Giovanny Fuentevilla-Álvarez

Aims: The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) has emerged as a potential marker of cardiometabolic dysfunction. However, evidence regarding its association with prediabetes remains limited in Hispanic populations. We evaluated the association between UHR and prediabetes in Mexican-Mestizo adults from the Genetics of Atherosclerotic Disease (GEA) study. Methods: This retrospective cross-sectional analysis included 1395 adults without diabetes or coronary artery disease. Prediabetes was defined as fasting glucose levels between 100 and 125 mg/dL. Participants were stratified into sex-specific UHR tertiles. Logistic regression models adjusted for demographic, lifestyle, and cardiometabolic variables were used to evaluate the association between UHR and prediabetes. Results: Mean age was 53 ± 6 years, 51% were women, and 17% had prediabetes. Individuals in the highest UHR tertile exhibited higher adiposity indices, triglycerides, Apo-B, hsCRP, HOMA-IR, and lower HDL-C and adiponectin levels. Prediabetes prevalence increased progressively across UHR tertiles (11%, 15%, and 24%; p < 0.001). After multivariable adjustment, each 0.1-unit increase in UHR was associated with prediabetes (OR 1.65, 95% CI 1.26–2.17). Compared with the lowest tertile, individuals in the highest UHR tertile had more than two-fold higher odds of prediabetes (OR 2.03, 95% CI 1.36–3.05, p < 0.001). A significant interaction between UHR and sex was observed, with a stronger association in women than in men (OR 3.39, 95% CI 2.1–5.5 vs. 1.19, 95% CI 0.84–1.67). Conclusions: Higher UHR was independently associated with prediabetes and an adverse cardiometabolic profile in Mexican-Mestizo adults. UHR may serve as a simple complementary marker of glucose metabolic disturbances.

Marfan syndrome (MS), Loeys–Dietz syndrome (LDS), Beals–Hecht syndrome (BHS), Ehlers–Danlos syndrome (EDS), and individuals with undifferentiated connective tissue disease (UCTD) exhibit phenotypic overlap, suggesting a likelihood of genotypic coexistence. Our objective was to evaluate genetic variants (GVs), encoding 174 genes related to aortopathies, cardiomyopathies, arrhythmias, structural heart disease, and hypercholesterolemia, and their relationship to clinical and cardiovascular damage in these syndromes. This was a prospective study in Mexican patients with MS, LDS, EDS, BHS, and UCTD. One hundred and seventy-four genes related to hereditary diseases were studied using next-generation sequencing targeting coding regions. Of the 136 patients, 25 were identified with the recurrent and coexisting GV of MYBPC3. In the MS group, in addition to the presence of GV in FBN1, eight patients had GV in MYBPC3, six in FBN2, and five in COL3A1 and COL5A1. In the LDS group, in addition to GV in TGFBR1, TGFBR2, and SMAD3, four patients presented with GV in MYBPC3 and two with FBN2. In the BHS group, in addition to FBN2, two patients had GV in MYBPC3 and one with TGFBR2. In the UCTD group, nine patients had GV in MYBPC3 and two in COL5A1 and COL5A2. All syndromes coexisted with GV in genes related to arrhythmias, sarcomeres, and hypercholesterolemia. In EDS, coexistence with several sarcomere proteins was found.

This case-control study investigated the association between polymorphisms in the dedicator of cytokinesis 2 (DOCK2) gene and susceptibility to COVID-19 in a Mexican population. Methods: Genotyping of five single-nucleotide polymorphisms (SNPs) in the DOCK2 gene (rs9307 A/G, rs1045176 G/T, rs1045168 C/T, rs2112703 A/C, and rs2287727 A/C) was performed using TaqMan assays in 248 COVID-19 patients and 288 healthy controls. Results: No significant differences were observed in the allelic or genotypic distributions of rs1045176 G/T and rs2287727 A/C between cases and controls. However, under multiple genetic inheritance models (co-dominant, dominant, recessive, heterozygous, and additive), the rs9307 A, rs1045168 C, and rs2112703 A alleles were significantly associated with a reduced risk of COVID-19 (p < 0.05). Furthermore, sub-analyses stratified by genotype in COVID-19 patients revealed that the rs9307 AA, rs1045168 CC, and rs2112703 AA genotypes correlated with altered plasma concentrations of lactic acid dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ferritin. Conclusions: The DOCK2 SNPs rs9307 A/G, rs1045168 C/T, and rs2112703 A/C are associated with decreased susceptibility to COVID-19 in this population and influence plasma levels of LDH, ALT, AST, and ferritin, suggesting a potential role in disease pathogenesis and severity.

