Jeffrey M. Schussler M.D.

Posted June 15th 2017

Residual thromboxane activity and oxidative stress: influence on mortality in patients with stable coronary artery disease.

Peter McCullough M.D.

Peter McCullough M.D.

Vasudevan, A., T. Bottiglieri, K. M. Tecson, M. Sathyamoorthy, J. M. Schussler, C. E. Velasco, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and P. A. McCullough (2017). “Residual thromboxane activity and oxidative stress: Influence on mortality in patients with stable coronary artery disease.” Coron Artery Dis 28(4): 287-293.

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BACKGROUND: Aspirin use is effective in the prevention of cardiovascular disease; however, not all patients are equally responsive to aspirin. Oxidative stress reflected by F2-isoprostane [8-iso-prostaglandin-F2alpha (8-IsoPGF2alpha)] is a potential mechanism of failure of aspirin to adequately inhibit cyclooxygenase-1. The objective was to examine the relation between all-cause mortality and the concentrations of urinary 11-dehydro thromboxane B2 (11dhTxB2) and 8-IsoPGF2alpha in patients with stable coronary artery disease (CAD). METHODS: The data for this analysis are from a prospective study in which patients were categorized into four groups based on the median values of 11dhTxB2 and 8-IsoPGF2alpha. RESULTS: There were 447 patients included in this analysis with a median (range) age of 66 (37-91) years. The median (range) values of 11dhTxB2 and 8-IsoPGF2alpha were 1404.1 (344.2-68296.1) and 1477.9 (356.7-19256.3), respectively. A total of 67 (14.9%) patients died over a median follow-up of 1149 days. The reference group for the Cox proportional hazards survival analysis was patients with values of 11dhTxB2 and 8-IsoPGF2alpha below their corresponding medians. Adjusting for the age and sex, patients with values of 11dhTxB2 greater than the median had a significantly higher risk of mortality when compared with the reference group (high 11dhTxB2 and low 8-IsoPGF2alphaadj: hazard ratio: 3.2, 95% confidence interval: 1.6-6.6, P=0.002; high 11dhTxB2 and 8-IsoPGF2alphaadj: hazard ratio: 3.6, 95% confidence interval: 1.8-7.3, P<0.001). The findings were similar when we adjusted for the comorbidities of cancer, kidney function, and ejection fraction. CONCLUSION: We found that 11dhTxB2 appears to be a better prognostic marker for mortality as compared with 8-IsoPGF2alpha, suggesting aspirin resistance itself is a stronger independent determinant of death in CAD patients treated with aspirin.


Posted March 15th 2017

Renal Function and Scaled Troponin in Patients Presenting to the Emergency Department with Symptoms of Myocardial Infarction.

Peter McCullough M.D.

Peter McCullough M.D.

Vasudevan, A., A. J. Singer, C. DeFilippi, G. Headden, J. M. Schussler, L. B. Daniels, M. Reed, M. P. Than, R. Birkhahn, S. W. Smith, T. W. Barrett, W. Arnold, W. F. Peacock and P. A. McCullough (2017). “Renal function and scaled troponin in patients presenting to the emergency department with symptoms of myocardial infarction.” Am J Nephrol 45(4): 304-309.

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BACKGROUND: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. METHODS: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m2 were considered to have renal dysfunction. RESULTS: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 +/- 12.3 and 57.3 +/- 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. CONCLUSIONS: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.


Posted February 15th 2017

Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease.

Peter McCullough M.D.

Peter McCullough M.D.

McCullough, P. A., A. Vasudevan, M. Sathyamoorthy, J. M. Schussler, C. E. Velasco, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2017). “Urinary 11-dehydro-thromboxane b2 and mortality in patients with stable coronary artery disease.” Am J Cardiol: 2017 Jan [Epub ahead of print].

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Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (+/-SD) of 67 +/- 10 and 65 +/- 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2 (p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.


Posted September 15th 2016

Comparative Efficacy of Transradial Versus Transfemoral Approach for Coronary Angiography and Percutaneous Coronary Intervention.

Peter McCullough M.D.

Peter McCullough M.D.

Schussler, J. M., A. Vasudevan, L. J. von Bose, J. I. Won and P. A. McCullough (2016). “Comparative efficacy of transradial versus transfemoral approach for coronary angiography and percutaneous coronary intervention.” Am J Cardiol 118(4): 482-488.

