Publications of Zini, C.
Association of body mass index with arterial stiffness and blood pressure components: a twin study. Atherosclerosis. 2013;229(2):388-95.
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. Respiratory Medicine. 2013;107(6):927-35.
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. 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.
Twins lead to the prevention of atherosclerosis. Preliminary findings of International twin study. Journal for Vascular Ultrasound. 2011;35(2):61-71.