Coronary Artery Disease: Newby LK

King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Hirshfeld JW, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM, Anonymous00143, Anonymous00144, Anonymous00145. · No affiliation provided · J Am Coll Cardiol. · Pubmed #17601554 No free full text.

This publication has no abstract.

Anonymous00180, King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM. · No affiliation provided · Circulation. · Pubmed #17592076 links to  free full text

This publication has no abstract.

Wang TY, AlJaroudi WA, Newby LK. · Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA. · Cardiol Clin. · Pubmed #16278119 No free full text.

Abstract: Because biomarkers of myocardial necrosis only become positive in the setting of myocardial necrosis and disruption of cellular integrity, the diagnosis of myocardial infarction can only be made in retrospect. Ideally, one would like to identify patients at risk for complications before myocardial necrosis occurs. Insights into the pathophysiology of atherothrombosis have allowed development of novel markers to detect not only early ischemia without myocyte death but also early indicators of coronary inflammation inpatients who have preclinical atherosclerosis.

Shah SH, Newby LK. · Department of Cardiology, Duke University Medical Center, Durham, North Carolina, USA. · Cardiol Rev. · Pubmed #12852794 No free full text.

Abstract: Patients without traditional cardiovascular risk factors continue to suffer from cardiovascular events, which has prompted a search for novel markers to better assess cardiovascular risk. Inflammatory biomarkers have surfaced as prime candidates, given the integral role of inflammation in atherosclerosis. C-reactive protein (CRP) measurements in particular have emerged as powerful predictors of cardiovascular risk in a broad spectrum of patient populations. Newer high sensitivity CRP assays now in use are standardized and reproducible, and can detect variations in CRP below the limit of standard assays. In primary prevention populations, studies have shown up to a 2-4-fold increased risk of cardiovascular events in healthy patients with elevated CRP levels. In this population, models incorporating CRP and lipid parameters appear to predict risk significantly better than lipids alone. In patients with established cardiovascular disease and in patients undergoing percutaneous coronary interventions, CRP levels may help predict short- and long-term prognosis, identifying subgroups of patients at increased risk of recurrent events. CRP levels may also prove useful in targeting therapy for primary and secondary prevention, by identifying patients who would most benefit from medications such as statins and aspirin. This review presents an overview of the data regarding CRP measurement for cardiovascular risk assessment.

Kassem-Moussa H, Mahaffey KW, Graffagnino C, Tasissa G, Sila CA, Simes RJ, White HD, Califf RM, Bhapkar MV, Newby LK, Anonymous00394. · Duke Clinical Research Institute, Durham, NC 27715, USA. · Am Heart J. · Pubmed #15389230 No free full text.

Abstract: BACKGROUND: Stroke is a rare but serious event that complicates the course of patients with acute coronary syndromes (ACS). The type, outcome, and risk factors of stroke occurring in stabilized patients with ACS have not been previously reported. METHODS: We evaluated stroke incidence, subtypes, and outcomes, in addition to demographics and clinical risk characteristics associated with stroke among patients enrolled in the Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials. RESULTS: Of 15,904 stabilized patients with ACS, 113 (0.71%) had a stroke over a median follow-up of 90 days. The majority of strokes occurred within 30 days of presentation, and the time course for stroke occurrence paralleled that of myocardial (re)infarction. Most strokes were ischemic (78%), and 52% resulted in moderate or severe disability or death. Patients with stroke were older and more often had hypertension, diabetes, peripheral vascular disease, and atrial fibrillation. Among patients with stroke who had cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass grafting, stroke occurred predominantly after the procedure. No difference in occurrence or type of stroke was observed in the assigned treatment groups. In multivariable modeling age, heart failure, prior stroke, left bundle branch block, and systolic blood pressure predicted the occurrence of stroke. CONCLUSIONS: In patients stabilized after presenting with a spectrum of ACS and treated with sibrafiban and/or aspirin, stroke occurred in fewer than 1% within 90 days but carried a significant mortality and morbidity risk.

Jneid H, Fonarow GC, Cannon CP, Hernandez AF, Palacios IF, Maree AO, Wells Q, Bozkurt B, Labresh KA, Liang L, Hong Y, Newby LK, Fletcher G, Peterson E, Wexler L, Anonymous00035. · Division of Cardiology, Michael E. DeBakey VA Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd, Houston, TX 77030, USA. · Circulation. · Pubmed #19064680 No free full text.

Abstract: BACKGROUND: Women receive less evidence-based medical care than men and have higher rates of death after acute myocardial infarction (AMI). It is unclear whether efforts undertaken to improve AMI care have mitigated these sex disparities in the current era. METHODS AND RESULTS: Using the Get With the Guidelines-Coronary Artery Disease database, we examined sex differences in care processes and in-hospital death among 78 254 patients with AMI in 420 US hospitals from 2001 to 2006. Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had higher unadjusted in-hospital death (8.2% versus 5.7%; P<0.0001) than men. After multivariable adjustment, sex differences in in-hospital mortality rates were no longer observed in the overall AMI cohort (adjusted odds ratio [OR]=1.04; 95% CI, 0.99 to 1.10) but persisted among STEMI patients (10.2% versus 5.5%; P<0.0001; adjusted OR=1.12; 95% CI, 1.02 to 1.23). Compared with men, women were less likely to receive early aspirin treatment (adjusted OR=0.86; 95% CI, 0.81 to 0.90), early beta-blocker treatment (adjusted OR=0.90; 95% CI, 0.86 to 0.93), reperfusion therapy (adjusted OR=0.75; 95% CI, 0.70 to 0.80), or timely reperfusion (door-to-needle time </=30 minutes: adjusted OR=0.78; 95% CI, 0.65 to 0.92; door-to-balloon time </=90 minutes: adjusted OR=0.87; 95% CI, 0.79 to 0.95). Women also experienced lower use of cardiac catheterization and revascularization procedures after AMI. CONCLUSIONS: Overall, no sex differences in in-hospital mortality rates after AMI were observed after multivariable adjustment. However, women with STEMI had higher adjusted mortality rates than men. The underuse of evidence-based treatments and delayed reperfusion among women represent potential opportunities for reducing sex disparities in care and outcome after AMI.

Kim JH, Newby LK, Clare RM, Shaw LK, Lodge AJ, Smith PK, Jolicoeur EM, Rao SV, Becker RC, Mark DB, Granger CB. · Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA. · Am Heart J. · Pubmed #19061702 No free full text.

Abstract: BACKGROUND: Short-term use of clopidogrel plus aspirin among patients with acute coronary syndrome reduces ischemic events, but concerns about coronary artery bypass graft (CABG) surgery-related bleeding limit its early use. METHODS: Using data from 4,794 consecutive CABG procedures in the Duke Databank for Cardiovascular Disease (January 1999 to December 2003), we developed multivariable models for associations with CABG-related bleeding defined as reoperation for bleeding, red cell transfusion, and a composite of reoperation/transfusion/hematocrit drop>or=15%. We examined clopidogrel use<or=5 days versus no clopidogrel<or=5 days before CABG in each model. Models were adjusted for propensity for clopidogrel use<or=5 days. RESULTS: Of 4,794 CABG patients, 332 (6.9%) received clopidogrel<or=5 days before CABG, 127 (2.6%) had reoperation for bleeding, 3,277 (68.4%) received red cell transfusion, and 4,387 (91.5%) had the composite outcome. After adjustment, clopidogrel use<or=5 days was not significantly associated with reoperation (odds ratio [OR] 1.24, 95% CI 0.63-2.41) or the composite end point (OR 1.23, 95% CI 0.72-2.10). Clopidogrel<or=5 days was modestly associated with red cell transfusion (OR 1.40, 95% CI 1.04-1.89) but more weakly than other factors, including which surgeon performed the procedure. CONCLUSION: Clopidogrel administration<or=5 days before CABG was not significantly associated with reoperation for bleeding or a bleeding composite, and only weakly with red cell transfusion after surgery. The impact of withholding clopidogrel acutely in those for whom clopidogrel has proven benefits and the impact of delaying CABG to prevent bleeding among patients treated with clopidogrel should be viewed in the context of other stronger determinants of bleeding.

Roe MT, Ou FS, Alexander KP, Newby LK, Foody JM, Gibler WB, Boden WE, Ohman EM, Smith SC, Peterson ED. · Department of Medicine, Division of Cardiovascular Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. · Eur Heart J. · Pubmed #18716006 No free full text.

Abstract: AIMS: The patterns and prognostic significance of low high-density lipoprotein (HDL) cholesterol levels have not been well characterized. We sought to determine the prevalence and prognostic significance of low HDL cholesterol levels in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: We evaluated HDL levels among NSTE ACS patients [ischaemic ECG (electrocardiogram) changes and/or positive cardiac markers] from the CRUSADE [Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC(American College of Cardiology)/AHA(American Heart Association) Guidelines] initiative treated at 555 US hospitals from January 2001 through June 2006. Clinical and angiographic characteristics, treatments, and in-hospital outcomes were analysed by categories of HDL levels measured during hospitalization. Among 93 263 NSTE ACS patients with HDL measurements, 16 854 (18.1%) had very low HDL levels (10-29 mg/dL), 32 185 (34.5%) had low HDL levels (30-39 mg/dL), 35 875 (38.5%) had normal HDL levels (40-59 mg/dL), and 8349 (9.0%) had high HDL levels (60-100 mg/dL). Patients with very low HDL levels were younger, more often male, and more commonly obese and diabetic. Patients with very low HDL levels had the greatest risk of multi-vessel coronary disease on angiography and in-hospital mortality compared with patients with normal and high HDL levels. CONCLUSION: Almost one-fifth of patients with NSTE ACS have very low HDL levels--a finding that adds incrementally to a greater burden of atherosclerosis and a higher risk of mortality. Consequently, strategies for mitigating the adverse prognosis associated with very low HDL levels warrant further exploration in patients with ACS.