Background: This longitudinal study assessed the Uric Acid/HDL-Cholesterol (UA/HDL-C) ratio as a prognostic biomarker for fatty liver disease (FLD) during a five-year follow-up of 1022 participants from the Genetics of Atherosclerotic Disease (GEA) Study. FLD is a multifactorial disease associated with cardiometabolic comorbidities, and genetic variants affecting uric acid transport (ABCG2 rs2231142) and hepatic lipid metabolism (PNPLA3 rs738409). Early diagnosis is essential to prevent disease progression; however, standard diagnostics are expensive and not widely accessible, highlighting the need for noninvasive tools. Objectives: The study aimed to validate the UA/HDL-C as a long-term predictor for FLD and its effectiveness in risk stratification, including adjustment for cardiometabolic factors and genetics. Methods: Non-contrast computed tomography was used to diagnose FLD and rs738409 and rs2231142 were genotyped by real-time PCR. ROC curves, Kaplan–Meier survival analysis, and logistic regression were used. Results: The findings show that FLD patients exhibited significantly higher UA/HDL-C than controls at both baseline and follow-up (p < 0.0001). Higher UA/HDL-C quartiles were associated with greater FLD prevalence, exceeding 50% in the highest quartile. The index cut-off points were 0.18 in men and 0.09 in women. ROC analysis showed significant discrimination for FLD (AUC: 0.637 overall, 0.650 in men, 0.626 in women). Conclusions: Logistic regression confirmed a strong independent association between UA/HDL-C and FLD over five years, even after adjustment for genetic, biochemical, and anthropometric factors, OR = 3.53, 95% CI: 2.39–4.68, p < 0.0001. Results suggest this ratio could be an alternative to find and follow FLD early on, especially in places with few resources.

Background: Fatty liver disease (FLD), the most common liver disease worldwide, is associated with cardiometabolic diseases and increases the risk of cardiovascular disease. It remains asymptomatic in its early stages, and late diagnosis heightens the likelihood of progression to severe liver diseases. Objectives: We aimed to evaluate the utility of serum uric acid to HDL cholesterol ratio (UA/HDL-C) as a biomarker for FLD and compare its diagnostic utility versus established liver disease index (FLI, LAP, HSI, NAFLD score (FLS), and ALT/AST ratio). Methods: This cross-sectional study, conducted between 2009 and 2013, included 1470 adults, 50.2% women and 49.8% men between 20 and 75 years old. FLD was diagnosed using non-contrast computed tomography. The population was stratified by sex and FLD. The associations with UA/HDL-C were analyzed using ROC curves and logistic regression analysis to evaluate and compare the predictive capacity of various indices for FLD. Results: Anthropometric, physiologic, biochemical variables, ratios, and indices were significantly higher in subjects with FLD (p < 0.001). In the unadjusted logistic regression model, UA/HDL-C is strongly associated with FLD (co-efficient 2.5, p < 0.001). The FLS, HSI, and ALT/AST ratios were also significant, whereas FLI and LAP showed no clear relationship. In the sex-adjusted model, the UA/HDL-C ratio remained strongly associated with FLD (3.47, p < 0.001). Conclusions: Our results suggest that the UA/HDL-C ratio is associated with FLD as an established liver disease index and may be a practical, useful marker for FLD. The results highlight its potential as a scrutiny and early biomarker for effective preventive strategies for FLD.

