• Performance of the GRACE Risk Score 2.0 Simplified Algorithm for Predicting 1-Year Death After Hospitalization for an Acute Coronary Syndrome in a Contemporary Multiracial Cohort

  Huang, Wei; FitzGerald, Gordon; Goldberg, Robert J.; Gore, Joel M.; McManus, Richard H.; Awad, Hamza H.; Waring, Molly E.; Allison, Jeroan J.; Saczynski, Jane S.; Kiefe, Catarina I.; et al. (2016-10-15)

  The GRACE Risk Score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome (ACS). GRACE Risk Score 2.0 substitutes several variables that may be unavailable to clinicians and, thus, limit use of the GRACE Risk Score. GRACE Risk Score 2.0 performed well in the original GRACE cohort. We sought to validate its performance in a contemporary multiracial ACS cohort, in particular in black patients with ACS. We evaluated the performance of the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality in 2,131 participants in Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE), a multiracial cohort of patients discharged alive after an ACS in 2011 to 2013 from 6 hospitals in Massachusetts and Georgia. The median age of study participants was 61 years, 67% were men, and 16% were black. Half (51%) of the patients experienced a non-ST-segment elevation myocardial infarction (NSTEMI) and 18% STEMI. Eighty patients (3.8%) died within 12 months of discharge. The GRACE Risk Score 2.0 simplified algorithm demonstrated excellent model discrimination for predicting 1-year mortality after hospital discharge in the TRACE-CORE cohort (c-index = 0.77). The c-index was 0.94 in patients with STEMI, 0.78 in those with NSTEMI, and 0.87 in black patients with ACS. In conclusion, the GRACE Risk Score 2.0 simplified algorithm for predicting 1-year mortality exhibited excellent model discrimination across the spectrum of ACS types and racial/ethnic subgroups and, thus, may be a helpful tool to guide routine clinical care for patients with ACS.
• Temporal trends in all-cause mortality according to smoking status: Insights from the Global Registry of Acute Coronary Events

  Arbel, Yaron; FitzGerald, Gordon; Yan, Andrew T.; Tan, Mary K.; Fox, Keith A. A.; Gore, Joel M.; Steg, Phillippe Gabriel; Eagle, Kim A.; Brieger, David; Montalescot, Gilles; et al. (2016-09-01)

  Objective Smoking has been shown to be a risk factor for heart disease. However, it was recently reported that despite the evolution in therapy for acute coronary syndrome (ACS), smokers have not demonstrated improved outcomes. The aim of the present study was to evaluate the temporal trends in the treatments and outcomes across a broad spectrum of ACS patients (STEMI and non-ST-elevation ACS [NSTEACS]) according to smoking status on presentation in the Global Registry of Acute Coronary Events (GRACE). Methods Our cohort was stratified into 3 groups: current smokers, former smokers and never smokers. We evaluated trends in demographics, treatment modalities and outcomes in these 3 groups from 1999 to 2007. Results The study population comprised a total of 63,015 patients admitted to hospital with an ACS and with identifiable baseline smoking status. Smokers presented with STEMI more often than non-smokers. There was an unadjusted decline in 30-day mortality in all 3 groups. However, the adjusted decline was not statistically significant among current smokers (HR = 0.98 per study year, 95% CI 0.94–1.01, p = 0.20). A subgroup analysis of 22,894 STEMI patients demonstrated no reduction in annual adjusted 30-day mortality rates among smokers (HR = 1.01, 95% CI 0.96–1.06 (Table 5), whereas former and never smokers' mortality declined. Conclusions Over the years 1999–2007, 30-day mortality declined in patients presenting with acute coronary syndrome. However, smokers presenting with STEMI did not demonstrate a reduction in mortality.
• Prognostic value of dynamic electrocardiographic T wave changes in non-ST elevation acute coronary syndrome

  Sarak, Bradley; Goodman, Shaun G.; Yan, Raymond T.; Tan, Mary K.; Steg, Phillippe Gabriel; Tan, Nigel S.; Fox, Keith A. A.; Udell, Jacob A.; Brieger, David; Welsh, Robert C.; et al. (2016-09-01)

