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Ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) (HDL-C/LDL-C) can be used to predict the prognosis of individuals at high risk for cardiovascular disease (CVD) without type 2 diabetes (T2D), with a ratio between 0.3 and 0.5 being the most helpful range for patients in this population, according to new data published by investigators in Chronic Diseases and Translational Medicine.¹

What is the HDL-C/LDL-C Ratio?

Lipid management is a hallmark of CVD prevention and can improve patient prognosis. Patients with T2D have an especially heightened risk of CVD morbidity and mortality and has been directly linked to lipid metabolism. It is essential to identify more valuable lipid indicators for prognosis improvement and primary prevention.^1,2

Accordingly, studies have affirmed that extremely high HDL-C and excessively low LDL-C can increase the risk of adverse prognoses, highlighting the potential role of the HDL-C/LDL-C ratio as a marker of cholesterol control. Controlling HDL-C/LDL-C ratio can be used to prevent coronary heart disease and stroke, with studies indicating that mortality from such diseases is lowest when HDL-C/LDL-C ratio is between 0.4 and 0.6. Critically, the ratio has been shown to be a more accurate predictor of clinical disease compared with individual lipoprotein levels.^3-5

There is a lack of existing research on the HDL-C/LDL-C ratio, especially in populations at high CVD risk. Furthermore, there is limited data on whether such a ratio could be a reliable prognostic biomarker in populations with high CVD risk who both do and do not have T2D. The current authors aimed to address the association between HDL-C/LDL-C ratio and adverse prognoses in populations at high risk for CVD, while comparing its usefulness between populations with and without T2D.¹

This analysis was based on the Fujian Cardiometabolic Diseases and Comorbidities Cohort trial (NCT06102187), which was an observational study conducted between 2017 and 2021 to assess CVD risk. Associations between HDL-C/LDL-C ratio and all-cause mortality were analyzed using restricted cubic spline curves (RCSs), and the investigators then categorized patients into 3 groups using thresholds of 0.3 and 0.5 for low HDL-C/LDL-C (less than 0.3), middle (HDL-C/LDL-C, between 0.3 and 0.5), and high HDL-C/LDL-C (more than 0.5).¹

What is the Ideal HDL-C/LDL-C Ratio for CVD Prevention?

A total of 32,609 participants were included in the cohort. Based on the RCS analysis, a nonlinear U-shaped relationship between HDL-C/LDL-C and the participants’ all-cause mortality was identified. Compared with the other groups, the RCS analysis indicated that the middle group had the lowest all-cause mortality risk. Kaplan-Meier survival analysis revealed that cumulative all-cause mortality rate was higher in the low and high groups than in the middle group (P < .05), which was verified by a Cox proportional analysis.¹

Additionally, the risk of all-cause mortality (hazard ratio [HR] = 1.40 [95% CI, 1.08—1.82], P < .05 for low; HR = 1.41 [95% CI, 1.15—1.71], P < .01 for high) was greater in the low and high groups than in the middle group in the univariate analysis. When the investigators controlled for covariates, the risk of all-cause mortality (HR = 1.48 [95% CI, 1.14—1.93], P < .01 for low; HR = 1.30 [95% CI, 1.06—1.58], P < .05 for high) was elevated in both groups.¹

The investigators specifically examined associations between HDL-C/LDL-C and all-cause mortality in individuals with and without type 2 diabetes. Kaplan-Meier analyses revealed that the middle group without T2D presented the lowest cumulative all-cause mortality, while no statistically significant differences in all-cause mortality were observed across subgroups in populations at high CVD risk with T2D. Concurrently, Cox proportional hazards regression analysis demonstrated greater risk of all-cause mortality in the low and high ratio groups than in the middle group.¹

Because HDL-C and LDL-C are widely available and simple-to-measure biomarkers, pharmacists and clinicians can easily calculate the ratio necessary to determine patient CVD prognosis. It is critical that the authors noted a range of a ratio of 0.3 to 0.5 was the most beneficial for patients, allowing pharmacists to specifically tailor treatment strategies and help patients reach their goals. Above all, another indicator that can provide early intervention in populations at high CVD risk is critical for primary prevention.¹

“Maintaining HDL-C/LDL-C ratios within the range of 0.3–0.5 may have clinical significance for cohorts without T2D, whereas its prognostic implications in individuals with T2DM necessitate further exploration,” the study authors wrote in their conclusion.¹

REFERENCES

1. Lin B, Ling Y, Zhou G, et al. HDL-C/LDL-C ratio and all-cause mortality in populations at high CVD risk: A prospective observational cohort study. Chronic Dis Transl Med. 2025;11(3):213-223. doi:10.1002/cdt3.70013

2. Haas ME, Attie AD, Biddinger SB. The regulation of ApoB metabolism by insulin. Trends Endrocrinol Metab. 2013;24(8):391-397. doi:10.1016/j.tem.2013.04.001

3. You S, Zhong C, Zu J, et al. LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage. Neurol Res. 2016;38(10):903-908. doi:10.1080/01616412.2016.1204797