Dipeptidyl peptidase-4 (DPP4) concentrations are known to correlate with nonalcoholic fatty liver (FL), which is also associated with subclinical atherosclerosis (SA). This study aimed to determine whether DPP4 concentrations and the DPP4 rs17574 polymorphism are associated with FL in individuals with SA. The study included 378 participants with SA, of whom 143 had FL and 235 did not. DPP4 serum concentrations were measured using a Bioplex system, and DPP4 rs17574 genotypes were determined using TaqMan assays. Logistic regression was used to assess the relationships between FL, DPP4 concentrations, and rs17574 genotypes. Overall, DPP4 concentrations did not differ significantly between individuals with and without FL. No significant differences in DPP4 levels were observed among DPP4 genotypes in the total sample. However, within the FL group, significant differences in DPP4 concentration were observed across genotypes: AA genotype (134 [106–175] ng/mL), AG genotype (128 [114–149] ng/mL), and GG genotype (80 [71–117] ng/mL); P = 0.019. The DPP4 rs17574 polymorphism was associated with FL under a recessive model (P = 0.037). DPP4 concentration was also significantly associated with FL: the likelihood of presenting with FL increased by 6.2% for every 10 ng/mL increase in DPP4 levels (P = 0.009). These findings suggest that DPP4 concentration may serve as a biochemical risk marker for FL in individuals with SA. Moreover, the rs17574 polymorphism may influence DPP4 protein levels, particularly in those with FL. To our knowledge, this is the first study to describe an association between DPP4 concentration, the rs17574 polymorphism, and FL. Assessing DPP4 levels may offer a novel and effective strategy for risk stratification of FL in SA populations.

La enfermedad arterial coronaria es un padecimiento crónico y multifactorial, considerado un problema de salud en el mundo. En su desencadenamiento participan factores ambientales y genéticos. Diversos estudios, incluyendo los del genoma completo y de genes candidatos, han sugerido la participación de múltiples genes en el desarrollo de esta patología. Sin embargo, la mayoría de estas investigaciones se ha realizado en poblaciones caucásicas y orientales. Se ha identificado que los mexicanos presentan una mezcla de genes caucásicos, indígenas y africanos, composición que varía conforme al sitio del país donde se analice. Considerando lo anterior, los resultados de estudios realizados en otras poblaciones no pueden aplicarse a los mexicanos. En 2008, por iniciativa del doctor Carlos Posadas Romero, se inició el proyecto GEA (Genética de la Enfermedad Aterosclerosa), con el objetivo de generar conocimiento sobre los factores ambientales y genéticos que contribuyen a la enfermedad arterial coronaria prematura en la población mexicana. La presente revisión muestra la participación de la genética en el desarrollo de la enfermedad arterial coronaria prematura en los mexicanos, con base en los resultados obtenidos en la cohorte GEA.

Marfan syndrome (MFS) is an inherited connective tissue disorder, with aortic root aneurysm and/or dissection being the most severe and life-threatening complication. These conditions have been linked to pathogenic variants in the FBN1 gene and dysregulated TGFβ signaling. Our objective was to evaluate the mRNA expression of FBN1, TGFBR1, TGFBR2, and TGFB2 in aortic tissue from MFS patients undergoing surgery for aortic dilation. This prospective study (2014–2023) included 20 MFS patients diagnosed according to the 2010 Ghent criteria, who underwent surgery for aneurysm or dissection based on Heart Team recommendations, along with 20 non-MFS controls. RNA was extracted, and mRNA levels were quantified using RT-qPCR. Patients with dissection showed significantly higher FBN1 mRNA levels [79 (48.1–110.1)] compared to controls [37.2 (25.1–79)] (p = 0.03). Conversely, TGFB2 expression was significantly lower in MFS patients [12.17 (6.54–24.70)] than in controls [44.29 (25.85–85.36)] (p = 0.029). A positive correlation was observed between higher FBN1 expression and a larger sinotubular junction diameter (r = 0.42, p = 0.07), while increased FBN1 expression was particularly evident in MFS patients with dissection. Additionally, TGFB2 expression showed an inverse correlation with ascending aortic diameter (r = 0.53, p = 0.01). In aortic tissue, we found decreased TGFB2 and receptor levels alongside increased FBN1 mRNA levels. These molecular alterations may reflect compensatory mechanisms in response to tissue damage caused by mechanical stress, leading to dysregulation of physiological signaling pathways and ultimately contributing to aortic dilation in MFS.