  OBJECTIVE: To assess the relationship between the evolution of T wave inversion (TWI) on the 24-48 h postadmission ECG and the patient characteristics, management and clinical outcomes among those with non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: We evaluated admission and 24-48 h follow-up ECGs of 7201 patients with NSTE-ACS from the prospective, multicentre Global Registry of Acute Coronary Events (GRACE) and Canadian ACS Registry I. We performed multivariable analyses to determine the association between new TWI (on follow-up ECG only), resolved TWI (on admission ECG only) and persistent TWI (on both admission and follow-up ECG) and inhospital and cumulative 6-month all-cause mortality. RESULTS: Patients with TWI were older, more likely to have cardiovascular risk factors, higher Killip class and GRACE risk scores. After adjustment for known prognostic factors, compared with patients presenting without TWI, new TWI was associated with significantly lower inhospital mortality (OR=0.60, 95% CI 0.38 to 0.95, p=0.029), whereas resolved (OR=1.06, 95% CI 0.65 to 1.75, p=0.81) and persistent (OR=0.73, 95% CI 0.48 to 1.11, p=0.14) TWI did not predict inhospital mortality. No TWI pattern independently predicted inhospital adverse cardiovascular events or cumulative 6-month mortality. In contrast, ST depression on the admission and follow-up ECG were independent predictors of inhospital and 6-month mortality. CONCLUSIONS: Across the spectrum of NSTE-ACS, TWI within 48 h of presentation was associated with high-risk clinical features, but its presence or dynamic change did not provide additional prognostic value beyond other established clinical predictors.
• Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women

  Compston, Juliet E.; Wyman, Allison; FitzGerald, Gordon; Adachi, Jonathan D.; Chapurlat, Roland D.; Diez-Perez, Adolfo; Gehlbach, Stephen H.; Greenspan, Susan L.; Hooven, Frederick H.; LaCroix, Andrea Z.; et al. (2016-07-01)

  Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of ≥10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of ≥10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age ± SD 68 ± 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. © 2016 American Society for Bone and Mineral Research.
• Clinical Characteristics, Management, and Outcomes of Acute Coronary Syndrome in Patients With Right Bundle Branch Block on Presentation

  Chan, William K.; Goodman, Shaun G.; Brieger, David; Fox, Keith A. A.; Gale, Chris P.; Chew, Derek P.; Udell, Jacob A.; Lopez-Sendon, Jose; Huynh, Thao; Yan, Raymond T.; et al. (2016-03-01)

  We examined the relations between right bundle branch block (RBBB) and clinical characteristics, management, and outcomes among a broad spectrum of patients with acute coronary syndrome (ACS). Admission electrocardiograms of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) electrocardiogram substudy and the Canadian ACS Registry I were analyzed independently at a blinded core laboratory. We performed multivariable logistic regression analysis to assess the independent prognostic significance of admission RBBB on in-hospital and 6-month mortality. Of 11,830 eligible patients with ACS (mean age 65; 66% non-ST-elevation ACS), 5% had RBBB. RBBB on admission was associated with older age, male sex, more cardiovascular risk factors, worse Killip class, and higher GRACE risk score (all p < 0.01). Patients with RBBB less frequently received in-hospital cardiac catheterization, coronary revascularization, or reperfusion therapy (all p < 0.05). The RBBB group had higher unadjusted in-hospital (8.8% vs 3.8%, p < 0.001) and 6-month mortality rates (15.1% vs 7.6%, p < 0.001). After adjusting for established prognostic factors in the GRACE risk score, RBBB was a significant independent predictor of in-hospital death (odds ratio 1.45, 95% CI 1.02 to 2.07, p = 0.039), but not cumulative 6-month mortality (odds ratio 1.29, 95% CI 0.95 to 1.74, p = 0.098). There was no significant interaction between RBBB and the type of ACS for either in-hospital or 6-month mortality (both p > 0.50). In conclusion, across a spectrum of ACS, RBBB was associated with preexisting cardiovascular disease, high-risk clinical features, fewer cardiac interventions, and worse unadjusted outcomes. After adjusting for components of the GRACE risk score, RBBB was a significant independent predictor of early mortality.
• Occurrence and predictors of recurrence after a first episode of acute venous thromboembolism: population-based Worcester Venous Thromboembolism Study