Jneid H, Fonarow GC, Cannon CP, Palacios IF, Kilic T, Moukarbel GV, Maree AO, LaBresh KA, Liang L, Newby LK, Fletcher G, Wexler L, Peterson E, Anonymous00440. · Division of Cardiology, Massachusetts General Hospital, 55 Fruit St, GRB 800 Boston, MA 02114. · Circulation. · Pubmed #18427127 links to  free full text

Abstract: BACKGROUND: Prior studies have demonstrated an inconsistent association between patients' arrival time for acute myocardial infarction (AMI) and their subsequent medical care and outcomes. METHODS AND RESULTS: Using a contemporary national clinical registry, we examined differences in medical care and in-hospital mortality among AMI patients admitted during regular hours (weekdays 7 am to 7 pm) versus off-hours (weekends, holidays, and 7 pm to 7 am weeknights). The study cohort included 62,814 AMI patients from the Get With the Guidelines-Coronary Artery Disease database admitted to 379 hospitals throughout the United States from July 2000 through September 2005. Overall, 33 982 (54.1%) patients arrived during off-hours. Compared with those arriving during regular hours, eligible off-hour patients were slightly less likely to receive primary percutaneous coronary intervention (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.89 to 0.98), had longer door-to-balloon times (median, 110 versus 85 minutes; P<0.0001), and were less likely to achieve door-to-balloon < or = 90 minutes (adjusted OR, 0.34; 95% CI, 0.29 to 0.39). Arrival during off-hours was associated with slightly lower overall revascularization rates (adjusted OR, 0.94; 95% CI, 0.90 to 0.97). No measurable differences, however, were found in in-hospital mortality between regular hours and off-hours in the overall AMI, ST-elevated MI, and non-ST-elevated MI cohorts (adjusted OR, 0.99; 95% CI, 0.93 to 1.06; adjusted OR, 1.05; 95% CI, 0.94 to 1.18; and adjusted OR, 0.97; 95% CI, 0.90 to 1.04, respectively). Similar observations were made across most age and sex subgroups and with an alternative definition for arrival time (weekends/holidays versus weekdays). CONCLUSIONS: Despite slightly fewer primary percutaneous coronary interventions and overall revascularizations and significantly longer door-to-balloon times, patients presenting with AMI during off-hours had in-hospital mortality similar to those presenting during regular hours.

Novaro GM, Asher CR, Bhatt DL, Moliterno DJ, Harrington RA, Lincoff AM, Newby LK, Tcheng JE, Hsu AP, Pinski SL. · Department of Cardiology, Cleveland Clinic Florida, Weston, Florida, USA. · Am J Cardiol. · Pubmed #18312767 No free full text.

Abstract: The development of atrial fibrillation (AF) in cardiac patients is multifactorial, including not well defined genetic factors. To determine if Asian ethnicity is associated with the development of AF in patients with coronary disease, a meta-analysis was conducted of patient-level data from 7 prospective randomized clinical trials that prospectively collected information on the development of AF: 3 trials in patients with ST-elevation myocardial infarction (Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] I, GUSTO III, and GUSTO V), 3 trials in patients with non-ST-elevation acute coronary syndromes (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy [PURSUIT], Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis-II [IMPACT II], and Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network [PARAGON A]), and 1 trial in patients with both conditions (GUSTO IIb). A total of 94,785 patients were identified (93,050 white, 1,735 Asian). At baseline, Asian patients were younger; had lower body mass indexes; had a lower prevalence of female gender, previous angioplasty, and previous coronary artery bypass grafting; and had a greater prevalence of diabetes compared with white patients. The development of AF was lower in Asian than in white patients (4.7% vs 7.6%, p <0.001), while rates of ventricular tachycardia and fibrillation were similar in the 2 groups. In multivariate logistic regression analysis, Asian ethnicity was associated with significantly lower rates of AF (odds ratio 0.65, 95% confidence interval 0.50 to 0.84, p = 0.001) compared with white ethnicity. In conclusion, similar to previous studies showing a lower incidence of AF in non-Caucasian populations, Asians experiencing acute ischemic syndromes have a significantly lower frequency of AF compared with whites. Further study is needed to investigate the mechanisms and potential genetic underpinnings behind this association.

