The Presence of Residual Vascular and Adipose Tissue Inflammation on 18F-FDG PET in Patients with Chronic Coronary Artery Disease.

Purpose: We evaluated the residual vascular and adipose tissue inflammation in patients with chronic coronary artery disease (CAD) using positron emission tomography (PET). Methods: Our study population consisted of 98 patients with known CAD and 94 control subjects who had undergone 18F-fluorodeoxyglucose (18F-FDG) PET due to non-cardiac reasons. Aortic root and vena cava superior 18F-FDG uptake were measured to obtain the aortic root target-to-background ratio (TBR). In addition, adipose tissue PET measurements were done in pericoronary, epicardial, subcutaneous, and thoracic adipose tissue. Adipose tissue TBR was calculated using the left atrium as a reference region. Data are presented as mean ± standard deviation or as median (interquartile range). Results: The aortic root TBR was higher in CAD patients compared to control subjects, 1.68 (1.55-1.81) vs. 1.53 (1.43-1.64), p < 0.001. Subcutaneous adipose tissue uptake was elevated in CAD patients 0.30 (0.24-0.35) vs. 0.27 (0.23-0.31), p < 0.001. Metabolic activity of CAD patients and control subjects was comparable in the pericoronary (0.81 ± 0.18 vs. 0.80 ± 0.16, p = 0.59), epicardial (0.53 ± 0.21 vs. 0.51 ± 0.18, p = 0.38) and thoracic (0.31 ± 0.12 vs. 0.28 ± 0.12, p = 0.21) adipose tissue regions. Aortic root or adipose tissue 18F-FDG uptake was not associated with the common CAD risk factors, coronary calcium score, or aortic calcium score (p value > 0.05). Conclusion: Patients with a chronic CAD had a higher aortic root and subcutaneous adipose tissue 18F-FDG uptake compared to control patients, which suggests residual inflammatory risk.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0-3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models. RESULTS: Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features. CONCLUSION: Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

Prognostic Value of 99mTc-HMDP Scintigraphy in Elderly Patients With Chronic Heart Failure.

BACKGROUND: This study evaluated the prevalence and prognostic significance of cardiac transthyretin amyloidosis (ATTR) diagnosed using 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy in an elderly heart failure population. METHODS: This retrospective study included 335 patients aged >70 years with heart failure and who underwent 99mTc-HMDP scintigraphy due to non-cardiac reasons in three imaging centres in Finland (Kymenlaakso Central Hospital, Jorvi Central Hospital, and Meilahti University Hospital). A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of ≥1.30 were considered positive for cardiac ATTR. The overall and cardiovascular mortality were obtained from the national statistical service (Statistics Finland). RESULTS: There were 234 deaths, of which 70 were classified as being due to cardiovascular causes during a median follow-up of 1 (1-3) year. Transthyretin amyloidosis was diagnosed in 22 patients (6.6%) using visual analysis and 17 patients using the H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs 80±5 yrs; p=0.002) and had higher N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels (1,451 [813-3,799] vs 6,192 [2,030-8,833] ng/L; p=0.02). Age, bone metastases, and glomerular filtration rate were independent predictors of overall mortality in multivariable analysis. Age, glomerular filtration rate, ≥grade 2 visual cardiac uptake, and H/CL ratio were independent predictors of cardiovascular mortality. CONCLUSIONS: Cardiac uptake suggestive of ATTR was found in 5% of elderly patients with chronic heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was independently associated with cardiovascular mortality.

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. METHODS: The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. RESULTS: There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. CONCLUSIONS: A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

Adalimumab and sulfasalazine in alleviating sacroiliac and aortic inflammation detected in PET/CT in patients with axial spondyloarthritis: PETSPA.