  Huang, Wei; Goldberg, Robert J.; Anderson, Frederick A. Jr.; Cohen, Alexander T.; Spencer, Frederick A. (2016-02-05)

  Venous thromboembolism (VTE) has multiple risk factors and tends to recur. Despite the benefits of anticoagulation, the prevalence of, and case-fatality rate associated with, recurrent VTE remains a concern after an acute episode; it is particularly high during the acute treatment phase. We sought to quantify the magnitude, identify predictors, and develop risk score calculator of recurrence within 3 years after first-time VTE. This was a population-based surveillance study among residents of central Massachusetts (MA), USA, diagnosed with an acute first-time pulmonary embolism and/or lower-extremity deep vein thrombosis from 1999 to 2009 in hospital and ambulatory settings in all 12 central MA hospitals. Medical records were reviewed and validated. The 2989 study patients were followed for 5836 person-years [mean follow-up 23.4 (median 30) months]. Mean age was 64.3 years, 44 % were men, and 94 % were white. The cumulative incidence rate of recurrent VTE within 3 years after an index VTE was 15 % overall, and 25, 13, and 13 % among patients with active cancer, provoked, or unprovoked VTE, respectively. Multivariable regression indicated that active cancer, varicose vein stripping, and inferior vena cava filter placement were independent predictors of recurrence during both 3-month and 3-year follow-up. A risk score calculator was developed based on the 3-month prognostic model. In conclusion, the rate of VTE recurrence over 3 years of follow-up remained high. The risk score calculator may assist clinicians at the index encounter in determining the frequency of clinical surveillance and appropriate outpatient treatment of VTE during the acute treatment phase.
• Cardiovascular Risk Factors and In-Hospital Mortality in Acute Coronary Syndromes: Insights From the Canadian Global Registry of Acute Coronary Events

  Wang, Jenny Y.; Goodman, Shaun G.; Saltzman, Ilana; Wong, Graham C.; Huynh, Thao; Dery, Jean-Pierre; Leiter, Lawrence A.; Bhatt, Deepak; Welsh, Robert C.; Spencer, Frederick A.; et al. (2015-04-17)

  BACKGROUND: There are conflicting data regarding the relationship between the number of modifiable traditional risk factors and prognosis in acute coronary syndromes (ACS). This controversy might in part be explained by the differential use of prehospital medications. METHODS: Using data from the Canadian, multicentre Global Registry of Acute Coronary Events (GRACE) (1999-2008), we stratified 13,686 ACS patients into 3 groups (0, 1-2, vs 3-4 risk factors) and compared their baseline characteristics, in-hospital treatments, and outcomes. Multivariable logistic regressions were performed to adjust for the components of the GRACE risk score and preadmission statin and acetylsalicylic acid (ASA) use. RESULTS: Among these patients (ST-elevation myocardial infarction 28.3%), 14.5%, 62.6%, and 22.9% had 0, 1-2, and 3-4 risk factors, respectively. Patients with fewer risk factors were less likely to be on ASA, statin, and other prehospital medications. Unadjusted in-hospital mortality was significantly different across risk factor groups (4.9%, 3.0%, and 3.1% for 0, 1-2, and 3-4 risk factor groups, respectively, P for trend = 0.002). This difference was no longer significant after adjusting for the components of the GRACE risk score (P for trend = 0.088) and further adjusting for preadmission statin and ASA use (P for trend = 0.96). For in-hospital mortality, there was no significant interaction between risk factor categories and ACS type (P = 0.26). CONCLUSIONS: The lower mortality observed in patients with ACS with more risk factors may be partially attributed to the protective effect of prehospital ASA and statin use. The number of risk factors does not provide incremental prognostic value beyond the validated GRACE risk score.
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  Impact of Thromboprophylaxis across the US Acute Care Setting

