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1.  Computed tomography-based diagnosis of diffuse compensatory enlargement of coronary arteries using scaling power laws 
Glagov's positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9±16.1 versus 91.5±13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length–volume scaling power law ( where Lc and Vc are crown length and volume) were found for both the high-fat and control groups (R2 = 0.95±0.04 and 0.99±0.01, respectively). The coefficient, KLV, decreased significantly in the high-fat diet group when compared with the control (14.6±2.6 versus 40.9±5.6). The flow–length scaling power law, however, was nearly unaffected by the positive remodelling. The length–volume and flow–length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. KLV < 18 in the length–volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans.
doi:10.1098/rsif.2012.1015
PMCID: PMC3627114  PMID: 23365197
coronary compensatory enlargement; scaling power law; computed tomography
3.  P2RY1 and P2RY12 polymorphisms and on-aspirin platelet reactivity in patients with coronary artery disease 
SUMMARY
Introduction
Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated.
Materials and Methods
Platelet reactivity was assessed by light transmission aggregometry and TxB2 assay in 423 CAD (coronary artery disease) patients on aspirin. High residual platelet reactivity (RPR) was defined by≥20% and ≥70% maximal aggregation stimulated with 0.5 mg/mL AA and 10 μM ADP, respectively. Moderate RPR was considered aggregation ≥20% with AA, ≥70% with ADP, or ≥1 ng/mL stimulated TxB2. Fourteen P2RY1 and 35 P2RY12 SNPs were genotyped.
Results
High RPR was detected in 24% of the patients. Moderate RPR was observed in 31% with AA, 57% with 5 μM ADP, and 82% with 10 μM ADP. Stimulated TxB2 was ≥1 ng/mL in 23% of patients. P2RY12 SNP rs9859538 was associated with high RPR (OR=2.16, 95% CI=1.24–3.75, p-value=0.004). Four P2RY12 SNPs, rs1491974, rs10513398, rs3732765, and rs10935841, showed association with moderate RPR (OR=1.79–2.94, p-value=0.04–0.028), while five, rs7615865, rs1388623, rs1388622, rs7634096, and rs7637803, were associated with low RPR (OR=0.50–0.55, p-value=0.008–0.026), following ADP stimulation. TxB2 level <1 ng/mL was linked to five P2RY1 SNPs, rs1439010, rs1371097, rs701265, rs12497578, and rs2312265, (OR=0.36–0.54, p-value=0.003–0.039).
Conclusions
Polymorphisms in P2RY1 and P2RY12 are associated with on-aspirin platelet reactivity in CAD patients.
doi:10.1111/j.1751-553X.2012.01420.x
PMCID: PMC3419334  PMID: 22574824
Coronary artery disease; aspirin; platelet reactivity; P2RY1 and P2RY12 receptors; SNP
4.  Use of Hydralazine‐Isosorbide Dinitrate Combination in African American and Other Race/Ethnic Group Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction 
Background
Hydralazine‐isosorbide dinitrate (H‐ISDN) therapy is recommended for African American patients with moderate to severe heart failure with reduced ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical characteristics associated with H‐ISDN therapy in clinical practice are unknown.
Methods and Results
An observational analysis of 54 622 patients admitted with HFrEF and discharged home from 207 hospitals participating in the Get With The Guidelines–Heart Failure registry from April 2008 to March 2012 was conducted to assess prescription, trends, and predictors of use of H‐ISDN among eligible patients. Among 11 185 African American patients eligible for H‐ISDN therapy, only 2500 (22.4%) received H‐ISDN therapy at discharge. In the overall eligible population, 5115 of 43 498 (12.6%) received H‐ISDN at discharge. Treatment rates increased over the study period from 16% to 24% among African Americans and from 10% to 13% among the entire HFrEF population. In a multivariable model, factors associated with H‐ISDN use among the entire cohort included younger age; male sex; African American/Hispanic ethnicity; and history of diabetes, hypertension, anemia, renal insufficiency, higher systolic blood pressure, and lower heart rate. In African American patients, these factors were similar; in addition, being uninsured was associated with lower use.
