Publications of P Maurovich-Horvat

Genetic and environmental determinants of longitudinal stability of arterial stiffness and wave reflection. A twin study

Background: We aimed at evaluating the impact of genetic and environmental factors on longitudinal changes in aortic pulse wave velocity (aPWV) and aortic augmentation index (aAIx). Method: Three hundred and sixty-eight Italian and Hungarian adult twins (214 monozygotic, 154 dizygotic) underwent repeated evaluations of aPWV and aAIx (TensioMed Arteriograph). Within-individual/cross-wave, cross-twin/within-wave and cross-twin/cross-wave correlations were calculated; bivariate Cholesky models were fitted to calculate additive genetic (A), shared environmental (C) and unique environmental (E) components. Results: For both aPWV and aAIx, cross-twin correlations in monozygotic pairs (r between 0.35 and 0.56) were all significant and always higher than in dizygotic pairs, both at wave 1 and at wave 2. Heritability and unshared environmental proportion of variance at each wave were substantially time-invariant for aPWV (heritability 0.51, 95% CI 0.36–0.63 at wave 1; 0.49, 95% CI 0.34–0.62 at wave 2), whereas for aAIx, we observed a diminished genetic effect (heritability 0.57, 95% CI 0.45–0.67 at wave 1; 0.37, 95% CI 0.21–0.51 at wave 2). Overlapping genetic factors explained a high proportion (0.88, 95% CI 0.61–1.00) of longitudinal covariance for aPWV, and had a relatively lower impact on aAIx (0.55, 95% CI 0.35–0.70). Genetic correlations of aPWV (r = 0.64, 95% CI 0.42–0.85) and aAIx (r = 0.70, 95% CI 0.52–0.87) between waves were lower than 1, suggesting a potential contribution of novel genetic variance on arterial stiffening. Conclusion: Changes in aPWV and aAIx over time are largely genetically determined. Our results might stimulate further studies on genetic and epigenetic factors influencing the process of vascular ageing.

Genetically determined pattern of left ventricular function in normal and hypertensive hearts

We sought to assess the inheritance of left ventricular (LV) function using speckle‐tracking echocardiography and the impact of hypertension on modifying the genetically determined pattern of contraction in a population of twins. We recruited 92 Caucasian twin pairs, including 74 hypertensive (HTN) siblings. Beyond standard echocardiographic protocol, a speckle‐tracking analysis was performed, including global longitudinal strain (GLS). Systolic function, as assessed by ejection fraction, showed moderate heritability (61%); however, GLS showed higher and dominant heritability (75%). Heterogeneity models revealed that there were no differences between the HTN and non‐HTN subjects regarding the heritability of GLS. However, the heritability estimates of diastolic function parameters, including early diastolic strain rate, were low. LV systolic biomechanics is highly heritable. GLS shows dominant heritability, despite the presence of early‐stage hypertensive heart disease. Early diastolic parameters are rather determined by environmental factors. These findings suggest the presence of a genetic framework that conserves systolic function despite the expression of diastolic dysfunction and may underlie the phenotypic progression towards heart failure with preserved ejection fraction.

Heritability of the femoral intima media thickness

Background The measurement of femoral intima-media thickness (IMT) is underutilized in the clinical practice, although it is a surrogate marker of cardiovascular disease. Materials and methods 388 Hungarian and Italian twins (121 monozygotic, 73 dizygotic pairs) underwent bilateral B-mode sonography of femoral arteries. IMT was measured by semiautomated software, where available, or by calipers. Results Within-pair correlation in monozygotic twins was higher than in dizygotics for each parameter. Age-, sex- and country-adjusted genetic effect accounted for 43.9% (95% confidence interval, CI 21.3%–65.2%) and 47.2% (95% CI, 31.4%–62.6%) of the variance of common and superficial femoral artery IMT, respectively, and unshared environmental effect for 56.1% (95% CI 34.6%–78.5%) and 52.8% (95% CI, 37.2%–68.5%). These results did not change significantly after correcting for body mass index or central systolic blood pressure. Conclusions Genetic factors have a moderate role in the determination of common and superficial femoral IMT; however, the influence of environmental (lifestyle) factors remains still relevant. Environmental factors may have a role in influencing the genetic predisposition for femoral vascular hypertrophy.

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.