  Huang, Wei; Anderson, Frederick A. Jr.; Rushton-Smith, Sophie K.; Cohen, Alexander T. (2015-03-27)

  BACKGROUND: The risk of venous thromboembolism (VTE) can be reduced by appropriate use of anticoagulant prophylaxis. VTE prophylaxis does, however, remain substantially underused, particularly among acutely ill medical inpatients. We sought to evaluate the clinical and economic impact of increasing use of American College of Chest Physicians (ACCP)-recommended VTE prophylaxis among medical inpatients from a US healthcare system perspective. METHODS AND FINDINGS: In this retrospective database cost-effectiveness evaluation, a decision-tree model was developed to estimate deaths within 30 days of admission and outcomes attributable to VTE that might have been averted by use of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Incremental cost-effectiveness ratio was calculated using "no prophylaxis" as the comparator. Data from the ENDORSE US medical inpatients and the US nationwide Inpatient Sample (NIS) were used to estimate the annual number of eligible inpatients who failed to receive ACCP-recommended VTE prophylaxis. The cost-effectiveness analysis indicated that VTE-prevention strategies would reduce deaths by 0.5% and 0.3%, comparing LMWH and UFH strategies with no prophylaxis, translating into savings of $50,637 and $25,714, respectively, per death averted. The ENDORSE findings indicated that 51.1% of US medical inpatients were at ACCP-defined VTE risk, 47.5% of whom received ACCP-recommended prophylaxis. By extrapolating these findings to the NIS and applying cost-effectives analysis results, the full implementation of ACCP guidelines would reduce number of deaths (by 15,875 if using LMWH or 10,201 if using UFH), and was extrapolated to calculate the cost reduction of $803M for LMWH and $262M for UFH. CONCLUSIONS: Efforts to improve VTE prophylaxis use in acutely ill inpatients are warranted due to the potential for reducing VTE-attributable deaths, with net cost savings to healthcare systems.
• In-hospital management and outcomes of acute coronary syndromes in relation to prior history of heart failure

  Zhang, Hanfei; Goodman, Shaun G.; Yan, Raymond T.; Steg, Phillippe Gabriel; Kornder, Jan M.; Gyenes, Gabor; Grondin, Francois R.; Brieger, David; DeYoung, J. Paul; Gallo, Richard; et al. (2015-03-12)

  INTRODUCTION: The prognostic significance of prior heart failure in acute coronary syndromes has not been well studied. Accordingly, we evaluated the baseline characteristics, management patterns and clinical outcomes in patients with acute coronary syndromes who had prior heart failure. METHODS AND RESULTS: The study population consisted of acute coronary syndrome patients in the Global Registry of Acute Coronary Events, expanded Global Registry of Acute Coronary Events and Canadian Registry of Acute Coronary Events between 1999 and 2008. Of the 13,937 eligible patients (mean age 66±13 years, 33% female and 28.3% with ST-elevation myocardial infarction), 1498 (10.7%) patients had a history of heart failure. Those with prior heart failure tended to be older, female and had lower systolic blood pressure, higher Killip class and creatinine on presentation. Prior heart failure was also associated with significantly worse left ventricular systolic function and lower rates of cardiac catheterization and coronary revascularization. The group with previous heart failure had significantly higher rates of acute decompensated heart failure, cardiogenic shock, myocardial (re)infarction and mortality in hospital. In multivariable analysis, prior heart failure remained an independent predictor of in-hospital mortality (odds ratio 1.48, 95% confidence interval 1.08-2.03, p=0.015). CONCLUSIONS: Prior heart failure was associated with high risk features on presentation and adverse outcomes including higher adjusted in-hospital mortality in acute coronary syndrome patients. However, acute coronary syndrome patients with prior heart failure were less likely to receive evidence-based therapies, suggesting potential opportunities to target more intensive treatment to improve their outcome.
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  Comparison between Frailty Index of Deficit Accumulation and Phenotypic Model to Predict Risk of Falls: Data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort

  Li, Guowei; Thabane, Lehana; Ioannidis, George; Kennedy, Courtney; Papaioannou, Alexandra (2015-03-12)

  OBJECTIVES: To compare the predictive accuracy of the frailty index (FI) of deficit accumulation and the phenotypic frailty (PF) model in predicting risks of future falls, fractures and death in women aged > /=55 years. METHODS: Based on the data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) 3-year Hamilton cohort (n = 3,985), we compared the predictive accuracy of the FI and PF in risks of falls, fractures and death using three strategies: (1) investigated the relationship with adverse health outcomes by increasing per one-fifth (i.e., 20%) of the FI and PF; (2) trichotomized the FI based on the overlap in the density distribution of the FI by the three groups (robust, pre-frail and frail) which were defined by the PF; (3) categorized the women according to a predicted probability function of falls during the third year of follow-up predicted by the FI. Logistic regression models were used for falls and death, while survival analyses were conducted for fractures. RESULTS: The FI and PF agreed with each other at a good level of consensus (correlation coefficients > /= 0.56) in all the three strategies. Both the FI and PF approaches predicted adverse health outcomes significantly. The FI quantified the risks of future falls, fractures and death more precisely than the PF. Both the FI and PF discriminated risks of adverse outcomes in multivariable models with acceptable and comparable area under the curve (AUCs) for falls (AUCs > /= 0.68) and death (AUCs > /= 0.79), and c-indices for fractures (c-indices > /= 0.69) respectively. CONCLUSIONS: The FI is comparable with the PF in predicting risks of adverse health outcomes. These findings may indicate the flexibility in the choice of frailty model for the elderly in the population-based settings.
• International management of bone health in glucocorticoid-exposed individuals in the observational GLOW study

  Silverman, S.; Flahive, Julie; Anderson, Frederick A. Jr.; Hooven, Fred H. (2015-01-01)
• High-grade atrioventricular block in acute coronary syndromes: insights from the Global Registry of Acute Coronary Events

  Singh, Sheldon M.; FitzGerald, Gordon; Yan, Andrew T.; Brieger, David; Fox, Keith A. A.; Lopez-Sendon, Jose; Yan, Raymond T.; Eagle, Kim A.; Steg, Phillippe Gabriel; Budaj, Andrzej; et al. (2014-09-08)

  BACKGROUND: While prior work has suggested that a high-grade atrioventricular block (HAVB) in the setting of an acute coronary syndrome (ACS) is associated with in-hospital death, limited information is available on the incidence of, and death associated with, HAVB in ACS patients receiving contemporary management. METHODS AND RESULTS: The incidence of HAVB was determined within The Global Registry of Acute Coronary Events (GRACE). The clinical characteristics, in-hospital therapies, and outcomes were compared between patients with and without HAVB. Factors associated with death in patients with HAVB were determined. A total of 59 229 patients with ACS between 1999 and 2007 were identified; 2.9% of patients had HAVB at any point during the index hospitalization; 22.7% of whom died in hospital [adjusted odds ratio (OR) = 4.2, 95% confidence interval (CI), 3.6-4.9, P < 0.001]. The association between HAVB and in-hospital death varied with type of ACS [OR: ST-segment elevation myocardial infarction (STEMI) = 3.0; non-STEMI = 6.4; unstable angina = 8.2, P for interaction < 0.001]. High-grade atrioventricular block present at the time of presentation to hospital (vs. occurring in-hospital) and early (12 h or no intervention) were associated with improved in-hospital survival, whereas temporary pacemaker insertion was not. Patients with HAVB surviving to discharge had similar adjusted survival at 6 months compared with those without HAVB. A reduction in the rate of, but not in-hospital mortality associated with, HAVB was noted over the study period. CONCLUSION: Although the incidence of HAVB is low and decreasing, this complication continues to have a high risk of in-hospital death.
• The Agency for Healthcare Research and Quality Inpatient Quality Indicator #11 overall mortality rate does not accurately assess mortality risk after abdominal aortic aneurysm repair

