Improved diabetes control in the elderly delays global cognitive decline.

OBJECTIVES: To examine whether improved diabetes control is related to better cognitive outcomes. DESIGN: Randomized control trial. SETTING: A randomized trial of telemedicine vs. usual care in elderly persons with type 2 diabetes. PARTICIPANTS: Participants were 2169 persons 55 years and older with type 2 diabetes from New York City and Upstate New York. INTERVENTION: The diabetes case management intervention was implemented by a diabetes nurse, via a telemedicine unit in the participant's home, and in coordination with the primary care physician. MEASUREMENTS: Hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low density lipoprotein cholesterol (LDL), were measured at a baseline visit and at up to 5 annual follow-up visits. Global cognition was measured at those visits with the Comprehensive Assessment and Referral Evaluation (CARE). RESULT: In mixed models the intervention was related to slower global cognitive decline in the intervention group (p = 0.01). Improvements in HbA1c (p = 0.03), but not SBP or LDL, mediated the effect of the intervention on cognitive decline. CONCLUSION: Improved diabetes control in the elderly following existing guidelines through a telemedicine intervention was associated with less global cognitive decline. The main mediator of this effect seemed to be improvements in HbA1c.

The relationship between inflammation, obesity and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA).

It has been suggested that inflammation is important in the aetiology of hypertension and that this may be most relevant among obese persons. To study this, we examined the independent relationships between obesity, inflammation-related proteins (interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen) and risk for hypertension in the Multi-Ethnic Study of Atherosclerosis (MESA). Hypertension status, defined as a blood pressure ≥140/90 mm Hg or a history of hypertension and use of blood pressure medications, was determined at baseline and two subsequent exams over 5 years. Among 3543 non-hypertensives at baseline, 714 individuals developed incident hypertension by Exam 3. Cox proportional hazard models were used to determine the relationship between baseline levels of IL-6, CRP and fibrinogen and future risk of hypertension. One s.d. difference in baseline concentration of IL-6, CRP or fibrinogen was associated with 20-40% greater risk of incident hypertension. This risk was attenuated after accounting for other hypertension risk factors (hazard ratio (HR) IL-6: 1.13 (95% CI: 1.04-1.23); CRP: 1.11 (95% CI: 1.02-1.21); fibrinogen 1.0 (95% CI: 0.92-1.08)). Conversely, obesity was an independent risk factor for hypertension risk, minimally impacted by other covariates, including IL-6 and CRP (HR 1.72 (95% CI: 1.36-2.16)). IL-6 and CRP did not modify the relationship between obesity and hypertension, though an adjusted twofold greater risk was observed for obese individuals with a CRP >3 mg l⁻¹ compared with CRP <1 mg l⁻¹. The relationship between inflammation-related proteins and hypertension risk was predominantly explained by other hypertension risk factors. Obesity, independent of inflammation, remained a potent risk factor for future hypertension.

Tissue factor pathway inhibitor, vascular risk factors and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage. OBJECTIVE: We hypothesized an association of higher total TFPI with subclinical atherosclerosis. PATIENTS/METHODS: Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45-84, from four ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI). RESULTS: TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th quartile versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0-1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1-4.0) and a 1.6-fold (95% CI 1.1-2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups. CONCLUSIONS: In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.

Incremental value of simultaneous assessment of myocardial function and perfusion with technetium-99m sestamibi for prediction of extent of coronary artery disease.

OBJECTIVES: This study assessed the incremental value of technetium-99m myocardial single-photon emission computed tomography (SPECT) and simultaneous first-pass radionuclide angiography, when added to treadmill exercise, for prediction of the extent of coronary artery disease. BACKGROUND: Technetium-99m count statistics permit the simultaneous assessment of myocardial perfusion and function. However, whether this characteristic improves prediction of the extent of coronary artery disease remains unknown. METHODS: We studied 70 consecutive patients who had coronary angiography within 6 months of the scintigraphic study. All patients underwent a symptom-limited treadmill exercise test. Treadmill data were summarized using a previously validated score. Left ventricular ejection fraction and regional wall motion were evaluated from a first-pass radionuclide angiogram acquired at peak treadmill exercise in the anterior view. Perfusion was assessed visually. Extent of angiographic disease was expressed as the presence or absence of multivessel disease (more than two coronary artery territories with > 50% stenosis) and as a score that reflects the location of severe (> 75%) stenosis. RESULTS: Stepwise addition of scintigraphic data (perfusion first, followed by function) to the treadmill score showed significant incremental value for prediction of the angiographic score at each step; exercise ejection fraction alone was the strongest independent predictor. Discriminant accuracy for detection of multivessel disease was also improved by the addition of perfusion information to the treadmill score and addition of regional wall motion analysis to both of them. In this case, ejection fraction failed to show independent value. CONCLUSIONS: The addition of simultaneously performed sestamibi perfusion SPECT and first-pass radionuclide angiography to the treadmill exercise test significantly improved prediction of the extent of coronary artery disease.

Incremental prognostic value of exercise thallium-201 myocardial single-photon emission computed tomography late after coronary artery bypass surgery.

