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Genes Sep 2023Anderson-Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency....
Anderson-Fabry Disease (AFD) is a rare, systemic lysosomal storage disease triggered by mutations in the GLA gene, leading to α-galactosidase A (α-Gal A) deficiency. The disease's X-linked inheritance leads to more severe, early-onset presentations in males, while females exhibit variable, often insidious, manifestations, notably impacting cardiac health. This study aims to examine gender-based AFD cardiac manifestations in correlation with the variant type: classical (CL), late-onset (LO), or variants of uncertain significance (VUS). We analyzed data from 72 AFD patients (53 females, 19 males) referred to the "G. Rodolico" University Hospital, employing enzyme activity measurements, genetic analysis, periodic lyso-Gb3 monitoring, comprehensive medical histories, and advanced cardiac imaging techniques. Statistical analysis was performed using SPSS version 26. Our AFD cohort, with an average age of 45 ± 16.1 years, comprised 12 individuals with hypertrophy (AFD-LVH) and 60 without (AFD-N). Women, representing about 75% of the subjects, were generally older than men (47.2 ± 16.2 vs. 38.8 ± 14.6, = 0.046). In the female group, 17% had CL variants, 43.3% LO, and 39.6% had VUS, compared to 21.1%, 36.8%, and 31.6% in the male group, respectively. Females exhibited significantly higher α-Gal A values (median 7.9 vs. 1.8 nmol/mL/h, < 0.001) and lower lyso-Gb3 levels (1.5 [IQR 1.1-1.7] vs. 1.9 [1.5-17.3] nmol/L, = 0.02). Regarding the NYHA class distribution, 70% of women were in class I and 28% in class II, compared to 84% and 16% of men, respectively. Among women, 7.5% exhibited ventricular arrhythmias (10.5% in men), and 9.4% had atrial fibrillation (10.5% in men). Cardiac MRIs revealed fibrosis in 57% of examined women, compared to 87% of men. Even among patients without LVH, significant differences persisted in α-Gal A and lyso-Gb3 levels ( = 0.003 and 0.04), as well as LVMi (61.5 vs. 77.5 g/sqm, = 0.008) and GLS values (-20% vs. -17%, = 0.01). The analysis underscored older age, decreased lyso-Gb3 deposition, reduced hypertrophy, and lesser GLS compromise in females, suggesting later disease onset. Severe cardiac patterns were associated with classic variants, while more nuanced manifestations were noted in those with VUS. Early GLS impairment in males, irrespective of hypertrophy, emphasized the role of subclinical damage in AFD.
Topics: Humans; Male; Female; Adult; Middle Aged; Sex Characteristics; Fabry Disease; alpha-Galactosidase; Cardiomyopathies; Hypertrophy
PubMed: 37761944
DOI: 10.3390/genes14091804 -
Frontiers in Endocrinology 2023Increasing evidence supports a causal relationship between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular disease, yet its association with left ventricular...
BACKGROUND AND AIMS
Increasing evidence supports a causal relationship between lipoprotein(a) [Lp(a)] and atherosclerotic cardiovascular disease, yet its association with left ventricular hypertrophy (LVH) assessed by electrocardiogram (ECG) remains unknown. The aim of this study was to explore the relationship between Lp(a) and LVH assessed by ECG in general population.
METHODS AND RESULTS
In this cross-sectional study, we screened 4,052 adults from the participants of the third National Health and Nutrition Examination Survey for analysis. Lp(a) was regarded as an exposure variable. LVH defined by the left ventricular mass index estimated from ECG was considered as an outcome variable. Multivariate logistic regression and restricted cubic spline (RCS) were used to assess the relationship between Lp(a) and LVH. Individuals with LVH had higher Lp(a) compared to individuals without LVH (P< 0.001). In the fully adjusted model, Lp(a) was strongly associated with LVH when as a continuous variable (per 1-unit increment, OR: 1.366, 95% CI: 1.043-1.789, P = 0.024), and higher Lp(a) remained independently associated with a higher risk of LVH when participants were divided into four groups according to quartiles of Lp(a) (Q4 vs Q1, OR: 1.508, 95% CI: 1.185-1.918, P = 0.001). And in subgroup analysis, this association remained significant among participants< 60 years, ≥ 60 years, male, with body mass index< 30 kg/m, with hypertension and without diabetes (P< 0.05). In addition, we did not observe a nonlinear and threshold effect of Lp(a) with LVH in the RCS analysis (P for nonlinearity = 0.113).
CONCLUSION
Lp(a) was closely associated with LVH assessed by ECG in general population.
Topics: Adult; Humans; Male; Cross-Sectional Studies; Electrocardiography; Hypertrophy, Left Ventricular; Lipoprotein(a); Nutrition Surveys; Risk Factors
PubMed: 38098866
DOI: 10.3389/fendo.2023.1260050 -
Diagnostics (Basel, Switzerland) Sep 2023Ventricular hypertrophy is associated with diastolic dysfunction, resulting in increased left atrial (LA) pressure, enlargement, fibrosis, and decreased LA function.... (Review)
Review
Ventricular hypertrophy is associated with diastolic dysfunction, resulting in increased left atrial (LA) pressure, enlargement, fibrosis, and decreased LA function. Hypertrophic cardiomyopathy (HCM) is characterized by myocyte disarray, myocardial fibrosis, and hypertrophy. Notably, a thickened and noncompliant LV results in the impairment of diastolic function. These conditions promote LA remodeling and enlargement, which contribute to developing and maintaining atrial fibrillation (AF). AF is an atrial arrhythmia that occurs frequently in HCM, and evaluating the morphology and physiology of the atrium and ventricle is important for treatment and prognosis determination in HCM patients with AF. In addition, it provides a clue that can predict the possibility of new AF, even in patients not previously diagnosed with AF. Cardiac magnetic resonance (CMR), which can overcome the limitations of transthoracic echocardiography (TTE), has been widely used traditionally and even enables tissue characterization; moreover, it has emerged as an essential imaging modality for patients with HCM. Here, we review the role of multimodal imaging in patients with HCM and AF.
PubMed: 37835790
DOI: 10.3390/diagnostics13193049 -
Journal of Clinical Medicine Oct 2023Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during... (Review)
Review
Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during adulthood. Acromegaly could cause a typical cardiomyopathy characterized by left ventricular hypertrophy associated with diastolic dysfunction, which later could progress to systolic dysfunction. Moreover, some valvular and vascular abnormalities are also associated with acromegaly. This present review aims to summarize available information regarding acromegaly-associated abnormalities in myocardial, valvular, and vascular structural and functional properties and their relationship to disease activity and treatment options.
PubMed: 37959322
DOI: 10.3390/jcm12216857 -
Clinical and Experimental Hypertension... Dec 2023Echocardiogram is commonly used to evaluate cardiac remodeling in hypertension (HTN). However, study on echocardiographic phenotypes and their prognostic implications in...
BACKGROUND
Echocardiogram is commonly used to evaluate cardiac remodeling in hypertension (HTN). However, study on echocardiographic phenotypes and their prognostic implications in HTN is limited.
OBJECTIVE
We aimed to evaluate the prognostic implications echocardiographic phenotypes in community hypertensive patients.
METHOD
A total of 1881 community hypertensive patients without overt cardiovascular disease and severe renal disease (mean age 62.8 years, women 57.9%) were included. Using Two-Step cluster analysis with four conventional echocardiographic variables, two clusters with distinct echocardiographic phenotypes were identified.
RESULT
The Cluster 1 (namely "mild-remodeling" HTN; = 1492) had low prevalence of enlarged left atrium (LA; 0.9%) and left ventricular hypertrophy (LVH; 16.2%) and better LV diastolic function. They were younger and more likely to be men and had lower comorbid burden. The Cluster 2 (namely "severe-remodeling" HTN; = 389) had higher prevalence of enlarged LA (26.0%) and LVH (83.0%) and worse LV diastolic function. They were older and more likely to be women and had higher comorbid burden. After a median follow-up of 4.2 years, compared to the Cluster 1, the Cluster 2 had higher incidence of cardiovascular (4.1% vs 1.7%; = .006) and all-cause (9.8% vs 4.8%; < .001) death, with adjusted hazard ratio of 2.80 (95% CI 1.39-5.62; = .004) and 2.04 (95% CI 1.32-3.14; < .001) respectively.
CONCLUSION
These findings indicate that the conventional echocardiographic variables-based algorithm could help identify asymptomatic community hypertensive patients at risk for cardiovascular and all-cause death. Further studies are needed to develop and validate phenotype-specific prevention and intervention strategies in HTN.
Topics: Female; Male; Humans; Prognosis; Hypertension; Echocardiography; Cardiovascular Diseases; Hypertrophy, Left Ventricular; Phenotype
PubMed: 37477238
DOI: 10.1080/10641963.2023.2236334 -
Journal of the American Heart... Sep 2023Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney...
Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time-to-event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11-7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40-3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15-3.32]). Conclusions In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.
Topics: Humans; Serotonin; Hypertrophy, Left Ventricular; Cross-Sectional Studies; Prospective Studies; Stroke Volume; Ventricular Function, Left; Heart Failure; Atherosclerosis
PubMed: 37609990
DOI: 10.1161/JAHA.123.029785 -
Life Sciences Jan 2024Cardiac hypertrophy and fibrosis are associated with cardiac remodeling and heart failure. We have previously shown that miRNA-217, embedded within the third intron of...
AIM
Cardiac hypertrophy and fibrosis are associated with cardiac remodeling and heart failure. We have previously shown that miRNA-217, embedded within the third intron of MIR217HG, aggravates pressure overload-induced cardiac hypertrophy by targeting phosphatase and tensin homolog. However, whether the MIR217HG transcript itself plays a role in cardiac remodeling remains unknown.
METHODS
Real-time PCR assays and RNA in situ hybridization were performed to detect MIR217HG expression. Lentiviruses and adeno-associated viruses with a cardiac-specific promoter (cTnT) were used to control MIR217HG expression in vitro and in vivo. Transverse aortic constriction (TAC) surgery was performed to develop cardiac remodeling models. Cardiac structure and function were analyzed using echocardiography and invasive pressure-volume analysis.
KEY FINDINGS
MIR217HG expression was increased in patients with heart failure. MIR217HG overexpression aggravated pressure-overload-induced myocyte hypertrophy and fibrosis both in vivo and in vitro, whereas MIR217HG knockdown reversed these phenotypes. Mechanistically, MIR217HG increased THBS1 expression by sponging miR-138. MiR-138 recognized the 3'UTR of THBS1 and repressed THBS1 expression in the absence of MIR217HG. Silencing THBS1 expression reversed MIR217HG-induced cardiac hypertrophy and remodeling.
CONCLUSION
MIR217HG acts as a potent inducer of cardiac remodeling that may contribute to heart failure by activating the miR-138/THBS1 pathway.
Topics: Humans; Animals; Mice; RNA, Long Noncoding; Ventricular Remodeling; Cardiomegaly; Heart Failure; MicroRNAs; Fibrosis; Myocytes, Cardiac; Mice, Inbred C57BL
PubMed: 38013141
DOI: 10.1016/j.lfs.2023.122290 -
Open Heart Nov 2023Left ventricular hypertrophy (LVH) is frequently seen in association with arterial hypertension and indicates poor prognosis. This study aimed to determine the...
BACKGROUND
Left ventricular hypertrophy (LVH) is frequently seen in association with arterial hypertension and indicates poor prognosis. This study aimed to determine the prevalence of LVH and associated factors in a multiethnic population from Mauritius.
METHODS
Population-based health surveys were performed in 2009 and 2015 and included in total 8961 individuals aged 35-75 years with recorded 12-lead ECG. LVH was defined according to three criteria: Sokolow-Lyon, Cornell voltage and Cornell product. Data were collected about health and lifestyle behaviour. Anthropometry and blood pressure were measured. Fasting levels of blood lipids and glucose were determined, oral glucose tolerance test was performed in people without glucose-lowering medications.
RESULTS
The age-standardised prevalence of LVH was 9% (n=875) according to any of the three ECG criteria. Individuals with LVH were older, more likely to have hypertension, diabetes, known cardiovascular disease (CVD) and elevated levels of cholesterol and creatinine. Further, they were more likely to be of African descent (Creole) and have lower educational level. In a multivariable model, Creole (OR (95% CI)) (1.56 (1.33 to 1.83)), low educational level (1.49 (1.28 to 1.75)), hypertension (3.01 (2.55 to 3.56)), known CVD (1.42 (1.11 to 1.83)) and elevated creatinine (1.08 (1.03 to 1.14)) remained associated with LVH. Individuals with non-treated or uncontrolled hypertension had a higher risk for LVH (3.09 (95% CI 2.57 to 3.71) and 4.07 (95% CI 3.29 to 5.05), respectively), than individuals with well controlled hypertension or normotension.
CONCLUSION
LVH occurs more frequently in individuals with hypertension, as well as in individuals with African ancestry and/or low education level.
Topics: Humans; Hypertrophy, Left Ventricular; Prevalence; Creatinine; Hypertension; Risk Factors; Cardiovascular Diseases; Electrocardiography; Glucose
PubMed: 37935562
DOI: 10.1136/openhrt-2023-002495 -
Medicina (Kaunas, Lithuania) Aug 2023Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype-phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.
Topics: Humans; Cardiomyopathy, Hypertrophic; Heart; Heart Diseases; Hypertrophy, Left Ventricular; Alcohol Drinking
PubMed: 37629714
DOI: 10.3390/medicina59081424