Introduction <p>Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (CVD), a risk that is often exacerbated in patients with familial hypercholesterolemia (FH). However, the dynamics between PCSK9, Lp(a), and FH status remain incompletely understood.</p> Objectives <p>This study aimed to (i) compare serum Lp(a) and PCSK9 levels across FH individuals, their related but unaffected family members (RUF), and unrelated normal controls (NC); (ii) to identify biochemical and clinical factors independently associated with Lp(a) levels within and across groups and (iii) to determine the association of Lp(a) with FH status.</p> Methods <p>A total of 339 participants (115 FH, 58 RUF, 166 NC) were recruited through a National Community Health Screening Programme. FH was diagnosed using the Dutch Lipid Clinic Criteria (DLCC). Serum lipid profiles and Lp(a) were measured on an automated analyser, and PCSK9 concentrations were quantified by ELISA.</p> Results <p>Median Lp(a) levels were highest in FH individuals, followed by RUF, and lowest in NC. PCSK9 concentrations were also significantly elevated in FH compared to NC and RUF. Among NC, HDL was modestly associated with Lp(a) (<i>p</i> = 0.029; r² = 0.035), accounting for 3.5% of variance. Across all participants, LDL-C was modestly but significantly associated with Lp(a) levels (<i>p</i> &lt; 0.001; r² = 0.074).</p> Conclusion <p>This study demonstrates a pronounced familial gradient in Lp(a) concentrations, alongside significantly elevated PCSK9 in FH patients. Crucially, RUF exhibited higher Lp(a) levels than NC. These findings highlight the critical need for Lp(a) screening across the FH pedigree. Identifying this cardiovascular risk in normolipidemic relatives is essential for early preventative therapies.</p>