According to the investigators of a study published in _Experimental Gerontology_, a high ratio of non-high-density lipoprotein cholesterol (HDL-C) to high-density lipoprotein cholesterol, called NHHR, was significantly associated with a heightened risk of sarcopenia in US adults.1
NHHR is emerging a novel biomarker for various conditions, including heart disease. | Image Credit: © Anusorn - stock.adobe.com
Sarcopenia, a progressive skeletal order that involves the accelerated loss of muscle mass and function, is associated with adverse outcomes such as functional decline, frailty, and mortality, according to experts. Although it is typically diagnosed in older adults, sarcopenia has been increasingly observed among younger patients due to changing lifestyle habits among the age group, necessitating a greater understanding among treatment providers as to the novel biomarkers that may indicate this condition.2,3
NHHR has begun to emerge as a novel lipid indicator with the potential to transform the diagnosing process of multiple diseases due to its ease of calculation—NHHR can be determined by using standard lipid panel results, making it a practical tool. Prior literature indicates that NHHR is a strong predictor for myriad conditions, including cardiovascular outcomes such as hypertension and heart disease. Still, a gap in research exists regarding the specific role of NHHR in the development of sarcopenia, one which the current investigators sought to fill through a retrospective analysis.1,4
The study authors examined data from 7069 participants that was garnered through use of the National Health and Nutrition Examination Survey (NHANES), a continuous, cross-sectional study conducted in coordination with the CDC. Patients aged 20 years or older who had undergone observations for blood lipid profiles, body mass index (BMI), and dual-energy X-ray absorptiometry (DXA) were included. DXA is used to quantify appendicular lean mass (ALM)—the sum of muscle mass in the 4 limbs—which is an indicator for sarcopenia.1
Key baseline characteristics were described by the authors. Sarcopenia was reported in 572 members of the study cohort (8.1% of the total population); median NHHR value was meaningfully higher (_P_ < .001) in patients with sarcopenia (3.18; IQR: 2.37-4.15) compared with those without sarcopenia (2.64; IQR: 1.89-3.66). Interestingly, there were large disparities in patient characteristics between those with and without sarcopenia, including BMI, smoking status, and alcohol consumption.1
Aligning with the hypothesis of the investigators, an unadjusted analysis indicated that higher NHHR was significantly linked with an increased risk of sarcopenia (OR: 2.188; 95% CI, 1.800-2.659; _P_ < .001). In their second model, the association retained statistical significance, even after adjusting for age and gender (OR: 2.202; 95% CI, 1.810–2.678; _P_ < 0.001). In the final model, which included further adjustments for covariates, each unit increase in NHHR was associated with a 32.2% increase in the risk of sarcopenia (OR: 1.322; 95% CI, 1.040–1.679; _P_ = 0.024), according to the investigators.1
Subgroup analyses were conducted to determine possible disparities in the association between NHHR and sarcopenia risk within specific demographic groups. In a notable discovery, the association between NHHR and the risk of sarcopenia was consistently significant across all stratified subgroups (_P_ < .05), with the only exception being participants with a BMI of 30 or more (_P_ = .412). In addition, the authors observed major interactions between NHHR levels and drinking status, BMI, and marital status.1
“The implications of this association are particularly noteworthy for the development of primary prevention strategies targeting individuals who are at an elevated risk of sarcopenia,” the investigators wrote in their conclusion. “Future research should focus on the pathophysiological processes that may explain how alterations in lipid profiles contribute to the development of sarcopenia.”1
###### **REFERENCES**
###### 1\. Yang X, Zhong Z. The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and sarcopenia: A cross-sectional study. _Experimental Gerontology_. 2025;200:112680. doi:10.1016/j.exger.2025.112680
###### 2\. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. _The Lancet_. 2019;393(10191):2636-2646. doi:10.1016/S0140-6736(19)31138-9
###### 3\. Jang HN, Hung CH, Hwang YC. Sarcopenia in youth. _Metabolism_. 2023;144:155557. doi:10.1016/j/metabol.2023.155557
###### 4\. Halpern L. High ratio of non-HDL cholesterol to HDL cholesterol associated with heightened hypertension, heart disease risk. _Pharmacy Times_. Published February 27, 2025. Accessed March 7, 2025. https://www.pharmacytimes.com/view/high-ratio-of-non-hdl-cholesterol-to-hdl-cholesterol-associated-with-heightened-hypertension-heart-disease-risk