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A study was conducted to determine the association of the common allele on chromosome 9p21 and poor glycemic control with a higher incidence of coronary artery disease (CAD) in patients with type 2 diabetes. Results confirmed that the incidence of CAD was higher in patients with the 9p21 chromosome variant along with poor glycemic control in type 2 diabetes.

The present study examined current and lifetime psychiatric morbidity, chest pain, and health care utilization in 229 patients with noncardiac chest pain (NCCP), angina-like pain in the absence of cardiac etiology. Diagnostic interview findings based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) revealed a psychiatrically heterogeneous sample of whom 44% had a current Axis I psychiatric disorder. A total of 41% were diagnosed with a current anxiety disorder, and 13% were diagnosed with a mood disorder. Overall, 75% of patients had an Axis I clinical or subclinical disorder. Lifetime diagnoses of anxiety (55%) and mood disorders (44%) were also prevalent, including major depressive disorder (41%), social phobia (25%), and panic disorder (22%). Patients with an Axis I disorder reported more frequent and more painful chest pain compared with those without an Axis I disorder. Presence of an Axis I disorder was associated with increased life interference and health care utilization. Findings reveal that varied DSM-IV Axis I psychiatric disorders are prevalent among patients with NCCP, and this psychiatric morbidity is associated with a less favorable NCCP presentation. Implications for early identification of psychiatric disorders are discussed. Keywords: morbidity, chest pain, panic, anxiety disorders, cardiac

Aims  We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL). Methods and results  Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N  = 59) had angiographically significant FLL (≥50% of left main or ≥70% of other epicardial coronary arteries ≥2 mm in diameter); controls (N  = 44) were normal or had non-FLL. TWH, i.e. interlead splay of T waves, was assessed from precordial leads V4–6 by second central moment analysis. Maximum TWHV4–6 levels during regadenoson stress were 68% higher in cases than in controls (P  < 0.0001). TWHV4–6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P  < 0.0001) and 0.71 in women (P  = 0.007). In men, the ROC-guided 54-µV TWHV4–6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3–41.5, P  = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-µV TWHV4–6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1–18.9, P  = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4–6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2–21.4, P  = 0.001) with specificity of 78% in men and 86% in women. Conclusion  This observational study is the first to demonstrate the benefit of combining TWHV4–6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women. [ABSTRACT FROM AUTHOR]

Normal aging is associated with an important in early left ventricular diastolic filling. To test the hypothesis that long-term endurance exercise training is associated with enhanced ventricular diastolic filling indices, we compared transmitral pulsed Doppler inflow spectra in healthy young adults; healthy elderly, sedentary subjects (sedentary old); and healthy elderly, endurance athletes (master athletes). Our data demonstrate that, despite an increase in left ventricular mass, early diastolic filling was enhanced in master athletes compared to the sedentary old. Blood pressure of both master athletes and the sedentary olds was greater than the young adults, but the higher blood pressure did not correlate to changes in filling parameters. Resting systolic function and heart rate were not significantly different in all three different groups. Early left ventricular filling indices in master athletes more closely resemble transmitral inflow patterns of healthy young adults. Long-term endurance exercise is associated with physiologic hypertrophy and ventricular filling dynamics more characteristic of the young than the old.

Heart-focused anxiety (HFA) is a fear of cardiac sensations driven by worries of physical health catastrophe. HFA is impairing and distressing and has been shown to disproportionately affect individuals with noncardiac chest pain (NCCP), chest pain that persists in the absence of an identifiable source. The Cardiac Anxiety Questionnaire (CAQ) is a measure designed to assess HFA. The aim of this study was to evaluate the psychometric properties and factor structure of the CAQ in a sample of 229 adults diagnosed with NCCP. Results demonstrated that the CAQ is a useful measure of HFA in patients with NCCP and that a four-factor model including fear of cardiac sensations, avoidance of activities that elicit cardiac sensations, heart-focused attention, and reassurance seeking was the best fit for the data. Additionally, associations between CAQ subscales and two measures of health-related behaviors—pain-related interference and health care utilization—provided evidence of concurrent validity. Treatment implications are also discussed. [ABSTRACT FROM AUTHOR]

