Sex and Race Differences in Electrocardiogram Use (The National Hospital Ambulatory Medical Care Survey)

There are sex and race differences in many aspects of health care delivery. For example, blacks and women are less likely to receive aspirin and thrombolytic drugs. Blacks and women presenting with chest pain are less likely to be referred for cardiac catheterization. Blacks and women diagnosed with acute myocardial infarction (AMI) are also less likely to undergo cardiac catheterization. The gender differences in diagnostic evaluation after AMI appear more pronounced among younger women. The American College of Cardiology and the American Heart Association joint electrocardiography guidelines state that all patients presenting to the emergency department (ED) with chest pain should undergo electrocardiography (ECG) to rule out acute ischemia or infarction, regardless of sex or age. It is possible that sex and race differences exist in the administration of this important screening tool among patients with chest pain, possibly reflecting a lower suspicion of coronary heart disease in women (especially young women) and blacks. These management differences may result in failure to diagnose coronary heart disease and may explain why these subgroups are referred less often for cardiac catheterization. Therefore, the purpose of this study was to examine whether this basic guideline is being implemented uniformly in a national sample of patients presenting to the ED with chest pain. Specifically, we hypothesized that young women and blacks presenting with chest pain would be significantly less likely to undergo ECG relative to their white male counterparts

Outcomes in heart failure patients with preserved ejection fraction Mortality, readmission, and functional decline

AbstractObjectivesWe evaluated the six-month clinical trajectory of patients hospitalized for heart failure (HF) with preserved ejection fraction (EF), as the natural history of this condition has not been well established. We compared mortality, hospital readmission, and changes in functional status in patients with preserved versus depressed EF.BackgroundAlthough the poor prognosis of HF with depressed EF has been extensively documented, there are only limited and conflicting data concerning clinical outcomes for patients with preserved EF.MethodsWe prospectively evaluated 413 patients hospitalized for HF to determine whether EF ≥40% was an independent predictor of mortality, readmission, and the combined outcome of functional decline or death.ResultsAfter six months, 13% of patients with preserved EF died, compared with 21% of patients with depressed EF (p = 0.02). However, the rates of functional decline were similar among those with preserved and depressed EF (30% vs. 23%, respectively; p = 0.14). After adjusting for demographic and clinical covariates, preserved EF was associated with a lower risk of death (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.26 to 0.90; p = 0.02), but there was no difference in the risk of readmission (HR 1.01, 95% CI 0.72 to 1.43; p = 0.96) or the odds of functional decline or death (OR 1.01, 95% CI 0.59 to 1.72; p = 0.97).ConclusionsHeart failure with preserved EF confers a considerable burden on patients, with the risk of readmission, disability, and symptoms subsequent to hospital discharge, comparable to that of HF patients with depressed EF

Posttraumatic Stress Disorder and Impaired Autonomic Modulation in Male Twins

BACKGROUND: Posttraumatic stress disorder (PTSD) has been linked to increased morbidity. An inflexibility of the autonomic nervous system may be the underlying mechanism. We aimed to assess whether PTSD and combat trauma exposure are associated with lower heart rate variability (HRV), a measure of autonomic function and a predictor of death. METHODS: We measured HRV by power spectral analysis on 24-hour ambulatory ECG in 459 middle-aged veteran male twins. Combat trauma was assessed with the combat exposure scale, and current and remitted PTSD with the Structured Clinical Interview for Psychiatry Disorders. Mixed-effects regression models were used to test associations of PTSD and HRV between and within twin pairs. RESULTS: Of all twins, 211 had combat exposure, 31 had current PTSD, and 43 had remitted PTSD. Current PTSD was inversely associated with very-low frequency (VLF) and low frequency (LF) HRV both in individual twins and within 20 pairs discordant for current PTSD. Twins with current PTSD had a 49% lower LF HRV than their brothers without PTSD (p<0.001). Remitted PTSD was not associated with HRV. Results were robust to adjustment for depression and other risk factors. Combat exposure was inversely associated with most HRV frequencies, but this association mostly diminished after adjustment for current PTSD. CONCLUSION: In middle-aged veteran men, combat exposure and current PTSD are associated with measures of autonomic inflexibility previously shown to have prognostic significance. The negative health impact of combat exposure on autonomic function is mediated largely through PTSD and may reverse with remission of PTSD

DNA Methylation of Five Core Circadian Genes Jointly Contributes to Glucose Metabolism: A Gene-Set Analysis in Monozygotic Twins

The timing of daily fluctuations in blood glucose is tightly controlled by the circadian rhythm. DNA methylation accompanies the circadian clock, and aberrant DNA methylation has been associated with circadian disruption and hyperglycemia. However, the precise role of circadian genes methylation in glucose metabolism is unknown. Using a gene-set approach in monozygotic (MZ) twin pairs, we examined the joint effect of 77 CpGs in five core circadian genes (CLOCK, BMAL1, PER1, PER2, PER3) on glucose-related traits in 138 middle-aged, male-male MZ twins (69 pairs). DNA methylation was quantified by bisulfite pyrosequencing. We first conducted matched twin pair analysis to examine the association of single CpG methylation with glucose metabolism. We then performed gene-based and gene-set analyses by the truncated product method to examine the combined effect of DNA methylation at multiple CpGs in a gene or all five circadian genes as a pathway on glucose metabolism. Of the 77 assayed CpGs, only one site was individually associated with insulin resistance at FDR &lt; 0.05. However, the joint effect of DNA methylation in all five circadian genes together showed a significant association with glucose metabolism. Our results may unravel a biological mechanism through which circadian rhythm regulates blood glucose, and highlight the importance of testing the joint effect of multiple CpGs in epigenetic analysis

