Novel plasma biomarkers of coronary artery calcium incidence or progression: Insights from the prospective multi-ethnic Dallas Heart Study cohort.

BACKGROUND AND AIMS: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation. METHODS: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis. RESULTS: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors. CONCLUSIONS: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression.

The obesity paradox in patients with acute coronary syndromes over 2 decades - the ACSIS registry 2000-2018.

BACKGROUND: Obesity is a worldwide epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial distant data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. Nonetheless, it is not fully elucidated whether the obesity paradox is still relevant in the contemporary cardiology era among patients with acute coronary syndrome (ACS). We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status. METHODS: Data from the ACSIS registry including all patients with calculated BMI data between the years 2002-2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d major cardiovascular events (MACE), and 1-year mortality. Temporal trends were examined in the late (2010-2018) vs. the early period (2002-2008). Multivariable models examined factors associated with clinical outcomes by BMI status. RESULTS: Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal weight, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend <0.001). 30-day MACE rates followed a similar pattern (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend<0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, but unchanged in patients who were underweight. Similarly, 1-year mortality has decreased in normal weight and obese patients but remained similarly high in underweight patients. CONCLUSIONS: In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared to underweight and even normal weight patients. Temporal trends revealed that 30-day MACE and 1-year mortality have decreased among all BMI groups other than the underweight ACS patients, among whom the adverse CV rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current cardiology era.

Implantable Cardioverter Defibrillator for the Primary Prevention of Sudden Cardiac Death among Patients With Cancer.

Data are limited regarding the characteristics and outcomes of patients with cancer who are found eligible for primary defibrillator therapy. We performed a single-center retrospective analysis of patients with preexisting cancer diagnoses who become eligible for a primary prevention implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) defibrillator. Multicenter Automatic Defibrillator Implantation Trial-ICD (MADIT-ICD) benefit scores were calculated. The study included 75 cancer patients at a median age of 73 (interquartile range 64, 81) years at heart failure diagnosis. Active cancer was present in 51%. Overall, 55% of the cohort had coronary artery disease and 37% were CRT eligible. We found that 48%, 49%, and 3% of cohorts had low, intermediate, and high MADIT-ICD Benefit scores, respectively. Only 27% of patients underwent primary defibrillator implantation. Using multivariate analysis, indication for CRT and intermediate/high MADIT-ICD Benefit categories were found as independent predictors for implantation (odds ratio 8.42 p <0.001 and odds ratio 3.74 p = 0.040, respectively). During a median follow-up of 5.3 (interquartile range 4.5, 7.2) years, one patient (5%) with a defibrillator had appropriate shock therapy and 2 patients (10%) had bacteremia. Of 13 patients with CRT defibrillator-implants, one patient was admitted for heart failure exacerbation (8%). Using a time-varying covariate model, we did not observe statistically significant differences in the survival of patients with cancer implanted versus those not implanted with primary defibrillators (hazard ratio 0.521, p = 0.127). In conclusion, although primary defibrillator therapy is underutilized in patients with cancer, its relative benefit is limited because of competing risk of nonarrhythmic mortality. These findings highlight the need for personalized cardiologic and oncologic coevaluation.

Current challenges in the diagnosis and management of acute coronary syndromes in women.

Cardiovascular disease remains the leading cause of death among women nowadays. However, there is a persistent lack of awareness of the impact of different risk factors on women's cardiovascular health, in specific pregnancy-related complications, hormonal changes, and psychological aspects. Moreover, there is still not enough awareness of the importance of coronary artery disease (CAD) in women, which leads to a delay in the diagnosis and prompt treatment, particularly during emergent coronary scenarios. Although guidelines suggest the same treatment for women and men who present with acute coronary syndrome (ACS), women are still undertreated. Contemporary data show an improvement over time in the management of ACS in women, however, women are still less likely than men to receive revascularization and pharmacological treatments. Women have higher rates of complications and mortality, in particular the young population, in which all outcomes are still worse in women compared to men. In this review, we aim to emphasize the importance of women's risk factors, women-specific pathophysiology, and clinical presentation in the setting of ACS. This is a review of current challenges in the diagnosis and treatment of women with ACS.

Assessment of Adult Patients with Long COVID Manifestations Suspected as Cardiovascular: A Single-Center Experience.

Background: Persistent symptoms affect a subset of coronavirus disease 2019 (COVID-19) survivors. Some of these may be cardiovascular (CV)-related. Objective: To assess the burden of objective CV morbidity among, and to explore the short-term course experienced by, COVID-19 patients with post-infectious symptomatology suspected as CV. Methods: This was a single-center, retrospective analysis of consecutive adult patients with new-onset symptoms believed to be CV following recovery from COVID-19, who had been assessed at a dedicated 'Cardio'-COVID clinic between June 2020 and June 2021. All participants were followed for 1 year for symptomatic course and the occurrence of new CV diagnoses and major adverse cardiovascular events (MACE). Results: A total of 96 patients (median age 54 (IQR, 44-64) years, 52 (54%) females) were included in the final analysis. Initial visits occurred within a median of 142 days after the diagnosis of acute COVID. Nearly all (99%) patients experienced a symptomatic acute illness, which was graded as severe in 26 (27%) cases according to the National Institutes of Health (NIH) criteria. Long-COVID symptoms included mainly dyspnea and fatigue. While the initial work-up was mostly normal, 45% of the 11 cardiac magnetic resonance studies performed revealed pathologies. New CV diagnoses were made in nine (9%) patients and mainly included myocarditis that later resolved. An abnormal spirometry was the only variable associated with these. No MACE were recorded. Fifty-two (54%) participants felt that their symptoms improved. No association was found between CV morbidity and symptomatic course. Conclusions: In our experience, long-COVID symptoms of presumed CV origin signified actual CV disease in a minority of patients who, irrespective of the final diagnosis, faced a fair 1-year prognosis.

Peripheral artery disease, abnormal ankle-brachial index, and prognosis in patients with acute coronary syndrome.

Objectives: Ankle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI. Approach and results: ABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001). Conclusion: Subclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.

Detecting Coronary Artery Disease Using Exhaled Breath Analysis.

INTRODUCTION: Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide, and there is an unmet need for a simple, inexpensive, noninvasive tool aimed at CAD detection. The aim of this pilot study was to evaluate the possible use of breath analysis in detecting the presence of CAD. MATERIALS AND METHODS: In a prospective study, breath from patients with no history of CAD who presented with acute chest pain to the emergency room was sampled using a designated portable electronic nose (eNose) system. First, breath samples from 60 patients were analyzed and categorized as obstructive, nonobstructive, and no-CAD according to the actual presence and extent of CAD as was demonstrated on cardiac imaging (either computerized tomography angiography or coronary angiography). Classification models were built according to the results, and their diagnostic performance was then examined in a blinded manner on a new set of 25 patients. The data were compared with the actual results of coronary arteries evaluation. Sensitivity, specificity, and accuracy were calculated for each model. RESULTS: Obstructive CAD was correctly distinguished from nonobstructive and no-CAD with 89% sensitivity, 31% specificity, 83% negative predictive value (NPV), 42% positive predictive value (PPV), and 52% accuracy. In another model, any extent of CAD was successfully distinguished from no-CAD with 69% sensitivity, 67% specificity, 54% NPV, 79% PPV, and 68% accuracy. CONCLUSION: This proof-of-concept study shows that breath analysis has the potential to be used as a novel rapid, noninvasive diagnostic tool to help identify presence of CAD in patients with acute chest pain.

Association of socioeconomic status measures with physical activity and subsequent frailty in older adults.

BACKGROUND: Despite increased recognition, frailty remains a significant public health challenge. OBJECTIVE: we aimed to assess the role of education and income, as well as neighborhood socioeconomic status, on physical activity and subsequent frailty in older adults. METHODS: Using a population-based cohort of older adults, this study examined the relationship between socioeconomic status (SES) factors, physical activity and frailty. The study included 1,799 participants (mean [SD], 74.6 (6.2), 53.3% female) from the "National Health and Nutrition Survey of Older Adults Aged 65 and Over in Israel", conducted in 2005-2006. A follow-up interview was performed 12-14 years later in a subgroup of 601 subjects (mean [SD], age 84[4]; 56% women). Self-reported leisure-time physical activity (LTPA) was measured at both baseline and follow-up. SES measures were assessed at baseline. Frailty was measured at follow-up, using the Fried's Phenotype Model. RESULTS: All SES measures were strongly and positively associated with LTPA (all p < 0.001). Eighty-two participants (14%) were classified as frail at follow-up. After age and sex adjustment and accounting for attrition bias using inverse probability weighting, baseline LTPA (OR = 2.77, 95% CI: 1.57-4.90, for inactivity; OR = 1.41, 95% CI: 0.75-2.68, for insufficient activity, compared with sufficient activity, Ptrend < 0.001) was inversely associated with incident frailty. The association persisted after further adjustment for SES and comorbidity. CONCLUSION: Among older individuals, multiple SES measures were positively associated with LTPA, which was a strong predictor of lower subsequent frailty risk.

Management and outcomes over time of acute coronary syndrome patients at particularly high cardiovascular risk : the ACSIS registry-based retrospective study.

OBJECTIVE: Some patients following acute coronary syndrome (ACS) are at particularly increased risk for recurrent cardiovascular events. We aimed to examine temporal trends in the management and outcomes across the spectrum of these particularly high-risk patients. DESIGN AND SETTING: A retrospective study based on the ACS Israeli survey (ACSIS) registry, a multicentre prospective national registry, taking place biennially in 25 cardiology departments in Israel. Temporal trends were examined in the early (2002-2008) and late (2010-2018) time periods. PARTICIPANTS: Consecutive patients with ACS enrolled in the ACSIS registry were stratified according to the Thrombolysis in Myocardial Infarction Risk Score for secondary prevention (TRS2°P) to high (TRS2°p=3), very high (TRS2°p=4) or extremely high risk (TRS2°p=5-9). Patients with TRS2°p<3 were excluded. From the initial 15 196 patients enrolled, 5359 patients were eventually included.Clinical outcome measures included 30-day major adverse cardiovascular events (MACE) and 1-year mortality. RESULTS: Among 5359 patients (50% high risk, 30% very high risk and 20% extremely high risk), those with a higher risk were older, had more comorbidities, presented more with non-ST elevation myocardial infarction, and were treated less often with guideline-recommended pharmacotherapy and percutaneous coronary intervention. Over time, treatment has improved in all risk strata, and the rate of 30-day MACE has significantly decreased in all risk groups (from 21% to 10%, from 22% to 15%, and from 26% to 16%, in high, very high and extremely high-risk groups, respectively, p<0.001 for each). However, 1-year mortality decreased only among high and very high-risk patients, and not among extremely high-risk patients in whom 1-year mortality rates remained very high (28.7% vs 28.9%, p=1). CONCLUSION: Within a particularly high-risk cohort of patients with ACS, treatment has significantly progressed over almost 2 decades. While short-term outcomes have improved in all risk groups, 1-year mortality has remained unchanged in extremely high-risk patients with ACS.

Edoxaban versus Warfarin in high-risk patients with atrial fibrillation: A comprehensive analysis of high-risk subgroups.

BACKGROUND: To compare the efficacy and safety of edoxaban vs warfarin in high-risk subgroups. METHODS: ENGAGE AF-TIMI 48 was a multicenter randomized, double-blind, controlled trial in 21,105 patients with atrial fibrillation (AF) within 12 months and CHADS2 score >2 randomized to higher-dose edoxaban regimen (HDER) 60 mg/reduced 30 mg, lower-dose edoxaban regimen (LDER) 30 mg/reduced 15 mg, or warfarin, and followed for 2.8 years (median). The primary outcome for this analysis was the net clinical outcome (NCO), a composite of stroke/systemic embolism events, major bleeding, or death. Multivariable risk-stratification analysis was used to categorize patients by the number of high-risk features. RESULTS: The annualized NCO rates in the warfarin arm were highest in patients with malignancy (19.2%), increased fall risk (14.0%), and very-low body weight (13.5%). The NCO rates increased with the numbers of high-risk factors in the warfarin arm: 4.5%, 7.2%, 9.9% and 14.6% in patients with 0 to 1, 2, 3, and >4 risk factors, respectively (Ptrend <0.001). Versus warfarin, HDER was associated with significant reductions of NCO in most of the subgroups: elderly, patients with moderate renal dysfunction, prior stroke/TIA, of Asian race, very-low body weight, concomitant single antiplatelet therapy, and VKA-naïve. With more high-risk features (0->4+), the absolute risk reductions favoring edoxaban over warfarin increased: 0.3%->2.0% for HDER; 0.4%->3.4% for LDER vs warfarin (P = .065 and P < .001, respectively). CONCLUSIONS: While underuse of anticoagulation in high-risk patients with AF remains common, substitution of effective and safer alternatives to warfarin, such as edoxaban, represents an opportunity to improve clinical outcomes.

The Interrelationship between Sarcoidosis and Atherosclerosis-Complex Yet Rational.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in affected organs [...].

Myocarditis following COVID-19 vaccination: magnetic resonance imaging study.

AIMS: To describe the cardiac magnetic resonance (CMR) imaging findings of patients who developed myocarditis following messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination. METHODS AND RESULTS: The present study retrospectively evaluated patients with clinically adjudicated myocarditis within 42 days of the first Pfizer-BNT162b2 mRNA COVID-19 vaccination, between 20 December 2020 and 24 May 2021 who underwent CMR. A total of 15 out 54 patients (28%) with myocarditis underwent a CMR and were included, 100% males, median age of 32 years (interquartile range = 22.5-40). Most patients presented with chest pain (87%) and had an abnormal electrocardiogram (79%). The severity of the disease was mild in 67% and intermediate in 33%. All patients survived and one patient was readmitted during the study period. CMR was performed at a median of 65 days (range 3-130 days) following diagnosis. Median ejection fraction was 58% (range 51-74%) global- and regional wall motion abnormalities were present in one and three patients, respectively. Native T1 was available in 13/15 patients (2/3 in 3 T and 11/12 in the 1.5 T), with increased values among 6/13. Late gadolinium enhancement (LGE) was found among 13/15 patients with a median of 2% (range 0-15%) with inferolateral wall being the most common location (8/13). The patterns of the LGE were: mid-wall in six patients; epicardial in five patients; and mid-wall and epicardial in two patients. CONCLUSIONS: Among patients who were diagnosed with post-vaccination clinical myocarditis, CMR imaging findings are mild and consistent with 'classical myocarditis'. The short-term clinical course and outcomes were favourable.

Worse outcomes of ACS patients without versus with traditional cardiovascular risk factors.

