Relationship between vascular stiffness and stress myocardial perfusion imaging in asymptomatic patients with diabetes.

PURPOSE: Vascular stiffness may potentially be used as a screening tool to identify asymptomatic patients with diabetes with abnormal myocardial perfusion. The purpose of this study was therefore to determine the association between vascular stiffness, measured in term of pulse wave velocity (PWV) and augmentation index (AIx), and abnormal myocardial perfusion imaging (MPI) in asymptomatic patients with diabetes. METHODS: Prospectively, 160 asymptomatic patients with diabetes (mean age 51 years, 87 men) underwent MPI with adenosine stress. The summed stress score (SSS) was determined in each patient according to a 17-segment and five-point score. Abnormal MPI (SSS ≥ 3) was classified as moderate (SSS 3-7) or severe (SSS ≥ 8) MPI defects. Using applanation tonometry, the carotid-femoral PWV and the radial AIx corrected to 75 beats per minute were determined noninvasively. RESULTS: MPI was abnormal in 61 patients (38%), with severe MPI defects in 22 patients (14%). Mean PWV increased with deteriorating MPI from 8.4 ± 2.2 m/s in normal MPI to 9.0 ± 2.2 m/s in moderate MPI defects (p = 0.11) and to 11.1 ± 2.5 m/s in severe MPI defects (p < 0.01). Likewise, mean AIx increased from 18.4 ± 13.4% to 19.4 ± 10.7% (p = 0.66) and to 25.4 ± 9.0% (p = 0.03). After adjustment for age and other risk factors, PWV remained a significant predictor of severe MPI defects (p = 0.01, OR 1.50, 95% CI 1.11-2.00), whereas AIx was no longer significant (p = 0.20). CONCLUSION: Vascular stiffness measured by PWV is associated with severe MPI defects in asymptomatic patients with diabetes.

Subclinical left ventricular dysfunction and coronary atherosclerosis in asymptomatic patients with type 2 diabetes.

AIMS: The aim of the present study was to evaluate whether subclinical left ventricular (LV) systolic dysfunction is independently related to subclinical coronary atherosclerosis in type 2 diabetic patients and if it could provide incremental information over baseline characteristics to identify high-risk patients. METHODS AND RESULTS: A total of 234 asymptomatic, type 2 diabetic patients without overt LV systolic dysfunction underwent coronary artery calcium (CAC) scoring and two-dimensional echocardiography. The LV global longitudinal strain (GLS) was assessed using automated function imaging. Patients with coronary atherosclerosis (CAC > 0; n = 139) had more impaired GLS when compared with patients without coronary atherosclerosis (CAC = 0; n = 95; -18.0 ± 2.8 vs. -16.3 ± 3.0%, P < 0.001). At multivariate analysis, male gender, hypertension, hypercholesterolaemia, and the LV GLS were independently associated with coronary atherosclerosis. The addition of the LV GLS to other selected independent clinical variables significantly improved the ability to predict coronary atherosclerosis in these patients (χ(2) = 58.92; P = 0.001). CONCLUSION: Type 2 diabetic patients with coronary atherosclerosis showed a more impaired LV GLS compared with patients without coronary atherosclerosis. The presence of subclinical LV systolic dysfunction provides significant incremental value for the identification of diabetic patients having coronary atherosclerosis.

Prevalence of coronary artery disease across the Framingham risk categories: coronary artery calcium scoring and MSCT coronary angiography.

