Lipoprotein-associated phospholipase A2 and outcome in patients with type 2 diabetes on haemodialysis.
BACKGROUND
Lipoprotein-associated phospholipase A2 (LpPLA2) is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. In a post hoc analysis of a controlled trial with atorvastatin in patients with type 2 diabetes (T2D) on haemodialysis, we examined the association between baseline and change by measuring baseline LpPLA2 activity on cardiovascular events (CVE) and mortality.


RESULTS
LpPLA2 activity was available of 1202 patients at baseline and 6 months after randomisation from 1255 patients in the German Diabetes Dialysis Study. During the 4-year follow-up, 445 patients (37%) suffered from CVE and 583 patients (49%) died. The highest quartile of LpPLA2 activity (≥615 U/L) was associated with elevated risk for CVE [HR 1·35 (1·02-1·87); P = 0·035]. This association was mainly driven by the placebo group [HR 1·51 (1·01-2·25); P = 0·046]. Receiver-operating characteristics analysis revealed that including LpPLA2 activity in an already adjusted model increased the area under the curve (AUC) for CVE from 0·586 (0·553-0·620) to 0·632 (0·599-0·664; P = 0·020) and for death from 0·704 (0·674-0·733) to 0·708 (0·679-0·737; P = 0·026). In atorvastatin-treated patients, the decrease in LpPLA2 was associated with reduced fatal risk [HR per standard deviation 0·74 (0·62-0·90); P = 0·002], an effect not seen in the placebo group. In contrast, those patients in the placebo group presenting a > 25% decrease in LpPLA2 activity (n = 33) had a more than doubled risk of dying [HR 2·48 (1·56-3·95); P < 0·001].


CONCLUSIONS
LpPLA2 activity is predictive for cardiovascular outcome and total mortality. Reducing LpPLA2 by atorvastatin was associated with reduced mortality in patients with T2D on haemodialysis.
Department of Clinical Chemistry, University Medical Center Freiburg, Hugstetter Strasse 55, Freiburg, Germany. karl.winkler@uniklinik-freiburg.de
Karl
K
Winkler
Michael M
MM
Hoffmann
Vera
V
Krane
Christiane
C
Drechsler
Christoph
C
Wanner
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000368:Aged; D019540:Area Under Curve; D000069059:Atorvastatin; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011758:Pyrroles / Q000627:therapeutic use*; D006435:Renal Dialysis; D012307:Risk Factors
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase