-
Circulation Jan 2024Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for (myosin light chain 3) to ≈55% for (myosin-binding protein C3), ≈60% for (troponin T2) and (troponin I3), and ≈65% for (myosin heavy chain 7). Population-based genetic studies demonstrate that P/LP sarcomere variants are present in the background population but at a low prevalence of <1%. The penetrance of HCM in incidentally identified P/LP variant carriers was also substantially lower at ≈11%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in UK Biobank. In longitudinal family studies, the pooled phenotypic conversion across all genes was 15% over an average of ≈8 years of follow-up, starting from a mean of ≈16 years of age. However, short-term gene-specific phenotypic conversion varied between ≈12% for and ≈23% for .
CONCLUSIONS
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.
Topics: Humans; Adult; Penetrance; Mutation; Cross-Sectional Studies; Pedigree; Cardiomyopathy, Hypertrophic; Troponin T
PubMed: 37929589
DOI: 10.1161/CIRCULATIONAHA.123.065987 -
Clinical Cardiology Jan 2024Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.
Topics: United States; Humans; Cardiomyopathy, Hypertrophic; Heart; Disease Progression; Heart Failure; Myosins
PubMed: 38269637
DOI: 10.1002/clc.24207 -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
International Journal of Sports Medicine Jul 2023The R577X polymorphism in the α-actinin-3 gene () is associated with muscle strength and power; there is an association between R577X polymorphism and range of motion... (Meta-Analysis)
Meta-Analysis
The R577X polymorphism in the α-actinin-3 gene () is associated with muscle strength and power; there is an association between R577X polymorphism and range of motion (ROM). We examined the effect of the R577X polymorphism on ROM through meta-analysis and systematic review. Relevant studies published before April 14, 2022 were identified from the PubMed database using the following keywords and Boolean operators: ("flexibility" or "Joint Range of Motion" or "Joint Flexibility" or "Range of motion") and ("ACTN3" or "alpha-actinin 3"). Studies that met the following criteria were included: (1) published in English, (2) included human subjects, (3) provided ROM measurements, and (4) analyzed the R577X genotype. A total of 2908 participants from seven studies were included in the meta-analysis. The additive genetic model was assessed using a meta-regression model, and dominant and recessive models were analyzed using a random effects model. The ROM in the XX+RX genotype was significantly higher than that in the RR genotype (recessive model: p<0.001), and it increased additively in the order XX>RX>RR (additive model: p=0.029). However, no significant association was observed in the dominant model. These findings further elucidate the association between flexibility and the R577X genotype.
Topics: Humans; Actinin; Genotype; Muscle Strength; Polymorphism, Genetic; Range of Motion, Articular
PubMed: 36787803
DOI: 10.1055/a-2035-8300 -
BMC Cardiovascular Disorders Feb 2024An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery...
An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.
Topics: Humans; Calcium; Cross-Sectional Studies; Coronary Vessels; Coronary Artery Disease; Cardiovascular Diseases; Risk Factors; Heart Diseases; Troponin; Vascular Calcification
PubMed: 38336618
DOI: 10.1186/s12872-024-03761-x -
PeerJ 2023High-sensitivity cardiac troponin (hs-cTn) is associated with cardiovascular outcomes in the general population, but the prognostic value of hs-cTn in the diabetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-sensitivity cardiac troponin (hs-cTn) is associated with cardiovascular outcomes in the general population, but the prognostic value of hs-cTn in the diabetic population remains inconclusive. This study aimed to systematically review current evidence regarding the association between hs-cTn and the prognosis of diabetic patients.
METHODS
MEDLINE, Embase, and the Cochrane Database were searched from inception to May, 2023. Observational studies that investigated the prognostic value of hs-cTn in diabetic patients were included in this meta-analysis. Studies were excluded if they did not report outcomes of interest, or urine hs-cTn were measured. Two independent investigators extracted and analyzed the data according to the PRISMA guidelines. The primary outcome was long-term major adverse cardiovascular events (MACE).
RESULTS
We included 30 cohort studies of 62,419 diabetic patients. After a median follow-up of 5 (4.1-9.5) years, the pooled results suggested elevation of hs-cTn was associated with a significantly increased risk of MACE (adjusted hazard ratio (HR) per standard deviation (SD) change 1.15, 95% CI [1.06-1.25], I = 0%) and heart failure (adjusted HR per SD change 1.33, 95% CI [1.08-1.63], I = 0%) in patients with diabetes. No significant association was found regarding the association between elevation of hs-cTn and risk of all-cause mortality (adjusted HR per SD change 1.24, 95% CI [0.98-1.57], I = 0%). The results of sensitivity analyses were similar in prospective cohort studies, high-quality studies, or population without major cardiovascular comorbidities at baseline. hs-cTn may represent a strong and independent predictor of MACE and heart failure in diabetic patients. Future research is warranted to determine the appropriate cutoff value for hs-cTn with different comorbidities, for instance, diabetic nephropathy, peripheral artery diseases, etc.
Topics: Humans; Prognosis; Prospective Studies; Heart Failure; Troponin; Diabetes Mellitus; Observational Studies as Topic
PubMed: 38025710
DOI: 10.7717/peerj.16376