Distinct phenotype of very early-onset coronary artery disease (≤35 years): baseline findings from a multicentre prospective cohort
X Ding, J J Xu, C D Guan, Y Y Geng, Y Jiang, R Zhang, J Y Feng, Y Zhang, L SongAbstract
Background
Premature coronary artery disease (CAD) is increasingly recognized as a distinct clinical entity with substantial long-term burden. However, data differentiating very early-onset CAD (≤35 years) from early-onset CAD (35–45 years) remain limited. A better understanding of baseline phenotypic differences may inform tailored prevention and management strategies.
Purpose
To compare baseline clinical characteristics, risk factor profiles, and angiographic features between very early- and early-onset CAD in a large multicentre prospective cohort.
Methods
This cross-sectional baseline analysis included 1,559 patients aged ≤45 years with imaging-confirmed CAD. Participants were categorized into very early-onset CAD (≤35 years, n=253) and early-onset CAD (35–45 years, n=1,306). Baseline assessments comprised sociodemographic characteristics, cardiovascular risk factors, medical history, lifestyle behaviors, anthropometric measures, laboratory biomarkers, and coronary angiographic findings.
Results
Overall, 94.2% (1468/1559) were male and 58.8% (898/1526) presented with acute coronary syndrome, with no significant difference in clinical presentation between groups. Very early-onset patients were characterized by pronounced central adiposity, exhibiting greater body mass index (28.35 [25.41-31.61] vs. 27.09 [24.99-29.77] kg/m², P<0.001) and waist circumference (95.00 [88.00-105.00] vs. 94.75 [88.00-102.00] cm, P=0.004). This group demonstrated a highly pro-thrombotic and inflammatory baseline milieu, with elevated uric acid (412.45 ± 98.73 vs. 388.84 ± 99.85 μmol/L, P<0.001), white blood cell counts (7.55 [6.41-8.37] vs. 7.24 [5.98-8.48] x10⁹/L, P=0.03), and platelets (250 [211-297] vs. 232 [197-272] x10⁹/L, P=0.003). In contrast, traditional atherosclerotic drivers were less prevalent in the ≤35 cohort, including diabetes (20.9% [53/253] vs. 28.4% [370/1,302], P=0.02) and hypertension (45.5% [115/253] vs. 52.5% [684/1,301], P=0.04). Angiographically, very early-onset CAD was heavily focal, featuring higher rates of single-vessel disease (38.7% [84/217] vs. 26.5% [304/1,147]) and significantly lower rates of three-vessel disease (35.5% [77/217] vs. 41.2% [473/1,147]). Despite this limited anatomical spread, very early-onset patients suffered a higher prevalence of prior myocardial infarction (38.7% [98/253] vs. 29.7% [387/1,300], P=0.005). Lipid profiles and statin use were comparable between groups.
Conclusion(s)
Very early-onset CAD is not merely premature disease but a distinct and potentially more aggressive phenotype marked by central obesity and systemic inflammation, with early myocardial infarction occurring despite limited angiographic extent. This challenges conventional metabolic paradigms and underscores the need for age-tailored prevention and management strategies.Table 1.Baseline CharacteristicsTable 1.Baseline Characteristics (Continued)