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Research Article: Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), atherogenic index of plasma and acute ischemic stroke classified by CISS

Date Published: 2026-07-23

Abstract:
Dyslipidemia is a significant contributor to ischemic stroke. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the atherogenic index of plasma (AIP) are emerging indicators of cardiovascular risk. However, the relationship between NHHR and AIP in the context of ischemic stroke subtypes, as classified by the Chinese ischemic stroke subclassification (CISS) system, warrants further investigation. Additionally, the roles of NHHR and AIP in relation to hypertension or diabetes within these ischemic stroke subtypes remain unclear. Therefore, this study aims to elucidate the connections among them. Patients diagnosed with acute ischemic stroke subtypes of large artery atherosclerosis (LAA) and penetrating artery disease (PAD) according to the CISS classification criteria from 2018 to 2022 at the Department of Neurology, Renmin Hospital of Wuhan University, were selected for analysis. We compared baseline demographic information, past medical history, and biochemical test results. Multivariable logistic regression analysis was employed to investigate the association between NHHR and AIP with acute ischemic stroke subtypes. Receiver operating characteristic (ROC) analysis was utilized to assess the diagnostic value of these factors for acute ischemic stroke subtypes. Mediation analyses were conducted to determine whether NHHR and AIP mediate the relationship between exposure variables (hypertension and diabetes) and outcomes (LAA and PAD subtypes). Univariate analysis revealed significant differences between the acute ischemic stroke subtype group and the non-stroke group regarding NHHR, AIP, gender, age, total bilirubin, direct bilirubin, high-sensitivity C-reactive protein, lipoprotein (a), diabetes, hyperhomocysteinemia, and hypertension ( p <?0.05). In the multivariable logistic regression analysis, after adjusting for potential confounders, NHHR was found to be significantly associated with both LAA subtype (odds ratio [OR]?=?1.323, 95% confidence interval [CI]: 1.131–1.547, p <?0.001) and PAD subtype (OR?=?1.195, 95% CI: 1.001–1.425, p =?0.048). AIP was significantly related to LAA subtype (OR?=?2.045, 95% CI: 1.094–3.823, p =?0.025), while the association with PAD subtype (OR?=?1.740, 95% CI: 0.857–3.531, p =?0.125) was not statistically significant. NHHR appears to play a marginal role in mediating the potential effects of hypertension or diabetes on LAA subtypes. Specifically, hypertension has a minor impact on LAA subtype mediated by NHHR, with an average causal mediation effect (ACME) of 0.007 and a proportion mediated (PM) of 3.0%. Meanwhile, diabetes has a relatively larger impact on LAA subtypes mediated by NHHR, with an ACME of 0.017 and a PM of 10.0%. Elevated NHHR is a significant risk factor for the occurrence of both LAA and PAD subtypes according to the CISS criteria, whereas AIP is solely associated with LAA subtypes. Additionally, increased levels of NHHR mediate the relationship between hypertension, diabetes, and LAA subtypes.

Introduction:
Dyslipidemia is a significant contributor to ischemic stroke. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and the atherogenic index of plasma (AIP) are emerging indicators of cardiovascular risk. However, the relationship between NHHR and AIP in the context of ischemic stroke subtypes, as classified by the Chinese ischemic stroke subclassification (CISS) system, warrants further investigation. Additionally, the roles of NHHR and AIP in relation to hypertension…

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