Risk of all-cause mortality and transcontinental differences in angiopoietin-like 4 protein and lipids in patients admitted with chest pain of suspected coronary origin.
D W Nilsen, R Leon de la Fuente, R Aarsetoey, P Naesgaard, S Dib Ashur, T Brugger Andersen, V Poenitz, H Grundt, A E Michelsen, P Aukrust, H Staines, T UelandAbstract
Background
The prognostic utility of angiopoietin-like 4 protein (ANGPTL4) has previously been explored [1). ANGPTL4 plays a key role in lipid and glucose metabolism. It inhibits lipoprotein lipase (LPL) and is positively related to increased triglyceride (TG) levels and risk of cardiovascular death. Sharing the same protocol, two consecutive, prospective studies of propensity matched patients admitted with chest pain of suspected coronary origin were performed in Norway (NOR) and Argentina (ARG), respectively. We investigated mortality and circulating levels of ANGPTL4, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) in each population, as well as the prognostic utility of ANGPTL4 in the combined population.
Aims
To evaluate the prognostic utility of ANGPT4 in two populations with significant differences in lipid risk profile.
Methods
There were 507 eligible patients in each population after propensity matching with respect to age, sex and statins, Stepwise Cox regression models, applying normalized continuous log values, were fitted for ANGPTL4 with 5 years' all-cause mortality as the dependent variable. The median value and Kruskal-Wallis test was applied for country comparisons of biomarker levels. Spearman Correlation Coefficient (r) was employed for analysis of correlations.
Results
Five-year mortality rates were similar across the two populations; ARG 20.1% and NOR 22.7%, p=0.32. ANGPTL4 levels were collectively available in 992 patients (ARG=504, NOR=488), of whom 212 (21.4%) had died. ANGPTL4 was independently associated with risk in both populations [ARG: HR 1.65 (95%CI 1.35-2.01), p<0.001] and [NOR: HR 1.30 (95%CI 1.07-1.57), p=0.008]. These HR do not not differ significantly (Z=1.68; p=0.093). In the combined population, ANGPTL4 yielded an HR (95%CI) for all-cause mortality of 1.87 (1.67-2.10) in the univariate and 1.43 (1.23-1.67) in the adjusted analysis. ANGPTL4 was significantly higher in the ARG as compared to the NOR population (3.74 vs. 2.89 ng/mL, p<0.0001), as was TG (1.60 vs. 1.30 mmol/L, p<0.0001, whereas the opposite was noted for the other lipid fractions (TC 4.60 vs. 5.50 mmol/L, HDL-C 1.00 vs. 1.30 mmol/L, LDL-C 2.67 vs. 3.46 mmol/L (each p<0.0001).
Conclusion
ANGPTL4 is independently and positively associated with total mortality in patients with chestpain of suspected coronary origin, but the weight of risk did not differ significantly between the Argentinian and the Norwegian population, despite significant differences in lipid fractions.