September 14, 2016
2 min read

Angiopoietin-like protein 2 levels may predict all-cause death, major CV adverse events

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Levels of angiopoietin-like protein 2 are independently associated with death and major cardiovascular adverse events, including myocardial infarction and stroke, according to data presented at the 52nd European Association for the Study of Diabetes Annual Meeting.

“Our study shows a strong association between [angiopoietin-like protein 2] levels and CV events,” Barnabas Gellen, MD, PhD, of the Polyclinique de Poitiers in Poitiers, France, told Endocrine Today. “However, at present, our results do not allow us to conclude that the clinical outcome of diabetic patients can be substantially improved by considering [angiopoietin-like protein 2] on top of validated risk factors included in risk calculator engines.”

Gellen and colleagues evaluated data from the SURDIAGENE study on 1,353 adults (mean age, 64 years) with type 2 diabetes to determine the prognostic value of angiopoietin-like protein 2 for improving death risk stratification. The primary endpoint was all-cause death, and secondary endpoints were CV death, MI and stroke. Angiopoietin-like protein 2 levels were evaluated at baseline. Follow-up was conducted for a median of 6 years.

Through follow-up, 367 participants died and 290 experienced a major CV adverse event.

Participants with high concentrations of angiopoietin-like protein 2 had a higher frequency of death (HR = 8.6; 95% CI, 5.36-13.78) and major CV adverse events (HR = 7.15; 95% CI, 4.19-12.18) compared with those with lower levels. After adjustment for sex, age and established CV risk factors, participants with angiopoietin-like protein 2 levels of 19.5 ng/mL or higher had a higher risk for death and major CV adverse events compared with those with levels of less than 19.5 ng/mL (P < .0001 for both).

“The first and most important take-home message is that, in the near future, CV risk stratification of diabetic patients could be significantly improved by integrating novel biomarkers, such as [angiopoietin-like protein 2], in risk stratification engines,” Gellen told Endocrine Today. “This might help to optimize targeted early CV screening in high-risk patient groups and thereby to prevent CV events and improve survival. The second take-home message is that [angiopoietin-like protein 2], such as other upcoming biomarkers related to low-grade inflammation and atherosclerosis, might become, in the more distant future, therapeutic targets in order to contain CV damage in diabetic patients. The way for a biomarker to become a proven and successful therapeutic target, such as brain natriuretic peptides in cardiology, is long and might take more than a decade.”

Although the findings of the study are promising, they are “merely hypothesis-generating,” Gellen said.

“Indeed, it showed up a strong association of CV adverse events and death with [angiopoietin-like protein 2] concentrations, but it does not prove causality, and it does not contribute to better understanding of the mechanistic link between circulating [angiopoietin-like protein 2] and CV events,” she told Endocrine Today. “Thus, further studies are needed to confirm our observations and to dig deeper into the underlying pathophysiological mechanisms.” – by Amber Cox


Fraty M, et al. OP 60. Presented at: 52nd EASD Annual Meeting; Sept. 12-16, 2016; Munich.

Disclosure: Gellen reports financial ties with AstraZeneca, Daiichi Sankyo, Novartis and Servier.