IMPORTANCE Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals. OBJECTIVE To identify genetic determinants of CHD that are specific to patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS We studied 5 independent sets of CHD cases and CHD-negative controls from the Nurses' Health Study (enrolled in 1976 and followed up through 2008), Health Professionals Follow-up Study (enrolled in 1986 and followed up through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1517 CHD cases and 2671 CHD-negative controls, all with type 2 diabetes. Results in diabetic patients were compared with those in 737 nondiabetic CHD cases and 1637 nondiabetic CHD-negative controls from the Nurses' Health Study and Health Professionals Follow-up Study cohorts. Exposures included 2 543 016 common genetic variants occurring throughout the genome. MAIN OUTCOMES AND MEASURES Coronary heart disease-defined as fatal or nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries. RESULTS A variant on chromosome lq25 (rs10911021) was consistently associated with CHD risk among diabetic participants, with risk allele frequencies of 0.733 in cases vs 0.679 in controls (odds ratio, 1.36 [95% CI, 1.22-1.51]; P = 2 x 10-8). No association between this variant and CHD was detected among nondiabetic participants, with risk allele frequencies of 0.697 in cases vs 0.696 in controls (odds ratio, 0.99 [95% CI, O.87-1.13]; P = .89), consistent with a significant gene x diabetes interaction on CHD risk (P = 2 x 10-4). Compared with protective allele homozygotes, rs10911021 risk allele homozygotes were characterized by a 32% decrease in the expression of the neighboring glutamate-ammonia ligase (GLUL) gene in human endothelial cells (P = .0048). A decreased ratio between plasma levels of γ-glutamyl cycle intermediates pyroglutamic and glutamic acid was also shown in risk allele homozygotes (P = .029). CONCLUSION AND RELEVANCE A single-nucleotide polymorphism (rsi0911021) was identified that was significantly associated with CHD among persons with diabetes but not in those without diabetes and was functionally related to glutamic acid metabolism, suggesting a mechanistic link. [ABSTRACT FROM AUTHOR]

Adiponectin -- an adipokine facilitating insulin action -- has direct protective effects on the arterial wall through inhibition of monocyte adhesion, SMC proliferation, and foam cell formation. We previously identified two haplotypes at the adiponectin receptor 1 (ADIPOR1) locus that are associated with an increased risk of coronary artery disease (CAD) risk in type 2 diabetes. In the present study we investigated whether genetic variability in another adiponectin receptor -- T-cadherin -- similarly modulates cardiovascular risk in type 2 diabetes. The T-cadherin gene (CDH13) is located on chromosome 16q23.3 and includes 14 exons spanning a total of 1.17 Mb. Sequencing of all the exons, exon-intron boundaries, and 2.5 kb of the upstream and downstream regions in 24 healthy individuals led to the identification of 34 SNPs. Twelve of these SNPs, which were placed in the coding, 5'-flanking or 3'-flanking regions were typed in 290 T2DM cases with angiographically diagnosed CAD and 353 T2DM controls with negative CAD history and normal exercise treadmill test. Two coding, synonymous SNPs (rs6565105 on exon 3 and rs17852798 on exon 13) showed nominal evidence of association with CAD (p=0.014 and 0.043, respectively). To further locate the polymorphism(s) that are responsible for the observed association, we extended the study to 13 other SNPs that were in high LD with these two SNPs (r²>0.5). Four of these other SNPs -- all placed in introns -- were found to be associated with CAD (p=0.012, 0.019, 0.033 and 0.054, respectively). Further studies are underway to replicate these association and define the functional variants as well as the mechanisms underlying this genetic effect. These findings potentially expand the evidence implicating adiponectin as one of the links between increased adipose mass and atherogenesis. [ABSTRACT FROM AUTHOR]

Objective: Systemic inflammation, aging, and type 2 diabetes (T2DM) all contribute to the development of cardiovascular dysfunction and impaired aerobic exercise capacity but their interplay remains unclear. This study evaluates the impact of age, sex, and inflammation on coronary and peripheral vascular function and exercise capacity in elderly individuals with and without type 2 diabetes (T2DM)., Research Design and Methods: Elderly individuals (age ≥65 years) underwent biochemical and tissue inflammatory phenotyping, cardiopulmonary exercise testing (CPET), cardiovascular magnetic resonance (CMR) imaging, and vascular reactivity testing. Correlation and regression analyses determined the effects of systemic inflammation, older age, and sex on cardiovascular health, stratified by T2DM status., Results: For the 133 recruited individuals (44% female; median age 71, IQR=7 years, 41% with T2DM) the presence of T2DM did not have an effect on most blood serum inflammatory markers and skin biopsies. Hyperemic myocardial blood flow (hMBF), flow-mediated, and flow-independent nitroglycerin induced brachial artery dilation were significantly impaired in males, but not females with T2DM. Peak VO2 was lower with T2DM (p=0.022), mostly because of the effect of T2DM in females. Females showed more adverse myocardial remodeling assessed by extracellular volume (p=0.008), independent of T2DM status., Conclusions: Our findings suggest that the pathophysiological manifestations of T2DM on vascular function and aerobic exercise capacity are distinct in elderly males and females and this may reflect underlying differences in vascular and myocardial aging in the presence of T2DM.

Aims: We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL)., Methods and Results: Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N = 59) had angiographically significant FLL (≥50% of left main or ≥70% of other epicardial coronary arteries ≥2 mm in diameter); controls (N = 44) were normal or had non-FLL. TWH, i.e., interlead splay of T waves, was assessed from precordial leads V4-6 by second central moment analysis. Maximum TWHV4-6 levels during regadenoson stress were 68% higher in cases than in controls (P < 0.0001). TWHV4-6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P < 0.0001) and 0.71 in women (P = 0.007). In men, the ROC-guided 54-µV TWHV4-6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3-41.5, P = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-µV TWHV4-6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1-18.9, P = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4-6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2-21.4, P = 0.001) with specificity of 78% in men and 86% in women., Conclusion: This observational study is the first to demonstrate the benefit of combining TWHV4-6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)