Faculty Bibliography

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.

BACKGROUND: Few data are available on the association of high-sensitivity C-reactive protein (hs-CRP) and mortality independent of low-density lipoprotein (LDL) cholesterol in patients undergoing percutaneous coronary intervention (PCI). METHODS: Consecutive patients (N = 8,834) undergoing PCI between October 28, 2002, and December 31, 2006, were followed through June 30, 2007 (average and maximum follow-up of 1.9 and 4.6 years, respectively). High-sensitivity CRP levels were classified into 4 groups: <1.0, 1.0 to 2.9, 3.0 to 9.9, and > or =10 mg/L. RESULTS: All-cause mortality rates were 14.4, 17.5, 25.7, and 56.4 per 1,000 person-years in patients with hs-CRP levels of <1.0, 1.0 to 2.9, 3.0 to 9.9, and > or =10 mg/L, respectively. Compared with patients with hs-CRP <1.0 mg/L, the hazard ratios of mortality after multivariable adjustment, including LDL cholesterol, associated with hs-CRP levels of 1.0 to 2.9, 3.0 to 9.9, and > or =10 mg/L were 1.27 (95% CI 0.91-1.75), 1.70 (95% CI 1.26-2.29), and 2.99 (95% CI 2.24-3.99), respectively (P trend < .001). After multivariable adjustment, trends of higher all-cause mortality at higher hs-CRP were present for patients with LDL cholesterol <70, 70 to 99, and > or =100 mg/dL (each P < .001). A test for interaction between LDL cholesterol and hs-CRP on all-cause mortality was not significant (P = .30). CONCLUSIONS: High-sensitivity CRP levels provide significant incremental prognostic information for all-cause mortality in long-term follow-up independent of LDL cholesterol.

Imaging has had an important role in cardiovascular disease over the past decade, with the increasing reliance on imaging outcomes as surrogates for clinical end points. Clinical trials now show a trend towards the use of functional, rather than anatomical, imaging modalities. Use of these powerful tools needs to be optimized in the design of cardiovascular trials. In the future, imaging modalities will be fundamental to research and drug development and an increased emphasis will be placed on the relationship between the results of imaging studies and clinical outcomes.

The metabolic syndrome is a clustering of cardiovascular risk factors and is associated with an increased risk of developing diabetes, cardiovascular disease, and kidney disease. Epidemiologic studies have demonstrated differences in prevalence by age, gender, and ethnicity. The prevalence of the metabolic syndrome increases with age through the sixth decade of life among men and seventh decade among women. Most, but not all, studies reported a higher prevalence of the metabolic syndrome among women compared with men. Although the metabolic syndrome is more common among Mexican Americans compared with non-Hispanic whites and blacks, among men the metabolic syndrome is more common among non-Hispanic whites than non-Hispanic blacks; the reverse is true among women. Understanding the basic pathophysiology underlying the metabolic syndrome may help explain the age, gender, and ethnic differences in its prevalence and guide preventive and therapeutic efforts.