Concurrent Cardiovascular Diseases Research Articles

Predicting adverse outcomes in adults with a community-acquired lower respiratory tract infection: a protocol for the development and validation of two prediction models for (i) all-cause hospitalisation and mortality and (ii) cardiovascular outcomes

BackgroundCommunity-acquired lower respiratory tract infections (LRTI) are common in primary care and patients at particular risk of adverse outcomes, e.g., hospitalisation and mortality, are challenging to identify. LRTIs are also linked to an increased incidence of cardiovascular diseases (CVD) following the initial infection, whereas concurrent CVD might negatively impact overall prognosis in LRTI patients. Accurate risk prediction of adverse outcomes in LRTI patients, while considering the interplay with CVD, can aid general practitioners (GP) in the clinical decision-making process, and may allow for early detection of deterioration. This paper therefore presents the design of the development and external validation of two models for predicting individual risk of all-cause hospitalisation or mortality (model 1) and short-term incidence of CVD (model 2) in adults presenting to primary care with LRTI.MethodsBoth models will be developed using linked routine electronic health records (EHR) data from Dutch primary and secondary care, and the mortality registry. Adults aged ≥ 40 years with a GP-diagnosis of LRTI between 2016 and 2019 are eligible for inclusion. Relevant patient demographics, medical history, medication use, presenting signs and symptoms, and vital and laboratory measurements will be considered as candidate predictors. Outcomes of interest include 30-day all-cause hospitalisation or mortality (model 1) and 90-day CVD (model 2). Multivariable elastic net regression techniques will be used for model development. During the modelling process, the incremental predictive value of CVD for hospitalisation or all-cause mortality (model 1) will also be assessed. The models will be validated through internal-external cross-validation and external validation in an equivalent cohort of primary care LRTI patients.DiscussionImplementation of currently available prediction models for primary care LRTI patients is hampered by limited assessment of model performance. While considering the role of CVD in LRTI prognosis, we aim to develop and externally validate two models that predict clinically relevant outcomes to aid GPs in clinical decision-making. Challenges that we anticipate include the possibility of low event rates and common problems related to the use of EHR data, such as candidate predictor measurement and missingness, how best to retrieve information from free text fields, and potential misclassification of outcome events.

Retrospective Analysis of Clinical Outcomes of Utilizing R-CHOP Plus Zanubrutinib for High-Risk Diffuse Large B Cell Lymphoma Patients with Extranodal Involvement or MYC/BCL2 Double Expression

Background: Diffuse large B-cell lymphoma (DLBCL) patients with extranodal involvement and double expression of MYC and BCL2 often have a poorer prognosis when treated with the standard first-line R-CHOP regimen. The 5-year progression-free survival (PFS) and overall survival (OS) rates are both below 40% for these high-risk DLBCL cases. In this study, we perform a retrospective analysis of the clinical outcomes and adverse events of the high-risk DLBCL patients with extranodal involvement and double expression, who were admitted to our center and used Bruton's tyrosine kinase inhibitor (BTKi) zanubrutinib on the basis of R-CHOP regimen. Methods: We conducted a retrospective analysis of 26 DLBCL patients with extranodal involvement or MYC/BCL2 double expression who were admitted to our center and used R-CHOP regimen in combination with zanubrutinib between 1 st January 2021 and 30 th April 2023 (Figure A). Of these patients, 19 had extranodal involvement, and 7 were identified as double expression cases. The patients had a median age of 70 years, ranging from 34 to 87. Among them, 20 cases (77%) were aged over 60, and 8 cases (30%) were aged over 75. Moreover, 20 cases (76.9%) exhibited an Eastern Cooperative Oncology Group (ECOG) performance status score higher than 2 points. All the patients received an induction regimen consisting of zanubrutinib in combination with R-CHOP for a total of 4 cycles. After the fourth cycle, treatment efficacy was assessed using 18FDG-PET/CT scans. Patients achieving partial response (PR) or better continued with rituximab in combination with zanubrutinib for consolidation maintenance therapy, lasting for 1 year. For patients at risk of central nervous system involvement, oral administration of zanubrutinib continued for 2 years. During the treatment period, imaging evaluations were performed every 3 months to assess treatment response (Figure B). Results: After the induction therapy, a mid-term PET/CT evaluation showed that all patients achieved PR or above, resulting in an overall response rate (ORR) of 100%. Among them, 19 patients (73.1%) achieved complete response (CR), while 7 patients (26.9%) achieved PR. During the consolidation and maintenance therapy, 7 patients who were initially in PR converted to CR. As of the latest follow-up, with a median follow-up duration of 11 months (ranging from 4.1 to 30.0 months), 2 patients (7.7%) were lost to follow-up, and 2 patients (7.7%) experienced disease progression. The median PFS and OS were not reached. The 2-year PFS was 69.7±13.4% (Figure C), and the 2-year OS was 77.4±12.2% (Figure D). Non-hematological adverse events included fatigue (38.5%), hypertension (15.38%), neurological symptoms (7.7%), and infections (100%). Among the infections, 3 cases (11.5%) were of >3-grade and led to treatment discontinuation. Additionally, one patient experienced immune encephalitis and went into a coma. Hematological adverse events included granulocytopenia (55%), anemia (26%), thrombocytopenia (42.3%), and bleeding (38.5%). Among them, >3-grade granulocytopenia occurred in 4.5% of the patients. Five patients who were on long-term anticoagulant therapy due to concurrent cardiovascular diseases experienced a reduction in zanubrutinib dosage during the follow-up period, resulting in an improvement in bleeding symptoms. Conclusions: The combination of 4 cycles of R-CHOP regimen with zanubrutinib in the induction treatment of DLBCL patients with high-risk factors, such as extranodal involvement or MYC/BCL2 double expression, has shown promising clinical outcomes especially in older or unfit/frail patients. This approach allows for a reduction in the number of cytotoxic drug cycles, thereby improving the patients' tolerance to the treatment. Moreover, the efficacy of this regimen is superior to the traditional 6-8 cycles of R-CHOP induction therapy. Furthermore, the consolidation and maintenance therapy with rituximab in combination with zanubrutinib has demonstrated good safety and manageable adverse effects. This approach exhibits hope for further enhancing the prognosis of high-risk DLBCL patients.

