Coronary artery disease (CAD) is the major cause of mortality and morbidity in patients with type 2 diabetes. But the utility of screening patients with type 2 diabetes for asymptomatic CAD is ...controversial.
To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes.
The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study is a randomized controlled trial in which 1123 participants with type 2 diabetes and no symptoms of CAD were randomly assigned to be screened with adenosine-stress radionuclide myocardial perfusion imaging (MPI) or not to be screened. Participants were recruited from diabetes clinics and practices and prospectively followed up from August 2000 to September 2007.
Cardiac death or nonfatal myocardial infarction (MI).
The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. Seven nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (hazard ratio HR, 0.88; 95% confidence interval CI, 0.44-1.88; P = .73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P = .001). Nevertheless, the positive predictive value of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P = .14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups.
In this contemporary study population of patients with diabetes, the cardiac event rates were low and were not significantly reduced by MPI screening for myocardial ischemia over 4.8 years.
clinicaltrials.gov Identifier: NCT00769275.
To assess the prevalence and clinical predictors of silent myocardial ischemia in asymptomatic patients with type 2 diabetes and to test the effectiveness of current American Diabetes Association ...screening guidelines.
In the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, 1,123 patients with type 2 diabetes, aged 50-75 years, with no known or suspected coronary artery disease, were randomly assigned to either stress testing and 5-year clinical follow-up or to follow-up only. The prevalence of ischemia in 522 patients randomized to stress testing was assessed by adenosine technetium-99m sestamibi single-photon emission-computed tomography myocardial perfusion imaging.
A total of 113 patients (22%) had silent ischemia, including 83 with regional myocardial perfusion abnormalities and 30 with normal perfusion but other abnormalities (i.e., adenosine-induced ST-segment depression, ventricular dilation, or rest ventricular dysfunction). Moderate or large perfusion defects were present in 33 patients. The strongest predictors for abnormal tests were abnormal Valsalva (odds ratio OR 5.6), male sex (2.5), and diabetes duration (5.2). Other traditional cardiac risk factors or inflammatory and prothrombotic markers were not predictive. Ischemic adenosine-induced ST-segment depression with normal perfusion (n = 21) was associated with women (OR 3.4). Selecting only patients who met American Diabetes Association guidelines would have failed to identify 41% of patients with silent ischemia.
Silent myocardial ischemia occurs in greater than one in five asymptomatic patients with type 2 diabetes. Traditional and emerging cardiac risk factors were not associated with abnormal stress tests, although cardiac autonomic dysfunction was a strong predictor of ischemia.
OBJECTIVE:--The purpose of this study was to assess whether the prevalence of inducible myocardial ischemia increases over time in patients with type 2 diabetes. RESEARCH DESIGN AND ...METHODS--Participants enrolled in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study underwent repeat adenosine-stress myocardial perfusion imaging 3 years after initial evaluation. Patients with intervening cardiac events or revascularization and those who were unable or unwilling to repeat stress imaging were excluded. RESULTS:--Of the initial 522 DIAD patients, 358 had repeat stress imaging (DIAD-2), of whom 71 (20%) had ischemia at enrollment (DIAD-1). Of 287 patients with normal DIAD-1 studies, 259 (90%) remained normal in DIAD-2, whereas 28 (10%) developed new ischemia in DIAD-2. Of the 71 patients with abnormal DIAD-1 studies, 56 (79%) demonstrated resolution of ischemia, whereas 15 (21%) remained abnormal. During this 3-year interval, medical treatment was intensified, with more patients using statins, aspirin, and ACE inhibitors than at baseline. Patients with resolution of ischemia had significantly greater increases in these medications than patients who developed new ischemia (P = 0.04). CONCLUSIONS:--Thus, the majority of asymptomatic patients with type 2 diabetes demonstrated resolution of ischemia upon repeat stress imaging after 3 years. This resolution was associated with more intensive treatment of cardiovascular risk factors.
ABSTRACT
Biochemical changes in vivo and pathway interactions were investigated using integrated physiological and metabolic responses of Arabidopsis thaliana L. to ultraviolet (UV) radiation ...(280–400 nm) at 9.96 kJ m−2 d−1 over the entire life cycle from seed to seed (8 weeks). Columbia‐0 (Col‐0) and a UV‐B sensitive accession (fah‐1) showed significant (P < 0.001) reductions in leaf growth after 6 weeks. Col‐0 recovered growth after 8 weeks, with recovery corresponding to a switch from production of phenylpropanoids to flavonoids. fah‐1 failed to recover, indicating that sinapate production is an essential component of recovery. Epidermal features show that UV radiation caused significant (P < 0.001) increases in trichome density, which may act as a structural defence response. Stomatal indices showed a significant (P < 0.0001) reduction in Col‐0 and a significant (P < 0.001) increase in fah‐1. Epidermal cell density was significantly increased under UV radiation on the abaxial leaf surface, suggesting that that a fully functioning phenylpropanoid pathway is a requirement for cell expansion and leaf development. Despite wild‐type acclimation, the costs of adaptation lead to reduced plant fitness by decreasing flower numbers and total seed biomass. A multi‐phasic acclimation to UV radiation and the induction of specific metabolites link stress‐induced biochemical responses to enhanced acclimation.