  Robinson, William P. III; Huang, Wei; Rosen, Amy K.; Schanzer, Andres; Fang, Hua (Julia); Anderson, Frederick A. Jr.; Messina, Louis M. (2014-07-24)

  OBJECTIVE: The Agency for Healthcare Research and Quality (AHRQ) Inpatient Quality Indicator (IQI) #11, abdominal aortic aneurysm (AAA) repair mortality rate, is a measure of hospital quality that is publically reported but has not been externally validated. Because the IQI #11 overall mortality rate includes both intact and ruptured aneurysms and open and endovascular repair, we hypothesized that IQI #11 overall mortality rate does not provide accurate assessment of mortality risk after AAA repair and that AAA mortality cannot be accurately assessed by a single quality measure. METHODS: Using AHRQ IQI software version 4.2, we calculated observed (O) and expected (E) mortality rates for IQI #11 for all hospitals performing more than 10 AAA repairs per year in the Nationwide Inpatient Sample for the years 2007 to 2011. We used Spearman correlation coefficient to compare expected rates as determined by IQI #11 overall mortality rate risk adjustment methodology and observed rates for all AAA repairs in four cohorts stratified by aneurysm stability (ruptured vs intact) and method of repair (open vs endovascular). RESULTS: Among 187,773 AAA repairs performed at 1268 U.S. hospitals, hospitals' IQI #11 overall expected rates correlated poorly with their observed rates (E: 5.0% ± 4.4% vs O: 6.0% ± 9.8%; r = .49). For ruptured AAAs, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 34% ± 7.2% vs O: 40.1% ± 38.2%; r = 0.20) and endovascular repair (E: 24.8% ± 9% vs O: 27.3% ± 37.9%; r = 0.08). For intact AAA repair, IQI #11 overall mortality rate methodology underestimated the mortality risk of open repair (E: 4.3% ± 2.4% vs O: 6.3% ± 16.1%; r = .24) but overestimated the mortality risk of endovascular repair (E: 1.3% ± 0.8% vs O: 1.1% ± 3.7%; r = 0.25). Hospitals' observed mortality rates after intact AAA repair were not correlated with their mortality rates after ruptured AAA repair (r = 0.03). CONCLUSIONS: IQI #11 overall mortality rate fails to provide accurate assessment of inpatient mortality risk after AAA repair. Thus, it is inappropriate to use IQI #11 overall mortality rate for quality reporting. The accuracy of separate quality measures that assess mortality risk after repair of ruptured and intact AAAs, stratified by the use of open or endovascular repair, should be examined.
• GRACE score predicts heart failure admission following acute coronary syndrome

  McAllister, David A.; Halbesma, Nynke; Carruthers, Kathryn F.; Denvir, Martin; Fox, Keith A. (2014-07-01)

  BACKGROUND: Congestive heart failure (CHF) is a common and preventable complication of acute coronary syndrome (ACS). Nevertheless, ACS risk scores have not been shown to predict CHF risk. We investigated whether the at-discharge Global Registry of Acute Coronary Events (GRACE) score predicts heart failure admission following ACS. METHODS AND RESULTS: Five-year mortality and hospitalization data were obtained for patients admitted with ACS from June 1999 to September 2009 to a single centre of the GRACE registry. CHF was defined as any admission assigned WHO International Classification of Diseases 10 diagnostic code I50. The hazard ratio (HR) for CHF according to GRACE score was estimated in Cox models adjusting for age, gender and the presence of CHF on index admission. Among 1,956 patients, CHF was recorded on index admission in 141 patients (7%), and 243 (12%) were admitted with CHF over 3.8 median years of follow-up. Compared to the lowest quintile, patients in the highest GRACE score quintile had more CHF admissions (116 vs 17) and a shorter time to first admission (1.2 vs 2.0 years, HR 9.87, 95% CI 5.93-16.43). Per standard deviation increment in GRACE score, the instantaneous risk was more than two-fold higher (HR 2.28; 95% CI 2.02-2.57), including after adjustment for CHF on index admission, age and gender (HR 2.49; 95% CI 2.06-3.02). The C-statistic for CHF admission at 1-year was 0.74 (95% CI 0.70-0.79). CONCLUSIONS: The GRACE score predicts CHF admission, and may therefore be used to target ACS patients at high risk of CHF with clinical monitoring and therapies.
• Insights from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

