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Biomarkers to Predict Cardiovascular Events in People with Type 2 Diabetes

Oct 20, 2018
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Arsalan Hashmi, PharmD. Candidate, LECOM College of Pharmacy

The SUMMIT VIP study shows conventional risk factors do not suffice in predicting heart complications.

Diabetes is a well-known risk factor for cardiovascular disease, with people who have diabetes twice as likely to have a MI or stroke. Because of this, all patients who have diabetes were assumed to be at high-risk of developing CV. However, recent studies have shown that subjects with type 2 diabetes do not all have higher risk, but instead the risk must be calculated on an individual basis. Calculating risk for cardiovascular disease has not been successful in patients with type 2 diabetes using conventional methods, and thus new prediction tests for type 2 diabetes are needed to better differentiate those at risk for a CV event. The SUMMIT Vascular Imaging  Prediction was an initiative to study new CV complication markers in patients with type 2 diabetes

At baseline, 458 participants had both type 2 diabetes (T2D) and cardiovascular disease (CVD), and 527 participants only had T2D with no signs of CVD. The diabetes diagnoses had to be within five years of the cardiovascular event. There was patient follow-up after 36 months and cardiovascular events were recorded. Forty-nine patients were lost to follow-up. Plaques in the carotid artery were measured by ultrasound. The average patient had 2.4 plaques with mean height and lengths of 1.9 mm and 11.2 mm respectively. Researchers also assessed atrial hyperemia, which occurred after five minutes of atrial occlusion. The study also examined the blood for biomarkers for a number of conditions pertaining to cardiovascular disease, which were examined by the proximity extension assay technique. X2, student T test and Mann-Whitney U tests were used to test clinical differences between groups, and biomarkers were statistically tested by integrated discrimination improvement.

There were 105 of the 936 subjects  who had a cardiovascular event. There were also 20 deaths from unrelated causes. Those with T2D and CVD at baseline were twice as likely to suffer from a CV event. The subjects who had type 2 diabetes and had CV events did not show increases in traditional CV risk factors, but did have higher HbA1c [HR:1.03 (CI 1.01-1.03)]. Biomarkers for inflammation, on the other hand, were higher in subjects with a CV event. Baseline biomarkers IL-6, CCL3 hs-CRP, among others were elevated. A binary logistic regression model for IL-6, an inflammatory biomarker, was improved significantly by 2.7 points [CI .064-.048].

For patients who had type 2 diabetes without CVD there were no differences in traditional risk factors for those who had a CV event. The intima-media thickness (IMT) and total carotid plaque area were both increased in CV event. There were two raised biomarkers TRAIL receptor 2 and GDF-15, but no elevation in inflammatory biomarkers.

This study reaffirmed that conventional risk factors do not suffice in predicting a cardiovascular event in type 2 diabetes. The presence or absence of cardiovascular disease changes which prediction markers are useful for predicting a CV event. Patients with cardiovascular disease had hs-CRP and inflammatory cytokines, among other factors elevated in their blood at baseline. This group did not have increased atherosclerosis because of medical interventions, but due to other mechanisms. This group was seen to have increased inflammatory biomarkers in the presence of statin therapy. Another study noted that the introduction of antibody IL-1B reduced chances of a CV event in this group.

Those patients without CVD did not have elevated biomarkers besides GDF-15 and apoptosis marker TRAIL receptor 2. The ultrasounds at baseline did reveal increased carotid atherosclerosis as a possible predictor of a cardiovascular event.

This study used both established and emerging biomarkers to better reflect the mechanism of the CV event. Another strength of this study is that it also compared patients who had T2D with and without cardiovascular disease. The study may have been underpowered due to the limited number of CV events in the non-CVD group. This study also used a lower measurement size for what was considered a carotid plaque than previous studies.

Practice Pearls:

  • Recent studies suggest that not all patients with diabetes are at high risk for a cardiovascular event, and that patients should be tested on an individual basis.
  • Patients with type 2 diabetes and cardiovascular disease who had a CV event were seen to have elevated blood proinflammatory biomarkers.
  • Patients who had type 2 diabetes without cardiovascular disease and who had a CV event had carotid plaques, due to the fact that they were not on statin therapy.

Reference:

Shore, Angela C., et al. “Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes: The SUMMIT VIP Study.” Diabetes Care, vol. 41, no. 10, 2018, pp. 2212–2219., doi:10.2337/dc18-0185.

Arsalan Hashmi, PharmD. Candidate, LECOM College of Pharmacy