Greater Non-HDL/HDL Cholesterol Ratio Linked to Lower Anemia Rates

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A study showed an inverse correlation between the non-HDL cholesterol to HDL cholesterol ratio and the prevalence of anemia in US adults.¹

“[This suggests] that lower [non-HDL cholesterol to HDL cholesterol ratio] could be a factor in the heightened occurrence of anemia,” wrote investigators, led by Nengneng Cao, MS, from the department of hematology at the Second Affiliated Hospital of Anhui Medical University, in China. “Concurrently, the study unveiled a threshold effect value of 4.28 for the NHHR when assessing its connection with anemia.”

The non-HDL cholesterol to HDL cholesterol ratio is a newly developed metric that can assess the risk for atherosclerosis, chronic kidney disease, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). The association between non-HDL cholesterol to HDL cholesterol ratio and anemia was under-evaluated.

Prior studies have shown the correlation between blood lipid abnormalities and anemia, with low-density lipoprotein (LDL) receptor activity in anemic patients negatively correlated with plasma cholesterol levels.² Research has suggested underlying mechanisms of this correlation include the change in serum cholesterol levels include altered absorption, abnormal synthesis, and changes in excretion, dilution, and redistribution. Studies have also indicated that high-density lipoprotein cholesterol (HDL-C) may contribute to iron-induced damage to kidney tissues in patients with diabetes, which can lead to chronic anemia.³

Investigators sought to investigate the connection between non-HDL cholesterol to HDL cholesterol ratio and the prevalence of anemia, along with their potential interactions.¹ Leveraging data from 4 NHANES cycles spanning from 2009 – 2010 to 2015 – 2026, the study included 17,019 participants with anemia defined by a hemoglobin level (g/dL) of <12 for women and <13 for men. Participants were excluded if they were < 20 years old, had missing non-HDL cholesterol to HDL cholesterol ratio data, no hemoglobin data, were pregnant, and did not have other covariates.

Covariates included gender, age, race, education level, marital status, familial income-to-poverty ratio, alcohol intake, smoking, body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Lactate dehydrogenase (LDH), potassium, albumin, uric acid, serum iron, calcium, diabetes, creatinine, and hypertension. Among the participants (n = 17,019), 15,285 were non-anemic, and the average age was 48.73 ± 17.40 years with 51.29% males. The non-anemia group and anemia group had a statistically significant difference in their mean non-HDL cholesterol to HDL cholesterol ratio which was 2.98 ± 1.47 and 2.54 ± 1.24, respectively. The study also revealed statistical differences between non-anemic and anemic groups for all covariates.

After adjusting for covariates, the model demonstrated showed an incremental increase in the non-HDL cholesterol to HDL cholesterol ratio correlates with a 18% decrease in the prevalence of anemia, indicating a strong inverse relationship (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78 – 0.86). The significance remained after segmenting the non-HDL cholesterol to HDL cholesterol ratio into quartiles. The anemia prevalence was 51% lower among participants in the highest quartile of non-HDL cholesterol to HDL cholesterol ratio compared with the participants in the lowest quartile (odds ratio [OR], 0.49; 95% CI, 0.41 – 0.59; P < .0001).

Another analysis showed a threshold effect value of 4.28 for the potential relationship between the non-HDL cholesterol to HDL cholesterol ratio and anemia. If the non-HDL cholesterol to HDL cholesterol ratio falls under 4.28, the anemia prevalence drops by 15% for every unit increase (OR, 0.75; 95% CI, 0.71 – 0.81). Furthermore, there was no drastic change in the anemia prevalence when the non-HDL cholesterol to HDL cholesterol ratio was above 4.28.

“…after reaching this inflection point, the correlation became statistically insignificant,” investigators wrote.

A subgroup analysis revealed alcohol consumption significantly affects the relationship between non-HDL cholesterol to HDL cholesterol ratio and anemia (P < .05).

“These findings highlight NHHR’s importance in managing anemia,” investigators concluded. “However, validation of these findings necessitates additional large-scale prospective studies.”

References

1. ^{Cao N, Wang J, Zhu J, Jiao X, An F, Zhai Z. The relationship between non-HDL cholesterol to HDL cholesterol ratio (NHHR) and anemia: A cross-sectional study of NHANES, 2009 to 2016. Medicine (Baltimore). 2024 Dec 13;103(50):e40976. doi: 10.1097/MD.0000000000040976. PMID: 39686411; PMCID: PMC11651433.}
2. ^{Atac B, Brahaj D, Frishman WH, Lerner R. Anemia and hypocholesterolemia. Heart Dis. 2003;5:65–71.}
3. ^{Strazzella, A., Ossoli, A., & Calabresi, L. High-density lipoproteins and the kidney. Cells. 2021.}