Anthra­cycline-Induced Cardiotoxicity: the Role of Genetic Predictors

Aim To evaluate the predictive significance of gene polymorphism in endothelin-1 type 2A receptor, NADPH oxidase, p53 protein, endothelial nitric oxide synthase, caspase 8, interleukin-1β, tumor necrosis factor-α, superoxide dismutase-2, glutathione peroxidase-1, β1-adrenoceptor, angiotensin-converting enzyme, and matrix metalloproteinase-3 (MMP-3) genes in evaluating the risk of anthracycline-induced cardiotoxicity (AIC) in women without concurrent cardiovascular diseases (CVD).Material and methods This study included 176 women aged 45.0 [42.0; 50.0] years with breast cancer without concurrent CVD who were scheduled for polychemotherapy (PCT) with anthracycline antibiotics. Echocardiography was performed for all patients at baseline and at 12 months after the end of PCT course. Genetic polymorphism was determined with the polymerase chain reaction.Results At 12 months, all patients were in remission of the underlying disease. They were retrospectively included into 2 groups: 1st group, 52 patients with AIC and 2nd group, 124 women without AIC symptoms. The development of AIC was associated with the presence of the p53 protein gene Arg / Arg genotype (odds ratio (OR), 2.972; p=0.001), NOS3 gene T / T genotype (OR, 3.059; p=0.018), NADPH oxidase gene T / T genotype (OR, 2.753; p=0.008), GPX1 gene C / C genotype (OR, 2.345; p=0.007), MMP-3 gene 5A / 5A genotype (OR, 2.753; p=0.008), and ADRB1 gene G / G genotype (OR, 3.271; p=0.043).Conclusion Evaluation of genetic polymorphism in p53 protein (rs1042522), NOS3 (rs1799983), NADPH-oxidase (rs4673), GPX1 (rs1050450), ADRB1 (Arg389Gly, rs1801253), and MMP-3 (rs3025058) genes can be recommended for use prior to starting chemotherapy in women with breast cancer without CVD for assessing the risk of AIC. A maximum risk of cardiotoxicity is associated with the presence of the p53 protein gene Arg / Arg genotype and NOS3 gene T / T genotype.