  Watts, Nelson B.; GLOW Investigators (2014-07-01)

  GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged ≥ 55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX(®) (upper arm, forearm, hip and clinical vertebral fractures) account for > 40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases.
• Beta-blocker Use in ST-segment Elevation Myocardial Infarction in the Reperfusion Era (GRACE)

  Lee Park, Kay; Goldberg, Robert J.; Anderson, Frederick A. Jr.; Lopez-Sendon, Jose; Montalescot, Gilles; Brieger, David; Eagle, Kim A.; Wyman, Allison; Gore, Joel M.; GRACE Investigators (2014-06-01)

  BACKGROUND: Current guidelines recommend early oral beta-blocker administration in the management of acute coronary syndromes for patients who are not at high risk of complications. METHODS: Data from patients enrolled between 2000 and 2007 in the Global Registry of Acute Coronary Events (GRACE) were used to evaluate hospital outcomes in three cohorts of patients admitted with ST-elevation myocardial infarction, based on beta-blocker use (early [first 24 hours] intravenous [± oral], only early oral, or delayed [after first 24 hours]). RESULTS: Among 13,110 patients with a ST-elevation myocardial infarction, 21% received any early intravenous beta-blockers, 65% received only early oral beta-blockers, and 14% received delayed (>24 hours) beta-blockers. Higher systolic blood pressure, higher heart rate, and chronic beta-blocker use were independent predictors of early beta-blocker use. Early beta-blocker use was less likely in older patients, patients with moderate to severe left ventricular dysfunction, and in those presenting with inferior myocardial infarction or Killip class III heart failure. Intravenous beta-blocker use and delayed beta-blocker use were associated with higher rates of cardiogenic shock, sustained ventricular fibrillation/ventricular tachycardia and acute heart failure, compared with oral beta-blocker use. In-hospital mortality was increased with IV beta-blocker use (propensity score adjusted odds ratio [OR] 1.41; 95% confidence interval [CI], 1.03-1.92) but significantly reduced with delayed beta-blocker administration (propensity adjusted OR, 0.44; 95% CI, 0.26-0.74). CONCLUSIONS: Early beta-blocker use is common in patients presenting with ST-elevation myocardial infarction, with oral administration being most prevalent. Oral beta-blockers were associated with a decrease in the risk of cardiogenic shock, ventricular arrhythmias, and acute heart failure. However, the early receipt of any form of beta-blockers was associated with an increase in hospital mortality.
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  Frailty index of deficit accumulation and falls: data from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort

  Li, Guowei; Ioannidis, George; Pickard, Laura; Kennedy, Courtney; Papaioannou, Alexandra; Thabane, Lehana; Adachi, Jonathan D. (2014-05-29)