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Transradial artery (TRA) approach is associated with fewer vascular complications and reduced mortality in patients at high risk compared with transfemoral approach (TFA). The objective of our study was to compare the characteristics and outcomes of patients who had coronary angiography by TRA and TFA over the course of hospital implementation of this approach. We included 12,928 patients from Baylor University Medical Center and Baylor Heart and Vascular Hospital, Dallas, Texas, who underwent a coronary angiography from January 2008 to March 2015. To control for selection bias and the learning curve, a nested matched study design was used for patients with percutaneous coronary intervention (PCI) with TRA patients matched with TFA by age (+/-2 years) and calendar year of the procedure in a ratio of 1:3. TRA for PCI increased from nearly 0% in 2008 to 9% in 2014. Including patients from 2011 to 2015 for the analysis, patients with TFA were older (65 +/- 12 vs 64 +/- 11) and had lower mean body mass index (30 +/- 7 vs 33 +/- 9 kg/m(2)) than patients with TRA. Patients with TRA had less bleeding, dialysis, pseudoaneurysm, and access site hematomas than the patients with TRA (0.7% vs 0%; p = 0.02). By a conditional logistic regression, we observed fewer complications, readmissions, and in-hospital deaths among TRA patients than the matched TFA patients. In conclusion, patients undergoing angiography with/without PCI through TRA had fewer complications, readmissions, and a shorter length of hospital stay after procedure versus TFA at our hospital.


Posted September 15th 2016

Comparison of Coronary Artery Calcium Scores Between Patients With Psoriasis and Type 2 Diabetes.

http://bhslibrary.tamhsc.edu/wp-content/uploads/2016/02/Alan-M.-Menter.jpg
Alan M. Menter M.D.

Mansouri, B., D. Kivelevitch, B. Natarajan, A. A. Joshi, C. Ryan, K. Benjegerdes, J. M. Schussler, D. J. Rader, M. P. Reilly, A. Menter and N. N. Mehta (2016). “Comparison of coronary artery calcium scores between patients with psoriasis and type 2 diabetes.” JAMA Dermatol: 2016 Aug [Epub ahead of print].

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Psoriasis is associated with an increased risk of cardiovascular diseases. Subclinical atherosclerosis in patients with psoriasis has not been compared with other conditions associated with increased cardiovascular risk and more rigorous cardiovascular disease screening, such as type 2 diabetes. Objective: To assess the burden of asymptomatic coronary atherosclerosis measured by coronary artery calcium score in patients with moderate to severe psoriasis compared with patients with type 2 diabetes and healthy controls. Design, Setting, and Participants: Three single-center, cross-sectional studies were performed in patients recruited from specialty outpatient clinics with moderate to severe psoriasis without type 2 diabetes (recruited from November 1, 2013, through April 31, 2015), patients with type 2 diabetes without psoriasis or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011), and age- and sex-matched healthy controls without psoriasis, type 2 diabetes, or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011). Exposures: Psoriasis, type 2 diabetes, and healthy control effect on coronary artery calcium score. Main Outcomes and Measures: Coronary artery calcium measured by Agatston score. Results: A total of 387 individuals participated in the study. Mean (SD) age was 51 (7.7), 52 (8.0), and 52 (8.0) years in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively. There were 64 men (49.6%) in each group, and most patients were white (119 [92.2%], 123 [95.3%], and 128 [99.2%] in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively). Patients with psoriasis had low cardiovascular risk measured by the Framingham Risk Score but had a high prevalence of cardiovascular and cardiometabolic risk factors, similar to patients with type 2 diabetes. In a fully adjusted model, psoriasis was associated with coronary artery calcium (Tobit regression ratio, 0.89; P < .001) similar to the association in type 2 diabetes (Tobit regression ratio, 0.79; P = .04). Likelihood ratio testing revealed incremental value for psoriasis in a fully adjusted model (chi2 = 4.48, P = .03) in predicting coronary artery calcium. Psoriasis was independently associated with the presence of any coronary artery calcium (odds ratio, 2.35; 95% CI, 1.12-4.94) in fully adjusted models, whereas the association of coronary artery calcium with type 2 diabetes was no longer significant after adding body mass index to the model (odds ratio, 2.18; 95% CI, 0.75-6.35). Conclusions and Relevance: Patients with psoriasis have increased coronary artery calcium by mean total Agatston scores, similar to that of patients with type 2 diabetes, suggesting that patients with psoriasis harbor high rates of subclinical atherosclerosis beyond adjustment for body mass index. Major educational efforts for patients and physicians should be undertaken to reduce the burden of cardiovascular disease in patients with psoriasis.