Temporal trends in outcome and patient characteristics in dilated cardiomyopathy, data from the Swedish Heart Failure Registry 2003-2015.

BACKGROUND: Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003-2015. METHODS: DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003-2007 (Period 1, n = 2029), 2008-2011 (Period 2, n = 3363), 2012-2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. RESULTS: Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). CONCLUSIONS: From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.

Revealed by degrees: Patients' experience of receiving information after in-hospital cardiac arrest.

AIMS AND OBJECTIVES: To describe patients' experience of receiving information about the event after having a cardiac arrest in hospital. BACKGROUND: In Sweden, approximately 2,600 people per year experience cardiac arrest in hospital. After a cardiac arrest, the patient is entitled to receive information about what has occurred. This information must be provided in a way that does not do the patient more harm than good. In order to provide information to patients in a satisfactory manner for them, knowledge about how patients react to information in this situation is valuable. DESIGN: We used a qualitative approach with interviews and content analysis. METHODS: Twenty patients participated in face-to-face interviews analysed by content analysis. Consolidated criteria for reporting qualitative studies were used. RESULTS: The analysis resulted in three categories: Getting the information gradually, Understanding information received and Seeking clarity. The subcategories that emerged were as follows: Indirect information, Short and direct information, Explanatory information, Lack of information, Unsatisfactory information, Hard-to-understand information, Insight, Unanswered questions, Hard-to-formulate questions, Requesting information and Searching independently for knowledge. CONCLUSIONS: The patients needed gradual and repeated information during their hospitalisation, and repeated information was continually required after their discharge from hospital. Whether or how the information was given varied. The patients' experience was that they sometimes lacked opportunities for conversation and asking questions, while they also found it hard to formulate questions. Patients who have a cardiac arrest in hospital appear to have similar information needs to patients whose cardiac arrest takes place outside the hospital context. RELEVANCE TO CLINICAL PRACTICE: Information on the patient's cardiac arrest should be given in gradual stages, according to the patient's needs. The information needs to be repeated during the hospital stay and after discharge. Healthcare professional should gain insight into patients' responses and create information that is adapted to the individual.

Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study.

BACKGROUND AND AIMS: Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia. METHODS: In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases. RESULTS: Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls. CONCLUSION: Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

Treatment response in recent-onset heart failure with reduced ejection fraction: non-ischaemic vs. ischaemic aetiology.

AIMS: In heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), the prognosis appears better in non-ischaemic than in ischaemic aetiology. Infrequent diagnostic work-up for ischaemic heart disease (IHD) in HF is reported. In this study, we compared short-term response to initiated guideline-directed medical treatment (GDMT) in recent-onset HFrEF of non-ischaemic (non-IHF) vs. ischaemic (IHF) aetiology and evaluated the frequency of coronary investigation. METHODS AND RESULTS: Patients hospitalized with recent-onset HFrEF [left ventricular ejection fraction (LVEF) < 40%] between 1 January 2016 and 31 December 2019 were included. Treatment response was determined by use of a hierarchical clinical composite outcome classifying each patient as worsened, improved, or unchanged based on hard outcomes (mortality, heart transplantation, and HF hospitalization) and soft outcomes (± ≥10 unit change in LVEF, ± ≥30% change in N-terminal pro-B-type natriuretic peptide, and ± ≥1 point change in New York Heart Association functional class) during 28 weeks of follow-up. The associations between baseline characteristics and composite changes were analysed with multiple logistic regression. Among the 364 patients analysed, 47 were not investigated for IHD. Comparing non-IHF (n = 203) vs. IHF (n = 114), patients were younger (mean age 61.0 vs. 69.4 years, P < 0.001) with lower mean LVEF (26% vs. 31%, P < 0.001), but with similar male predominance (70.4% vs. 75.4%, P = 0.363). For non-IHF vs. IHF, the composite outcomes were worsened (19.1% vs. 43.9%, P < 0.001) and improved (74.2% vs. 43.9%, P < 0.001). After multivariable adjustments, IHF was associated with increased odds for worsening [odds ratio (OR) 2.94; 95% confidence interval (CI) 1.51-5.74; P = 0.002] and decreased odds for improvement (OR 0.35; 95% CI 0.18-0.65; P < 0.001). In cases without previous IHD or new-onset myocardial infarction (n = 261), a decision for coronary investigation was made in 69.0%. CONCLUSIONS: In recent-onset HFrEF, patients with non-IHF responded better to GDMT than patients with IHF. Almost one-third of patients selected for follow-up at HF clinics were never investigated for IHD.

