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Genetic Mapping Predicts Risk of Cardiovascular Events in People With Type 2 Diabetes

CVD, cardiovascular, heart MRI, cardiac

Risk scores based on genetic mapping were found to correlate with hypertensive blood pressure (BP) traits and an increased likelihood of adverse cardiovascular events, such as stroke, myocardial infarction, and cardiovascular death, in individuals with type 2 diabetes (T2D), according to results of a study published in Hypertension. The risk of adverse cardiovascular events in those with higher genetic risk scores were unchanged by intensive glycemic therapy approaches.

Researchers conducted a post hoc analysis of the National Institutes of Health’s ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial (ClinicalTrials.gov Identifier: NCT00000620) to assess whether genetic variants influenced BP traits and adverse cardiovascular outcomes in individuals with T2D. Out of the 10,251 participants with T2D in the ACCORD trial, 6335 individuals had genetic data that were needed to calculate polygenic risk scores.

During the ACCORD trial, BP data were calculated using an average of 3 BP measurements with 5 minutes rest in between measurements. Overall, the median systolic blood pressure was 147 mm Hg, the median diastolic blood pressure was 83 mm Hg, and the median HbA1C was 8.1%.

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For the post hoc assessment, the researchers collected participant genotype data and compared these data with the Trans-OMICs Precision Medicine (TOPMed) Freeze 8 gene map, which consists of more than 1000 genetic variants known to affect blood pressure. The researchers calculated polygenic risk scores based on the number of matches between each participant’s DNA and the genetic variants known to influence BP. The greater the number of matches, the higher the risk score. The median polygenic risk score was 168.4 (range, 166.6-170.6).

After analyzing BP polygenic risk scores in relation to adverse cardiovascular outcomes, each degree of increase in the risk score was found to correlate with a 12% increased risk of cardiovascular events. Glycemic control therapy did not influence the BP polygenic risk scores, nor did it influence the primary outcome of cardiovascular risk prevention.

Study limitations included the pre-existing nature of the subset of participants available for analysis, as well as a lack of power to evaluate possible interactions due to the study’s post hoc design.

“These results invigorate the potential implications of [using] BP polygenic risk score in the primordial prevention of microvascular and macrovascular complications in T2D through early intensification of life-style measures such as healthy diet, exercise, smoking cessation, weight management, and BP control among those with high genetic risk,” the authors said.

This genetic risk assessment may especially benefit those with newly diagnosed T2D and those with prediabetes to encourage earlier adoption of a healthier lifestyle.

Reference

Parcha V, Pampana A, Bress AP, Irvin MR, Arora G, Arora P. Association of polygenic risk score with blood pressure and adverse cardiovascular outcomes in individuals with type II diabetes: insights from the ACCORD trial. Hypertension. Published online April 4, 2022. doi:10.1161/hypertensionaha.122.18976

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Diagnostic GI endoscopy linked to subsequent cardiovascular, respiratory events

Within 30 days of day-case diagnostic gastroscopies, 5.1% were followed by emergency hospital admissions and 3.8% were followed by a primary care consultation.

April 27, 2022

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Disclosures:
The authors report no relevant financial disclosures.


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Diagnostic gastrointestinal endoscopy was associated with an excess of unexpected events requiring primary care consultation or emergency hospitalization, according to research in Alimentary Pharmacology & Therapeutics.

“There is reported to be inappropriate overuse of gastroscopy worldwide which is worryingly increasing over time. While the majority of endoscopy is perceived as safe, more than 10% of procedures are performed in those over 80 years of age, who have increasing levels of frailty and complex comorbidity, which may predispose them to adverse events,” Colin J Crooks, PhD, clinical associate professor at the University of Nottingham, and colleagues wrote. “The data reported to date, therefore, do not allow us with any confidence to describe to our patients the overall risk of a routine day-case gastroscopy.”


Within 30 days of day-case diagnostic gastroscopies, 5.1% were followed by emergency hospital admissions and 3.8% were followed by a primary care consultation.



In a cohort study, Crooks and colleagues sought to determine the excess risk for acute medical events among 225,304 patients who underwent 277,535 diagnostic day-case gastroscopies in the United Kingdom. They further frequency-matched 1,383,535 30-day periods without gastroscopy within 991,249 patients by year, gender and decade of birth. Recorded outcomes included non-cancer deaths, emergency non-cancer admissions and cardiovascular or respiratory (CVR) primary care consultations.

According to study results, 5.1% of day-case diagnostic gastroscopies were followed by emergency hospital admissions within 30 days, of which 1.4% were unrelated to a GI or cancer diagnosis and 0.4% had a CVR diagnoses. Compared with controls, there was a 0.1% excess of CVR-related admissions, which reduced to 0.05% (95% CI, 0.04-0.06) among patients younger than 40 years and increased to 1.1% (95% CI, 0.6-1.6) among patients older than 90 years with high comorbidities.

Further, 3.8% of gastroscopies were followed by a primary care consultation for a CVR event within 30 days, with excess risk increasing from 0.13% in 40-year-old patients with no comorbidities to 0.31% in patients aged 90 years. The 30-day risk for emergency hospital admission increased 30-fold with age from 0.03% to 0.9% for those with no comorbidities to 0.1% to 2.7% in those with high comorbidities.

“We have shown that one in 245 day-case diagnostic gastroscopies were followed by an unexpected medically attended cardio, vascular or respiratory event resulting in either primary care consultation or emergency admission to hospital,” Crooks and colleagues concluded. “However, this risk varies in magnitude and consequence depending on age and morbidity of the patient undergoing the gastroscopy. It is important for clinicians to weigh up these risks against the expected benefits of a diagnostic gastroscopy when planning to do this test and in consenting their patients.”


