The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Increased Amazon carbon emissions mainly from decline in law enforcement.

The Amazon forest carbon sink is declining, mainly as a result of land-use and climate change1-4. Here we investigate how changes in law enforcement of environmental protection policies may have affected the Amazonian carbon balance between 2010 and 2018 compared with 2019 and 2020, based on atmospheric CO2 vertical profiles5,6, deforestation7 and fire data8, as well as infraction notices related to illegal deforestation9. We estimate that Amazonia carbon emissions increased from a mean of 0.24 ± 0.08 PgC year-1 in 2010-2018 to 0.44 ± 0.10 PgC year-1 in 2019 and 0.52 ± 0.10 PgC year-1 in 2020 (± uncertainty). The observed increases in deforestation were 82% and 77% (94% accuracy) and burned area were 14% and 42% in 2019 and 2020 compared with the 2010-2018 mean, respectively. We find that the numbers of notifications of infractions against flora decreased by 30% and 54% and fines paid by 74% and 89% in 2019 and 2020, respectively. Carbon losses during 2019-2020 were comparable with those of the record warm El Niño (2015-2016) without an extreme drought event. Statistical tests show that the observed differences between the 2010-2018 mean and 2019-2020 are unlikely to have arisen by chance. The changes in the carbon budget of Amazonia during 2019-2020 were mainly because of western Amazonia becoming a carbon source. Our results indicate that a decline in law enforcement led to increases in deforestation, biomass burning and forest degradation, which increased carbon emissions and enhanced drying and warming of the Amazon forests.

Amazonia as a carbon source linked to deforestation and climate change.

Amazonia hosts the Earth's largest tropical forests and has been shown to be an important carbon sink over recent decades1-3. This carbon sink seems to be in decline, however, as a result of factors such as deforestation and climate change1-3. Here we investigate Amazonia's carbon budget and the main drivers responsible for its change into a carbon source. We performed 590 aircraft vertical profiling measurements of lower-tropospheric concentrations of carbon dioxide and carbon monoxide at four sites in Amazonia from 2010 to 20184. We find that total carbon emissions are greater in eastern Amazonia than in the western part, mostly as a result of spatial differences in carbon-monoxide-derived fire emissions. Southeastern Amazonia, in particular, acts as a net carbon source (total carbon flux minus fire emissions) to the atmosphere. Over the past 40 years, eastern Amazonia has been subjected to more deforestation, warming and moisture stress than the western part, especially during the dry season, with the southeast experiencing the strongest trends5-9. We explore the effect of climate change and deforestation trends on carbon emissions at our study sites, and find that the intensification of the dry season and an increase in deforestation seem to promote ecosystem stress, increase in fire occurrence, and higher carbon emissions in the eastern Amazon. This is in line with recent studies that indicate an increase in tree mortality and a reduction in photosynthesis as a result of climatic changes across Amazonia1,10.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

Warm winter is associated with low incidence of ST elevation myocardial infarctions and less frequent acute coronary angiographies in an alpine country.

BACKGROUND: Weather conditions influence symptoms in chronic stable coronary artery disease (CAD). Whether the ongoing climate change, with continuous and rapid temperature increases, also has an impact on the incidence and outcome of non-ST elevation (NSTEMI) and ST elevation (STEMI) myocardial infarctions referred for acute coronary angiography (CA) is less clear. METHODS: According to weather data from the Institute of Meteorology and Geophysics, Innsbruck University, the 2005/2006 winter was very cold (CW) and the 2006/2007 winter extraordinarily warm (WW). As the overall invasive management of patients with acute coronary syndromes did not change substantially within these winters, we compared patients referred for acute CA suffering an acute STEMI or NSTEMI, their risk factors and in-hospital mortality rates between these two consecutive winters. RESULTS: As expected, the average temperature was lower (- 1.6 vs. + 5.9°C; p < 0.001) and humidity was higher (82 vs. 79%; p < 0.012) in CW compared to WW, with no significant differences in other weather conditions (rainfall: 59 vs. 39 days; sunshine: 3.9 vs. 4.3 h/day; air pressure: 713.04 vs. 713.76 hPa). There were no differences in the number of overall CA (987 vs. 983) between these two winters, whereas the number of acute CA (12.9 vs. 10.4% of overall CA; p = 0.046) and the diagnosis of STEMI as an indication of acute CA (74.0% vs. 62.7%; p = 0.046) were higher in CW. Furthermore, patients in CW were younger (58.2 ± 12.4 vs. 61.7 ± 11.7 years; p < 0.03), had higher LDL cholesterol (134.8 ± 44.6 vs. 116.7 ± 36.0 mg/dl; p < 0.003) and were less frequently hypertensives (52.8 vs. 70.6%; p < 0.01). Other traditional risk factors were not different between WW and CW. In addition, there were no differences in in-hospital mortality rates in invasively diagnosed CAD, patients' nationalities (Austrians: 78.0 vs. 77.5%) and time from pain to arrival in the cath lab in STEMI patients (3.9 ± 3.5 vs. 3.8 ± 3.1 h). CONCLUSION: The average temperature increase of 7.5°C from the cold to the warm winter was associated with a decrease in acute coronary angiographies, in particular due to a lower incidence of STEMI referred for primary percutaneous intervention.

