Thomas Karlsson

Circulating Osteoprotegerin Levels and Long-Term Prognosis in Patients With Acute Coronary Syndromes

OBJECTIVES This study was designed to assess the association between osteoprotegerin (OPG) levels on admission and long-term prognosis in patients with acute coronary syndromes (ACS). BACKGROUND Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system. METHODS Serum samples for OPG analysis were obtained within 24 h of admission in 897 ACS patients (median age 66 years, 71% men) and related to the incidence of death, heart failure (HF) hospitalizations, myocardial infarction (MI), and stroke. RESULTS A total of 261 patients died during a median follow-up of 89 months. The baseline OPG concentration was strongly associated with increased long-term mortality (hazard ratio [HR] for HR per 1 SD increase in logarithmically transformed OPG level 1.7 [range 1.5 to 1.9] p < 0.0001) and HF hospitalizations (HR 2.0 [range 1.6 to 2.5]; p < 0.0001) but weaker with recurrent MI (HR 1.3 [range 1.0 to 1.5]; p = 0.02) and not with stroke (HR 1.2 [range 0.9 to 1.6]; p = 0.35). After adjustment for conventional risk markers, including troponin I, C-reactive protein (CRP), B-type natriuretic peptide (BNP), and ejection fraction, the association remained significant for mortality (HR 1.4 [range 1.2 to 1.7]; p < 0.0001) and HF hospitalization (HR 1.6 [range 1.2 to 2.1]; p = 0.0002), but not recurrent MI. By comparison of the area under the receiver-operating characteristics curves, OPG performed similarly to BNP and ejection fraction and significantly better than CRP and troponin I as a predictor of death. CONCLUSIONS Serum OPG is strongly predictive of long-term mortality and HF development in patients with ACS, independent of conventional risk markers.

Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective

Objectives In a national perspective, to describe survival among patients found in ventricular fibrillation or pulseless ventricular tachycardia witnessed by a bystander and with a presumed cardiac aetiology and answer two principal questions: (1) what are the changes over time? and (2) which are the factors of importance? Design Observational register study. Setting Sweden. Patients All patients included in the Swedish Out of Hospital Cardiac Arrest Register between 1 January 1990 and 31 December 2009 who were found in bystander-witnessed ventricular fibrillation with a presumed cardiac aetiology. Interventions Bystander cardiopulmonary resuscitation (CPR) and defibrillation. Main outcome measures Survival to 1 month. Results In all, 7187 patients fulfilled the set criteria. Age, place of out-of-hospital cardiac arrest (OHCA) and gender did not change. Bystander CPR increased from 46% to 73%; 95% CI for OR 1.060 to 1.081 per year. The median delay from collapse to defibrillation increased from 12 min to 14 min (p for trend 0.0004). Early survival increased from 28% to 45% (95% CI 1.044 to 1.065) and survival to 1 month increased from 12% to 23% (95% CI 1.058 to 1.086). Strong predictors of early and late survival were a short interval from collapse to defibrillation, bystander CPR, female gender and OHCA outside the home. Conclusion In a long-term perspective in Sweden, survival to 1 month after ventricular fibrillation almost doubled. This was associated with a marked increase in bystander CPR. Strong predictors of outcome were a short delay to defibrillation, bystander CPR, female gender and place of collapse.

Prognostic value of circulating chromogranin A levels in acute coronary syndromes

Aims To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs). Methods and results We measured circulating CgA levels on day 1 in 1268 patients (median age 67 years, 70% male) with ACS admitted to a single coronary care unit of a Scandinavian teaching hospital. The merit of CgA as a biomarker was evaluated after adjusting for conventional cardiovascular risk factors. During a median follow-up of 92 months, 389 patients (31%) died. The baseline CgA concentration was strongly associated with increased long-term mortality [hazard ratio per 1 standard deviation increase in logarithmically transformed CgA level: 1.57 (1.44–1.70), P < 0.001], heart failure hospitalizations [1.54 (1.35–1.76), P < 0.001], and recurrent myocardial infarction (MI) [1.27 (1.10–1.47), P < 0.001], but not stroke. After adjustment for conventional cardiovascular risk markers, the association remained significant for mortality [hazard ratio 1.28 (1.15–1.42), P < 0.001] and heart failure hospitalization [hazard ratio 1.24 (1.04–1.47), P = 0.02], but not recurrent MI. Conclusion CgA is an independent predictor of long-term mortality and heart failure hospitalizations across the spectrum of ACSs and provides incremental prognostic information to conventional cardiovascular risk markers.

Mechanical active compression-decompression cardiopulmonary resuscitation (ACD-CPR) versus manual CPR according to pressure of end tidal carbon dioxide (P(ET)CO2) during CPR in out-of-hospital cardiac arrest (OHCA).

