Concordance between vessel-specific and vascular territory coronary functional assessment: A comparison of quantitative flow ratio and myocardial perfusion scintigraphy.

BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.

The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study.

BACKGROUND: Percutaneous coronary intervention (PCI) is one of the most performed well-succeeded therapeutic procedures worldwide, reducing symptoms and improving quality of life. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) produced early after an ischemic renal insult. Osmotic diuresis and the vasoconstriction of the afferent arteriole promoted by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) generate a concern regarding the possibility of dehydration and consequent AKI. There is no consensus on the maintenance or discontinuation of SGTL2i in patients who will undergo PCI. This study aimed to evaluate the safety of empagliflozin in diabetic patients submitted to elective PCI regarding kidney function. METHODS: SAFE-PCI trial is a prospective, open-label, randomized (1:1), single-center pilot study and a follow-up of 30 days. The SGLT2i empagliflozin 25 mg daily was initiated at least 15 days before PCI in the intervention group and maintained until the end of the follow-up period. Serum NGAL was collected 6 h after PCI and creatinine before PCI, 24 h, and 48 h after the procedure. As per protocol, both groups received optimal medical treatment and standard protocol of nephroprotection. RESULTS: A total of 42 patients were randomized (22 patients in the iSGLT-2 group and 20 patients in the control group). There was no difference between-group baseline data. The primary outcome (NGAL and creatinine values post PCI) did not differ in both groups: the mean NGAL value was 199 ng/dL in the empagliflozin group and 150 ng/dL in the control group (p = 0.249). Although there was an initial increase in creatinine in the SGLT-2i group compared to the control group between baseline creatinine and pre-PCI and 24 h post-PCI creatinine, no difference was detected in creatinine 48 h post-PCI (p = 0.065). The incidence of CI-AKI, determined by KDIGO criteria, in the iSGLT2-group was 13.6% and 10.0% in the control group without statistical difference. CONCLUSION: The present study showed that the use of empagliflozin is safe regarding kidney function during elective PCI in patients with T2D when compared with no use of SGLT2i. Trial registration Our clinical study is registered on ClinicalTrials.gov with the following number: NCT05037695.

Coronary calcification and bone microarchitecture by high-resolution peripheral quantitative computed tomography from the São Paulo Ageing and Health (SPAH) Study.

Epidemiological studies reveal a link between osteoporosis and the risk of ischemic cardiovascular disease. We illustrate an association between coronary calcification and bone microarchitecture in older adults based on the SPAH study. This cross-sectional research comprised 256 individuals subjected to cardiac coronary computed tomography angiography (CCTA) for coronary artery calcification (CAC), high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius with standardized z score parameters, and dual-energy X-ray absorptiometry (DXA) to evaluate bone status. We used Student's t test and the Mann-Whitney and Chi-squared tests for comparison of basal measurements. Association analysis was performed using the Poisson regression model with adjustment for CAC and sex. Multivariate analysis revealed different bone variables for predicting CAC in DXA and HR-pQCT scenarios. Although most of the bone parameters are related to vascular calcification, only cortical porosity (Ct.Po) remained uniform by HR-pQCT. Results for were as follows: the tibia-women (exp ß = 1.12 (95% CI 1.10-1.13, p < 0.001) and men (exp ß = 1.44, 95% CI 1.42-1.46, p < 0.001); the radius-women (exp ß = 1.07 (95% CI 1.07-1.08, p < 0.001) and men (exp ß = 1.33 (95% CI 1.30-1.37, p < 0.001). These findings suggest an inverse relationship between CAC and cortical bone content, as assessed by HR-pQCT, with higher coronary calcification in individuals older than 65 years.

Transcriptomic analysis of elderly women with low muscle mass: association with immune system pathway.

