Ádám Levente Jermendy

Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study

BackgroundBoth genetic and environmental factors play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. The magnitude of genetic and environmental influences may vary in different populations and can be investigated by twin studies.MethodsIn this cross-sectional study, 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n = 202; mean age: 44.3 ± 15.8 years) were investigated. Past medical history was recorded and physical examination was performed. Fasting venous blood samples were taken for measuring laboratory parameters. For assessing heritability of 14 cardiovascular risk factors, the structural equation (A-C-E) model was used.ResultsThe following risk factors were highly (> 70.0%) or moderately (50.0 - 69.0%) heritable: weight (88.1%), waist circumference (71.0%), systolic blood pressure (57.1%), diastolic blood pressure (57.7%), serum creatinine (64.1%), fibrinogen (59.9%), and serum C-reactive protein (51.9%). On the other hand, shared and unique environmental influences had the highest proportion of total phenotypic variance in serum total cholesterol (46.8% and 53.2%), serum HDL-cholesterol (58.1% and 14.9%), triglycerides (0.0% and 55.9%), fasting blood glucose (57.1% and 42.9%), fasting insulin (45.4% and 54.5%), serum uric acid (46.0% and 31.3%), and serum homocysteine (71.8% and 28.2%, respectively).ConclusionSome cardiometabolic risk factors have strong heritability while others are substantially influenced by environmental factors. Understanding the special heritability characteristics of a particular risk factor can substantiate further investigations, especially in molecular genetics. Moreover, identifying genetic and environmental contribution to certain cardiometabolic risk factors can help in designing prevention and treatment strategies in the population investigated.

Effects of genetic vs. environmental factors on cardiovascular autonomic function: a twin study

Diabet. Med. 28, 1241–1248 (2011)

[Heritability of the risk factors characteristic for the metabolic syndrome: a twin study].

UNLABELLED Both genetic and environmental factors play role in the pathogenesis of the metabolic syndrome. The magnitude of genetic and environmental influences on the components of metabolic syndrome may vary in different populations. AIMS The present study was aimed to determine the effects of genetic and environmental factors on risk factors characteristic for the metabolic syndrome. METHODS A total of 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n=202; mean age: 43.3±15.8 years) were investigated. Medical history was recorded and physical examination was carried out for each subject. Fasting venous blood samples were used for measuring laboratory parameters. The presented estimates include the heritability structural equation (A-C-E) model results. In Model-1, all presented parameters are age- and gender- corrected. In Model-2, parameters were corrected for age, gender, body mass index and waist circumference. RESULTS Heritability in waist circumference (as well as in other anthropometric parameters such as weight and height) was high (Model-1: 71.0-88.1%). Similarly, genetic factors had the highest proportion of total phenotypic variance in systolic and diastolic blood pressure (Model-2: 57.1% and 57.7%, respectively). Based on the results of Model-2, unique environmental factors dominate alterations in serum triglycerides values (55.9%) while shared environmental factors proved to be substantial in alterations of HDL-cholesterol and fasting blood glucose values (58.1% and 57.1%, respectively). Comparing the results of Model-1 and Model-2, the difference in A-C-E model varied from 0.0% to 17.1%, indicating that only a minor proportion of genetic and environmental influences can be explained by the effects of anthropometric parameters. CONCLUSIONS Among adult Hungarian healthy people, genetic factors have substantial influence on waist circumference and blood pressure values while environmental factors dominate alterations in serum triglycerides, HDL-cholesterol and fasting blood glucose values. The different heritability of individual risk factors challenges the original unifying concept of the metabolic syndrome. The results may be useful for establishing and implementing primary cardiovascular prevention both at individual and population levels.

Clinical importance of epicardial adipose tissue

Different visceral fat compartments have several systemic effects and may play a role in the development of both insulin resistance and cardiovascular diseases. In the last couple of years special attention has been paid to the epicardial adipose tissue (EAT), which can be quantified by non-invasive cardiac imaging techniques. The epicardial fat is a unique fat compartment between the myocardium and the visceral pericardium sharing a common embryologic origin with the visceral fat depot. Epicardial adipose tissue has several specific roles, and its local effects on cardiac function are incorporated in the complex pathomechanism of coronary artery disease. Importantly, EAT may produce several adipocytokines and chemokines that may influence – through paracrine and vasocrine effects – the development and progression of coronary atherosclerosis. Epicardial adipose tissue volume has a relatively strong genetic dependence, similarly to other visceral fat depots. In this article, the anatomical and physiological as well as pathophysiological characteristics of the epicardial fat compartment are reviewed.

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.

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.

