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Using Novel and Vascular Biomarkers to Predict Cardiovascular Events in Diabetes

by Kirti Salunkhe, MD

Research has shown the links between type 2 diabetes (T2D) and cardiovascular disease (CVD) to be tightly intertwined and it is very common for patients to have both conditions concurrently. As the Centers for Disease Control (CDC) list both conditions among the top 10 leading causes for death in the United States, these twin healthcare concerns need to be addressed with urgency so as to reduce morbidity, mortality and improve patient outcomes.1-2 

Patients with T2D often present in the clinic with one or more of the following conditions that the American Heart Association (AHA) states are major contributors to increased risk for CVD in T2D:3

  • Hypertension (HTN) – numerous studies have found a positive association between high blood pressure and insulin resistance,4-5
  • Abnormal lipid panels – raised LDL, lowered HDL and elevated triglycerides (TG) and increased risk for atherogenesis are also commonly found with insulin resistance6
  • Obesity – along with insulin resistance, obesity is a primary risk factor for CVD7
  • Sedentary Lifestyles – Lack of physical activity increases fat mass and overweight as well as increasing insulin resistance which ultimately lead to T2D
  • Smoking – due to the vasoconstriction that occurs with smoking and nicotine, the risks for HTN increase as well as potential for arteriosclerosis

In patients who have any, or all, of the above mentioned comorbid conditions, healthcare providers (HCPs) require labs to rule in dysglycemia and develop appropriate patient management plans. Traditionally, labs include: spot glucose, fasting plasma glucose or the ‘gold standard,’ and oral glucose tolerance testing (OGTT). In recent years however, there has been a push to develop new laboratory techniques and biomarkers in order to get ahead of T2D—to catch it in its earliest stages so as to initiate interventions (or even preventive management) and improve outcomes. This has resulted in the understanding (and approved use) of novel biomarkers as well as the increased utilization of vascular measurements to predict cardiovascular (CV) events in patients of T2D before they become irreversible. CV events are defined as: all-cause mortality, myocardial infarction (MI) or coronary revascularization (stent placement).8

In 2009, a pan-European research consortium  was developed to identify markers that predicted the risks of chronic micro and macrovascular complications of T2D and CVD. This consortium was named SUMMIT (SUrrogate markers for Micro and Macrovascular hard endpoints for Innovative diabetes Tools)  and has been responsible for numerous peer reviewed publications as well increasing understanding of diabetic complications in various organs including the eye, heart, and the nervous system through non-invasive imaging techniques, animal models and genetic markers to gain better knowledge of managing both T2D and CVD.9

Recently, the SUMMIT investigators  evaluated results of vascular imaging, functional assessments, and novel biomarkers to find markers for CV events in individuals with T2D with or without CVD. They titled this study the SUMMIT VIP study.10 It was composed of a cohort of 936 individuals with T2D of which 440 were diagnosed with CVD at baseline. The subjects were assessed by established imaging techniques for carotid intima thickness (CIMT) and plaque, ankle-brachial pressure index, and arterial stiffness. Novel CV biomarkers were used to evaluate endothelial function. These markers included: interleukin 6 (IL-6), chemokine ligand 3, pentraxin 3 and hs-CRP. Other endothelial markers included hepatocyte growth factor and vascular endothelial growth factor A.

The findings of this study showed:10

  • A significantly increased rate for CV events was predicted in those subjects with T2D and CVD
    • (5.53 vs 2.15/100 life-years; P<0.0001)
  • In patients with T2D and CVD at baseline, there was an association with the raised baseline levels of inflammatory and endothelial biomarkers and CV events
  • In patients without CVD at baseline, there was (only) an association with more severe baseline atherosclerosis
  • CV events were not associated with conventional risk factors, arterial stiffness, or endothelial reactivity

Why is this Clinically Relevant?

  • The results of this study have delineated the type of CV events and risk for patients of T2D with, and without, concurrent CVD10
    • Patients with T2D and CVD have raised levels of inflammatory and endothelial markers which predict potential for CV events
    • Patients with T2D and no CVD have a greater association for atherosclerosis and no overt prediction for CV events
  • Healthcare providers should be able to develop appropriate management plans for their patients with T2D to improve or optimize long term outcomes
    • In patients with T2D and CVD
      • These patients are at increased risk for major adverse cardiovascular events (MACE) which include all-cause mortality, myocardial infarction or coronary revascularization
        • Clinicians can encourage such patients to reduce/eliminate modifiable risk factors such as smoking, obesity and overweight, poor nutritional and dietary intake as well as increasing physical activity
      • For optimal outcomes, these patients should be monitored regularly for compliance and adherence
    • In patients with T2D with early or no CVD
      • These patients are at increased risk for atherogenesis and increased arterial plaque
        • HCPs should focus on reducing atherogenesis by managing dysglycemia and insulin resistance by weight reduction, smoking cessation, improving dietary and nutritional intake and recommending increased activity
      • To ensure improved outcomes and possible regression/reversal of T2D, patients should be monitored regularly for compliance and adherence

View the abstract

Citations

  1. CDC. Diabetes. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf Accessed August 16, 2018.
  2. CDC. Heart Disease. https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_disease.htm Accessed August 16, 2018.
  3. Heart.org. Cardiovascular Disease. https://www.heart.org/en/health-topics/diabetes/why-diabetes-matters/cardiovascular-disease–diabetes Accessed August 16, 2018.
  4. Hu FB, Stampfer MJ. Insulin resistance and hypertension: The chicken-egg question revisited. Circulation. 2005; 112:1678-1680.
  5. Welborn TA, Breckenridge A, Rubinstein AH, et al. Serum-insulin in essential hypertension and in peripheral vascular disease. Lancet. 1966;1:1336–1337.
  6. Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015;58(5):886-899.
  7. Barnes AS, Coulter SA. The epidemic of obesity and diabetes: trends and treatments. Tex Heart Inst J. 2011;38(2):142-144.
  8. MD Calc. Heart Score. https://www.mdcalc.com/heart-score-major-cardiac-events   Accessed August 16, 2018
  9. Innovative Medicines Initiative. http://www.imi-summit.eu/ Accessed August 16, 2018.
  10. 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. Diabetes Care. 2018. doi: 10.2337/dc18-0185. [Epub ahead of print].

 

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