Genetic Influences on Resting Electrocardiographic Variables in Older Women: A Twin Study

Background: Previous studies in young and middle‐aged men and women have shown that resting electrocardiographic (ECG) variables are influenced by genetic factors. However, the extent to which resting ECG variables are influenced by genetic factors in older women is unknown. Thus, the aim of this study was to estimate the relative contribution of genetic and environmental influences to individual differences in resting ECG variables among older female twins without overt cardiac diseases. Methods: Resting ECG recordings were obtained from 186 monozygotic and 203 dizygotic twin individuals, aged 63–76 years. Quantitative genetic modeling was used to decompose the phenotypic variance in each resting ECG variable into additive genetic, dominance genetic, shared environmental, and unique environmental influences. Results: The results showed that individual differences in the majority of the resting ECG variables were moderately to highly explained by additive genetic influences, ranging from 32% for T axis to 72% for TV₅. The results also suggested dominance genetic influences on QRS duration, TV₁, and Sokolow–Lyon voltage (36%, 53%, and 57%, respectively). Unique environmental influences were important for each resting ECG variable, whereas shared environmental influences were detected only for QT interval and QTc. Conclusion: In older women without overt cardiac diseases, genetic influences explain a moderate to high proportion of individual differences in the majority of the resting ECG variables. Genetic influences are especially strong for T‐wave amplitudes, left ventricular mass, and hypertrophy indices, whereas other variables, including heart rate, intervals, and axes, are more affected by environmental influences.     

Genetic Influences on Use and Abuse of Alcohol: A Study of 5638 Adult Finnish Twin Brothers

To evaluate genetic influences on the use and abuse of alcohol, we compared questionnaire measures of the frequency, quantity, and density of social drinking, and the frequency of alcohol-induced passouts self-reported by 879 monozygotic (MZ) and 1940 dizygotic (DZ) pairs of twin brothers, aged 24-49 yr. The measures of frequency, quantity, and density (heavy drinking once or more a month) significantly intercorrelate, and the self-reported alcohol consumption by this sample is satisfactorily stable and consistent with nationwide sales figures. None of the drinking measures was associated with twin type (zygosity), and only density correlated with age. Similarity of drinking habits among twin brothers was evaluated as a function of their genetic resemblance and age, the frequency of their social contact with one another, and the interactions of these terms. The effects were estimated from hierarchical linear regressions of a double-entry data matrix from which each twin's drinking was predicted from that of his twin brother, and that pair's age, zygosity, cohabitation status, and frequency of social contact. Significant genetic variance was found for each of the drinking measures with heritability estimates ranging from 0.36 to 0.40. Co-twins in more frequent social contact with one another reported greater similarity in their use of alcohol, but heritable variance remained after the effects of age and social contact were removed from both mean levels and co-twin resemblance. Reported frequency of passouts yielded significant, but equivalent, correlations in both MZ and DZ twins and no evidence of genetic influence.     

Genetic Influence on Capillary Oxygen Saturation: A Twin Study

Background

While heritability has been shown for daytime sleepiness, the heritability of daytime capillary oxygen saturation (SpO₂) has not been described in detail. Our aim was to estimate the role of genes and environmental factors—both shared and unshared—in the variation of daytime SpO₂.

Methods

A total of 193 adult healthy twin pairs (138 monozygotic, 55 dizygotic) were recruited in Hungary and in the United States [age = 43.6 ± 15.6 years (mean ± SD)]. SpO₂ was measured by pulse oximetry. Univariate quantitative genetic modeling was performed to decompose the phenotypic variance of the considered parameter into heritability (A), shared (C), and unshared (E) environmental effects.

Results

SpO₂ twin correlation in monozygotic twins was stronger than in dizygotic twins (0.30 and ?0.15, respectively, p < 0.05). Age-, sex-, country-, and body mass index-adjusted genetic effects accounted for 26 % (95 % CI 10, 45 %) of the variance of SpO₂, and the unshared environmental component explained the remaining 74 % (95 % CI 59, 89 %). No shared environmental influence on SpO₂ was detected. The heritability of SpO₂ was not different between smokers and nonsmokers.

Conclusion

In summary, individual differences in daytime SpO₂ are explained by genetic and unshared environmental effects. The strong unshared environmental influence highlights the role of prevention of known environmental risk factors.     

Electrocardiographic Indices of Left Ventricular Hypertrophy and Repolarization Phase Share the Same Genetic Influences: A Twin Study

Background: Both left ventricular hypertrophy (LVH) and repolarization phase (RP) are known to be attributable to genetic influences, but less is known whether they share same genetic influences. The aim of this study was to investigate to what extent individual differences in electrocardiographic (ECG) LVH and RP are explained by genetic and environmental influences and whether these influences are shared between these two traits. Methods: Resting ECG recordings were obtained from 186 monozygotic and 203 dizygotic female twin individuals, aged 63 to 76 years. Latent factors, called LVH and RP, were formed to condense the information obtained from LVH indices (Cornell voltage and Cornell product) and T‐wave amplitudes (leads V₅ and II), respectively. Multivariate quantitative genetic modeling was used both to decompose the phenotypic variances into additive genetic, common environmental, and unique environmental influences, and for the calculation of genetic and environmental correlations between LVH and RP. Results: Additive genetic influences explained 16% of individual differences in LVH and 74% in RP. The remaining individual differences were explained by both common and unique environmental influences. The genetic correlation and unique environmental correlation between LVH and RP were ?0.93 and ?0.05, respectively. Conclusions: In older women without overt cardiac diseases, RP is under stronger genetic control than LVH. The majority of genetic influences are shared between LVH and RP whereas environmental influences are mainly specific to each.     

Pulmonary Function Changes after Large Volume Paracentesis

Large volume paracentesis (LVP) is a safe, rapid, and effective treatment of ascites in cirrhotic patients. We investigated the effects of a 5-L aspiration of ascites on pulmonary function parameters in eight hemodynamically stable patients with cirrhosis and tense ascites. None had known lung disease or abnormal chest roentgenograms. At baseline, mean lung volumes, diffusing capacity, and arterial pO₂ were all reduced from normal predicted values. Airflow, however, when related to lung volume, was normal. Post-LVP, lung volumes increased significantly; the mean expiratory reserve volume showed the greatest percent increase (105%) and correlated with the increases in the vital capacity, functional residual capacity, and total lung capacity. Airflow, the mean diffusing capacity, and arterial oxygenation were not significantly changed after LVP. We conclude that LVP significantly increases indices of lung volume but does not significantly alter parameters of airflow or gas exchange.     

Genetic Influences on Circulating Vitamin D Level: A Review

Over the last decade, there has been renewed interest in vitamin D due to increasing evidence of its importance in a wide range of health outcomes in addition to its traditional role in bone health. Although environmental factors play important roles in determining vitamin D levels, recent large-scale genetic studies also confirmed strong genetic influences. Recent genome-wide association studies (GWAS) have found genetic variations associated with vitamin D metabolism on several genes such as 7 dehydrochlesterol reductase (DHCR7), vitamin D binding protein (GC), 25-hydroxlase (CYP2R1), and 24-hydroxylase (CYP24A1). Vitamin D receptor (VDR), 25-hydroxyvitamin D 1-?? hydroxylase (CYP27B1) and another 25- and 24-hydroxylase (CYP3A4) have also shown significant association in various candidate gene studies. Despite recent success in genetic studies, currently identified genes could only explain a small fraction of genetic variation in 25-hydroxyvitamin D level. With advances in next generation sequencing technologies, additional genetic variants and epigenetic mechanisms are expected to further reveal the genetic architecture of vitamin D metabolism.     

Cardiac Function and Its Evolution with Pulmonary Vasodilator Therapy: A Myocardial Deformation Study

Speckle tracking echocardiography–derived myocardial strain has useful clinical applications in adults with pulmonary hypertension (PH) as well as preterm infants with chronic lung disease. It is considered more sensitive compared to conventional indices. This report presents a 3‐month‐old infant with PH and poor right ventricular function who was treated with inhaled nitric oxide. Myocardial strain was noted to be impaired with paradoxical segmental strain. Impairment in strain improved after inhaled nitric therapy. Strain analysis can help improve understanding of cardiac adaptation in critical clinical situations.     

Clinical Characteristics and Surgical Outcomes in Patients With Intermittent Exotropia: A Large Sample Study in South China

