Subsequent Cardiovascular Events Research Articles

Cardiovascular Manifestations, Imaging, and Outcomes in Systemic Lupus Erythematosus: An Eight-Year Single Center Experience in the United States.

Systemic lupus erythematosus (SLE) is a challenging autoimmune and multi-system condition. With advances in cardiovascular screening and therapies for SLE patients, we evaluated the cardiovascular characteristics, multi-modality imaging, and outcomes of SLE at our tertiary referral center over an 8year period. Consecutive patients from our SLE registry from April 2012 to March 2020 were retrospectively analyzed. Data pertaining to cardiovascular manifestations, investigations, management, and outcomes were assessed. We studied 258 SLE patients (mean age 42.2 ± 14.7 years); 233 (90.3%) were female. The main cardiac manifestations at index SLE clinic were pericardial disease in 33.3%, valve disease in 18%, cardiomyopathy in 9.6%, and stroke in 7.4%. During a mean follow-up of 3.0 ± 2.2years after index SLE clinic, there were 5 (1.9%) deaths, 24 (9.3%) cardiovascular events, and 44 (17.1%) SLE-related hospitalizations. A history of stroke and hypertension were independently associated with cardiovascular events, hazard ratio (HR) (95% confidence intervals (CI)) of 5.38 (1.41-20.6) and 3.31 (1.02-10.7), respectively, while younger age and lower albumin predicted SLE-related hospitalizations. Cardiovascular manifestations are prevalent in SLE, especially for pericardial, valvular, and atherosclerotic diseases. With contemporary SLE and cardiovascular management, subsequent adverse cardiovascular events were infrequent in this study.

Sepsis, Septic Shock, and Differences in Cardiovascular Event Occurrence.

Introduction: Mortality estimates from sepsis and septic shock ranged from 18% to 35% and 40% to 60%, respectively, prior to 2014. Sepsis patients who experience subsequent cardiovascular events have increased mortality; however, data are limited among septic shock patients. This study reports in-hospital mortality, incident cardiovascular events, and cardiovascular procedures among sepsis patients with and without subsequent septic shock. Methods: Patients with a primary diagnosis of sepsis with and without a secondary diagnosis of septic shock were identified from the 2016 and 2017 National Readmissions Database. These patients were then evaluated for the occurrence of cardiovascular events and procedures. Results: A total of 2,127,137 patients were included in the study, with a mean age of 66 years. Twenty percent of patients (n = 420,135) developed subsequent septic shock. In-hospital mortality among patients with a primary diagnosis of sepsis was 5.3%, and it was 31.2% for those with subsequent septic shock. Notable cardiovascular events occurring among sepsis patients with and without subsequent septic shock, respectively, included: acute kidney injury (65.1% vs. 32.8%, P < .0001), acute systolic heart failure (9.8% vs. 5.1%, P < .0001), NSTEMI (8.8% vs. 3.2%, P < .0001), and ischemic stroke (2.3% vs. 0.9%, P < .0001). Similarly, the most common cardiovascular procedures between the two groups were: percutaneous coronary intervention (0.37% vs. 0.20%, P < .0001), intra-aortic balloon pump (0.19% vs. 0.02%, P < .0001), and extracorporeal membrane oxygenation (0.18% vs. 0.01%, P < .0001). Conclusions: Sepsis with subsequent septic shock is associated with an increased frequency of in-hospital cardiovascular events and procedures.

Abstract P125: Change In Low-density Lipoprotein Cholesterol And Risk Of Subsequent Cardiovascular Events Among Patients With Myocardial Infarction

Background: Among patients who experience a myocardial infarction (MI), elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for experiencing a subsequent cardiovascular (CV) event; however, real-world evidence is lacking in regard to how changes in LDL-C levels after a MI hospitalization are related to subsequent CV events. Methods: Adults with a hospitalized MI and an available baseline LDL-C (closest LDL-C within 2 years prior to hospital discharge) between 2012 and 2018 within a 27-county region across MN and WI were included for study. For each LDL-C measurement during follow-up (starting with the first LDL-C &gt;30 days after baseline and ≤1-year post-discharge), percent change from baseline LDL-C was calculated. Patients were followed for subsequent CV events (composite endpoint 1: MI, ischemic stroke [IS], coronary artery bypass grafting [CABG], percutaneous coronary intervention [PCI]; composite endpoint 2: MI, IS, CABG, PCI, CV death). Cox models were used to evaluate the association between time-dependent LDL-C percent change and CV events, stratified by baseline LDL-C (&lt;70, 70-99, ≥100 mg/dL). Results: Among 3,034 MI patients identified, 740 (24%), 940 (31%) and 1354 (45%) had a baseline LDL-C &lt;70, 70-99 and ≥100 mg/dL, respectively. After a mean follow-up of 3.4 years, 471 and 667 patients experienced the composite endpoint 1 and 2, respectively. After covariate adjustment, a trend towards a lower risk of CV events with decreasing LDL-C from baseline, compared to those with no change or an increase in LDL-C, was observed among those with a LDL-C &lt;70 and &gt; 100 mg/dl but not in those with a LDL-C 70-99 mg/dL (Table). Conclusions: In a population-based cohort of MI patients, there is evidence that patients with a decrease in LDL-C after MI may have a reduced risk of subsequent CV events. These results underscore the importance of lowering LDL-C after a MI and may help to identify subgroups at highest risk for additional CV events and those who may benefit from targeted LDL-C treatment recommendations.

Persistence of Depressive Symptoms and Risk of Incident Cardiovascular Disease With and Without Diabetes: Results from the REGARDS Study.

Baseline depressive symptoms are associated with subsequent adverse cardiovascular (CV) events in subjects with and without diabetes but the impact of persistent symptoms vs. improvement remains controversial. Examine long-term changes in depressive symptoms in individuals with and without diabetes and the associated risk for adverse CV events. REGARDS is a prospective cohort study of CV risk factors in 30,000 participants aged 45 years and older. N = 16,368 (16.5% with diabetes mellitus) who remained in the cohort an average of 11.1 years later and who had complete data. Depressive symptoms were measured using the 4-item Centers for Epidemiologic Study of Depression (CES-D) questionnaire at baseline and again at a mean follow-up of 5.07 (SD = 1.66) years. Adjudicated incident stroke, coronary heart disease (CHD), CV mortality, and a composite outcome were assessed in a subsequent follow-up period of 6.1 (SD = 2.6) years. The association of changes in depressive symptoms (CES-D scores) across 5 years with incident CV events was assessed using Cox proportional hazards modeling. Compared to participants with no depressive symptoms at either time point, participants without diabetes but with persistently elevated depressive symptoms at both baseline and follow-up demonstrated a significantly increased risk of incident stroke (HR (95% CI) = 1.84 (1.03, 3.30)), a pattern which was substantially more prevalent in blacks (HR (95% CI) = 2.64 (1.48, 4.72)) compared to whites (HR (95% CI) = 1.06 (0.50, 2.25)) and in those not taking anti-depressants (HR (95% CI) = 2.01 (1.21, 3.35)) in fully adjusted models. The persistence of depressive symptoms across 5 years of follow-up in participants without diabetes identifies individuals at increased risk for incident stroke. This was particularly evident in black participants and among those not taking anti-depressants.

Incident Cardiovascular Disease Among Adults With Cancer: A Population-Based Cohort Study

BackgroundPatients with cancer and cancer survivors are at increased risk for incident heart failure, but there are conflicting data on the long-term risk for other cardiovascular events and how such risk may vary by cancer site. ObjectivesThe aim of this study was to determine the impact of a new cancer diagnosis on the risk for fatal and nonfatal cardiovascular events. MethodsUsing administrative health care databases, a population-based retrospective cohort study was conducted among 4,519,243 adults residing in Alberta, Canada, from April 2007 to December 2018. Participants with new cancer diagnoses during the study period were compared with those without cancer with respect to risk for subsequent cardiovascular events (cardiovascular mortality, myocardial infarction, stroke, heart failure, and pulmonary embolism) using time-to-event survival models after adjusting for sociodemographic data and comorbidities. ResultsA total of 224,016 participants with new cancer diagnoses were identified, as well as 73,360 cardiovascular deaths and 470,481 nonfatal cardiovascular events during a median follow-up period of 11.8 years. After adjustment, participants with cancer had HRs of 1.33 (95% CI: 1.29-1.37) for cardiovascular mortality, 1.01 (95% CI: 0.97-1.05) for myocardial infarction, 1.44 (95% CI: 1.41-1.47) for stroke, 1.62 (95% CI: 1.59-1.65) for heart failure, and 3.43 (95% CI: 3.37-3.50) for pulmonary embolism, compared with participants without cancer. Cardiovascular risk was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system and hematologic malignancies. ConclusionsA new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site. These findings highlight the need for a collaborative approach to health care for patients with cancer and cancer survivors.

The Nevada peripheral artery disease screening effort in a Medicare Advantage population and subsequent mortality and major adverse cardiovascular event risk

BackgroundContemporary estimates of undetected asymptomatic lower extremity peripheral artery disease (PAD) in the community and its association with adverse outcomes in the population are lacking. We investigated the long-term association between previously undetected PAD and subsequent all-cause mortality and major adverse cardiovascular events (MACE) for Medicare Advantage beneficiaries aged ≥65 years in a large metropolitan area characterized by concentrations of atherosclerotic risk factors and a more vulnerable socioeconomic risk profile. MethodsData were derived from the patients’ electronic medical records and linked with claims outcomes data for 13,971 Medicare Advantage beneficiaries aged ≥65 years who had undergone PAD screening in 2016 as a part of their routine annual health assessment in the greater Las Vegas, Nevada, metropolitan area. PAD screening was performed with their primary care provider using volume plethysmography system methods. The association between PAD screening status and 1- and 3-year all-cause mortality and MACE rates was documented. ResultsThe cohort had a mean age of 75.3 ± 6.6 years, and 57.7% were women. Of the 13,768 patients, 4351 (31.6%) had had a positive PAD screening result. Almost 60% had had a lower socioeconomic income level, with 15.1% living under the poverty level. The risk estimates associated with a positive vs negative PAD screening result for both all-cause mortality and MACE were as follows: unadjusted hazard ratio (HR) for mortality, 2.17 (95% confidence interval [CI], 1.79-2.63) and unadjusted HR for MACE, 2.00 (95% CI, 1.15-3.49) at 1 year and unadjusted HR for mortality, 2.04 (95% CI, 1.84-2.26) and unadjusted HR for MACE, 1.67 (95% CI, 1.37-2.02) at 3 years. After multivariable adjustment, all associations persisted (P < .001), with HRs ranging from 1.41 to 1.69, except for that for 1-year MACE (similar risk estimate but P = .09). ConclusionsA positive screening result for previously undetected lower extremity PAD was independently associated with short- and long-term increased risks of mortality and MACE for individuals aged ≥65 years living in a large, metropolitan area.

Sepsis hospitalization and risk of subsequent cardiovascular events in adults: a population-based matched cohort study.

To determine whether surviving a first sepsis hospitalization is associated with long-term cardiovascular events. Population-based matched cohort study conducted in Ontario, Canada (2008-2017). Adult survivors (older than 18years) of a first sepsis hospitalization were matched to adult survivors of a non-sepsis hospitalization using hard-matching and propensity score methods. Patients with pre-existing cardiovascular disease were excluded. The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5years of follow-up. Secondary outcomes included venous thromboembolism and all-cause death. Cox proportional hazards models with robust standard errors were used to estimate the association of sepsis with all outcomes of interest; hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Sensitivity analyses included Fine and Gray models to account for the competing risk of all-cause death and probabilistic bias analyses. 254,241 adult sepsis survivors were matched to adult survivors of non-sepsis hospitalization episodes. Sepsis survivors experienced an increased hazard of major cardiovascular events compared to non-sepsis survivors (HR 1.30; 95% CI 1.27-1.32), which was more pronounced in younger patients (HR 1.66; 95% CI 1.36-2.02 for patients aged 40 or younger; HR 1.21; 95% CI 1.18-1.24 for patients older than 80years). Sepsis survivors also faced an increased hazard of venous thromboembolism (HR 1.61; 95% CI 1.55-1.67) and all-cause death (HR 1.26; 95% CI 1.25-1.27). Sensitivity analyses yielded consistent results. Adult sepsis survivors experience an increased hazard of major cardiovascular events compared to survivors of a non-sepsis hospitalization.

Early systolic lengthening in patients with ST-elevation myocardial infarction: a novel tool for risk stratification

Abstract Funding Acknowledgements Type of funding sources: None. Background After an ST-elevation myocardial infarction (STEMI), the risk of subsequent cardiovascular events is high. Risk stratification at index hospitalization remains a core challenge, especially in patients with subtle changes in LV function. Early systolic lengthening (ESL) may occur in ischemic myocardial segments with reduced contractile force and it has been correlated with infarct size and prognosis in STEMI patients with mildly impaired LV function. In this study, we aimed to evaluate the correlation of ESL with common echocardiographic parameters and its prognostic value in STEMI patients with preserved LV function. Methods We retrospectively included all the patients admitted to an intensive care unit with STEMI and a left ventricle ejection fraction ≥55% from January to June of 2016. Patients with inadequate image quality for speckle tracking echocardiographic examination were excluded (n = 14). We evaluated the ESL index, defined as follows: [−100×(peak positive systolic strain/peak negative strain in cardiac cycle)], and ESL duration. Results A total of 37 patients were included in the study. Mean age was 63 ± 12 years with a male preponderance (81%). All patients were submitted to complete revascularization. Median values of the ESL index and ESL duration were 7% (IQR, 4%–10%) and 37 msec (IQR, 21–55 msec), respectively. No significant differences were found between ESL index and ESL duration groups, except for a higher prevalence of heart failure at hospitalization in both highest groups, and women were more prevalent in the ESL index higher group (Tables 1 and 2). ESL index was correlated with post-systolic index (PSI) (r2 = 0.34, p = 0.04) and showed a weak correlation with E/A ratio (r2=-0.37, p = 0.02). ESL duration was correlated with ESL index (r2 = 0.76, p &amp;lt; 0.001) and PSI (r2 = 0.43, p = 0.008). During a median follow-up of 3.2 years (interquartile range, 2.9–3.4 years), 7 (18.9%) patients experienced major adverse cardiovascular events (MACE), a composite of heart failure admission, myocardial infarction, and all-cause mortality Both ESL index (HR 2.5; 95%CI 1.2–5.3; P = 0.02) and ESL duration (HR 1.7; 95%CI 1.1–2.7; P = 0.02) were independent predictors of MACE. Both associations remained significant after adjusting for clinical confounders. Conclusions In our cohort of STEMI patients with preserved LV function, assessment of ESL yielded important and significant prognostic information on MACE. ESL may be a useful tool to enhance routine risk stratification in this population. Abstract TABLE 1 Abstract TABLE 2

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Clinical and Economic Impact of Early Rreatment Initiation with Evolocumab in Patients with a Recent Myocardial Infarction in the United States

<h3>Lead Author's Financial Disclosures</h3> Employee and stockholder of Amgen Inc. <h3>Study Funding</h3> Amgen Inc. <h3>Background/Synopsis</h3> Current ACC/AHA dyslipidemia guidelines recommend initiating non-statin therapies such as PCSK9 inhibitors in very high risk (VHR) patients with atherosclerotic cardiovascular disease (ASCVD) who do not reach the threshold of 70 mg/dL with statins alone. Patients with a recent myocardial infarction (MI) (in the past 12 months) constitute a subset of VHR patients who have a significantly higher risk of subsequent cardiovascular (CV) events (CVE) in the months and years following the event. <h3>Objective/Purpose</h3> This study aimed to estimate the clinical and economic impact of early initiation of evolocumab after an MI from a US perspective. <h3>Methods</h3> A published evolocumab partitioned survival model was used to simulate a cohort of 100,000 ASCVD patients with a recent MI and LDL-C above 100 mg/dL. CVE rates for non-fatal events (MI and stroke) and CV death were estimated using the US Prognos LDL-C database and NHANES with National Vital Statistics data, respectively. Treatment effect was modelled using the LDL-C percentage reduction and CVE rate ratios per mmol/L observed in the FOURIER trial. CVE costs were estimated from a US database representing healthcare claims from 2018 through 2020. We modelled the impact, over a 2-year time horizon, of early initiation of evolocumab (<10 days after the MI) compared to standard of care (SoC) of statins ± ezetimibe alone and compared to initiating evolocumab between 3 to 9 months after the MI. <h3>Results</h3> Early initiation of evolocumab in the simulated cohort of patients with a recent MI avoided a total of 5,356 CVE, corresponding to CVE cost savings of $310 million over the following 2 years, compared to treating patients with SoC alone. Treating patients with evolocumab early after the MI, in comparison to starting treatment at 3, 6 and 9 months after the MI, led to the avoidance of 1,150; 2,013; and 2,876 CVE with associated CVE cost savings of $67, $116,and $166 million, respectively. <h3>Conclusions</h3> Our model shows that the earliest initiation of evolocumab after an MI has the highest potential to decrease the predicted number of CVE substantially, resulting in significant CVE cost savings compared to a later initiation of evolocumab or treatment with SoC alone. These results underscore the value of early initiation of intensive lipid-lowering therapy in VHR ASCVD patients, especially in patients with a recent MI.

Кардиоваскулярные риски подросткового ожирения

The problem of overweight in young people is highly relevant now, because the prevalence of obesity-related complications, including cardiovascular risks, is rapidly increasing. The most common complication of overweight is metabolic syndrome, when obesity is often associated with essential hypertension (EH), dyslipidemia and insulin resistance. Objective. To analyze the risks of cardiovascular disorders in obese adolescents. This is a literature review, where we used theoretical methods, such as analysis, classification, systematization, and generalization of data. In all age groups, the first clinical complication of obesity is EH, the degree and course of which significantly affect the obesity prognosis and determine the probability of early cardiovascular complications. Up to 80% of obese children and adolescents are found to have high blood pressure (BP). Each extra kilogram increases systolic BP by 0.36 mmHg and diastolic BP by 0.1 mmHg. The prevalence of EH increases with increasing body weight. Obese people are 2 to 3 times more likely to develop coronary heart caused by atherosclerotic lesions in the coronary arteries with subsequent fatal cardiovascular events. Higher incidence of cardiovascular diseases in obese patients is presumably associated with endothelial dysfunction and subclinical inflammation. Cardiovascular disorders became more prevalent in young people over the last decade. They are often diagnosed in adolescence. Conclusion. Despite the significance of this healthcare problem, no universal clinical and metabolic markers of cardiovascular damage have been identified so far. The structural and geometric rearrangement of the myocardium in obese patients have not been sufficiently studied. Key words: cardiovascular risks, cardiovascular pathology, obesity, metabolic syndrome, adolescence, puberty, essential hypertension

POSA199 Risk of Cardiovascular Events after Streptococcus Pneumoniae Infections: Life Study

Streptococcus pneumoniae is a common cause of diseases such as community-acquired pneumonia, meningitis, and sepsis across all age groups. In Japan, routine pneumococcal vaccinations are carried out for children aged ≤5 years and older persons aged ≥65 years due to their higher risk of infection. Acute S. pneumoniae infections are reported to elevate the risk of subsequent cardiovascular events such as coronary heart disease, heart failure, arrhythmia, and stroke. In order to generate evidence for the development of optimal vaccination strategies, this study analyzed the effects of S.

The Complex Role of C-Reactive Protein in Systemic Lupus Erythematosus.

C-reactive protein (CRP) is well-known as a sensitive albeit unspecific biomarker of inflammation. In most rheumatic conditions, the level of this evolutionarily highly conserved pattern recognition molecule conveys reliable information regarding the degree of ongoing inflammation, driven mainly by interleukin-6. However, the underlying causes of increased CRP levels are numerous, including both infections and malignancies. In addition, low to moderate increases in CRP predict subsequent cardiovascular events, often occurring years later, in patients with angina and in healthy individuals. However, autoimmune diseases characterized by the Type I interferon gene signature (e.g., systemic lupus erythematosus, primary Sjögren’s syndrome and inflammatory myopathies) represent exceptions to the general rule that the concentrations of CRP correlate with the extent and severity of inflammation. In fact, adequate levels of CRP can be beneficial in autoimmune conditions, in that they contribute to efficient clearance of cell remnants and immune complexes through complement activation/modulation, opsonization and phagocytosis. Furthermore, emerging data indicate that CRP constitutes an autoantigen in systemic lupus erythematosus. At the same time, the increased risks of cardiovascular and cerebrovascular diseases in patients diagnosed with systemic lupus erythematosus and rheumatoid arthritis are well-established, with significant impacts on quality of life, accrual of organ damage, and premature mortality. This review describes CRP-mediated biological effects and the regulation of CRP release in relation to aspects of cardiovascular disease and mechanisms of autoimmunity, with particular focus on systemic lupus erythematosus.

Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort.

BackgroundCarotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes.Methods and ResultsWe studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT.ConclusionsIn the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.

Blood and Urine Biomarkers Predicting Worsening Kidney Function in Patients with Type 2 Diabetes Post-Acute Coronary Syndrome: An Analysis from the EXAMINE Trial

Introduction: Worsening kidney function (WKF) is frequent among patients with type 2 diabetes (T2D) and a recent acute coronary syndrome (ACS) and is associated with a poor prognosis. An accurate prediction of WKF is clinically important. Aims: Using data from the Cardiovascular Outcomes Study of Alogliptin in Patients with Type 2 Diabetes and Acute Coronary Syndrome trial including patients with T2D and a recent ACS, and a large biomarker panel incorporating proteins measured both in blood and urine, we aim to determine those with best performance for WKF prediction. Methods: WKF was defined as a ≥40% estimated glomerular filtration rate (eGFR) drop from baseline, eGFR <15 mL/min, or dialysis. Mixed-effects and time-updated Cox models were used. Results: 5,131 patients were included from whom 222 (4.3%) developed at least one WKF episode over a median follow-up of 18 months. Patients who developed WKF were more frequently women, had longer diabetes duration, a more frequent heart failure history, higher anemia prevalence, and impaired kidney function. In multivariable models including all variables (clinical and biomarkers) independently associated with WKF with a p value ≤0.0001, blood kidney injury molecule 1 (KIM-1) was (by far) the variable with strongest WKF association, followed by anemia. KIM-1 alone provided good discrimination for WKF prediction (area under the curve = 0.73). Patients in the high KIM-1-derived risk tertile had a 6.7-fold higher risk of any WKF than patients classified as low risk. In time-updated Cox models, the occurrence of WKF was independently associated with a higher risk of death: adjusted hazard ratio = 4.93 (3.06–7.96), p value <0.0001. Conclusion: Blood KIM-1 was the biomarker with the strongest association with WKF. The occurrence of WKF was independently associated with a higher risk of subsequent cardiovascular events and mortality.

Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent

BackgroundUnderlying cardiovascular disease (CVD) is a concern in patients with esophageal cancer (EC) receiving curative treatment with chemoradiation and surgery. ObjectivesThe aim of this study was to characterize the CVD profile and describe the incidence and characteristics of cardiovascular (CV) events in patients with EC following chemoradiation and surgery. MethodsConsecutive patients with EC referred for curative treatment were enrolled. Clinical CVD status, ongoing CVD treatment, cardiac function, and physical performance were assessed before chemoradiation. During a 90-day follow-up period, all CV events were noted and classified after in-depth medical record review. CV events were defined by major adverse CV events (transient ischemic attack, imaging-verified new stroke, unstable angina, heart failure or cardiomyopathy) or by Common Terminology Criteria for Adverse Events grade ≥3 (arrhythmia, thromboembolic events, or pericardial effusion requiring pericardiocentesis). ResultsAmong 55 patients enrolled (median age 67 years; range: 50-86 years; 89% men), 22% had CVD prior to chemoradiation, and 11% with pre-existing CVD were inadequately treated according to current CV guidelines. Thirteen patients (24%) developed 15 events during follow-up. Pre-existing atrial fibrillation and a dilated left atrium were significantly associated with subsequent CV events. Left ventricular (LV) systolic dysfunction was frequently noted; 51% had impaired LV global longitudinal strain (<18%), and 16% had LV ejection fraction <50%. ConclusionsA systematic cardiac evaluation prior to chemoradiation in patients with EC revealed a high prevalence of undetected CVD, inadequately treated pre-existing CVD, and a high incidence of CV events after chemoradiation. These findings highlight the need for a systematic baseline cardiac examination in patients with EC to optimize CVD treatment. (Impact of Cancer Therapy on Myocardial Function in Patients With Esophagus Cancer [Heartcheck]; NCT03619317)

Multi-omics of a pre-clinical model of diabetic cardiomyopathy reveals increased fatty acid supply impacts mitochondrial metabolic selectivity

The incidence of type 2 diabetes (T2D) is increasing globally, with long-term implications for human health and longevity. Heart disease is the leading cause of death in T2D patients, who display an elevated risk of an acute cardiovascular event and worse outcomes following such an insult. The underlying mechanisms that predispose the diabetic heart to this poor prognosis remain to be defined. This study developed a pre-clinical model (Rattus norvegicus) that complemented caloric excess from a high-fat diet (HFD) and pancreatic β-cell dysfunction from streptozotocin (STZ) to produce hyperglycaemia, peripheral insulin resistance, hyperlipidaemia and elevated fat mass to mimic the clinical features of T2D. Ex vivo cardiac function was assessed using Langendorff perfusion with systolic and diastolic contractile depression observed in T2D hearts. Cohorts representing untreated, individual HFD- or STZ-treatments and the combined HFD + STZ approach were used to generate ventricular samples (n = 9 per cohort) for sequential and integrated analysis of the proteome, lipidome and metabolome by liquid chromatography-tandem mass spectrometry. This study found that in T2D hearts, HFD treatment primed the metabolome, while STZ treatment was the major driver for changes in the proteome. Both treatments equally impacted the lipidome. Our data suggest that increases in β-oxidation and early TCA cycle intermediates promoted rerouting via 2-oxaloacetate to glutamate, γ-aminobutyric acid and glutathione. Furthermore, we suggest that the T2D heart activates networks to redistribute excess acetyl-CoA towards ketogenesis and incomplete β-oxidation through the formation of short-chain acylcarnitine species. Multi-omics provided a global and comprehensive molecular view of the diabetic heart, which distributes substrates and products from excess β-oxidation, reduces metabolic flexibility and impairs capacity to restore high energy reservoirs needed to respond to and prevent subsequent acute cardiovascular events.

Outpatient diuretic intensification as endpoint in heart failure with preserved ejection fraction trials: an analysis from TOPCAT.

Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT-Americas. Time-updated Cox models and win ratio analysis. ODI was defined by a post-randomization loop diuretic dose increase or new initiation. The median follow-up was 2.9 years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow-up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36-2.04; HR for cardiovascular death 2.17, 95% CI 1.64-2.87); and HR for all-cause mortality 1.75, 95% CI 1.41-2.16] (p< 0.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three-fold in the placebo group (from 10.4 to 29.9 events per 100 person-years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65-0.85; p< 0.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70-0.99; p= 0.044). Using win ratio provided similar estimates. In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.

Abstract 10858: Comparison of Clinical Effect of Living Alone Between Urban Area and Rural Area in Patient with Acute Coronary Syndrome

Background and Objective: Living alone is reported as an independent risk factor for worse clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Manifestations of psychological stress in patients living alone is reported to be associated with subsequent cardiovascular events. The impact of living alone on the psychological factors of patients may be differ depending on their living environment. However, comparison of the effects of living alone in different living environment on the prognosis of patients with ACS has not been reported. Purpose: The aim of the study was to compare the effect of living alone on clinical outcomes in patients with ACS between urban and rural area. Methods: Data from a multi-center, observational study of consecutive ACS patients who underwent emergency PCI between January 2012 and December 2016 were analyzed. The clinical endpoint was major adverse cardiovascular events (MACE) which defined as composite of cardiovascular death, ACS, and stroke. Results: In this study, 1349 patients were enrolled and divided into two population according to their living environment; urban area (n=417), and rural area (n=932). 87 patients (20.9 %) in urban area, and 169 patients (18.1 %) in rural were living alone. There were no significant differences in baseline characteristics between the living alone and the living together group in both urban and rural area. During a median follow-up period of 2.1 years, Kaplan-Meier curves showed the living alone group had higher risk of MACE than the living together group in urban area (log-rank, p=0.01). On the other hands, no significant differences were shown in the incidences of MACE between two groups in rural area (p=0.86). After adjustment for other covariates, the living alone was significantly associated with MACE (hazard ratio [HR], 2.83; 95 % confidential interval [CI], 1.16-6.91; p=0.02) compared with the living together in urban area. However, in rural area, the living alone group was not significantly associated with MACE (HR, 1.02; 95 % CI, 0.66-1.57; p=0.92) compared with the living together group. Conclusion: Living alone was significantly associated with worse clinical outcomes after emergency PCI of ACS in urban area but not in rural area.

Abstract 12457: Atrial Fibrillation is a Cardiovascular Risk Factor for Worse Prognosis in COVID-19

Background: In the presence of comorbid conditions, COVID-19 infections are known to require more advanced treatment, poorer outcomes and have longer-term sequelae. New-onset atrial fibrillation (AF) during COVID-19 infection has been associated with worse cardiovascular outcomes but not mortality. However, it remains unclear whether a prior history (hx) of atrial fibrillation is a cardiovascular risk factor predicting a worse outcome in COVID-19 patients. As such, we examined, using propensity matching accounting for possible confounders, the need for advanced treatment and subsequent major cardiovascular events (MACE) in patients with a prior hx of AF with COVID-19 infection. Methods: From March 2020 to May 2021, patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n=3119) were propensity matched for age, gender, race/ethnicity, prior coronary artery disease (CAD), prior heart failure (HF), prior stroke and hypertension to non-AF SARS-CoV-2 positive patients. Cox hazard regression analysis with multivariable adjustment was used to determine risk of subsequent MACE (all-cause death, myocardial infarction, HF and stroke). Results: Baseline characteristics, treatments, and outcomes stratified by AF status are shown in the Table. While the groups had similar baseline characteristics, AF COVID-19 patients were more likely to require hospitalization, ICU care, and ventilator support. Consistent with our hypothesis, composite MACE event rates were higher in the AF patients (HR=1.60, p&lt;0.0001) secondary to increases in heart failure and all-cause mortality rates. Conclusions: These data support AF as a cardiovascular risk factor predicting worse outcomes in COVID-19 patients. Specifically, AF increases the need for advanced treatments such as hospitalization, ICU care and ventilator support resulting in an increase in subsequent heart failure and all-cause mortality.