AIM: Inflammatory signals in the sacroiliac (SI) joints and the aorta of patients with axial spondyloarthritis (axSpA) were graded by positron emission tomography/computed tomography (PET/CT) imaging before and after treatment with sulfasalazine (SSZ) or adalimumab (ADA). METHODS: Patients with axSpA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, were recruited. Disease-modifying antirheumatic drug-naïve patients started SSZ for 12 weeks, whereas those with prestudy treatment with or contraindication to SSZ commenced ADA for 16 weeks. In addition, those patients in the SSZ group with insufficient response commenced ADA for 16 weeks. 18F-fluorodeoxyglucose PET/CT was performed after inclusion and after treatment with SSZ and ADA. Maximum standardized uptake value (SUVmax) was assessed for the aorta and the SI joints, and maximal target-to-blood-pool ratio (TBRmax) only for the aorta. RESULTS: Among five SSZ patients, mean ± SD BASDAI was 4.7 ± 1.6 before and 3.5 ± 1.4 after treatment (p = .101). In 13 ADA patients, the BASDAI decreased from 5.4 ± 1.6 to 2.8 ± 2.2 (p < .001). Among the SSZ patients, SUVmax in SI joints decreased from 2.35 ± 0.55 to 1.51 ± 0.22 (-35.8%, p = .029). Aortic TBRmax decreased from 1.59 ± 0.43 to 1.26 ± 0.26 (-33.2%, p = .087). In the ADA patients, SUVmax in the SI joints was 1.92 ± 0.65 before and 1.88 ± 0.54 after treatment (-1.8%, p = .808) and TBRmax in the aorta 1.50 ± 0.60 before and 1.40 ± 0.26 after treatment (-6.7%, p = .485). CONCLUSIONS: Our small open-label study showed that SSZ may reduce PET-CT-detectable inflammation in the SI joints, with a trend towards a reduction in the aorta.

Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass.

INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.

Heterogeneity of myocardial 2-[18F]fluoro-2-deoxy-D-glucose uptake is a typical feature in cardiac sarcoidosis: a study of 231 patients.

Aims: The goal of the investigation was to evaluate whether a semi-quantitative method reflecting myocardial 2-[18F]fluoro-2-deoxy-D-glucose (FDG) uptake heterogeneity has added value in addition to visual analysis in the diagnosis of cardiac sarcoidosis (CS). Methods and results: This retrospective analysis included 271 consecutive patients suspected of CS attending cardiac positron emission tomography combined with computed tomography (PET-CT) at our institution between 2007 and 2013. Visual analysis of PET-CT and semi-quantitative analysis of heterogeneity [coefficient of variation (CoV)] of myocardial FDG uptake were performed. The presence of CS and initial symptoms were verified from patient data. The criteria for CS included histological verification from the myocardium or from an extracardiac site. Thirty cancer patients without cardiac disease were included as controls. CS was diagnosed in 48/231 (20.8%) of analysed patients. Of these, 13 (27.1%) had no extracardial signs of the disease and 30 (62.5%) had FDG positive mediastinal lymph nodes. Visual analysis of PET-CT identified 48.9% of the CS patients. We found a cut-off value of 0.184 for CoV to have the best accuracy to detect CS from a patient population with suspected CS (75.0% sensitivity and 51.4% specificity). Compared to controls, CoV identified CS patients with a good accuracy (68.8% sensitivity and 93.3% specificity). CS patients with FDG positive mediastinal lymph nodes had higher CoV than CS patients without lymph node involvement (0.282 vs. 0.208, P = 0.016). CS patients with more severe initial symptoms had a higher CoV than patients with more benign symptoms (0.283 vs. 0.195, P = 0.01). Conclusion: CoV provides a good addition to visual analysis of cardiac FDG PET-CT in diagnosis of CS. As a semi-quantitative measure, it reduces intra-observer variability. It also seems to indicate more severe disease, but to confirm this, prospective studies are needed.

Bile Reflux Scintigraphy After Mini-Gastric Bypass.

BACKGROUND: Significant weight-loss and diabetes remission have been reported after mini-gastric bypass (MGB). Concern has been raised regarding postoperative bile reflux (BR), but it has not been demonstrated in previous studies. We set out to find out if BR is evident in hepatobiliary scintigraphy after MGB. METHODS: Nine consecutive patients, seven with type 2 diabetes, underwent MGB (15 cm gastric tube, 250-275 cm biliary limb) at our institution with a 12-month follow-up, with none lost to follow-up. Then, 10.7 months (8.6-13.0) after MGB, all patients underwent hepatobiliary scintigraphy and a reflux symptom questionnaire (GerdQ) was filled out. A gastroscopy with biopsies was done for all patients with a bile-reflux-positive scintigraphy. RESULTS: Mean age at operation was 56 years (41-65) and preoperative BMI 43.1 kg/m2 (34.2-54.6). Mean %EWL was 83.9 (49.5-128.3) at 12 months. Four patients reached diabetes remission and two became insulin-independent. Hepatobiliary scintigraphy showed a transient BR into the gastric tube for five patients. Bile tracer was found in the gastric tube at 23-58 min after the tracer injection and highest activity was 8% (1-8%) at 58 min. Bile tracer was not found in the esophagus of any of the patients. One patient with a positive scintigraphy in the gastric tube required re-operation. Two patients with reflux symptoms had a negative scintigraphy. CONCLUSION: Our results indicate that transient bile reflux is common after MGB in the gastric tube, but not in the esophagus. The clinical relevance of bile reflux needs further studies.