4. Zimmer F, Riebeling V, Benke B, Schuster J, Roskamm H. The LDL-HDL ratio in patients with coronary arteriosclerosis. Z Kardiol. 1980;69(3):149-153. PMID: 7456590. https://pubmed.ncbi.nlm.nih.gov/7456590/

5. Sun T, Chen M, Shen H, et al. Predictive value of LDL/HDL ratio in coronary atherosclerotic heart disease. BMC Cardio Disord. 2022;22(273). doi:10.1186/s12872-022-02706-6

6. Cohort study in Fuijan province. ClinicalTrials.gov Identifier: NCT06102187. Last Updated November 3, 2023. Accessed October 13, 2025. https://clinicaltrials.gov/study/NCT06102187

Data published in the Journal of Clinical Investigation demonstrated that patients with asthma have significantly elevated levels of cyclic adenosine monophosphate (cAMP), a certain molecule within the blood. With this discovery, the researchers determined that a simple blood test may be able to diagnose asthma and its severity, which could be significant when identifying and monitoring patients with asthmatic symptoms.^1,2

The authors wrote that β2-agonists are cornerstone treatments of asthma when attempting to prevent or reverse the shortening of human airway smooth muscle (HASM), the pivotal cell regulating bronchomotor tone. β2-agonists act upon β2-adrenoceptor (β2AR) and activate adenylyl cyclase, which generates 3′,5′-cAMP. An increase in intracellular cAMP levels stimulates protein kinase A, which modulates multiple downstream targets to promote HASM relaxation and reverse airflow obstruction.¹

To further explore the clinical utility of detecting circulating cAMP, the authors conducted their study to measure cAMP levels in a serum biobank from the Severe Asthma Research Program 3 (SARP-3). The investigators obtained 87 serum samples of patients with asthma, of whom 39 were diagnosed with severe disease, as well as 273 serum samples of participants without a known history of asthma or other lung diseases.¹

“What we discovered is a specific transporter, a protein on the membrane of airway smooth muscle cells, allows cAMP to leak into the blood,” senior study author Reynold Panettieri, vice chancellor and director of translational medicine and science at Rutgers University, said in a news release. “For decades, we believed that an enzyme called phosphodiesterase was the critical factor in decreasing cAMP. We now refute that and say this transporter simply leaks it out.”²

A high variability—or a wide spread of cAMP levels—was detected in the 87 serum samples of patients with asthma, ranging from about 0.291 to 563.9 picomoles. Conversely, the range of cAMP levels in the 273 serum samples of individuals without asthma was markedly smaller (0–27.72 picomoles), and compared with the nonasthma group (median: 0.520 picomole), serum cAMP levels were significantly higher in patients with asthma (median: 6.220 picomoles).¹

“We would anticipate maybe in the next 6 months, we’ll have nailed the fidelity of it, get it into our intellectual property and patent the test itself, and then in a year to 2, it could become available,” Panettieri said. “Every disease we study or treat is not one disease. There are different aspects and attributes within a disease entity.”²

To further test the hypothesis that cAMP levels can differentiate asthma severity (severe vs nonsevere) in Severe Asthma Research Program 3 (SARP-3) samples, the investigators applied linear regression models with age and sex as covariates across clinical groups. They observed no significant difference of serum cAMP levels between the 2 severities; however, each asthma group showed significantly higher cAMP levels (adjusted P < .00001) than the nonasthma group.¹

The SARP-3 data were also leveraged to assess whether measured serum cAMP levels are associated with any clinical traits of asthma, such as asthma endotypes, poor control indicators, and postbronchodilator airflow reversibility. There were no significant differences in cAMP levels among or between groups stratified by eosinophilic or neutrophilic asthma nor any of the poor control indicators. In addition, the investigators reported they did not detect significant differences in serum cAMP levels with maximum FEV1 reversibility with albuterol. Also of note, serum cAMP levels increased with the number of inhaled corticosteroid puffs and controllers used, and in the nonsevere asthma group, increased with the increases of postbronchodilator lung function.¹

The authors explained that lung function tests in kids under the age of 5 years are difficult; therefore, pinprick or blood tests may be more feasible options in this age group.² Future research is needed to further confirm the link between serum cAMP levels in asthma severity and other disease characteristics.¹

“Further studies are necessary to explore the link between serum cAMP levels with bronchodilator or treatment responses by asthma severity; ABCC1 expression and activity in health and disease, including specific cell types of origin; and, whether these physiological outcomes and clinical phenotypes are affected by variations in ABCC1 genotypes in a large cohort of patients with and without asthma,” the authors concluded.¹

REFERENCES

1. An SS, Cao G, Ahn K, et al. Serum cAMP levels are increased in patients with asthma. J Clin Invest. 2025;135(5):e186937. doi.org/10.1172/JCI186937

2. Rutgers University. Scientists discover potential blood test for asthma diagnosis and severity. News release. September 29, 2025. Accessed October 13, 2025. https://www.rutgers.edu/news/scientists-discover-potential-blood-test-asthma-diagnosis-and-severity