Conclusions
Overall, few potentially eligible patients with HFrEF are treated with H‐ISDN, and among African‐Americans fewer than one‐fourth of eligible patients received guideline‐recommended H‐ISDN therapy. Improved ways to facilitate use of H‐ISDN therapy in African American patients with HFrEF are needed.
doi:10.1161/JAHA.113.000214
PMCID: PMC3828812  PMID: 23966379
guideline adherence; heart failure; quality; race/ethnicity; registry
5.  Polyvascular Disease and Long-term Cardiovascular Outcomes in Older Patients with Non–ST-segment Elevation Myocardial Infarction 
Background
The impact of polyvascular disease (peripheral arterial disease [PAD] and/or cerebrovascular disease [CVD]) on long-term cardiovascular outcomes among older patients with acute myocardial infarction (MI) has not been well studied.
Methods
Non–ST-elevation MI (NSTEMI) patients aged ≥65 years from the CRUSADE registry who survived to hospital discharge were linked to longitudinal data from the Centers for Medicare and Medicaid Services (n=34,205). All patients were presumed to have coronary artery disease (CAD) and were classified into 4 groups: 10.7% had prior CVD (CAD+CVD group); 11.5% had prior PAD (CAD+PAD); 3.1% had prior PAD and CVD (CAD+PAD+CVD); and 74.7% had no polyvascular disease (CAD alone). Cox proportional hazard modeling was used to examine the hazard of long-term mortality and the composite of death, readmission for MI, or readmission for stroke (median follow-up 35 months, IQR 17–49) among the 4 groups.
Results
Compared with the CAD-alone group, patients with polyvascular disease had a greater comorbidity burden, were less likely to undergo revascularization, and less often received recommended discharge interventions. Three-year mortality rates increased with a greater number of arterial beds involved: 33% for CAD alone, 49% for CAD+PAD, 52% for CAD+CVD, and 59% for CAD+PAD+CVD. Relative to the CAD-alone group, patients with all 3 arterial beds involved had the highest risk of long-term mortality (adjusted HR [95% CI]: 1.49 [1.38–1.61], with a lower risk for those with CAD+CVD, 1.38 [1.31–1.44], and those with CAD+PAD, 1.29 [1.23–1.35]). Similarly, the adjusted risk of long-term composite ischemic events was highest among the CAD+PAD+CVD group.
Conclusions
Older NSTEMI patients with polyvascular disease have substantially higher long-term risk, such that the 3-year mortality rate is >50%. Future studies targeting greater adherance to secondary prevention strategies and novel therapies are needed to help reduce long-term cardiovascular events in this vulnerable population.
doi:10.1161/CIRCOUTCOMES.111.964379
PMCID: PMC3707283  PMID: 22715460
6.  Paradoxical Association of Smoking With In‐Hospital Mortality Among Patients Admitted With Acute Ischemic Stroke 
Background
Compared to those who never smoked, a paradoxical effect of smoking on reducing mortality in patients admitted with myocardial ischemia has been reported. We sought to determine if this effect was present in patients hospitalized with ischemic stroke.
Methods and Results
Using the local Get with the Guidelines‐Stroke registry, we analyzed 4305 consecutively admitted ischemic stroke patients (March 2002–December 2011). The sample was divided into smokers versus nonsmokers. The main outcome of interest was the overall inpatient mortality. Compared to nonsmokers, tobacco smokers were younger, more frequently male and presented with fewer stroke risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, and atrial fibrillation. Smokers also had a lower average NIH Stroke Scale (NIHSS) and fewer received tissue plasminogen activator (tPA). Patients in both groups had similar adherence to early antithrombotics, dysphagia screening prior to oral intake, and deep vein thrombosis (DVT) prophylaxis. Smoking was associated with lower all‐cause in‐hospital mortality (6.6% versus 12.4%; unadjusted OR 0.46; CI [0.34 to 0.63]; P<0.001). In multivariable analysis, adjusted for age, gender, ethnicity, hypertension, diabetes mellitus, hyperlipidemia, CAD, atrial fibrillation, NIHSS, and tPA, smoking remained independently associated with lower mortality (adjusted OR 0.64; CI [0.42 to 0.96]; P=0.03).