Pulmonary embolism and deep venous thrombosis after COVID-19: long-term risk in a population-based cohort study.

Background: Venous thromboembolism (VTE) (pulmonary embolism (PE) or deep venous thrombosis (DVT)) is common during acute COVID-19. Long-term excess risk has not yet been established. Objective: To study long-term VTE risk after COVID-19. Methods: Swedish citizens aged 18-84 years, hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5) non-exposed population-derived subjects without COVID-19. Outcomes were incident VTE, PE or DVT recorded within 60, 60-<180, and ≥180 days. Cox regression was used for evaluation and a model adjusted for age, sex, comorbidities and socioeconomic markers developed to control for confounders. Results: Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age 60.6 years) and 894,121 were without hospitalization (mean age 41.4 years). Among patients hospitalized for COVID-19, fully adjusted hazard ratios (HRs) during 60-<180 days were 6.05 (95% confidence interval (CI) 4.80─7.62) for PE and 3.97 (CI 2.96─5.33) for DVT, compared to non-exposed with corresponding estimates among COVID-19 without hospitalization 1.17 (CI 1.01─1.35) and 0.99 (CI 0.86─1.15), based on 475 and 2,311 VTE events, respectively. Long-term (≥180 days) HRs in patients hospitalized for COVID-19 were 2.01 (CI 1.51─2.68) for PE and 1.46 (CI 1.05─2.01) for DVT while non-hospitalized had similar risk to non-exposed, based on 467 and 2,030 VTE events, respectively. Conclusions: Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to the non-exposed.

Prognostic differences in long-standing vs. recent-onset dilated cardiomyopathy.

AIMS: This study aimed to evaluate the outcome and prognostic factors in patients with dilated cardiomyopathy (DCM) and long-standing heart failure (LDCM) vs. recent-onset heart failure (RODCM). METHODS AND RESULTS: We compared 2019 patients with RODCM (duration <6 months, mean age 58.6 years, 70.7% male) with 1714 patients with LDCM (duration ≥6 months, median duration 3.5 years, mean age 62.5 years, 73.7% male) included in the Swedish Heart Failure Registry in the years 2003-16. Outcome measures were all-cause, cardiovascular (CV), and non-CV death and hospitalizations; heart transplantation; and a combined outcome of all-cause death, heart transplantation, or heart failure (HF) hospitalization. Multivariable risk factor analyses were performed for the combined endpoint. All outcomes were more frequent in LDCM than in RODCM. The multivariable-adjusted hazard ratios (HRs) (95% confidence interval) for LDCM vs. RODCM were 1.56 (1.34-1.82), P < 0.0001, for all-cause death over a median follow-up of 4.2 and 5.0 years, respectively; 1.67 (1.36-2.05), P < 0.0001, for CV death; 2.12 (1.14-3.91), P < 0.0001, for heart transplantation; 1.36 (1.21-1.53), P < 0.0001, for HF hospitalization; and 1.37 (1.24-1.52), P < 0.0001, for the combined outcome. A propensity score-matched analysis yielded similar results. CV death was the main cause of mortality in LDCM and was higher in LDCM than in RODCM (P < 0.0001). Almost all co-morbidities were significantly more frequent in LDCM than in RODCM, and the mean number of co-morbidities increased significantly with increased duration of disease, also after age adjustment. Age, New York Heart Association functional class, ejection fraction, and left bundle branch block were prognostically adverse. The only co-morbidity associated with the combined outcome regardless of HF duration was diabetes, in LDCM [HR 1.34 (1.15-1.56), P = 0.0002] and in RODCM [HR 1.29 (1.04-1.59), P = 0.018]. Male sex [HR 1.38 (1.18-1.63), P < 0.0001] and aspirin use [HR 1.33 (1.14-1.55), P = 0.0004] carried increased risk only in RODCM. Heart rate ≥75 b.p.m. [HR 1.20 (1.04-1.37), P = 0.01], atrial fibrillation [HR 1.24 (1.08-1.42), P = 0.0024], musculoskeletal or connective tissue disorder [HR 1.36 (1.13-1.63), P = 0.0014], and diuretic therapy [HR 1.40 (1.17-1.67), P = 0.0002] were prognostically adverse only in LDCM. CONCLUSIONS: This nationwide study of patients with DCM demonstrates that longer disease duration is associated with worse prognosis. Co-morbidities are more common in long-standing HF than in recent-onset HF and are associated with worse outcome. With the increased survival seen in the last decades, our results highlight the importance of careful attention to co-morbid conditions in patients with DCM.

