AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Serum Alpha-1-Acid Glycoprotein and Cardiovascular-Kidney-Metabolic Stage Among Reproductive-Age U.S. Women: NHANES 2015-2023
By Shah V, Singh S, Jaiswal V
Background: Alpha-1-acid glycoprotein (AGP, or orosomucoid) is an acute-phase reactant associated with inflammation, obesity, insulin resistance, and cardiometabolic dysfunction. However, its relationship with the recently proposed Cardiovascular-Kidney-Metabolic (CKM) syndrome framework has not been well characterized. We evaluated the association between circulating AGP levels and CKM stage among reproductive-age women in the United States. Methods: We analyzed women aged 20-49 years from NHANES 2015-2016, 2017-March 2020, and 2021-2023 with available AGP measurements. Survey weights specific to AGP sampling were applied. CKM stages were approximated using American Heart Association CKM concepts: Stage 1 (overweight/obesity or abdominal obesity), Stage 2 (hypertension, prediabetes, diabetes, or hypertriglyceridemia), Stage 3 (chronic kidney disease defined by albuminuria or eGFR <60 mL/min/1.73m ² ), and Stage 4 (self-reported cardiovascular disease). Participants were categorized into AGP quartiles. Survey-weighted logistic and linear regression models adjusted for age and race/ethnicity. Results: Among 4,028 women, weighted CKM stage prevalence was 23.8% for Stage 0, 35.9% for Stage 1, 31.0% for Stage 2, 7.5% for Stage 3, and 1.8% for Stage 4. Mean CKM stage increased progressively across AGP quartiles (Q1: 0.91, Q2: 1.16, Q3: 1.41, Q4: 1.65; p-trend <0.001). Compared with the lowest AGP quartile, women in Q3 and Q4 had significantly higher odds of advanced CKM syndrome (Stage ≥2) after adjustment (Q3: OR 1.75, 95% CI 1.30-2.34; Q4: OR 2.98, 95% CI 2.24-3.96). Women in the highest AGP quartile also had increased odds of Stage ≥3 CKM disease (OR 1.46, 95% CI 1.01-2.11). Higher AGP levels were additionally associated with obesity (Q4 vs Q1: OR 16.83, 95% CI 12.49-22.68), abdominal obesity (OR 13.35, 95% CI 9.67-18.43), hypertension (OR 2.25, 95% CI 1.63-3.10), and diabetes (OR 3.70, 95% CI 2.13-6.42); however, associations with hypertension and diabetes were attenuated after adjustment for BMI. Conclusions: Higher circulating AGP concentrations were strongly associated with progressively advanced CKM stages among reproductive-age U.S. women. These findings suggest that AGP may serve as a readily available inflammatory biomarker identifying women at increased risk for cardiometabolic and kidney disease progression and warrant further investigation as a potential marker for CKM risk stratification. The attenuation of associations with hypertension and diabetes after BMI adjustment suggests that AGP may primarily reflect adiposity-related inflammatory burden within the CKM continuum.