Louai Razzouk

NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis

BACKGROUND Studies have demonstrated the success of augmentation of antidepressant therapy with nonsteroidal anti-inflammatory drugs (NSAID) in decreasing depressive symptoms; however, little is known about the benefit of NSAID therapy on depressive symptoms. METHODS This study pooled data from 5 postapproval trials, each trial a 6-week, multicenter, randomized, double-blinded, placebo-controlled, active-comparator, parallel-group study in subjects with active osteoarthritis. Subjects were randomized to placebo group, ibuprofen 800 mg 3 times daily or naproxen 500 mg twice daily group, or Celebrex 200 mg daily group. Apart from different ethnicities enrolled, these trials had identical study designs. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Outcomes measured were change in PHQ-9 score after 6 weeks of NSAID therapy and change in classification of depression with a PHQ-9 score ≥10 as a marker of depression. RESULTS There were 1497 patients included. Median PHQ-9 score was similar in all 3 groups at baseline and after 6 weeks of treatment. Multivariable regression analysis demonstrated a detectable effect in lowering PHQ-9 score in the ibuprofen or naproxen group (-0.31) and Celebrex group (-0.61) (P = .0390). With respect to the change in classification of depression, logistic regression analysis demonstrated a trend towards significant treatment effect of all NSAIDs compared with placebo. CONCLUSION Our analysis of pooled data from 5 postapproval trials shows that NSAID usage demonstrates a trend towards reduction of depression symptoms in patients with osteoarthritis based upon PHQ-9 scores. Future clinical trials should investigate this association with maximum dosage of drugs, increased treatment duration, and monitoring of social and environmental changes.

Clinical risk stratification in the emergency department predicts long-term cardiovascular outcomes in a population-based cohort presenting with acute chest pain: primary results of the Olmsted county chest pain study.

The long-term cardiovascular outcomes of a population-based cohort presenting to the emergency department (ED) with chest pain and classified with a clinical risk stratification algorithm are not well documented. The Olmsted County Chest Pain Study is a community-based study that included all consecutive patients presenting with chest pain consistent with unstable angina presenting to all EDs in Olmsted County, Minnesota. Patients were classified according to the Agency for Health Care Policy and Research (AHCPR) criteria. Patients with ST elevation myocardial infarction and chest pain of noncardiac origin were excluded. Main outcome measures were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days and at a median follow-up of 7.3 years, and mortality through a median of 16.6 years. The 2271 patients were classified as follows: 436 (19.2%) as high risk, 1557 (68.6%) as intermediate risk, and 278 (12.2%) as low risk. Thirty-day MACCE occurred in 11.5% in the high-risk group, 6.2% in the intermediate-risk group, and 2.5% in the low-risk group (p < 0.001). At 7.3 years, significantly more MACCE were recorded in the intermediate-risk (hazard ratio [HR], 1.91; 95% confidence intervals [CI], 1.33-2.75) and high-risk groups (HR, 2.45; 95% CI, 1.67-3.58). Intermediate- and high-risk patients demonstrated a 1.38-fold (95% CI, 0.95-2.01; p = 0.09) and a 1.68-fold (95% CI, 1.13-2.50; p = 0.011) higher mortality, respectively, compared to low-risk patients at 16.6 years. At 7.3 and at 16.6 years of follow-up, biomarkers were not incrementally predictive of cardiovascular risk. In conclusion, a widely applicable rapid clinical algorithm using AHCPR criteria can reliably predict long-term mortality and cardiovascular outcomes. This algorithm, when applied in the ED, affords an excellent opportunity to identify patients who might benefit from a more aggressive cardiovascular risk factor management strategy. Abbreviations: ACC = American College of Cardiology, AHA = American Heart Association, AHCPR = Agency for Health Care Policy and Research, CI = confidence intervals, ECG = electrocardiogram, ED = emergency department, GRACE = Global Registry of Acute Coronary Events, HR = hazard ratio, MACCE = major adverse cardiovascular and cerebrovascular events, STEMI = ST elevation myocardial infarction, TIMI = Thrombolysis in Myocardial Infarction, TRS = derivation of the TIMI risk score, UA/NSTEMI = unstable angina/non-ST-segment elevation myocardial infarction.

Iron Oxide Magnetic Resonance Imaging for Atherosclerosis Therapeutic Evaluation: Still “Rusty?”⁎

Multicenter, randomized, placebo-controlled “outcome” trials with long-term follow-up of thousands of patients are currently being used to evaluate new therapies for cardiovascular disease. Owing to improvements in risk factor modifications as well as to the concomitant use of established treatments, such as statins, leading to a drop in clinical event rates, it is projected that the number of patients enrolled in trials may need to be increased to separate the effect of new therapies from those of established ones. Recently, the JUPITER (Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin) study (1) showed the importance of serologic measures of inflammation. These new in-blood markers may, however, be insufficient when used alone as predictive models of mortality and morbidity (2). Several recent cardiovascular trials have opted to use imaging (quantitative coronary angiography, carotid intima media thickness with ultrasonography, coronary intravascular ultrasonography, and so forth) to measure the impact of promising novel therapeutics (3). Validation of these in vivo diagnostic imaging methods may allow for shorter follow-up times and eventually, for smaller patient populations tested.