OBJECTIVES: This study assessed the incremental prognostic value of exercise thallium-201 myocardial perfusion single-photon emission computed tomography (SPECT) performed > or = 5 years after coronary artery bypass surgery. BACKGROUND: Thallium-201 scintigraphy has shown significant prognostic value in a variety of populations with suspected and known coronary artery disease. However, its value in patients with previous bypass surgery remains unknown. METHODS: We studied 294 patients who were prospectively followed up. Cox proportional hazards models for prediction of "hard" events (cardiac death and nonfatal infarctions) were constructed, with variables considered for inclusion in hierarchic order: clinical and exercise data first, followed by scintigraphic information. RESULTS: Mean (+/- SD) follow-up duration after scintigraphy was 31 +/- 11 months. There were 20 cardiac deaths and 21 nonfatal acute myocardial infarctions. Twenty-nine patients had late (> 60 days after thallium-201 SPECT) revascularization procedures or underwent repeat bypass surgery or percutaneous transluminal angioplasty. Shortness of breath and peak exercise heart rate were the most important clinical predictors of hard events. Two scintigraphic variables added significant prognostic information to the clinical model: the thallium-201 summed reversibility score (summation of segmental differences between stress and redistribution scores) and the presence of increased lung uptake of the radiotracer. The global chi-square statistic for this model was twice as high as that for the clinical/exercise model alone (49.7 vs. 24.2). When a second multivariate Cox model was built adding "soft" events (i.e., late revascularization procedures) as outcomes of interest, the summed reversibility score was selected as an independent scintigraphic predictor of events. The global chi-square statistic for this model was 50.7, three times as high as that for the clinical/exercise model alone. CONCLUSIONS: After evaluation of treadmill and exercise data, thallium-201 myocardial perfusion SPECT provided incremental prognostic information in patients late after bypass.

Afterimages: integration of diagnostic information through Bayesian enhancement of scintigraphic images.

Although the diagnostic accuracy of myocardial perfusion scintigraphy can be improved by additional consideration of clinical and exercise information, multivariate prediction models are infrequently used for this purpose in the clinical setting. We therefore developed a Bayesian algorithm that instead transforms the scintigraphic image itself, modifying defect contrast as a function of the pretest likelihood of coronary artery disease. The algorithm was tested in computer simulations of myocardial perfusion scintigraphy with data from 378 patients (166 from California and 212 from West Virginia) who underwent planar exercise thallium-201 scintigraphy and coronary angiography. Images were interpreted before and after enhancement by eight readers (four at each medical center) with different training orientations (internist, radiologist, cardiologist, nuclear cardiologist, and nuclear medicine technologist) who used a four-point score (from 0, normal to 3, severe defect). Accuracy was quantified as area under a receiver-operating characteristic (ROC) curve. Improvements in accuracy obtained by the algorithm were compared to those provided by multiple logistic regression. Overall, Bayesian enhancement increased ROC area from 0.63 +/- 0.04 to 0.71 +/- 0.04 (p < 0.01). The improvement was consistent for all 16 reading sets (eight readers multiplied by two patient populations; p < 0.05). In comparison, multiple logistic regression increased ROC area from 0.63 +/- 0.04 to 0.79 +/- 0.03 (p < 0.01), outperforming interpretation of the enhanced images in 13 of the 16 reading sets. Bayesian enhancement improves diagnostic accuracy of conventional scintigraphic image interpretation. The improvement is stable across individuals, training orientations, and patient populations. Although this approach is not as accurate as multiple logistic regression, it may be more practical for widespread clinical application.

Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease.

The aim of this study was to test the hypothesis that regional myocardial washout of technetium-99m teboroxime is slowed in the presence of coronary stenosis. Washout was assessed in 33 catheterized patients and in 13 with a low likelihood of coronary artery disease, using a triple detector camera and dynamic single-photon emission computed tomography, with serial 1-minute acquisitions after injection of 20 to 25 mCi of teboroxime at the third minute of adenosine-induced hyperemia. Washout was measured as the percent change in counts between the first, second and third minutes after injection, as measured in 6 short-axis myocardial regions of interest. Myocardial regions were classified as ischemic (> or = 50% diameter stenosis and no prior myocardial infarct), infarcted, normal (no significant coronary stenosis) or "low likelihood" (from the 13 patients with a low likelihood of coronary artery disease). Teboroxime washout was significantly (p < 0.001) slowed in the ischemic myocardium (12.7 +/- 8.3%) compared with the normal (18.5 +/- 5.7%), low-likelihood (17.8 +/- 6.1%) and infarcted (17.8 +/- 4.4%) zones. There was regional variability in washout rates (% washout/min), with the anterior wall having the lowest (13.8 +/- 3.4%/min) and the inferior wall the highest (20.7 +/- 7.9%/min) values. In regard to individual coronary territories, 21 of 41 ischemic, noninfarcted territories (51%) had abnormal washout compared with 3 of 43 normal territories (7%) (p = 0.001). In conclusion, regional washout of teboroxime is detectably slowed in ischemic, noninfarcted myocardium. The clinical value of washout analysis in teboroxime single-photon emission computed tomography warrants further investigation.