BACKGROUND: Non-invasive assessment of subclinical atherosclerosis by means of coronary artery calcium scoring (CACS) and multi-slice computed tomography (MSCT) coronary angiography could improve patients' risk stratification. However, data relating observations on CACS and MSCT coronary angiography to traditional risk assessment are scarce. METHODS AND RESULTS: In 314 consecutive outpatients (54 +/- 13 years, 56% males) without known CAD, CACS and 64-slice MSCT coronary angiography were performed. According to the Framingham risk score (FRS), 51% of patients were at low, 24% at intermediate and 25% at high risk, respectively. MSCT angiograms showing atherosclerosis were classified as showing obstructive (> or =50% luminal narrowing) CAD or not. Both CACS and MSCT coronary angiography showed a high prevalence of normal coronary arteries in low FRS patients (70% and 61%, respectively). An increase in the prevalence of CACS >400 (4% low vs 19% intermediate vs 36% high), CAD (39% low vs 79% intermediate vs 91% high), and obstructive CAD (15% low vs 43% intermediate vs 58% high) was observed across the FRS categories (P < .0001 for all comparisons). CONCLUSIONS: A strong positive relationship exists between FRS and the prevalence and extent of atherosclerosis. Especially in intermediate FRS patients, CACS and MSCT coronary angiography provide useful information on the presence of subclinical atherosclerosis.

Impact of Diabetes and Increasing Body Mass Index Category on Left Ventricular Systolic and Diastolic Function.

BACKGROUND: Diabetes and obesity are both worldwide growing epidemics, and both are independently associated with increased risk for heart failure and death. The aim of this study was to examine the additive detrimental effect of both diabetes and increasing body mass index (BMI) category on left ventricular (LV) myocardial systolic and diastolic function. METHODS: The present retrospective multicenter study included 653 patients (337 with type 2 diabetes and 316 without diabetes) of increasing BMI category. All patients had normal LV ejection fractions. LV myocardial systolic (peak systolic global longitudinal strain and peak systolic global longitudinal strain rate) and diastolic (average mitral annular e' velocity and early diastolic global longitudinal strain rate) function was quantified using echocardiography. RESULTS: Increasing BMI category was associated with progressively more impaired LV myocardial function in patients with diabetes (P < .001). Patients with diabetes had significantly more impaired LV myocardial function for all BMI categories compared with those without diabetes (P < .001). On multivariate analysis, both diabetes and obesity were independently associated with an additive detrimental effect on LV myocardial systolic and diastolic function. However, obesity was associated with greater LV myocardial dysfunction than diabetes. CONCLUSION: Both diabetes and increasing BMI category had an additive detrimental effect on LV myocardial systolic and diastolic function. Furthermore, increasing BMI category was associated with greater LV myocardial dysfunction than diabetes. As they frequently coexist together, future studies on patients with diabetes should also focus on obesity.

Relationship between left ventricular diastolic function and arterial stiffness in asymptomatic patients with diabetes mellitus.

Left ventricular (LV) diastolic dysfunction and increased arterial stiffness are common in patients with diabetes mellitus (DM). However, the relation between these two pathophysiological factors remains unclear. The aim of this study was to investigate the relationship between LV diastolic function and arterial stiffness as assessed with applanation tonometry. In 142 asymptomatic patients with DM (mean age 48 years, 75 (53 %) men, 72 (51 %) patients with type 2 DM) LV diastolic function was assessed with echocardiography. Arterial stiffness was evaluated measuring the aortic pulse wave velocity (PWV) whereas wave reflection was assessed measuring central systolic blood pressure (cSBP), central pulse pressure (cPP), and augmentation index (AIx) with applanation tonometry. Mean E/A ratio, E' and E/E' ratio were 1.1 ± 0.3, 8.1 ± 2.3 and 9.2 ± 3.3 cm/s, respectively. Mean PWV, mean cSBP, median cPP and mean AIx were 7.9 ± 2.4 m/s, 122 ± 17 mmHg, 40 [35-51] mmHg and 17.9 ± 12.1 %, respectively. PWV was independently associated with LV diastolic dysfunction grade (ß = 0.76, p = 0.03). In contrast, measures of wave reflection, cPP, cSBP and AIx were independently related with E/A ratio, but not with the LV diastolic dysfunction grade. Parameters of arterial stiffness and wave reflection are associated with echocardiographic indices of LV diastolic function in asymptomatic patients with DM. Therapies that prevent progression of arterial stiffness and reduce late-systolic pressure overload may help to reduce the prevalence of LV diastolic dysfunction in this population.

Non-invasive assessment of microcirculation by sidestream dark field imaging as a marker of coronary artery disease in diabetes.