[Update on Current Care Guidelines. Current Care Guideline: Stable Coronary Artery Disease]. / Kaypa Hoite-Suosituksen Paivitystiivistelma. Stabiili sepelvaltimotauti.

This guideline covers coronary heart disease symptoms, diagnosis and treatment. Stable coronary heart disease refers to a disease in, which patients have stable symptoms and evidence of ischemia or significant stenosis of coronary artery. Diagnosis is based on medical history and exercise test, which is the primary diagnostic test. Coronary angiography is in selected cases necessary to confirm the diagnosis and assess invasive treatment. Pharmacotherapy aims to improve the survival of the patient, relieve symptoms and improve quality of life. The guideline also deals with invasive treatment either with PCI or CABG.

Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism.

FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary.

[68Ga-DOTA-PET for neuroendocrine tumours]. / Somatostatiinireseptoreiden PET-TT-kuvaus 68Ga-DOTA-peptideillä parantaa neuroendokriinisten kasvainten diagnostiikkaa.

Neuroendocrine tumors (NET) are found in several organs and called NET tumors. They are relatively rare, most of them giving no symptoms and remaining undetected. Most NETs arise from the gut, stomach and bronchus. These tumors are diagnosed either by histology or by imaging. A typical feature of NETs is abundance of somatostatin receptors on the cell surface, which makes it possible to image the tumor by nuclear methods as well as estimate the response to treatment by somatostatin analogues ("theranostics"). In order to improve the diagnosis of NETs we started to produce 68Ga-DOTA peptides for PET.

Effect of long-term endurance and strength training on metabolic control and arterial elasticity in patients with type 2 diabetes mellitus.

Poor glucose control increases the risk of vascular complications and cardiovascular mortality in patients with diabetes mellitus (DM). Our aim was to evaluate the efficacy of a long-term exercise training program on metabolic control and arterial stiffness in patients with type 2 DM. Fifty men with DM (age 52.3 +/- 5.6 years) were randomly assigned to the exercise training (E) or standard treatment for DM (control [C]) group for 24 months. Supervised exercise training included both endurance and muscle strength training 4 times/week. All exercise sessions were controlled by heart rate and intensity. Glycated hemoglobin A1c, insulin, leptin, blood lipids, blood pressure, maximal oxygen consumption in spiroergometry, and muscle strength were measured every 6 months. Arterial stiffness was assessed by measuring pulse wave velocity. Maximal oxygen consumption in spiroergometry (E 31.9 to 34.8 vs C 32.6 to 31.8 ml/kg/min; p = 0.003), muscle strength (sit-up test, E 12.7 to 20.8 vs C 14.6 to 13.1 times; p <0.001), hemoglobin A1c (E 8.2% to 7.6% vs C 8.0% to 8.3%; p = 0.006), and leptin (E 7.4 to 6.7 vs C 7.4 to 7.9 microg/L; p = 0.013) improved significantly in the E group, but no change or worsening in these variables occurred in the C group. Body weight was not different between groups at 2 years. However, pulse wave velocity increased in both groups (E +0.600 vs C +1.300 m/s; p = 0.27). In conclusion, long-term endurance and strength training was effective and resulted in improved metabolic control of DM compared with standard treatment. Despite significant cardiovascular risk reduction, conduit arterial elasticity did not improve.

The association of myeloperoxidase promoter polymorphism with carotid atherosclerosis is abolished in patients with type 2 diabetes.