BMI, sex and outcomes in hospitalised patients in western Sweden during the COVID-19 pandemic.

High body mass index (BMI) is associated with severe COVID-19 but findings regarding the need of intensive care (IC) and mortality are mixed. Using electronic health records, we identified all patients in western Sweden hospitalised with COVID-19 to evaluate 30-day mortality or assignment to IC. Adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for outcomes. Of totally 9761 patients, BMI was available in 7325 (75%), included in the study. There was a marked inverse association between BMI and age (underweight and normal weight patients were on average 78 and 75 years, whereas overweight and obese were 68 and 62 years). While older age, male sex and several comorbidities associated with higher mortality after multivariable adjustment, BMI did not. However, BMI ≥ 30 kg/m2 (OR 1.46, 95% CI 1.21-1.75) was associated with need of IC; this association was restricted to women (BMI ≥ 30; OR 1.96 (95% CI 1.41-2.73), and not significant in men; OR 1.22 (95% CI 0.97-1.54). In this comprehensive hospital population with COVID-19, BMI was not associated with 30-day mortality risk. Among the obese, women, but not men, had a higher risk of assignment to IC.

A negative T-wave in electrocardiogram at 50 years predicted lifetime mortality in a random population-based cohort.

BACKGROUND: Severe electrocardiographic (ECG) abnormalities in asymptomatic subjects correlate with cardiovascular risk. HYPOTHESIS: The role of minor ECG abnormalities is less well-known. We evaluated the association between a negative T-wave and mortality, as a possible marker for prognosis. METHODS: A prospective, population-based cohort, examined at 50 years, and followed until death. Time to death (event rates) and predictive role of a negative T-wave (Cox regression) were analyzed. RESULTS: Participants (n = 839) with a negative T-wave (7.3%) had significantly higher blood pressure (BP) (mean systolic 157.9 mmHg vs 136.8 mmHg without negative T-wave, P = <.0001). A negative T-wave correlated with elevated risk (hazard ratio [HR] [95% CI] [confidence interval]) for all-cause and cardiovascular (CV) death (1.59 (1.20-2.11) P = .0012 vs 1.91 (1.34-2.73) P = .0004). The association remained after excluding coexisting Q/QS patterns and ST-junction/segment depression ECG abnormalities (1.66 [1.13-2.44] P = .0098 for all-cause vs 1.87 [1.13-3.09] P = .015 for CV death). Death from other causes was not associated with a negative T-wave. A major negative T-wave carried higher risk than a minor (2.17 [1.25-3.76] P = .0062 vs 1.78 [1.13-2.79] P = .012) for CV death. CONCLUSION: A negative T-wave at 50 years, in asymptomatic individuals, carried an increased risk of all-cause and CV death during lifetime follow-up.

Prognostic impact over time of ischaemic heart disease vs. non-ischaemic heart disease in heart failure.

AIMS: The aim of this study is to investigate the prognostic impact of ischaemic heart disease (IHD) in heart failure (HF) and its association to age, sex, left ventricular ejection fraction (EF), and HF duration, and furthermore, to evaluate if the impact of IHD has changed over time, in light of improved therapy. METHODS AND RESULTS: We studied 30 946 patients with non-valvular HF, by accessing the Swedish Heart Failure Registry, from years 2000 to 2012. The mortality in 17 778 patients with clinical IHD was compared with 13 168 patients without IHD (non-IHD). There was a significantly worse outcome in IHD, with the crude mortality of 41.1% and the event rate per 100 person-years [95% confidence interval (CI)] of 14.8 (14.4-15.1), compared with 28.2% and 9.7 (9.4-10.0) in non-IHD. After multivariable adjustment, the hazard ratio (HR) (95% CI) for mortality, IHD vs. non-IHD, was 1.16 (1.11-1.22; P < 0.0001). Subgroup analyses showed significantly increased mortality in IHD, in all age subgroups, in all subgroups with EF < 50%, in both men and women, and regardless of heart failure duration more or less than 6 months. Analyses for the combination of age and EF showed the highest HR for time to death in the youngest with the lowest EF, HR (95% CI) 2.05 (1.59-2.64) for patients <60 years of age with EF < 30%. Although a numerical reduction of the HR for mortality was seen over time, the risk for mortality in IHD, compared with the non-IHD group, was greater throughout the study period. CONCLUSIONS: In non-valvular heart failure, IHD was associated with significantly increased mortality, compared with non-IHD, in groups of EF below 50%, in all age groups, and regardless of sex or HF duration. The risk increase associated with EF reduction diminished with increasing age. The mortality in IHD, compared with non-IHD, remained significantly higher throughout the 13 year study period.

