Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study

Abstract

OBJECTIVE Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD. RESEARCH DESIGN AND METHODS The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period. RESULTS The CV event rate in subjects with T2D was higher in those with (n = 440) than in those without (n = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, P < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm2 [16.1–92.2] vs. 19.5 mm2 [9.5–40.5], P = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events. CONCLUSIONS Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.

Serum pentraxin 3 concentration in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease

“…36 In the MESA (Multi -Ethnic Study of Atherosclerosis) study, PTX3 was positively associated with age, obesity, Imaging Prediction) study demonstrated that markers of inflammation, including PTX3, as well as markers of endothelial stress reflect cardiovascular risk in patients with T2D with manifest macroangiopathy, whereas conventional risk factors were not associated with cardiovascular events in these patients. 42 Treatment of lipid disorders in patients with NAFLD could be of value in reducing cardiovascular risk as well as preventing liver disease progression, as suggested by expert panels. 43,44 The limitations of this study include a relatively small number of examined patients in the group without NAFLD and lack of confirmation of NAFLD diagnosis by liver biopsy.…”

Cardiovascular organ damage in type 2 diabetes mellitus: the role of lipids and inflammation

“…Glycosylated hemoglobin (HbA1c) was measured by high-performance liquid chromatography and standardized against Diabetes Control and Complications Trial (DCCT ) standard. Plasma levels of biomarkers reflecting inflammation (IL-6 and IL-18) and extracellular matrix proteolysis (MMP-12) were analyzed by the Proximity Extension Assay (PEA) technique using the Proseek Multiplex CVD 96×96 reagents kit (Olink Bioscience, Uppsala, Sweden) at the Clinical Biomarkers Facility, Science for Life Laboratory, Uppsala as previously described [9, 26]. All samples were analyzed in the same run.…”

Astragaloside IV inhibits oxidized low‑density lipoprotein‑induced endothelial damage via upregulation of miR‑140‑3p

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