Hitinder S. Gurm

Profile and prevalence of aspirin resistance in patients with cardiovascular disease

We determined the prevalence and clinical predictors of aspirin resistance by prospectively studying 325 patients with stable cardiovascular disease who were receiving aspirin (325 mg/day for > or =7 days) but no other antiplatelet agents. We also compared the detection of aspirin resistance with optical platelet aggregation, a widely accepted method, with a newer, more rapid method, the platelet function analyzer (PFA)-100, a whole blood test that measures platelet adhesion and aggregation ex vivo. Blood samples were analyzed in a blinded fashion for aspirin resistance by optical aggregation using adenosine diphosphate (ADP) and arachidonic acid, and by PFA-100 using collagen and/or epinephrine and collagen and/or ADP cartridges to measure aperture closure time. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and a mean aggregation of > or =20% with 0.5 mg/ml arachidonic acid. Aspirin semiresponders were defined as meeting one, but not both of the above criteria. Aspirin resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time (< or =193 seconds). By optical aggregation, 5.5% of the patients were aspirin resistant and 23.8% were aspirin semiresponders. By PFA-100, 9.5% of patients were aspirin resistant. Of the 18 patients who were aspirin resistant by aggregation, 4 were also aspirin resistant by PFA-100. Patients who were either aspirin resistant or aspirin semiresponders were more likely to be women (34.4% vs 17.3%, p = 0.001) and less likely to be smokers (0% vs 8.3%, p = 0.004) compared with aspirin-sensitive patients. There was a trend toward increased age in patients with aspirin resistance or aspirin semiresponders (65.7 vs 61.3 years, p = 0.06). There were no differences in aspirin sensitivity by race, diabetes, platelet count, renal disease, or liver disease.

The impact of body mass index onshort- and long-term outcomes inpatients undergoing coronary revascularization: insights from the bypass angioplasty revascularization investigation (BARI)☆

OBJECTIVESnWe sought to investigate the impact of body mass index (BMI) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft surgery (CABG).nnnBACKGROUNDnEquivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG, and no long-term mortality data exist from a large series of revascularized patients.nnnMETHODSnFrom the randomized series and observational registry of the Bypass Angioplasty Revascularization Investigation (BARI), 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry. They were classified as follows: low (< 20 kg/m(2)), normal (20 to 24.9 kg/m(2)), overweight (25 to 29.9 kg/m(2)), class I obese (30 to 34.9 kg/m(2)) and class II/III obese (greater-than-or-equal 35 kg/m(2)). In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization.nnnRESULTSnAmong patients who had PTCA, each unit increase in BMI was associated with a 5.5% lower adjusted risk of a major in-hospital event (death, myocardial infarction, stroke, coma); among patients who had CABG, no difference in the in-hospital outcome was observed according to BMI. In contrast, BMI was not associated with five-year mortality in the PTCA group; among the CABG group, adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 (low), 1.0 (normal), 2.02 (overweight), 3.16 (class I obese) and 4.85 (class II/III obese) (linear p < 0.001).nnnCONCLUSIONSnBody mass index appears to have a differential impact on short- and long-term outcomes after coronary revascularization. These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG.

Renal failure after percutaneous coronary intervention is associated with high mortality

Renal failure is a marker of poor outcome in the general population. Renal failure after percutaneous coronary artery intervention (PCI) is associated with an increased hazard of in‐hospital mortality. We hypothesized that post‐PCI renal insufficiency would be a predictor of long‐term mortality in patients undergoing PCI who survive for over 30 days after the procedure. A retrospective analysis was conducted from a registry of 9,067 patients undergoing PCI at our center from 1997 to 2001. A rise in creatinine by 1 mg/dl from baseline was defined as post‐PCI renal insufficiency. Vital status was assessed using Social Security Death Index. There were a total of 996 deaths over a mean follow‐up period of 3.2 years. In a multivariate analysis, history of recent acute myocardial infarction, older age, insulin‐dependent diabetes, baseline creatinine greater than 1.5 mg/dl, and presence of mitral regurgitation were associated with post‐PCI renal insufficiency. Developing post‐PCI renal insufficiency was associated with a 4.31‐fold hazard of mortality in univariate analysis and a 1.77‐fold hazard after adjustment for known predictors of mortality after PCI. The 1‐year survival in patients with renal failure was 70.3% ± 3.91%, compared to a survival of 93.6% ± 0.27% in those without any post‐PCI renal insufficiency (P < 0.0001). Acute renal insufficiency after PCI is a strong and independent predictor of long‐term mortality in patients who survived for 30 days after the procedure. Catheter Cardiovasc Interv 2005;64:442–448.

Impact of preprocedural white blood cell count on long term mortality after percutaneous coronary intervention: insights from the EPIC, EPILOG, and EPISTENT trials

Background: Raised inflammatory markers are associated with worse outcome after percutaneous coronary interventions (PCI). An increase in the white blood cell (WBC) count is a non-specific response to inflammation. We hypothesised that a raised baseline WBC count would be a predictor of mortality in patients undergoing PCI. Methods: The association between preprocedural WBC count and long term mortality was studied in 7179 patients enrolled in the EPIC, EPILOG, and EPISTENT trials. The end points were the incidence of myocardial infarction at one year, and one and three year mortality. Results: There were 188 deaths and 582 myocardial infarctions at one year. While WBC count was a strong predictor of death at one year, with every increase of 1 k/μl (1×106/l) being associated with a hazard ratio (HR) of 1.109 (95% confidence interval (CI) 1.072 to 1.147, p < 0.001), there was no association with myocardial infarction at one year (HR 1.020, 95% CI 0.990 to 1.052, p = 0.195). There were a total of 406 deaths at three years with a strong association between WBC count and three year mortality (HR for every 1 k/μl increase 1.089, 95% CI 1.058 to 1.121, p < 0.001). WBC count remained a significant predictor of mortality after multivariable adjustment (HR for every 1 k/μl increase 1.100, 95% CI 1.069 to 1.131, p < 0.001). The association was significant across multiple subgroups, including diabetes, female sex, clinical presentation, and cigarette smoking. Conclusion: A raised pre-procedural WBC count in patients undergoing PCI is associated with an increased risk of long term death. These results suggest a key role for inflammation in coronary artery disease.

Preprocedural white blood cell count and death after percutaneous coronary intervention

BACKGROUNDnElevated inflammatory markers are associated with worse outcome after percutaneous coronary artery interventions (PCI). An elevation in the white blood cell (WBC) count is a nonspecific response to inflammation. We hypothesized that an elevated WBC count would be a predictor of death in patients undergoing PCI.nnnMETHODSnA total of 4450 patients undergoing percutaneous coronary artery intervention were divided into quintiles, based on their preprocedural WBC count (mean WBC count: quintile 1, 5.08 x 10(3)/muL; quintile 2, 6.58 x 10(3)/muL; quintile 3, 7.70 x 10(3)/muL; quintile 4, 9.14 x 10(3)/muL; and quintile 5, 13.4 x 10(3)/muL). Vital status was assessed through the use of the Social Security Death Index.nnnRESULTSnThere were a total of 504 deaths over a follow-up period of 48 months. The best survival was seen in quintile 2, with an increase in long-term mortality rates seen with both a higher or a lower WBC count (P <.001). This J-shaped curve was preserved after multivariate adjustment, with the adjusted hazard ratio of mortality relative to quintile 2 being 1.95 (95% CI, 1.40 to 2.73) in quintile 1, 1.66 (95% CI, 1.18 to 2.33) in quintile 3, 2.31 (95% CI, 1.67 to 3.17) in quintile 4, and 2.42 (95% CI, 1.76 to 3.34) in quintile 5.nnnCONCLUSIONSnA low or an elevated preprocedural WBC count in patients undergoing PCI is associated with an increased risk of long-term death. Our result provides further evidence to support the important role of inflammation in coronary artery disease.

Outcome of acute myocardial infarction in patients with prior coronary artery bypass grafting treated with combination reduced fibrinolytic therapy and abciximab

ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.

The ECG in acute coronary syndromes: new tricks from an old dog

The ECG remains the pre-eminent test for myocardial ischaemia, directing therapeutic management and prognostic stratification.

