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Atherosclerotic cardiovascular diseases (CVDs) are closely linked to factors such as familial hypercholesterolemia (FH), often caused by mutations in low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB). Through a comprehensive bioinformatic analysis, we identified novel LDLR and APOB mutations and their cardiovascular disease (CVD) implications, focusing on unique variants in the Vietnamese population. We used homology modeling to predict protein structures; in addition, through protein-protein molecular docking, we assessed how these mutations affect binding affinities. We identified 10 novel binding residues exclusive to the wild-type and precursor LDLR isoforms, including ASP-47, GLY-48, and GLU-51. Analyses of 154 complexes revealed 5 isoforms with low binding affinities and notable hydrogen-bonding interactions—APOB (Arg3527Trp)-LDLR (Cys318Arg), APOB (His3583Leu)-LDLR (Cys104Tyr), APOB wild-LDLR (Glu228Lys), APOB (Phe2469Cys)-LDLR (Glu288Lys), and APOB wild-LDLR (Ser130Ter). These results suggest strong and potentially detrimental interactions among these proteins. Furthermore, they highlight the molecular mechanisms underlying CVD development, reveal potential therapeutic targets, enhance our understanding of genetic variations, and could guide FH research. [ABSTRACT FROM AUTHOR]

Background: In developing countries, fewer women have access to multidisciplinary congenital heart disease and reproductive programs staffed by experts. We report pregnancy outcomes of a multidisciplinary healthcare strategy utilizing an in-hospital teamwork approach in Vietnam. Methods: This retrospective cohort study included pregnant women with unrepaired congenital heart disease managed at a referral cardiovascular center. Results: Undiagnosed congenital heart disease before pregnancy, a lack of pre-pregnancy cardiology counseling, and modified World Health Organization class III/IV were common. Under the multispecialty healthcare strategy, although the rate of maternal death was 8.2% in the modified World Health Organization class IV group, no deaths occurred in any other group. Fetal/neonatal complications occurred in 54% of pregnancies, and 49.4% of neonates survived. Poor pregnancy outcomes were associated with admission during the first/seconde trimester for fetus/neonates, third trimester for mother, modified World Health Organization class III/IV, cyanosis, and heart failure. Conclusion: The outcomes of pregnant women with unrepaired congenital heart disease were poor but seemed to improve with a multidisciplinary in-hospital healthcare teamwork strategy. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Familial hypercholesterolaemia has not been previously described in the Vietnamese population. We aimed to describe the features of patients with homozygous familial hypercholesterolaemia (hoFH) in Vietnam and the outcomes of screening family members using genetic and cholesterol testing. Methods Mutation testing by massively parallel sequencing for genes causative of FH was undertaken in five index cases presenting to a single cardiac center with a presumptive diagnosis of hoFH. Cascade testing of all available family members was subsequently undertaken. The number of new cases of FH detected and commenced on lipid-lowering treatment was evaluated. Results All five index cases had true homozygous mutations in the LDL receptor gene (LDLR). Cascade screening was undertaken in four families. 107 relatives were screened and FH was identified in 56 relatives (52%), including 3 new cases of hoFH. Only 5 FH relatives (9%) were subsequently treated owing to the adverse perceptions and comparative high cost of drug treatment, and lack of awareness of FH among patients and local doctors. Conclusions HoFH due to LDLR mutations is a severe disorder in Vietnam that needs early detection and treatment with LDL-cholesterol lowering drugs. Cascade testing of families allows effective detection of new cases of FH that may also benefit from early treatment. However, convincing patients to commence statin treatment is a challenge. Extended education and awareness programs and treatment subsidies are imperative to improve the care of patients and families suffering from FH in Vietnam. Highlights • Familial hypercholesterolaemia (FH) is not well studied in Vietnam. • Homozygous and heterozygous FH are severe disorders that requires early detection and treatment, however treatment with statins, apheresis and novel therapies is a challenging healthcare gap in Vietnam. • Owing to large pedigrees, cascade screening in Vietnam is a highly effective method of diagnosing new cases of FH in family members once an index case has been identified. • A lower LDL-cholesterol thresholds should be employed in the Vietnamese population for diagnosing FH. [ABSTRACT FROM AUTHOR]