Lipoprotein(a) and Cumulative Low-Density Lipoprotein Cholesterol as Predictors of Coronary Artery Disease in Statin-Naïve Elderly Individuals with Hyperlipidemia-Uncorrected Proof

Objective: Advanced age is a well-recognized risk factor for atherosclerotic cardiovascular disease (ASCVD). Given the ongoing debate regarding the initiation of statin therapy in elderly individuals, identifying those with underlying coronary artery disease (CAD) who may benefit from lipid-lowering treatment is essential. This study aimed to identify predictors of CAD in statin-naïve adults aged ≥ 70 years with elevated low-density lipoprotein cholesterol (LDL-C), with particular emphasis on risk assessment, cumulative LDL-C burden, and lipoprotein(a) [Lp(a)] levels.

Method: The analysis included consecutive patients aged ≥ 70 years with LDL-C ≥ 160 mg/dL, available Lp(a) measurements, no prior history of ASCVD or diabetes, who underwent evaluation for CAD by coronary imaging or functional stress testing. Global ASCVD risk was estimated using the Systematic Coronary Risk Estimation 2–Older Persons (SCORE2-OP) and the Spanish Familial Hypercholesterolemia Cohort Study (SAFEHEART) risk scores.

Results: A total of 202 patients were included (mean age 76 years; 68.3% female). CAD was diagnosed in 30.7% of participants. In multivariable analysis, male sex (odds ratio [OR]: 2.109), Lp(a) level (OR: 1.012 per mg/dL), and cumulative LDL-C (OR: 1.155 per g/dL) were independently associated with CAD. The highest CAD prevalence was observed among individuals with cumulative LDL-C ≥ 14 g/dL and Lp(a) ≥ 50 mg/dL. While the SCORE2-OP algorithm failed to predict CAD, the SAFEHEART risk score was significantly associated with CAD.

Conclusion: In statin-naïve elderly individuals with elevated LDL-C levels, male sex, cumulative LDL-C exposure, and high Lp(a) levels were independently associated with CAD. These findings underscore the potential utility of incorporating cumulative LDL-C and Lp(a) into risk stratification for older adults.

Keywords: Cardiovascular risk stratification, cumulative low-density lipoprotein cholesterol, elderly, primary prevention, Spanish Familial Hypercholesterolemia Cohort Study risk score, statin-naïve, Systematic Coronary Risk Estimation 2–Older Persons