OBJECTIVES: Type 2 diabetes mellitus (DM) enhances the development of atherosclerosis and reduces the activity of the oxidative myeloperoxidase (MPO) enzyme. MPO gene has a functional promoter polymorphism -463G/A which leads to high- (GG) and low-expression (AG, AA) genotypes. DESIGN AND METHODS: We studied the association of MPO polymorphism with carotid artery intima-media thickness (IMT) in 198 randomly selected Finnish men of Caucasian origin, 161 non-diabetics and 37 with type 2 DM. Their carotid IMT was measured by high-resolution ultrasonography, and the overall mean IMT value was calculated. MPO genotypes were determined by the PCR-RFLP method. RESULTS: We found significant MPO genotype-by-study-group (control/DM) interactions with the overall mean IMT and internal carotid IMT (p=0.05 and p=0.04, respectively). Among non-diabetic subjects, the overall carotid IMT was 7.3% higher in subjects with the low-activity genotype when compared to the high-activity (G/G) group. The results remained significant after adjustment for total cholesterol and smoking (p=0.015). No similar genotypic association was found for the subjects with type 2 DM. CONCLUSIONS: This data suggests that in subjects with normal glucose metabolism, MPO gene variation may modify the carotid artery IMT.

Exercise training does not improve myocardial diastolic tissue velocities in Type 2 diabetes.

BACKGROUND: Myocardial diastolic tissue velocities are reduced already in newly onset Type 2 diabetes mellitus (T2D). Poor disease control may lead to left ventricular (LV) systolic dysfunction and heart failure. The aim of this study was to assess the effects of exercise training on myocardial diastolic function in T2D patients without ischemic heart disease. METHODS: 48 men (52.3 +/- 5.6 yrs) with T2D were randomized to supervised training four times a week and standard therapy (E), or standard treatment alone (C) for 12 months. Glycated hemoglobin (HbA1c), oxygen consumption (VO2max), and muscle strength (Sit-up) were measured. Tissue Doppler Imaging (TDI) was used to determine the average maximal mitral annular early (Ea) and late (Aa) diastolic as well as systolic (Sa) velocities, systolic strain (epsilon) and strain rate (epsilon) from the septum, and an estimation of left ventricular end diastolic pressure (E/Ea). RESULTS: Exercise capacity (VO2max, E 32.0 to 34.7 vs. C 32.6 to 31.5 ml/kg/min, p = .001), muscle strength (E 12.7 to 18.3 times vs. C 14.6 to 14.7 times, p < .001), and HbA1c (E 8.2 to 7.5% vs. C 8.0 to 8.4%, p = .006) improved significantly in the exercise group compared to the controls (ANOVA). Systolic blood pressure decreased in the E group (E 144 to 138 mmHg vs. C 146 to 144 mmHg, p = .04). Contrary to risk factor changes diastolic long axis relaxation did not improve significantly, early diastolic velocity Ea from 8.1 to 7.9 cm/s for the E group vs. C 7.4 to 7.8 cm/s (p = .85, ANOVA). Likewise, after 12 months the mitral annular systolic velocity, systolic strain and strain rate, as well as E/Ea were unchanged. CONCLUSION: Exercise training improves endurance and muscle fitness in T2D, resulting in better glycemic control and reduced blood pressure. However, myocardial diastolic tissue velocities did not change significantly. Our data suggest that a much longer exercise intervention may be needed in order to reverse diastolic impairment in diabetics, if at all possible.

Blood leukocyte count is a risk factor for intima-media thickening and subclinical carotid atherosclerosis in middle-aged men.

Leukocytosis is known to predict future cardiovascular events even in subjects without coronary heart disease (CHD), but its association with early atherosclerotic changes has remained less certain. The aim of the present study was to investigate how the blood leukocyte count compares with several other risk factors for CHD in determining carotid artery intima-media thickness (IMT) and subclinical carotid atherosclerosis in a population sample. Both carotid arteries were investigated with high-resolution B-mode ultrasound in a community-based sample of 219 randomly selected men aged 50-59 years to calculate the mean maximum IMT (MMax IMT) of 12 standard sites. Risk factor assessment included several traditional biochemical risk factors, blood pressure, maximal oxygen consumption and work load on ergometry, life-style habits and hematologic parameters. As genetic determinants, apolipoprotein E and A-IV polymorphisms were studied. According to multivariate regression analysis, age (P<0.0001), blood leukocyte count (P<0.0001) and systolic blood pressure (P<0.042) were the only significant predictors of MMax IMT. MMax IMT increased linearly from the lowest tertile of blood leukocyte count (1.14+/-0.20mm) to the second (1.18+/-0.25 mm) and to the highest tertile (1.25+/-0.27 mm, P=0.019). This difference remained significant after adjustment with age, systolic blood pressure and smoking (P=0.032). Leukocytes seem to have an independent role in the early arterial damage and they may reflect subclinical disease. This implies that leukocyte count is undervalued in the diagnostics and prognostics of carotid atherosclerosis.