Despite the well-established association of gene expression deregulation with low muscle mass (LMM), the associated biological mechanisms remain unclear. Transcriptomic studies are capable to identify key mediators in complex diseases. We aimed to identify relevant mediators and biological mechanisms associated with age-related LMM. LMM-associated genes were detected by logistic regression using microarray data of 20 elderly women with LMM and 20 age and race-matched controls extracted from our SPAH Study (GSE152073). We performed weighted gene co-expression analysis (WGCNA) that correlated the identified gene modules with laboratorial characteristics. Gene enrichment analysis was performed and an LMM predictive model was constructed using Support Vector Machine (SVM). Overall, 821 discriminating transcripts clusters were identified (|beta coefficient| >1; p-value <0.01). From this list, 45 predictors of LMM were detected by SVM and validated with 0.7 of accuracy. Our results revealed that the well-described association of inflammation, immunity and metabolic alterations is also relevant at transcriptomic level. WGCNA highlighted a correlation of genes modules involved in immunity pathways with vitamin D level (R = 0.63, p = 0.004) and the Agatston score (R = 0.51, p = 0.02). Our study generated a predicted regulatory network and revealed significant metabolic pathways related to aging processes, showing key mediators that warrant further investigation.

The crosstalk between bone metabolism, lncRNAs, microRNAs and mRNAs in coronary artery calcification.

The association between Coronary Artery Calcification (CAC) and osteoporosis has been reported but not fully understood. Therefore, using an original bioinformatic framework we analyzed transcriptomic profiles of 20 elderly women with high CAC score and 31 age- and sex-matching controls from São Paulo Ageing & Health study (SPAH). We integrated differentially expressed microRNA (miRNA) and long-noncoding RNA (lncRNA) interactions with coding genes associated with CAC, in the context of bone-metabolism genes mined from literature. Top non-coding regulators of bone metabolism in CAC included miRNA 497-5p/195 and 106a-5p, and lncRNA FAM197Y7. Top non-coding RNAs revealed significant interplay between genes regulating bone metabolism, vascularization-related processes, chromatin organization, prostaglandin and calcium co-signaling. Prostaglandin E2 receptor 3 (PTGER3), Fibroblasts Growth Factor Receptor 1 (FGFR1), and One Cut Homeobox 2 (ONECUT2) were identified as the most susceptible to regulation by the top non-coding RNAs. This study provides a flexible transcriptomic framework including non-coding regulation for biomarker-related studies.

Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.

BACKGROUND: Vertebral fractures (VFs) are the most common clinical manifestation of osteoporosis associated with high morbimortality. A personal/familiar history of fractures increases the risk of fractures. The purpose of this study is to identify possible molecular markers associated with osteoporotic VFs in elderly women from community. METHODS: Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population-based survey (Sao Paulo Ageing & Health [SPAH] study). Only elderly women with osteoporosis diagnosis by densitometry were analyzed, and divided in two groups: VF: women with osteoporosis and VFs versus no vertebral fracture (NVF): women with osteoporosis and NVFs. They were matched for age, chronic disease, medication use, and bone mineral density (BMD). The logistic regression model adjusted for age was applied for transcriptome data analysis. SYBR green-based quantitative polymerase chain reaction (qPCR) was used to validate the most significant expression changes obtained in the microarray experiment. RESULTS: Microarray analysis identified 142 differentially expressed genes (DEGs, p < .01), 57 upregulated and 85 downregulated, compared VF versus NVF groups. The DEG with the greatest expression difference was the Gamma2-Syntrophin (SNTG2) (ß = 31.88, p = .005). Validation by qPCR confirmed increased expression in VF group of Syntrophin (SNTG2, fold change = 2.79, p = .009), TRAF3 Interacting Protein2 (TRAF3IP2, fold change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038). CONCLUSION: Our data identified and validated the association of SNTG2 (608715), TRAF3IP2 (607043), and ITGA6 (147556) with osteoporotic VF in elderly women, independently of BMD. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of vertebral fracture.

Pathophysiological and Genetic Aspects of Vascular Calcification.

Recent evidence suggests that vascular calcification is an independent cardiovascular risk factor (CRF) of morbidity and mortality. New studies point out the existence of a complex physiopathological mechanism that involves inflammation, oxidation, the release of chemical mediators, and genetic factors that promote the osteochondrogenic differentiation of vascular smooth muscle cells (VSMC). This review will evaluate the main mechanisms involved in the pathophysiology and genetics modulation of the process of vascular calcification. Objective. A systematic review of the pathophysiology factors involved in vascular calcification and its genetic influence was performed. Methods. A systematic review was conducted in the Medline and PubMed databases and were searched for studies concerning vascular calcification using the keywords and studies published until 2020/01 in English. Inclusion Criteria. Studies in vitro, animal models, and humans. These include cohort (both retrospective and prospective cohort studies), case-control, cross-sectional, and systematic reviews. Exclusion Criteria. Studies before 2003 of the existing literature.