The clinical characteristics and surgical outcomes in a large sample of patients with intermittent exotropia (IXT) as well as an analysis of risk factors associated with surgical failures are presented in this article. Data from IXT patients who received surgical management at the Eye Hospital, in the Zhongshan Ophthalmic Center, of Sun Yat-Sen University, China from January 2009 to December 2013 were reviewed retrospectively. Included within this analysis were data from pre- and postoperative ocular motility, primary alignment, and binocular vision.A total of 1228 patients with IXT were reviewed. Males (50.4%) and females (49.6%) were nearly equally represented in this sample. Thirty-two patients (2.6%) had a family history of strabismus. The mean age at onset was 6.77 ± 6.43 years (range 7 months –48.5 years), mean duration at presentation was 7.35 ± 6.68 years (range 6 months–47 years), and mean age at surgery was 13.7 ± 8.8 years (range 3–49 years). The mean refractive error was −0.84 ± 2.69 diopter in the right eye and −0.72 ± 2.58 diopter in the left eye. Amblyopia (4.2%), oblique muscle dysfunction (7.0%), and dissociated vertical deviation (4.7%) were also present in these patients. The most common subtype of IXT was the basic type (88.1%). Orthophoria was observed in 80.5% of patients and the ratios of surgical undercorrection and overcorrection were 14.7% and 4.8%, respectively, as determined with a mean follow-up time of 7.8 ± 3.7 months. When combining ocular alignment with binocular vision as the success criteria, the success rate decreased to 35.6%. Multivariate risk factor analysis showed that only the loss of stereoacuity (P = 0.002) was associated with a poor outcome. There were no differences in the long-term results between bilateral lateral rectus recession and unilateral lateral rectus recession with medial rectus resection.Most IXT patients displayed normal vision, with few having positive family histories, amblyopia, oblique muscle dysfunction, and dissociated vertical deviation. The most common subtype of IXT was the basic type. Long-term surgical results were less favorable when sensory status was included in the criteria for success. Patients with stereoacuity loss were at an increased risk for poor outcomes.     

Genetic and Environmental Influences on Forced Expiratory Volume in Midlife: A Cross-Cultural Replication

Previous research has shown that forced expiratory volume (FEV) is a useful predictor of remaining life in older adults . The present analyses are an attempt to replicate results from a study of Swedish twins which demonstrated substantial heritability of FEV with a sample of middle aged Russian adult twins . Data were collected from 116 pairs of Russian twins (monozygote = 71, dizygotic = 45, mean age = 40.9 years). Phenotypic correlations between FEV , age , gender , height , and cigarette consumption ( in pack years ) were all significant , ranging from - . 72 to . 31 . After the effects of age , gender , height , and smoking were partialled out of FEV , quantitative genetic analyses were conducted . Shared environmental effects were significant , accounting for 47 % of the variance in FEV . Genetic effects , which accounted for about 28 % of the variance , could be dropped from the model without a significant decrease in the fit . These results are discussed in relation to previous research conducted in other countries .     

Genetic Influences on Insulinemia in Normotensive Twins

The aim of this study was to establish the contribution of genetic factors to the variance of plasma insulin concentration in healthy, normotensive twins. Seventeen pairs of monozygotic (MZ) and 17 pairs of dizygotic (DZ) twins were investigated. The test of genetic variance revealed a significantly larger within-pair variance of fasting plasma insulin (FPI) and a relative insulin resistance (RIR) in the DZ twins, in comparison with the MZ twins. Both FPI and RIR had a higher intraclass correlation coefficient in the MZ twins than in the DZ twins; the corresponding heritability estimates were 0.54 for FPI and 0.66 for RIR. Adjusting for age, gender, and body mass index did not affect heritability estimates for either FPI or RIR. Our data indicate that genetic factors are important determinants of insulinemia in normal subjects, independent of body mass index.     

Pulmonary Embolism in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study

Background: To evaluate the incidence of pulmonary embolism (PE) in patients with chronic obstructive pulmonary disease (COPD) in Taiwan. Methods: This was a retrospective population-based cohort study using data retrieved from Taiwan's National Health Insurance Research Database (2000 to 2008), which contains 99% of Taiwanese healthcare data. The evaluations included 355,878 COPD patients and 355,878 non-COPD patients for comparison. Results: The incidence of PE in the COPD cohort was 12.31 per 10,000 person-years (1.37/10,000 persons/y), which was approximately 4-times higher than in the comparison cohort (0.35/10,000 persons/y). In the COPD cohort, risk of PE was higher in the young age group (20-59 y, HR 4.64, 95% CI 3.06-7.03) than in other age groups. Risk of PE was higher in patients with COPD combined with hypertension, coronary artery disease, and cancer, or those with previous operation (HR 4.16, 4.75, 4.56, and 4.50 respectively) than in those with COPD and no comorbidity. Conclusions: The overall incidence of PE is lower in Taiwan than in western countries. However, the prevalence of PE in COPD patients is higher than in non-COPD patients and increases with age. It is crucial to incorporate PE into the differential diagnosis of COPD exacerbation for clinical physicians.     

The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension

ObjectivesThe REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC).BackgroundRV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials.MethodsREPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints.ResultsAt a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials.ConclusionsIn the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672)