Conclusions
Similar to myocardial ischemia, smoking was independently associated with lower inpatient mortality in acute ischemic stroke. This effect may be due to tobacco‐induced changes in cerebrovascular vasoreactivity, or may be due in part to residual confounding. Larger, multicenter studies are needed to confirm the finding and the effect on 30‐day and 1‐year mortality.
doi:10.1161/JAHA.113.000171
PMCID: PMC3698779  PMID: 23782919
cerebrovascular disease; embolic stroke; mortality; thrombolysis
7.  Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes 
The New England Journal of Medicine  2012;366(17):1567-1576.
BACKGROUND
Observational studies have shown improvement in patients with type 2 diabetes mellitus after bariatric surgery.
METHODS
In this randomized, nonblinded, single-center trial, we evaluated the efficacy of intensive medical therapy alone versus medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy in 150 obese patients with uncontrolled type 2 diabetes. The mean (±SD) age of the patients was 49 ± 8 years, and 66% were women. The average glycated hemoglobin level was 9.2 ± 1.5%. The primary end point was the proportion of patients with a glycated hemoglobin level of 6.0% or less 12 months after treatment.
RESULTS
Of the 150 patients, 93% completed 12 months of follow-up. The proportion of patients with the primary end point was 12% (5 of 41 patients) in the medical-therapy group versus 42% (21 of 50 patients) in the gastric-bypass group (P = 0.002) and 37% (18 of 49 patients) in the sleeve-gastrectomy group (P = 0.008). Glycemic control improved in all three groups, with a mean glycated hemoglobin level of 7.5 ± 1.8% in the medical-therapy group, 6.4 ± 0.9% in the gastric-bypass group (P<0.001), and 6.6 ± 1.0% in the sleeve-gastrectomy group (P = 0.003). Weight loss was greater in the gastric-bypass group and sleeve-gastrectomy group (−29.4 ± 9.0 kg and −25.1 ± 8.5 kg, respectively) than in the medical-therapy group (−5.4 ± 8.0 kg) (P<0.001 for both comparisons). The use of drugs to lower glucose, lipid, and blood-pressure levels decreased significantly after both surgical procedures but increased in patients receiving medical therapy only. The index for homeostasis model assessment of insulin resistance (HOMA-IR) improved significantly after bariatric surgery. Four patients underwent reoperation. There were no deaths or life-threatening complications.
CONCLUSIONS
In obese patients with uncontrolled type 2 diabetes, 12 months of medical therapy plus bariatric surgery achieved glycemic control in significantly more patients than medical therapy alone. Further study will be necessary to assess the durability of these results. (Funded by Ethicon Endo-Surgery and others; ClinicalTrials.gov number, NCT00432809.)
doi:10.1056/NEJMoa1200225
PMCID: PMC3372918  PMID: 22449319
8.  Trends in Clinical, Demographic, and Biochemical Characteristics of Patients With Acute Myocardial Infarction From 2003 to 2008: A Report From the American Heart Association Get With The Guidelines Coronary Artery Disease Program 
Background
An analysis of the changes in the clinical and demographic characteristics of patients with acute myocardial infarction could identify successes and failures of risk factor identification and treatment of patients at increased risk for cardiovascular events.
Methods and Results
We reviewed data collected from 138 122 patients with acute myocardial infarction admitted from 2003 to 2008 to hospitals participating in the American Heart Association Get With The Guidelines Coronary Artery Disease program. Clinical, demographic, and laboratory characteristics were analyzed for each year stratified on the electrocardiogram at presentation. Patients with non–ST-segment–elevation myocardial infarction were older, more likely to be women, and more likely to have hypertension, diabetes mellitus, and a history of past cardiovascular disease than were patients with ST-elevation myocardial infarction. In the overall patient sample, significant trends were observed of an increase over time in the proportions of non–ST-segment–elevation myocardial infarction, patient age of 45 to 65 years, obesity, and female sex. The prevalence of diabetes mellitus decreased over time, whereas the prevalences of hypertension and smoking were substantial and unchanging. The prevalence of “low” high-density lipoprotein increased over time, whereas that of “high” low-density lipoprotein decreased. Stratum-specific univariate analysis revealed quantitative and qualitative differences between strata in time trends for numerous demographic, clinical, and biochemical measures. On multivariable analysis, there was concordance between strata with regard to the increase in prevalence of patients 45 to 65 years of age, obesity, and “low” high-density lipoprotein and the decrease in prevalence of “high” low-density lipoprotein. However, changes in trends in age distribution, sex ratio, and prevalence of smokers and the magnitude of change in diabetes mellitus prevalence differed between strata.