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Prognostic factors for cardiovascular events in elderly pati | CIA

Angiotensinogen and Risk of Stroke Events in Patients with Type 2 Diab | DMSO

Background

The burden of community-acquired pneumonia (CAP) ranks the first among all infectious diseases, especially in the elderly people, with higher morbidity and mortality, more comorbidities and complications, higher need for admission to intensive care unit (ICU) and rate of clinical failure (CF), and more medical expenses.1–5 Cardiovascular diseases (ischemic heart disease, stroke) are the world’s biggest killers, responsible for 27% of the world’s total deaths in 2019, according to the World Health Organization (WHO).6 The incidence of CAP and cardiovascular diseases significantly increases with advanced age.5,7 Previous study indicated that older patients hospitalized with pneumonia had fourfold increased risk of subsequent occurrence of acute cardiovascular events (CVEs) in the first 30 days after pneumonia.8 A clinical rule that stratifies the risk of cardiac complications in patients hospitalized for CAP revealed that older patients are at major risk of CVEs after pneumonia.9 A global systematic review and meta‐analysis of observational studies demonstrated that the overall rates of cardiac complications after CAP were 13.9%, and the rate of heart failure was 9.2%, arrhythmias 7.2%, acute coronary syndromes 4.5%, and stroke 1.7%.10 Meanwhile, the occurrence of CVEs complicated the course of hospitalization with CAP. Compared to CAP patients without CVEs, CAP patients with CVEs had higher rate of mechanical ventilation, more need to ICU admission, prolonged length of stay (LOS), higher rate of short-term and long-term mortality, and higher 30-day re-hospitalization.10–12 Therefore, the mutual interaction between these two diseases should arouse more attention of respiratory physicians and cardiologists.

Current studies mainly focus on the overall population of patients with CAP, yet rare data are for the certain elderly population.13 Accordingly, we performed a multicenter, retrospective study to evaluate the burden of CVEs during hospitalization and to explore the independent prognostic factors for the occurrence of CVEs and 30-day mortality in elderly patients with CAP.

Methods

Study Setting, Design and Participants

This study is a multicenter, retrospective research on hospitalized elderly patients with CAP from the CAP-China network. Data of patients aged 65 years or older were abstracted from 13 centers in seven cities in three provinces between January 1, 2014 and December 31, 2014 (details are made available in the study by Han et al4). The study was approved by the Human Subject Protection Program Institutional Review Board at China-Japan Friendship Hospital. Additional approval was obtained from the local institutional review board of each participating hospital. Patient consent was waived owing to the retrospective and observational study design.

Inclusion/Exclusion Criteria and CAP Definition

Inclusion criteria included (1) age ≥ 65 years; (2) one of the top five discharge diagnoses defined as CAP. Exclusion criteria included (1) hospital-acquired pneumonia; (2) active tuberculosis; (3) non-infectious diseases, such as pulmonary infarction, tumor or pulmonary edema; (4) acquired immune deficiency syndrome; (5) re-admission within 72 hours after discharge.

CAP was defined as follows: (1) community onset; (2) presence of new infiltrate on chest X-ray or computed tomography scan together with at least one of the following: (i) new or increased cough (productive, non-productive or with a change in sputum characteristics) with or without dyspnea, chest pain or hemoptysis, (ii) fever, (iii) rales and/or signs of consolidation, (iv) peripheral WBC counts >10,000 cells·mm−3 or <4000 cells·mm−3, with or without a left shift toward immature forms.

Immunocompromised patients referred to these with solid-organ or stem cell transplant or bone marrow transplantation within one year of admission, chemotherapy for hematological disease or solid-tumor malignancy within six months of admission or neutropenia <500 cells·m−3, chest radiation therapy within one month of admission, prescription with immunosuppressive therapy within three months of admission or splenectomy.

Data Collection

Details on admission such as demographic data, a series of clinical information, hematological data, evaluation of initial antimicrobial treatment, are also available in the study by Han et al.4

Clinical failure (CF) is divided into early (≤72 hours) CF and late (>72 hours) CF. The detailed definitions are available in the study by Han et al.3

Definition of CVEs

The CVEs considered during the hospitalization were defined as follows:

  1. Events related with cardiac diseases: ① congestive heart failure (CHF) (new onset heart failure, or worsening preexisting heart failure with typical signs and/or symptoms associated with elevation of brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP);②new onset arrhythmia, or worsening preexisting arrhythmia (multifocal atrial tachycardia, atrial fibrillation or flutter; ventricular tachycardia, flutter or fibrillation; new onset of high degree atrio-ventricular block (2nd and 3rd));③ acute myocardial infarction (AMI) with typical signs or symptoms associated with troponin level above the normal value (according to the reference range values of local laboratory) and/or ischemic electrocardiographic changes (new ST-T changes or new left bundle branch block).
  2. Events related with cerebrovascular diseases (CVDs): new onset of hemorrhagic or ischemic stroke or transient ischemic attack defined as clinical manifestations and was confirmed by computed tomography or magnetic resonance imaging.
  3. Events related with thromboembolic diseases: pulmonary embolism (PE) or deep venous thrombosis (DVT) was confirmed by clinical manifestations and by pulmonary artery angiography computed tomography or eco-Doppler ultrasound, respectively.

All the patients diagnosed with CVEs (International Classification of Diseases, tenth revision [ICD-10] codes (in the Additional file 1: Table S1)) were based on clinical manifestations, laboratory tests and consultation with specialists.

Statistical Analysis

According to the occurrence of CVEs during hospitalization, the patients were divided into CVEs group and non-CVEs group. Categorical variables are presented as frequencies or percentages, and continuous variables are presented as median (interquartile range, IQR). The χ2 test is used for categorical variables and the Mann–Whitney U-test for continuous variables.

Variables showing significant difference in univariate analysis (p<0.10) are included in multivariate logistic regression analysis model for the occurrence of any CVEs and 30-day mortality in elderly patients with CAP, and a stepwise forward model is used to select independent risk factor. The 95% confidence intervals (CIs) and level of significance are reported.

All data are analyzed with SPSS (version 20, IBM Corp., New York, USA); p<0.05 is considered statistically significant.

Results

Study Population and Clinical Characteristics

Excluding immunosuppressed patients, 2941 patients aged ≥ 65 years were finally analyzed. 13.7% (n=402) of elderly patients with CAP occurred CVEs during hospitalization. Among them, 80.3% (n=323) were with acute CHF, 25.9% (n=104) with arrhythmia, 8.2% (n=33) with AMI, 6.2% (n=25) with CVDs, 4.0% (n=16) with thromboembolic diseases (six with PE and 10 with DVT). 73.1% (n=294) of patients had any one of CVEs, 22.6% (n=91) had two types of CVEs, 4.2% (n=17) had three types of CVEs.

Clinical characteristics of patients with or without CVEs are provided in Table 1. Patients with CVEs during hospitalization were older, higher risk of aspiration, long-term bedridden confinement and more comorbidities, especially cardiovascular disease and CVDs. Compared with non-CVEs patients, the pneumonia severity in patients with CVEs was more severe, history of CAP in past one year and use of glucocorticoids during hospitalization were more common.

Table 1 Comparison of Clinical Characteristics in Hospitalized Elderly CAP Patients with or without CVEs (n=2941)

Clinical Manifestations, Laboratory and Radiologic Findings

Compared with non-CVEs patients, the rates of wheezing, cyanosis and lower extremity edema were more common in patients with CVEs, as well as unstable vital signs. Leukocytosis, hyperglycemia, azotemia, hyponatremia, hypoxemia, acidosis, hypoproteinemia, multilobe infiltration and pleural effusion were more prone to occur in patients with CVEs. During hospitalization, the incidence of related acute organ failure, diffuse intravascular coagulation (DIC) and gastrointestinal bleeding was notably different between the two groups (Table 2).

Table 2 Comparison of Clinical Manifestations, Laboratory and Radiologic Findings in Hospitalized Elderly CAP Patients with or without CVEs (n=2941)

Outcomes

Compared with non-CVEs patients, patients with CVEs during hospitalization were more prone to be admitted to ICU, administrated more guideline-discordant antibiotic therapy, higher rate of CF, and lower rate of clinical stability before discharge. The median LOS in patients with CVEs was 12 days, significantly longer than that (11 days) in non-CVEs patients (p=0.019). The in-hospital mortality and 30-day mortality were also significantly higher in CVEs patients than those in non-CVEs patients (p<0.001), 27.1% versus 2.0%, 30.3% versus 3.4% respectively. Median total cost for one elderly CAP patient with CVEs was RMB 20,315.5, significantly higher than that (RMB 12,207.1) for non-CVEs patient (p<0.001). All the data are provided in Table 1.

The occurrence of CVEs significantly increased with age (p<0.001), and the incidence in patients aged ≥ 86 years was as high as 25.9%, nearly fourfold than that in patients aged 65–70 years (Figure 1). The rate of CF, in-hospital mortality and 30-day mortality significantly increased with the numbers of CVEs (p<0.001). The rate of in-hospital mortality and 30-day mortality in patients with three types of CVEs was 64.7% and 70.6%, respectively, threefold than that in patients with one type of CVEs and 20–30 folds than that in patients without CVEs (p<0.001) (Figure 2).

Figure 1 The occurrence of CVEs, CF, in-hospital mortality, and 30-day mortality in elderly patients of different age groups. 1) As for the occurrence of CVEs, there are statistical differences between the two groups (p<0.05), except for the group aged 65–70 years and 71–75 years, group aged 76–80 years and 81–85 years. 2) As for the rate of CF, there are statistical differences between the group aged ≥86 years and all other groups (p<0.05). 3) As for the rate of in-hospital, there are statistical differences between the group aged 65–70 years versus group aged 81–85 years and group aged ≥86 years (p<0.05); There are statistical differences between the group aged ≥86 years and all other groups (p<0.05). 4) As for the rate of 30-day mortality, there are statistical differences between the group aged ≥86 years and all other groups (p<0.05).

Abbreviations: CVE, cardiovascular event; CF, clinical failure.

Figure 2 The occurrence of CF, in-hospital mortality, and 30-day mortality in elderly patients with different numbers of cardiovascular events. As for the rate of CF, in-hospital and 30-day mortality, there are statistical differences between the two groups (p<0.05), except for group with two and three types of CVEs.

Abbreviation: CF, clinical failure.

Predictive Factors for the Occurrence of CVEs During Hospitalization

Table 3 shows that previous history of CHF (OR 6.16; 95% CI, 4.14–9.18, p<0.001), CF (OR 4.69; 95% CI, 3.392–6.48, p<0.001), previous history of ischemic heart disease (OR 2.22; 95% CI, 1.61–3.07, p<0.001), use of glucocorticoids during hospitalization (OR 2.0; 95% CI, 1.39–2.89, p<0.001), aspiration (OR 1.88; 95% CI, 1.26–2.81, p=0.002), pleural effusion (OR 1.66; 95% CI, 1.25–2.20, p<0.001), multilobe infiltration (OR 1.50; 95% CI, 1.15–1.96, p=0.003), age (OR 1.05; 95% CI, 1.04–1.07, p<0.001), and blood urea nitrogen (BUN) (OR 1.03; 95% CI, 1.01–1.06, p=0.007) were independent predictors for the occurrence of any CVE during hospitalization in the multivariable logistic regression model. While level of blood sodium (OR 0.98; 95% CI, 0.97–0.99, p=0.007) was a protective factor.

