TP53 polymorphisms in sporadic North Indian breast cancer patients.

BACKGROUND: The purpose of this study was to evaluate the potential association of five (p.P47S, p.R72P, PIN3 Ins16bp, p.R213R and r.13494g>a) polymorphisms of TP53 with the risk of developing breast cancer in North Indian Punjabi population. METHODS: We screened DNA samples of 200 sporadic breast cancer patients (197 females and 3 males) and 200 unrelated healthy, gender and age matched individuals for the polymorphisms. RESULTS: For the p.P47S polymorphism, we observed the PP genotype in 99.5% of the patients and PS genotype in only 1 patient. All the controls had the wild type PP genotype. The frequency of RR, RP and PP genotype of p.R72P was 23.5% vs 33.5%, 51.5% vs 45.5% and 25% vs 21% in patients and controls respectively. Heterozygous (RP) genotype was increased in breast cancer patients as compared to controls (51.5 vs 45.5%) and showed 1.61 fold significantly increased risk for breast cancer (OR=1.61, 95% CI, 1.01-2.58, p=0.04). In breast cancer patients the frequencies of A1A1, A1A2 and A2A2 genotypes of PIN3 Ins16bp polymorphism were 67%, 26% and 7% respectively whereas in controls the genotype frequencies were 68.5%, 27.5% and 4% respectively, with no significant difference. For p.R213R (c.639A>G), all individuals had homozygous wild type genotype. The frequencies of GG, GA and AA genotypes of TP53 r.13494g>a polymorphism were 62 vs 67.5%, 33 vs 28% and 5 vs 4.5% in patients and controls respectively, again without significant difference. We observed that RP- A1A1 genotype combination of p.R72P and PIN3 Ins16bp and RP-GG combination of p.R72P and r.13494g>a polymorphism showed significant risk of breast cancer (OR=1.65, 95%CI: 0.98-2.78, p=0.05; OR=1.72, 95%CI: 1.01-2.92, p=0.04). CONCLUSION: The results of present study indicated that among the five TP53 polymorphisms investigated, the p.R72P polymorphism, and the RP-A1A1 and RP-GG genotype combination contribute to breast cancer susceptibility in North Indians.

Hybrid coronary revascularization for the treatment of left main coronary stenosis: a feasibility study.

OBJECTIVE: To determine the feasibility of a hybrid coronary revascularization (HCR) approach for the treatment of left main (LM) coronary artery stenosis. BACKGROUND: The recommended therapy for significant LM stenosis is coronary artery bypass grafting (CABG). Percutaneous coronary intervention (PCI) of unprotected LM lesions is reserved for patients at high risk for complications with CABG. HCR in LM disease has not been studied. METHODS: Twenty-two consecutive patients with LM stenosis >70% underwent staged HCR. Following a robotic or thoracoscopic-assisted minimally invasive left internal mammary artery (LIMA) to left anterior descending artery (LAD) coronary bypass, PCI of the LM, and non-LAD targets was performed after angiographic confirmation of LIMA patency. Intravascular ultrasound confirmed optimal stent deployment. Thirty-day adverse outcomes and long term follow up was obtained. RESULTS: In the 22 patients with LM lesions, 6 were ostial, 5 mid, and 11 distal. LIMA patency was FitzGibbon A in all cases. LM stenting was successful in all patients with drug-eluting stents (DES) placed in 21 of 22 cases. Three patients underwent stent implantation in the right coronary artery. There were no 30-day major adverse cardiac or cerebrovascular events. At a mean of 38.8 ± 22 months postprocedure, 21 patients were alive without reintervention; one death occurred at 454 days. CONCLUSIONS: HCR for LM coronary disease is a feasible alternative to CABG and unprotected LM PCI. This approach combines the long-term durability of a LIMA-LAD bypass with the less invasive option of PCI in non-LAD targets with DES.

Effect of chronic angiotensin converting enzyme inhibitor therapy on myocardial injury in patients undergoing percutaneous coronary interventions.

