Publications of Lannert, A.

Genetic effects on refraction and correlation with hemodynamic variables: a twin study

Spherical equivalent (SE) has not been linked to increased cardiovascular morbidity. Methods: 132 Hungarian twins (age 43.3±16.9 years) underwent refraction measurements (Huvitz MRK-3100 Premium AutoRefractokeratometer) and oscillometry (TensioMed Arteriograph). Results: Heritability analysis indicated major role for genetic components in the presence of right and left SE (82.7%, 95%CI, 62.9 to 93.7%, and 89.3%, 95%CI, 72.8 to 96.6%), while unshared environmental effects accounted for 17% (95%CI, 6.3% to 37%), and 11% (95%CI, 3.4% to 26.7%) of variations adjusted for age and sex. Bilateral SE showed weak age-dependent correlations with augmentation index (AIx), aortic pulse wave velocity (r ranging between 0.218 and 0.389, all p < 0.01), aortic systolic blood pressure and pulse pressure (r between 0.188 and 0.289, p < 0.05). Conclusions: These findings support heritability of spherical equivalent, which does not coexist with altered hemodynamics (e.g. accelerated arterial aging). Accordingly, SE and the investigated hemodynamic parameters seem neither phenotypically nor genetically associated. Keywords: arterial stiffness, augmentation index, genetics, heritability, refraction

Heritability of Venous Biomechanics

Objective-Altered venous biomechanics may contribute to the pathogenesis of venous diseases, and their heritability is less known. Methods and Results-Seventy-eight monozygotic twin pairs (aged 42.4±16.8 years) and 24 same-sex dizygotic twin pairs (aged 50.5±16.1 years) were examined. Anteroposterior and mediolateral diameters of the common femoral vein were measured by ultrasonography. Measurements were made both in supine and in standing body positions, with or without controlled forced expiration (Valsalva test). High correlation of diameter, capacity, and distensibility values was found between twin pairs. The univariate heritability (A), shared (C), and unshared (E) environmental effects model has shown 39.3% genetic component of the variance of low pressure, 37.9% of high-pressure venous capacity, and 36.4% of maximal capacity changes, even after elimination of sex, age, and body weight effects. Bivariate Cholesky analysis revealed substantial covariance of inherited body weight and venous capacity components (57.0%-81.4%). Conclusion-Femoral vein capacity and elasticity depend 30% to 40% on genetic factors, and this value in the standing body position can reach 50%. A relatively high genetic covariance was found between weight and femoral vein capacity and elasticity. Our work might yield some new insights into the inheritance of venous diseases that are associated with altered venous biomechanics and help elucidate the involved genes.

Association of body mass index with arterial stiffness and blood pressure components: a twin study

Rationale Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown. Methods We studied 228 monozygotic and 150 dizygotic twin pairs aged 18–82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m2). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph. Results Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p < 0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%–58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = −0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors (65%–77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15–0.17, p < 0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p < 0.05). Conclusion Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.

Genetic and environmental factors on the relation of lung function and arterial stiffness

Background An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. Methods 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. Results Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45–85%), 28% (95% CI: 0–67%), 68% (95% CI: 20–81%) and 45% (95% CI: 0–66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between −0.12 and −0.17. No genetic covariance between lung function and arterial stiffness was found. Conclusions Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.

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.

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.

Heritability of non-alcoholic fatty liver disease and association with abnormal vascular parameters: A twin study

Background Non‐alcoholic fatty liver disease (NAFLD) has been linked to increased cardiovascular morbidity. However, genetic factors have an unclear role in this condition. Aims To analyse heritability of NAFLD and its association with abnormal vascular parameters in a large twin cohort. Methods Anthropometric and lipid metabolic parameters were obtained from 208 adult Hungarian twins (63 monozygotic and 41 dizygotic pairs; 58 men and 150 women; age 43.7 ± 16.7 years). B‐mode ultrasonography was performed to detect steatosis and categorize severity. Brachial and aortic augmentation indices and aortic pulse wave velocity were assessed using oscillometry (TensioMed Arteriograph). Carotid intima media thickness (IMT) was measured using ultrasonography on the proximal common, distal common and internal carotid arteries. Results NAFLD was identified in 47 subjects (22.6%), of which 44 (93.6%) had mild and 3 (6.4%) had moderate steatosis. These subjects were older (age: 50.9 ± 14.3 vs. 41.5 ± 16.7 years, P < 0.001) and had a higher body mass index (BMI; 30.1 ± 5.2 vs. 24.6 ± 4.1 km/m2, P < 0.001) than non‐NAFLD twins. Based on 91 same‐sex twin pairs, heritability analysis indicated no discernible role for genetic components in the presence of NAFLD (95% confidence interval, 0.0–36.0%), while shared and unshared environmental effects accounted for 74.2% and 25.8% of variations adjusted for age and BMI. Augmentation indices and carotid IMT in twins with NAFLD were increased at most examined locations (P < 0.05–P < 0.001). Conclusion These findings do not support heritability of NAFLD, although it coexists with vascular parameters linked to increased cardiovascular risk, underscoring the importance and value of prevention in this very common disorder.