Novel Biomarkers for Risk Stratification and Identification of Lifethreatening Cardiovascular Disease: Troponin and Beyond

Chest pain and other symptoms that may represent acute coronary syndromes (ACS) are common reasons for emergency department (ED) presentations, accounting for over six million visits annually in the United States [1]. Chest pain is the second most common ED presentation in the United States. Delays in diagnosis and inaccurate risk stratification of chest pain can result in serious morbidity and mortality from ACS, pulmonary embolism (PE), aortic dissection and other serious pathology. Because of the high morbidity, mortality, and liability issues associated with both recognized and unrecognized cardiovascular pathology, an aggressive approach to the evaluation of this patient group has become the standard of care. Clinical history, physical examination and electrocardiography have a limited diagnostic and prognostic role in the evaluation of possible ACS, PE, and aortic dissection, so clinicians continue to seek more accurate means of risk stratification. Recent advances in diagnostic imaging techniques particularly computed-tomography of the coronary arteries and aorta, have significantly improved our ability to diagnose life-threatening cardiovascular disease. In an era where health care utilization and cost are major considerations in how disease is managed, it is crucial to risk-stratify patients quickly and efficiently. Historically, biomarkers have played a significant role in the diagnosis and risk stratification of several cardiovascular disease states including myocardial infarction, congestive heart failure, and pulmonary embolus. Multiple biomarkers have shown early promise in answering questions of risk stratification and early diagnosis of cardiovascular pathology however many do not yet have wide clinical availability. The goal of this review will be to discuss these novel biomarkers and describe their potential role in direct patient care.

In-stent restenosis in the superficial femoral artery.

As the number of endovascular peripheral arterial interventions is increasing nationwide, so is the rate of observed in-stent restenosis, specifically in the superficial femoral artery. A paucity of literature is available regarding the pathophysiology, risk factors, and therapies associated with in-stent restenosis of the superficial femoral artery. This article summarizes the accumulated knowledge on these topics and sheds some light on the prospects for future therapies.

Is Measuring C-Reactive Protein Useful for Guiding Treatment in Women ≥60 Years and Men ≥50 Years of Age?

Using the results of the JUPITER trial, a recent report estimated that up to 11 million older United States (US) adults with C-reactive protein (CRP) levels > or =2 mg/L not currently recommended statins may benefit from treatment. However, the need to measure CRP in making this treatment decision has not been evaluated. Using data from 887 older US men and women (men > or =50 years old, women > or =60 years old) not currently on or recommended statin therapy participating in the National Health and Nutrition Examination Survey 2003 to 2006, we determined the sensitivity, specificity, and positive and negative predictive values of patient characteristics in identifying the presence of CRP > or =2 mg/L. If CRP > or =2 mg/L were included as an indication for statin therapy, then 90% of older US adults would be recommended treatment. Patients with CRP > or =2 mg/L were more likely (p <0.05) to be current smokers, obese, and have chronic kidney disease. However, characteristics (including demographics, cigarette smoking, obesity, chronic kidney disease, and metabolic syndrome) had low positive predictive values (<70%) for identifying patients with CRP > or =2 mg/L and negative predictive values (<60%) for those with CRP <2 mg/L. In conclusion, these findings suggest patient characteristics cannot be easily used to identify patients with CRP > or =2 mg/L. Given the demonstrated benefits of statin therapy, cost of measuring CRP, and large percentage of older US adults with high CRP, universal statin therapy for older US adults warrants investigation.

Usefulness of Diabetes Mellitus to Predict Long-Term Outcomes in Patients With Unstable Angina Pectoris

The objective of this study was to determine short- and long-term cardiovascular outcomes in unselected patients with diabetes mellitus (DM) with acute ischemic chest pain (AICP). In patients with DM presenting to the emergency department with AICP, short-term cardiovascular outcomes remain discordant between trials and registries, whereas long-term outcomes are not well-described. A consecutive cohort of all residents of Olmsted County, Minnesota, presenting with AICP from January 1, 1985, to December 31, 1992, was followed for a median duration of 16.6 years. The primary outcome was long-term all-cause mortality. Other outcomes included a composite of death, myocardial infarction, stroke, and revascularization (major adverse cardiovascular and cerebrovascular events [MACCEs]) as well as heart failure (HF) events at 30 days and at a median of 7.3 years, respectively. Of the 2,271 eligible patients, 336 (14.8%) were classified with DM. The crude 30-day MACCE rate was 10.1% in patients with DM and 6.1% in those without DM (p = 0.007). HF events were more common in patients with DM at 30 days (9.8% vs 3.1%, p <0.001). At 7.3 years, patients with DM were more likely to experience MACCEs and HF events than those without DM (71.2% vs 45.1%, unadjusted hazard ratio 2.15%, 95% confidence interval 1.87 to 2.48, p <0.001, and 45.1% vs 18.2%, p <0.001, respectively). Over the follow-up period, 272 patients with DM (81.9%) died, compared with 936 (49.2%) without DM (p <0.001). In conclusion, DM is associated with a higher short-term risk for MACCEs and HF and a higher long-term risk for mortality in unselected patients with AICP. DM should be included as a high-risk variable in national acute coronary syndrome guidelines.

Left ventricular hypertrophy by electrocardiography and echocardiography in the African American Study of Kidney Disease Cohort Study

Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m(2.7) in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease.

Aspirin use is associated with an improved long-term survival in an unselected population presenting with unstable angina.

Few published data are available on the benefits of aspirin use in patients with unstable angina (UA).

The Windsock Syndrome: Subpulmonic Obstruction by Membranous Ventricular Septal Aneurysm in Congenitally Corrected Transposition of Great Arteries

Anomalies of the membranous portion of the interventricular septum include perimembranous ventricular septal defect and/or membranous septal aneurysm (MSA). In congenitally corrected transposition of the great arteries (L‐TGA in sinus solitus), the combination of ventricular inversion and arterial transposition creates a unique anatomic substrate that fosters subpulmonic left ventricular outflow tract obstruction by an MSA. The combination of an L‐TGA with subpulmonic obstruction by an MSA is referred to as the windsock syndrome. We report a case of windsock syndrome in a 25‐year‐old man which is to our knowledge the first three‐dimensional echocardiographic description of this congenital entity.