OBJECTIVE: To estimate baseline cardiovascular risk of 1,123 participants in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study and to assess cardiac event rates and the effect of ...screening on outcomes in these higher-risk participants. RESEARCH DESIGN AND METHODS: Baseline cardiovascular risk was assessed using four established methods: Framingham score, UK Prospective Diabetes Study (UKPDS) risk engine, criteria of the French-Speaking Association for the Study of Diabetes and Metabolic Diseases, and the presence or absence of metabolic syndrome. Cardiac events (cardiac death or nonfatal myocardial infarction) were assessed during the 4.8-year follow-up in participants with intermediate/high cardiovascular risk. RESULTS: By various risk-stratification approaches, 53-75% of participants were defined as having intermediate or high cardiovascular risk. The prevalence of inducible ischemia on screening in these individuals ranged from 21 to 24%, similar to lower-risk participants (19-23%). Cardiac event rates were greater in intermediate-/high-risk versus low-risk groups, but this was only significant for the UKPDS risk engine (4.2 vs. 1.2%, P = 0.002). The annual cardiac event rate was <1% in all risk groups, except in the high-risk UKPDS group (~2% per year). In intermediate-/high-risk participants randomized to screening versus no screening, 4.8-year cardiac event rates were similar (2.5-4.8% vs. 3.1-3.7%). CONCLUSIONS: A substantial portion of the DIAD population was defined as having intermediate/high baseline cardiovascular risk. Nevertheless, their annual cardiac event rate was low and not altered by routine screening for inducible ischemia.
Pulse pressure has been related to higher risk of cardiovascular events in older persons. Isolated systolic hypertension is common among the elderly and is accompanied by elevated pulse pressure. ...Treatment of isolated systolic hypertension may further increase pulse pressure if diastolic pressure is lowered to a greater extent than systolic pressure. Little is known regarding pulse pressure as a predictor of cardiovascular outcomes in elderly persons with isolated systolic hypertension, and the influence of treatment on the pulse pressure effect. We assessed the relation between pulse pressure, measured throughout the follow-up period, and the incidence of coronary heart disease (CHD), heart failure (HF), and stroke in 4,632 participants in the Systolic Hypertension in the Elderly Program, a 5-year randomized, placebo-controlled clinical trial of treatment of isolated systolic hypertension in older adults. In the treatment group, a 10-mm Hg increase in pulse pressure was associated with a statistically significant 32% increase in risk of HF and a 24% increase in risk of stroke after controlling for systolic blood pressure and other known risk factors, as well as with a 23% increase in risk of HF and a 19% increase in risk of stroke after controlling for diastolic blood pressure and other risk factors. Pulse pressure was not significantly associated with HF or stroke in the placebo group, nor with incidence of CHD in either the placebo or treatment group. These results suggest that pulse pressure is a useful marker of risk for HF and stroke among older adults being treated for isolated systolic hypertension.
Objective:
The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 ...diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures.
Methods:
Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization.
Results:
Over 5 years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity.
Conclusion:
Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.
The objective of this study was to determine the relationship of sociodemographics; diabetes-related factors, including diabetes-related microvascular complications; cardiac risk factors; and ...psychological factors with quality of life (QOL). Participants enrolled at three sites in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study were invited to participate in this ancillary study. Questionnaires assessing psychological factors were completed by participants, and the remainder of the data was obtained as part of the DIAD study. Many participants had elevated levels of anxiety (n = 91; 82%), depressive symptoms (n = 16; 14%), anger (n = 38; 34%), and hostility (n = 17; 17%). Results of multivariate analyses conducted for each of the eight domains on the Medical Outcomes Study Short Form-36 and two Diabetes Quality of Life domains demonstrated that in the majority of models (42% to 68% of the variance explained), female sex, peripheral or autonomic neuropathy, physical inactivity, higher body mass index, and the presence of depressive symptoms and anxiety were associated with poorer QOL (p = .0001). These findings demonstrate that anxiety, depressive symptoms, and neuropathy are prevalent in older adults with type 2 diabetes. In addition, potentially important correlations were demonstrated between psychological factors, neuropathy, body mass index, and physical inactivity.
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