Plasma renin activity has a complex prognostic role in patients with acute coronary syndromes.

BACKGROUND: Plasma renin activity (PRA) has been related to all-cause mortality and cardiovascular events in patients with cardiovascular disease. However, data from patients with acute coronary syndromes (ACS) are sparse. METHODS: Determination of PRA was made in 550 patients with ACS, including a subgroup of 287 patients not on treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or diuretics, and without heart failure. We evaluated the relations between PRA and all-cause mortality after three years and long-term, and to cardiovascular events after median 8.7 years. Adjustments were made for variables that influenced the hazard ratio (HR) > 5% for the relation between PRA and outcome. RESULTS: Baseline PRA was associated with all-cause mortality during three-years (unadjusted HR 1.74 per 1 SD increase in logarithmically transformed PRA; 95% confidence interval (CI) 1.39-2.16, p < 0.0001) and long-term (HR 1.12, CI 1.00-1.25, p = 0.046). After adjustments, only the three-year association remained significant. In unadjusted analyses, PRA was associated with cardiovascular death, but not with nonfatal cardiovascular events. In the subgroup there was an inverse relation between PRA and long-term all-cause mortality. CONCLUSION: Higher PRA was a significant independent predictor of all-cause mortality after three years, but not at long-term follow-up and not significantly associated with cardiovascular incidence. The renin-angiotensin-system pathophysiology is of great interest, not least due to its association with the COVID-19 pandemic. Our findings indicate a need for further research on the prognostic/predictive aspects of the renin-angiotensin-system in ACS.

Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden.

BACKGROUND: Our understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging. METHODS: As part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18-50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations. RESULTS: In faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge. INTERPRETATION: In contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection.

Homeostatic Chemokines and Prognosis in Patients With Acute Coronary Syndromes.

BACKGROUND: The chemokines CCL19 and CCL21 are up-regulated in atherosclerotic disease and heart failure, and increased circulating levels are found in unstable versus stable coronary artery disease. OBJECTIVES: The purpose of this study was to evaluate the prognostic value of CCL19 and CCL21 in acute coronary syndrome (ACS). METHODS: CCL19 and CCL21 levels were analyzed in serum obtained from ACS patients (n = 1,146) on the first morning after hospital admission. Adjustments were made for GRACE (Global Registry of Acute Coronary Events) score, left ventricular ejection fraction, pro-B-type natriuretic peptide, troponin I, and C-reactive protein levels. RESULTS: The major findings were: 1) those having fourth quartile levels of CCL21 on admission of ACS had a significantly higher long-term (median 98 months) risk of major adverse cardiovascular events (MACE) and myocardial infarction in fully adjusted multivariable models; 2) high CCL21 levels at admission were also independently associated with MACE and cardiovascular mortality during short-time (3 months) follow-up; and 3) high CCL19 levels at admission were associated with the development of heart failure. CONCLUSIONS: CCL21 levels are independently associated with outcome after ACS and should be further investigated as a promising biomarker in these patients.

Seventeen-Year Mortality following the Acute Coronary Syndrome: Gender-Specific Baseline Variables and Impact on Outcome.

BACKGROUND: Gender differences in outcome and its predictors in patients with acute coronary syndrome (ACS) continue to be debated. OBJECTIVES: To assess long-term mortality and explore its association with the baseline variables in women and men. METHODS: We followed 2,176 consecutive patients (665 women and 1,511 men) with ACS admitted to a single hospital and still alive after 30 days for a median of 16 years 8 months. RESULTS: At the end of the follow-up, 415 (62.4%) women and 849 (56.2%) men had died (unadjusted hazard ratio [HR] for women/men 1.18 (95% confidence interval [CI], 1.05-1.33, p =0.005). After adjustment for age, the HR was reversed to 0.88 (95% CI, 0.78-1.00, p =0.04). Additional adjustment for potential confounders yielded a HR of 0.86 (95% CI, 0.76-0.98, p = 0.02). Using multivariable Cox regression, previous heart failure, previous or new-onset atrial fibrillation, and psychotropic drugs at discharge were significantly associated with increased long-term mortality in men only. Known hypertension, elevated creatinine, and inhospital Killip class >1/cardiogenic shock were significantly associated with mortality only in women. For late mortality, hypertension and inhospital Killip class >1/cardiogenic shock interacted significantly with gender. CONCLUSION: For patients with ACS surviving the first 30 days, late mortality was lower in women than in men after adjusting for age. The effects of several baseline characteristics on late outcome differed between women and men. Gender-specific strategies for long-term follow-up of ACS patients should be considered.

Serum neutrophil gelatinase-associated lipocalin (NGAL) concentration is independently associated with mortality in patients with acute coronary syndrome.

BACKGROUND: Circulating neutrophil gelatinase-associated lipocalin (NGAL) concentration increases in cardiovascular disease, but the long-term prognostic value of NGAL concentration has not been evaluated in acute coronary syndrome (ACS). We examined the association between NGAL concentration and prognosis in patients with ACS after non-ST-elevation myocardial infarction (NSTEMI) or STEMI. METHODS AND RESULTS: NGAL concentration was measured in blood from 1121 consecutive ACS patients (30% women, mean age 65 years) on the first morning after admission. After adjustment for 14 variables, NGAL concentration predicted long-term (median 167 months) mortality (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.61, P = 0.003) for quartile (q) 4 of NGAL concentration. NGAL concentrations also predicted long-term mortality (HR = 1.63, 95% CI 1.31-2.03, P < 0.001, N = 741) when adjusting for Global Registry of Acute Coronary Events (GRACE) score, left ventricular ejection fraction (LVEF), and pro-B-type natriuretic peptide (proBNP) and C-reactive protein (CRP) concentrations. With these adjustments, NGAL concentration predicted long-term mortality in NSTEMI patients (HR = 2.02, 95% CI 1.50-2.72, P < 0.001) but not in STEMI patients (HR = 1.32, 95% CI 0.95-1.83, P = 0.100). In all patients, the combination of NGAL concentration and GRACE score yielded an HR of 5.56 (95% CI 4.37-7.06, P < 0.001) for q4/q4 for both variables. CONCLUSION: NGAL concentration in ACS is associated with long-term prognosis after adjustment for clinical confounders. Measuring circulating NGAL concentration may help to identify patients-particularly those with NSTEMI-needing closer follow-up after ACS.

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

BACKGROUND: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat. METHODS: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined. RESULTS: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study. CONCLUSIONS: Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility. CLINICAL TRIALS REGISTRATION: EudraCT 2011-004804-38.

Value of the QRS-T area angle in improving the prediction of sudden cardiac death after acute coronary syndromes.

BACKGROUND: Prediction of sudden cardiac death (SCD) after acute coronary syndromes (ACS) remains a challenge. Although electrophysiology measures obtained by 3-D vectorcardiography (VCG) shortly after ACS may be useful predictors of SCD, they have not been adopted into clinical practice. The main objective of our study was to assess whether the VCG-derived QRS-T area angle (between area vectors) and the QRS-T angle (between maximum vectors) have additional value beyond standard risk factors in predicting SCD after ACS. METHODS AND RESULTS: We studied 643 consecutive ACS patients for whom data on VCG and echocardiography during the index hospitalization were available. Seventy-seven patients (12%) died, 37 (6%) from SCD and 21 (3%) from other cardiac causes during the 30-month follow-up. After adjusting for 9 standard risk factors (age, sex, diabetes, previous stroke, left ventricular ejection fraction; and estimated glomerular filtration rate, heart rate, systolic blood pressure<100mmHg, and Killip class>1 on admission), QRS-T area angle and QRS-T angle were shown to have independent predictive value for both SCD and all cardiac deaths. Reclassification analysis showed that both measures had additional predictive value beyond the 9 standard risk factors. For SCD, net reclassification improvements for QRS-T area angle and QRS-T angle were 46% and 45% and relative integrated discriminative improvements were 16% and 13% (vs the average~11% of the 9 standard risk factors). CONCLUSIONS: The VCG-derived QRS-T area angle and QRS-T angle improved prediction of SCD after ACS beyond standard risk factors. Further evaluation of their clinical utility and cost-effectiveness is therefore warranted.

