Simple Blood Ratio Flags Heart Risk in Women, but Falls Short as a Standalone Predictor

A routine blood test that most people receive during an annual check-up may carry a hidden message about heart disease in women. Researchers in Wuhan, China, have found that a simple mathematical ratio—dividing the level of the liver enzyme gamma-glutamyl transferase, or GGT, by the level of high-density lipoprotein cholesterol, the so-called good cholesterol—was strongly associated with the presence of coronary heart disease in female patients and with their risk of suffering a major adverse cardiovascular event over the following months. The study, published in BMC Endocrine Disorders, followed more than three thousand women and offers one of the most detailed looks yet at this combined marker, known as the GGT-to-HDL-cholesterol ratio, or GHR. Yet the same research also delivers a sobering caveat: while the ratio tracks risk in groups, it performs poorly as a standalone short-term prediction tool, and the authors caution that it should not be used alone to forecast who will have a heart attack or stroke within a year.

The logic behind the ratio rests on two well-studied biological threads. GGT is an enzyme found mainly in the liver and biliary tract, and elevated blood levels have long been linked not only to liver disease but also to oxidative stress, inflammation, and metabolic dysfunction. Population studies have repeatedly associated higher GGT with diabetes, high blood pressure, fatty liver disease, and atherosclerosis, the gradual narrowing of arteries that underlies heart attacks. HDL cholesterol, meanwhile, is widely regarded as protective because it participates in reverse cholesterol transport, ferrying cholesterol away from artery walls back to the liver. When GGT is high and HDL is low at the same time, the resulting ratio captures two damaging tendencies in a single number: a burden of oxidative and metabolic stress paired with a weakened defense system. Combining the two into one indicator, researchers hoped, might outperform either measurement alone and offer clinicians a cheap, readily available window into cardiovascular risk.

To test that idea, the team led by Sisi Chen and colleagues at Wuhan Fourth Hospital conducted a retrospective longitudinal cohort study of 3,123 female patients. The women were evaluated for coronary heart disease, and the researchers used multivariable logistic regression to ask whether a higher standardized GHR was independently associated with having the disease, after accounting for a broad range of clinical and laboratory covariates. The answer was a clear yes. Each one-standard-deviation increase in the ratio was associated with roughly two and a half times the odds of coronary heart disease, with a fully adjusted odds ratio of 2.466 and a 95 percent confidence interval of 1.943 to 3.130, a result that remained highly statistically significant. In conventional receiver operating characteristic analysis, the ratio showed modest ability to discriminate between women with and without the disease, achieving an area under the curve of 0.741.

The investigators then turned to the forward-looking question: among women who already had coronary heart disease, did the ratio predict future trouble? During a median follow-up of 665 days, 611 major adverse cardiovascular events occurred in the cohort. In a complete-case Cox regression model that included 683 patients with 183 events, and that was additionally adjusted for low-density lipoprotein cholesterol along with other clinical and laboratory variables, each one-standard-deviation rise in GHR was associated with a 49.8 percent higher rate of major adverse cardiovascular events, corresponding to a hazard ratio of 1.498 with a confidence interval of 1.358 to 1.653. The dose-response pattern was striking. When patients were divided into tertiles, or thirds, by their baseline ratio, women in the middle third had nearly double the event rate of those in the lowest third, with a fully adjusted hazard ratio of 1.902, while those in the highest third had more than three times the rate, at 3.291. The trend across tertiles was highly significant.

These findings place the GHR in a growing family of combined lipid-and-enzyme markers that researchers have proposed as refinements to traditional cholesterol panels. Standard risk assessment relies heavily on low-density lipoprotein cholesterol, total cholesterol, and related measures, yet many women who suffer cardiovascular events do not have dramatically abnormal values on those tests. Coronary heart disease in women has historically been under-recognized and under-studied, and sex-specific risk markers remain an active frontier in cardiology. A ratio assembled from two tests that are already ordered routinely—liver function panels include GGT, and lipid panels include HDL cholesterol—would cost nothing extra to calculate, which is precisely what makes such markers attractive. The Wuhan study’s large female-only cohort and its adjustment for numerous confounders, including lipid-lowering therapy, lend considerable weight to the observed associations.