Association between Posttraumatic Stress Disorder and Inflammation: A Twin Study

The association of posttraumatic stress disorder (PTSD) with cardiovascular disease risk may be mediated by inflammation. Our objective was to examine the association between PTSD and measures of inflammation and to determine whether these associations are due to shared familial or genetic factors. We measured lifetime history of PTSD using the Structured Clinical Interview for DSM-IV in 238 male middle-aged military veteran twin pairs (476 individuals), selected from the Vietnam Era Twins Registry, who were free of cardiovascular disease at baseline. We assessed inflammation using levels of high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), fibrinogen, white blood cells, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 (ICAM-1). Geometric mean levels and percent differences by PTSD were obtained from mixed-model linear regression analyses with adjustment for potential confounders. Within-pair analysis was conducted to adjust for shared family environment and genetics (monozygotic pairs). Overall, 12.4% of participants had a lifetime history of PTSD. Adjusted mean levels of hsCRP and ICAM-1 were significantly higher among those with vs. without PTSD [hsCRP: 1.75 vs. 1.31 mg/l (33% difference); ICAM-1: 319 vs. 293 ng/ml (9% difference)]. Adjustment for depression rendered the association of PTSD with hsCRP non-statistically significant. For IL-6, no consistent association was seen. Within-pair analysis produced associations that were similar in direction for all three markers but lesser in magnitude for hsCRP and IL-6. There was no evidence of interaction by zygosity. Elevated hsCRP and ICAM-1 are associated with PTSD, and these associations may be confounded by shared non-genetic, antecedent familial and environmental factors

Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors?: Position Paper from the Working Group on Coronary Pathophysiology and Microcirculation of the European Society of Cardiology

Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in wome

Association Between Ideal Cardiovascular Health and Carotid Intima-Media Thickness: A Twin Study

Background The American Heart Association (AHA) recently developed the Cardiovascular Health Index (CVHI), a health metric consisting of 7 modifiable risk factors. The relationship of the CVHI with preclinical markers, such as carotid intima-media thickness (CIMT) has not been assessed. Methods We examined 490 male monozygotic and dizygotic twins without overt cardiovascular disease. CIMT was measured using B-mode ultrasonography. Each of the 7 CVHI components (blood pressure, fasting glucose, total cholesterol, body mass index, physical activity, healthy diet, and smoking) was given a point score of 0, 1, or 2 to represent poor, intermediate, or ideal health, respectively. A CVHI summation score was computed (range 0 to 14) and categorized as inadequate (0 to 4), average (5 to 9), or optimum (10 to 14) cardiovascular health. Mixed-model regression was used to examine the association of the CVHI with CIMT. Results The mean age of the twins was 55.4 years, and 61% were monozygotic. The mean CIMT was 0.75 (±0.11) mm and the mean CVHI score was 7.7 (±2.1). There was an inverse correlation between CVHI and CIMT (Spearman r=−0.22, P\u3c0.01). For every 5-unit increase in overall CVHI score (indicating better cardiovascular health category), CIMT decreased by 0.045 mm (P\u3c0.001) after adjusting for demographic variables and other confounders. Within monozygotic twin pairs, a 5-unit increment in CVHI score was associated with a 0.05 mm lower CIMT (P\u3c0.001). Conclusions The CVHI is independently associated with CIMT and the association is not confounded by shared genetic and other familial factors

Endothelial dysfunction is associated with occult coronary artery disease detected by positron emission tomography

Objective: Silent myocardial ischemia is common in asymptomatic subjects without a prior history of coronary artery disease (CAD) and is associated with increased morbidity and mortality. Our objective was to determine whether endothelial dysfunction is associated with silent myocardial ischemia and whether the association is independent of genetic and familial factors. Material and methods: We examined 416 male monozygotic and dizygotic twins aged 47 to 63 years, free of symptomatic CAD. Subclinical ischemia was diagnosed by [13N] ammonia positron emission tomography at rest and after adenosine stress. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. Generalized estimating equations were used for analysis. Results: Fixed perfusion defects were found in 24 (6%) twins and reversible perfusion defects in 90 (22%) twins, indicating subclinical ischemia. There was an inverse correlation between FMD and the reversible perfusion defect score (r = − 0.14, p = 0.01) but not the fixed defect score (r = − 0.017, p = 0.73). From the lowest to the highest quartiles of FMD, the prevalence of reversible defects decreased from 28% to 14%, p = 0.008. In multivariable analysis, reversible defects were significantly associated with each quartile of decreasing FMD (OR = 1.3; 95% 1.1, 2.5). In 54 twin pairs discordant for endothelial dysfunction (FMD ≤ 7% dilation from baseline), twins with endothelial dysfunction had 9% higher likelihood of having perfusion defects than their co-twins without endothelial dysfunction (p = 0.041). Conclusions: Endothelial dysfunction is independently associated with silent ischemia and this association is not confounded by genetic or other shared familial factors