👤 Frédéric Maes

Structural valve degeneration (SVD) is the leading cause of late bioprosthetic valve failure. Lipoprotein(a) [Lp(a)] contributes to native aortic valve calcification, but its role in SVD is unclear. We investigated whether elevated Lp(a) is associated with SVD after bioprosthetic aortic valve replacement (AVR) and whether this differs between stenotic and regurgitant phenotypes. We studied 174 bioprosthetic AVR patients with available Lp(a) levels over a median echocardiographic follow-up of 7.3 years (1372 studies). SVD was defined by VARC-3 criteria, and associations were analysed with Fine-Gray competing risk models. Lp(a) was evaluated categorically (≤ or > 125 nmol/L) and continuously using spline modelling. During follow-up, 40 patients developed SVD (22 stenotic, 9 mixed, and 9 regurgitant). The 15-year cumulative incidence was 51% with a median onset at 14.8 years. Elevated Lp(a) was associated with a higher risk of overall SVD (62% vs. 47%; SHR 2.06, 95% CI 1.09-3.91; P = 0.026) and specifically with stenotic/mixed phenotypes (SHR 2.57, 95% CI 1.26-5.23; P = 0.009). No association was observed with regurgitant phenotypes (SHR 0.85, 95% CI 0.19-3.92; P = 0.84). After multivariable adjustment, elevated Lp(a) remained an independent predictor of stenotic/mixed SVD (adjusted SHR 3.00, 95% CI 1.48-6.07; P = 0.002). Spline modelling showed a linear dose-response, with each 25 nmol/L increase in Lp(a) conferring 13% higher risk. Elevated Lp(a) is independently associated with long-term risk of stenotic/mixed SVD. These findings highlight Lp(a) as a promising biomarker of prosthetic valve vulnerability and support investigation of emerging Lp(a)-lowering therapies to improve valve durability. Show less

Significant associations exist between major depressive disorder (MDD), metabolic syndrome (MetS), and cardiovascular disease, potentially attributable to heightened atherogenicity. This study aimed to ascertain if MDD, depression severity, suicidal behaviors, and neuroticism associate with elevated pro-atherogenic indices and reduced anti-atherogenic indices, including a reverse cholesterol transport (RCT) index. This study comprised 34 healthy controls and 33 MDD patients without MetS, and 35 controls and 31 MDD patients with MetS. It assessed total cholesterol (TC) and free cholesterol (FC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), apolipoprotein (ApoA), ApoB, cholesterol esterification rate, and a RCT composite. No significant associations between MDD and lipids were seen in the total study group that combined individuals with and without MetS. In individuals devoid of MetS, MDD is significantly correlated with (a) elevated FC, TG, ApoB, Castelli risk index 1, and ApoB/ApoA, and (b) diminished HDLc, ApoA, and RCT index. In individuals without MetS, there are notable correlations between the severity of depression, suicidal tendencies, neuroticism, and ApoB/ApoA, Castelli risk, and RCT indices. The link between lipids and MDD features cannot be adequately estimated by combining participants with and without MetS. It should be examined in a study sample that excludes subjects with MetS. The depression phenome, suicidal behaviors, and neuroticism correlate with diminished RCT and heightened atherogenicity, which are likely implicated in the pathophysiology of MDD. Increased atherogenicity and lowered RCT may represent novel drug targets for the treatment and prevention of MDD, neuroticism, and suicidal behaviors. Show less

Major depressive disorder (MDD) and bipolar disorder (BD) often coexist with metabolic syndrome. Both are linked to increased atherogenicity and a higher risk of cardiovascular diseases. Nevertheless, a comprehensive analysis of key atherogenic biomarkers in MDD/BD is still lacking. This meta-analysis evaluates the relationship between atherogenic indices and MDD/BD, while identifying the most effective atherogenic biomarker. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched electronic databases, including PubMed, Google Scholar, and Web of Science, for articles published up to August 1, 2024. We included 85 eligible studies (14 on BD and 71 on MDD), covering 70,856 participants: 18,738 patients and 52,118 healthy controls. MDD/BD patients showed significant increases (p < 0.001) in the Castelli Risk Index 2 (CRI2), Atherogenic Index of Plasma (AIP), and (triglyceride or TG + low-density lipoprotein + very low-density lipoprotein)/(high-density lipoprotein cholesterol or HDL + Apolipoprotein A or ApoA) ratio, but not CRI1 and ApoB/ApoA ratio. Significant lower HDL and lecithin: cholesterol acyltransferase activity, and higher TG levels were observed in MDD/BD patients compared with controls. There were no significant differences between MDD and BD patients. Most included studies lacked the most essential information on the inclusion and exclusion of important confounders. AIP is the most effective atherogenicity index for mood disorders. Regular lipid profiling and metabolic syndrome screening are crucial in MDD/BD. Early intervention with lipid-lowering therapies is recommended to prevent the worsening of atherogenicity and disease progression. Show less

