Myocardial Scintigraphy in Diagnosing Cardiac Transthyretin Amyloidosis.

Myocardial scintigraphy with technetium-99m pyrophosphate is a minimally invasive technique that can distinguish between transthyretin amyloidosis (ATTR) and light-chain amyloidosis. We present a case in which it helped determine the amyloidosis type in a 74-year-old man with cardiac amyloidosis and multiple previous admissions for acute decompensated heart failure. The patient presented with increasing abdominal girth and bilateral lower extremity edema. His medical history also included atrial fibrillation, liver cirrhosis, hypertension, stage 3 chronic kidney disease, and peripheral vascular disease. We prescribed guideline-directed medical therapy for his acute decompensated heart failure with cardiorenal syndrome and his decompensated cirrhosis. Two years previously, a presumptive diagnosis of ATTR cardiomyopathy had been made on the basis of the patient's age, predominantly cardiac involvement, an unremarkable serum protein electrophoresis result, and an abnormal free κ/λ light-chain ratio of 2.24. Over the next year, the patient's clinical condition had worsened with the development of liver cirrhosis and peripheral neuropathy, and his free κ/λ light-chain ratio had become even more abnormal. At the current presentation, a technetium-99m pyrophosphate nuclear scintigram revealed a free κ/λ light-chain ratio of 1.52. This, combined with the patient's age and slow progression of primarily cardiac disease, supported the diagnosis of ATTR, and we prescribed tafamadis. This case suggests that technetium-99m pyrophosphate scintigraphy is valuable in definitively diagnosing ATTR cardiomyopathy and selecting patients who may benefit from disease-modifying therapy.

Benefits of Adding Glucagon-Like Peptide 1 Receptor Agonists to Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetic Patients With Atherosclerotic Disease and Heart Failure.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of cardiovascular events and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), diabetes mellitus type 2 (DM2), and atherosclerotic cardiovascular disease (ASCVD). The role of glucagon-like peptide 1 agonists (GLP1a) in these patients is unclear. We designed this study to assess if the addition of GLP1a to SGLT2i therapy improves outcomes in patients with HFrEF, DM2, and ASCVD. This was a retrospective cohort study of patients with DM2, ASCVD, and HFrEF in the national Veterans Affairs database. Patients on SGLT2i were propensity matched to patients on both SGTL2i and GLP1a. The co-primary outcomes were HFH and the composite of all-cause death, myocardial infarction, and stroke. We assessed them through a Cox regression model including unbalanced baseline characteristics. From a cohort of 5,576 patients, 343 were propensity matched to each study arm. The addition of GLP1a was associated with a 67% reduction in the 1-year risk of a composite event compared with therapy with SGLT2i (confidence interval 0.138 to 0.714, p = 0.007). The risk of HFH was not significantly different between both arms (p = 0.199). Sensitivity analyses in the unmatched dataset confirmed these findings. In conclusion, the addition of GLP1a to SGLT2i may reduce the risk of adverse events in patients with HFrEF who have DM2 and ASCVD, but it does not affect the risk of HFH.

Open extent IV thoracoabdominal aneurysm repair: 22-year experience of the Scottish National Service.

BACKGROUND: Since 1999, the Scottish National Service for Thoracoabdominal Aneurysms has offered repair of thoracoabdominal aneurysms (TAAAs) to a population of 5.5 million people. The open operation most commonly performed by the service is the extent IV TAAA repair. METHODS: All extent IV open TAAA repairs performed at the Scottish National Service for TAAAs from June 1999 until April 2021 were evaluated for clinical features, technical details, and clinical outcomes. The primary outcome measure was 30-day mortality; secondary outcomes included short-term (90 days, 6 months, 1 and 2 years) and long-term (5 and 10 years) survival, perioperative complications, and reintervention. Survival was assessed using Kaplan-Meier analysis. RESULTS: Some 248 patients underwent extent IV TAAA repair, with elective surgery in 204 (82.3 per cent). A totally abdominal transperitoneal approach was used for all patients, with a median visceral ischaemia time of 40 (i.q.r. 35-48) min. Overall, 18 patients (7.3 per cent) died within 30 days. The proportion of patients surviving at 90 days, 6 months, 1, 2, 5, and 10 years was 0.91, 0.90, 0.89, 0.85, 0.72, and 0.41, respectively. Ten patients (4.0 per cent) required a reintervention while in hospital, four (1.6 per cent) experienced permanent spinal cord ischaemia, 19 (7.9 per cent) required temporary renal replacement therapy (RRT), and four (1.6 per cent) required permanent RRT. CONCLUSION: Open extent IV TAAA repair performed in a high-volume national centre is associated with favourable short- and long-term survival, and acceptable complication rates.