Safety and efficacy of femoral artery closure with the FemoSeal(R) device after coronary angiography using a 7 French sheath.

Post-cardiac catheterization femoral artery hemostasis can be accomplished with several mechanisms, including the FemoSeal® hemostasis device which has been designed and approved for closure of 6 French (F) arterial puncture sites. The aim of this study was to investigate whether the FemoSeal® vascular closure device can effectively and safely seal 7F arterial puncture sites after diagnostic and interventional cardiac catheterizations. Femoral artery puncture sites of 50 consecutive patients undergoing cardiac catheterization were closed with the FemoSeal® vascular closure device, according to the manufacturer's instructions. Efficacy endpoints were time to hemostasis and successful ambulation. Safety endpoints included bleeding complications, vessel occlusion and pseudoaneurysms. Mean time to hemostasis was 57.8±26.3 seconds (0-125 seconds). Hemostasis was achieved in 100 percent of the 50 patients. One patient suffered minor bleeding the next day, i.e. local hematoma. This clinical study demonstrates that the FemoSeal® vascular closure device, initially approved for closure of 6F arterial puncture sites, shows promising efficacy and safety to seal a larger (7F) femoral arterial puncture sites after diagnostic and interventional cardiac catheterizations.

Occurrence of acute myocardial infarction in winter tourists: data from a retrospective questionnaire.

BACKGROUND: Every year millions of tourists spend their vacation in Tyrol, Austria during the winter season. They often perform sports at high altitudes and at low temperatures, factors that might cause acute myocardial infarction (AMI). This study aimed to evaluate the relationship of first physical activity and the onset of AMI in winter tourists. METHODS: We carried out a retrospective analysis of consecutive patients admitted to the Department of Internal Medicine III at the Medical University of Innsbruck with the diagnosis of an AMI between 2006 and 2010. We identified 172 patients as potential candidates for the questionnaire. We successfully contacted 110 patients (mean age: 60 ± 10 years). The location of visit, duration of stay, time of arrival, first sportive activity and onset of symptoms were assessed. RESULTS: During the first 2 days of physical activity , 56% of AMIs occurred. In tourists who suffered AMI during, or within 1 h after cessation of activity (52%), the mean time from the start of the activity to the onset of symptoms was 2.0 ± 1.7 h. 56% of patients performed less than 2.5 h of sport per week before their vacation and 70% had ≥2 cardiovascular risk factors. Although the mean planned vacation time was 8.3 ± 3.7 days, 39% of the patients suffered from AMI on the day of arrival or the day after. CONCLUSION: The majority of AMIs in winter tourists happens within the first 2 days after arrival and within the first 2 days of physical activity.

Limited utilities of N-terminal pro B-type natriuretic peptide and other newer risk markers compared with traditional risk factors for prediction of significant angiographic lesions in stable coronary artery disease.

OBJECTIVE: To investigate the usefulness of N-terminal pro-brain natriuretic peptide (NT-proBNP) as a predictive marker for angiographically significant coronary artery disease (CAD) and CAD severity compared with other newer biochemical risk markers and classic risk factors in patients with clinically suspected CAD. DESIGN: Cross-sectional evaluation of NT-proBNP in a large consecutive series of patients without a history of myocardial infarction referred for elective coronary angiography (CAG) between March 2004 and January 2005. The value of NT-proBNP for predicting CAD was assessed and compared with high sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT) and traditional risk factors. SETTING: Tertiary care centre, Department of Cardiology, Innsbruck Medical University, Austria. PATIENTS: 561 men and 287 women aged between 20-86 years (median 65 years). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Association of NT-proBNP with the severity of CAD, left ventricular dysfunction and comparison of predictive values of NT-proBNP, hs-CRP, GGT and traditional CAD risk factors. RESULTS: Of all tested newer biochemical risk markers NT-proBNP performed best. In a multinomial logistic regression model NT-proBNP but not hs-CRP or GGT was significantly associated with three-vessel CAD adjusted for age, sex, ventricular, renal function and classic risk factors (odds ratio = 1.667; 95% CI 1.003 to 2.772; p = 0.049). However, NT-proBNP had no additive predictive value to traditional cardiovascular risk factors for the prediction of angiographically significant CAD in a binary logistic regression model. CONCLUSIONS: The predictive value of NT-proBNP for CAD severity is better than that of hs-CRP or GGT. However, NT-proBNP is also of limited value compared with traditional risk factors for predicting significant CAD.

High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography.