Safety and immunogenicity of an improved oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine administered alone and together with dmLT adjuvant in a double-blind, randomized, placebo-controlled Phase I study.

BACKGROUND: We have developed a new oral vaccine against enterotoxigenic Escherichia coli (ETEC), which is the most common cause of bacterial diarrhea in children in developing countries and in travelers. METHODS: The vaccine was tested for safety and immunogenicity alone and together with double-mutant heat-labile toxin (dmLT) adjuvant in a double-blind, placebo-controlled Phase I study in 129 Swedish adults. The vaccine consists of four inactivated recombinant E. coli strains overexpressing the major ETEC colonization factors (CFs) CFA/I, CS3, CS5, and CS6 mixed with an LT B-subunit related toxoid, LCTBA. Volunteers received two oral doses of vaccine alone, vaccine plus 10 µg or 25 µg dmLT or placebo. Secretory IgA antibody responses in fecal samples and IgA responses in secretions from circulating intestine-derived antibody secreting cells were assessed as primary measures of vaccine immunogenicity. RESULTS: The vaccine was safe and well tolerated; adverse events were few and generally mild with no significant differences between subjects receiving placebo or vaccine with or without adjuvant. As many as 74% of subjects receiving vaccine alone and 83% receiving vaccine plus 10 µg dmLT showed significant mucosal IgA responses to all five primary vaccine antigens and about 90% of all vaccinees responded to at least four of the antigens. Subjects receiving vaccine plus 10 µg dmLT responded with significantly increased intestine-derived anti-CS6 responses compared to subjects receiving vaccine alone. CONCLUSIONS: The vaccine was safe and broadly immunogenic. dmLT further enhanced mucosal immune responses to CF antigens present in low amounts in the vaccine. Based on these encouraging results, the vaccine will be tested for safety and immunogenicity in different age groups including infants in Bangladesh and for protective efficacy in travelers.

Transient repolarization alterations dominate the initial phase of an acute anterior infarction--a vectorcardiography study.

OBJECTIVE: To study effects of ischemia-reperfusion on ventricular electrophysiology in humans by three-dimensional electrocardiography. METHODS: Fifty-seven patients with first-time acute anterior ST elevation myocardial infarction were monitored from admission and >24h after symptom onset with continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global ventricular depolarization and repolarization (VR) measures were compared at maximum vs. minimum ST vector magnitude (STVM) (median 208; 111-303 vs. 362; 165-1359min after symptom onset). RESULTS: At maximum vs. minimum STVM the Tarea (overall VR dispersion) almost tripled (118 vs. 41µVs; p<0.0001), the T-loop bulginess was 90% greater (Tavplan 0.91 vs 0.48µV; p<0.0001), and Tpeak-end/QT was 39% larger (0.32 vs 0.23; p<0.0001). QRSarea (overall dispersion of depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer at minimum STVM. CONCLUSIONS: Ischemia-reperfusion was accompanied by profound and transient alterations of VR dispersion, while changes in depolarization were modest and delayed.

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.

Multimarker risk assessment including osteoprotegerin and CXCL16 in acute coronary syndromes.

OBJECTIVE: CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes. METHODS AND RESULTS: We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84-5.82; P<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62-2.92; P<0.0001), and 2.22 for heart failure (95% CI, 1.67-2.96; P<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months. CONCLUSIONS: Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.

Vectorcardiography analysis of the repolarization response to pharmacologically induced autonomic nervous system modulation in healthy subjects.