Table 3 Predictive Factors for the Occurrence of CVEs During Hospitalization in Univariate and Multivariable Logistic Regression Analysis

Predictive Factors for 30-Day Mortality in Elderly Patients with CAP

Table 4 shows that renal failure (OR 9.46; 95% CI, 4.17–21.48, p<0.001), respiratory failure (OR 9.32; 95% CI, 5.91–14.71, p<0.001), sepsis/sepsis shock (OR 7.87; 95% CI, 3.58–17.31, p<0.001), new CVDs (OR 5.94; 95% CI, 1.78–19.87, p=0.004), new heart failure (OR 4.04; 95% CI, 1.15–14.14, p=0.029), new arrhythmia (OR 2.38; 95% CI, 1.11–5.14, p=0.027), aspiration (OR 1.95; 95% CI, 1.09–3.50, p=0.025), CURB-65 (OR 1.57; 95% CI, 1.21–2.02, p=0.001), and white blood cell (WBC) count (OR 1.05; 95% CI, 1.02–1.09, p=0.006) were independent predictors for 30-day mortality in elderly patients with CAP in multivariable logistic regression model. While lymphocyte count (OR 0.63; 95% CI, 0.46–0.87, p=0.006) was a protective factor.

Table 4 Predictive Factors for 30-Day Mortality in Elderly CAP Patients in Univariate and Multivariable Logistic Regression Analysis

Discussion

This is the first retrospective multicenter study to evaluate the disease burden of CVEs and risk factors for incidence of CVEs in hospitalized elderly patients with CAP in China. Our study discovers that: 1) 13.7% of elderly patients with CAP experience CVEs during hospitalization with higher rate of CF and poorer prognosis. 2) Independent risk factors associated with CVEs are age, aspiration, previous history of CHF and ischemic heart disease, level of BUN, CF, use of systematic glucocorticoids during hospitalization, pleural effusion, and multilobe infiltration; while level of blood sodium is a protective factor. 3) Independent risk factors associated with 30-day mortality are renal failure, respiratory failure, sepsis/sepsis shock, new CVDs, new heart failure, new arrhythmia, aspiration, CURB-65, and WBC count; while lymphocyte count is a protective factor.

Nowadays, there were some researches on CVEs during the course of or after CAP. However, the incidence of CVEs differs as the different inclusion criteria of CVEs. In a multicenter prospective study enrolled 1266 patients with CAP, data indicated that 23.8% of patients experienced at least a CV event (excluded the thromboembolic diseases),12 higher than that in our study. We considered the gap is mainly related to the low proportion of patients in PSI class IV or V or CURB-65 class 3–5. The most common CVE during hospitalization is newly diagnosed acute heart failure (11.0%), followed by arrhythmia (3.5%) and AMI (1.1%), similar with the data from systematic review and meta-analysis of observational studies.10 As to the mechanisms about the occurrence of CVEs in patients with CAP, previous studies demonstrated acute or persistent inflammation after CAP became the fuse of potential triggers for cardiac events, leading to the increased pro-inflammatory cytokines or activation of pro-coagulant factors. Plaque-related CVEs (AMI) and plaque-unrelated CVEs (arrhythmias and heart failure) occurred after plaque rupture, in-situ thrombus formation, and alteration of the balance of arterial perfusion or diffuse organ abnormalities with cellular dysfunction.14–18 Additionally, the occurrence of type 2 myocardial infarction (T2MI) after acute infection is considered to be related to“demand ischemia” (a mismatch in myocardial oxygen supply and demand).19 In older adults, coronary stenosis from chronic plaques and possibly toxin-mediated vasoconstriction after acute infection may lead to increased cardiac metabolic mismatch.20 Data discovered T2MI gradually increased with advanced age, especially among patients aged over 75 years old.21 Thence, appropriate antimicrobial regimens, effective treatment against other underlying diseases, anticoagulation therapy, dynamic monitoring of laboratory indicators, and timely adjustment of therapeutic plans can play an important role in the control of inflammation.

The disease burden of elderly patients with CAP experienced CVEs is heavier. In a prospective multicenter cohort of 1182 CAP inpatients enrolled between 2011 and 2016, Francesco Violi et al reported patients who experienced a CVE were older, had a higher prevalence of underlying diseases and complications, higher disease severity, unstable vital signs and 30-day mortality,22 in line with our results. In our study, a significant increasing trend in the proportion of patients with CVEs, CF, and short-term mortality was found across the advanced age; meanwhile, the increased numbers of CVEs lead to poorer prognosis. Patients with CVEs had significantly lower proportion of guideline-concordant antibiotic therapy than that in patients without CVEs, thus, the proportion of CF significantly increased accordingly as well as prolonged LOS and higher short-term mortality.3 This result suggests that appropriated evaluation of pathogens plays an important role in the choice of optimal antimicrobial regimen.