  BACKGROUND: To investigate the association between frailty index (FI) of deficit accumulation and risk of falls, fractures, death and overnight hospitalizations in women aged 55 years and older. METHODS: The data were from the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton Cohort. In this 3-year longitudinal, observational cohort study, women (N=3,985) aged ≥ 55 years were enrolled between May 2008 and March 2009 in Hamilton, Canada. A FI including co-morbidities, activities of daily living, symptoms and signs, and healthcare utilization was constructed using 34 health deficits at baseline. Relationship between the FI and falls, fractures, death and overnight hospitalizations was examined. RESULTS: The FI was significantly associated with age, with a mean rate of deficit accumulation across baseline age of 0.004 or 0.021 (on a log scale) per year. During the third year of follow-up, 1,068 (31.89%) women reported at least one fall. Each increment of 0.01 on the FI was associated with a significantly increased risk of falls during the third year of follow-up (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02-1.03). The area under the curve (AUC) of the predictive model was 0.69 (95% CI: 0.67-0.71). Results of subgroup and sensitivity analyses indicated the relationship between the FI and risk of falls was robust, while bootstrap analysis judged its internal validation. The FI was significantly related to fractures (hazard ratio [HR]: 1.02, 95% CI: 1.01-1.03), death (OR: 1.05, 95% CI: 1.03-1.06) during the 3-year follow-up period and overnight hospitalizations (incidence rate ratio [IRR]: 1.02, 95% CI: 1.02-1.03) for an increase of 0.01 on the FI during the third year of follow-up. Measured by per standard deviation (SD) increment of the FI, the ORs were 1.21 and 1.40 for falls and death respectively, while the HR was 1.17 for fractures and the IRR was 1.18 for overnight hospitalizations respectively. CONCLUSION: The FI of deficit accumulation increased with chronological age significantly. The FI was associated with and predicted increased risk of falls, fractures, death and overnight hospitalizations significantly.
• Clinical characteristics and outcomes of acute coronary syndrome patients with left anterior hemiblock

  Zhang, Hanfei; Goodman, Shaun G.; Steg, Gabriel P.; Budaj, Andrzej; Lopez-Sendon, Jose; Dorian, Paul; Huynh, Thao; Mangat, Iqwal; Wong, Graham C.; Spencer, Frederick A.; et al. (2014-05-19)

  OBJECTIVE: We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS). METHODS: Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality. RESULTS: Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99). CONCLUSIONS: Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models.
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  Empirically based composite fracture prediction model from the Global Longitudinal Study of Osteoporosis in Postmenopausal Women (GLOW)

  FitzGerald, Gordon; Hosmer, David W. Jr.; Anderson, Frederick A. Jr.; Hooven, Fred H.; Gehlbach, Stephen H. (2014-03-01)

  CONTEXT: Several fracture prediction models that combine fractures at different sites into a composite outcome are in current use. However, to the extent individual fracture sites have differing risk factor profiles, model discrimination is impaired. OBJECTIVE: The objective of the study was to improve model discrimination by developing a 5-year composite fracture prediction model for fracture sites that display similar risk profiles. DESIGN: This was a prospective, observational cohort study. SETTING: The study was conducted at primary care practices in 10 countries. PATIENTS: Women aged 55 years or older participated in the study. INTERVENTION: Self-administered questionnaires collected data on patient characteristics, fracture risk factors, and previous fractures. MAIN OUTCOME MEASURE: The main outcome is time to first clinical fracture of hip, pelvis, upper leg, clavicle, or spine, each of which exhibits a strong association with advanced age. RESULTS: Of four composite fracture models considered, model discrimination (c index) is highest for an age-related fracture model (c index of 0.75, 47 066 women), and lowest for Fracture Risk Assessment Tool (FRAX) major fracture and a 10-site model (c indices of 0.67 and 0.65). The unadjusted increase in fracture risk for an additional 10 years of age ranges from 80% to 180% for the individual bones in the age-associated model. Five other fracture sites not considered for the age-associated model (upper arm/shoulder, rib, wrist, lower leg, and ankle) have age associations for an additional 10 years of age from a 10% decrease to a 60% increase. CONCLUSIONS: After examining results for 10 different bone fracture sites, advanced age appeared the single best possibility for uniting several different sites, resulting in an empirically based composite fracture risk model.
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  Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score

  Fox, Keith A. A.; FitzGerald, Gordon; Puymirat, Etienne; Huang, Wei; Carruthers, Kathryn; Simon, Tabassome; Coste, Pierre; Monsegu, Jacques; Steg, Phillippe Gabriel; Danchin, Nicolas; et al. (2014-02-21)

  OBJECTIVES: Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices. DESIGN AND SETTING: The GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005. PARTICIPANTS: Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes. OUTCOME MEASURES: The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors. RESULTS: For key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p CONCLUSIONS: The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.

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