Publications of Horvath, T.
Vertebral artery diameter and flow: nature or nurture. Neuroimaging. 2017;27(5).
Vertebral artery diameter and flow: nature or nurture
BACKGROUND AND PURPOSE In contrast with the carotid arteries, the vertebral arteries (VAs) show considerable variation in length, caliber, and vessel course. This study investigated whether the variation in diameter and flow characteristics of the VAs might be inherited. METHODS A total of 172 Italian twins from Padua, Perugia, and Terni (54 monozygotic, 32 dizygotic) recruited from the Italian Twin Registry underwent B‐mode and pulsed‐wave Doppler ultrasound assessment of their VAs. VA diameters, peak systolic velocity (PSV) and end diastolic velocity (EDV) were assessed at the level of a horizontal V2 segment. Univariate quantitative genetic modeling was performed. RESULTS Fourteen percent of the sample had VA hypoplasia. Within pair correlation in monozygotic twins was higher than in dizygotics (.552 vs. .229) for VA diameter. Age‐ and sex‐adjusted genetic effect, under the most parsimonious model, accounted for 54.7% (95% CI: 42.2‐69.1%) of the variance of VA diameter, and unshared environmental effect for 45.3% (95% CI: 30.9‐57.8%). No heritability was found for the PSV of VA, but shared (34.1%; 95% CI: 16.7‐53.7%) and unshared (65.9%; 95% CI: 45.9‐83.1%) environmental factors determined the variance. EDV of VA is moderately genetically influenced (42.4%; 95% CI: 16.1‐64.9%) and also determined by the unshared environment (57.6%; 95% CI: 34.7‐83.7%). CONCLUSIONS The diameter of the VAs is moderately genetically determined. Different factors influence the PSV and EDV of VAs, which may highlight the complex hemodynamic background of VA flow and help to understand the vertebral flow anomalies found by ultrasound.
Rationale, design and methodological aspects of the BUDAPEST-GLOBAL study (Burden of Atherosclerotic Plaques Study in Twins - Genetic Loci and the Burden of Atherosclerotic Lesions)
The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST‐GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single‐center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same‐sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non–contrast‐enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non–contrast‐enhanced image slice was acquired at the level of L3‐L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3‐dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per‐patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST‐GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders.
Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study. Journal of Breath Research. 2014;8(1).
Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study
Electronic noses can distinguish various disorders by analyzing exhaled volatile organic compound (VOC) pattern; however it is unclear how hereditary and environmental backgrounds affect the exhaled VOC pattern. A twin study enrolling monozygotic (MZ) and dizygotic (DZ) twins is an ideal tool to separate the influence of these factors on the exhaled breath pattern. Exhaled breath samples were collected in duplicates from 28 never smoking twin pairs (in total 112 samples) without lung diseases and processed with an electronic nose (Cyranose 320). Univariate quantitative hereditary modeling (ACE analysis) adjusted for age and gender was performed to decompose the phenotypic variance of the exhaled volatile compound pattern (assessing principal components (PCs) derived from electronic nose data) into hereditary (A), shared (C), and unshared (E) environmental effects. Exhaled VOC pattern showed good intra-subject reproducibility as assessed with the Bland-Altman plot. Significant correlations were found between exhaled VOC patterns of both MZ and DZ twins. The hereditary background did not influence the VOC pattern. The shared environmental effect on PC 1, 2 and 3 was estimated to be 93%, 94% and 54%, respectively. The unshared (unique) environmental influence explained a smaller variance (7%, 6% and 46%). For the first time using the twin design, we have shown that the environmental background largely affects the exhaled volatile compound pattern in never smoking volunteers without respiratory disorders. Further studies should identify these environmental factors and also assess their influence on exhaled breath patterns in patients with lung diseases.
Genetic impact dominates over environmental effects in development of carotid artery stiffness: a twin study. Hypertension Research. 2014;37:88-93.
Genetic impact dominates over environmental effects in development of carotid artery stiffness: a twin study
Arterial stiffness is an independent predictor of cardiovascular, cerebrovascular and all-cause mortality. Quantifying the genetic influence on the stiff arterial phenotype allows us to better predict the development of arterial stiffness. In this study, we aimed to determine the heritability of carotid artery stiffness in healthy twins. We studied 98 twin pairs of both sexes. We determined carotid artery stiffness locally using echo tracking and applanation tonometry. We estimated the heritability of stiffness parameters using structural equation modeling. The carotid distensibility coefficient showed the highest heritability (64%, 95% confidence interval 45–77%). The incremental elastic modulus, compliance and stiffness index β also showed substantial heritability (62%, 61% and 58%, respectively). The remaining 36–42% phenotypic variance was attributed to unshared environmental effects. Genetic influence appears to dominate over environmental factors in the development of carotid artery stiffness. Environmental factors may have an important role in favorably influencing the genetic predisposition for accelerated arterial stiffening.
Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection. Journal of Breath Research. 2013;7(2).
