STAR-Lp(a) study of 2,594 patients finds Lp(a)-driven atherosclerosis risk is largely mitigated by managing obesity, diabetes and inflammation (Arch Med Sci 2025)

Introduction: Lipoprotein (a) (Lp(a)) is a largely genetically determined (70-90%) independent risk factor for cardiovascular disease (CVD). However, clinicians often encounter adults/elder adults with elevated Lp(a), who are otherwise healthy and asymptomatic for atherosclerosis. We aimed to identify additional risk factors and conditions, apart from elevated Lp(a), which lead to atherosclerosis progression and CVD, and whether any protective factors mitigate Lp(a)-related risk.

Material And Methods: In the STAR (Specialist Care Patients) Lp(a) study, we prospectively enrolled 2,594 consecutive patients aged over 50 years, who had elevated Lp(a), referred to two outpatient cardiology clinics. These patients were either healthy, or had established CVD or three or more cardiovascular risk factors. Lp(a) concentration was measured by enzyme-linked immunosorbent assay.

Results: Among adults > 50 years with Lp(a) ≥ 30 mg/dl (75 nmol/l) (mean Lp(a), 65.4 vs. 72.7 mg/dl, p = 0.118), healthy individuals and patients differed significantly in mean age (62.8 vs. 69.6 years, p < 0.001), body mass index (BMI) and prevalence of overweight/ obesity (16.0% vs. 32.7%, p = 0.001), mean hsCRP (2.12 vs. 2.35 mg/l, p = 0.007), dyslipidemia, mean glucose and HbA1c levels (5.44% vs. 5.86%, p < 0.001), and coronary artery calcium (CAC) scores (43.1 vs. 339.9, p < 0.001). In multivariable analysis, the independent predictors of increased CAC in healthy individuals were gender and non-HDL-C, while in patients, the independent predictors were non-HDL-C and age. Correlation analysis showed that in healthy individuals, CAC correlated with gender and non-HDL-C, while in patients, CAC correlated with age, gender, non-HDL-C, HbA1c, and Lp(a). Comparing sub-groups with Lp(a) > 50 mg/dl (125 nmol/l) (mean age: 62.3 vs. 69.2 years, p < 0.001; female: 77.8% vs. 68.5%, p = 0.021; mean Lp(a) : 87.8 vs. 88.8 mg/dl, p = 0.838), the independent predictors of CAC in healthy individuals were elevated hsCRP and gender, whereas in patients, they were age and Lp(a). Correlation analysis confirmed that Lp(a) was significantly associated with CAC in patients only, and LDL-C and hsCRP correlated with CAC in patients only.

Conclusions: In adults > 50 years with elevated Lp(a), Lp(a) - related risk of atherosclerosis progression can be substantially mitigated by addressing modifiable CVD risk factors, such as obesity, diabetes, inflammation, and dyslipidemia, preferably by early preventive measures. In our study cohort, Lp(a) was independently associated with atherosclerosis progression in the patient group only.