BACKGROUND: Although high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP) are well-established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). MATERIAL AND METHODS: Five thousand six hundred forty-one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of >or= 70%. Coronary angiograms were graded as one-, two- or three-vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non-CAD. RESULTS: HDL-C (60.3 +/- 18.5 vs. 51.9 +/- 15.3 mg dL(-1); P < 0.001) was higher and CRP was lower (0.65 +/- 1.68 vs. 1.02 +/- 2.38 mg dL(-1); P < 0.001) in non-CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65.2 +/- 10.5 years vs. 59.9 +/- 11.4 years), more often diabetics (19.2% vs. 10.6%) and hypertensives (79.2% vs. 66.0%) and included more smokers (18.8% vs. 16.5%) (all P < 0.005). Low-density lipoprotein cholesterol (124.5 +/- 38.3 vs. 126.0 +/- 36.3 mg dL(-1); P = NS) was similar in overall CAD and non-CAD patients with more statin users (43.4% vs. 27.9%; P < 0.001) among CAD patients. Comparing non-CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL-C and CRP remained independently associated with the prevalence of CAD. In addition, HDL-C is also a potent predictor for the severity of CAD. CONCLUSIONS: In this large consecutive patient cohort, HDL-C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL-C is an even stronger predictor for CAD than some other major classical risk factors.

Determinants of health-related quality of life in coronary artery disease patients: a prospective study generating a structural equation model.

The authors used structural equation modeling to test a conceptual model of HRQL in coronary artery disease. The model, which included biomedical factors and individual and environmental characteristics, was tested in a multicenter group of 465 patients at three timepoints (baseline evaluation of chest pain and 1- and 3-month follow-ups). A satisfactory fit was obtained for the model over time. Depression and anxiety symptoms exerted the most significant influence on HRQL. HRQL and the mediating factors were found to be distinct phenomena. The authors concluded that mediating factors, especially depression and anxiety symptoms, should be taken into consideration in clinical routine if HRQL is regarded as a clinical outcome.

Endothelin-1 directly modulates its own secretion: studies utilising the cell immunoblot technique.

Endothelin-1 is an important factor in vasoregulation and circulating levels of the peptide are increased in a number of cardiovascular disorders. However, control of endothelin-1 secretion is only sketchily understood. The possibility that endothelin-1 influences its own release was investigated. A cell immunoblot method, which can detect local secretion of peptide from individual human vascular endothelial cells, was employed. Cells were dispersed onto a protein-binding membrane. Endothelin-1 in cells or secreted and adhering to the protein-binding membrane outside the cells was detected using immunohistochemical techniques. The numbers of cells that contained endothelin-1 and secreted endothelin-1 were counted after the cells had been incubated in control conditions, or with added endothelin-1, angiotensin-II, or endothelin receptor antagonists, bosentan and BQ788. Endothelin-1 and angiotensin-II increased the numbers of cells that secreted endothelin-1. On the other hand, bosentan and BQ788 caused a reduction in the numbers of endothelin-1-secreting cells. These results indicate that human endothelial cells contain a pathway by which endothelin-1 induces its own release. The receptor antagonists, bosentan and BQ788, inhibited basal secretion of endothelin-1.

Vascular endothelial growth factor synthesis in vascular smooth muscle cells is enhanced by 7-ketocholesterol and lysophosphatidylcholine independently of their effect on nitric oxide generation.

Nitric oxide (NO) generated by inducible NO synthase (iNOS) enhances vascular endothelial growth factor (VEGF) synthesis in vascular smooth muscle cells (VSMC) and both NO and modified low density lipoprotein (LDL) augment VEGF production in macrophages. Oxidized LDL (oxLDL) are known inhibitors of NO generation in the cells of vascular wall. As the relationship between VEGF, iNOS and oxLDL has not been well elucidated, we studied the effect of two main components of oxLDL, 7-ketocholesterol (7-Kchol) and lysophosphatidylcholine (LPC), on VEGF and NO synthesis in rat VSMC and on VEGF synthesis in human VSMC. Both LPC and 7-Kchol significantly augmented VEGF production in rat and human VSMC. Increase in VEGF generation was related to the activation of VEGF promoter by both 7-Kchol and LPC and enhancement of VEGF mRNA transcription. In rat, VSMC IL-1beta-induced NO generation and enhanced VEGF synthesis. 7-Kchol decreased rat iNOS promoter activity, iNOS expression and NO generation, but it did not impair IL-1beta-induced VEGF synthesis. LPC did not significantly influence IL-1beta-induced NO production in rat VSMC and VEGF synthesis was significantly enhanced by combined treatment with IL-1beta and LPC in comparison to the effect of either compound alone. The results indicate that VEGF and NO synthesis in VSMC can be modulated by oxLDL. Those interactions might have an effect on the plaque growth and might be of relevance for the physiology of vascular wall cells.