Genetic influence on the relation between exhaled nitric oxide and pulse wave reflection
Nitric oxide has an important role in the development of the structure and function of the airways and vessel walls. Fractional exhaled nitric oxide (FENO) is inversely related to the markers and risk factors of atherosclerosis. We aimed to estimate the relative contribution of genes and shared and non-shared environmental influences to variations and covariation of FENO levels and the marker of elasticity function of arteries. Adult Caucasian twin pairs (n = 117) were recruited in Hungary, Italy and in the United States (83 monozygotic and 34 dizygotic pairs; age: 48 ± 16 SD years). FENO was measured by an electrochemical sensor-based device. Pulse wave reflection (aortic augmentation index, Aixao) was determined by an oscillometric method (Arteriograph). A bivariate Cholesky decomposition model was applied to investigate whether the heritabilities of FENO and Aixao were linked. Genetic effects accounted for 58% (95% confidence interval (CI): 42%, 71%) of the variation in FENO with the remaining 42% (95%CI: 29%, 58%) due to non-shared environmental influences. A modest negative correlation was observed between FENO and Aixao (r = -0.17; 95%CI:-0.32,-0.02). FENO showed a significant negative genetic correlation with Aixao (rg = -0.25; 95%CI:-0.46,-0.02). Thus in humans, variations in FENO are explained both by genetic and non-shared environmental effects. Covariance between FENO and Aixao is explained entirely by shared genetic factors. This is consistent with an overlap among the sets of genes involved in the expression of these phenotypes and provides a basis for further genetic studies on cardiovascular and respiratory diseases.
Evidence for a strong genetic influence on carotid plaque characteristics: an international twin study
Background and Purpose— Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. Methods— One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. Results— Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%–90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%–87%), 69% for plaque size (area in mm2 in longitudinal plane; < or >50 percentile; 95% CI, 16%–86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%–90%), 74% for plaque numerosity (95% CI, 26%–86%), 68% (95% CI, 40%–84%), and 66% (95% CI, 32%–90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%–34%). Controlling for relevant covariates did not change the results significantly. Conclusions— The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.
Heritability of central blood pressure and arterial stiffness: a twin study. Journal of Hypertension. 2012;30(8):1564-71.
Heritability of central blood pressure and arterial stiffness: a twin study
OBJECTIVE: Central blood pressure and aortic stiffness have been consistently reported as strong cardiovascular risk factors. Twin studies by comparing identical with nonidentical twins produce information on the relative contribution of genes and environment. METHODS: One hundred and fifty-four monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43 ± 17 years) from Hungary and the United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic pulse wave velocity (PWV) measurements with the invasively validated Arteriograph device. Bivariate Cholesky decomposition models were applied. RESULTS: Age-adjusted, sex-adjusted and country-adjusted heritability was 60.0% for central SBP [95% confidence interval (CI), 44.8-69.6%], 50.1% for aortic PWV (95%CI, 26.0-66.8%), 48.7% for aortic AIx (95%CI, 1.7-74.0%), 46.8% for brachial AIx (95%CI, 1.1-73.8%), 46.7% for central pulse pressure (PP) (95%CI, 12.4-61.4%), and 30.0% for brachial PP (95%CI, 0.0-53.4%). Central SBP and PP had strong bivariate correlations with brachial (r = 0.461 and 0.425) and central AIx (r = 0.457 and 0.419), as well as with aortic PWV (r = 0.341 and 0.292, all P < 0.001). Brachial PP had a weak correlation with brachial AIx (r = -0.118, P < 0.05), central AIx (r = -0.122, P < 0.05), and none with aortic PWV (r = 0.08, P = n.s.). Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic PWV. CONCLUSIONS: Central systolic and PPs, brachial PP, AIx, aortic PWV are moderately heritable. A moderate genetic covariance among aortic PWV and central PP, central SBP and brachial SBP was found.
Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study. Cardiovascular Diabetology. 2011;10(96).
Genetikai és környezeti tényezők szerepe a kardiometabolikus kockázati tényezők alakulásában: ikervizsgálatok eredményei. Metabolizmus. 2011;10(96):304-9.
Effects of genetic versus environmental factors on cardiovascular autonomic function: a twin study. Diabetic Medicine. 2011;28(10):1241-8.
Twins lead to the prevention of atherosclerosis. Preliminary findings of International twin study. Journal for Vascular Ultrasound. 2011;35(2):61-71.
Reversible autonomic dysfunction during antiviral treatment in patients with chronic hepatitis C virus infection. Hepatitis Monthly. 2011;11(2):114-8.
Chronic hepatitis C virus infection associated with autonomic dysfunction. Liver International. 2009;29(10):1473-8.
Chronic hepatitis C virus infection associated with autonomic dysfunction
Background: Impaired autonomic function has been described in patients with chronic liver diseases from different aetiologies, and has proven to be a poor prognostic indicator. To date, it is not known how chronic hepatitis C virus (HCV) infection affects the autonomic nervous system. Aims: In the present study, we compared cardiovagal autonomic function in patients with chronic HCV infection and healthy controls and examined the relation between autonomic function and serum levels of aminotransferases, HCV RNA, cryoglobulins, albumin and glucose. Methods: Autonomic function was assessed in 45 treatment-naïve patients with chronic HCV infection and in 40 healthy controls by determining spontaneous baroreflex sensitivity (BRS) and heart rate variability (HRV) indices. The R–R interval was determined by electrocardiogram recording; continuous radial artery pressure was monitored simultaneously by applanation tonometry. Laboratory analyses and quantitative polymerase chain reaction for serum HCV RNA level were performed by standard procedures. Results: BRS and HRV time and frequency domain indices were lower in patients with HCV infection compared with healthy controls [7.1±3.4 vs. 11.5±6.5 ms/mmHg for BRS, 168.5±160.9 vs. 370.7±349.4 ms<sup>2</sup> for low-frequency HRV (mean±SD); P<0.01]. Multivariate analysis showed that autonomic dysfunction in HCV-infected patients correlated with elevated alanine aminotransferase levels, but was not associated with serum HCV RNA levels and cryoglobulins. Conclusion: Our results suggest that impaired autonomic function is caused by chronic HCV infection. Further studies are needed, however, to identify the underlying mechanisms.
Zur Situation der Sozialdemokratie nach 1945. In: Horvath T, editor. Richard Berczeller, 1902 – 1994 : Sopron – Mattersburg – New York. St. Margareten: Kanica; 1996. p. 97-101.