👤 Evagelos Liberopoulos

Oxidative modification of apolipoprotein B-100 (apoB) containing particles and subsequent immune responses contribute to the pathogenesis of atherosclerosis. Circulating IgG and IgM apoB-containing immune complexes (apoB-IC) and autoantibodies to a malondialdehyde mimotope (anti-MDA-mimotope) serve as biomarkers of oxidative stress and immune activation in atherosclerotic cardiovascular disease. Elevated lipoprotein(a) [Lp(a)] is associated with increased oxidative burden and immune activation. To investigate the effect of lipid-lowering medications on IgG and IgM apoB-IC and IgG and IgM autoantibodies to an MDA-mimotope in individuals with elevated lipoprotein(a) [Lp(a)] concentrations. In this prospective study, patients (n = 70) with Lp(a) levels ≥ 75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). IgG and IgM apoB-IC and IgG and IgM anti-MDA-mimotope were measured at baseline and 3 months after treatment initiation. Patients had a mean age of 51 ± 15 years and 40% were male. Significant reductions in IgG apoB-IC levels were observed following treatment with high-intensity statins, add-on ezetimibe and add-on PCSK9i (by 18.3%, 17.5% and 25.5%, respectively, all p < 0.05). No significant changes in IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels were observed in any treatment group. In individuals with Lp(a) levels ≥ 75 nmol/L, high-intensity statins, add-on ezetimibe and add-on PCSK9i reduced IgG apoB-IC but did not affect IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels. The clinical significance of these findings warrants further investigation. Show less

Dyslipidemia remains a major, modifiable determinant of global stroke burden, accounting for more than one-fifth of ischemic strokes (IS) worldwide. Recent evidence has shifted emphasis from conventional lipid fractions to apolipoprotein B (ApoB)-containing lipoproteins, including lipoprotein(a) [Lp(a)], which more accurately reflect atherogenic particle burden than low-density lipoprotein cholesterol (LDL-C) alone and are increasingly used for stroke risk stratification. While the principle "the faster and the lower, the better" underpins dyslipidemia management, evidence-based, subtype-specific lipid strategies in stroke remain limited. Intensive LDL-C reduction significantly lowers recurrent IS risk; however, uniform lipid targets are often applied without accounting for stroke etiology. High-intensity statins remain first-line therapy, with pleiotropic benefits extending beyond LDL-C reduction. For statin intolerance or suboptimal response, ezetimibe and PCSK9 inhibitors provide potent, bleeding-neutral LDL-C lowering. Inclisiran and bempedoic acid broaden therapeutic options, although stroke-specific efficacy data are still pending. Lp(a)-lowering agents, including pelacarsen, olpasiran, and lepodisiran, are under active evaluation and may address residual cardiovascular risk. For triglyceride lowering, recent randomized evidence supports icosapent ethyl for reducing IS risk. In intracerebral hemorrhage (ICH), the optimal intensity and thresholds of lipid lowering remain uncertain, warranting individualized weighting of ischemic against hemorrhagic risk, particularly in patients with lobar ICH or suspected cerebral amyloid angiopathy (CAA). In such cases, hydrophilic statins, ezetimibe, or PCSK9 inhibitors may represent reasonable options. This review synthesizes current evidence and proposes a phenotype-guided, individualized framework for dyslipidemia management across stroke subtypes. Moving beyond uniform targets toward etiologic and genetically informed lipid modulation may improve post-stroke outcomes and refine individualized stroke prevention. Show less

This study investigated the relationship between apolipoprotein B (apoB), "excess apoB" (apoB beyond low-density lipoprotein cholesterol (LDL-C)), and apoB/apolipoprotein A1 (apoA1) ratio with 20-year atherosclerotic cardiovascular disease (ASCVD) incidence, using an age- and sex-specific approach. In 2002, a cohort of 3042 adults, free of cardiovascular disease (CVD) residing in the greater Athens area (Greece) was recruited. A 20-year follow-up was conducted in 2022, comprising of 2169 participants, of whom 1988 had complete data for CVD incidence. Cox proportional hazards models were used to assess the association of apoB, excess apoB, and apoB/apoA1 with 20-year ASCVD risk and residual risk (events not predicted by standard factors). Older participants and males had higher levels of apoB, excess apoB, and apoB/apoA1. In the overall cohort, only apoB was significantly associated with ASCVD risk (hazard ratio (HR), 1.006; p = 0.003). However, age- and sex-dependent associations were observed as apoB, excess apoB, and apoB/apoA1 significantly predicted increased ASCVD incidence only in males under 40 years (HR 1.025, p = 0.005; 1.052, p = 0.003; 1.396, p = 0.002; respectively). Significant associations were observed with residual ASCVD risk in the overall cohort, with the most pronounced associations seen in males under 40 (HR 1.023, p = 0.001; 1.039, p < 0.001; 1.285, p = 0.002; respectively). The association of apoB, excess apoB, and apoB/apoA1 with long-term ASCVD incidence and residual risk demonstrates age- and sex-dependent variations, with younger males showing elevated risk, highlighting the value of these markers beyond traditional risk factors and emphasizing the need for age- and sex-specific considerations in ASCVD risk assessment. Show less

