Metabolic Syndrome Severity Score Tracks With Coronary Artery Complexity in New Study

Patients whose metabolic dysfunction was more severe, measured as a continuous score rather than a simple yes-or-no diagnosis, tended to have more anatomically complex coronary artery disease, according to a retrospective cross-sectional study published in Frontiers in Cardiovascular Medicine. Researchers in Trabzon, Türkiye, reviewed the records of 156 patients with chronic coronary syndrome who had undergone coronary angiography during 2024 and found that a metabolic syndrome severity Z-score, or MetS-Sz, was strongly and positively correlated with the SYNTAX score, an angiographic measure of how extensive and technically difficult coronary lesions are. The study was observational, so it cannot show that metabolic severity caused the more complex disease, but the association persisted after statistical adjustment for several clinical and metabolic variables.

The metabolic syndrome is conventionally defined as a cluster of interrelated abnormalities, including central obesity, elevated blood pressure, hyperglycemia, high triglycerides, and low high-density lipoprotein cholesterol. Standard clinical definitions classify people categorically, based on whether a predefined number of components is present. The severity Z-score takes a different approach: it integrates multiple metabolic components into a single continuous value, using sex- and race/ethnicity-specific equations derived from the National Health and Nutrition Examination Survey, so that higher values indicate a greater cumulative burden of metabolic abnormalities relative to a reference population. In this study, the score was calculated with an online calculator using age, sex, body mass index, systolic blood pressure, fasting glucose, triglycerides, and HDL cholesterol drawn from electronic medical records, with the non-Hispanic White equations applied to all participants.

The SYNTAX score, meanwhile, quantifies coronary artery disease from angiographic images by incorporating the number, location, and morphological characteristics of lesions with at least 50 percent diameter stenosis in vessels of at least 1.5 millimeters reference diameter. Higher scores indicate more extensive and anatomically complex disease, and the score is widely used to help decide between percutaneous coronary intervention and coronary artery bypass grafting. In this study, scores of 22 or below were classified as low complexity, 23 to 32 as intermediate, and 33 or above as high. An experienced interventional cardiologist evaluated the existing angiography images using the original scoring algorithm and the online calculator; because a second independent observer was not available, interobserver reproducibility could not be assessed.

The study population came from 243 patients screened at a family medicine outpatient clinic who were subsequently referred to cardiology. Eighty-seven were excluded, including 24 with HbA1c above 7 percent, 16 with insufficient data for the severity score, and 19 whose angiographic data could not be scored, leaving 156 patients: 123 men and 33 women. Patients with cardiogenic shock, pulmonary edema, active infection, hematologic or chronic inflammatory disease, or malignancy were also excluded. Participants were split into a lower severity group with MetS-Sz below zero and a higher severity group at or above zero, corresponding to values below and at or above the reference population mean.

The two groups differed markedly across metabolic and angiographic measures. The higher severity group had significantly higher body mass index, triglycerides, total cholesterol, LDL cholesterol, fasting glucose, and diastolic blood pressure, along with lower HDL cholesterol, more diabetes, more smoking, and higher SYNTAX scores, with all reported comparisons reaching p < 0.05. The median SYNTAX score was 4.0 in the lower severity group versus 16.0 in the higher severity group. No significant differences emerged in age, sex, systolic blood pressure, or hypertension prevalence. The correlation between MetS-Sz and the SYNTAX score was strong and positive, with a Spearman coefficient of 0.675 and a p-value below 0.001.

In a multiple linear regression model that included MetS-Sz, body mass index, diastolic blood pressure, LDL cholesterol, triglycerides, diabetes, and smoking status, the overall model was statistically significant, with F = 22.84 and p < 0.001, and explained 51.9 percent of the variance in SYNTAX scores. MetS-Sz showed the strongest positive association, with an unstandardized coefficient of 6.934, meaning each one-unit increase in the severity score corresponded to roughly seven points of SYNTAX score, holding the other variables constant. LDL cholesterol and smoking were also positively associated, while body mass index and triglycerides showed inverse adjusted associations. The authors cautioned that these inverse coefficients should not be read as protective effects, because body mass index and triglycerides are components of the composite score, and including a score alongside its own constituents can produce statistical suppression even when conventional variance inflation factors remain below 5.

