Comparison and Evaluation of Cardiac Biomarkers in Patients with Intermittent Claudication: Results from the CAVASIC Study

Abstract

BACKGROUND Plasma concentrations of the peptides midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), and C-terminal endothelin-1 precursor fragment (CT-proET-1) are increased in various cardiovascular conditions. However, there is limited information about the association and comparative performance of these peptides in peripheral arterial disease (PAD). METHODS The associations of MR-proADM, MR-proANP, and CT-proET-1 plasma concentrations with symptomatic PAD were investigated in the CAVASIC (Cardiovascular Disease in Intermittent Claudication) Study. Study participants were a male cohort of 238 patients with a diagnosis of intermittent claudication (IC) and 245 age- and diabetes-matched controls. Results were compared to those for N-terminal pro-B-type natriuretic peptide (NT-proBNP). RESULTS Each increase of MR-proADM, MR-proANP, and CT-proET-1 by 1 SD was significantly associated with symptomatic PAD: odds ratio (OR) = 1.78 (95% CI, 1.41–2.25, P < 0.001), OR = 1.32 (95% CI, 1.06–1.66, P = 0.014), and OR = 1.80 (95% CI, 1.43–2.28, P < 0.001), respectively. The association remained significant for all 3 markers after additional adjustment for log C-reactive protein, serum creatinine, HDL cholesterol, and current smoking. When one adjusts for log NT-proBNP and excluding individuals with prevalent cardiovascular disease, MR-proADM and CT-proET-1 still predicted symptomatic PAD. Extended adjustment models including MR-proADM or CT-proET-1 showed significantly improved model fits compared to models including classical cardiac risk factors or NT-proBNP and led to significant reclassification (P < 0.05). CONCLUSIONS This study in a male cohort of patients with IC and age- and diabetes-matched controls indicates a significant association of high MR-proADM, MR-proANP, and CT-proET-1 concentrations with PAD. MR-proADM and CT-proET-1 provide additive information in comparison to NT-proBNP. Moreover, MR-proADM and CT-proET-1 significantly predict PAD in those patients and controls free from prevalent CVD.

Left ventricular ejection fraction is associated with prevalent and incident cardiovascular disease in patients with intermittent claudication – results from the CAVASIC Study

“…The CAVASIC (Cardiovascular Disease in Intermittent Claudication) Study, a case-control study with a prospective follow-up investigation, was designed to identify cardiovascular risk factors in patients with intermittent claudication [17,18]. Patients and controls were recruited in 2 clinical centers: the Department of Vascular Surgery, Medical University of Innsbruck, and the 3rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria (in the years 2002e2006).…”

“…NT-proBNP and hs-cTnT (recalibrated assay, 5th generation) concentrations were measured using a commercially available assay on an E170 instrument (Modular ® , Roche Diagnostics). Details on the characteristics of these assays were reported previously [18].…”

The Fate of Patients with Intermittent Claudication in the 21st Century Revisited – Results from the CAVASIC Study

“…The CAVASIC (CArdioVAScular disease in Intermittent Claudication) Study is a case-control study with a prospective follow-up investigation of patients to identify cardiovascular risk factors in male patients with intermittent claudication [8][9][10] Inclusion criterion for patients (n = 256) was a history of intermittent claudication (PAD IIa or IIb according to the criteria of Fontaine) irrespective of any former treatment procedure (bypass surgery or intervention). Patients who presented with acute or critical limb ischemia (Fontaine III or IV), impaired kidney function with serum creatinine > 1.5 mg/dL, malignancy, previous organ transplantation, and therapy with nicotinic acid or corticosteroids were excluded from the study.…”

High-sensitivity cardiac troponin T in patients with intermittent claudication and its relation with cardiovascular events and all-cause mortality – The CAVASIC Study

“…The CAVASIC (Cardiovascular Disease in Intermittent Claudication) Study is a case-control study with a prospective follow-up examination primarily initiated to detect atherosclerotic risk factors in patients with intermittent claudication [29,30]. PAD patients (n ¼ 248) were enrolled in the study when they presented with a history of intermittent claudication (PAD stages IIa or IIb corresponding to the criteria of Fontaine), irrespective of a former treatment (bypass surgery or intervention).…”

“…The inter-assay CV for low concentration samples was 1.08%, and for high concentration samples 1.04%, respectively. More details on the characteristics of these assays were described previously [30].…”