S1327 Nonalcoholic Steatohepatitis and Atrial Fibrillation: Baseline Characteristics and Outcomes: A Propensity-Matched Analysis From National Inpatient Sample Database

Introduction: Non-alcoholic steatohepatitis (NASH) affects at least 3 to 5% of Americans, which imposes a higher risk of concurrent cardiovascular diseases including arrhythmias, of which atrial fibrillation (Afib) is the most prevalent. Nonetheless, data on the burden of concurrent Afib in NASH patients is still lacking. Our aim is to define baseline characteristics of NASH patients with and without Afib and related in-hospital outcomes such as mortality, length of stay (LOS), and total hospital costs. Methods: Using the National Inpatient Sample database, we analyzed all NASH-related adult hospitalizations with or without Afib from September 2015 to December 2020. We applied propensity score matching to the 2 groups to balance baseline characteristics. SAS 9.4 software was used for statistical analysis. Results: Out of 435,845 NASH hospitalizations, 62,335 (14.3 %) had concurrent Afib. The NASH with Afib cohort consisted of older patients (mean age, 69.4 vs. 60.6 years) compared to those without Afib (p< 0.001). NASH with the Afib cohort had more females (54.5%) and Caucasians (82.5%). NASH patients with Afib had an almost 3-times higher prevalence of congestive heart failure (52.5% vs. 17.1%)(p< 0.001) and almost 2-times higher prevalence of coronary artery disease (40.2% vs. 20.2%), Peripheral vascular disease (7.5% vs 4.1%), and Renal failure (42.6% vs 24.7%) (p< 0.001). Moreover, NASH patients with Afib had higher prevalence of hypertension (65.7% 61.9%), Diabetes mellitus (64% vs 60.9%), COPD (28.5% vs 21.2%), and obesity (39.3% vs 36.3%). Compared to the NASH without Afib cohort, the NASH with Afib cohort had higher mortality (6.5% vs. 4.1%) with a mortality-adjusted odds ratio of 1.63 (95% CI: 1.55-1.71) (p< 0.001). In addition, the mean LOS (6.8 vs. 5.9), and mean hospital cost ($ 18701 vs. $16,220) were also higher (p< 0.001). (Figure) (Table) Conclusion: Our results indicate a higher burden imposed by the presence of Afib in NASH patients. The NASH with Afib cohort had significantly higher in-hospital mortality, mean length of stay, and hospitalization cost. This conclusion supports the need for further studies to better illustrate the pathogenesis, early diagnosis, possible preventive measures, and treatment modalities tailored towards NASH-associated Afib.Figure 1.: A) Racial disparity in NASH with Afib and NASH without Afib. B) Propensity mathced outcomes. C) Comorbidity in Nash with Afib and NASH without Afib Table 1. - Baseline characteristics, comorbidities and Outcomes of NASH patients with Afib versus NASH patients without Afib Variables NASH with AfibN=62,335(14.3%) NASH without AfibN=373,510(85.7%) P- Value Age, in years (Mean ± SD) 69.4 ± 10.2 60.6 ± 13.2 < 0.001 Age groups, % < 0.001 18 - 34 years 0.4% 4.6% 35 – 49 years 3.3% 14.1% 50 – 64 years 24.5% 38.6% 65 - 79 56.0% 37.5% >79 years 15.8% 5.1% Gender, % < 0.001 Male 45.5% 36.8% Female 54.5% 63.2% Race, % < 0.001 Caucasians 82.0% 73.5% African Americans 3.5% 4.3% Others 14.5% 22.2% Comorbidities, % Hypertension 65.7% 61.9% < 0.001 Diabetes mellitus 64% 60.9% < 0.001 Congestive heart failure 52.2% 17.1% < 0.001 CAD 40.2% 20.2% < 0.001 Peripheral vascular disease 7.5% 4.1% < 0.001 COPD 28.5% 21.2% < 0.001 Renal failure 42.6% 24.7% < 0.001 Coagulopathy 32% 32.5% 0.01 Obesity 39.3% 36.3% < 0.001 Drug abuse 1.5% 2.5% < 0.001 Alcohol abuse 2.3% 3.9% < 0.001 Smoking 30.5% 32.1% < 0.001 Admission Type, % < 0.001 Emergent 90.3% 86.8% Elective 9.7% 13.2% Insurance type, % < 0.001 Medicare 75.2% 53.6% Medicaid 5.4% 13% Private 16.4% 27.8% Other 3% 5.5% Location/Teaching status of the hospital, % < 0.001 Rural 7.7% 7.6% Urban nonteaching 19.5% 18.1% Urban teaching 72.8% 74.3% Propensity-Matched Outcomes NASH with AfibN=62175 NASH without AfibN= 62190 p-value In-hospital mortality, % 6.5% 4.1% < 0.001 Mortality adjusted odds ratio 1.63 (1.55 – 1.71) < 0.001 Length of stay, in days (mean ± SD) 6.8 ± 7.5 5.9 ± 6.3 < 0.001 Total hospitalization cost, in US $ (mean ± SD) 18701 ± 28527 16220 ± 26589 < 0.001 Disposition, % < 0.001 Discharge to home 40.3% 45.3% Transfer other: includes Skilled Nursing Facility, Intermediate Care Facility, or another type of facility 26.5% 23.6% Home health care 23% 23.7% Against medical advice 0.4% 0.4% *Abbreviations (NASH - Non-alcoholic steatohepatitis, Afib - Atrial Fibrillation, SD - Standard deviation, CAD - Coronary artery disease, COPD - Chronic obstructive pulmonary disease).

