MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction - DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy

Background Midregional proadrenomedullin ( MR ‐pro ADM ) has demonstrated prognostic potential after myocardial infarction ( MI ). Yet, the prognostic value of MR ‐pro ADM at admission has not been examined in patients with ST‐segment–elevation MI ( STEMI ). Methods and Results The aim of this substudy, DANAMI‐3 (The Danish Study of Optimal Acute Treatment of Patients with ST ‐segment–elevation myocardial infarction), was to examine the associations of admission concentrations of MR ‐pro ADM with short‐ and long‐term mortality and hospital admission for heart failure in patients with ST ‐segment–elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR ‐pro ADM was 0.64 nmol/L (25th–75th percentiles, 0.53–0.79). Within 30 days 23 patients (2.0%) died and during a 3‐year follow‐up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR ‐pro ADM was, in adjusted models, associated with an increased risk of 30‐day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01–7.11; P =0.049), long‐term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97–5.29; P &lt;0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32–5.58; P =0.007). For 30‐day and 3‐year mortality, the area under the curve for MR ‐pro ADM was 0.77 and 0.78, respectively. For 3‐year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P =0.02) after addition of MR ‐pro ADM . Conclusions Elevation of admission MR ‐pro ADM was associated with long‐term mortality and heart failure, whereas the association with short‐term mortality was borderline significant. MR ‐pro ADM may be a marker of prognosis after ST‐segment–elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models. Clinical Trial Registration URL : http:/www.ClinicalTrials.gov /. Unique identifiers: NCT 01435408 and NCT 01960933. </jats:sec

Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans

The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via F-18-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (beta: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (beta: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.</p

Association of apolipoprotein M and sphingosine-1-phosphate with brown adipose tissue after cold exposure in humans

The HDL-associated apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) may control energy metabolism. ApoM deficiency in mice is associated with increased vascular permeability, brown adipose tissue (BAT) mass and activity, and protection against obesity. In the current study, we explored the connection between plasma apoM/S1P levels and parameters of BAT as measured via F-18-FDG PET/CT after cold exposure in humans. Fixed (n = 15) vs personalized (n = 20) short-term cooling protocols decreased and increased apoM (- 8.4%, P = 0.032 vs 15.7%, P < 0.0005) and S1P (- 41.0%, P < 0.0005 vs 19.1%, P < 0.005) plasma levels, respectively. Long-term cooling (n = 44) did not affect plasma apoM or S1P levels. Plasma apoM and S1P did not correlate significantly to BAT volume and activity in the individual studies. However, short-term studies combined, showed that increased changes in plasma apoM correlated with BAT metabolic activity (beta: 0.44, 95% CI [0.06-0.81], P = 0.024) after adjusting for study design but not BAT volume (beta: 0.39, 95% CI [- 0.01-0.78], P = 0.054). In conclusion, plasma apoM and S1P levels are altered in response to cold exposure and may be linked to changes in BAT metabolic activity but not BAT volume in humans. This contrasts partly with observations in animals and highlights the need for further studies to understand the biological role of apoM/S1P complex in human adipose tissue and lipid metabolism.Metabolic health: pathophysiological trajectories and therap