Rao SV, Chiswell K, Sun JL, Granger CB, Newby LK, Van de Werf F, White HD, Armstong PW, Califf RM, Harrington RA. · The Duke Clinical Research Institute, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #18157960 No free full text.

Abstract: The purpose of this study was to determine international patterns of blood transfusion in patients with acute coronary syndrome (ACS). Previous studies showed geographic heterogeneity in some aspects of ACS care. Data for variability in the use of blood transfusion in ACS management are limited. Pooled data from 3 international randomized trials of patients with non-ST-segment elevation ACS (n = 23,906) were analyzed to determine the association between non-United States (US) location and blood transfusion after stratifying by the use of invasive procedures. The analysis adjusted for differences in patient characteristics and was repeated using a 2-stage mixed-model approach and in patients who underwent in-hospital coronary artery bypass grafting. Compared with US patients, both unadjusted and adjusted hazards for blood transfusion were significantly lower in non-US patients who did not undergo invasive procedures (unadjusted hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.17 to 0.33; adjusted HR 0.20, 95% CI 0.14 to 0.28). This was also true in non-US patients who underwent invasive procedures (unadjusted HR 0.34, 95% CI 0.27 to 0.44; adjusted HR 0.31, 95% CI 0.23 to 0.42). Results were similar in both validation analyses. In conclusion, there was substantial international variation in blood transfusion use in patients with ACS. These results, along with the controversy regarding the appropriate use of transfusion in patients with coronary heart disease, emphasize the need for understanding the role of blood transfusion in the management of patients with ACS and factors that influence transfusion decisions.

Sherwood A, Bower JK, McFetridge-Durdle J, Blumenthal JA, Newby LK, Hinderliter AL. · Duke University Medical Center, Durham, NC 27710, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #17541023 links to  free full text

Abstract: OBJECTIVE: We evaluated age and coronary heart disease (CHD) as potential moderators of the effects of 17beta-estradiol on vascular endothelial function in postmenopausal women. METHODS AND RESULTS: In a double-blind crossover design, 100 postmenopausal women aged 50 to 80 years were randomized to each of 3 transdermal patches, releasing 17beta-estradiol (0.05 mg/d), 17beta-estradiol (0.05 mg/d) + norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated dilation (FMD) and response to 400 microg sublingual glyceryl trinitrate (GTN-D) were assessed approximately 18 hours after patch placement. Age, but not CHD, moderated the FMD response to treatment (P=0.01). For women in their fifties, the estradiol patch was associated with improved FMD (7.69+/-4.79%) compared with placebo (4.81+/-5.97%, P<0.05), but the estradiol+norethindrone patch response (5.81+/-4.85%) was not significantly different from placebo. Women in their sixties and seventies showed no alterations in FMD response to either active patch. GTN-D response declined with advancing age (P<0.01), with women in their seventies exhibiting blunted GTN-D response compared with younger women. CONCLUSIONS: The cardiovascular benefits of natural estrogen supplementation on vascular endothelial function may be dependent on postmenopausal age, with improved vascular function evident only in the early postmenopausal years. Short-term FMD response to estradiol might help stratify individual differences in risks versus benefits of HRT.

Roe MT, Halabi AR, Mehta RH, Chen AY, Newby LK, Harrington RA, Smith SC, Ohman EM, Gibler WB, Peterson ED. · Duke University Medical Center, Duke Clinical Research Institute, Durham, NC 27705, USA. · Am Heart J. · Pubmed #17383286 No free full text.

Abstract: BACKGROUND: Although documented traditional cardiovascular risk factors (hypertension, diabetes, smoking, and dyslipidemia) increase the risk of developing coronary artery disease, their influence on the treatments and outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) has not been fully elucidated. METHODS: Using data from the CRUSADE Quality Improvement Initiative, we sought to characterize the effect that the absence of documented traditional risk factors has on inhospital treatments and outcomes in a population of patients with NSTEMI treated in routine practice. We compared clinical characteristics and inhospital outcomes according to the presence and number of risk factors in 74,220 patients with NSTEMI (defined as creatine kinase-MB and/or troponin I/T values above the local upper limit of normal) treated in 476 US hospitals from January 2001 through March 2004. RESULTS: The 7755 (10.5%) patients with no documented traditional risk factors on admission were less likely to receive short-term guideline-recommended therapies and revascularization procedures. Despite a higher prevalence of normal left ventricular function and insignificant angiographic coronary artery disease, these patients had a slightly higher risk of adjusted inhospital mortality (odds ratio 1.15, 95% CI 1.03-1.29) compared with patients with any combination of risk factors. CONCLUSIONS: Patients without documented traditional cardiovascular risk factors represent 10.5% of the non-ST-segment elevation myocardial infarction population. Because the absence of documented traditional risk factors does not yield a favorable prognosis, further study is needed to delineate the effects of the interplay between novel and documented traditional risk factors and treatment differences on the outcomes of these patients.