Updated geriatric cardiology guidelines of the brazilian society of cardiology ­ 2019 / Atualização das diretrizes em cardiogeriatria da sociedade brasileira de cardiologia ­ 2019

Development: The Department of Geriatric Cardiology of the Brazilian Society of Cardiology (Departamento de Cardiogeriatria da Sociedade Brasileira da Cardiologia) and the Brazilian Geriatrics and Gerontology Society (Sociedade Brasileira de Geriatria e Gerontologia). (AU)

Association of moderate/severe vertebral fractures with reduced trabecular volumetric bone density in older women and reduced areal femoral neck bone density in older men from the community: A cross-sectional study (SPAH).

BACKGROUND: Many vertebral fractures (VF) occur in individuals classified by DXA as being at low risk of fragility fractures. The aim of this study was to verify the association between VF and peripheral bone microarchitecture and strength parameters (SP) using, in addition to DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) and axial bone microarchitecture using the trabecular bone score (TBS). STUDY DESIGN: Cross-sectional study of 276 community-dwelling subjects aged ≥65 years from the SPAH study cohort. METHODS: Lateral DXA scans of the spine were analyzed to assess VF. HR-pQCT was performed at the radius and tibia. TBS was determined using DXA. RESULTS: VF was observed in 42.6% of women and 28% of men. At the tibia, women with moderate/severe VF had lower volumetric bone density (vBMD), trabecular number (Tb.N), and SP, and higher trabecular separation (Tb.Sp); and men with VF had lower Tb.N and SP, and higher Tb.Sp. At the radius, women with moderate/severe VF had lower vBMD, trabecular and cortical thickness and SP; and men with VF had lower trabecular vBMD and SP. No associations between TBS and VF were observed in either gender. Logistic regression analysis revealed that trabecular vBMD at the tibia in women (OR:0.980, 95%CI:0.963-0.997, p = 0.022) and femoral neck aBMD in men (OR:0.445, 95%CI:0.212-0.935, p = 0.033) were independently associated with VF. CONCLUSION: HR-pQCT images detected differences in bone microstructure in older women with VF independent of aBMD and TBS by DXA, and HR-pQCT could be a useful tool to assess fracture risk. In men, femoral neck aBMD was associated with VF, and DXA continues to be an important tool for predicting VF.

Effects of aging on the effectiveness of smoking cessation medication.

BACKGROUND: Considering the pharmacokinetic and pharmacodynamic aspects of different medications, it is plausible that the age of a smoker could affect the half-life of these drugs. The aim of this study was to compare the effectiveness of smoking cessation drugs (nicotine replacement therapy, bupropion, and varenicline) used either in isolation or in combination in adults under and over 60 years of age. METHODS: Data were collected from 940 Brazilian patients participating in a smoking cessation program. Participants were prescribed smoking cessation medication to be used for at least 12 weeks and were followed for 52 weeks. RESULTS: Cessation rates were significantly different among younger and older participants who were using nicotine replacement therapy (NRT) alone. Being over 60 years of age was significantly associated with increased cessation success among those who used NRT alone (OR 2.34, 95% CI: 1.36 to 4.04, p = 0.002). The effectiveness of varenicline and bupropion were not significantly different according to age groups. CONCLUSION: Using age as a predictor for tailoring smoking cessation drugs might potentially lead to a more individualized prescription of smoking cessation therapy. These results should be tested in randomized controlled trials.

Sex, Prescribing Practices and Guideline Recommended, Blood Pressure, and LDL Cholesterol Targets at Baseline in the BARI 2D Trial.

Background. Research has shown less aggressive treatment and poorer control of cardiovascular disease (CVD) risk factors in women than men. Methods. We analyzed sex differences in pharmacotherapy strategies and attainment of goals for hemoglobin A1c (HbA1c), blood pressure (BP), and low density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and established coronary artery disease enrolled into the BARI 2D trial. Results. Similar numbers of drugs were prescribed in both women and men. Women were less frequent on metformin or sulfonylurea and more likely to take insulin and to be on higher doses of hydroxymethylglutaryl-CoA reductase inhibitors (statins) than men. After adjusting for baseline differences and treatment prescribed, women were less likely to achieve goals for HbA1c (OR = 0.71, 95% CI 0.57, 0.88) and LDL-C (OR = 0.64, 95% CI 0.53, 0.78). More antihypertensives were prescribed to women, and yet BP ≤ 130/80 mmHg did not differ by sex. Conclusions. Women entering the BARI 2D trial were as aggressively treated with drugs as men. Despite equivalent treatment, women less frequently met targets for HbA1c and LDL-C. Our findings suggest that there may be sex differences in response to drug therapies used to treat diabetes, hypertension, and hyperlipidemia.

