HADK1MAG-61K MilliporeMILLIPLEX MAP Human Adipokine Magnetic Bead Panel 1 - Endocrine Multiplex Assay

Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts mortality in patients with chronic stable angina or acute coronary syndrome. However, the association of GDF-15 with cardiovascular (CV) events and the mechanisms of this association are not well understood.We measured plasma GDF-15 and cardiac disease severity in 984 patients with stable ischemic heart disease who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent CV events (myocardial infarction, stroke, and CV death), hospitalization for heart failure, and all-cause mortality were determined by chart review during an average of 8.9-year follow-up.Each doubling in GDF-15 was associated with a 2.5-fold increased rate of CV events (hazard ratio [HR] 2.53, 95% CI 2.13-3.01, P < .001). This association persisted after extensive adjustment for covariates including comorbid conditions, measures of cardiac disease severity, cardiac function, inflammatory markers, and adipokines (HR 1.44, 95% CI 1.11-1.87, P < .01). Participants who had GDF-15 levels in the highest tertile had higher mortality compared with those in the lowest tertile (HR 2.73, 95% CI 1.80-4.15, P ≤ .001 adjusted for all covariates). Addition of GDF-15 to existing risk factors resulted in a 50% change in net reclassification of patients' risk for mortality.Higher levels of GDF-15 are associated with major CV events in patients with stable ischemic heart disease. This suggests that GDF-15 is capturing an element of risk not explained by other known risk factors.

Insulin resistance (IR) is associated with increased cardiovascular risk in multiple patient populations, including those undergoing chronic hemodialysis (CHD). Active vitamin D deficiency has been proposed to play a role in the extent of IR observed in patients with CHD. We postulated that administration of paracalcitol, an active vitamin D medication, influences IR in patients with CHD.This was a pilot randomized controlled trial. Ten prevalent CHD patients receiving a stable dose of paracalcitol were recruited. Paracalcitol was withheld for 8 weeks in all patients (phase I). Parathyroid hormone levels were managed with the calcium-sensing receptor agonist cinacalcet. At week 8, patients were randomized to continue cinacalcet or to restart paracalcitol for 8 weeks (phase II). The primary outcome was the change in IR measured by the glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp (HEGC) method. Secondary outcomes included changes in IR between groups in indirect indices of IR, biomarkers of inflammation, and adipokine levels.The mean age was 49 years (range, 46-57 years) and 40% of patients were women. There was no detectable change in the GDR at the end of phase I (P = .7) when compared with baseline values. There was also no statistically significant difference in GDR between groups at the end of phase II (P = .9). No changes were observed in indirect indices of IR, adipokine levels, or biomarkers of inflammation in either phase.The results of this pilot study suggest that withdrawal of paracalcitol over 8 to 16 weeks and replacement for 8 weeks after withdrawal does not influence IR measured by HEGC in patients receiving CHD.