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p&lt;0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus.

Background: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival. Objectives: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer. Materials and methods: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II–IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52–129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan–Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy. Results: The Kaplan–Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005). Conclusions: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.

Relationship between Low Vegetable Consumption, Increased High-Sensitive C-Reactive Protein Level, and Cardiometabolic Risk in Korean Adults with Tae-Eumin: A Cross-Sectional Study.

An anti-inflammatory diet has many beneficial effects on cardiometabolic diseases. Constitution type of traditional Korean medicine can predict cardiometabolic risk factors. We examined the relationship between vegetable consumption and the high-sensitive C-reactive protein (hs-CRP) level on cardiometabolic risk factors in Korean adults by constitution types. Data from 1,983 eligible participants (mean age, 44.3 years) were included in the present cross-sectional study. The inflammatory status of the participants was categorized into low- (<3.0 mg/L) or high-risk (≥3.0 mg/L) groups based on their constitution types. Cardiometabolic risk factors (abdominal obesity, elevated triglycerides, reduced high-density lipoprotein-cholesterol, elevated blood pressure, elevated fasting plasma glucose, and ≥2 concurrent cardiovascular diseases (CVDs) risk factors) and dietary assessment of the participants were assessed. A total of 11.1% of Tae-eumin (TE) and 4.9% of non-TE groups had a higher hs-CRP level (TE: 6.6 ± 0.2, non-TE: 8.4 ± 0.3) than a low hs-CRP level TE and non-TE (TE: 0.9 ± 0.1, non-TE: 0.6 ± 0.1). Vegetable consumption of <91.5 g/day was highly associated with a high-risk hs-CRP level (adjusted odds ratio (ORs): second tertile (T2): 2.290, (95% confidence interval (CI): 1.285–4.082); first tertile (T1): 2.474 (95% CI: 1.368–4.475), P=0.003) compared with that of the highest (T3) in TE. Low (T1 and T2) vegetable consumption was associated with a 54–63% increased prevalence of more than two concurrent CVDs risk factors compared with that of the highest in the TE group (P=0.012). Higher vegetable consumption greatly decreased the prevalence of CVDs risk factors by 63–86% in the low-risk and high-risk hs-CRP TE groups. Our results highlight the cardioprotective effects of higher consumption of vegetables in Korean adults with TE. Evidence-based clinical risk factor management and multifaceted approaches at the community and population levels targeting prevention in high-burden groups are recommended to reduce the premature mortality attributed to CVD.

Significance of NETs Formation in COVID-19.

Severe contagious respiratory disease—COVID-19—caused by the SARS-CoV-2 coronavirus, can lead to fatal respiratory failure associated with an excessive inflammatory response. Infiltration and spread of SARS-CoV-2 are based on the interaction between the virus’ structural protein S and the cell’s receptor–angiotensin-converting enzyme 2 (ACE2), with the simultaneous involvement of human trans-membrane protease, serine 2 (TMPRSS2). Many scientific reports stress the importance of elevated recruitment and activity of neutrophils, which can form extracellular neutrophil traps (NETs) playing a significant role in the mechanism of combating pathogens, in the pathogenesis of COVID-19. Excessive generation of NETs during prolonged periods of inflammation predisposes for the occurrence of undesirable reactions including thromboembolic complications and damage to surrounding tissues and organs. Within the present manuscript, we draw attention to the impact of NET generation on the severe course of COVID-19 in patients with concurrent cardiovascular and metabolic diseases. Additionally, we indicate the necessity to explore not only the cellular but also the molecular bases of COVID-19 pathogenesis, which may aid the development of dedicated therapies meant to improve chances for the successful treatment of patients. We also present new directions of research into medications that display NETs formation regulatory properties as potential significant therapeutic strategies in the progress of COVID-19.