Protein disulfide isomerase increases in myocardial endothelial cells in mice exposed to chronic hypoxia: a stimulatory role in angiogenesis.

Previous studies have shown that exposure to chronic hypoxia protects against myocardial infarction, but little is known about the cellular and molecular mechanisms involved. Here we observed that chronic hypoxia for 3 wk resulted in improved survival of mice (from 64% to 83%), reduced infarction size (from 45 +/- 4% to 32 +/- 4%, P < 0.05), increased cardiac ejection fraction (from 19 +/- 4% to 35 +/- 5%, P < 0.05), coronary flow velocity under adenosine-induced hyperemia (from 58 +/- 2 to 75 +/- 5 cm/s, P < 0.05), myocardial capillary density (from 3,772 +/- 162 to 4,760 +/- 197 capillaries/mm(2), P < 0.01), and arteriolar density (from 8.04 +/- 0.76 to 10.34 +/- 0.69 arterioles/mm(2), P < 0.05) 3 wk after myocardial infarction. With two-dimensional gel electrophoresis, we identified that protein disulfide isomerase (PDI) was highly upregulated in hypoxic myocardial capillary endothelial cells. The loss of PDI function in endothelial cells by small interfering RNA significantly increased the number of apoptotic cells (by 3.4-fold at hypoxia, P < 0.01) and reduced migration (by 52% at hypoxia, P < 0.001) and adhesion to collagen I (by 42% at hypoxia, P < 0.01). In addition, the specific inhibition of PDI by PDI small interfering RNA (by 46%, P < 0.01) and bacitracin (by 72%, P < 0.001) reduced the formation of tubular structures by endothelial cells. Our data indicate that chronic hypoxic exposure improves coronary blood flow and protects the myocardium against infarction. These beneficial effects may be partly explained by the increased endothelial expression of PDI, which protects cells against apoptosis and increases cellular migration, adhesion, and tubular formation. The increased PDI expression in endothelial cells may be a novel mechanism to protect the myocardium against myocardial ischemic diseases.

Symptoms of chest pain and dyspnea and factors associated with chest pain and dyspnea 10 years after coronary artery bypass grafting.

BACKGROUND: The purpose of the study is to describe (a) changes in physical activity and symptoms of chest pain and dyspnea during 10 years after coronary artery bypass grafting (CABG) and (b) risk indicators for chest pain and dyspnea 10 years after CABG. METHODS: This is a prospective observational study in Western Sweden. The study includes all patients who underwent CABG without simultaneous valve surgery and with no previous CABG between June 1, 1988, and June 1, 1991. All patients were prospectively followed up for 10 years. Evaluation of symptoms took place via postal inquiries before, 5, and 10 years after the operation. RESULTS: In all, 2,000 patients participated in a survey evaluating chest pain and dyspnea during 10 years after CABG. The overall 10-year mortality was 32%. The proportion of patients with no chest pain increased from 3% before surgery to 56% 5 years after the operation and 54% after 10 years. There was only one predictor for chest pain after 10 years and that was the duration of angina pectoris before surgery. The proportion of patients with no dyspnea increased from 12% before surgery to 40% after 5 years but decreased to 31% after 10 years. The most significant predictors for dyspnea after 10 years were female sex, obesity, diabetes mellitus, high age, duration of angina pectoris, functional class before CABG, and number of days in intensive care unit after CABG. CONCLUSION: During 10 years after CABG, one third died. After 10 years, 54% of the survivors were free from chest pain and 31% were free from dyspnea. Predictors for chest pain and dyspnea could be defined and reflected age, history, sex, obesity, preoperative complications, and symptom severity.

