👤 Demosthenes Panagiotakos

Apolipoprotein B (apoB) is a recognized risk factor for acute coronary syndrome (ACS); however, its prognostic value in secondary prevention and superiority over other lipid biomarkers, especially in younger populations, remains uncertain. To investigate whether elevated baseline apoB predicts recurrent cardiovascular events in patients who experienced an ACS at ≤40 years of age and compare its incremental predictive value with that of other lipid biomarkers. We recruited 405 consecutive patients who survived an ACS at ≤40 years of age. Clinical endpoints included major adverse cardiovascular events (MACE): cardiac death, readmission for ACS or ventricular arrhythmias, ischemic stroke, and coronary revascularization due to clinical deterioration. The association between baseline lipid biomarkers and recurrent MACE risk was assessed using multivariable Cox regression. Model performance was evaluated based on discrimination and reclassification. Of 378 young ACS survivors (33.7 ± 4.3 years) with follow-up data, 139 (36.8%) experienced a MACE over a median 8-year (5.2-12.5 years) follow-up. Elevated baseline apoB was independently associated with a higher risk of recurrent MACE (hazard ratio per 10 mg/dL: 1.082, P= .007). This association remained significant even after additionally accounting for low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). Conversely, apoB adjustment attenuated the LDL-C and non-HDL-C associations. Compared with LDL-C and non-HDL-C, apoB was associated with greater risk of recurrent MACE, and upon addition to conventional cardiovascular risk factors, yielded the greatest improvement in discrimination and reclassification. Baseline apoB may act as a driver for long-term recurrence of MACE in very young ACS survivors, highlighting its potential clinical utility to improve risk stratification beyond traditional lipid measurements. 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

Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease, and it is particularly associated with premature acute coronary syndrome (ACS). We investigated whether elevated Lp(a) can predict recurrent cardiovascular events in patients who experienced their first ACS less than or equal to 40 years of age. Within the STudy of eArly Myocardial INfArction registry, we recruited 405 consecutive patients who survived their first ACS less than or equal to 40 years of age; of them 378 had complete follow-up data. Clinical endpoint was the development of major adverse cardiovascular events (MACE; i.e. cardiac death, readmission for ACS or malignant ventricular arrhythmias, ischemic stroke, or coronary revascularization due to clinical deterioration). Multi-adjusted Cox regression was used to assess the association between Lp(a) and first recurrent MACE risk. Of the 378 ACS survivors (33.7 ± 4.3 years), 139 (36.8%) experienced a MACE over a median 8-year (5.2-12.5 years) follow-up. Elevated Lp(a) showed a borderline independent association with higher recurrent MACE [hazard ratio per 1 mg/dl: 1.004, 95% confidence interval (CI): 0.999-1.009, P = 0.051]. Moreover, patients with baseline Lp(a) levels greater than or equal to 50 mg/dl had 82.6% higher risk of MACE as compared with those below (hazard ratio 1.826, 95% CI: 1.141-2.925, P = 0.012); similarly, patients with Lp(a) ≥ 70 mg/dl had 118% higher risk as compared with those below (hazard ratio 2.180, 95% CI: 1.330-3.573, P = 0.002). Elevated Lp(a) concentrations demonstrate an independent association with recurrent MACE among very young ACS survivors. Until targeted Lp(a)-lowering treatments become clinically available, an aggressive lipid-lowering approach may be warranted to partially attenuate Lp(a)-related residual cardiovascular risk. 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

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