High Ratio of Non-HDL Cholesterol to HDL Cholesterol Associated With Heightened Hypertension, Heart Disease Risk

The ratio of high-density lipoprotein cholesterol (HDL-C) to non-HDL-C, called NHHR, is closely associated with a heightened risk of developing hypertension and various heart diseases, according to the investigators of a nationally representative trial conducted among adults ages 45 and older in China. The results, published in Aging Clinical and Experimental Research, provide further context surrounding the use of NHHR as a novel lipid marker for poor cardiovascular outcomes.¹

High levels of LDL cholesterol can obstruct blood flow and clog arteries. | Image Credit: © Kien - stock.adobe.com

Both hypertension and heart disease represent major global health concerns. NHHR can provide further insight into lipid metabolism, a key factor in elucidating cardiovascular risk factors, and acts as a more comprehensive lipid indicator by reflecting the balance between harmful and protective cholesterol. Studies have found an association between NHHR and myriad health conditions, including hypertension and cardiovascular diseases. Furthermore, investigations among the US population have indicated that NHHR is positively correlated with hypertension and cardiovascular mortality.^2,3

Given the global risks that hypertension and heart disease pose, it is critical to evaluate data from other populations to validate such an association. Unfortunately, there is a lack of related research in different populations around the world to corroborate the research in Americans. The authors of the current study sought to rectify this lack of data by leveraging data from the China Health and Retirement Longitudinal Study (CHARLS) to assess the association between NHHR and the incidence of hypertension and cardiovascular disease over a 7-year follow-up period.¹

Study investigators utilized data from the 2011 population survey results of CHARLS as a baseline and subsequently examined the incidence of hypertension and heart diseases among enrollees through follow-up surveys in 2013, 2015, 2018, and 2020. The primary outcomes of the analysis were new-onset hypertension and heart diseases—including stroke—at each of the respective follow-up years. Self-reported doctor diagnoses and the reported use of antihypertensive or other treatment were used to determine the incidence of hypertension or heart disease.¹

In total, 5349 participants were included, with an average age of 57.78 years. Across the follow-up surveys conducted from 2013 to 2010, 1631 patients (30.5%) were diagnosed with hypertension. The highest event ratio was observed in patients with high NHHR (34.7%), followed by medium NHHR (29.4%) and low NHHR (27.1%). This statistically significant association between NHHR and hypertension was consistent across multiple regression models, indicating its strength. Correspondingly, 1233 participants (23.1%) were diagnosed with new-onset heart diseases during the follow-up period, and the incidence rate—similarly to new-onset hypertension—rose as NHHR levels rose. Patients with high NHHR (34.2%) had the highest incidence, followed by medium NHHR (23.2%) and low NHHR (13.5%) patients.¹

Noting its status as a novel lipid indicator, the investigators also compared NHHR with low-density lipoprotein cholesterol (LDL-C), HDL-C, and non-HDL-C regarding their respective associated risks of hypertension and heart disease. According to the comparison, an increase in NHHR was associated with the highest risk of new-onset heart diseases (OR = 1.651; 95% CI, 1.569-1.737; P < .001) and hypertension (OR = 1.263; 95% CI, 1.209-1.319; P < .001), followed by non-HDL-C and LDL-C. The investigators confirmed these results using partially adjusted and fully adjusted models, which exhibited the same trends.¹

Unlike other complex marks, NHHR can be easily calculated by utilizing standard lipid panel results, which the study authors describe as a major benefit compared with more complex markers and make it a practical tool for standard use. Furthermore, due to its inclusion of both non-HDL-C and HDL-C, it provides a thorough lens into a patient’s metabolism compared with using one indicator alone, according to the investigators.¹

“In the prevention and treatment of heart diseases, managing both lipid levels and blood pressure is crucial,” the study authors wrote in their conclusion. “Further studies on improving NHHR could be beneficial for preventing hypertension and heart diseases.”¹

REFERENCES

1. Zhang F, Li Z, Wang M, Wang Y, Lu C. Association of non-highdensity lipoprotein cholesterol to highdensity lipoprotein cholesterol ratio (NHHR) and subsequent hypertension and heart diseases: findings from the CHARLS cohort. Aging Clin Experi Research. 2025;37(26). doi:10.1007/s40520-024-02919-z

2. Wu J, Guo J. Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and hypertension in American adults: a NHANES cross-sectional study. Front Physiol. 2024;15. doi:10.3389/fphys.2024.1398793

3. Yu B, Li M, Yu Z, et al. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999–2018. BMC Med. 2024;22(317). doi:10.1186/s12916-024-03536-3