Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies ...suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors.
Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied.
The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index.
OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening.
Summary
The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of ...effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b‐9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 0–338.5 ng ml−1) and in the morning (85.5 0–247.8 ng ml−1) compared with controls (30.3 0–176.8 ng ml−1 and 36.3 0–167.1 ng ml−1, evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b‐9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 1.6–47.4 ng ml−1 to 9.3 0–46.4 ng ml−1, p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C‐reactive protein and low high‐density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.
Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus ...environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease.
In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use.
We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% 95% CI, 56%-67%, unique environment, 37% 95% CI, 33%-44%), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% 95% CI, 50%-66%; unique environmental, 42% 95% CI, 34%-50% and additive genetic, 78% 95% CI, 73%-80%; unique environmental, 22% 95% CI, 20%-27%), respectively.
Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation.
URL: https://www.
gov; Unique identifier: NCT01738828.
Background and Objectives: Brain atrophy is related to cognitive decline. However, the heritability of brain atrophy has not been fully investigated in the Eastern Asian population. Materials and ...Methods: Brain imaging of 74 Japanese twins registered in the Osaka University Twin Registry was conducted with voxel-based morphometry SPM12 and was processed by individual voxel-based morphometry adjusting covariates (iVAC) toolbox. The atrophy of the measured lobes was obtained by comparing the focal volume to the average of healthy subjects. Classical twin analysis was used to measure the heritability of its z-scores. Results: The heritability of brain atrophy ranged from 0.23 to 0.97, depending upon the lobes. When adjusted to age, high heritability was reported in the frontal, frontal-temporal, and parietal lobes, but the heritability in other lobes was lower than 0.70. Conclusions: This study revealed a relatively lower heritability in brain atrophy compared to other ethnicities. This result suggests a significant environmental impact on the susceptibility of brain atrophy the Japanese. Therefore, environmental factors may have more influence on the Japanese than in other populations.
Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using ...coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non‐calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty‐one adult subjects (59 ± 9 years, 15 men) underwent a 256‐slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty‐two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea‐hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.
: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. ...This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited.
We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects.
39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7-75.2%; E: 37%; 95% CI: 24.8-54.3%) and volume (A: 60.1%; 95% CI: 42.4-73.2%; E: 39.9%; 95% CI: 26.8-57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment.
The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system.
: Aortic arch calcification (AoAC) is associated with a variety of cardiovascular complications. The measurement and grading of AoAC using posteroanterior (PA) chest X-rays are well established. The ...cardiothoracic ratio (CTR) can be simultaneously measured with PA chest X-rays and used as an index of cardiomegaly. The genetic and environmental contributions to the degree of the AoAC and CTR are not well understood. The purpose of this study was to investigate the effect of genetics and environmental factors on the AoAC and CTR.
: A total of 684 twins from the South Korean twin registry (261 monozygotic, MZ and 81 dizygotic, DZ pairs; mean age 38.6 ± 7.9 years, male/female = 264/420) underwent PA chest X-rays. Cardiovascular risk factors and anthropometric data were also collected. The AoAC and CTR were measured and graded using a standardized method. A structural equation method was used to calculate the proportion of variance explained by genetic and environmental factors behind AoAC and CTR.
: The within-pair differences were low regarding the grade of AoAC, with only a few twin pairs showing large intra-pair differences. We found that the thoracic width showed high heritability (0.67, 95% CI: 0.59-0.73,
= 1). Moderate heritability was detected regarding cardiac width (0.54, 95% CI: 0.45-0.62,
= 0.572) and CTR (0.54, 95% CI: 0.44-0.62,
= 0.701).
: The heritable component was significant regarding thoracic width, cardiac width, and the CTR.
The mechanism underlying the association between personality profile and subclinical atherosclerosis is poorly understood. This study explores the association between personality, carotid ...atherosclerosis and arterial stiffness, and the contribution of genes and environment to this association.
Early atherosclerotic traits, including carotid intima-media thickness (CCA-IMT), aortic pulse wave velocity (PWVao) and heart rate, were assessed in 318 adult twins, who also completed a Big Five personality questionnaire. Using the co-twin control approach, the association between intra-pair differences in clinical and personality scores was assessed in dizygotic (DZ) and monozygotic (MZ) twins separately.
An association between CCA-IMT and extroverted personality, as well as between PWVao and openness to experience was detected. The inverse association between CCA-IMT and extraversion was persistent in DZ and disappeared in MZ twins, suggesting genetic confounding. In contrast, the association between PWVao and openness to experience was of the same magnitude in DZ and MZ twins, thus surviving the adjustment for genetic and shared environmental factors.
This study highlights that the association between some psychological factors and cardiovascular traits may be partly explained by genetic factors. This result may provide support for the feasibility of prevention programs based on assessing familiarity for personality disorders to detect genetic risk for subclinical cardiovascular disease.
•Personality profile and early traits of atherosclerosis are weakly associated.•Association of personality with atherosclerotic traits is mostly due to genetics.•Results draw attention on early detection of cardiovascular risk based on personality.
Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary ...calcification (CAC) might incorporate genetic links between different arteries' atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet.
We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries.
CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 95% CI: 0.37-1 and 0.69 95% CI: 0.38-1, respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 95% CI: 0-0.76). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 95% CI: 0.30-0.63 and the underlying genetic correlation was 0.86 95% CI: 0.42-1.
Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.
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