# Triglyceride-to-HDL Cholesterol Ratio Is Associated with Ischemic Stroke Risk in Patients—With Paroxysmal Atrial Fibrillation

**Authors:** Ciprian Ilie Rosca, Daniel Florin Lighezan, Doina Georgescu, Horia Silviu Branea, Nilima Rajpal Kundnani, Ariana Violeta Nicoras, Romina Georgiana Bita, Daniel Dumitru Nisulescu

PMC · DOI: 10.3390/metabo16020110 · Metabolites · 2026-02-03

## TL;DR

This study shows that a high triglyceride-to-HDL cholesterol ratio is linked to a greater risk of ischemic stroke in patients with paroxysmal atrial fibrillation.

## Contribution

The study introduces TG/HDL-C as a potential biomarker to improve stroke risk stratification in PAF beyond existing clinical scores.

## Key findings

- Patients with a TG/HDL-C ratio > 2.5 had a significantly higher stroke prevalence (37.4% vs. 21.1%).
- Elevated TG/HDL-C was associated with a 68% higher hazard of first ischemic stroke.
- TG/HDL-C > 2.5 was independently linked to type 2 diabetes, hyperuricemia, and cortical atrophy.

## Abstract

Background: Ischemic stroke remains the most feared complication of atrial fibrillation (AF), and thromboembolic risk is commonly estimated using clinical scores that may not fully capture the cardiometabolic dimension of cerebrovascular vulnerability. The aim of this research was to assess whether additional parameters can be used, to predict ischemic stroke risk in patients with AF, in order to explore whether TG/HDL-C may complement conventional clinical risk scores for ischemic stroke risk stratification in PAF, and to better characterize a metabolically high-risk phenotype beyond the recommendations provided by the CHA2DS2-VA score, which is useful but still far from perfect in predicting AF-associated ischemic stroke risk. Methods: In this retrospective, single-center observational study, we evaluated whether the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDLc), a simple surrogate of atherogenic dyslipidemia and insulin resistance, is associated with ischemic stroke risk in patients with paroxysmal atrial fibrillation (PAF). We screened 1111 consecutive AF admissions between 1 January 2015 and 31 December 2016 and, from these 1111 AF cases, we extracted only the patients with PAF for analysis. Patients were stratified based on TG/HDLc values into two groups, Group 1 (TG/HDLc > 2.5; n = 155) and Group 2 (TG/HDLc < 2.5; n = 194). Statistical analysis was performed with MedCalc v23.4.0 using Chi-square and unpaired/Welch’s t-tests as appropriate, Pearson correlations, Kaplan–Meier analysis with log-rank testing, Cox regression for first ischemic stroke, and multivariable logistic regression to identify independent correlates of TG/HDLc > 2.5. Results: Patients with TG/HDLc > 2.5 had a significantly higher prevalence of ischemic stroke after AF onset compared with those with TG/HDLc < 2.5 (37.4% vs. 21.1%, p = 0.0008), despite similar CHA2DS2-VA and HAS-BLED scores, and also exhibited a higher burden of cerebrovascular and neurodegenerative findings, including cortical atrophy and cerebral lacunarism. Ischemic stroke-free survival curves diverged significantly over time (log-rank p = 0.0186), and an elevated TG/HDLc ratio was associated with a 68% higher hazard of first ischemic stroke (HR 1.68; 95% CI 1.09–2.60). In multivariable analysis, type 2 diabetes mellitus (OR 4.53), hyperuricemia (OR 3.83), dyslipidemia (OR 1.94), stroke (OR 1.77), and cortical atrophy (OR 4.48) were independently associated with TG/HDLc > 2.5. Conclusions: These findings suggest that TG/HDLc identifies a metabolically high-risk PAF phenotype associated with greater cerebrovascular burden and reduced ischemic stroke-free survival, providing an inexpensive and broadly available marker that may complement conventional clinical risk scores.

## Linked entities

- **Diseases:** ischemic stroke (MONDO:1060198), atrial fibrillation (MONDO:0004981), paroxysmal atrial fibrillation (MONDO:1030011), type 2 diabetes mellitus (MONDO:0005148), hyperuricemia (MONDO:0002144), dyslipidemia (MONDO:0002525)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, COG2 (component of oligomeric golgi complex 2) [NCBI Gene 22796] {aka CDG2Q, LDLC}
- **Diseases:** MetSy (MESH:D024821), carotid atheromatosis (MESH:D016893), varicose veins (MESH:D014648), tophaceous disease (MESH:D004194), cerebrovascular and neurodegenerative lesions (MESH:D019636), injury to (MESH:D014947), inflammation (MESH:D007249), chronic coronary syndrome (MESH:D054058), PD (MESH:D010300), Paroxysmal (MESH:D002819), mitochondrial dysfunction (MESH:D028361), Dyslipidemia (MESH:D050171), heart valve (MESH:D006349), Vascular disease (MESH:D014652), Diabetes (MESH:D003920), bronchial asthma (MESH:D001249), Hemorrhagic strokes (MESH:D000083302), anxiety (MESH:D001007), cortical atrophy (MESH:D001284), disturbances in glucose metabolism (MESH:D044882), neuroinflammation (MESH:D000090862), cardiac arrhythmia (MESH:D001145), Bleeding (MESH:D006470), obese (MESH:D009765), Stroke (MESH:D020521), overweight (MESH:D050177), COPD (MESH:D029424), mitral stenosis (MESH:D008946), neurological deficit (MESH:D009461), cerebral microangiopathy (MESH:D059345), metabolic dysfunction (MESH:D008659), Cerebral microvascular injury (MESH:D017566), thrombosis (MESH:D013927), atherogenic (MESH:D050197), brain lesions (MESH:D001927), Hypertension (MESH:D006973), venous thromboembolism (MESH:D054556), hypothyroidism (MESH:D007037), AF (MESH:D001281), Ischemic Stroke (MESH:D002544), Cardiovascular comorbidities (MESH:D002318), congestion (MESH:D002311), Insulin resistance (MESH:D007333), deep vein thrombosis (MESH:D020246), cerebrovascular complications (MESH:D002561), endothelial injury (MESH:D057772), Congestive heart failure (MESH:D006333), kidney disease (MESH:D007674), depressive disorders (MESH:D003866), T2DM (MESH:D003924), dementia (MESH:D003704), coronary artery disease (MESH:D003324), Thromboembolic (MESH:D013923), Abnormal renal and liver function (MESH:D056486), lipid abnormality (MESH:D011017), H (MESH:D000848), Hyperuricemia (MESH:D033461), hypertriglyceridemia (MESH:D015228), HFpEF (MESH:D054144), cerebral lacunarism (MESH:D059409)
- **Chemicals:** TGs (MESH:C026285), alprazolam (MESH:D000525), uric acid (MESH:D014527), TG (MESH:D014280), metformin (MESH:D008687), branched-chain amino acids (MESH:D000597), blood glucose (MESH:D001786), ceramides (MESH:D002518), Cholesterol (MESH:D002784), nitric oxide (MESH:D009569), ACEI (-), Propafenone (MESH:D011405), Na (MESH:D012964), TG (MESH:D013866), K (MESH:D011188), furosemide (MESH:D005665), acylcarnitines (MESH:C116917), spironolactone (MESH:D013148), Lipid (MESH:D008055), alcohol (MESH:D000438), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942535/full.md

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Source: https://tomesphere.com/paper/PMC12942535