However, the study’s most instructive finding may be the one that tempers enthusiasm. When the researchers applied a more rigorous, time-dependent form of receiver operating characteristic analysis focused specifically on the first 365 days of follow-up—a method that properly accounts for censoring, meaning patients whose follow-up ends before the full year—the ratio’s discriminative power collapsed. The area under the curve fell to just 0.594 overall, and across age subgroups it ranged only from 0.593 to 0.623, with no statistically significant differences between age groups. This is a stark contrast with the exploratory conventional ROC analysis, which had suggested the best discrimination among patients aged 75 and older, with an area under the curve of 0.737. The discrepancy illustrates a methodological pitfall in biomarker research: conventional ROC analyses that ignore censoring can overstate a marker’s predictive performance, and the authors’ decision to run both analyses side by side provides an unusually honest appraisal.

The authors are explicit about the implication. Higher GHR, they conclude, is associated with coronary heart disease and with the occurrence of major adverse cardiovascular events in women with the disease, but baseline GHR alone shows limited discrimination for one-year events and should not be considered a standalone short-term risk prediction marker. In practical terms, a high ratio may flag a woman as belonging to a higher-risk stratum, but it cannot tell a clinician with confidence whether a specific patient will experience a heart attack, stroke, or cardiovascular death within the next twelve months. The researchers also emphasize that prospective external validation is required before GHR can be incorporated into clinical risk assessment. Because the study was retrospective and conducted at a single institution in China, its findings must be reproduced in independent, diverse populations before any change to practice could be justified.

The study also has structural limitations worth understanding. Retrospective designs rely on data collected for clinical rather than research purposes, which can introduce measurement variability and missing information; the complete-case Cox model included only 683 of the 3,123 enrolled patients, a substantial reduction that may affect precision and generalizability. Residual confounding remains possible even after extensive adjustment, since factors such as diet, physical activity, alcohol consumption, and detailed medication adherence are difficult to capture fully in routine records. The authors note that they examined variance inflation factors to check for multicollinearity among covariates, and their supplementary analyses included correlations between GHR and the Gensini score, a measure of coronary artery disease severity, as well as Kaplan-Meier survival curves stratified by GHR tertiles, which visually confirmed the gradient in event-free survival across risk groups.

What emerges from this research is a nuanced picture rather than a breakthrough headline. The GGT-to-HDL-cholesterol ratio is a genuine and statistically robust signal: it reflects the convergence of oxidative stress and impaired cholesterol handling, it correlates with the presence and severity of coronary disease in women, and it stratifies patients into meaningfully different risk tiers over a follow-up period approaching two years. At the same time, the study demonstrates that association and prediction are not the same thing, and that a biomarker cheap enough to calculate on the back of any lab report still needs to clear a high bar before it can guide individual decisions. For now, the ratio is best viewed as a promising adjunct—a number that may enrich risk conversations between women and their cardiologists—while the search for reliable, sex-specific short-term predictors continues. The full open-access study is available with the DOI 10.1186/s12902-026-02534-1.

Subject of Research: The GGT-to-HDL-cholesterol ratio as a biomarker for coronary heart disease and cardiovascular outcomes in women

Article Title: Association between the gamma-glutamyl transferase to high-density-lipoprotein-cholesterol ratio and clinical outcomes in female patients with coronary heart disease

Article References: Association between the gamma-glutamyl transferase to high-density-lipoprotein-cholesterol ratio and clinical outcomes in female patients with coronary heart disease. (n.d.). https://doi.org/10.1186/s12902-026-02534-1

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02534-1

Keywords: GGT-to-HDL ratio, coronary heart disease, women's health, biomarkers, cardiovascular risk, major adverse cardiovascular events, HDL cholesterol, gamma-glutamyl transferase, Cox regression, risk prediction, BMC Endocrine Disorders, retrospective cohort study