Major depression is classified into distinct subtypes: simple (SDMD) and major dysmood disorder (MDMD). MDMD patients exhibit elevated atherogenicity and decreased reverse cholesterol transport (RCT). However, comprehensive data regarding lipid metabolism is absent in first episode (FE)-SDMD. In this case-control study, plasma lipid levels, lecithin-cholesterol acyltransferase (LCAT), free cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE are compared between academic students with first episode SDMD (FE-SDMD) (n = 44) or SDMD (n = 64) and control students (n = 44), after excluding those with metabolic syndrome (MetS). LCAT is decreased, and free cholesterol and ApoE increased in subjects with SDMD and FE-SDMD as compared with controls. There were no significant alterations in high-density lipoprotein cholesterol (HDLc), ApoA1, RCT, ApoB and triglycerides in SDMD. LCAT, free cholesterol and atherogenicity indices are significantly associated with suicidal behaviors and the SDMD phenome. The effects of LCAT on those phenome features is completely mediated by free cholesterol and brooding. SDMD and FE-SDMD patients without signs of subclinical MetS show lowered LCAT and increased free cholesterol as compared with normal controls. There are significant interactions between the SDMD and FE-SDMD diagnosis and subclinical MetS, which result in decreased HDLc and RCT, and an increased ApoB/ApoA ratio. FE-SDMD and SDMD are pre-proatherogenic states, because of decreased LCAT, and increased free cholesterol and ApoE, and their intersections with subclinical MetS. These aberrations may drive atherogenicity, and activation of peripheral and central oxidative, neuro-immune, and degenerative pathways. Individuals with FE-SDMD should be screened and treated for increased atherogenicity risk by measuring free cholesterol and ApoE. Show less

We analysed intestinal tissues from groups of fast growing (Ross 308) broilers with natural or experimental coccidiosis, by genomic microarray. We identified genes that were differentially expressed (DE) in all groups and analysed expression of a panel of these, by qPCR, in Ross 308 and slow growing (Ranger classic) broilers, infected with 2500 or 7000 oocysts of Eimeria maxima for 6 or 13 days post-infection (dpi). Four genes (ADD3, MLLT10, NAV2 and PLXNA2) were upregulated (P <0.05) in Ross 308 but were not DE in Ranger Classic at 6 dpi with 2500 oocysts. Six genes (PTPRF, NCOR1, CSF3, SGK1, CROR and CD1B) were upregulated (P <0.05) in both Ross 308 and Ranger Classic infected with 2500 oocysts at 6 dpi but were not DE at 6 dpi with 7000 oocysts. At 13 dpi with 7000 oocysts, NAV2 and NCOR1 were upregulated in Ross 308 (P <0.05) and PTPRF was upregulated in both genotypes (P <0.05). DE of immune genes within the biomarker panel also occurred, with CSF3 upregulated in both genotypes infected with 2500 oocysts at 6 dpi and in Ranger Classic infected with 7000 oocysts, at 6 and 13 dpi (P <0.05). IL-22 was down-regulated in Ranger Classic infected with 2500 or 7000 oocysts at 6 dpi (P <0.05) but upregulated in both genotypes at 13 dpi (P <0.05). CD72 was down-regulated in Ranger Classic infected with 2500 oocysts at 6 dpi and with 7000 oocysts at 6 and 13 dpi (P <0.05). CD72 was upregulated in Ross 308 infected with 2500 oocysts at 6 dpi but was down-regulated following infection with 7000 oocysts at 13 dpi (P <0.05). In conclusion, differential gene expression occurs in fast and slow growing broiler genotypes with coccidiosis. In addition, we highlight a potential genetic biomarker panel for early diagnosis of coccidiosis. Show less

The autopsy of a 16-year-old boy who had died suddenly revealed hypertrophic cardiomyopathy (HCM). Molecular genetic investigation revealed mutations in the MYBPC3 gene. His surviving family members could then be examined and reassured that they did not carry the mutation. An 18-year-old boy who died suddenly turned out to have known HCM. No further investigations were done and no tissue was saved. Genetic investigation of his immediate family was impossible due to the lack of a known mutation in the family. Periodic examination in clinically unaffected family members was therefore advised. Sudden cardiac death at young age is not infrequently the first symptom of an inherited cardiac disease. Because these diseases usually inherit as an autosomal dominant trait, first-degree family members have a 50% chance of carrying the same genetic defect. Besides clinical cardiologic examination of the remaining family members, post-mortem molecular genetic investigation can be of value in reaching a diagnosis and in determining the subsequent therapeutic options for immediate relatives. Show less