INTRODUCTION: Up to 20% of patients presenting with acute coronary syndrome (ACS) have no traditional cardiovascular risk-factors (RFs). Data regarding the determinants, management, and outcomes of these patients are scarce. OBJECTIVES: To evaluate the management, outcomes, and time-dependent changes of ACS patients without RFs. METHODS: Evaluation of clinical characteristics, management strategies, and outcomes as well as time-dependent changes [by 3 time periods: early (2000-2006), mid (2008-2013), and late (2016-2018)] of ACS patients without RFs (diabetes mellitus, hypertension, dyslipidemia, family history of ischemic heart disease, and smoking) or known coronary artery disease, enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. We compared ACS patients without RFs (no-RF group) to those with ≥1 RFs (RF group). RESULTS: Overall, 554/9,683 (5.7%) eligible ACS patients did not have any RFs [median age 63 (IQR 52-76) years, 25% females]. The no-RF group were older, with lower body mass index and prevalence of other cardiovascular comorbidity and chronic kidney disease compared with the RF group. The in-hospital percutaneous coronary intervention rates were lower among the no-RF vs. the RF group (55% vs. 66%, respectively p<0.001). Furthermore, lower rate of guideline-recommended medical therapy upon discharge was prescribed in the no-RF group. The rate of in-hospital complications was greater in the no-RF vs. RF group (31.6% vs. 26.1%, respectively p=0.005). The rates of 30-day major adverse cardiovascular events (MACE; 17.6% vs.12.8%, respectively, p=0.002) and of 30-day and 1-year all-cause mortality (8.4% vs. 4.2%, p<0.001 and 11.4% vs. 7.7%, p=0.003 respectively) were higher among patients with no-RF vs. RF. Following propensity score matching 30-day MACE, 30-day and 1-year mortality risk remained higher in the no-RF group. The rate of 30-day MACE decreased between the early and the late study period in the no-RF group (21.5% vs. 10.5%, p=0.003, respectively). CONCLUSIONS: ACS patients without traditional cardiovascular risk-factors comprise a unique group with reduced prevalence of comorbidities yet significantly worse outcomes. Additional research to identify unique risk-factors and targets for interventions to improve outcomes of this group of patients is warranted.

Diffused coronary involvement in Takayasu arteritis with concomitant malignancy.

Large vessel vasculitis (LVV) is composed of conditions in which inflammation of blood vessel walls affects mainly large arteries, such as the aorta and its main branches, and in some cases the coronary arteries. Coronary artery involvement in systemic vasculitis is associated with significant morbidity and mortality. We present a case of a young patient diagnosed with extensive coronary disease diagnosed as Takayasu arteritis, when whom a concomitant diagnosis of Hodgkin's lymphoma was made. The literature review revealed ten cases of malignancies associated with Takayasu arteritis. We discuss the complexity of the management of concurrent hematological malignancy with TAK and extensive coronary arteritis. This complicated and cross-disciplinary case also represents the pivotal importance of multi-disciplinary team decision in order to achieve the best clinical outcome of both disorders.

The Effect of Proprotein Convertase Subtilisin Kexin Type 9 Inhibitors on Circulating Endothelial Progenitor Cells in Patients with Cardiovascular Disease.

PURPOSE: Circulating endothelial progenitor cells (cEPCs) are vital to vascular repair by re-endothelialization. We aimed to explore the effect of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) on cEPCs hypothesizing a possible pleiotropic effect. METHODS: Patients with cardiovascular disease (CVD) were sampled for cEPCs at baseline and following the initiation of PCSK9i. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+), and by the formation of colony-forming units (CFUs) and production of VEGF. RESULTS: Our cohort included 26 patients (median age 68 (IQR 63, 73) years; 69% male). Following 3 months of treatment with PCSK9i and a decline in low-density lipoprotein cholesterol levels (153 (IQR 116, 176) to 56 (IQR 28, 72) mg/dl), p < 0.001), there was an increase in CD34(+)/CD133(+) and VEGFR-2(+) cell levels (0.98% (IQR 0.37, 1.55) to 1.43% (IQR 0.90, 4.51), p = 0.002 and 0.66% (IQR 0.22, 0.99) to 1.53% (IQR 0.73, 2.70), p = 0.05, respectively). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with PCSK9i (1 CFUs (IQR 0.0, 1.0) to 2.5 (IQR 1.5, 3), p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (0.15 (IQR 0.11, 0.19) to 0.21 (IQR 0.18, 0.23), p < 0.001). VEGF levels increased following PCSK9i treatment (57 (IQR 18, 24) to 105 (IQR 43, 245), p = 0.006). CONCLUSIONS: Patients with CVD treated with PCSK9i demonstrate higher levels of active cEPCs, reflecting the promotion of endothelial repair. These findings may represent a novel mechanism of action of PCSK9i.