Impaired myocardial function in newly onset type 2 diabetes associates with arterial stiffness.

AIM: The aim of this study was to evaluate myocardial function using pulsed and color-coded tissue Doppler imaging (TDI) and vascular wall elasticity using whole-body impedance cardiography (ICG) in patients with newly diagnosed Type 2 diabetes mellitus (DM2), and to compare the measurements with those of healthy controls. METHODS: Systolic (SBP) and diastolic (DBP) blood pressure and glycosylated hemoglobin (HbA1c) were measured in 49 men (mean age 52.3+/-5.6 years, duration of DM2 1.8 years), and 15 healthy male control subjects (48.3+/-7.4 years). Mitral annular peak systolic (Svm), early (Evm), and late (Avm) diastolic velocities as well as myocardial peak systolic (Sv), early (Ev) and late diastolic (Av) velocity from middle segments of the anterior, inferior and lateral wall and the inferior septum were measured by TDI. ICG at rest was used to measure cardiac index (CI) and pulse wave velocity (PWV). RESULTS: The patients had higher body mass index (BMI 29.1+/-3.7 vs. 25.2+/-2.4 kg/m(2), p=0.000) and SBP (142+/-15 vs. 120+/-7 mmHg, p=0.005) than the controls, CI was comparable (2.8+/-0.5 vs. 2.8+/-0.6l/min/m(2)). The patients had lower age adjusted myocardial Sv (3.8+/-1.1 vs. 4.8+/-1.1cm/s, p=0.002) and Ev (4.6+/-1.6 vs. 6.2+/-1.7 cm/s, p=0.011), and also mitral annulus peak early diastolic velocity (Evm 7.8+/-1.9 vs. 10.4+/-2.6 cm/s, p=0.001). In diabetic patients PWV (14.2+/-2.7 vs. 10.0+/-1.7 m/s, p=0.002) was higher. Age (r=-0.39, p=0.001), BMI (r=-0.44, p=0.000) and PWV (r=-0.52, p=0.000) correlated significantly with Evm. PWV correlated with age (r=0.50, p=0.000), SBP (r=0.67, p=0.000), and HBA1c (r=0.36, p=0.010). In stepwise regression analysis, PWV (beta=-0.39, p=0.000) was the major determinant of Evm. CONCLUSION: Myocardial function is impaired in asymptomatic patients with newly detected DM2 consistent with diabetic heart muscle disease. Arterial stiffness is strongly related to myocardial dynamics, and both may have the same pathophysiologic background.

The association of the apolipoprotein E gene promoter polymorphisms and haplotypes with serum lipid and lipoprotein concentrations.

BACKGROUND: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport and metabolism. The common APOE epsilon2/epsilon3/epsilon4 polymorphism explains part of the variation in plasma cholesterol levels. Polymorphisms of the APOE gene regulatory region are suggested to be involved in explaining variation of lipoprotein levels within the APOE epsilon2/epsilon3/epsilon4 genotypes. OBJECTIVES: To study the associations of the APOE gene promoter polymorphisms -219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein concentrations, especially within the most common APOE epsilon3/epsilon3 genotype group. SUBJECTS AND METHODS: From 219 middle-aged Finnish men, APOE genotypes were determined and haplotypes estimated. Plasma lipoproteins were isolated by ultracentrifugation and their lipids were measured. RESULTS: The studied APOE promoter polymorphisms and haplotypes associated with certain lipid variables independently of the APOE epsilon2/epsilon3/epsilon4 genotype. Within the APOE epsilon3/epsilon3 group, both -219G/G and +113G/G genotypes associated statistically significantly with higher levels of very low-density lipoprotein (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower HDL-cholesterol concentrations than the other genotypes. Compared with the -219T/+113C/epsilon3 haplotype, the more common -219G/+113G/epsilon3 haplotype was found more frequently among the group having high (over median) VLDL-cholesterol and triglyceride concentrations (OR 2.6, p<0.001 and OR=2.1, p=0.009, respectively). CONCLUSIONS: In addition to the APOE epsilon2/epsilon3/epsilon4 polymorphism, the promoter polymorphisms -219G/T and +113G/C as well as their haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish men.