BACKGROUND: Procedural MI is a frequent complication of percutaneous coronary intervention (PCI). Angiotensin converting enzyme inhibitors (ACE-I) have been shown to reduce ischemic events in the setting of acute myocardial infarction (MI) and heart failure. OBJECTIVE: We sought to evaluate whether chronic ACE-I treatment prior to PCI reduces the incidence of procedural MI. METHODS: The study cohort included consecutive patients from January 2003 to August 2004 undergoing PCI with normal baseline serum creatinine kinase (CK) and cardiac CK isoform (CK-MB) (n = 265). Procedural MI was defined as CK-MB elevation ≥ 3 times the upper limit of normal. RESULTS: Patients on chronic ACE-I had a higher baseline prevalence of adverse prognostic features including diabetes (p = 0.02) and a trend towards a lower incidence of drug-eluting stent use (p = 0.07). Using multiple logistic regression, patients on chronic ACE-I therapy (n = 138) had a 64% reduction in procedural MI compared with those not on ACE-I (n = 127; odds ratio = 0.36; 95% confidence intervals 0.13-0.99; p = 0.05). Long-term outcomes, including death and major adverse cardiac events (MACE) (combined total of death, MI and target lesion revascularization were similar in the two groups. Procedural MI was, however, associated with increased MACE during follow up (60% vs. 35.4%; p = 0.035). CONCLUSION: Chronic ACE-I therapy before PCI may reduce the incidence of procedural MI.

Racial disparities in prescriptions for cardioprotective drugs and cardiac outcomes in Veterans Affairs Hospitals.

Previous reports have suggested that blacks receive life-saving cardioprotective therapies less often than whites, probably because of a lower socioeconomic status, which leads to poor access to physicians. We questioned whether racial disparity existed in the Veterans Affairs Healthcare System. We examined the Veterans' Integrated Service Network (VISN 16) database with regard to the prescription rates for 4 cardiovascular agents-aspirin, beta blockers, statins, and angiotensin-converting enzyme inhibitors. The database, encompassing 474,565 patients (117,071 blacks and 357,494 whites), was analyzed. Cardioprotective drugs were prescribed significantly less often to black patients than compared to white patients (beta blockers 19.7% vs 24.8%, odds ratio [OR] 0.74, 95% confidence interval [CI] 0.72 to 0.75; statins 20.5% vs 30.2%, OR 0.54, 95% CI 0.52 to 0.55; and angiotensin-converting enzyme inhibitors 27.7% vs 30.0%, OR 0.94, 95% CI 0.92 to 0.96; all p <0.0001, after adjustment for all covariates used in the analysis). Nonetheless, the prescription rates for aspirin were greater among the black patients than among the white patients (OR 1.31, 95% CI 1.27 to 1.35, p <0.001) after adjustment. The black patients received coronary artery bypass grafting less often than did the white patients (0.4% vs 1.21%, OR 0.40% to 0.48%, 95% CI 1.34 to 1.42, p <0.001). After adjustment for the use of cardioprotective drugs and coronary artery bypass grafting, black patients still had greater odds of developing angina (OR 1.38, 95% CI 1.34 to 1.42, p <0.001) and acute myocardial infarction (OR 1.11, 95% CI 1.03 to 1.19, p <0.006) than did white patients in the Department of Veterans Affairs Veterans' Integrated Service Network 16 hospitals. In conclusion, the lower prescription rates of cardioprotective drugs and lower rates of coronary artery bypass grafting might be a partial basis for the high rates of cardiac morbidity among black patients.

Risk of adverse clinical outcomes with concomitant use of clopidogrel and proton pump inhibitors following percutaneous coronary intervention.

BACKGROUND: Recent studies have suggested that proton pump inhibitors (PPIs) attenuate the benefits of clopidogrel. The clinical relevance of this interaction in patients who have undergone percutaneous coronary intervention (PCI) is unknown. We hypothesized that post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. AIMS: To determine whether post-PCI patients discharged on clopidogrel will have higher cardiovascular events if concomitant PPI therapy is used. METHODS: We reviewed the medical records of all the patients discharged on clopidogrel who underwent PCI from January 2003 to August 2004. The primary outcome studied was a major adverse cardiovascular event (MACE), which was defined as a composite of death, myocardial infarction, and target vessel failure. RESULTS: Of the 315 post-PCI patients who were discharged on clopidogrel, 72 were discharged on PPI. During a mean follow-up period of 50 months, patients discharged on concomitant clopidogrel-PPI therapy had a MACE rate of 56% (vs. 38% in the clopidogrel alone group) (P = 0.025) and had 95% excess risk of MACE. CONCLUSION: Concomitant use of clopidogrel and PPI in post-PCI patients is associated with a higher risk of MACE. This suggests that PPIs may attenuate clopidogrel's beneficial antiplatelet effect, which is crucial after PCI. Prospective randomized studies are warranted to provide definitive evidence for this interaction.

Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients.

BACKGROUND: The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) reduce serum cholesterol level and cardiovascular morbidity and mortality. However, the effect of statins on glucose metabolism is unclear. Some studies have suggested that statins may cause hyperglycemia by increasing calcium concentration in the islet cells leading to decrease in insulin release or by decreasing GLUT 4-mediated peripheral glucose uptake. METHODS: We analyzed the data in 345,417 patients (mean age 61 +/- 15 years, 94% males, 6% diabetic, 20% statin users) from the Veterans Affairs VISN 16 database. We studied change in fasting plasma glucose (FPG) in this population over a mean time of 2 years between the first available measurement and the last measurement form the most recent recorded visit. Data were limited to patients who had 2 FPG measurements. Diagnosis of diabetes had to be present before the first FPG measurement. RESULTS: Among patients without diabetes, FPG increased with statin use from 98 mg/dL to 105 mg/dL, and among nonstatin users, FPG increased from 97 mg/dL to 101 mg/dL (increase in FPG with statin use P < 0.0001). Among patients with diabetes, FPG increased with statin use from 102 mg/dL to 141 mg/dL, and among nonstatin users, FPG increased from 100 mg/dL to 129 mg/dL (increase in FPG with statin use; P < 0.0001). After adjustment for age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors, the change in FPG in nondiabetic statin users was 7 mg/dL (vs 5 mg/dL in nonstatin users, P < 0.0001) and for diabetic statin users it was 39 mg/dL (vs 32 in nonstatin users, P < 0.0001). CONCLUSIONS: Statin use is associated with a rise of FPG in patients with and without diabetes. This relationship between statin use and rise in FPG is independent of age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors.

Treatment of chronic total occlusion by retrograde passage of stents through an epicardial collateral vessel.

Chronic total occlusion (CTO) may occur in as many as 30-40% of patients with coronary artery disease. Retrograde revascularization through a collateral channel has been described earlier. We report the first case of retrograde passage of a stent through an epicardial collateral to revascularize a right coronary artery CTO.

Effect of statins on the development of renal dysfunction.

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) decrease serum cholesterol. Dyslipidemia is believed to be associated with the development of renal dysfunction. It was postulated that statins may reduce the development of renal dysfunction. The effect of statin use on the development of renal dysfunction in 197,551 patients (Department of Veterans Affairs, Veterans Integrated Service Network 16 [VISN16] database) was examined. Of these patients, 29.5% (58,332 patients) were statin users and 70.5% (139,219 patients) were not. Development of renal dysfunction was defined as doubling of baseline creatinine or increase in serum creatinine > or =0.5 mg/dl from the first to last measurement with a minimum of 90 days in between. During 3.1 years of follow-up, 3.4% of patients developed renal dysfunction. After adjustment for demographics, diabetes mellitus, smoking, hypertension, and other medications (mainly angiotensin-converting enzyme inhibitors, calcium channel blockers, and aspirin), use of statins decreased the odds of developing renal dysfunction by 13% (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82 to 0.92, p <0.0001). The beneficial effect of statins appeared to be independent of the decrease in cholesterol. Other variables that affected the development of renal dysfunction were age (OR 1.04, 95% CI 1.03 to 1.04, p <0.0001), diabetes (OR 1.77, 95% CI 1.68 to 1.86, p <0.0001), hypertension (OR 1.11, 95% CI 1.02 to 1.2, p = 0.0153), and smoking (OR 1.12, 95% CI 1.02 to 1.24, p = 0.0244). In conclusion, statin use may retard the development of renal dysfunction. The beneficial effect of statins in preventing the development of renal dysfunction appears to be independent of their lipid-lowering effect.

Percutaneous intervention on the saphenous vein bypass grafts--long-term outcomes.