Usefulness of Complement C1q to Predict 10-Year Mortality in Men With Diabetes Mellitus Referred for Coronary Angiography.

The complement system consists of a family of proteins that play a critical role in the innate immune system. Complement activation has been implicated in many chronic inflammatory diseases, including atherosclerosis. However, a number of experimental studies have highlighted a beneficial role of component C1q in early atherosclerosis and in diabetes mellitus (DM). Despite these data, there have been no studies that have specifically examined the utility of plasma complement C1q as a clinical biomarker in patients with known or suspected coronary artery disease. In this study, baseline plasma complement C1q levels were measured in 159 men with DM who were referred for coronary angiography and who were followed up prospectively for the development of all-cause mortality for 10 years. After adjustment for baseline clinical, angiographic, and laboratory parameters, reduced plasma complement C1q levels were an independent predictor of all-cause mortality at 10 years (hazard ratio 0.66, 95% confidence interval 0.52 to 0.84, p = 0.0006). In additional multivariate models that adjusted for a variety of biomarkers with established prognostic efficacy, complement C1q remained an independent predictor of all-cause mortality at 10 years. In conclusion, reduced levels of complement C1q are associated with an increased risk of all-cause mortality at 10 years in patients with DM referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy in the prediction of adverse cardiovascular outcomes.

Usefulness of Plasma Tissue Inhibitor of Matrix Metalloproteinase-4 to Predict Death and Myocardial Infarction in Patients With Diabetes Mellitus Referred for Coronary Angiography.

TIMP-4 is the newest member of a family of secreted proteins known as the tissue inhibitors of metalloproteases that selectively inhibit matrix metalloproteases. TIMP-4 is abundantly expressed in human cardiovascular structures and has been implicated in cardiovascular disease. Furthermore, it has also been shown to be a novel target of peroxisome proliferator-activated receptor gamma in rat smooth muscle cells, suggesting a potential role in diabetes mellitus as well. However, there have been no studies that have specifically examined the utility of baseline plasma TIMP-4 levels for the prediction of long-term adverse cardiovascular outcomes. In this study, baseline plasma TIMP-4 levels were measured in 162 male patients with diabetes mellitus who were referred for coronary angiography and followed prospectively for the development of all-cause mortality and enzymatically confirmed myocardial infarction (MI) out to 5 years. After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, plasma TIMP-4 levels were an independent predictor of all-cause mortality (hazard ratio 1.60, 95% CI 1.13 to 2.26; p = 0.0082) and MI (hazard ratio 1.61, 95% CI 1.19 to 2.18; p = 0.0021) at 5 years. Furthermore, in additional multivariate models that adjusted for a variety of biomarkers with established prognostic efficacy, TIMP-4 remained an independent predictor of adverse outcomes. In conclusion, elevated levels of TIMP-4 are associated with an increased risk of long-term all-cause mortality and MI in patients with diabetes mellitus referred for coronary angiography. Moreover, this association is independent of a variety of clinical, angiographic, and laboratory variables, including biomarkers with established prognostic efficacy in the prediction of adverse cardiovascular outcomes.

Usefulness of Plasma Matrix Metalloproteinase-3 Levels to Predict Myocardial Infarction in Men With and Without Acute Coronary Syndrome.

Matrix metalloproteinase-3 (MMP-3), or stromelysin-1, is a matrix metalloproteinase which is expressed in atherosclerotic plaques and which has been implicated in the pathogenesis of acute coronary syndrome (ACS). Functional polymorphisms in the promoter region of the human MMP-3 gene resulting in an increased expression of MMP-3 have been shown to predict the risk of incident myocardial infarction (MI). However, there have been no studies that have specifically examined the utility of baseline plasma MMP-3 levels for the prediction of long-term MI. In this study, baseline plasma MMP-3 levels were measured in 355 male patients who were referred for coronary angiography and followed prospectively for the development of enzymatically confirmed MI out to 5 years. After adjustment for a variety of baseline clinical, angiographic, and laboratory parameters, plasma MMP-3 levels were an independent predictor of MI at 5 years (hazards ratio 1.42, 95% CI 1.13 to 1.79; p = 0.0023). Furthermore, in 5 additional multivariate models that included a variety of contemporary biomarkers associated with adverse outcomes and MI, MMP-3 remained an independent predictor of MI at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with ACS. In conclusion, elevated levels of MMP-3 are associated with an increased risk of long-term MI in patients with and without ACS referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy for the prediction of MI.