Cardiovascular Manifestations of SARS CoV-2: A Review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is a public health emergency of global concern. Besides the profound severe pulmonary damage, SARS-CoV-2 infection also causes a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Number of mechanisms have been postulated for SARS CoV-2-associated cardiovascular damage including direct myocardial injury, systemic inflammation, hypoxemia, coronary thrombosis and drug-induced cardiac damage. Special attention should be given towards patients of SARS CoV-2 with concurrent cardiovascular diseases. Knowledge of the injury caused by SARS CoV-2 to the cardiovascular system and the mechanisms behind it is of the utmost importance to reduce the morbidity and mortality of these patients by treating them in time.

Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study.

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146‒17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755‒8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132‒14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166‒14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case–control study, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1. The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

Differential changes in the pharmacokinetics of statins in collagen-induced arthritis rats

The elevated systemic levels of cytokines in rheumatoid arthritis (RA) can change the expression of metabolic enzymes and transporters. Given that statins are lipid-lowering agents frequently used in RA patients with concurrent cardiovascular diseases, the objective of the present study was to investigate the impacts of RA on the pharmacokinetics of statins of different disposition properties in rats with collagen-induced arthritis (CIA). The expression of metabolic enzymes and transporters in tissues of CIA rats were analyzed by RT-qPCR. Statins were given to CIA rats and controls through different routes, respectively. Blood samples were collected and analyzed by UPLC/MS/MS. Isolated microsomes and hepatocytes were used to determine the metabolic and uptake clearance of statins. The results showed that, compared with controls, the mRNA levels of intestinal Cyp3a1 and hepatic Cyp2c6, Cyp2c7, Cyp3a1, Oatp1a1, Oatp1b2, Oatp1a4, and Mrp2 were markedly decreased in the CIA rats. The maximal metabolic activities of Cyp2c and Cyp3a were reduced in liver microsomes of CIA rats. When given orally or injected through hepatic portal vein, the systemic levels of fluvastatin, simvastatin, and atorvastatin, but not of rosuvastatin and pravastatin, were increased in CIA rats. The metabolic clearance of simvastatin and hepatic uptake clearance of fluvastatin and atorvastatin were decreased in CIA rats. These findings suggest that the changes in the expression of enzymes and/or transporters in CIA rats differentially affect the pharmacokinetics of statins.

Opportunity for cardiovascular risk factor reduction in AAA surveillance programs: a systematic review and meta-analysis of cardiovascular mortality in patients with small AAA

Opportunity for cardiovascular risk factor reduction in AAA surveillance programs: a systematic review and meta-analysis of cardiovascular mortality in patients with small AAA

The amputation and mortality rates of diabetic patients with critical limb ischemia: A nationwide population-based follow-up study in Taiwan

Summary Purpose To describe the epidemiological profiles and the amputation and mortality rates of diabetic patients in Taiwan with critical limb ischemia. Materials and methods Data were collected from the Longitudinal Health Insurance Database 2000 (LHID2000), a database composed of one million randomly selected beneficiaries in Taiwan. To measure major amputation and mortality, diabetic patients with critical limb ischemia (CLI) were identified by specific ICD-9-CM diagnostic, procedure, and order codes. The patients were traced until the end of 2009. Cox proportional hazard regressions were used to determine the crude and adjusted hazard ratios for the risk factors for amputation and mortality during the follow-up period. Results We identified 6418 diabetic patients with CLI from the LHID database during 1997–2006. Of these patients, 256 (3.99%) patients underwent surgical revascularization and 6418 (96.01%) patients received conservative treatment only. The revascularization cohort had more comorbidities than the surgical group (e.g., cardiovascular, 13.28% vs. 8.62%, respectively, p = 0.0099; renal, 23.05% vs. 5.34%, respectively, p 50 years), male gender, and comorbid cardiovascular, renal, neurological, and pulmonary diseases. Conclusion Diabetic patients who needed surgical revascularization or who needed conservative treatment for CLI had different comorbid profiles. The common risk factors for amputation and mortality in diabetic CLI patients include male gender, age of >50 years, and concurrent cardiovascular and renal diseases.