BACKGROUND/OBJECTIVE: In this era of drug eluting stents (DES), the long-term outcome of percutaneous intervention (PCI) on saphenous venous grafts (SVG) is unknown. The objective of the study was to compare the long-term outcomes of DES versus bare metal stent (BMS) in this population and to determine the predictors of outcomes. METHODS: We reviewed the medical records of all patients who had PCI performed during January 2003 to February 2005 to obtain data cardiac risk factors, medications at discharge, angiographic details and outcomes. RESULTS: One hundred and nine patient had PCI to SVG; of these, 37 patients received DES and the remaining had BMS. Over a mean follow-up of 33 months, the PCI using DES was associated with 30% restenosis, 35% target vessel revascularization (TVR) and major adverse cardiac event (MACE) rate of 46% versus 35% restenosis, 38% TVR and 50% MACE rate with BMS. There was no significant difference in long-term outcome with DES as compared to BMS. CONCLUSION: There was no difference in the long-term outcomes of PCI on SVG irrespective of the type of stent used.

Assessment of left ventricular function: comparison of cardiac multidetector-row computed tomography with two-dimension standard echocardiography for assessment of left ventricular function.

OBJECTIVE: To compare global Left Ventricular (LV) systolic function assessment by 16-detector row Computed Tomography (MDCT) with Two-Dimensional Standard Echocardiography (2DSE) in a routine cardiology practice setting and to ascertain the degree of correlation between LV volumes and measurements obtained by 2DSE with those measured by MDCT. METHODS: In 52 patients with suspected coronary artery disease, a contrast enhanced MDCT study was performed using retrospective gating without dose modulation for better endocardial delineation. Eight phases of the cardiac cycle were analyzed to identify the end-diastolic and end-systolic phases. 2DSE was performed on the same day. Left ventricular systolic and diastolic volumes and ejection fraction were calculated in 4-chamber, 2-chamber and biplane (average of the two) views. Endocardial tracing was used to measure ventricular volumes by area length method for CT and Simpson's method for echocardiography. RESULTS: On MDCT, mean LV ejection fraction (LVEF) in 4-chamber, 2-chamber and biplane views were 58.4 +/- 12, 59.3 +/- 12 and 59.7 +/- 12% respectively. On 2DSE, mean LVEF in 4-chamber, 2-chamber and biplane views were 58 +/- 14, 57 +/- 16 and 58 +/- 13% respectively. LVEF correlated best using the biplane views (r = 0.59 and P < 0.01) compared to 2-chamber (r = 0.57 and P < 0.01) and 4-chamber views (r = 0.32 and P = 0.02). Biplane measurement by these two techniques correlated well for LV volumes in both diastole (r = 0.69 and P < 0.01) and systole (r = 0.73 and P < 0.01), although MDCT consistently gave higher values. CONCLUSIONS: MDCT can be a useful tool to measure LVEF while patients are undergoing CT coronary angiography.

Traditional risk factors and acute myocardial infarction in patients hospitalized with cocaine-associated chest pain.

BACKGROUND: Cocaine causes coronary artery constriction and may cause acute myocardial infarction (AMI). The role of traditional coronary risk factors in cocaine-associated myocardial infarction is unclear. HYPOTHESIS: We hypothesized that traditional risk factors play a major role in predicting AMI in patients admitted with cocaine-associated chest pain METHODS: After reviewing 165 admissions for chest pain in patients with a history of recent cocaine use and/or a positive drug screen from January 2001 to December 2004, we identified 151 patients with information available on at least 6 of the following 7 risk factors: gender, hypertension, hyperlipidemia, diabetes, smoking, family history of coronary artery disease (CAD) and known CAD. AMI was diagnosed using WHO criteria. A risk score was calculated on the basis of the number of risk factors, gender and age. Association of AMI was evaluated with the individual risk factors and with the risk score. RESULTS: AMI was identified in 21 patients (14%). All patients diagnosed with AMI were smokers. Continuous risk score (p < 0.0001), highest vs. lowest quartile of risk score (p = 0.007), known CAD, age, hyperlipidemia and family history of CAD were individually associated with the diagnosis of AMI (p>or=0.05). Each quartile of risk score was associated with increased odds of the diagnosis of AMI and score of 8 or higher was statistically significant. CONCLUSION: Several traditional risk factors are associated with the diagnosis of AMI among patients hospitalized with cocaine-associated chest pain and increasing risk factor score was associated with increasing odds of AMI diagnosis.

Myxedema coma in a patient with Down's syndrome.

