Inflammation and Endothelial Stress Associated With CV Risk in Type 2 Diabetes With Manifest CVD

Markers of inflammation and endothelial stress are indicators of cardiovascular (CV) risk in patients with type 2 diabetes with manifest cardiovascular disease (CVD), according to a study published in Diabetes Care. Risk for CV events occurring in diabetic patients without CVD, however, was mostly associated with the severity of atherosclerosis.

This cohort study sought to identify novel markers for predicting risk of CV complications in patients with type 2 diabetes. Study investigators performed a panel of vascular imaging, vascular function tests, and emerging biomarkers that reflected different disease mechanisms to predict risk for CV events.  

The study included 936 patients with type 2 diabetes from 4 centers in Europe: 440 patients were classified with manifest CVD, and 496 patients were classified with no clinical signs of CVD. Participants with and without CVD were matched at each center based on gender, age, and duration of diabetes. Clinical characteristics and patient demographics were recorded at baseline, as were incident CV events that occurred less than 5 years prior to being diagnosed with type 2 diabetes. Nonfatal and fatal CV events were reported during a 3-year follow-up period.

Vascular assessments taken at baseline included intima-media thickness of the left and right common carotid artery, thickness of the carotid bulbs, and total carotid plaque area. An EndoPat device was used to measure endothelial function, and arterial stiffness was calculated by carotid-femoral pulse wave velocity. Finally, left and right ankle-brachial pressure index was used to calculate the ratio between the highest systolic blood pressure values from the ipsilateral foot and arm. Biomarker analysis involved measuring plasma levels of biomarkers related to inflammation (interleukin 6, chemokine ligand 3, and pentraxin 3), endothelial growth activation (hepatocyte growth factor, placental growth factor, and vascular endothelial growth factor A), extracellular matrix proteolysis (matrix metalloproteinase 3, 7, and 12), apoptosis (Fas, TNF receptor 1, and TRAIL receptor 2), and other emerging risk markers for CV events.

Results of the study found a higher rate of CV events at baseline in diabetic patients with manifest CVD compared to patients without CVD (5.53 vs 2.15/100 life-years; P <.0001). Of the 936 study participants, 105 reported experiencing new CV events during follow-up. CV events in patients with CVD were associated with elevated levels of inflammatory biomarkers and endothelial mitogens at baseline; in participants without CVD, CV events were associated with severe baseline atherosclerosis. Study findings showed arterial stiffness, endothelial dysfunction, and conventional risk factors were not linked to CV events.

Limitations of the study included the lack of assessments related to the coronary arteries and a small number of CV events during follow-up, especially in participants without CVD. A lower threshold for defining carotid plaques was also considered a potential limiting factor of the study.

Elevated biomarkers related to inflammation and endothelial stress were predictors of CV risk in diabetic patients with manifest CVD; however, an increased intima-media thickness of the carotid artery was a better predictor for diabetic patients without manifest CVD. This indicates that patients with CVD may benefit from anti-inflammatory therapies.

Reference

Shore AC, Colhoun HM, Natali A, et al. Use of vascular assessments and novel biomarkers to predict cardiovascular events in type 2 diabetes: the SUMMIT VIP study [published online July 30, 2018]. Diabetes Care. doi: 10.2337/dc18-0185.