Conclusions
There were notable differences in risk factors and patient characteristics among patients with ST-elevation myocardial infarction and those with non–ST-segment–elevation myocardial infarction. The increasing prevalence of dysmetabolic markers in a growing proportion of patients with acute myocardial infarction suggests further opportunities for risk factor modification. (J Am Heart Assoc. 2012;1:e001206 doi: 10.1161/JAHA.112.001206.)
doi:10.1161/JAHA.112.001206
PMCID: PMC3487339  PMID: 23130159
coronary disease; epidemiology; myocardial infarction; population; risk factors
9.  Clopidogrel resistance – A clear problem with an unclear solution 
Indian Heart Journal  2012;64(4):353-355.
doi:10.1016/j.ihj.2012.06.002
PMCID: PMC3861305  PMID: 22929816
10.  Ethnic Differences in Cardiovascular Risks and Mortality in Atherothrombotic Disease: Insights From the REduction of Atherothrombosis for Continued Health (REACH) Registry 
Mayo Clinic Proceedings  2011;86(10):960-967.
OBJECTIVE: To determine whether ethnic-specific differences in the prevalence of cardiovascular risk factors and outcomes exist worldwide among individuals with stable arterial disease.
PATIENTS AND METHODS: From December 1, 2003, to June 30, 2004, the prospective, observational REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled 49,602 out-patients with coronary artery disease, cerebrovascular disease, and/or peripheral arterial disease from 7 predefined ethnic/racial groups: white, Hispanic, East Asian, South Asian, Other Asian, black, and Other (comprising any race distinct from those specified). The baseline demographic and risk factor profiles, medication use, and 2-year cardiovascular outcomes were assessed among these groups.
RESULTS: The prevalence of traditional atherothrombotic risk factors varied significantly among the ethnic/racial groups. The use of medical therapies to reduce risk was comparable among all groups. At 2-year follow-up, the rate of cardiovascular death was significantly higher in blacks (6.1%) compared with all other ethnic/racial groups (3.9%; P=.01). Cardiovascular death rates were significantly lower in all 3 Asian ethnic/racial groups (overall, 2.1%) compared with the other groups (4.5%; P<.001).
CONCLUSION: The REACH Registry, a large international study of individuals with atherothrombotic disease, documents the important ethnic-specific differences in cardiovascular risk factors and variations in cardiovascular mortality that currently exist worldwide.
doi:10.4065/mcp.2011.0010
PMCID: PMC3184025  PMID: 21964173
11.  One-year costs associated with cardiovascular disease in Canada: Insights from the REduction of Atherothrombosis for Continued Health (REACH) registry 
The Canadian Journal of Cardiology  2010;26(8):e297-e305.
BACKGROUND AND OBJECTIVES:
To provide a contemporary estimate of the economic burden of atherothrombosis in Canada, annual cardiovascular-related hospitalizations, medication use and associated costs across the entire spectrum of atherothrombotic disease were examined.
METHODS:
The REduction of Atherothrombosis for Continued Health (REACH) registry enrolled 1964 Canadian outpatients with coronary artery disease, cerebrovascular disease or peripheral arterial disease (PAD), or three or more cardiovascular risk factors. Baseline data on cardiovascular risk factors and associated medication use, and one-year follow-up data on cardiovascular events, hospitalizations, procedures and medication use were collected. Annual hospitalization and medication costs (Canadian dollars) were derived and compared among patients according to the presence of established atherothrombotic disease at baseline, specific arterial beds affected and the number of affected arterial beds.
RESULTS:
Average annualized medication costs were $1,683, $1,523 and $1,776 for patients with zero, one, and two or three symptomatic arterial beds, respectively. Average annual hospitalization costs increased significantly with the number of beds affected ($380, $1,403 and $3,465, respectively; P<0.0001 for overall linear trend). Mean hospitalization costs for patients with any coronary artery disease, any cerebrovascular disease and any PAD were $1,743, $1,823 and $4,677, respectively. After adjusting for other clinical factors, PAD at baseline was independently associated with a significant increase in hospitalization costs.