INTRODUCTION: hyroid dysfunction is common in Down's syndrome, most common being hypothyroidism. Longstanding, untreated hypothyroidism can lead to myxedema coma. METHODS: Here we report a patient with Down's syndrome who presented with myxedema coma. DISCUSSION: The three essential elements for the diagnosis of myxedema coma include altered mental status, defective thermoregulation and a precipitating event or illness; all of these were present in our patient. Also, very high TSH, low T3 and T4, and the rapid response to the treatment with levothyroxine confirmed the diagnosis. CONCLUSION: Patients with Down's syndrome should have regular screening for thyroid dysfunction.

Prevention of heart failure.

PURPOSE OF REVIEW: Chronic heart failure imposes a significant health burden and remains a substantial and increasing problem despite advances in therapy. Hence, prevention of heart failure is a priority. RECENT FINDINGS: Various risk factors have been identified that contribute to the development of heart failure. In this review, we will discuss the various recently reported clinical trials, epidemiological studies, meta-analyses, and subanalyses that have identified these risk factors and have provided evidence regarding the strategies to prevent heart failure. SUMMARY: Heart failure is a costly, disabling, and potentially fatal disease. It is therefore important to incorporate the strategies for prevention of heart failure on the basis of the current available evidence into routine clinical practice.

Pleuropericarditis and pericardial tamponade associated with inflammatory bowel disease.

Extraintestinal manifestations have been described with inflammatory bowel disease (IBD). Cardiac involvement in IBD is rare and may present as pericardial effusion, myopericarditis and conduction defects. Here we present a case of IBD with asymptomatic pericardial tamponade. A 37-year-old African-American man with ulcerative colitis with history of previous colectomy with ileorectal anastomosis was hospitalized for resection of the stricture of ileorectal anastomosis. The patient was afebrile with stable vitals and modest jugular venous distension, but no pulsus paradoxus. Cardiopulmonary examination was normal. A CT scan done to evaluate rise in liver function tests following removal of stricture showed a large 3.1 cm pericardial effusion. A transthoracic 2-D echocardiogram showed a moderate-sized posterior pericardial effusion limiting left ventricular filling. Central venous pressure was 18 mm Hg and the patient underwent drainage of 300 ml of old bloody pericardial effusion. Pericardial biopsy showed organizing fibrinohemorrhagic chronically inflamed pericardium without granuloma or neoplastic process. Serologies for EBV, Coxsackie virus and hepatitides were negative. Drug-related pericarditis seems less likely as the patient was not on sulfasalazine, and ANA, dsDNA and rheumatoid factor titers were negative. The patient was diagnosed to have pericardial tamponade associated with IBD.

Trends in the care of patients with acute myocardial infarction at a university-affiliated Veterans Affairs Medical Center.

BACKGROUND: Acute cardiac care of the veterans at Veterans Administration (VA) hospitals has been thought of as poor in quality. We examined the use of life-saving, evidence-based medical therapy in patients admitted with acute myocardial infarction to the University of Arkansas for Medical Sciences-affiliated VA Medical Center in Little Rock and compared the use of this therapy with other hospitals in Arkansas and in the rest of the nation. METHODS: Use of life-saving medical therapy in 117 patients admitted with acute myocardial infarction from January 2002 to December 2002 was compared with the National Registry of Myocardial Infarction database for the identical period. RESULTS: Heparin/low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitors were used in 88% and 66% of patients, respectively. Aspirin, beta adrenergic-blocking agents, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) were used in 92%, 93%, 62%, and 79% of the patients, respectively. The use of these therapies was better than in similar patients in Arkansas (P < .001) and the United States as a whole (P < .01). Calcium-channel blockers were used in 16% of the patients. At a mean follow-up period of 1.5 years, use of beta blockers and aspirin had decreased, whereas the use of statins and ACE inhibitors/ARBs was unchanged. CONCLUSION: This study shows that patients with acute myocardial infarction admitted to this university-affiliated VA Medical Center receive evidence-based life-saving medical therapy more often than in the rest Arkansas or in the entire United States. More important, patients at this federal institution continue to receive life-saving medical therapy during follow-up. Better use of evidence-based therapy may be related to affiliation of this VA Medical Center with a teaching institution where board certified cardiologists are involved in short- and long-term care of these patients.