AIM In animal and human studies, measuring the pressure of end tidal carbon dioxide (P(ET)CO2) has been shown to be a practical non-invasive method that correlates well with the pulmonary blood flow and cardiac output (CO) generated during cardiopulmonary resuscitation (CPR). This study aims to compare mechanical active compression-decompression (ACD) CPR with standard CPR according to P(ET)CO2 among patients with out-of-hospital cardiac arrest (OHCA), during CPR and with standardised ventilation. METHODS This prospective, on a cluster level, pseudo-randomised pilot trial took place in the Municipality of Göteborg. During a 2-year period, all patients aged >18 years suffering an out-of-hospital cardiac arrest (OHCA) of presumed cardiac etiology were enrolled. The present analysis included only tracheally intubated patients in whom P(ET)CO2 was measured for 15 min or until the detection of a pulse-giving rhythm. RESULTS In all, 126 patients participated in the evaluation, 64 patients in the mechanical chest compression group and 62 patients in the control group. The group receiving mechanical ACD-CPR obtained the significantly highest P(ET)CO2 values according to the average (p=0.04), initial (p=0.01) and minimum (p=0.01) values. We found no significant difference according to the maximum value between groups. CONCLUSION In this hypothesis generating study mechanical ACD-CPR compared with manual CPR generated the highest initial, minimum and average value of P(ET)CO2. Whether these data can be repeated and furthermore be associated with an improved outcome after OHCA need to be confirmed in a large prospective randomised trial.

Impact of coronary artery bypass grafting on various aspects of quality of life.

OBJECTIVE To prospectively study the improvement in quality of life (QoL) after coronary artery bypass surgery (CABG). PATIENTS AND METHODS Consecutive patients (n = 2121) who underwent CABG at Sahlgrenska University Hospital between 1988 and 1991 received 3 questionnaires for the study of QoL: the Physical Activity Score, the Nottingham Health Profile and the Psychological General Well-being Index, which were responded both before surgery and at 3 months (n = 1059), 1 year (n = 1045) and 2 years (n = 1027) postoperatively. RESULTS All differences were tested against baseline. The Physical Activity Score improved (mean 4.3 before CABG, 3.1, 3 months after (P < 0.0001), and 2.8, 2 years postoperatively (P < 0.0001)). The Nottingham Health Profile score improved (mean 20.5 before CABG, 11.4, 3 months (P < 0.0001), and 10.4, 2 years postoperatively (P < 0.0001)). The Psychological General Well-being Index improved (mean 91.1 before CABG, 103.8, 3 months (P < 0.0001), and 105.8 (P < 0.0001), 2 years after CABG). The subscale analyses of the Nottingham Health Profile and the Psychological General Well-being Index 2 years after CABG showed the greatest improvement in areas reflecting physical capacity and pain, to be followed by mental qualities. At 2 years after CABG only sexual problems were still markedly frequent, and independent predictors for sexual problems after surgery were preoperative problems (P < 0.00001), male sex (P < 0.0001), and diabetes mellitus (P = 0.0008). CONCLUSION QoL was markedly and significantly improved after CABG. The major improvement was seen already at 3 months, with further slight improvement observed 2 years after surgery. The major improvement was found in areas reflecting physical capacity and pain, which is consistent with symptomatic and objective measurements after CABG. In contrast to the overall improvement in QoL sexual problems were still markedly common 2 years after CABG. The mechanism for this is not fully understood and needs further investigation.

Factors surrounding cardiopulmonary resuscitation influencing bystanders' psychological reactions.

The incidence of Swedens out-of-hospital cardiac arrests averages 10000 annually. Each year bystanders initiate cardiopulmonary resuscitation (CPR) approximately 2000 times prior to arrival of emergency medical service (EMS). The aim of this study was to identify factors influencing the bystanders psychological reactions to performing CPR. We mailed a questionnaire to all bystanders who reported performing CPR to the CPR Centre of Sweden from autumn 1992 to 1995. The study included 544 bystander reports. Nine factors were found to be associated with bystanders experience in a univariate analysis. Among these were victim outcome (p < 0.0001), CPR duration (p = 0.0009) and their experience of the attitude of the EMS personnel (p = 0.004). In a multivariate logistic regression model, lack of debriefing following the intervention (p = 0.0001) and fatal victim outcome (p = 0.03) were independent predictors of a negative bystander psychological reaction. The importance of having someone to talk to following an intervention and the EMS personnel concern for the rescuer should be emphasised. The goal should be that critical incident debriefing is available to every bystander following his or her CPR attempt.

Cardiac arrest outside and inside hospital in a community: Mechanisms behind the differences in outcome and outcome in relation to time of arrest

BACKGROUND The aim was to compare characteristics and outcome after cardiac arrest where cardiopulmonary resuscitation was attempted outside and inside hospital over 12 years. METHODS All out-of-hospital cardiac arrests (OHCAs) in Göteborg between 1994 and 2006 and all in-hospital cardiac arrests (IHCAs) in 1 of the citys 2 hospitals for whom the rescue team was called between 1994 and 2006 were included in the survey. RESULTS The study included 2,984 cases of OHCA and 1,478 cases of IHCA. Patients with OHCA differed from those with an IHCA; they were younger, included fewer women, were less frequently found in ventricular fibrillation, and were treated later. If patients were found in a shockable rhythm, survival to 1 month/discharge was 18% after OHCA and 61% after IHCA (P < .0001). Corresponding values for a nonshockable rhythm were 3% and 21% (P < .0001). Survival was higher on daytime and weekdays as compared with nighttime and weekends after IHCA but not after OHCA. Among patients found in a shockable rhythm, a multivariate analysis considering age, gender, witnessed status, delay to defibrillation, time of day, day of week, and location showed that IHCA was associated with increased survival compared with OHCA (adjusted odds ratio 3.18, 95% CI 2.07-4.88). CONCLUSION Compared with OHCA, the survival of patients with IHCA increased 3-fold for shockable rhythm and 7-fold for nonshockable rhythm in our practice setting. If patients were found in a shockable rhythm, the higher survival after IHCA was only partly explained by a shorter treatment delay. The time and day of CA were associated with survival in IHCA but not OHCA.

