👤 Ibrahim S Alhomoud

Apolipoprotein B (apoB), a direct measure of atherogenic lipoprotein particles, is recommended by clinical guidelines for cardiovascular risk assessment, particularly when low-density lipoprotein cholesterol (LDL-C) underestimates risk. Despite these endorsements, apoB testing remains significantly underutilized in clinical practice. This study evaluated the knowledge and practices of physicians and pharmacists in Saudi Arabia regarding apoB testing and its role in lipid management and cardiovascular risk stratification. Cross-sectional survey-based study conducted with physicians and pharmacists across healthcare institutions using a validated questionnaire. A total of 158 participants completed the questionnaire, including 80 physicians (50.6%) and 78 pharmacists (49.4%). The overall mean knowledge score was 4.70 ± 3.13 (out of a maximum score of 10). Participants specializing in family medicine, cardiology, and ambulatory care had the highest mean knowledge scores among specialties. Physicians demonstrated a significantly higher knowledge score than pharmacists (6.00 ± 2.99 vs 3.36 ± 2.69; P < 0.001). While 69.6% recognized apoB as a direct measure of atherogenic lipoprotein particles, only 53.8% correctly identified it as the most reliable marker of residual atherosclerotic cardiovascular disease risk in patients with lipid profile discordance. A significantly higher proportion of participants with high knowledge reported measuring apoB levels or considering it whenever available in their practice than those with moderate and low levels of knowledge (88.2%, 53.1%, and 24.1%, respectively; P < 0.001). ApoB testing remains underutilized among physicians and pharmacists in Saudi Arabia despite guideline recommendations. Targeted educational initiatives and national-level strategies are needed to enhance awareness and integration of apoB testing in risk assessment practices. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle composed of apolipoprotein B-100 covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The Lp(a) particle is enriched with oxidized phospholipids (OxPLs), which confer enhanced atherogenic and pro-inflammatory properties compared with low-density lipoprotein (LDL). Robust genetic and epidemiologic evidence demonstrates that elevated Lp(a) levels are independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. However, no pharmacologic therapy has yet been approved that specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and oral small-molecule Lp(a) inhibitors (e.g., muvalaplin) have demonstrated profound reductions in circulating Lp(a) concentrations, typically achieving decreases of 80-90%. In some studies, the reductions approached or achieved a near-complete suppression. Current genetic and modeling evidence suggests that an absolute reduction of at least 50 mg/dL in Lp(a) levels is required to achieve meaningful cardiovascular benefits. Large-scale outcome trials are now underway to assess the effects of these emerging therapies on cardiovascular and valvular outcomes. Early findings indicate favorable effects on oxidized phospholipids and vascular inflammation, suggesting broader anti-atherogenic potential. As these agents progress toward clinical use, routine Lp(a) measurement and risk stratification will become increasingly essential for personalized cardiovascular prevention. This review summarizes the molecular biology of Lp(a), highlights the limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk. Show less