Echols MR, Mahaffey KW, Banerjee A, Pieper KS, Stebbins A, Lansky A, Cohen MG, Velazquez E, Santos R, Newby LK, Gurfinkel EP, Biasucci L, Ferguson JJ, Califf RM. · Duke Clinical Research Institute, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #17261389 No free full text.

Abstract: Management and outcomes of patients with acute coronary syndromes (ACSs) may vary according to patient race and ethnicity. To assess racial differences in presentation and outcome in high-risk North American patients with non-ST-segment elevation (NSTE) ACS, we analyzed baseline racial/ethnic differences and all-cause death or nonfatal myocardial infarction (MI) in 6,077 white, 586 African-American, and 344 Hispanic patients through 30-day, 6-month, and 1-year follow-up. Frequencies of hypertension were 66% for whites, 83% for African-Americans, and 78% for Hispanics (overall p <0.001). Use of angiography was similar across groups. Use of percutaneous coronary intervention (46% for whites, 41% for African-Americans, and 45% for Hispanics, overall p = 0.046) and coronary artery bypass grafting (20% for whites, 16% for African-Americans, and 22% for Hispanics, overall p = 0.044) differed. African-American patients had significantly fewer diseased vessels compared with white patients (p = 0.0001). Thirty-day death or MI was 14% for whites, 10% for African-Americans, and 14% for Hispanics (overall p = 0.034). After adjustment for baseline variables, African-American patients had lower 30-day death or MI compared with white patients (odds ratio 0.73, 95% confidence interval 0.55 to 0.98). There were no differences in 6-month death or MI across racial/ethnic groups. In conclusion, baseline clinical characteristics differed across North American racial/ethnic groups in the SYNERGY trial. African-American patients had significantly better adjusted 30-day outcomes but similar 6-month outcomes compared with white patients.

Patel MR, Chen AY, Peterson ED, Newby LK, Pollack CV, Brindis RG, Gibson CM, Kleiman NS, Saucedo JF, Bhatt DL, Gibler WB, Ohman EM, Harrington RA, Roe MT. · Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. · Am Heart J. · Pubmed #16996828 No free full text.

Abstract: BACKGROUND: Unlike ST-segment elevation myocardial infarction, the degree of stenosis and physiology of ischemia varies in patients with non-ST-segment elevation myocardial infarction (NSTEMI). The prevalence, predictors, and outcomes of patients with NSTEMI who lack significant epicardial coronary artery disease (CAD) in routine clinical practice remain poorly characterized. We sought to determine the prevalence, predictors, and outcomes of patients with NSTEMI and insignificant CAD. METHODS: We analyzed 38301 patients with NSTEMI in the CRUSADE quality improvement initiative who underwent cardiac catheterization to determine the prevalence and factors associated with insignificant CAD (all coronary stenoses <50%) and inhospital outcomes for patients with and without CAD. A multivariable model was used to determine the factors associated with insignificant CAD. RESULTS: A total of 3306 (8.6%) of 38301 patients had insignificant CAD. The strongest multivariable predictors of insignificant CAD were female sex (odds ratio 2.8, 95% CI 2.6-3.1), younger age (odds ratio per 10-year decrease 1.5, 95% CI 1.5-1.6), and lack of current/recent smoking (odds ratio 1.9, 95% CI 1.7-2.0). Inhospital rates of death were 0.65% for patients with insignificant CAD compared with 2.36% for patients with CAD (P < .0001). CONCLUSION: Insignificant CAD is present in 9% of patients with NSTEMI and is associated with a low incidence of adverse outcomes. The strongest predictors of insignificant CAD are female sex and younger age. These findings underscore the need for research to understand the pathophysiology of myocardial infarction in this population.

Xiong GL, Jiang W, Clare R, Shaw LK, Smith PK, Mahaffey KW, O'Connor CM, Krishnan KR, Newby LK. · Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #16784918 No free full text.

Abstract: Depression is increasingly recognized as an independent prognostic risk factor in patients with coronary artery disease and coronary artery bypass grafting (CABG). The use of selective serotonin reuptake inhibitors (SSRIs) for depression in patients with cardiac disease is becoming more prevalent. We examined the long-term outcomes of patients on SSRIs before CABG. We prospectively examined collected data in the Duke Databank for Cardiovascular Disease from January 1, 1999 to December 31, 2003. The median and maximum follow-up periods were 3 and 6 years, respectively. We screened patients who underwent CABG (n = 5,364) and excluded those who underwent simultaneous CABG and valvular surgery (n = 570). SSRI antidepressants included fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, venlafaxine, and clomipramine, and their use was determined from the inpatient pharmacy records during the index hospitalization. Outcomes included event-free survival from all-cause mortality, rehospitalization, and a composite end point of all-cause mortality or rehospitalization. Of 4,794 CABG-only patients, 246 (5.1%) took SSRIs before CABG. The SSRI group had a higher prevalence of diabetes, hypercholesterolemia, hypertension, cerebrovascular disease, peripheral vascular disease, and previous cardiovascular intervention. After adjustment for baseline differences, patients on SSRIs before CABG had increased risks of mortality, rehospitalization, and the composite end point (hazard ratio 1.61, 95% confidence interval 1.17 to 2.21, p = 0.003; hazard ratio 1.52, 95% confidence interval 1.30 to 1.77, p <0.0001; and hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, p <0.0001, respectively). In conclusion, SSRI use before CABG was associated with a higher risk of long-term post-CABG mortality and rehospitalization. The explanation behind these findings requires further research.

Newby LK, LaPointe NM, Chen AY, Kramer JM, Hammill BG, DeLong ER, Muhlbaier LH, Califf RM. · Centers for Education and Research on Therapeutics, Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. · Circulation. · Pubmed #16401776 links to  free full text

Abstract: BACKGROUND: Studies have examined the use of evidence-based therapies for coronary artery disease (CAD) in the short term and at hospital discharge, but few have evaluated long-term use. METHODS AND RESULTS: Using the Duke Databank for Cardiovascular Disease for the years 1995 to 2002, we determined the annual prevalence and consistency of self-reported use of aspirin, beta-blockers, lipid-lowering agents, and their combinations in all CAD patients and of angiotensin-converting enzyme inhibitors (ACEIs) in those with and without heart failure. Logistic-regression models identified characteristics associated with consistent use (reported on > or =2 consecutive follow-up surveys and then through death, withdrawal, or study end), and Cox proportional-hazards models explored the association of consistent use with mortality. Use of all agents and combinations thereof increased yearly. In 2002, 83% reported aspirin use; 61%, beta-blocker use; 63%, lipid-lowering therapy use; 54%, aspirin and beta-blocker use; and 39%, use of all 3. Consistent use was as follows: For aspirin, 71%; beta-blockers, 46%; lipid-lowering therapy, 44%; aspirin and beta-blockers, 36%; and all 3, 21%. Among patients without heart failure, 39% reported ACEI use in 2002; consistent use was 20%. Among heart failure patients, ACEI use was 51% in 2002 and consistent use, 39%. Except for ACEIs among patients without heart failure, consistent use was associated with lower adjusted mortality: Aspirin hazard ratio (HR), 0.58 and 95% confidence interval (CI), 0.54 to 0.62; beta-blockers, HR, 0.63 and 95% CI, 0.59 to 0.67; lipid-lowering therapy, HR, 0.52 and 95% CI, 0.42 to 0.65; all 3, HR, 0.67 and 95% CI, 0.59 to 0.77; aspirin and beta-blockers, HR, 0.61 and 95% CI, 0.57 to 0.65; and ACEIs among heart failure patients, HR, 0.75 and 95% CI, 0.67 to 0.84. CONCLUSIONS: Use of evidence-based therapies for CAD has improved but remains suboptimal. Although improved discharge prescription of these agents is needed, considerable attention must also be focused on understanding and improving long-term adherence.

Rao SV, O'Grady K, Pieper KS, Granger CB, Newby LK, Van de Werf F, Mahaffey KW, Califf RM, Harrington RA. · The Duke Clinical Research Institute, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #16253582 No free full text.