Survival in out-of-hospital cardiac arrest before and after use of advanced postresuscitation care ☆: A survey focusing on incidence, patient characteristics, survival, and estimated cerebral function after postresuscitation care

BACKGROUND Knowledge of the epidemiology of postresuscitation care is insufficient. We describe the epidemiology of postresuscitation care in a community from a 26-year perspective, focusing on incidence, patient characteristics, survival, and estimated cerebral function in relation to intensified postresuscitation care and initial arrhythmia. METHODS The study included patients with out-of-hospital cardiac arrest (OHCA) who were brought alive to a hospital ward in Göteborg, Sweden, between 1980 and 2006. Two periods (1980-2002 and 2003-2006) were compared. RESULTS In all, 1603 patients were included. For age, sex, and history, no significant differences between the 2 periods were seen. There was a significant multiple increase in bystander cardiopulmonary resuscitation, the use of coronary angiography, coronary revascularization, and therapeutic hypothermia. The number of patients found in ventricular fibrillation (VF) decreased (P = .011). For all patients, 1-year survival did not change significantly (27% vs 32%; P = .14). Among patients found in VF, an increase in 1-year survival was found (37% vs 57%; P < .0001), whereas no significant change was seen in nonshockable rhythm (10% vs 7%; P = .38). Survivors to discharge displaying low cerebral function (ie, cerebral performance categories score >or=3) decreased from 28% to 6% (P = .0006) among all patients. CONCLUSION After the introduction of a more intensified postresuscitation care, there was no overall improvement in survival but signs of an improved cerebral function among survivors. There was a marked increase in survival among patients found in a shockable rhythm but not among those found in a nonshockable rhythm.

IgM-phosphorylcholine autoantibodies and outcome in acute coronary syndromes

BACKGROUND Antibodies against proinflammatory phosphorylcholine (anti-PC) seem to be protective and reduce morbidity. We sought to determine whether low levels of immunoglobulin-M (IgM) autoantibodies against PC add prognostic information in acute coronary syndromes (ACS). METHODS IgM anti-PC titers were measured in serum obtained within 24h of admission from 1185 ACS patients (median age 66 years, 30% women). We evaluated major acute cardiovascular events (MACE) and all-cause mortality short--(6 months), intermediate--(18 months) and long--(72 months) terms. RESULTS Low anti-PC titers were associated with MACE and all-cause mortality at all follow-up times. After adjusting for clinical variables, plasma troponin-I, proBNP and CRP levels, associations remained at all times with MACE, short and intermediate terms also with all-cause mortality. With anti-PC titers below median, adjusted hazard ratios at 18months were for MACE 1.79 (95% confidence interval [CI]: 1.31 to 2.44; p=0.0002) and for all-cause mortality 2.28 (95% CI: 1.32 to 3.92; p=0.003). Anti-PC and plasma CRP were unrelated and added to risk prediction. CONCLUSIONS Serum IgM anti-PC titers provide prognostic information above traditional risk factors in ACS. The ease of measurement and potential therapeutic perspective indicate that it may be a valuable novel biomarker in ACS.

Physical training after percutaneous coronary intervention in patients with stable angina: effects on working capacity, metabolism, and markers of inflammation.

Objective Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease. Methods Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n = 33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n = 29). The training program started 2 months before PCI and terminated 6 months afterwards. Clinical examination, blood sampling (fasting glucose, glycated hemoglobin, lipid profile, apolipoprotein B, apolipoprotein A1, C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, and interleukin-10), and maximal exercise tests were performed at inclusion, 1 week before PCI, and 3 and 6 months afterwards. Results Fifty-six patients [28 per group, 45 men, mean age 63 (SD 7.8) years] completed the follow-up. According to self-reports, patients in the training group exercised more often and longer [4.9 (SD 1.1) vs. 0.6 (SD 1.3) days/week, 36 (SD 12) vs. 15 (SD 31) min/session, P <0.0001]. Improvement in maximal exercise capacity was significantly better in the training group [27 (SD 27) vs. 9 (SD 27)W, P = 0.02]. Exercise had no significant effects on glucose and lipid metabolism, plasma cytokines, or acute-phase reactants. Conclusion A home-based training program significantly improved maximal exercise capacity but did not affect glucose or lipid metabolism or markers of inflammation. Eur J Cardiovasc Prev Rehabil 17:349-354