We confirmed previous reports showing that history of heart failure, previously diagnosed coronary artery disease, pleural effusion, multilobe infiltration, age and BUN were independently associated with CVEs.12,16,23–26 In the first analysis of prospectively collected data from the Pneumonia Patient Outcomes Team cohort study in patients with CAP, sodium<130 mmol/L was considered as independent risk factor for incident cardiac complications.25 In our data, level of blood sodium (OR 0.98; 95% CI, 0.97–0.99, p=0.007) was protective factor for the occurrence of CVEs, suggesting the similar conclusion. Adjunctive use of corticosteroids for patients with CAP has been controversial, even for severe CAP.27–29 In a propensity-score adjusted Cox model by Cangemi et al, use of corticosteroid for patients with CAP was associated with a lower incidence of intra-hospital myocardial infarction (OR 0.46; 95% CI 0.24–0.88, p=0.02), albeit not reducing either overall mortality or cardiovascular death.30 Conversely, we found adjunctive use of corticosteroids during hospitalization was associated with a higher incidence of CVEs (OR 2.0; 95% CI, 1.39–2.89, p<0.001). In an observational study of 500 consecutive patients hospitalized with CAP who were enrolled in the Community-Acquired Pneumonia Organization (CAPO) cohort study, data addressed CF was significantly related to the occurrence of AMI (OR, 4.22; 95% CI, 1.10–16.29),31 generally consistent with our conclusion. 21.4% of elderly patients with CVEs in our population had higher risk of aspiration. Aspiration can bring about chemical pneumonia, bacterial pneumonia, or lipoid pneumonia, and thus lead to acute or chronic infection and inflammation. Acute infections not only destabilize vascular endothelium and result in an imbalance between myocardial oxygen supply and demand, but also have both systemic and local effects on coronary vessels, thence creating an increased risk of cardiovascular events.32,33 In our multivariable logistic regression analysis, aspiration was confirmed as an independent predictor for CVEs.

The results of the current study are concordant with previous evidence that aspiration, CURB-65, WBC count, sepsis/sepsis shock and respiratory failure were independent predictors for short-term mortality for elderly patients with CAP.4,34–37 We found the complication after CAP, renal failure was significantly associated with increased 30-day mortality (OR 9.46; 95% CI, 4.17–21.48, p<0.001). Yet, in the past literatures, BUN is more used to an evaluation indicator. A retrospective cohort study from China by Kang and coworkers assessing 4880 CAP patients aged ≥ 65 years showed that BUN was a prognostic factor for in-hospital mortality.35 Data from a multicenter prospective study on the Implications of acute Cardiovascular Events in patients hospitalized for Community-Acquired Pneumonia (ICECAP), enrolling patients consecutively hospitalized from 2016 to 2018, indicated the occurrence of any CVE during hospitalization independently and significantly increased the risk of 30-day mortality (HR 1.69; 95% CI, 1.14–2.51, p = 0.009); while newly diagnosed heart failure, new onset atrial fibrillation or flutter, acute coronary syndrome, separately, were not associated with increased risk of 30-day mortality.12 The current study is the first to our knowledge to illustrate new CVDs, new heart failure, and new arrhythmia were independently and significantly increased the risk of 30-day mortality for elderly patients with CAP.

There are some limitations in our study that should be acknowledged. The present study was a retrospective design; thus, missing data were inevitable There were no records about the timing of onset of CVEs, the detailed type of new arrhythmia and CVDs during hospitalization. Furthermore, medications like statins and anticoagulants during hospitalization were also not evaluated. Meanwhile, we did not evaluate the association between pathogens or antimicrobial treatment and the occurrence of CVEs. Finally, biomarkers such as D-dimer, BNP, NT-proBNP presented lots of missing values, thereby, the relationship between biomarkers and the occurrence of CVEs could not be explored.

Conclusions

CVEs during hospitalization are common in elderly patients with CAP in China. Patients with CVEs have heavier disease burden and poorer outcomes, especially those with new CVDs, new heart failure, and new arrhythmia, which are independently and significantly prognostic factors for short-term mortality. It is critical for clinicians to early identify risk factors and strengthen the hierarchical management of elderly patients with CAP.

Abbreviations

CVEs, cardiovascular events; CAP, community-acquired pneumonia; CHF, congestive heart failure; CVDs, cerebrovascular diseases; CF, clinical failure; OR, odds ratio; ICU, intensive care unit; WHO, World Health Organization; LOS, length of stay; BNP, brain natriuretic peptide; NT-proBNP, N-terminal pro-B-type natriuretic peptide; AMI, acute myocardial infarction; PE, pulmonary embolism; DVT, deep venous thrombosis; IQR, interquartile range; CIs, confidence intervals; DIC, diffuse intravascular coagulation; BUN, blood urea nitrogen; WBC, white blood cell; PSI, pneumonia severity index; T2MI, type 2 myocardial infarction; CAPO, Community-Acquired Pneumonia Organization; ICECAP, Implications of acute Cardiovascular Events in patients hospitalized for Community-Acquired Pneumonia; DIC, disseminated intravascular coagulation; COPD, chronic obstructive pulmonary disease; HCAP, healthcare-associated pneumonia; RR, respiratory rate; HR, heart rate; HCT, hematocrit; Cr, creatinine; Na, sodium; PaO2/FiO2, partial arterial oxygen pressure/fraction of inspired oxygen; PaO2, partial arterial oxygen pressure; SaO2, arterial oxygen saturation; CT, computed tomography.

Data Sharing Statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Ethics Approval and Informed Consent

This study was approved by the China-Japan Friendship Hospital Ethics Committee (No. 2015–85) on October 12, 2015. We also confirmed that all patient data was treated with confidentiality, in accordance with the Declaration of Helsinki.

Consent for Publication

All authors have confirmed that the details of the paper.

Acknowledgments

The authors are grateful for the contributions of all the staff of the CAP-China network for their help with data collection and input. Thanks to Yimin Wang, Guangqiang Wang, Xuexin Yao, Hongxia Yu, Guohua Yu, Meng Liu, Chunxue Xue, Bo Liu, Xiaoli Zhu, Yanli Li, Ying Xiao, Xiaojing Cui, Lijuan Li, and Lei Wang for collecting the information. Thanks to Yi Wang for revising the figures.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This work was supported by the National Science Grant for Distinguished Young Scholars (grant number 81425001/H0104), the National Key Technology Support Program from Ministry of Science and Technology (grant number 2015BAI12B11) and the Beijing Science and Technology Project (grant number D151100002115004).

Disclosure

The authors declare that they have no competing interests.

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23. Aliberti S, Ramirez J, Cosentini R, et al. Acute myocardial infarction versus other cardiovascular events in community-acquired pneumonia. ERJ Open Res. 2015;1(1):00020–2015. doi:10.1183/23120541.00020-2015

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Bariatric Surgery Cuts Cardiovascular Events, Even in Seniors

Bariatric Surgery Cuts Cardiovascular Events, Even in Seniors

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years, suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction) as compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation in Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select healthcare networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute in Bethesda, Maryland, and colleagues in an accompanying editorial.

Moreover, other long-term and observational studies have shown that bariatric surgery can decrease the risk of myocardial infarction, death, and stroke in young and middle-aged patients with obesity, but the evidence is less clear for older patients and those without diabetes, noted Mentias in a phone interview.

“To date, this is one of the first studies to support bariatric surgery for CVD risk reduction in patients older than 65 years, a population at highest risk for developing heart failure,” the editorial points out.

“We should consider referring patients who qualify for bariatric surgery based on BMI; it really should be considered as a treatment option for patients with class 3 obesity, especially with a body mass index (BMI) over 40 kg/m2,” Powell-Wiley told Medscape.

“We know that patients are generally under referred for bariatric surgery, and this highlights the need to refer patients for bariatric surgery,” she added.

“There should be discussion about expanding insurance coverage to include bariatric surgery for eligible patients,” Mentias added.

Contemporary Cohort of Patients

“A lot of the studies showed long-term outcomes outside of the US, specifically in Europe,” Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Females comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

  • Myocardial infarction (hazard ratio [HR], 0.63; 95% CI, 0.59 – 0.68)

  • Stroke (HR, 0.71; 95% CI, 0.65 – 0.79)

  • New-onset heart failure (HR, 0.46; 95% CI, 0.44 – 0.49)

  • Reduced risk of death (9.2 vs 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60 – 0.66)

Findings for those over the age of 65 were similar — lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr Milind Y. Desai’s research. Mentias has disclosed no relevant financial relationships. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

J Am Coll Cardiol. 2022;79:1429-1437, 1438-1440. Abstract, Editorial

Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University’s Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University, where she also took premedical classes. Her work has taken her to Honduras, Cambodia, France, and Ghana and has appeared in outlets like The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, TCTMD, Insider, and Tonic (Health by Vice), among other publications.

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Heart complications after a stroke increase the risk of future cardiovascular events

Heart complications after a stroke increase the risk of future cardiovascular events
stroke
A blood clot forming in the carotid artery. Credit: copyright American Heart Association

People who survive an ischemic stroke are much more likely to develop major heart complications during the first month after their stroke, and, as a result, they also have an increased risk of death, heart attack or another stroke within five years, compared to people who don’t develop heart problems soon after a stroke, according to new research published today in Stroke.

Ischemic is the most common type of stroke—accounting for 87% of all strokes—and occurs when blood flow to the brain is blocked. After a stroke, people often have cardiovascular complications, known as stroke-heart syndrome. Heart complications include acute coronary syndrome, angina (), heart rhythm issues such as atrial fibrillation, arrhythmia and ; ; heart failure or Takotsubo syndrome (broken heart syndrome), a type of stress-induced temporary enlargement of a part of the heart that impacts its ability to pump effectively. These conditions increase the risk of disability or death in the short term, yet the long-term consequences for people with stroke-heart syndrome is unknown.

“We know and stroke share similar risk factors, and there’s a two-way relationship between the risk of stroke and heart disease. For example, heart conditions such as atrial fibrillation increase the risk of stroke, and stroke also increases the risk of heart conditions,” said Benjamin J.R. Buckley, Ph.D., lead author of the study and a postdoctoral research fellow in preventive cardiology at the Liverpool Centre for Cardiovascular Science, University of Liverpool in the United Kingdom. “We wanted to know how common newly diagnosed are after a stroke and, importantly, whether stroke-heart syndrome is associated with increased risk of long-term major adverse events.”

Researchers analyzed the medical records of more than 365,000 adults treated for ischemic stroke at more than 50 health care sites predominantly in the United States, between 2002 and 2021. People who were diagnosed with stroke-heart complications within four weeks after a stroke were matched to an equal number of stroke survivors who did not have these heart complications within four weeks (the ).

After adjusting for potential confounding factors, such as age, sex and race/ethnicity, and comparing the stroke survivors who had new heart complications to those who did not, the analysis found:

  • Overall, among all stroke survivors in the study, about 1 in 10 (11.1%) developed acute coronary syndrome, 8.8% were diagnosed with atrial fibrillation, 6.4% developed heart failure, 1.2% exhibited severe ventricular arrythmias and 0.1% developed ‘broken heart’ syndrome within four weeks after the stroke.
  • Risk of death within five years after a stroke significantly increased among the participants with new heart complications: 49% more likely if they had developed ; 45% more likely if they had developed atrial fibrillation/flutter; and 83% more likely if they developed . Severe ventricular arrhythmias doubled the risk of death.
  • Chance of hospitalization and heart attack within five years after a stroke was also significantly higher among those who developed heart complications within the one-month window.
  • Stroke survivors with Takotsubo syndrome were 89% more likely to have a major heart event within the five years after their stroke.
  • People who developed after stroke were 10% more likely to have a second stroke within five years after their stroke.
  • People with stroke and newly diagnosed were 50% more likely to have a recurrent stroke within five years after the first stroke.