CONCLUSION:
Costs associated with vascular-related hospitalizations and interventions for Canadian patients increased with the number of affected arterial beds, and were particularly high for patients with PAD and/or polyvascular disease. These contemporary data provide insight into the economic burden associated with atherothrombotic disease in Canada, and highlight the need for increased preventive strategies to lessen the burden for patients and society.
PMCID: PMC2954538  PMID: 20931098
Cerebrovascular disease; Coronary disease; Costs; Hospitalization; Peripheral vascular disease
12.  Smoking, Clopidogrel, and Mortality in Patients with Established Cardiovascular Disease 
Circulation  2009;120(23):2337.
Background
Smoking increases platelet aggregability, and the degree of platelet inhibition by clopidogrel on ex vivo platelet function tests. Whether smoking status affects the relationship between clopidogrel and clinical outcomes is unknown.
Methods and Results
We evaluated the relationship between smoking status (current smoker (CS), former smoker (FS), and never smoker (NS)) and treatment with clopidogrel on the risk of all-cause, cardiovascular, and cancer mortality among the 12,152 participants from the CHARISMA trial with established cardiovascular disease. Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, [1.85–3.60]), cardiovascular (HR 2.26, [1.48–3.45]), and cancer mortality (HR 4.16, [2.46–7.03]) compared to NS. The impact of clopidogrel and mortality differed by smoking status (P for interaction = 0.018 for current smokers). Among CS, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, [0.49–0.94]); clopidogrel did not reduce all cause mortality among FS (HR 0.95, [0.75–1.19]) or NS (HR 1.14, [0.83–1.58]). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding seemed to differ according to smoking status; randomized clopidogrel was associated with a significantly increased hazard of severe or moderate bleeding (HR 1.62, P=0.04) among CS, but a smaller and nonsignificant increase among NS (HR 1.31, P=0.15).
Conclusion
Clopidogrel therapy may be more effective, but with a greater bleeding risk in CS than in patients who are not smokers. Further studies are needed to investigate this possibility.
doi:10.1161/CIRCULATIONAHA.109.866533
PMCID: PMC2814172  PMID: 19933933
Smoking; Clopidogrel; Mortality; Cardiovascular disease
13.  Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease 
European Heart Journal  2010;31(21):2601-2613.
Aims
Two multicentre, randomized, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease-activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD).
Methods and results
Patients with ACS (n = 241) or high-risk CAD (n = 263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and three CURE major bleeds (two with placebo; one with 100 mg E5555). There was a numerical increase in ‘any’ TIMI bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P = 0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major cardiovascular adverse events in the combined E5555 group was not different from placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0% E5555, P = 0.066). There was a statistically significant dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was >90% with 100 and 200 mg E5555, and 20–60% with 50 mg E5555.
Conclusion
E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Although further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy.
doi:10.1093/eurheartj/ehq320
PMCID: PMC2966970  PMID: 20805115
E5555; Atherothrombosis; Thrombin; PAR-1; Acute coronary syndrome; Coronary artery disease
14.  Risk score to predict serious bleeding in stable outpatients with or at risk of atherothrombosis 
European Heart Journal  2010;31(10):1257-1265.
Aims
To develop a risk score to quantify bleeding risk in outpatients with or at risk of atherothrombosis.
Methods and results
We studied patients in the REACH Registry, a cohort of 68 236 patients with/at risk of atherothrombosis. The outcome of interest was serious bleeding (non-fatal haemorrhagic stroke or bleeding leading to hospitalization and transfusion) over 2 years. Risk factors for bleeding were assessed using modified regression analysis. Multiple potential scoring systems based on the least complex models were constructed. Competing scores were compared on their discriminative ability via logistic regression. The score was validated externally using the CHARISMA population. From a final cohort of 56 616 patients, 804 (1.42%, 95% confidence interval 1.32–1.52) experienced serious bleeding between baseline and 2 years. A nine-item bleeding risk score (0–23 points) was constructed (age, peripheral arterial disease, congestive heart failure, diabetes, hypertension, smoking, antiplatelets, oral anticoagulants, hypercholesterolaemia). Observed incidence of bleeding at 2 years was: 0.46% (score ≤6); 0.95% (7–8); 1.25% (9–10); 2.76% (≥11). The score's discriminative performance was consistent in CHARISMA and REACH (c-statistics 0.64 and 0.68, respectively); calibration in the CHARISMA population was very good (modified Hosmer-Lemeshow c2 = 4.74; P = 0.69).