PURPOSE: In diabetes, generalised microvascular disease and coronary artery disease (CAD) are likely to occur in parallel. We used a sidestream dark field (SDF) handheld imaging device to determine the relation between the labial microcirculation parameters and CAD in asymptomatic patients with diabetes. METHODS: SDF imaging was validated for assessment of labial capillary density and tortuosity. Thereafter, mean labial capillary density and tortuosity were evaluated and compared in non-diabetic controls, and in asymptomatic patients with type 1 and type 2 diabetes. In diabetic patients, mean capillary density and tortuosity were compared according to the presence of CAD. RESULTS: Both type 1 and type 2 diabetes were associated with increased capillary density and tortuosity. In diabetes, mean capillary density was an independent predictor of elevated coronary artery calcium (CAC) (p = 0.03) and obstructive CAD on computed tomography angiography (p = 0.01). Using a cut-off mean capillary density of 24.9 (per 0.63 mm(2)) the negative predictive value was 84% and 89% for elevated CAC and obstructive CAD. Likewise, capillary tortuosity was an independent predictor of increased CAC (p = 0.01) and obstructive CAD (p = 0.04). CONCLUSION: Assessment of labial microcirculation parameters using SDF imaging is feasible and conveys the potential to estimate vascular morbidity in patients with diabetes, at bedside.

Increased carotid intima-media thickness as a predictor of the presence and extent of abnormal myocardial perfusion in type 2 diabetes.

OBJECTIVE: Identification of asymptomatic patients with type 2 diabetes at increased risk for coronary artery disease (CAD) remains a challenge. We evaluated the potential of carotid intima-media thickness (CIMT) for prediction of abnormal myocardial perfusion in this population. RESEARCH DESIGN AND METHODS: CIMT and SPECT myocardial perfusion imaging were assessed in 98 asymptomatic patients with type 2 diabetes. An increased CIMT was defined as > or =75th percentile of reference values. RESULTS Increased CIMT was an independent predictor of the extent of abnormal perfusion (P < 0.001). In patients with increased CIMT as compared with patients with normal CIMT, abnormal perfusion (75 vs. 9%) and severely abnormal perfusion (28 vs. 3%) were observed more frequently. CONCLUSIONS: Increased CIMT was significantly related to the presence and extent of abnormal myocardial perfusion. Assessment of CIMT may be useful to identify asymptomatic patients with type 2 diabetes at higher risk for CAD.

Usefulness of hypertriglyceridemic waist phenotype in type 2 diabetes mellitus to predict the presence of coronary artery disease as assessed by computed tomographic coronary angiography.

The present study tested whether in patients with type 2 diabetes mellitus (DM) the combination of increased waist circumference and increased plasma triglyceride (TG) levels can predict the presence of coronary artery disease (CAD) as assessed by multidetector computed tomographic coronary angiography (CTA). In 202 patients with type 2 DM who were clinically referred for CTA, waist circumference and TG levels were measured. Patients were divided into 4 groups according to waist circumference measurements and TG levels. Increased waist circumference and TG levels (n = 61, 31%) indicated the presence of the hypertriglyceridemic waist phenotype. Patients with low waist circumference and TG (n = 49, 24%) were considered the reference group. Physical examination and blood measurements were performed. CTA was used to determine presence and severity of CAD. In addition, plaque type was evaluated. Plasma cholesterol levels were significantly increased in the group with increased TG levels and waist circumference, whereas high-density lipoprotein cholesterol was significantly lower than in the reference group. There was a significant increase in the presence of any CAD (odds ratio 3.3, confidence interval 1.31 to 8.13, p <0.05) and obstructive CAD (≥50%, odds ratio 2.9, confidence interval 1.16 to 7.28, p <0.05) in the group with increased TG level and waist circumference. In addition, a significantly larger number of noncalcified and mixed plaques was observed. In conclusion, in patients with type 2 DM, presence of the hypertriglyceridemic waist phenotype translated into a deteriorated blood lipid profile and more extensive CAD on CTA. Accordingly, the hypertriglyceridemic waist phenotype may serve as a practical clinical biomarker to improve risk stratification in patients with type 2 DM.