Assessing genetic and environmental influences on epicardial and abdominal adipose tissue quantities: A classical twin study

Background/Objectives:Various adipose tissue compartments play an important role in the development of cardiometabolic diseases. The quantity of different fat compartments is influenced by genetic and environmental factors. The aim of our study was to evaluate the magnitude of genetic and environmental effects on epicardial, subcutaneous and visceral adipose tissue (EAT, SAT and VAT) quantities in a cohort of adult twin pairs.Subjects/Methods:In this cross-sectional study we investigated adult twins (57 monozygotic (MZ) and 33 dizygotic (DZ) same-gender twin pairs; 180 twin subjects). We measured EAT volume using electrocardiogram-gated native computed tomography (CT) scan of the heart, and abdominal SAT and VAT areas were quantified between the third and fourth lumbar vertebra on native CT images. We calculated genetic and environmental impact on the size of various adipose tissue compartments by analyzing co-twin correlations in MZ and DZ pairs separately, and furthermore by using genetic structural equation models.Results:In co-twin analysis, MZ twins had stronger correlations than DZ twins for EAT (rMZ=0.81, rDZ=0.32), similar to SAT and VAT quantities (rMZ=0.80, rDZ=0.68 and rMZ=0.79, rDZ=0.48, respectively). In multi-trait model fitting analysis, the overall contribution of genetic factors to EAT, SAT and VAT volumes were 80%, 78% and 70%, whereas environmental factors were 20%, 22% and 30%, respectively. Common pathway model analyses indicated that none of the EAT, SAT and VAT phenotypes was independent of the other two.Conclusions:Genetic factors have substantial influence, while environmental factors have only a modest impact on EAT volume, abdominal SAT and VAT quantities. There is a considerable amount of common genetic background influencing the quantities of all three adipose tissue compartments.

Iterative model reconstruction reduces calcified plaque volume in coronary CT angiography

OBJECTIVE To assess the impact of iterative model reconstruction (IMR) on calcified plaque quantification as compared to filtered back projection reconstruction (FBP) and hybrid iterative reconstruction (HIR) in coronary computed tomography angiography (CTA). METHODS Raw image data of 52 patients who underwent 256-slice CTA were reconstructed with IMR, HIR and FBP. We evaluated qualitative, quantitative image quality parameters and quantified calcified and partially calcified plaque volumes using automated software. RESULTS Overall qualitative image quality significantly improved with HIR as compared to FBP, and further improved with IMR (p<0.01 all). Contrast-to-noise ratios were improved with IMR, compared to HIR and FBP (51.0 [43.5-59.9], 20.3 [16.2-25.9] and 14.0 [11.2-17.7], respectively, all p<0.01) Overall plaque volumes were lowest with IMR and highest with FBP (121.7 [79.3-168.4], 138.7 [90.6-191.7], 147.0 [100.7-183.6]). Similarly, calcified volumes (>130 HU) were decreased with IMR as compared to HIR and FBP (105.9 [62.1-144.6], 110.2 [63.8-166.6], 115.9 [81.7-164.2], respectively, p<0.05 all). High-attenuation non-calcified volumes (90-129 HU) yielded similar values with FBP and HIR (p=0.81), however it was lower with IMR (p < 0.05 both). Intermediate- (30-89 HU) and low-attenuation (<30 HU) non-calcified volumes showed no significant difference (p=0.22 and p=0.67, respectively). CONCLUSIONS IMR improves image quality of coronary CTA and decreases calcified plaque volumes.

2D.05: RELATIONSHIP OF CORONARY ATHEROSCLEROSIS WITH ARTERIAL STIFFNESS AND CENTRAL SYSTOLIC BLOOD PRESSURE.

Objective: Arterial stiffness, an independent predictor of cardiovascular disease has been associated with the presence and extent of coronary artery calcification (CAC). We sought to assess the relationship between various hemodynamic parameters and presence of coronary atherosclerotic plaques. Design and method: In a prospective study 213 subjects (76 men and 137 women, mean age 56 ± 9 years) underwent oscillometry (TensioMed Arteriograph, Medexpert Ltd., Budapest, Hungary), CAC scoring and coronary CT angiography (CTA) (256-slice Brilliance iCT, Philips Healthcare, Best, The Netherlands). The association of aortic pulse wave velocity (PWV), brachial and central systolic blood pressure (SBP) with the presence of calcified and non-calcified plaques was analyzed with multivariate logistic regression (SPSS Statistics 17). Results: Those presenting with CAC were on average 10 years older (n = 47). Subjects with > 0 total CAC score in comparison to subjects with no CAC had a significantly higher brachial (128 ± 16.3 vs. 122 ± 14 mmHg) and central systolic blood pressure (SBP, 129 ± 22 vs. 121 ± 17 mmHg) and aortic pulse wave velocity (10 ± 2 vs. 8 ± 2 m/s), all p < 0.01. Subjects with any calcified or non-calcified plaques on coronary CTA had a higher brachial SBP, aortic PWV (both p < 0.01) and SBP (p < 0.05). Controlling for sex, age and age-squared in a regression, >0 total CACS (B = 0.983, p < 0.01), any atherosclerotic plaque (B = 1.286, p < 0.001) were both significantly associated with higher aortic PWV, but not with brachial or central systolic blood pressure. Conclusions: Patients with coronary atherosclerosis have a higher arterial stiffness. However, we did not find a association between arterial stiffness and systolic or central blood pressure. Further studies are warranted to evaluate the predictive value of arterial stiffness in coronary atherosclerotic risk assessment.

Genetic influence on femoral plaque and its relationship with carotid plaque: an international twin study

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.