Analysis of arrhythmia for the patients of chest tumor after operation JIN Wen-bo,ZHANG Xiang-hua,

Objective To discuss the causes of postoperative arrhythmia patients with thoracic tumor and to explore the preventive and therapeutic measures.Methods A retrospective data of 551 patients with thoracic tumor was analyzed.Results There were 86 cases suffering postoperative arrhythmia,among which the incidence was 10.4% below 60 years old and 20.6% above.The incidence of those with preoperative cardiovascular diseases was 56.4%,of those with mediastinum tumor was 16.6%.The incidence of those with lung cancer was 12.5%,individually 20.5% for those receiving total pneumonectomy,10.6% for pulmonary lobectomy,and 8.5% for wedge-shape escision of lung.Of those with esophageal tumor the incidence was 23.5%,individually 22.0% for those receiving ccrvical anastomosis,and 15.3% for intrathoracic anastomosis Besides,the incidence of those with cardiac cancer was 20.1%.Conclusions Postoperative arrhythmia on patients with thoracic tumor is intimately correlated with the age,concurrent preoperative cardiovascular diseases,surgical methods and imraoperative conditions.It's feasible to prevent and reduce the incidence of postoperative arrhythmia by sufficient preoperative preparation,intensive postoperative custody and corrective anoxia. Key words: Thoracic neoplasms; Thoracic surgical procedures; Arrhythmia

Selective Cyclooxygenase-2 Inhibitors Development in Cardiovascular Medicine

At the end of September 2004, Merck & Co announced the voluntary withdrawal of rofecoxib (Vioxx) worldwide because of an increased risk of cardiovascular events. Since its approval in 1999, Vioxx, a selective cyclooxygenase-2 (COX-2) inhibitor, has been Merck & Co’s leading drug for control of acute pain and chronic pain associated with osteoarthritis, rheumatoid arthritis, and menstruation. Last year, worldwide sales of rofecoxib reached US $2.5 billion, and it is estimated that the drug was prescribed ≈10 million times per month in the United States.1 Thus, given the number of patients involved and the serious nature of the side effects, the withdrawal raised serious concerns about the safety of other selective COX-2 inhibitors, collectively called coxibs, that are on the market and those currently under development. Celecoxib (Celebrex) and rofecoxib were the first 2 coxibs approved by the US Food and Drug Administration (FDA) and launched in 1999 by Pfizer and Merck & Co, respectively. Since then, a second generation of these drugs has emerged onto the market. Valdecoxib (Bextra) was approved by the FDA and launched in 2002. In that same year, the European regulatory authority approved 2 other coxibs: etoricoxib (Arcoxia) and parecoxib sodium (Dynastat), the prodrug of valdecoxib. Today, etoricoxib and a fifth coxib, lumiracoxib (Prexige), are under consideration for FDA approval. In view of the rapid development in this area, the main concern is whether the reported cardiovascular effects of rofecoxib are a class effect applicable to all coxibs that were initially designed to reduce the gastric toxicity of nonselective COX inhibitors. Although most of the data accumulated so far would suggest a class effect related to the general mode of action of all coxibs and the physiological role of COX-2, recent in vitro data would theoretically support the hypothesis that the cardiovascular side …

Is Prosthesis–Patient Mismatch a Clinically Relevant Entity?

In this issue of Circulation , Koch and associates1 from the Cleveland Clinic published a study on the relationship between prosthetic valve size and the Duke Activity Status Index (DASI) after aortic valve replacement (AVR). The study was conducted with 1014 patients operated on from 1995 through 1998, completed 1 year later, and published now. DASI scores increased from a mean of 29 preoperatively to 46 postoperatively after a mean follow-up of 8.3 months. The investigators could find no obvious relationship between prosthetic valve size and postoperative DASI score. One of the limitations of the study was that prosthetic valve gradients and effective orifice areas were not measured by echocardiography to quantify prosthesis–patient mismatch. It is also interesting to note that more than two thirds of the patients were in New York Heart Association functional classes I and II preoperatively, and yet the DASI mean score before surgery was only 29 out of a maximum of 58.2. For this reason alone, it must be assumed that factors other than the aortic valve disease played a role in the DASI score. Nevertheless, this is not the first study to suggest that valve size plays no role in the clinical outcomes of AVR. See p 3221 Valve prosthesis–patient mismatch (PPM) is a term introduced by Rahimtoola in 1978 to describe a condition in which the in vivo prosthetic valve effective orifice area is smaller than that of the native valve.2 According to this broad definition, every patient with a prosthetic heart valve has PPM because the leaflets of both mechanical and bioprosthetic valves are mounted into frames that occupy …