Lack of very strong association between pre-treatment fibrinogen and PAI-1 with long-term mortality after coronary bypass surgery.

AIM: To explore the association between the coagulation protein fibrinogen and the fibrinolytic biomarker plasminogen activator inhibitor-1 (PAI-1) and the long-term mortality after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: In 729 patients undergoing CABG at Sahlgrenska University Hospital, a blood sample for fibrinogen and PAI-1 was collected prior to the procedure. Patients were followed for 10 years. RESULTS: Among patients with high levels of fibrinogen (>3.6 g/l; median), the 10-year mortality was 32.3 vs. 20.7% among patients with fibrinogen levels below the median (p = 0.0005). However, patients with higher levels of fibrinogen were older and had an adverse risk factor pattern. When adjusting for these differences, pre-operative fibrinogen levels did not clearly appear as an independent predictor of long-term mortality. The 10-year mortality was similar in patients with high (25.3%) and low (26.5%) levels of PAI-1. CONCLUSION: Our results do not suggest that fibrinogen and PAI-1, when evaluated prior to the operative procedure, are strongly associated with increased mortality in the long-term after CABG, when other co-morbidity factors are simultaneously considered.

Determinants for an impaired quality of life 10 years after coronary artery bypass surgery.

OBJECTIVE: To identify determinants of an inferior quality of life (QoL) 10 years after coronary artery bypass grafting (CABG). SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: All patients from Western Sweden who underwent CABG between 1988 and 1991 without simultaneous valve surgery and no previous CABG. MAIN OUTCOME MEASURES: Questionnaires for evaluating QoL 10 years after the operation. Three different instruments were used: The Nottingham health profile (NHP), the psychological general wellbeing index (PGWI), and the Physical Activity Score (PAS). RESULTS: 2000 patients underwent CABG, of whom 633 died during 10 years of follow-up. Information on QoL at 10 years was available in 976 patients (71% of survivors). A history of diabetes and chronic obstructive pulmonary disease were the two independent predictors for an inferior QoL with all three instruments. Furthermore, there were three predictors of an inferior QoL with two of the instruments: high age, female sex and a history of hypertension. A number of factors predicted an inferior QoL with one of the instruments. These were the duration of angina pectoris and functional class prior to CABG, renal dysfunction, a history of cerebrovascular disease, obesity, height, duration of respirator treatment and requirement of inotropic drugs postoperatively. In addition, when introducing preoperative QoL into the model a low QoL before surgery was a strong independent predictor also of an inferior QoL 10 years after CABG. CONCLUSION: Variables independently predictive of an impaired QoL 10 years after CABG, irrespective of the instrument used, were an impaired QoL prior to surgery, chronic obstructive pulmonary disease and a history of diabetes. However, other factors reflecting gender, the previous history as well as postoperative complications were also associated with the QoL 10 years later in at least one of these instruments.

Trends in Gender Differences in Cardiac Care and Outcome After Acute Myocardial Infarction in Western Sweden: A Report From the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).

BACKGROUND: Cardiovascular disease is the most common cause of death for both genders. Debates are ongoing as to whether gender-specific differences in clinical course, diagnosis, and management of acute myocardial infarction (MI) exist. METHODS AND RESULTS: We compared all men and women who were treated for acute MI at cardiac care units in Västra Götaland, Sweden, between January 1995 and October 2014 by obtaining data from the prospective SWEDEHEART (Swedish Web-System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. We performed unadjusted and adjusted Cox proportional hazards and logistic regression analyses on complete case data and on imputed data sets. Overall, 48 118 patients (35.4% women) were diagnosed with acute MI. Women as a group had better age-adjusted prognosis than men, but this survival benefit was absent for younger women (aged <60 years) and for women with ST-segment elevation MI. Compared with men, younger women and women with ST-segment elevation MI were more likely to develop prehospital cardiogenic shock (adjusted odds ratio 1.67, 95% CI 1.30 to 2.16, P<0.001 and adjusted odds ratio 1.31, 95% CI 1.16 to 1.48, P<0.001) and were less likely to be prescribed evidence-based treatment at discharge (P<0.001 for ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and P2Y12 antagonists). Differences in treatment between the genders did not decrease over the study period (P>0.1 for all treatments). CONCLUSIONS: Women on average have better adjusted prognosis than men after acute MI; however, younger women and women with ST-segment elevation MI have disproportionately poor prognosis and are less likely to be prescribed evidence-based treatment.

Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo.

The present study investigates the regulation of small ubiquitin-related modifier-1 (SUMO-1) expression in response to hypoxia in adult mouse brain and heart. We observed a significant increase in SUMO-1 mRNAs and proteins after hypoxic stimulation in vivo. Because SUMO-1 interacts with various transcription factors, including hypoxia-inducible factor-1beta (HIF-1beta) in vitro, we not only demonstrated that the HIF-1alpha expression is increased by hypoxia in brain and heart, but also provided evidence that SUMO-1 co-localizes in vivo with HIF-1alpha in response to hypoxia by demonstrating the co-expression of these two proteins in neurons and cardiomyocytes. The specific interaction between SUMO-1 and HIF-1alpha was additionally demonstrated with co-immunoprecipitation. These results indicate that the increased levels of SUMO-1 participate in the modulation of HIF-1alpha function through sumoylation in brain and heart.

Predictors of death during 10 years after coronary artery bypass grafting with particular emphasis on age.

OBJECTIVES: To describe predictors of death during 10 years of follow-up after coronary artery bypass grafting (CABG); to evaluate whether age interacts with the influence of various predictors on outcome; and to compare the mortality during 10 years after CABG with the mortality in an age- and sex-matched control population. DESIGN: Prospective, observational study. SETTING: Department of Thoracic and Cardiovascular Surgery at Sahlgrenska University Hospital and Scandinavian Heart Centre in Göteborg, Sweden. PARTICIPANTS: All patients from western Sweden who underwent CABG between 1 June 1988 and 1 June 1991 without simultaneous valve surgery and with no previous CABG. MAIN OUTCOME MEASUREMENTS: All-cause mortality during 10 years but more than 30 days after CABG. RESULTS: In all, 2000 patients participated in the survey. The following factors appeared as independent predictors of death: preoperative factors-age, history of congestive heart failure, cerebrovascular disease, history of intermittent claudication, current smoking, degree of left ventricular impairment, valvular disease and duration of angina pectoris; peroperative factors-ventilator time and neurological complications; postoperative factors-arrhythmia, requirement of digitalis and requirement of antidiabetics. There was an interaction between age and history of cerebrovascular disease with a stronger impact on outcome in younger patients. The late (>30 days after CABG) 10-year mortality in the study cohort was 29.6% compared with 25.9% in the control population (P=0.02). CONCLUSION: Among patients who underwent CABG, 13 independent predictors for mortality were found, mainly among preoperative factors but also among peroperative factors, postoperative complications and medication requirement after CABG.

Improvement and factors associated with improvement in quality of life during 10 years after coronary artery bypass grafting.

AIM: To describe (1) the improvement in various aspects of quality of life (QoL) and (2) predictors of improvement, during 10 years after coronary artery bypass grafting (CABG). PATIENTS AND METHODS: All patients who underwent CABG in western Sweden between June 1988 and June 1991 without simultaneous valve surgery and with no previous CABG were approached with an inquiry prior to and 5 and 10 years after the operation. QoL was measured with three different instruments: (1) Nottingham health profile (NHP), (2) psychological general well-being index (PGWBI) and (3) physical activity score (PAS). RESULTS: There was a significant improvement in QoL with all three instruments from before to 10 years after the operation. The mean improvements +/-SD were for NHP, - 4.2+/-17.0 (P<0.0001), for PGWBI, +9.7+/-17.6 (P<0.0001) and for PAS, -0.96+/-1.23 (P<0.0001). However, there was also a deterioration with all three instruments between 5 and 10 years after surgery. The mean deteriorations +/-SD were for NHP, +4.4+/-12.8 (P<0.0001), for PGWBI, -4.6+/-14.8 (P<0.0001) and for PAS, +0.44+/-0.94 (P<0.0001). Independent predictors for an improvement in QoL with at least one of the instruments were low preoperative QoL, a younger age, being a man, high functional class (New York Heart Association), no hypertension, proximal left anterior descending coronary artery stenosis, short extracorporeal circulation time, use of internal mammary artery and a short postoperative time in the intensive care unit. CONCLUSION: There is a higher estimated QoL 10 years after CABG than before, despite the fact that the patients are 10 years older. However, there is also a deterioration in QoL between 5 and 10 years after surgery. Predictors of improvement during the 10 years included age, sex, previous history, localization of stenosis, type of graft and preoperative and postoperative factors.