Because of that conceptual overlap, the researchers ran a sensitivity analysis that adjusted only for age, sex, and smoking status, without separately entering the metabolic variables that make up the score. In that model, MetS-Sz remained positively associated with the SYNTAX score, with a coefficient of 4.694 and an HC3 robust 95 percent confidence interval of 3.812 to 5.576, and the model explained 43.7 percent of the variance. However, the diagnostics revealed heteroscedasticity and departure from a strictly linear functional form; a quadratic MetS-Sz term was statistically significant, and although omitting six influential observations flagged by Cook’s distance retained a positive coefficient, functional-form concerns persisted. Diabetes and diastolic blood pressure were not significantly associated with the SYNTAX score in the adjusted analysis, but the authors noted that excluding patients with HbA1c above 7 percent restricted the glycemic range of the sample and may have altered the observed diabetes association in ways the data cannot determine.

The authors state that, to their knowledge, this is the first study to directly evaluate the association between the metabolic syndrome severity Z-score and the SYNTAX score in patients with chronic coronary syndrome. They place the finding in the context of prior work linking metabolic syndrome to coronary artery disease, cardiovascular events, and mortality through mechanisms including insulin resistance, endothelial dysfunction, chronic low-grade inflammation, oxidative stress, dyslipidemia, and hypertension. They also connect the result to earlier research on organ-specific markers of metabolic dysfunction, noting that a previous study found a positive correlation between a hepatic steatosis measure and the SYNTAX score, and that the present findings extend the concept to an integrated metabolic severity index. The study’s principal strength, they write, is the simultaneous evaluation of a continuous metabolic severity measure and an established angiographic complexity score using routinely available clinical data.

Several limitations temper the conclusions. The single-center, retrospective, cross-sectional design cannot establish the temporal sequence between metabolic severity and coronary complexity, and no longitudinal cardiovascular outcomes were collected, so the prognostic value of the score remains untested. The severity score was calculated with equations derived from non-Hispanic White individuals in a US population, and their applicability to the Turkish study population was not specifically validated. Information on medication use, inflammatory biomarkers, physical activity, and diet was not consistently available, SYNTAX scoring relied on a single observer, and the HbA1c restriction may have introduced selection bias. The authors emphasize that the findings concern an anatomical association and do not establish causality, diagnostic performance, prediction of future cardiovascular events, or clinical utility for risk stratification. They call for prospective, multicenter studies with larger and more diverse populations to determine whether the metabolic syndrome severity Z-score adds prognostic information beyond established cardiovascular risk assessment tools.

Subject of Research: The association between a continuous metabolic syndrome severity score and angiographic coronary artery disease complexity in patients with chronic coronary syndrome.

Article Title: Association between metabolic syndrome severity score and coronary artery disease complexity assessed by the SYNTAX score in patients with chronic coronary syndrome

Article References: Vatansever, M., Özderya, A., Yılmaz Tulumcu, F., Sezgin, Y., & Özer Yaman, S. (2026). Association between metabolic syndrome severity score and coronary artery disease complexity assessed by the SYNTAX score in patients with chronic coronary syndrome. Frontiers in Cardiovascular Medicine, 13, Article 1907964. https://doi.org/10.3389/fcvm.2026.1907964

Image Credits: AI Generated

DOI: 10.3389/fcvm.2026.1907964

Keywords: metabolic syndrome, coronary artery disease, SYNTAX score, MetS-Sz, chronic coronary syndrome, coronary angiography, cardiometabolic risk, retrospective study, atherosclerosis, risk stratification, lipids, smoking