Elevated baseline plasma IL-8 levels are an independent predictor of long-term all-cause mortality in patients with acute coronary syndrome.

OBJECTIVES: To investigate the long-term prognostic significance of baseline plasma IL-8 levels in a group of well-characterized male patients presenting with acute coronary syndrome. BACKGROUND: IL-8 is a cytokine that has been implicated in the pathogenesis of atherosclerosis and acute coronary syndrome. Elevated plasma levels have been reported in patients with acute coronary syndrome. METHODS: Baseline plasma IL-8 levels were measured in 180 male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years. RESULTS: In a multivariate model that included a wide variety of baseline clinical, laboratory and angiographic parameters in the selection process, baseline plasma IL-8 levels (analyzed as a continuous variable) emerged as a significant predictor of all-cause mortality at 5 years (HR, 1.43; 95% CI, 1.08-1.88; p = 0.0123). Furthermore, in 3 additional multivariate models that also included in the selection process a number of contemporary biomarkers with established prognostic efficacy in ACS (i.e., NT-proBNP, hs-CRP, hemoglobin and RDW), IL-8 remained an independent predictor of all-cause mortality at 5 years. CONCLUSION: Elevated baseline plasma levels of IL-8 are associated with an increased risk of long-term all-cause mortality in patients with acute coronary syndrome. Furthermore, this association is independent of a variety of clinical, laboratory and angiographic variables, including contemporary biomarkers with established prognostic efficacy in acute coronary syndrome.

Elevated baseline plasma phospholipid protein (PLTP) levels are an independent predictor of long-term all-cause mortality in patients with diabetes mellitus and known or suspected coronary artery disease.

OBJECTIVES: To investigate the long-term prognostic significance of baseline plasma PLTP levels in a group of well-characterized male patients with diabetes mellitus and known or suspected coronary artery disease referred for coronary angiography. BACKGROUND: PLTP is a plasma protein that mediates the net transfer and exchange of phospholipids between lipoproteins. It has been implicated in the pathogenesis of atherosclerosis and elevated plasma levels have been reported in patients with diabetes mellitus. METHODS: Baseline plasma PLTP levels were measured in 154 male patients with diabetes mellitus who were referred for coronary angiography and followed prospectively for 5 years for the development of all-cause mortality. RESULTS: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, plasma PLTP levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.55; 95% CI, 1.22-2.00; P = 0.0009). Furthermore, in 3 additional multivariate models that also included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, Fibrinogen, and NT-proBNP), PLTP remained an independent predictor of all-cause mortality at 5 years. CONCLUSIONS: Elevated baseline plasma levels of PLTP are associated with an increased risk of long-term all-cause mortality in patients with diabetes and known or suspected coronary disease. Furthermore, this association is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy.

Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography.

OBJECTIVES: To investigate the long-term prognostic significance of baseline plasma MMP-1 levels in a group of well-characterized male patients with known or suspected coronary artery disease, including those presenting with acute coronary syndrome. BACKGROUND: MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. In addition, MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. METHODS: Baseline plasma MMP-1 levels were measured in 364 male patients who were referred for coronary angiography and followed prospectively for five years for the development of all-cause mortality. RESULTS: After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, baseline plasma MMP-1 levels (analyzed as a continuous variable) were an independent predictor of all-cause mortality at 5 years (HR, 1.49; 95% CI, 1.23-1.80; P < 0.0001). Furthermore, in 3 additional multivariate models that included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, Cystatin C, hs-CRP, Myeloperoxidase, NT-proBNP, TIMP-1, Adiponectin, RDW, hemoglobin, and Erythropoietin), MMP-1 remained an independent predictor of all-cause mortality at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with acute coronary syndrome. CONCLUSIONS: Elevated levels of MMP-1 are associated with an increased risk of long-term all-cause mortality in patients with known or suspected coronary disease that is independent of a variety of clinical, angiographic, and laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy representing multiple different pathophysiologic processes.

