suPAR stayed raised after a year of intensive treatment in BARI 2D, and predicted events

Design

Ancillary biomarker analysis of a randomised trial (BARI 2D)

Population

2,277 adults with type 2 diabetes and coronary artery disease; 1,978 at one-year landmark

Primary outcome

All-cause death, non-fatal myocardial infarction or non-fatal stroke

Effect

Adjusted HR 1.40 per SD suPAR (95% CI 1.27–1.55); event rates 7.1% to 21.6% across joint classes

In an ancillary analysis of BARI 2D, plasma suPAR and hs-CRP were measured at baseline in 2,277 people with type 2 diabetes and coronary disease, and again at one year in 1,978. The randomised strategies compared insulin sensitisation with insulin provision, and revascularisation with medical therapy.

Over a year hs-CRP fell substantially, from a median of about 2.1 to 1.3 mg/L, but suPAR did not move in any arm. Each standard deviation of suPAR was associated with a 40% higher hazard of death, myocardial infarction or stroke (HR 1.40, 95% CI 1.27–1.55), unchanged after adjustment for hs-CRP. In people whose hs-CRP normalised, baseline suPAR still predicted risk. Combining the two markers separated event rates from 7.1% to 21.6%.

An exploratory finding suggested insulin provision was associated with worse outcomes in the highest suPAR tertile, but that is an interaction test in a secondary analysis and should be treated as a hypothesis. suPAR is not a routine test, and no therapy has been shown to lower it or to change outcomes by doing so.

• Do not read a normalised hs-CRP as proof that residual inflammatory risk has gone in diabetes with coronary disease.
• Keep focus on the established levers of residual risk: LDL cholesterol, blood pressure, smoking and organ-protective drugs.
• Do not order suPAR clinically yet; there is no treatment target or pathway linked to it.
• Treat the insulin-by-suPAR interaction as unproven until it is tested prospectively.

Why it matters

It challenges the assumption that bringing hs-CRP down means inflammation has been dealt with.

Don't overread it

An association with risk does not show that lowering suPAR would prevent events.

The statistics, in plain English

A hazard ratio of 1.40 per standard deviation means each step up the suPAR distribution carried about 40% more risk of an event. The subgroup interaction (P = 0.005) came from an exploratory analysis, so it may be chance and needs confirmation before it guides insulin decisions.

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