“I was particularly surprised by how common stroke-heart syndrome was and the high rate of recurrent stroke in all subgroups of adults with stroke-heart syndrome” Buckley said. “This means that this is a high-risk population where we should focus more secondary prevention efforts.”

The study’s results build on the understanding of the two-way link between the brain and the heart and extend this understanding to long-term health outcomes. “We are working on additional research to determine how stroke-heart syndrome may be better predicted,” Buckley said.

“We also need to develop and implement treatments to improve outcomes for people with stroke-heart syndrome,” Buckley said. “For example, comprehensive exercise-based rehabilitation may be helpful after a stroke, so for people with stroke and newly developed heart complications, it should also be beneficial, maybe even more so. I think this is an interesting area for future research.”

Study limitations include that it is a retrospective analysis and knowing whether the complications diagnosed following an were caused by stroke or rather contributed to the stroke, is unclear.

“This research underscores why it’s so important for neurologists and cardiologists to work hand-in-hand with their patients and each other to understand why the first stroke occurred and perform a comprehensive assessment to identify new risk factors for another stroke and for cardiovascular disease that may require initiation of prevention therapies,” said Lee H. Schwamm, M.D., volunteer chair of the American Stroke Association Advisory Committee and the C. Miller Fisher Chair in Vascular Neurology at Massachusetts General Hospital in Boston. “The American Stroke Association recommends a personalized secondary stroke prevention plan for every stroke survivor.”

Even with statins, high triglycerides may increase risk of second stroke

More information:
Stroke (2022). www.ahajournals.org/doi/STROKEAHA.121.037316

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American Heart Association


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People with elevated blood pressure upon standing more likely to have risk for cardiovascular events

People with elevated blood pressure upon standing more likely to have risk for cardiovascular events

Among young and middle-aged adults with high blood pressure, a substantial rise in blood pressure upon standing may identify those with a higher risk of serious cardiovascular events, such as heart attack and stroke, according to new research published today in the American Heart Association’s peer-reviewed journal Hypertension.

This finding may warrant starting blood-pressure-lowering treatment including medicines earlier in patients with exaggerated blood pressure response to standing.”


Paolo Palatini, M.D., lead author of the study and professor of internal medicine at the University of Padova in Padova, Italy

Nearly half of Americans and about 40% of people worldwide have high blood pressure, considered to be the world’s leading preventable cause of death. According to the American Heart Association’s 2022 heart disease statistics, people with hypertension in mid-life are five times more likely to have impaired cognitive function and twice as likely to experience reduced executive function, dementia and Alzheimer’s disease.

Typically, systolic (top number) blood pressure falls slightly upon standing up. In this study, researchers assessed whether the opposite response – a significant rise in systolic blood pressure upon standing – is a risk factor for heart attack and other serious cardiovascular events.

The investigators evaluated 1,207 people who were part of the HARVEST study, a prospective study that began in Italy in 1990 and included adults ages 18-45 years old with untreated stage 1 hypertension. Stage 1 hypertension was defined as systolic blood pressure of 140-159 mm Hg and/or diastolic BP 90-100 mm Hg. None had taken blood pressure-lowering medication prior to the study, and all were initially estimated at low risk for major cardiovascular events based on their lifestyle and medical history (no diabetes, renal impairment or other cardiovascular diseases). At enrollment, participants were an average age of 33 years, 72% were men, and all were white.

At enrollment, six blood pressure measurements for each participant were taken in various physical positions, including when lying down and after standing up. The 120 participants with the highest rise (top 10%) in blood pressure upon standing averaged an 11.4 mm Hg increase; all increases in this group were greater than 6.5 mm Hg. The remaining participants averaged a 3.8 mm Hg fall in systolic blood pressure upon standing.

The researchers compared heart disease risk factors, laboratory measures and the occurrence of major cardiovascular events (heart attack, heart-related chest pain, stroke, aneurysm of the aortic artery, clogged peripheral arteries) and chronic kidney disease among participants in the two groups. In some analyses, the development of atrial fibrillation, an arrhythmia that is a major risk factor for stroke, was also noted. Results were adjusted for age, gender, parental history of heart disease, and several lifestyle factors and measurements taken during study enrollment.

During an average 17-year follow-up 105 major cardiovascular events occurred. The most common were heart attack, heart-related chest pain and stroke.

People in the group with top 10% rise in blood pressure:

  • were almost twice as likely as other participants to experience a major cardiovascular event;

  • did not generally have a higher risk profile for cardiovascular events during their initial evaluation (outside of the exaggerated blood pressure response to standing);

  • were more likely to be smokers (32.1% vs. 19.9% in the non-rising group), yet physical activity levels were comparable, and they were not more likely to be overweight or obese, and no more likely to have a family history of cardiovascular events;

  • had more favorable cholesterol levels (lower total cholesterol and higher high-density-lipoprotein cholesterol);

  • had lower systolic blood pressure when lying down than the other group (140.5 mm Hg vs. 146.0 mm Hg, respectively), yet blood pressure measures were higher when taken over 24 hours.

After adjusting for average blood pressure taken over 24 hours, an exaggerated blood pressure response to standing remained an independent predictor of adverse heart events or stroke.

“The results of the study confirmed our initial hypothesis – a pronounced increase in blood pressure from lying to standing could be prognostically important in young people with high blood pressure. We were rather surprised that even a relatively small increase in standing blood pressure (6-7 mm Hg) was predictive of major cardiac events in the long run,” said Palatini.