Plasma interleukin-10 levels and adverse outcomes in acute coronary syndrome.

UNLABELLED: PURPOSE OR BACKGROUND: Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by a variety of cell types, such as macrophages and activated monocytes. IL-10 possesses numerous anti-inflammatory, anti-thrombotic and anti-atherosclerotic properties. Furthermore, patients with acute coronary syndrome have been demonstrated to have reduced levels of IL-10 compared to their stable counterparts. For these reasons, it has been proposed that IL-10 plays a protective role in both atherogenesis and plaque vulnerability. However, 2 short-term studies on the prognostic utility of IL-10 in patients with acute coronary syndrome have provided conflicting results, with one study showing that reduced levels of IL-10 were predictors of adverse outcomes and another showing that elevated levels predicted poor outcomes. The objective of the present study was to investigate the long-term prognostic significance of baseline IL-10 levels in patients with acute coronary syndrome. METHODS: Baseline plasma IL-10 levels were measured in 193 well-characterized male patients with acute coronary syndrome who were referred for coronary angiography and followed prospectively for 5 years for the development of major adverse cardiovascular events. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and N-terminal-pro-B-type natriuretic peptide), plasma IL-10 levels (whether analyzed as a continuous variable or as a categorical variable using receiver operating characteristic-derived cut point) were a strong and independent predictor of the composite outcome of death or non-fatal myocardial infarction when using a Cox proportional hazards model. CONCLUSIONS: These data demonstrate that, despite biologic plausibility for IL-10 as being a cardioprotective cytokine, elevated baseline plasma levels of IL-10 are a strong and independent predictor of long-term adverse cardiovascular outcomes in patients with acute coronary syndrome.

Is directly measured low-density lipoprotein clinically equivalent to calculated low-density lipoprotein?

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can either be calculated or measured directly. Clinical guidelines recommend the use of calculated LDL-C (C-LDL-C) to guide therapy because the evidence base for cholesterol management is derived almost exclusively from trials that use C-LDL-C, with direct measurement of LDL-C (D-LDL-C) being reserved for those patients who are nonfasting or with significant hypertriglyceridemia. OBJECTIVE: Our aim was to determine the clinical equivalence of directly measured-LDL-C, using a Siemens Advia Chemistry System, and fasting C-LDL-C. METHODS: Eighty-one subjects recruited for two cholesterol treatment studies had at least one C-LDL-C and D-LDL-C performed simultaneously; 64 had a repeat lipid assessment after 4 to 6 weeks of therapy, resulting in 145 pairs of C-LDL-C and D-LDL-C. RESULTS: There was significant correlation between D-LDL-C and C-LDL-C (r² = 0.86). Correlation was significantly better in those with lower total cholesterol, triglycerides, and high-density lipoprotein. In 60% of subjects, the difference between D-LDL-C and C-LDL-C was more than 5 mg/dL and greater than 6%. Clinical concordance between D-LDL-C and C-LDL-C was present in 40% of patients, whereas clinical discordance was noted in 25%. One-third had greater than a 15 mg/dL difference between D-LDL-C and C-LDL-C, whereas 25% had a greater than 20 mg/dL difference. In 47% of subjects, the difference between D-LDL-C and C-LDL-C at baseline and follow-up changed by a minimum of 10% or 10 mg/dL. CONCLUSIONS: Our findings suggest that D-LDL-C is not clinically equivalent to C-LDL-C. This puts into question the current recommendation of using D-LDL-C in situations in which C-LDL-C would be inaccurate.

Comparison of the postoperative analgesic efficacy of intravenous patient-controlled analgesia with tramadol to intravenous patient-controlled analgesia with opioids.

