Increased visceral adipose tissue as a potential risk factor in patients with embolic stroke of undetermined source (ESUS)

Abstract

Purpose: The etiology of an ischemic stroke remains undetermined in 20-35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke.

Methods: Altogether 58 patients (mean age 57.7 ± 10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered.

Results: Mean VAT area was significantly higher in stroke patients (205 ± 103 cm2 for men and 168 ± 99 cm2 for women) compared to all reference populations (P < 0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors.

Conclusion: Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients.

Fig 1. Flow chart of patient recruitment.

Neurologists recruited consecutive patients with acute ischemic stroke/TIA with undetermined etiology or a suspicion of cardiogenic etiology. Stroke/TIA patients with atrial fibrillation were excluded. Patients who had undergone the assessment of visceral adipose tissue were included in the current study. Six patients were excluded from the study due to technically unsuccessful assessment of stroke etiology. The remaining patients were further categorized according to the modified TOAST classification, denoting five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) embolic stroke of undetermined source (ESUS). The classification was updated by applying the more recent EAE recommendations for defining cardiac sources of embolism.

Fig 2. The image illustrates how the area of visceral adipose tissue (VAT) within the abdominal cavity (white line) was determined by CT scanning.

Pixels with the density of adipose tissue between −30 and −190 Hounsfield Units (HU) were included in the VAT area calculated automatically by the CT software. In the illustrative case, the VAT area is 110 cm².

Fig 3. Age adjusted mean values and their 95% confidence intervals of visceral adipose tissue (VAT) and the conventional risk factors in patients with ESUS compared to the three control populations.

Statistically significant differences between patients with ESUS and reference populations are marked by * (p<0.05) and ** (p<0.01).

Fig 4. Patient examples with the same body mass index (BMI) and normal or increased (>188.4 cm² for men) areas of visceral adipose tissue (VAT).

(A) Male, age 69 years, BMI 25 kg/m², VAT area 80 cm². (B) Male, age 71 years, BMI 25 kg/m², VAT area 230 cm².