Abstract
Background: Although low-density-lipoprotein cholesterol (LDL-C) remains the primary target of lipid-lowering therapy, many patients with atherosclerotic cardiovascular disease (ASCVD) continue to experience cardiovascular events. This residual risk suggests that LDL-C alone does not fully capture the total atherogenic burden. Alternative lipid measures, including non-high-density lipoprotein cholesterol (non-HDL-C) and cholesterol ratios, may provide a more comprehensive risk assessment, particularly in populations with a high prevalence of metabolic disorders. This study assessed the prevalence and clinical determinants of elevated non-HDL cholesterol and adverse cholesterol ratios among Middle Eastern patients with established ASCVD. Methods: This pooled cross-sectional analysis included 2763 adults with confirmed ASCVD from the Jordan SMuRF-less Study and six cardiovascular registries across the Middle East. Patients were stratified by standard modifiable cardiovascular risk factors (SMuRFs). Demographic, clinical, treatment, and lifestyle data were harmonized and analyzed using multivariable regression models. Results: Elevated non-HDL-C was observed in 54% of patients. Those with elevated non-HDL-C were younger (55.0 vs. 59.9 years) and more frequently current smokers (52.6% vs. 43.1%). Hypertension (64.2% vs. 51.0%) and heart failure (25.0% vs. 15.4%) were more common among patients with lower non-HDL-C, whereas dyslipidemia (90.8% vs. 75.8%) and acute coronary syndrome (88.1% vs. 83.7%) were more prevalent in the elevated group. Elevated non-HDL-C was associated with higher baseline LDL-C levels measured prior to the initiation of lipid-lowering therapy (141.3 vs. 81.1 mg/dL) and higher triglycerides (221.4 vs. 140.9 mg/dL). In multivariable analyses, age > 60 years (OR = 0.45), hypertension (OR = 0.74), and heart failure (OR = 0.61) were inversely associated with elevated non-HDL-C. Conclusions: Elevated non-HDL cholesterol is common among Middle Eastern patients with ASCVD, particularly younger individuals, reflecting early metabolic risk and increased atherogenic burden. Non-HDL-C is a valuable marker of residual cardiovascular risk, supporting earlier screening and region-specific prevention strategies.