BACKGROUND: Intravenous patient-controlled analgesia (IV PCA) with tramadol is an accepted method to deliver postoperative analgesia outside North America; however, the analgesic efficacy of this analgesic agent when compared with IVPCA with opioids is uncertain. As such, the authors undertook a systematic review to compare the analgesic efficacy of IVPCA tramadol with that of IVPCA with opioids. METHODS: The authors used the National Library of Medicine's Medline database to search for terms related to tramadol and patient-controlled analgesia. Inclusion criteria were randomized controlled trials (RCTs) comparing IVPCA tramadol with IVPCA opioid and RCTs published in the English language. Relevant data were abstracted from accepted studies. Meta-analysis was performed using RevMan 4.2.10 (The Cochrane Collaboration, 2004). A random effects model was used. RESULTS: A total of 190 abstracts were obtained from the above search, and a total of 12 RCTs met the above inclusion criteria. There was no difference in weighted visual analog scale pain scores between IVPCA tramadol versus IVPCA opioid at 48 hours postoperatively or risk of sedation or fatigue. IVPCA tramadol was associated with a higher odds of postoperative nausea and vomiting [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.07-2.14) but a lower odds of pruritus (OR = 0.43, 95% CI = 0.19-0.98). DISCUSSION: IVPCA tramadol appears to produce similar pain scores when compared with that from IVPCA opioids; however, the side effect profile is different between the two groups. Because of the relatively small sample size, no determination of the relative "safety" (eg, respiratory depression) of one regimen over the other can be made, and larger RCTs would be needed for such a determination.

Relation of baseline plasma ADMA levels to cardiovascular morbidity and mortality at two years in men with diabetes mellitus referred for coronary angiography.

BACKGROUND: Patients with diabetes mellitus (DM) have been shown to have higher levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Higher plasma levels of ADMA have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis by lowering NO levels. High baseline plasma levels of ADMA in patients with DM have been shown to predict diabetes related complications. However, there are limited data on the prognostic significance of baseline ADMA levels in patients with established DM. METHODS: The present study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 170 high-risk diabetic men with known or suspected coronary artery disease who were referred for coronary angiography. All patients were followed prospectively for the development of vascular outcomes, including all-cause mortality. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as hs-CRP and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of all-cause mortality (HR 2.63, 95% CI 1.13-6.11, p=0.0247) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality or MI (fatal or non-fatal) (HR 2.44, 95% CI 1.26-4.72, p=0.0079), as well as the composite outcome of all-cause mortality, MI (fatal or nonfatal), or stroke (HR 2.00, 95% CI 1.10-3.62, p=0.0232). CONCLUSION: These data demonstrate that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including all-cause mortality) in patients with DM.

Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography.

BACKGROUND: Red blood cell distribution width (RDW), a numerical measure of the variability in size of circulating erythrocytes, has recently been shown to be a strong predictor of adverse outcomes in patients with heart failure and in patients with prior myocardial infarction but no symptomatic heart failure at baseline, even after adjustment for hematocrit. However, there are no data in other cardiac populations, including patients with acute coronary syndromes (ACS). METHODS: The present study investigated the long-term prognostic significance of baseline RDW in a well-characterized cohort of 389 male patients who were referred to coronary angiography for a variety of indications. All patients were followed prospectively for all-cause mortality, and data regarding this endpoint was available for 97% of the population at 24 months. RESULTS: After controlling for a variety of baseline variables (including hemoglobin and the presence of heart failure), RDW (analyzed as a categorical variable comparing the upper tertile of baseline values to the lower two levels combined) was a strong and independent predictor of all-cause mortality using a Cox proportional hazards model [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.50-4.84, p=0.0008]. In addition, baseline RDW was also an independent predictor of all-cause mortality in the non-anemic (HR 4.73, 95% CI 2.06-10.86, p=0.0003) and ACS (HR 2.90, 95% CI 1.32-6.38, p=0.0082) subpopulations of patients. CONCLUSIONS: These data demonstrate that elevated RDW is a strong and independent predictor of all-cause mortality in an unselected population of male patients across a broad spectrum of risk (including ACS) referred for coronary angiography.

Relation of baseline plasma phospholipid transfer protein (PLTP) activity to left ventricular systolic dysfunction in patients referred for coronary angiography.