Conclusion
Bleeding risk increased substantially with a score >10. This score can assist clinicians in predicting the risk of serious bleeding and making decisions on antithrombotic therapy in outpatients.
doi:10.1093/eurheartj/ehq021
PMCID: PMC2869443  PMID: 20181681
Bleeding risk; Atherothrombosis; Antithrombotic therapy
15.  Three-year follow-up and event rates in the international REduction of Atherothrombosis for Continued Health Registry 
European Heart Journal  2009;30(19):2318-2326.
Aims
To determine 3-year event rates in outpatients with vascular disease enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry.
Methods and results
REACH enrolled 67 888 outpatients with atherothrombosis [established coronary artery disease (CAD), cerebrovascular disease, or peripheral arterial disease (PAD)], or with at least three atherothrombotic risk factors, from 44 countries. Among the 55 499 patients at baseline with symptomatic disease, 39 675 were eligible for 3-year follow-up, and 32 247 had data available (81% retention rate). Among the symptomatic patients at 3 years, 92% were taking an antithrombotic agent, 91% an antihypertensive, and 76% were on lipid-lowering therapy. For myocardial infarction (MI)/stroke/vascular death, 1- and 3-year event rates for all patients were 4.2 and 11.0%, respectively. Event rates (MI/stroke/vascular death) were significantly higher for patients with symptomatic disease vs. those with risk factors only at 1 year (4.7 vs. 2.3%, P < 0.001) and at 3 years (12.0 vs. 6.0%, P < 0.001). One and 3-year rates of MI/stroke/vascular death/rehospitalization were 14.4 and 28.4%, respectively, for patients with symptomatic disease. Rehospitalization for a vascular event other than MI/stroke/vascular death was common at 3 years (19.0% overall; 33.6% for PAD; 23.0% for CAD). For patients with symptomatic vascular disease in one vascular bed vs. multiple vascular beds, 3-year event rates for MI/stroke/vascular death/rehospitalization were 25.5 vs. 40.5% (P < 0.001).
Conclusion
Despite contemporary therapy, outpatients with symptomatic atherothrombotic vascular disease experience high rates of recurrent vascular events and rehospitalizations.
doi:10.1093/eurheartj/ehp355
PMCID: PMC2755116  PMID: 19720633
Atherothrombosis; Risk factors; Coronary artery disease; Cerebrovascular disease; Peripheral arterial disease
16.  Modifiable risk factors control and its relationship with 1 year outcomes after coronary artery bypass surgery: insights from the REACH registry 
European Heart Journal  2008;29(24):3052-3060.
Aims
To evaluate the influence of achieving secondary prevention target treatment goals for cardiovascular (CV) risk factors on clinical outcomes in patients with prior coronary artery bypass surgery (CABG).
Methods and results
Accordingly, we analysed treatment to target goals in patients with prior CABG and atherothrombotic disease or known risk factors (diabetes, hypertension, hypercholesterolaemia, smoking, obesity) enrolled in the global REduction in Atherothrombosis for Continued Health (REACH) Registry, and their association with 1 year outcomes. A total of 13 907 of 68 236 patients (20.4%) in REACH had a history of prior CABG, and 1 year outcomes data were available for 13 207 of these. At baseline <25, 25–<50, 50–<75, and ≥75% risk factors were at goal in 3.7, 12.9, 31.7, and 51.7% of patients, respectively. One-year composite rates of CV death, non-fatal MI, non-fatal stroke were inversely related to the proportion of risk factors at goal at baseline (age, gender, and region adjusted rates 6.1, 5.6, 5.2, and 4.3% of patients with <25, 25–<50, 50–<75, and >75% risk factors at goal, respectively; P for trend 0.059).