Homocysteine and carotid atherosclerosis in chronic renal failure--the confounding effect of renal function.

Since total homocysteine (tHcy) level is markedly elevated in patients with chronic renal failure (CRF), it has been presented as a potential factor contributing to the high risk of cardiovascular disease (CVD) in CRF. Our aim was to examine the significance of elevated tHcy level and other cardiovascular risk factors for carotid atherosclerosis in patients with CRF. In this cross-sectional study, 135 study patients with CRF (52 +/- 11 years) included 58 patients with moderate to severe predialysis CRF, 36 dialysis patients and 41 renal transplant recipients. In addition, 58 control subjects were examined. The association of tHcy level and classic risk factors for atherosclerosis with common carotid artery intima-media thickness (IMT) or carotid artery plaque score was examined. We found no association between tHcy and carotid IMT or a high carotid plaque score in the CRF patient groups. No consistent association was found between elevated tHcy and coronary artery disease, cerebrovascular disease or peripheral arterial disease. Renal function, described as creatinine clearance, was the strongest determinant for tHcy level. Significant predictors of carotid atherosclerosis were age, duration of hypertension and elevated low-density lipoprotein cholesterol level. In conclusion, the present study shows no apparent association between tHcy level and atheromatous carotid findings in patients with CRF. However, because of the changing renal function in the course of renal disease, the strong confounding effect of renal function may not be adequately controlled for the analysis of the significance of elevated tHcy level for CVD in patients with CRF.

Carotid atherosclerosis in chronic renal failure-the central role of increased plaque burden.

Studies on carotid artery atherosclerosis have been performed in order to understand the high risk for cardiovascular disease in chronic renal failure (CRF). The purpose of this study was to evaluate the extent and nature of carotid artery atherosclerosis in patients with CRF. Of the 135 patients with CRF (52 +/- 11 years), 58 had moderate to severe predialysis CRF (PR), 36 were on dialysis treatment (DI), and 41 were renal transplant recipients (TR). In addition, 58 control subjects (CO) were examined. Common carotid artery intima-media thickness (IMT), plaque prevalence, plaque score, and stiffness index beta were determined. Furthermore, plaque calcification and internal carotid artery stenoses were classified. Plaque prevalence (PR 64%, DI 61%, TR 51%, CO 28%; P < 0.001) and plaque score (PR 3.3 +/- 4.3, DI 3.0 +/- 3.4, TR 2.5 +/- 3.2, CO 0.8 +/- 1.7 mm; P < 0.001) were significantly greater in the CRF patient groups compared to the controls, whereas no difference in IMT was noted between the study groups. The prevalences of plaque calcification and internal carotid artery stenoses were higher among the CRF patient groups. In addition, the stiffness index beta was higher in the CRF patient groups. The present study shows that the characteristic alterations of the carotid arteries in CRF include increased plaque burden, calcification and increased arterial stiffness.

Exercise training improves baroreflex sensitivity in type 2 diabetes.

Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death. It is associated with reduced baroreflex sensitivity (BRS) and heart rate variability (HRV), which are indicators of increased risk for mortality and morbidity in various patient populations. This study was designed to assess the effects of exercise training on BRS, HRV, and hemodynamics in patients with type 2 diabetes. Subjects (50 men, mean age 53.3 +/- 5.1 years) with type 2 diabetes were randomized into either a control group, in which they received conventional treatment only, or an exercise group, in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months. Measurements taken at baseline and follow-up included VO(2max), standard time and frequency domain measures of HRV during 24-h recording, and BRS by the phenylephrine method. Cardiac index, systemic vascular resistance index, stroke index, and pulse wave velocity were measured by whole-body impedance cardiography. Significant improvements in VO(2max) (exercise group: +2.3 ml x kg(-1) x min(-1); P < 0.005 vs. control group), muscle strength, and glycemic control (exercise group: HbA(1c) -0.9%; P < 0.001 vs. control group) were observed in the exercise group. BRS increased in the exercise group, from 6.8 to 8.6 ms/mmHg, and decreased in the control group, from 7.5 to 6.4 ms/mmHg (95% CI for the difference between 0.05 and 4.36 ms/mmHg; P < 0.05). No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed. We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control. These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients.