Combined value of AIP and NHR for identifying obstructive coronary heart disease in premature cases with zero calcium

A coronary artery calcium (CAC) score of zero is generally considered a strong negative predictor for coronary heart disease (CHD). However, it does not exclude obstructive disease in symptomatic adults, particularly younger patients with non-calcified plaque. We evaluated whether Atherogenic Index of Plasma (AIP) and Neutrophil-to-HDL Ratio (NHR) improve identification of obstructive CHD in this population. We analyzed 362 symptomatic adults with suspected premature CHD (men < 55, women < 65 years) and CAC = 0 from an invasive angiography registry. AIP and NHR were calculated from fasting laboratory tests. The endpoint was angiographic obstructive CHD (≥ 50% stenosis). Obstructive CHD occurred in 115/362 (31.8%). Adding AIP to traditional risk factors improved discrimination (area under the curve [AUC] 0.798 to 0.814) and model fit (Akaike information criterion [AIC] 337.8 to 333.1); adding NHR provided incremental improvement (AIC 331.6, AUC 0.818). Using internally derived cutoffs (AIP > 0.13, NHR > 3.08), the dual-high phenotype was associated with higher odds of obstructive CHD (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.90–11.07, P < 0.001) compared with the low AIP/low NHR group. In symptomatic adults with suspected premature CHD and CAC = 0, the dual-high phenotype (elevated AIP and NHR) identifies a higher-risk subgroup for non-calcified obstructive disease. These findings underscore the limitations of CAC scoring alone in this population.