Sex differences in presentation and outcome among patients with type 2 diabetes and coronary artery disease treated with contemporary medical therapy with or without prompt revascularization: a report from the BARI 2D Trial (Bypass Angioplasty Revascularization Investigation 2 Diabetes).

OBJECTIVES: This study evaluated differences in outcome among women and men enrolled in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. BACKGROUND: Women and men with coronary artery disease have different clinical presentations and outcomes that might be due to differences in management. METHODS: We compared baseline variables, study interventions, and outcomes between women and men enrolled in the BARI 2D trial and randomized to aggressive medical therapy alone or aggressive medical therapy with prompt revascularization. RESULTS: At enrollment, women were more likely than men to have angina (67% vs. 58%, p < 0.01) despite less disease on angiography (Myocardial Jeopardy Index 41 ± 24 vs. 46 ± 24, p < 0.01; number of significant lesions 2.3 ± 1.7 vs. 2.8 ± 1.8, p < 0.01). Over 5 years, no sex differences were observed in BARI 2D study outcomes after adjustment for difference in baseline variables (death/myocardial infarction/cerebrovascular accident: hazard ratio: 1.11, 99% confidence interval [CI]: 0.85 to 1.44). However, women reported more angina than men (adjusted odds ratio: 1.51, 99% CI: 1.21 to 1.89, p < 0.0001) and had lower scores for the Duke Activity Status Index (adjusted beta coefficient: -1.58, 99% CI: -2.84 to -0.32, p < 0.01). CONCLUSIONS: There were no sex differences in death, myocardial infarction, or cerebrovascular accident among patients enrolled in the BARI 2D trial. However, compared with men, women had more symptoms and less anatomic disease at baseline, with persistence of higher angina rates and lower DASI scores after 5 years of medical therapy with or without prompt revascularization. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Teratoma of the mediastinum: a case report.

INTRODUCTION: This case report illustrates a rare case of teratoma of the mediastinum which was continuous to the pericardium and caused extrinsic compression to the right atrium. CASE PRESENTATION: A 22-year-old Caucasian man with no complaints or comorbid conditions presented to our hospital with obliteration of the right cardiophrenic sinus by a mass. A non-invasive investigation demonstrated a tumoral mass which was continuous to the pericardium and caused extrinsic compression to the right atrium. The clinical suspicion was a pericardial or bronchogenic cyst. Surgical and anatomopathologic findings led to the diagnosis of a mature cystic teratoma with atrophic thymic tissue at the external teratoma surface. CONCLUSION: We present an original report of a mature teratoma causing obliteration of the right cardiophrenic sinus with extrinsic heart compression. The diagnosis of this tumor is very difficult through non-invasive investigation.

The impact of race/ethnicity on baseline characteristics and the burden of coronary atherosclerosis in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