Predicting incidence of some critical events by sun signs—the Pisces study☆

Abstract Background Zodiac signs are believed to influence personality and health. Those born under the sun sign Leo are alleged to be big-hearted and at risk for heart disease. Methods We compared the demographic and exercise variables among a cohort of 32,386 patients undergoing stress testing at a large academic center. Further, we studied the association of Leo sun sign with long-term mortality. Results There were only minor differences in the baseline or exercise variables among Leos and the remainder of the cohort. There was a total of 2586 deaths over a period of 5 years. There was a slight excess of deaths among the Leos (9.6% vs. 8.7%). This relationship acquired a borderline significance after multivariate adjustment (hazard ratio, 1.17; 95% confidence interval [CI], 1.03 to 1.33, p=0.019). However, no significant difference in risk of mortality was seen in a propensity-adjusted model (adjusted hazard ratio, 1.10; 95% CI, 0.92 to 1.31; p=0.30). Conclusion Being a Leo is not associated with any adverse cardiac risk. Our findings should provide reassurance to the large population of Leos that together make up approximately one twelfth of mankind.

Relation of Cyclooxygenase Isoenzyme Expression and Coronary Artery Remodeling

Inflammation plays a key role in coronary atherosclerosis. Increased markers of inflammation have been consistently associated with a worse outcome in patients with clinical or subclinical coronary artery disease. 1 Cyclooxygenase (COX) or prostaglandin synthase G/H are key enzymes responsible for the metabolism of arachidonic acid, and they exist in 2 isoforms—COX-1 and COX-2. COX activity has been described in both healthy human coronary arteries and in association with atherosclerosis and transplant vasculopathy. 2,3 Coronary arteries undergo changes in lumen size in response to coronary atherosclerosis; a phenomenon described as coronary remodeling. 4,5 Coronary remodeling encompasses outward expansion or positive remodeling, and conversely, narrowing or negative remodeling. Positive remodeling, although serving to maintain luminal size and thus possibly maintaining adequate coronary flow, is associated with a higher incidence of unstable coronary syndromes. 6 Although a previous studies 7 has suggested a relation between inflammation and coronary remodeling, the role of the COX pathway has not been explored. We sought to determine the relation between the localization of COX isoenzymes and coronary artery remodeling in patients who underwent directional coronary atherectomy (DCA). ••• The study population consisted of 21 patients who had DCA performed for a single epicardial lesion in a native coronary artery. Clinical presentation was defined as stable or unstable using standard clinical criteria. 8 Intravascular ultrasound imaging was performed using standard techniques as previously reported. 9 All images were obtained using a 30-MHz 3.5Fr monorail ultrasound catheter (Boston Scientific, Watertown, Massachusetts) interfaced with a scanner (Hewlett-Packard, Andover, Massachusetts). After coronary angiography, intravenous heparin and intracoronary nitroglycerin were administered, and the ultrasound catheter was inserted over a guide wire distal to the target lesion site. The ultrasound catheter was then withdrawn manually during continuous imaging, and images were recorded on 1/2-in SuperVHS videotape. The lesion site was identified using cine angiography and verbal annotation. Each piece of tissue was fixed for 8 hours in Histochoice (Amresco, Solon, Ohio). The tissue was then processed and paraffin was embedded according to standard laboratory procedures. Sections were cut from each block at 4 m, collected onto electrostatically charged slides, and baked at 60°C for 60 minutes. Two sections were collected and immunostained for each antibody. The antibodies used in this study were anti-HAM56 (Dako, Carpinteria California), anti-COX-1 (Cayman Chemical, Ann Arbor, Michigan), anti-COX-2 (Cayman Chemical), and anti--actin (Dako). The paraffin was removed from the baked tissue sections in 3 changes of xylene, and the tissue was hydrated through graded alcohols before rinsing them in phosphate-buffered saline (PBS). Immunohistochemical staining was performed using a Jung Histostainer (Leica, Illinois), with processing occurring at 30°C. The first stage of the procedure involved the application of a 1% hydrogen peroxide solution in methanol for 5 minutes to remove any endogenous peroxidase present in the tissue section. A blocking solution comprising a 1:10 dilution of normal rabbit serum (Dako) in PBS was added for 10 minutes before application of the primary antibody. The required dilutions of antibody were prepared using 1% bovine serum albumin in PBS. Incubation occurred at 30°C for 60 minutes, and a 1:200 dilution of biotinylated rabbit anti-mouse polyclonal antibody (Dako) was added for an additional 30 minutes. The antibodies were labeled using an Elite avidin/biotin/peroxidase complex (Vector Laboratories, Burlingame, California) applied for 30 minutes. The final stage comprised the addition of 3,3diaminobenzidine as a chromogen (DAB Kit, Vector