👤 Godfrey Lema

Residual cardiovascular risk remains substantial despite widespread adoption of intensive lipid-lowering strategies-statins, PCSK9 inhibitors, and RNA-based agents-that achieve very low LDL-C and apoB levels. Over the past three years, converging epidemiologic and mechanistic evidence has highlighted emotional stress-including anger, grief, anxiety, and chronic psychosocial strain-as a biologically active determinant of atherosclerotic disease and a frequent trigger of acute events. We propose the Emotion-Lipid Synergy Model, in which lipid burden establishes the atherothrombotic substrate while emotion-driven autonomic and vascular perturbations amplify endothelial dysfunction, microvascular constriction, inflammation, and thrombogenicity-thereby widening the residual-risk gap even when lipid targets are met. From this perspective, prevention should evolve toward precision psychocardiology: systematically screening for distress and stress reactivity; leveraging wearables to detect high-risk emotional states; and delivering timely, scalable, just-in-time behavioral interventions alongside guideline-directed lipid management. Particular attention is warranted for women and patients with angina and no obstructive coronary disease, who appear disproportionately susceptible to mental-stress ischemia. We outline a research agenda-flagship outcomes trials, mechanistic studies, and multimodal phenotyping-and discuss implementation pathways that integrate emotion metrics into cardiac rehabilitation and routine care. Integrating emotion assessment and modulation with lipid control offers a pragmatic route to reduce residual risk and advance equitable, personalized cardiovascular prevention. Show less

Gender Dysphoria is characterized by a marked incongruence between the cerebral sex and biological sex. To investigate the possible influence of karyotype on the etiology of Gender Dysphoria we carried out the cytogenetic analysis of karyotypes in 444 male-to-females (MtFs) and 273 female-to-males (FtMs) that attended the Gender Identity Units of Barcelona and Málaga (Spain) between 2000 and 2016. The karyotypes from 23 subjects (18 MtFs and 5 FtMs) were also analysed by Affymetrix CytoScan™ high-density (HD) arrays. Our data showed a higher incidence of cytogenetic alterations in Gender Dysphoria (2.65%) than in the general population (0.53%) (p < 0.0001). When G-banding was performed, 11 MtFs (2.48%) and 8 FtMs (2.93%) showed a cytogenetic alteration. Specifically, Klinefelter syndrome frequency was significantly higher (1.13%) (p < 0.0001), however Turner syndrome was not represented in our sample (p < 0.61). At molecular level, HD microarray analysis revealed a 17q21.31 microduplication which encompasses the gene KANSL1 (MIM612452) in 5 out of 18 MtFs and 2 out of 5 FtMs that corresponds to a copy-number variation region in chromosome 17q21.31. In conclusion, we confirm a significantly high frequency of aneuploidy, specifically Klinefelter syndrome and we identified in 7 out of 23 GD individuals the same microduplication of 572 Kb which encompasses the KANSL1 gene. Show less

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2') lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps. Show less