National epidemiologic data are needed to inform country-specific healthcare policies for prevention and new developing treatments. We aimed to analyze Greek epidemiologic data in clinically relevant special populations for targeted treatments and to evaluate the utility of lipoprotein(a) [Lp(a)] as a risk enhancer METHODS: Two independent cohorts were included in this analysis: (1) consecutively recruited patients assessed in a tertiary outpatients' lipid clinic (Athens Angiometabolic cohort [AAC], n = 1106) with available peripheral vascular markers, and (2) sample of the Greek general population (ATTICA study [AS], n = 2682) with available 20-year follow-up data for atherosclerotic cardiovascular disease (ASCVD) events. Increased Lp(a) was found in 8.3% of the AS (≥50 mg/dL) and in 18.9% of the AAC (≥125 nmol/L) (16.0% without ASCVD and 22.1% with ASCVD, P = .006). Elevated Lp(a) levels were associated with increased carotid, coronary artery, and lower extremity atherosclerosis (P < .05 for all). Both the European Atherosclerosis Society (EAS) recommendations (net reclassification index [NRI]: 0.170) and a derived sex-specific inflation factor for HellenicSCOREII+ (NRI: 0.176) were efficient in incorporating Lp(a) as a risk enhancer over HellenicSCOREII+ for 20-year major adverse cardiovascular events. For 10-year cardiovascular death, only the EAS consensus provided significant reclassification. Finally, Lp(a) conferred increased eligibility for more aggressive primary prevention measures both by EAS recommendations (23.6% in AAC/13.6% in AS) and by sex-specific inflation factors (25.6% in AAC/22.3% in AS). Elevated Lp(a) levels were observed in 8.3% of the general population cohort and up to 23.9% in participants with ASCVD from the lipid clinic cohort, highlighting a risk gradient across ASCVD categories. Incorporating Lp(a) as a risk enhancer improves ASCVD risk reclassification beyond the validated HellenicSCOREII+. Show less

Oxidized phospholipids (OxPLs) are bound to apolipoprotein B-100 (OxPL-apoB) and apolipoprotein(a) [OxPL-apo(a)] and are present freely within the phospholipid shell of apoB-containing lipoproteins. OxPLs have been linked with the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPLs carried on plasminogen (OxPL-PLG) may extend the time to fibrinolysis. To evaluate the effect of lipid-lowering medications on OxPLs levels in individuals with elevated Lp(a) concentrations. In this prospective study, patients (n = 70) with Lp(a) levels ≥75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). Follow-up duration was 3 months. Patients had a mean age of 51 ± 15 years, 40 % were male, 39 % were diagnosed with familial hypercholesterolemia, 16 % had atherosclerotic cardiovascular disease, and 36 %, 33 % and 15 % were at very high, high, and moderate cardiovascular risk, respectively. Lp(a) levels did not change significantly with high-intensity statin and add-on ezetimibe but significantly decreased with add-on PCSK9i treatment. OxPL-apoB and OxPL-apo(a) significantly increased, while OxPL-PLG significantly decreased with both high-intensity statin and add-on ezetimibe. Add-on PCSK9i treatment was associated with no significant changes in OxPL-apoB, OxPL-apo(a) and OxPL-PLG levels. Among patients with elevated Lp(a), both high-intensity statin and add-on ezetimibe significantly increased OxPL-apoB and OxPL-apo(a) levels, while significantly decreased OxPL-PLG levels. Add-on PCSK9i had no significant effect on OxPLs levels. The clinical implications of these findings should be further explored. Show less

A strong correlation exists between low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B100 (apoB). However, evidence suggests that LDL-C and non-HDL-C may underestimate apoB, potentially obscuring residual cardiovascular risk. Furthermore, interactions between apoB and lipoprotein(a) are implicated in atherogenesis. This study sought to determine whether discordance between apoB, LDL-C, non-HDL-C, or lipoprotein(a) is associated with 20-year atherosclerotic cardiovascular disease (ASCVD) risk within a cohort of apparently healthy adults. A cohort of 3042 CVD-free adults residing in greater Athens, Greece, was recruited in 2002. A 20-year follow-up was conducted in 2022, comprising n = 2169 participants, of which n = 1988 had complete data for cardiovascular disease incidence. Discordance between biomarkers was defined based on recommended lipid thresholds. Cox proportional hazards models were used to assess the association between discordant/concordant biomarker pairs and 20-year ASCVD risk. ApoB strongly correlated with LDL-C and non-HDL-C, though concordance was limited. Increased 20-year ASCVD cumulative incidence with elevated apoB levels, beyond LDL-C, non-HDL-C, and lipoprotein(a). Discordance analysis revealed that elevated apoB independently predicted increased 20-year ASCVD risk, regardless of non-HDL-C and lipoprotein(a). However, this effect was observed only on concomitantly elevated LDL-C levels. Incorporating apoB into the assessment of traditional modifiable risk factors elucidated part of the previously residual 20-year ASCVD risk, especially in individuals with elevated LDL-C, non-HDL-C, or lipoprotein(a) levels. ApoB may be a superior biomarker for assessing long-term ASCVD risk, indicating that apoB-containing lipoprotein particle number, rather than cholesterol content, is a more robust predictor of ASCVD risk. Show less

HDL-cholesterol (HDL-C) is inversely related to the risk of ischemic heart disease. Many genes are reported to affect HDL-C serum levels in both hyperlipidemic and normolipidemic populations, though the data are controversial. We examined the effect of common gene polymorphisms known to interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in normolipidemic subjects. The study population consisted of 200 normolipidemic individuals visiting our clinic for a routine check-up. None of the above gene polymorphisms affected HDL-C levels in our population. However, participants carrying the allele E4 of the apolipoprotein (apo) E gene, the allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site 347) (n = 28) had statistically significantly lower HDL-C levels compared to those not carrying the above allele combination (0.99+/-0.33 vs 1.28+/-0.35 mmol/L, p = 0.04). In this study, we describe a subgroup of normolipidemic individuals with low HDL-C levels due to genetic variability, and we discuss the underlying possible mechanisms involved. Show less