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Biomarker Could Warn of CV Event Risk in Absence of Being Overweight

Mary Caffrey
Adding measurement of a key protein during metabolic assessment could help identify those at higher risk of heart attacks and strokes even if they have normal body mass index.
Maintaining a healthy weight is a chief recommendation for avoiding heart attacks, strokes, and type 2 diabetes (T2D). Yet, scientists know there are some people with a body mass index (BMI) above the benchmark for obesity who are nonetheless metabolically healthy. At the same time, there are people who are not overweight who are at risk of having a cardiovascular (CV) event.

In recent years, researchers have looked for biomarkers to identify people in both groups, so that clinicians can customize care for each and prevent CV events in those who might look healthy on the outside.

A study appearing in the September issue of Diabetes Care led by authors from Canada’s McMaster University has identified one such a biomarker: insulin-like growth factor-blinding protein 3 concentration, or IGFBP-3.

The researchers validated a weighted polygenic risk score (PRS) for metabolically “favorable adiposity” using data from 341,872 patient records at the UK Biobank, as well as data from the Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Previous studies using the UK Biobank have identified genetic variants associated with favorable adiposity, in which a person has high body fat but low risk of hypertension, T2D, and heart disease.

The 8197-person ORIGIN trial measured whether patients at high risk for vascular disease who took insulin glargine (Lantus) to achieve glycemic control would reduce CV morbidity and death. The trial also measured whether omega-3 fatty acids could reduce CV mortality in people with impaired fasting glucose, impaired glucose tolerance or early T2D.

The validated PRS was tested against 238 possible biomarkers to see which ones suggested a causal link with T2D or could predict major adverse CV events, such as heart attacks or strokes. Of all the biomarkers tested, only IGFBP-3 was found to have an associated with the PRS:
  • Each 1 unit increase in the PRS predicted a 0.28 standard deviation (SD) decrease in IGFBP-3 blood levels (P < .05/238).
  • Higher IGFBP-3 levels causally increased T2D risk; the odds ratio was 1.26/1 SD genetically IGFBP-3 level (95% CI, 1.07-1.20).
  • Adding IGFBP-3 concentrations to the clinical assessment of metabolic health improved the ability to predict major CV events, with a net reclassification improvement of 11.5% in those at normal weight (P = .004).
“Using IGFBP-3 blood concentrations may improve the risk assessment of cardiometabolic diseases,” the authors wrote.

Reference

Pigeyre M, Sjaarda J, Mao S, et al. Identification of novel causal blood biomarkers linking metabolically favorable adiposity with type 2 diabetes risk. Diabetes Care. 2019;42(9):1800-1808. doi.org/10.2337/dc18-2444.

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