Background: Type 4 cardiorenal syndrome (CRS) involves cardiovascular alterations caused by chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF23), carboxy-terminal propeptide of procollagen type I (PIP), and parathyroid hormone (PTH) have been proposed as biomarkers of pathological cardiac remodeling in CKD. In contrast, it has been suggested that MicroRNA 221 has a cardioprotective role. Available evidence shows that, 12 months after kidney transplantation (KT), type 4 CRS reverts in only half of the patients.Objective: To assess long-term cardiac reverse remodeling after KT and its association with FGF23, PIP, and PTH levels.Methods: Patients with end-stage renal disease were assessed before and 28 months after KT using FGF23, PIP, and PTH serum concentrations and transthoracic echocardiography.Results: Fifty-three patients were followed for 28 months after KT. All the patients showed cardiac abnormalities upon inclusion. A follow-up assessment showed a reduction in left ventricle (LV) mass (121 ± 48 vs. 65 ± 14 gr/m²) and left atrial volume (46 vs. 30 ml/m²). The LV ejection fraction (53 vs. 63%), LV global longitudinal strain (-15.9 vs.-19.4%), and LV diastolic function improved. miR-221 expression increased after KT (8.73 RIQ= 3.7-25 vs. 40.16 RIQ= 24-223, p=0.001) and was correlated with the Ee´ratio (r= -0.32, p= 0.02). Multivariate analysis showed that post-KT LV mass was determined by pre-KT LV mass, serum Cr level, post-KT PIP, and hypertension (R² = 0.65, F=12.1, p=0.001).Conclusions: Contrary to other evidence, this study demonstrated that type 4 CRS is reversible over the long term. This is a paramount finding because KT normalizes cardiac structure and function independently of the severity of basal cardiac abnormalities.

Deregulation of micro-RNAs (miRNAs) may contribute to mechanisms of injury in the bicuspid aortic valve (BAV). Our objective was to investigate the expression of miRNAs in aortic tissue from patients who underwent aortic valve replacement for aortic stenosis and its relationship with aortic dilatation. The study included 78 patients, 40 with bicuspid aortic valve (BAV) and 38 with tricuspid aortic valve (TAV). The expression of miRNA-17-5p, hsa-let-7e, and miRNA-196a-5p in human aortic tissue was evaluated by a reverse transcriptase polymerase chain reaction (RT-qPCR). Comparative analysis between patients with BAV and controls with TAV explored the association between the miRNAs and aortic dilatation (AD), calcification, valve dysfunction, and stenosis. The results showed that the expression levels of miRNA-Let-7e-5p and miRNA-196-5p were mostly increased in patients with BAV and aortic dilatation (p = 0.01 and p = 0.01), respectively. In contrast, the levels of miRNA-17a-5p (p < 0.20) were lower but without a statistically significant difference. The downregulation of miRNA-17a-5p and the upregulation of miR-Let-7e-5p and miR-196-5p were related to an increased risk of AD risk. Subjects with BAVs with or without double aortic lesions had higher expression levels of Let-7e-5p and miRNA-17a-5p vs. TAV. In all patients, we found an inverse correlation of MiRNA-196-5p with High-Density Lipoprotein-Cholesterol (HDL-C) and indexed valvular area. In subjects with a higher expression of miRNA196, lower levels of HDL-C correlation (r²) [r² 0.27 (p = 0.02)] and a lower indexed valvular area [r² 0.28 (p = 0.05)] were observed. In the specific analysis for each patient group, it was found that in control subjects with tricuspid aortic valve (TAV), miRNA-196-5p had a positive correlation with valvular calcification (r² = 0.60, p = 0.02). Deregulation of miRNAs in the aortic tissue of a BAV may influence valvular stenosis, dysfunction, and concomitant aortic dilation. This information could help to define potential therapeutic target strategies to improve the prognosis and treatment of BAV.