Differences in atherosclerotic plaque burden and morphology between type 1 and 2 diabetes as assessed by multislice computed tomography.

OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 asymptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. RESULTS No difference was observed in average CAC score (217 +/- 530 vs. 174 +/- 361) or in the prevalence of coronary atherosclerosis (65% vs. 71%) in patients with type 1 and type 2 diabetes. However, the prevalence of obstructive atherosclerosis was higher in patients with type 2 diabetes (n = 24; 34%) compared with that in patients with type 1 diabetes (n = 11; 17%) (P = 0.02). In addition, a higher mean number of atherosclerotic and obstructive plaques was observed in patients with type 2 diabetes. In addition, the percentage of noncalcified plaques was higher in patients with type 2 (66%) versus type 1 diabetes (27%) (P < 0.001), resulting in a higher plaque burden for each CAC score compared with that in type 1 diabetic patients. CONCLUSIONS Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes type.

Relation between Framingham risk categories and the presence of functionally relevant coronary lesions as determined on multislice computed tomography and stress testing.

Noninvasive assessment of subclinical atherosclerosis by multislice computed tomographic (MSCT) coronary angiography and demonstration of significant, flow-limiting coronary artery disease (CAD) by stress testing may improve patients' risk stratification. However, data relating the complementary information provided by these noninvasive techniques to traditional risk assessment are scarce. In 255 subjects (45% women, mean age 54 +/- 12 years) without known CAD, 64-slice MSCT coronary angiography and stress testing (exercise electrocardiographic test or myocardial perfusion imaging) were performed. Framingham risk score (FRS) was calculated from baseline characteristics (50% low, 22% intermediate, 28% high). Angiograms showing atherosclerosis were classified as obstructive (> or =50% luminal narrowing) CAD or not. Stress tests were classified as normal or abnormal. Multislice computed tomogram identified 155 patients (61%) with CAD, of whom 78 (31%) showed obstructive CAD. A positive stress test result was observed in 36 patients (46%) with obstructive CAD. In line with increasing FRS categories, a significant increase in the prevalence of functionally relevant obstructive CAD was observed (6% low vs 45% intermediate vs 63% high, p <0.001). In conclusion, a strong positive relation exists between FRS and prevalence of functionally relevant obstructive CAD. Selective use of MSCT coronary angiography and stress testing may refine the traditional risk assessment of CAD events, especially in patients deemed at intermediate and high risk.

Endothelial dysfunction in diabetic patients with abnormal myocardial perfusion in the absence of epicardial obstructive coronary artery disease.

UNLABELLED: In patients with diabetes mellitus, myocardial perfusion defects are often observed in the absence of obstructive epicardial coronary artery disease (CAD), thereby presenting a diagnostic problem. We hypothesized that these perfusion abnormalities may be explained by endothelial dysfunction or occult coronary atherosclerosis. METHODS: Prospectively, 130 asymptomatic patients with diabetes mellitus underwent cardiovascular screening by coronary artery calcium (CAC) scoring, multislice CT coronary angiography, and myocardial perfusion imaging by SPECT. Multislice CT images were evaluated for the presence of obstructive epicardial CAD (>or=50% luminal narrowing). To quantify abnormal myocardial perfusion on SPECT images, we determined the summed stress score for each patient. The presence of abnormal myocardial perfusion was defined as a summed stress score of 3 or more. In addition, flow-mediated dilatation of the brachial artery, a marker of endothelial function, was determined using ultrasonography. RESULTS: In 35 patients (27%), obstructive epicardial CAD was observed on multislice CT, and these patients were excluded from further analysis. In the remaining 95 patients, abnormal myocardial perfusion was observed in 30 (32%) of patients. Flow-mediated dilatation was significantly lower in patients with abnormal myocardial perfusion (3.6% +/- 2.4%) than in those with normal myocardial perfusion (6.4% +/- 2.6%) (P < 0.001). Importantly, flow-mediated dilatation remained a significant predictor of the extent of abnormal myocardial perfusion after correction for cardiovascular risk factors and CAC score (P < 0.001). In contrast, no association was observed between nonobstructive plaque burden as reflected by CAC scores and extent of abnormal myocardial perfusion. CONCLUSION: In patients with diabetes mellitus, myocardial perfusion abnormalities in the absence of obstructive epicardial CAD are associated with endothelial dysfunction.