Abstract: Bleeding is a complication of current therapies for acute coronary syndrome (ACS). No studies have examined the effect of bleeding events on clinical outcomes. We analyzed pooled data from 4 multicenter, randomized clinical trials of patients who had ACS (n = 26,452) to determine an association between bleeding severity as measured by the GUSTO scale and 30-day and 6-month mortality rates using Cox proportional hazards modeling that incorporated bleeding as a time-dependent covariate. The analysis was repeated to examine procedure- and non-procedure-related bleeding and after censoring at the time of coronary artery bypass grafting. Of all the patients included, 27.6% had > or =1 bleeding episode. Patients who bled were older and sicker at presentation than were those who did not bleed. Unadjusted rates of 30-day and 6-month mortality increased as bleeding severity increased. There were stepwise increases in the adjusted hazards of 30-day mortality (mild bleeding, hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3 to 1.9; moderate bleeding, HR 2.7, 95% CI l 2.3 to 3.4; severe bleeding, HR 10.6, 95% CI 8.3 to 13.6) and 6-month mortality (mild bleeding, HR 1.4, 95% CI 1.2 to 1.6; moderate bleeding, HR 2.1, 95% CI 1.8 to 2.4; severe bleeding, HR 7.5, 95% CI 6.1 to 9.3) as bleeding severity increased. Results were consistent after censoring for coronary artery bypass grafting and for procedure- and non-procedure-related bleeds. In conclusion, the GUSTO bleeding classification identifies patients who are at risk for short- and long-term adverse events. Therapies that minimize bleeding risk and maintain an anticoagulant effect may improve outcomes among patients who have ACS.

Heitner JF, Curtis JP, Haq SA, Corey GR, Newby LK, Jollis JG. · Department of Medicine, Division of Cardiology, New York Methodist Hospital, 506 6th Street, 2 Buckley Pavilion, Brooklyn, NY 11215, USA. · Clin Cardiol. · Pubmed #16075826 No free full text.

Abstract: BACKGROUND: Patients with elevated troponin are at high risk of adverse outcomes, future cardiac events, and are more likely to have hemodynamically significant coronary artery stenoses. Elevated troponin T (cTnT) in patients with poor renal function portends a poor prognosis; however, findings of significant coronary artery disease (CAD) by coronary angiography have not been demonstrated in patients with poor renal function and elevated cTnT. HYPOTHESIS: The purpose of this study was to correlate the angiographic findings of patients with elevated cTnT with respect to renal function in patients with nondialysis-dependent renal insufficiency. METHODS: We retrospectively identified 342 patients with elevated cTnT who underwent coronary angiography in the setting of acute coronary syndrome. Patients were divided into poor (< 40 ml/min) and normal (> 40 ml/min) renal function by measuring their glomerular filtration rate. Our primary outcome was CAD stenosis, defined as epicardial stenosis > or = 70%. Secondary outcomes were rates of contrast nephropathy, initiation of hemodialysis, revascularization, length of stay (LOS), and in-hospital mortality. RESULTS: There was no significant difference in the prevalence of CAD between patients who had positive cTnT with poor renal function versus patients with positive cTnT and normal renal function (87.1 vs. 89.7%, p = 0.54). This finding persisted after stratifying by age. Patients with impaired renal function had a higher mortality, longer LOS, and a higher rate contrast nephropathy requiring hemodialysis. CONCLUSION: The association between elevated cTnT and significant CAD stenosis does not vary with renal function.

Kaul P, Newby LK, Fu Y, Mark DB, Goodman SG, Wagner GS, Harrington RA, Granger CB, Van de Werf F, Ohman EM, Armstrong PW, Anonymous00139. · University of Alberta, Edmonton, Alberta, Canada. · Heart. · Pubmed #15958353 links to  free full text

Abstract: OBJECTIVES: To examine the interaction between ST segment depression on the baseline ECG and subsequent in-hospital revascularisation on six month mortality among patients with non-ST elevation acute coronary syndromes. To examine whether ST segment depression influenced clinical decision making and whether there was international variation in the use of cardiac procedures across ST segment depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa antagonism for the reduction of acute coronary syndrome events in a global organisation network) -A, and PARAGON-B were studied. Patients were categorised as having no ST segment depression, 1 mm ST segment depression in two contiguous leads, and ST segment depression > or = 2 mm in two contiguous leads. International practice across four geographic regions was examined: USA, Canada, Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no impact on survival among patients with no ST segment depression; however, revascularisation was associated with a significant survival benefit among patients with ST segment depression > or = 1 mm. There was an inverse relation between the extent of ST segment depression and the use of angiography as well as angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm were more likely to undergo bypass surgery. The only significant trend of increasing use of revascularisation procedures with increasing ST segment depression was observed in the USA. CONCLUSIONS: International practice patterns in procedure use appear to be insensitive to the extent of ST segment depression. Major opportunities for more efficient delivery of care exist in all regions.

McGuire DK, Newby LK, Bhapkar MV, Moliterno DJ, Hochman JS, Klein WW, Weaver WD, Pfisterer M, Corbalán R, Dellborg M, Granger CB, Van De Werf F, Topol EJ, Califf RM, Anonymous00416. · Donald W. Reynolds Cardiovascular Clinical Research Center at the University of Texas-Southwestern Medical Center, Dallas, Tex, USA. · Am Heart J. · Pubmed #14760321 No free full text.

Abstract: BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.

Wang Q, Rao S, Shen GQ, Li L, Moliterno DJ, Newby LK, Rogers WJ, Cannata R, Zirzow E, Elston RC, Topol EJ. · Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA. · Am J Hum Genet. · Pubmed #14732905 links to  free full text

Abstract: The most frequent causes of death and disability in the Western world are atherosclerotic coronary artery disease (CAD) and acute myocardial infarction (MI). This common disease is thought to have a polygenic basis with a complex interaction with environmental factors. Here, we report results of a genomewide search for susceptibility genes for MI in a well-characterized U.S. cohort consisting of 1,613 individuals in 428 multiplex families with familial premature CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4+/-9.7 years. Genotyping was performed at the National Heart, Lung, and Blood Institute Mammalian Genotyping Facility through use of 408 markers that span the entire human genome every 10 cM. Linkage analysis was performed with the modified Haseman-Elston regression model through use of the SIBPAL program. Three genomewide scans were conducted: single-point, multipoint, and multipoint performed on of white pedigrees only (92% of the cohort). One novel significant susceptibility locus was detected for MI on chromosomal region 1p34-36, with a multipoint allele-sharing P value of <10(-12) (LOD=11.68). Validation by use of a permutation test yielded a pointwise empirical P value of.00011 at this locus, which corresponds to a genomewide significance of P<.05. For the less restrictive phenotype of CAD, no genetic locus was detected, suggesting that CAD and MI may not share all susceptibility genes. The present study thus identifies a novel genetic-susceptibility locus for MI and provides a framework for the ultimate cloning of a gene for the complex disease MI.

McCarthy JJ, Meyer J, Moliterno DJ, Newby LK, Rogers WJ, Topol EJ, Anonymous00305. · School of Public Health, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-4162, USA. · Hum Genet. · Pubmed #14557872 No free full text.

Abstract: Major genetic determinants of the metabolic syndrome - a clustering of abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high fasting glucose - remain elusive. We surveyed 207 single-nucleotide polymorphisms in 110 candidate genes among coronary artery disease patients, a population enriched for metabolic abnormalities. The number of abnormalities (0-5) was determined in the 214 male and 91 female patients, and the association with each polymorphism evaluated by means of ordinal regression analysis. Polymorphisms in eight genes, including LDLR, GBE1, IL1R1, TGFB1, IL6, COL5A2, SELE and LIPC, were associated with metabolic syndrome in the whole population ( P values ranged from 0.047 to 0.008). Variants in seven additional genes showed significant gene by gender interaction. Among these, separate analyses in men and women revealed a strong association with a silent polymorphism in the low-density lipoprotein receptor-related protein gene, LRPAP1, among females ( P=0.0003), but not males ( P=0.292). Other genes associated only in females included THBS1, ACAT2, ITGB3, F2 and SELP ( P values ranging from 0.032 to 0.002). Only one gene ( PRCP) was significantly associated in men alone ( P=0.039). Our results propose several new candidate genes for the metabolic syndrome and suggest that the genetic basis of this syndrome may be strongly modified by gender.

Sánchez CD, Newby LK, Hasselblad V, McNulty SE, Storrow AB, Gibler WB, Garvey JL, Schreiber DH, Tucker JF, Ohman EM. · Duke University School of Medicine and Duke Clinical Research Institute, Durham, North Carolina 27715-7969, USA. · Am J Cardiol. · Pubmed #12745106 No free full text.

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Newby LK, Califf RM, White HD, Harrington RA, Van de Werf F, Granger CB, Simes RJ, Hasselblad V, Armstrong PW. · Duke Clinical Research Institute, Durham, North Carolina 27707, USA. · Am J Med. · Pubmed #12034415 No free full text.

Abstract: PURPOSE: Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations have failed to show benefit and have been associated with increased mortality. To understand these findings, we performed a meta-analysis of results from four phase 3 trials. SUBJECTS AND METHODS: Trials were identified by MEDLINE search; review of abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions; or querying investigators in the field. Published, phase 3, randomized, placebo-controlled trials involving more than 1000 patients with coronary artery disease that compared an oral glycoprotein IIb/IIIa antagonist with or without background aspirin versus aspirin, and that had a planned follow-up of > or =30 days, were included. Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were generated from results, and combined using an empirical Bayes random-effects model. RESULTS: Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31% increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI: 1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among patients with acute coronary syndromes, the incidence of myocardial infarction was increased (OR = 1.16; 95% CI: 1.03 to 1.29). CONCLUSION: Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality and myocardial infarction. No single explanation for these findings is satisfactory; the problem is likely to be multifactorial.