OBJECTIVES: We aimed to test the impact of race/ethnicity on coronary artery disease (CAD) after adjusting for baseline risk factors. BACKGROUND: Whether race/ethnicity remains an important determinant of the burden of CAD even among patients with long-standing type 2 diabetes (diabetes mellitus) and established CAD is unknown. METHODS: Analysis of baseline data from the BARI 2D trial (January 1, 2001, to March 31, 2005) was performed. Myocardial jeopardy index (MJI) was evaluated by a blinded core angiographic laboratory. Multivariate regression analysis was performed to determine the independent association of race/ethnicity on the burden of CAD after adjusting for baseline risk factors. Data were collected from US and Canadian academic and community hospitals. The baseline analysis was performed on patients with long-standing diabetes and documented CAD with no prior revascularization at study entry (n = 1,331). The main outcome measure was MJI, which represents the percentage of myocardium jeopardized by significant lesions (≥50%). The secondary outcome measure was ≥2 lesions with ≥50% stenosis. RESULTS: Risk factors varied significantly among racial/ethnic groups. Blacks were significantly more likely to be women, have no health insurance, be current smokers, have higher body mass index, have hypertension, have a longer duration of diabetes, a higher hemoglobin A(1c) level, and were more likely to be taking insulin. Their mean total, low-density lipid, and high-density lipid cholesterol levels were higher, whereas their triglycerides were lower than others. After controlling for baseline risk factors, blacks had a significantly lower burden of CAD; the adjusted MJI was 5.43 U lower (95% CI -9.13 to -1.72), and the adjusted number of lesions was 0.53 fewer (95% CI -0.88 to -0.18) in blacks compared to whites. CONCLUSIONS: In the BARI 2D trial, self-reported race/ethnicity is associated with important differences in baseline risk factors and is a powerful predictor of the burden of CAD adjusting for such baseline differences. These findings may help direct medical intervention and resources and further investigation into the basis of racial/ethnic differences in CAD burden.

Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.

OBJECTIVE: To determine whether information from genetic risk variants for diabetes is associated with cardiovascular events incidence. METHODS: From the about 30 known genes associated with diabetes, we genotyped single-nucleotide polymorphisms at the 10 loci most associated with type-2 diabetes in 425 subjects from the MASS-II Study, a randomized study in patients with multi-vessel coronary artery disease. The combined genetic information was evaluated by number of risk alleles for diabetes. Performance of genetic models relative to major cardiovascular events incidence was analyzed through Kaplan-Meier curve comparison and Cox Hazard Models and the discriminatory ability of models was assessed for cardiovascular events by calculating the area under the ROC curve. RESULTS: Genetic information was able to predict 5-year incidence of major cardiovascular events and overall-mortality in non-diabetic individuals, even after adjustment for potential confounders including fasting glycemia. Non-diabetic individuals with high genetic risk had a similar incidence of events then diabetic individuals (cumulative hazard of 33.0 versus 35.1% of diabetic subjects). The addition of combined genetic information to clinical predictors significantly improved the AUC for cardiovascular events incidence (AUC = 0.641 versus 0.610). CONCLUSIONS: Combined information of genetic variants for diabetes risk is associated to major cardiovascular events incidence, including overall mortality, in non-diabetic individuals with coronary artery disease. CLINICAL TRIAL REGISTRATION INFORMATION: Medicine, Angioplasty, or Surgery Study (MASS II). Unique identifier: ISRCTN66068876 URL.

Sex, clinical symptoms, and angiographic findings in patients with diabetes mellitus and coronary artery disease (from the Bypass Angioplasty Revascularization Investigation [BARI] 2 Diabetes trial).

Previous studies have reported differences in presenting symptoms and angiographic characteristics between women and men undergoing evaluation for suspected coronary artery disease (CAD). We examined the relation between symptoms and extent of CAD in patients with type 2 diabetes mellitus and known CAD enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Of 1,775 patients (533 women, 30%, and 1,242 men, 70%), women were more likely than men to have angina (65% vs 56%, p <0.001) or an atypical angina/anginal equivalent (71% vs 58%, p <0.001). More women reported unstable angina (17% vs 13%, p = 0.047) or were in a higher Canadian Cardiology Society class compared to men (Canadian Cardiology Society classes II to IV 78% vs 68%, p = 0.002). Fewer women than men had no symptoms (14% vs 22%, p <0.001). Women had a lower mean myocardial jeopardy index (42.5 ± 24.3 vs 47.9 ± 24.3, p <0.001), smaller number of total significant lesions (2.3 ± 1.7 vs 2.7 ± 1.8, p <0.001), and fewer jeopardized left ventricular regions (p <0.001 for distribution) or long-term occlusions (29% vs 42%, p <0.001). After adjustment for relevant covariates, the odds of having CAD symptoms were still higher in women than men (odds ratio for angina 1.31, 95% confidence interval 1.02 to 1.69; odds ratio for atypical angina 1.52, 95% confidence interval 1.17 to 1.96). In conclusion, in a high-risk group of patients with known CAD and diabetes mellitus, women were more symptomatic than men but had less obstructive CAD. These data suggest that factors other than epicardial CAD severity influence symptom presentation in women in this population.