The Effect of Tafamidis on Circulating Endothelial Progenitor Cells in Patients with Transthyretin Cardiac Amyloidosis.

AIMS: Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs. METHODS AND RESULTS: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34(+)/CD133(+) and vascular endothelial growth factor receptor (VEGFR)-2(+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34(+)/VEGFR-2(+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133(+)/VEGFR-2(+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039). CONCLUSIONS: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA.

Temporal Trends and Outcome of Patients with Acute Coronary Syndrome and Prior Myocardial Infarction.

Patients who have previously had a myocardial infarction (MI) are considered a high-risk group with increased risk for cardiovascular (CV) events. During the last decade, the outcome of acute coronary syndrome (ACS) patients has improved due to advances in medical therapy and interventional techniques. We aimed to examine temporal trends and outcomes of patients with prior MI admitted due to ACS from the Acute Coronary Syndrome Israeli Survey (ACSIS). Included were 16,934 ACS patients, of whom 31.4% had prior MI. For temporal trend analysis, the cohort was divided into an early period (2000-2008) and late period (2010-2018). For patients with prior MI, patients in the late period had a higher rate of CV risk factors and were treated more frequently with revascularization and guidelines-directed medical therapy. Recurrent MI (6.7% vs. 12%, p < 0.001), MACE (10.6% vs. 21%, p < 0.001) and 1-year mortality (10.7% vs. 14.6%, p < 0.001) were significantly lower in the late period. However, the mortality rate for patients with prior MI remained higher compared with patients without prior MI (10.7% vs. 6.8% p < 0.001) with an overall higher mortality rate in the STEMI group. Thus, despite significant improvement in outcome measures in the contemporary era, ACS patients with prior MI are still at increased risk for recurrent ischemic CV events and mortality.

Acute Kidney Injury Following Admission with Acute Coronary Syndrome: The Role of Diabetes Mellitus.

PURPOSE: To evaluate the role of diabetes mellitus in the incidence, risk factors, and outcomes of AKI (acute kidney injury) in patients admitted with ACS (acute coronary syndrome). METHODS: We performed a comparative evaluation of ACS patients with vs. without DM who developed AKI enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. AKI was defined as an absolute increase in serum creatinine (≥0.5 mg/dL) or above 1.5 mg/dL or new renal replacement therapy upon admission with ACS. Outcomes included 30-day major adverse cardiovascular events (MACE) and 1-year all-cause mortality. RESULTS: The current study included a total of 16,879 patients, median age 64 (IQR 54-74), 77% males, 36% with DM. The incidence of AKI was significantly higher among patients with vs. without DM (8.4% vs. 4.7%, p < 0.001). The rates of 30-day MACE (40.8% vs. 13.4%, p < 0.001) and 1-year mortality (43.7% vs. 10%, p < 0.001) were significantly greater among diabetic patients who developed vs. those who did not develop AKI respectively, yet very similar among patients that developed AKI with vs. without DM (30-day MACE 40.8% vs. 40.3%, p = 0.9 1-year mortality 43.7 vs. 44.8%, p = 0.8, respectively). Multivariate analyses adjusted to potential confounders, showed similar independent predictors of AKI among patients with and without DM, comprising; older age, chronic kidney disease, congestive heart failure, and peripheral arterial disease. CONCLUSIONS: Although patients with DM are at much greater risk for AKI when admitted with ACS, the independent predictors of AKI and the worse patient outcomes when AKI occurs, are similar irrespective to DM status.

Coronary Artery Disease in Women: A Comprehensive Appraisal.

Coronary artery disease (CAD) is a significant cause of illness and death amongst women. The pathophysiology, manifestations, and outcomes of CVD and CAD differ between sexes. These sex differences remain under-recognized. The aim of this review is to highlight and raise awareness of the burden and unique aspects of CAD in women. It details the unique pathophysiology of CAD in women, cardiovascular risk factors in women (both traditional and sex-specific), the clinical presentation of CAD in women, and the range of disease in obstructive and non-obstructive CAD in women.