Usefulness of carotid intima-media thickness in patients with diabetes mellitus as a predictor of coronary artery disease.

Identification of asymptomatic patients with diabetes mellitus (DM) at increased risk for coronary artery disease (CAD) remains a challenge. Carotid intima-media thickness (CIMT) has been proposed as a surrogate marker for CAD but only limited data are available. The purpose of the study was to evaluate the potential of CIMT for prediction of CAD in asymptomatic patients with DM. Prospectively, CIMT of the left and right common carotid arteries was assessed by B-mode ultrasound in 150 asymptomatic diabetic patients (50 +/- 13 years old, 83 men). In addition, noninvasive multislice computed tomographic coronary angiography was performed to relate CIMT to the presence and severity of CAD. For this purpose, patients were classified as having (1) no atherosclerosis, (2) nonobstructive atherosclerosis, or (3) obstructive stenosis with >or=50% luminal diameter narrowing. Mean CIMT increased significantly from 0.58 +/- 0.08 mm in patients with normal coronary arteries (n = 59, 39%) to 0.67 +/- 0.12 mm in patients with nonobstructive atherosclerosis (n = 54, 36%). Highest mean CIMT (0.75 +/- 0.12 mm) was observed in patients with obstructive stenosis (n = 36, 25%, p <0.01). Receiver operating characteristics curve analysis yielded a sensitivity and specificity of 85% and 72%, respectively, with a CIMT cut-off value of 0.67 mm, for predicting obstructive coronary atherosclerosis. Multivariate analysis of baseline risk factors showed CIMT to be an independent predictor of any and obstructive atherosclerosis (p <0.01). In conclusion, a significant relation was shown between CIMT and the presence and severity of CAD in asymptomatic patients with DM. Assessment of CIMT may be useful to identify diabetic patients at higher risk for CAD.

Relation of epicardial adipose tissue to coronary atherosclerosis.

Adipose tissue surrounding the coronary arteries has been suggested to induce development of atherosclerosis. We explored the relation between epicardial adipose tissue (EAT) volume and coronary atherosclerosis using multislice computed tomography. The study population consisted of 190 patients who had undergone multislice computed tomographic coronary angiography. Coronary artery calcium score was assessed. In addition, patients were classified as having (1) no atherosclerosis, (2) nonobstructive atherosclerosis (luminal narrowing <50%), (3) obstructive atherosclerosis (luminal narrowing >or=50%) in a single vessel, or (4) obstructive atherosclerosis in the left main coronary artery and/or multiple vessels. Cross-sectional tomographic cardiac slices (3.00-mm thickness, range 35 to 40 slices per heart) were traced semiautomatically from the border of EAT below the apex to a point at the center of the left atrium. Tissue with values from -250 to -30 HU was assigned as EAT. EAT volume within the traced area was then automatically quantified. Mean EAT volume was 84 +/- 41 ml. Patients with a coronary artery calcium score >10 had significantly larger average EAT volume (100 +/- 40 ml) compared with patients with calcium scores 10 were 77% and 70% with a cut-off EAT value of 73 ml. In patients with normal coronaries mean EAT volume (63 +/- 31 ml) was significantly smaller than in patients with atherosclerosis (99 +/- 40 ml, p <0.001). Using a cut-off EAT volume of 75 ml, the sensitivity and specificity for presence of atherosclerosis were 72% and 70%. Interestingly, quantity of EAT did not significantly increase with increasing extent or severity of atherosclerosis. After adjustments for risk factors EAT volume remained a significant predictor of coronary atherosclerosis (p = 0.001). In conclusion, a significant relation was shown between EAT volume and presence of coronary atherosclerosis. Quantification of EAT may be useful to identify patients at risk for coronary artery disease.