Phospholipid transfer protein (PLTP) is an important modulator of phospholipid transfer and exchange among proteins. It also plays a role in inflammation and oxidative stress. Accordingly, PLTP has been implicated in the development of atherosclerosis. Left ventricular (LV) systolic dysfunction is common in patients with atherosclerosis, and both inflammation and oxidative stress have also been implicated in its development and progression. The goal of the present study was to examine the relation between plasma PLTP activity and LV systolic function. Baseline plasma PLTP activity was measured in 389 male patients referred for coronary angiography for a variety of indications. Detailed clinical, angiographic and laboratory characteristics were available for the patients. Compared to those patients with normal LV function (defined as an ejection fraction of >or=55% on ventriculography), patients with any degree of LV dysfunction had elevated PLTP activity (median PLTP 17.8 pmol/microl/h versus 15.9 pmol/microl/h, p=0.0038). Using multivariate analysis, and adjusting for a variety of confounding variables known to affect both LV function and PLTP activity, PLTP activity was an independent predictor of the presence of any left ventricular systolic dysfunction in the entire population (OR 1.47, 95% CI 1.12-1.93, p=0.0052). Furthermore, PLTP activity was an independent predictor of the presence of LV dysfunction in both patients with and without myocardial infarction on presentation (OR 2.39, 95% CI 1.18-4.86, p=0.0161 and OR 1.41, 95% CI 1.05-1.89, p=0.0206, respectively). In conclusion, PLTP activity may represent a novel marker of LV systolic dysfunction in patients with known or suspected coronary artery disease.

Effect on serum lipid levels of switching dose of ezetimibe from 10 to 5 mg.

Although during its initial development, lower doses of ezetimibe reduced low-density lipoprotein (LDL) significantly, ezetimibe is available only in 10-mg form. Compliant patients receiving ezetimibe 10 mg were randomized in a blinded fashion to continue therapy with ezetimibe 10 mg or to convert to a split-tablet 5-mg dose. Lipid panels were collected at baseline and after 4 weeks of therapy. The impact of the 2 ezetimibe dosing strategies on LDL and the achievement of the Adult Treatment Panel III LDL goal was evaluated. One hundred thirty patients receiving ezetimibe 10 mg were screened for eligibility. Thirty-nine of the 130 patients were randomized; 36 patients successfully completed the study. All patients who had achieved their Adult Treatment Panel III LDL goals at baseline remained at their LDL goals after conversion to 5 mg. In conclusion, conversion to the lower dose of ezetimibe did not result in any clinically meaningful or statistically significant changes in any lipid parameter.

Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography.

BACKGROUND: Nitric oxide (NO) is produced from L-arginine by NO synthase and is an important molecule with antiatherogenic properties. Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of endothelial NO synthase. As such, it has been associated with endothelial dysfunction and elevated circulating levels of ADMA have been found in patients with cardiovascular risk factors. In addition, high baseline plasma levels of ADMA have been shown to be an independent predictor of adverse outcomes in a variety of patient populations. However, there are very limited data in patients with acute coronary syndromes (ACS). METHODS: This study investigated the long-term prognostic significance of baseline plasma ADMA levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography. All patients were followed up prospectively for the development of vascular outcomes. RESULTS: After controlling for a variety of baseline variables (including established biomarkers such as high-sensitivity C-reactive protein and fibrinogen), plasma ADMA levels (analyzed as the upper tertile of baseline values compared with the lower two tertiles) were a strong and independent predictor of each of the individual endpoints of all-cause mortality [hazard ratio (HR): 2.45, 95% confidence interval (CI): 1.08-5.57; P=0.0325] and myocardial infarction (HR: 2.28, 95% CI: 1.14-4.57; P=0.0204) when using a Cox proportional hazards model. In addition, baseline ADMA values were also an independent predictor of the composite outcome of all-cause mortality, fatal or nonfatal myocardial infarction, or stroke (HR: 1.81, 95% CI: 1.01-3.25; P=0.0482). CONCLUSION: These data show that elevated baseline levels of ADMA are a strong and independent predictor of cardiovascular outcomes (including mortality) in patients with ACS.

Ezetimibe 5 and 10 mg for lowering LDL-C: potential billion-dollar savings with improved tolerability.

