Background— Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non–ST-elevation acute coronary syndrome. Methods and Results— Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non–ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P <0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro–B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro–B-type natriuretic peptide, C-reactive protein, and creatinine clearance. Conclusions— GDF-15 is a new biomarker of the risk for death in patients with non–ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.

In MI patients, use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life. Use of a disease-specific interactive patient support tool may be an appreciated, simple, and promising complement to standard secondary prevention.

Background: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor ␤ (TGF-␤) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. Methods: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). Results: The assay had a detection limit of 20 ng/L, an intraassay imprecision of <10.6%, and an interassay imprecision of <12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-␤. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly indi-

Background— Cardiac troponin I (cTnI), a standard for detection of myocardial damage, has recently been reported to predict acute myocardial infarction or death in patients with unstable coronary heart disease (CHD). Cardiac TnI concentrations increase with age in subjects free from clinical signs of CHD, suggesting silent myocardial damage. We investigated the association between cTnI and future CHD and mortality in a community-based cohort of men. Methods and Results— A community-based study was conducted from August 1991 to May 1995 among 1203 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10.4 years with the use of registry data (National Board of Health and Welfare, Sweden). CHD was defined with the use of data taken from the Cause of Death Registry or from first-time hospitalization for CHD as recorded in the Hospital Discharge Registry. Cardiac TnI concentrations were measured blinded for outcome, in frozen baseline plasma samples, with the use of the AccuTnI from Beckman Coulter, Inc. Hazard ratios (HRs) from Cox proportional hazards are presented with 95% confidence intervals (CIs) for a 1-SD increase. In men free from cardiovascular disease (CVD), cTnI predicted death (HR, 1.26; 95% CI, 1.08 to 1.46; P =0.003) or first CHD event (HR, 1.31; 95% CI, 1.11 to 1.54; P =0.001) after adjustment for conventional risk factors: total and HDL cholesterol, plasma glucose, body mass index, smoking, and systolic blood pressure. Conclusions— In this first longitudinal report, cTnI was shown to predict death and first CHD event in men free from CVD at baseline, indicating the importance of silent cardiac damage in the development of CHD and mortality.

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Background: B-Type natriuretic peptide (BNP) is released from the left ventricle of the heart into the circulation in response to ventricular stretching and volume overload. Increased BNP concentrations are associated with heart failure (HF).