 In animal models, MPO knockout mice showed an important role of MPO in facilitating HF disease progression.10 In humans, systemic MPO was increased in patients with established chronic systolic HF and correlated with diastolic dysfunction independent of age and plasma B-type natriuretic peptide.8 Recent studies also showed that systemic MPO in subjects with myocardial infarction (MI)7 or chronic systolic HF9 may predict long-term adverse clinical events. Here, we hypothesized that MPO may be associated with the long-term risk of developing HF in apparently healthy elderly subjects.
Am J Cardiol. 2009 May 1; 103(9): 1269–1274.