Impact of a History of Hypertension on Symptoms and Quality of Life Prior to and at Five Years after Coronary Artery Bypass Grafting.

AIM: To describe symptoms and other aspects of health-related quality of life (QoL) prior to and 5 years after coronary artery bypass grafting (CABG) in relation to a history of hypertension. METHODS: Patients who underwent CABG in western Sweden were approached prior to surgery and 5 years after the operation . Health-related QoL was estimated with the Physical Activity Score, the Nottingham Health Profile and the Psychological General Well-Being Index. RESULTS: In patients with a history of hypertension (n = 740) the 5-year mortality was 16.9% versus 12.4% among patients with no history (n = 1257; p = 0.004). Of 1717 patients available for the survey, 876 (51%) responded both prior to and 5 years after CABG. Of these, 36% had a hi story of hypertension. Compared with the situation prior to surgery there was an improvement in both hypertensive and non-hypertensive patients in terms of physical activity, symptoms of dyspnea and chest pain and other estimates of health-related QoL. However, physical activity and dyspnea improved less in hypertensive than in non-hypertensive patients. CONCLUSION: Five years after CABG, a marked and significant improvement in terms of symptoms and other aspects of health-related QoL was observed among both hypertensive and non-hypertensive patients. However, improvement in physical activity was less marked in patients with a history of hypertension. Overall, a hi story of hypertension seemed to have a minor impact on improved well-being 5 years after coronary surgery. However, because of the limited response rate the results may not be applicable in a non-selected CABG population.

Sleep habits and their association with mortality during 5-year follow-up after coronary artery bypass surgery.

OBJECTIVE: To study various aspects of sleep quality and sleep patterns prior to and after coronary artery bypass surgery and their implications for 5-year survival. METHODS: All patients from western Sweden who underwent coronary artery bypass grafting (CABG) between 1988 and 1991 (n = 2,121) received a questionnaire addressing sleep habits prior to and I year after surgery. Various symptoms and habits related to sleep at the two evaluations were compared. Symptoms and habits related to sleep prior to CABG were then related to 5-year survival. RESULTS: In all, 1,224 patients took part in the evaluation. A highly significant improvement was observed with regard to the following symptoms and habits related to sleep: feeling refreshed upon awakening, feeling tired during daytime, waking up with headache, nightmares, sweating during night time, medication for pain relief at bedtime, involuntarily falling asleep during daytime, apnoea during sleep and mouth dryness during the night. Various symptoms and habits associated with sleep prior to CABG were generally not strongly related to prognosis. Exceptions were feeling refreshed upon awakening and infrequent consumption of pain relief medication at bedtime which both were associated with an improved long-term survival. CONCLUSIONS: A variety of symptoms associated with sleep improve highly significantly after CABG. The occurrence of these symptoms prior to CABG do not generally seem to influence the long-term prognosis.

Prevalence and severity of abnormal glucose regulation and its relation to long-term prognosis after coronary artery bypass grafting.

BACKGROUND: Diabetes is a strong predictor of a poor outcome after coronary artery bypass grafting (CABG). The prevalence of prediabetes and its impact on the prognosis after CABG is not well described. In this study, we evaluated the prevalence and prognostic impact of the different states of abnormal glucose regulation (AGR) after CABG. PATIENTS AND METHODS: In this prospective study, we included 244 patients undergoing CABG. An oral glucose tolerance test was used to stratify patients into three groups: normoglycaemia, prediabetes and diabetes. The primary outcome was a composite of all-cause mortality and hospitalization for a nonfatal cardiovascular event. RESULTS: Among the patients, 86 (35%) were normoglycaemic and 58 (24%) had prediabetes; 100 (41%) patients had diabetes, of whom 28 (28%) had newly diagnosed diabetes on the basis of oral glucose tolerance test. During a mean follow-up period of 5.3 years, 25% of the study population suffered the primary outcome. There was a successive increase in the primary outcome rate from normoglycaemia through prediabetes to diabetes (adjusted hazard ratio 1.40; 95% confidence interval 1.01-1.96; P=0.045). CONCLUSION: With increasing severity of AGR, there is an increasing risk of new cardiovascular events after CABG. AGR is prevalent and predicts a poor outcome after CABG. Systematic screening for AGR seems reasonable to identify these high-risk patients.