Autonomic nervous system activity is essential for regulation of ventricular repolarization (VR) and plays an important role in several arrhythmogenic conditions. This study in 31 healthy adult subjects (16 men, 15 women) evaluated the VR response to pharmacologically modulated autonomic nervous system activity applying vectorcardiography (VCG) analysis. During continuous VCG recording, 0.01-0.1 µg·kg(-1)·min(-1) isoprenaline (Iso) was infused at an increasing flow rate until three targeted heart rates (HR) were reached. After Iso washout, one intravenous bolus of 0.04 mg/kg atropine was given followed by an intravenous bolus of 0.2 mg/kg propranolol. A 5-min steady-state VCG recording was analyzed for each of the seven phases (including baseline 1 and 2). Furthermore, during the first 4 min following atropine, six periods of 10-s VCG were selected for subanalysis to evaluate the time course of change. The analysis included QRS, QT, and T-peak to T-end intervals, measures of the QRS and T vectors and their relation, as well as T-loop morphology parameters. By increasing HR, Iso infusion decreased HR dependent parameters reflecting total heterogeneity of VR (T area) and action potential morphology (ventricular gradient). In contrast, Iso prolonged QT HR corrected according to Bazett and increased the T-peak to T-end-to-QT ratio to levels observed in arrhythmogenic conditions. HR acceleration after atropine was accompanied by a transient paradoxical QT prolongation and delayed HR adaptation of T area and ventricular gradient. In addition to the expected HR adaptation, the VR response to ß-adrenoceptor stimulation with Iso and to muscarinic receptor blockade with atropine thus included alterations previously observed in congenital and acquired long QT syndromes, demonstrating substantial overlap between physiological and pathophysiological electrophysiology.

Effect of new versus known versus no atrial fibrillation on 30-day and 10-year mortality in patients with acute coronary syndrome.

Coronary artery disease promotes the development of atrial fibrillation (AF). The aim of this study was to determine short- and long-term mortality in patients with acute coronary syndromes (ACS) and AF, depending on the AF presentation. A total of 2,335 consecutive patients with ACS were included. AF was classified as known persistent or permanent AF, known paroxysmal AF, new AF at admission, and new AF during hospitalization for ACS. Four hundred forty-two patients had any AF: 54 with known persistent or permanent AF, 150 with known paroxysmal AF, 54 with new AF at admission, and 184 with new AF during hospitalization. Statistically significant differences among subgroups related to previous heart failure (p <0.0001), stroke (p = 0.04), myocardial infarction (p <0.0001), angina pectoris (p <0.0001), hypercholesterolemia (p = 0.007), coronary artery bypass grafting (p <0.0001), and percutaneous coronary intervention (p = 0.03) were observed. Thirty-day mortality differed among the subgroups (p = 0.02) and was lowest in patients with known paroxysmal AF (7.3%). Ten-year mortality ranged from 53% to 78% among the subgroups. There were 5 predictors of long-term mortality across the subgroups: age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04 to 1.09, p <0.0001), previous myocardial infarction (HR 1.4, 95% CI 1.0 to 1.8, p = 0.04), heart failure (HR 1.8, 95% CI 1.3 to 2.4, p = 0.0002), diabetes (HR 1.7, 95% CI 1.2 to 2.2, p = 0.0005), and smoking (HR 1.7, 95% CI 1.2 to 2.3, p = 0.001). In conclusion, patient characteristics and 30-day mortality differed significantly among the subgroups, but long-term mortality did not. Any AF associated with ACS almost doubled the long-term mortality risk. AF in patients with ACS should therefore be regarded as an important risk factor irrespective of its presentation.

Role of the CHADS2 score in acute coronary syndromes: risk of subsequent death or stroke in patients with and without atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients with acute coronary syndromes (ACS). We aimed to describe the value of the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke or transient ischemic attack) score as a risk assessment tool for mortality and stroke in patients with ACS, irrespective of the presence or absence of AF. METHODS: Consecutive patients with ACS admitted to the coronary care unit were prospectively included in a risk stratification study. We calculated the CHADS(2) scores from the data collected at admission, and all patients were followed until January 1, 2007, or death. RESULTS: Of 2,335 patients with ACS in this study, 442 (age 71 ± 8 years, 142 women) had AF. Their mean CHADS(2) score was 1.6 ± 1.4 vs 1.0 ± 1.1 in patients without AF (P < .0001). The all-cause mortality at 10 years was strongly associated with the CHADS(2) score in patients with AF (hazard ratio [HR] and 95% CI per unit increase in the six-grade CHADS(2) score, 1.21 [1.07-1.36]; P = .002), but the same association was also present in patients without AF (HR 1.38 [1.28-1.48], P < .0001), after adjustment for potential confounders. The more complicated GRACE (Global Registry of Acute Coronary Events) risk score provided a better prediction for short- and long-term mortality than the simpler CHADS(2) score (P < .0001). Hospitalization for stroke was significantly associated with the CHADS(2) score in patients without AF (but not in those with AF) after adjustment (HR 1.46 [1.27-1.68], P < .0001). CONCLUSIONS: In patients with ACS, AF is associated with poor prognosis. The CHADS(2) score developed for AF has even greater prognostic value in patients who do not have AF, and it may help to identify patients with high risk for subsequent stroke or death and a need for optimization of risk-reducing treatment.

