Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease

Background: The obesity paradox refers to the finding in observational studies that patients with obesity have a better prognosis after stroke than normal weight patients.

Aim: To test the hypothesis that there might be important heterogeneity within the obese stroke population, such that those with metabolic syndrome would be at higher risk for stroke or myocardial infarction and all-cause mortality compared to patients without metabolic syndrome.

Methods: The Insulin Resistance Intervention after Stroke trial enrolled non-diabetic patients with a recent ischemic stroke or transient ischemic attack and insulin resistance. We examined the association between metabolic syndrome and outcome risk in patients with normal weight at entry (body mass index (BMI) = 18.5-24.9 kg/m²), overweight (BMI = 25-29.9 kg/m²), or obesity (BMI ≥ 30 kg/m²). Analyses were adjusted for demographic features, treatment assignment, smoking, and major comorbid conditions.

Results: Metabolic syndrome was not associated with greater risk for stroke or myocardial infarction among 1536 patients who were overweight (adjusted hazard ratio (HR), 0.95; 95% confidence interval (CI): 0.69-1.31) or 1626 obese patients (adjusted HR, 1.00; 95% CI: 0.70-1.41). However, among 567 patients with a normal BMI, metabolic syndrome was associated with increased risk for stroke or myocardial infarction (adjusted HR, 2.05; 95% CI: 1.25-3.37), and all-cause mortality (adjusted HR, 1.70; 95% CI: 1.03-2.81) compared to patients without metabolic syndrome.

Conclusions: The presence of metabolic syndrome identified normal weight patients with insulin resistance but no diabetes who have a higher risk of adverse cardiovascular outcomes, compared with patients without metabolic syndrome.