Faculty Bibliography

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.

Current models incompletely risk-stratify patients with acute chest pain. In this study, N-terminal pro-B-type natriuretic peptide and cystatin C were incorporated into a contemporary chest pain triage algorithm in a clinically stratified population to improve acute coronary syndrome discrimination. Adult patients with chest pain presenting without myocardial infarction (n = 382) were prospectively enrolled from 2008 to 2009. After clinical risk stratification, N-terminal pro-B-type natriuretic peptide and cystatin C were measured and standard care was performed. The primary end point was the result of a clinical stress test. The secondary end point was any major adverse cardiac event at 6 months. Associations were determined through multivariate stratified analyses. In the low-risk group, 76 of 78 patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 97%). Normal biomarkers predicted normal stress test results with an odds ratio of 10.56 (p = 0.006). In contrast, 26 of 33 intermediate-risk patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 79%). Biomarkers and stress test results were not associated in the intermediate-risk group (odds ratio 2.48, p = 0.09). There were 42 major adverse cardiac events in the overall cohort. No major adverse cardiac events occurred at 6 months in the low-risk subgroup that underwent stress testing. In conclusion, N-terminal pro-B-type natriuretic peptide and cystatin C levels predict the results of stress tests in low-risk patients with chest pain but should not be substituted for stress testing in intermediate-risk patients. There is potential for their use in the early discharge of low-risk patients after clinical risk stratification.

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.

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.

Although current literature demonstrates metabolic abnormalities are associated with mortality, obese patients who tend to have more metabolic abnormalities paradoxically have lower overall mortality rates compared to their normal-weight counterparts. In this study, we examined the prevalence of metabolic abnormality clustering and its relation to mortality in obese and normal-weight patients after percutaneous coronary intervention (PCI). Patients (n = 9,673) undergoing elective PCI from October 2003 through December 2006 at a single urban hospital were categorized by body mass index (BMI) levels of 18.5 to 24.9, 25.0 to 29.9, 30.0 to 34.9, and >/=35 kg/m(2) and by number of metabolic abnormalities possessed (hypertension, impaired fasting glucose/diabetes, triglycerides >/=150 mg/dl, high-density lipoprotein cholesterol < 40 mg/dl, and C-reactive protein >/=2.0 mg/L). All-cause mortality was assessed through June 30, 2007. Mean age of patients was 65.9 years and 66% were men. Prevalences of 4 or 5 metabolic abnormalities were 12%, 18%, 24%, and 31% in patients with BMI levels of 18.5 to 24.9, 25.0 to 29.9, 30 to 34.9, and >/=35 kg/m(2), respectively. In patients with BMI of 30.0 to 34.9 kg/m(2), hazard ratios (95% confidence intervals) for mortality associated with 2, 3, and 4 to 5 metabolic abnormalities versus 0 to 1 metabolic abnormality were 1.31 (0.79 to 2.17), 1.42 (0.83 to 2.43), and 2.39 (1.24 to 4.59), respectively. Analogous hazard ratios for patients with BMI >/=35 kg/m(2) were 1.94 (0.90 to 4.20), 1.44 (0.63 to 3.28), and 2.17 (0.91 to 5.18). All-cause mortality rates per 1,000 person-years were 55.5, 33.7, 28.3, and 33.8 in patients with BMI levels of 18.5 to 24.9, 25 to 29.9, 30 to 34.9, and >/=35 kg/m(2), respectively. In conclusion, BMI levels of 25.0 to 29.9 and 30 to 34.9 kg/m(2) were associated with lower all-cause mortality after PCI. However, an increased number of metabolic abnormalities translated into increased all-cause mortality.

BACKGROUND: Few published data are available on the benefits of aspirin use in patients with unstable angina (UA). HYPOTHESIS: Aspirin use carries a mortality benefit in a population-based cohort of patients presenting with UA. METHODS: All residents of Olmsted County, Minnesota presenting to local emergency departments with acute chest pain from January 1985 through December 1992 having symptoms consistent with UA were identified through medical records. A total of 1628 patients were identified with UA and were stratified by aspirin use in-hospital and at discharge. Cardiovascular mortality and nonfatal myocardial infarction and stroke were assessed over a median of 7.5 years follow-up and all-cause mortality data over a median of 16.7 years. The mean age of patients with UA was 65 years, and 60% were men. RESULTS: After a median of 7.5 years follow-up, all-cause and cardiovascular-mortality rates were lower among patients prescribed versus not prescribed aspirin on discharge. There were 949 postdischarge deaths over the median follow-up of 16.7 years. After multivariable adjustment, aspirin use at discharge was associated with a lower long-term mortality (hazard ratio 0.78; 95% confidence interval, 0.65-0.93). CONCLUSIONS: Aspirin use at hospital discharge following UA is associated with a reduction in long-term mortality. This long-term study extends prior trial results from select populations to a population-based cohort.

BACKGROUND: Stress-only imaging saves time and radiation exposure, but apprehension remains about the reliability, diagnostic, and prognostic accuracy of a normal stress-only study. The objective of this study was to determine the prognosis of stress-only SPECT MPI in routine clinical practice. METHODS: Patients at lower pre-test risk for CAD presenting for a Tc-99m SPECT MPI over a 2-year period underwent a stress-only protocol. If the stress images were normal (attenuation correction was routinely acquired on all patients), rest imaging was not done. Outcomes of the stress-only group were compared to a full rest-stress protocol cohort. Only patients with normal perfusion and left ventricular function, and no known CAD, were included. All-cause mortality was determined using the Social Security Death Index and specific causes of death were determined using the National Death Index. The difference in all-cause and cardiac mortality between groups in the presence of competing risks was assessed using log-normal survival models. RESULTS: Out of 10,609 patients studied during the time period, 1,673 had a normal stress-only study and 3,237 had a normal rest-stress study. At one year, there were 20 total and 3 cardiac deaths (1.2% and 0.2% mortality) in the stress-only group, and 40 total and 4 cardiac deaths (1.2% and 0.1% mortality) in the rest-stress cohort. At the end of follow-up (40 +/- 9 months), there were 46 total and 7 cardiac deaths (2.7% and 0.4% mortality) in the stress-only group, and 119 total and 17 cardiac deaths (3.7% and 0.5% mortality) in the rest-stress cohort. No significant difference between the stress-only and rest-stress cohorts was found after controlling for confounding variables for both all-cause mortality (p = .94) and cardiac mortality (p = .82). CONCLUSIONS: A normal stress-only MPI has an excellent short-term prognosis (both for all-cause and cardiac mortality) comparable to that of a normal rest-stress MPI 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.

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.

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.