Long-term prognostic value of mitral regurgitation in acute coronary syndromes.

OBJECTIVES: To determine the additional prognostic value of mitral regurgitation (MR) over B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF) and clinical characteristics in patients with acute coronary syndromes (ACS). DESIGN: Long-term follow-up in a prospective ACS cohort with Doppler-assessed MR, echocardiographically-determined LVEF and plasma BNP levels by ELISA. SETTING: Single-centre university hospital. PATIENTS: 725 patients with ACS. MAIN OUTCOME MEASURES: Death and readmission for congestive heart failure. RESULTS: During a median follow-up of 98 months, 235 patients (32%) died. Significant MR (grade >1 of 4) was found in 90 patients (12%). In a multivariate model including MR grade >1, LVEF <0.40 and BNP >373 pg/ml (75th percentile), MR was significantly associated with long-term mortality (HR 2.28, 95% CI 1.67 to 3.12; p<0.0001). When also adjusting for conventional risk factors, MR remained significantly associated with mortality (HR 1.53, 95% CI 1.06 to 2.19; p=0.02), as well as with congestive heart failure (HR 2.08, 95% CI 1.29 to 3.35; p=0.003). CONCLUSIONS: MR is common in patients with ACS, provides independent risk information and should be taken into account in the evaluation of the long-term prognosis.

Interleukin-18 as a predictor of future events in patients with acute coronary syndromes.

OBJECTIVE: The aim of this study was to assess the short- and long-term prognostic significance of interleukin-18 (IL-18) levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: In patients hospitalized with ACS (median age, 66 years; 30% females), we evaluated associations of serum IL-18 levels from day 1 (n=1261) with the short- (<3 months) and long-term (median, 7.6 years) risk of death, development of congestive heart failure (CHF), and myocardial infarction (MI). IL-18 was not significantly associated with short-term mortality. In the long term, IL-18 levels were significantly related to all-cause mortality, even after adjustment for clinical confounders (hazard ratio [HR], 1.19; 95% confidence interval, 1.07 to 1.33; P=0.002). Long-term, cardiovascular mortality was univariately related to IL-18, and the adjusted relation between noncardiovascular mortality and IL-18 was highly significant (HR, 1.36; 95% confidence interval, 1.11 to 1.67; P=0.003). IL-18 independently predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long term. Measurements from day 1 of ACS and 3 months after ACS had a similar power to predict late outcome. CONCLUSIONS: The addition of the measurement of IL-18 to clinical variables improved the prediction of risk of all-cause and noncardiovascular mortality. The association between IL-18 and noncardiovascular mortality is intriguing and warrants further study.

Symptoms of chest pain and dyspnoea during a period of 15 years after coronary artery bypass grafting.

AIM: To describe changes in chest pain and dyspnoea during a period of 15 years after coronary artery bypass grafting (CABG) and to define factors at the time of operation that were associated with the occurrence of these symptoms after 15 years. DESIGN: Prospective observational study in western Sweden. SUBJECTS: All patients who underwent first-time CABG, without simultaneous valve surgery, between 1 June 1988 and 1 June 1991. There were no exclusion criteria. FOLLOW-UP: All patients were followed up prospectively for 15 years. The evaluation of symptoms took place through postal questionnaires prior to and 5, 10 and 15 years after the operation. RESULTS: Totally, 2000 patients were included in the survey and 904 (45%) of them survived to 15 years. Among these 904 survivors, the percentage of patients with chest pain increased from 44% to 50% between the 5- and 15-year follow-up (p=0.004). The percentage of patients who reported symptoms of dyspnoea increased from 60% after 5 years to 74% after 15 years (p<0.001). Factors at the time of surgery that independently tended to predict chest pain after 15 years were higher age (p=0.04) and prolonged duration of symptoms prior to surgery (p=0.04). Predictors of dyspnoea after 15 years were higher age (p<0.0001), the use of inotropic drugs at the time of surgery (p=0.001), a history of diabetes (p=0.01) and obesity (p=0.01). CONCLUSION: After CABG, relief from chest pain and dyspnoea is generally maintained over a long period of time. Eventually, however, functional-limiting symptoms tend to recur and about half the patients report symptoms of chest pain, while three-quarters report dyspnoea after 15 years. Even if no clear predictor of chest pain was found at the time of surgery, age, the use of inotropic drugs, diabetes and obesity predicted dyspnoea.