Conclusion
Risk-factor control varied greatly in CABG patients. Although CABG patients are frequently treated with appropriate therapies, these treatments fail to achieve an adequate level of prevention in many. This failure was associated with a trend for worse age-, gender-, and region-adjusted clinical outcomes. Thus, perhaps secondary prevention after CABG needs to focus on more comprehensive modification of risk factors to target goals in the hope of preventing subsequent CV events, and represents an opportunity to improve CV health.
doi:10.1093/eurheartj/ehn478
PMCID: PMC2638656  PMID: 18996953
Coronary disease; Bypass; Revascularization; Stroke; Risk factors
17.  Cardiologists' and Emergency Physicians' Perspectives on and Knowledge of Reperfusion Guidelines Pertaining to ST-Segment–Elevation Myocardial Infarction 
Texas Heart Institute Journal  2008;35(2):152-161.
We sought to determine U.S. physicians' knowledge and perspectives regarding the 2004 American College of Cardiology/American Heart Association guidelines for management of patients who have ST-segment–elevation myocardial infarction (STEMI). We invited 45,998 physicians from the American Medical Association's roster to take an Internet survey of U.S. cardiologists and emergency physicians who were hospital-based or who had hospital-admitting privileges. To represent individual and combined populations, data were weighted on the basis of years in practice, sex, and geographic region. Of 505 cardiologists and 509 emergency physicians who completed the survey, 90% worked in an urban or suburban setting and 82% at hospitals with a cardiac catheterization laboratory. Sampling error was ±3.4%. Most respondents (61%) believed that overall myocardial infarction treatment needed a “great deal” or “fair amount” of improvement; 24% were “somewhat” or “not at all” familiar with the guidelines. Although 84% knew the recommended STEMI treatments for a patient who presents within 3 hours of symptom onset without contraindications to reperfusion or delay to invasive treatment, only 11% knew that there is no preferred approach. If percutaneous coronary intervention proved impossible within 90 minutes of presentation, 21% reported that eligible patients—assuming early presentation, confirmed STEMI diagnosis, and no high-risk STEMI or contraindications to fibrinolysis—would “rarely” or “never” receive guideline-recommended fibrinolysis.
Many cardiologists and emergency physicians are unfamiliar with the guidelines and with the uncertainty that surrounds therapeutic approaches, which suggests the need for increased education on effective treatments to expedite myocardial reperfusion in STEMI.
PMCID: PMC2435452  PMID: 18612446
Angioplasty, transluminal, percutaneous coronary/standards/utilization; cardiovascular diseases/epidemiology/mortality; chronology as topic; delivery of health care/standards; fibrinolysis; guideline adherence; hospitals/standards; practice guidelines as topic; quality assurance/health care; randomized controlled studies as topic; statistics & numerical data; statistics as topic; time factors; treatment outcome
18.  Debate: PCI or CABG for multivessel disease? Viewpoint: No clear winner in an unfair fight 
The Arterial Revascularization Therapy Study (ARTS) and the Stent or Surgery (SoS) trial each randomized patients with multivessel disease to either stenting or bypass surgery. The ARTS showed no difference in mortality between the two strategies, other than in diabetic patients, who fared better with surgery. The SoS trial demonstrated increased mortality in the stent arm, a difference that was not attributable to diabetes. Both trials found that the rates of repeat revascularization were lower with surgery, although the rate with stenting was much lower than had been seen in previous trials of angioplasty. Use of antiplatelet therapy such as intravenous glycoprotein IIb/IIIa inhibitors, especially with their pronounced effects in diabetics and in those with multivessel disease, could potentially equalize the playing field or perhaps even tip the balance in favor of percutaneous intervention.
doi:10.1186/cvm-2-6-260
PMCID: PMC64821  PMID: 11806809
balloon angioplasty; coronary artery bypass surgery; diabetes; stents
19.  Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials 
Objective To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity.
Design Systematic review and meta-analysis based on a random effects model.
Data sources Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status.
Eligibility criteria Eligible studies were randomised controlled trials with ≥6 months of follow-up that included individuals with a body mass index ≥30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events.
Results The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference −26 kg (95% confidence interval −31 to −21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference −0.7 mmol/L (−1.0 to −0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%).
Conclusions Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals.
Systematic review registration PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).
doi:10.1136/bmj.f5934
PMCID: PMC3806364  PMID: 24149519

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