OBJECTIVE: To compare the clinical efficacy of ezetimibe 5 mg (prescribed as a 10-mg tablet split in half) with a whole 10-mg tablet. STUDY DESIGN: From January 2003 through July 2005, all Bronx Veterans Administration ezetimibe prescriptions were for 10 mg. In August 2005, it was mandated that all new ezetimibe prescriptions be 5 mg, prescribed as a 10-mg tablet split in half. METHODS: The impact of the 2 ezetimibe dosing strategies on percent lowering of low-density lipoprotein cholesterol (LDL-C) and achievement of National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals was assessed in all patients prescribed ezetimibe 5 or 10 mg. RESULTS: A total of 272 patients were prescribed ezetimibe; 86 received 5 mg and 186 received 10 mg. Of those 272 patients, 197 had evaluable baseline and posttreatment LDL-C (55 taking the 5-mg dose and 142 taking the 10-mg dose). The effects of ezetimibe 5 and 10 mg on all lipid parameters were similar. Ezetimibe 10 mg reduced LDL-C by 26.1%, whereas 5 mg reduced LDL-C by 25.8%. The percentages of patients achieving goal LDL-C were similar: 61.8% (5 mg) and 60.5% (10 mg). CONCLUSION: These data strongly suggest that ezetimibe 5 mg and ezetimibe 10 mg are clinically equivalent with respect to LDL-C reduction and achievement of ATP III LDL-C goals. Widespread adoption of this low-dose strategy could result in a potential cost savings of more than a billion dollars annually, with a potential reduction in hepatotoxicity.

Prognostic implications of normal (<0.10 ng/ml) and borderline (0.10 to 1.49 ng/ml) troponin elevation levels in critically ill patients without acute coronary syndrome.

Borderline increase of troponin I (cTnI) is associated with higher rates of cardiovascular events compared with normal levels in the setting of acute coronary syndrome (ACS), but the significance of borderline cTnI levels in patients without chest pain may differ. The aim of this study was to determine the prognostic implications of intermediate serum cTnI levels in patients without ACS in the intensive care unit (ICU). This was a 12-month retrospective study of 240 patients without ACS in the ICU with normal (<0.1 ng/ml) or intermediate (0.1 to 1.49 ng/ml) cTnI levels. End points included in-hospital mortality, lengths of ICU and hospital stays, and rates of postdischarge readmission and mortality. Overall in-hospital mortality was 13%, with 5% in the normal cTnI group and 28% in the intermediate cTnI group. By multivariate analysis, intermediate cTnI was independently associated with in-hospital mortality (p = 0.004) and length of ICU stay (p = 0.028). The only other independent risk factor for inpatient mortality was a standardized ICU prognostic measurement (Simplified Acute Physiology Score II score). Intermediate cTnI had no prognostic implications regarding length of hospital stay, readmission rate, or postdischarge mortality at 6 months. In conclusion, an intermediate level of cTnI in patients without ACS in the ICU is an independent prognostic marker predicting in-hospital mortality and length of ICU stay. Patients with intermediate cTnI levels who survive to discharge have equivalent out-of-hospital courses for up to 6 months compared with patients with normal cTnI levels.

Baseline plasma adiponectin levels as a predictor of left ventricular systolic dysfunction in patients referred for coronary angiography.

The objective of the present study was to determine the association between plasma adiponectin and left ventricular (LV) systolic function. Baseline plasma adiponectin was measured in 389 patients undergoing coronary angiography for a variety of indications at a Veterans Affairs Medical Center. Detailed demographic, clinical, laboratory, and angiographic data were available for patients. LV systolic function was assessed using ventriculography, and patients were grouped into those with normal or mild dysfunction (ejection fraction > or =45%) versus those with moderate to severe systolic dysfunction (ejection fraction <45%). After adjusting for a variety of clinically relevant covariates known to affect LV systolic function, adiponectin was independently associated with LV systolic function in the entire cohort of patients (p = 0.0002) using multivariate linear regression analysis. In addition, using multivariate logistic regression analysis, adiponectin was an independent predictor of the presence of moderate to severe LV dysfunction (odds ratio 1.54, 95% confidence interval 1.21 to 1.97, p = 0.0005). Moreover, baseline adiponectin was also independently associated with LV function in both the myocardial infarction (MI) and non-MI subpopulations of patients (p = 0.0401 and p= 0.0023, respectively). Finally, in the non-MI subpopulation, baseline adiponectin was an independent predictor of moderate to severe LV systolic dysfunction (odds ratio 1.52, 95% confidence interval 1.15 to 2.02, p = 0.0034). In conclusion, baseline plasma adiponectin was an independent predictor of LV systolic dysfunction in a population of patients referred for coronary angiography.