In a subset of 630 participants who had stress hormones measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in the people with a rise in standing blood pressure compared to those whose standing blood pressure did not rise (118.4 nmol/mol vs. 77.0 nmol/mol, respectively).

“Epinephrine levels are an estimate of the global effect of stressful stimuli over the 24 hours. This suggests that those with the highest blood pressure when standing may have an increased sympathetic response [the fight-or-flight response] to stressors,” said Palatini. “Overall, this causes an increase in average blood pressure.”

“The findings suggest that blood pressure upon standing should be measured in order to tailor treatment for patients with high blood pressure, and potentially, a more aggressive approach to lifestyle changes and blood-pressure-lowering therapy may be considered for people with an elevated [hyperreactor] blood pressure response to standing,” he said.

Results from this study may not be generalizable to people from other ethnic or racial groups since all study participants reported white race/ethnicity. In addition, there were not enough women in the sample to analyze whether the association between rising standing blood pressure and adverse heart events was different among men and women. Because of the relatively small number of major adverse cardiac events in this sample of young people, the results need to be confirmed in larger studies.

Source:

American Heart Association

Journal reference:

Palatini, P., et al. (2022) Blood Pressure Hyperreactivity to Standing: a Predictor of Adverse Outcome in Young Hypertensive Patients. Hypertension. doi.org/10.1161/HYPERTENSIONAHA121.18579.

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New cancer diagnosis associated with risk for fatal, nonfatal cardiovascular events

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March 15, 2022

3 min read

Disclosures:
Paterson reports no relevant financial disclosures. Please see the study for all other authors’ relevant disclosures. Ohtsu and colleagues report no relevant financial disclosures.


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New cancer diagnosis appeared associated with increased risk for cardiovascular death, as well as incident heart failure, stroke or pulmonary embolism, according to a retrospective cohort study published in JACC: CardioOncology.

“This risk persisted to at least 7 years from cancer diagnosis and appeared most pronounced in patients with hematologic, gastrointestinal, genitourinary and thoracic malignancies,” D. Ian Paterson, MD, FRCPC, professor of medicine in the division of cardiology, director of the Edmonton Cardio-Oncology Program and director of academic and research cardiac MRI at University of Alberta, told Healio.

HRs among patients with vs. without new cancer diagnosis
Data derived from Paterson DI, et al. JACC CardioOncol. 2022;doi:10.1016/j.jaccao.2022.01.100.

Background and methodology

Paterson and colleagues pursued the research because, despite the knowledge that patients with cancer and cancer survivors are at increased risk for heart failure, previous data conflicted regarding long-term risk for other cardiovascular events, as well as risk according to cancer site.

“Population studies to date have largely evaluated the risk [for] cardiovascular disease — and usually only heart failure — in patients with breast cancer,” Paterson said. “We performed a comprehensive analysis of the risk [for] incident cardiovascular disease in patients with a new cancer diagnosis of any type.”

D. Ian Paterson, MD, FRCPC

D. Ian Paterson

The analysis included 4,519,243 adults who resided in Alberta, Canada, from April 2007 to December 2018. Among them, 224,016 (median age, 56 years; range, 43-67; 56.8% women) had a new cancer diagnosis and 4,295,227 (median age, 34 years; range, 23-49; 48.5% women) comprised the control population.

Paterson and colleagues used time-to-event survival models, after adjusting for comorbidities and sociodemographic factors, to compare the two cohorts with respect to risk for subsequent cardiovascular events, which included cardiovascular mortality, myocardial infarction, stroke, heart failure and pulmonary embolism.

Determining the impact of new cancer diagnosis on risk for fatal and nonfatal cardiovascular events served as the primary outcome.

Key findings

At median follow-up of 11.8 years, results showed 73,360 cardiovascular deaths and 470,481 nonfatal cardiovascular events. After adjustment, researchers reported participants with cancer demonstrated the following HRs compared with participants without cancer:

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, 3.37-3.5) for pulmonary embolism.

Additionally, patients with genitourinary, gastrointestinal, thoracic, neurologic and hematologic malignancies demonstrated the highest cardiovascular risk.

“We were surprised that the risk [for] incident cardiovascular disease remained elevated in patients with cancer, even after fully adjusted risk modeling,” Paterson told Healio. “This suggests that the cancer itself, cancer therapies and/or other less traditional risk factors, such as physical activity and body composition, may have also contributed to cardiovascular risk.”

Implications

Paterson and colleagues wrote that future studies should investigate other potential contributors to cardiovascular risk, including cancer therapies and emerging risk factors for cardiotoxicity.

“We would like to identify effective intervention strategies to mitigate cardiovascular risk in patients with cancer, especially in the higher-risk cancer types (eg, hematologic),” Paterson said.

Paterson noted that as life expectancy of patients with cancer increases, so does their likelihood of developing other illnesses after diagnosis, necessitating a more collaborative approach to their health care. The authors of a corresponding editorial concurred.

“Perhaps the lesson we need to learn from [this study] is that it is time for cardiology and oncology to collaborate in order to travel upstream and build a powerhouse to generate information from the new flow of data efficiently,” Hiroshi Ohtsu, MS, manager of clinical epidemiology and director of JCRAC data center at National Center for Global Health and Medicine, Center for Clinical Sciences in Japan, and colleagues wrote.

“Cardiology and oncology need to collaborate to launch and successfully execute projects to establish new techniques to use real-world data for real-world evidence,” they added.

Reference s :

For more information:

D. Ian Paterson, MD, FRCPC, can be reached at Division of Cardiology, University of Alberta, 8440 112 St., 2C2.43 WCM, Edmonton, Alberta T6G2B7, Canada; email: ip3@ualberta.ca.


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Cardio-Oncology Resource Center

Cardio-Oncology Resource Center