Quality of life 15 years after coronary artery bypass grafting.

OBJECTIVES: To describe changes in quality of life (QoL) during 15 years after coronary artery bypass grafting (CABG) and prediction of impaired QoL after 15 years. METHODS: All patients in western Sweden who underwent primary CABG without simultaneous valve surgery between 1988 and 1991 were included. QoL during a period of 15 years after CABG was evaluated with three instruments: the Nottingham Health Profile, the Psychological General Well-Being Index, and the Physical Activity Score. RESULTS: A total of 2000 patients took part in the survey, (none excluded) of whom 808 were still alive after 15 years and 79% answered the inquiry. Despite an ongoing decline in QoL over the years, an improvement in QoL was maintained in most sub-dimensions at the 15-year follow-up compared with that prior to surgery. Seven factors emerged as predictors of impaired QoL 15 years after CABG. They are as follows: (i) high age, (ii) female sex, (iii) history of diabetes, (iv) obesity, (v) prolonged stay in the intensive care unit, (vi) prolonged treatment on a ventilator, (vii) need for inotropic drugs at the time of surgery; of which the latter three might be secondary to left ventricular dysfunction. CONCLUSION: Despite an ongoing decline in QoL over the years, there was still an improvement in most aspects of QoL 15 years after CABG compared with that before surgery. Intensified early treatment of diabetes, obesity, and left ventricular dysfunction in CABG patients might allow an even better long-term QoL.

Soluble CXCL16 predicts long-term mortality in acute coronary syndromes.

BACKGROUND: CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor for oxidized low-density lipoprotein that is expressed in atherosclerotic lesions. Proteolytic cleavage of membrane-bound CXCL16 releases soluble CXCL16, which may promote migration of effector T cells and augment a proatherogenic inflammatory response. We hypothesized that soluble CXCL16 concentrations are associated with long-term outcome in patients with acute coronary syndromes. METHODS AND RESULTS: We assessed the association between circulating CXCL16 levels obtained within 24 hours after admission and time to death in 1351 patients (median age 67 years, 30% female) with a diagnosis of unstable angina, non-ST-segment-elevation myocardial infarction, or ST-segment-elevation myocardial infarction. During a median follow-up time of 81 months, 377 patients died. Increased levels of CXCL16 were prognostically unfavorable; the fourth versus first quartile was associated with higher risk of death (hazard ratio 2.1; 95% CI 1.6 to 2.8; P<0.0001), triple risk of developing heart failure (hazard ratio 3.0; 95% CI 1.8 to 5.1; P<0.0001), and a doubling of the risk of rehospitalization for myocardial infarction (hazard ratio 2.1; 95% CI 1.3 to 3.3; P=0.002). After adjustment for conventional risk markers, logarithmically transformed CXCL16 level remained a strong independent indicator of long-term mortality (hazard ratio 1.21; 95% CI 1.09 to 1.36 per 1 SD increase in CXCL16; P=0.0006) and congestive heart failure development (hazard ratio 1.25; 95% CI 1.05 to 1.48; P=0.01). In a subsample of 714 patients, after further adjustment for troponin T, high-sensitive C-reactive protein, pro-B-type natriuretic peptide, and left ventricular ejection fraction, CXCL16 still provided significant additional prognostic information on mortality (hazard ratio 1.21; 95% CI 1.02 to 1.42 per 1 SD increase in CXCL16; P=0.02). CONCLUSIONS: In patients with an acute coronary syndrome, CXCL16 levels obtained within 24 hours of admission are associated with long-term mortality after adjustment for other risk factors.