Prognostic Role of Hypertriglyceridemia in Patients With Stroke of Atherothrombotic Origin

Neurology. 2022 Apr 19;98(16):e1660-e1669. doi: 10.1212/WNL.0000000000200112. Epub 2022 Mar 16.


Background and objectives: Hypertriglyceridemia is perceived to promote atherosclerotic pathology, but its role in stroke has not been well defined. Our aim was to assess the contribution of hypertriglyceridemia to residual vascular risk in patients with atherothrombotic stroke.

Methods: The Tokyo Women's Medical University Stroke Registry is an ongoing prospective, observational registry in which 870 patients with acute ischemic stroke or TIA within 1 week of onset were consecutively enrolled and followed up for 1 year. Hypertriglyceridemia was defined as serum triglycerides levels of ≥150 mg/dL under fasting conditions. Significant stenosis of the cervicocephalic arteries was defined as having ≥50% stenosis or occlusion. The primary outcome was major adverse cardiovascular events, including nonfatal stroke, nonfatal acute coronary syndrome, and vascular death.

Results: Of 870 patients (mean age 70.1 years, male 60.9%), 217 (24.9%) had hypertriglyceridemia. High triglycerides levels were significantly associated with an increased prevalence of intracranial artery stenosis, particularly in the anterior circulation, rather than extracranial artery stenosis. Patients with hypertriglyceridemia had a greater risk of major adverse cardiovascular events than those without (annual rate 20.9% vs 9.7%; p < 0.001), even after adjustment for potential confounders, including baseline low-density lipoprotein cholesterol and statin use (adjusted hazard ratio 2.46, 95% CI 1.62-3.74). The higher risk of vascular events in patients with hypertriglyceridemia vs without hypertriglyceridemia was observed among patients with stroke of atherothrombotic origin (n = 174, annual rate 35.1% vs 14.2%; p = 0.001), those with significant intracranial artery stenosis (n = 247, annual rate 29.9% vs 14.7%; p = 0.006), and those with significant extracranial carotid artery stenosis (n = 123, annual rate 23.0% vs 9.4%; p = 0.042). In contrast, hypertriglyceridemia was not predictive of recurrent vascular events in patients with cardioembolic stroke (n = 221, annual rate 19.1% vs 10.5%; p = 0.18).

Discussion: Hypertriglyceridemia is an important modifiable risk factor that drives residual vascular risk in patients with stroke of atherothrombotic origin, even while on statin therapy.

Trial registration information: UMIN000031913 at

Classification of evidence: This study provides Class I evidence that in patients with atherothrombotic stroke, hypertriglyceridemia is associated with an increased risk of major cardiovascular events.

MeSH terms

  • Aged
  • Constriction, Pathologic / complications
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Hypertriglyceridemia* / complications
  • Hypertriglyceridemia* / epidemiology
  • Ischemic Stroke*
  • Male
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Stroke* / complications
  • Stroke* / epidemiology
  • Triglycerides


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Triglycerides

Associated data

  • UMIN-CTR/UMIN000031913