The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.     

Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril

OBJECTIVES: The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). CONCLUSIONS: The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.     

中国心力衰竭流行病学调查及其患病率

目的　了解我国成年人慢性心力衰竭 (心衰 )的患病率和分布特征。方法　中国心血管健康多中心合作研究应用四阶段整群随机抽样方法 ,在全国 1 0个省市 (南方和北方各 5个省市 )抽取具有代表性的样本 ,年龄在 35～ 74岁之间 ,城市和农村各半 ,男、女人数均衡。统计不同年龄组、不同性别和不同地区人群的心衰患病率。结果　共抽样调查 35～ 74岁城乡居民 1 5 51 8人 ,心衰患病率为0 9% ;其中男性为 0 7% ,女性为 1 0 % ,女性患病率高于男性 (P <0 0 5)。 35～ 44岁、45～ 54岁、55～64岁、65～ 74岁年龄组的心衰患病率分别为 0 4%、1 0 %、1 3 %和 1 3 % ;随着年龄增高 ,心衰的患病率显著上升 (P <0 0 1 )。我国北方地区心衰患病率为 1 4% ,南方地区心衰患病率为 0 5 % ,北方明显高于南方 (P <0 0 1 ) ;城市人群心衰患病率为 1 1 % ,农村人群心衰患病率为 0 8% ,城市人群心衰患病率高于农村。结论　心衰正在成为我国心血管病领域的重要公共卫生问题     

Risk of infective endocarditis in mitral valve prolapse with and without precordial systolic murmurs

The risk of infective endocarditis (IE) associated with a systolic murmur in patients with mitral valve prolapse (MVP) was investigated in a case-control study. The case group comprised all patients with MVP (n = 19) from a series of 136 consecutive adult admissions for IE. Three matched control subjects were chosen for each case from a series of 144 MVP patients without IE. Seventeen of the 19 cases (89%) had documented evidence of systolic murmurs existing before the IE episode; systolic murmurs were documented in 25 of the 57 control subjects (47%). The data indicate a significant increase in the risk of IE in MVP patients with a systolic murmur (p less than 0.01). The absolute probability of IE developing in a patient with MVP and a murmur was estimated to be approximately 1 in 1,400 per year; this was 35 times greater than the probability in a patient with MVP without a murmur. The results suggest that by restricting prophylaxis to MVP patients with a systolic murmur, cover would be provided for almost 90% of those with MVP in whom IE would be likely to develop.     

Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

Aims/hypothesis

There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA_1c and the risks of vascular complications and death in such patients.

Methods

Eleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA_1c measurements during follow-up and prior to the first event. Adjusted risks for each HbA_1c decile were estimated using Cox models. Possible differences in the association between HbA_1c and risks at different levels of HbA_1c were explored using linear spline models.

Results

There was a non-linear relationship between mean HbA_1c during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA_1c studied (5.5?C10.5%), there was evidence of ??thresholds??, such that below HbA_1c levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p?>?0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA_1c level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p?Conclusions/interpretation In patients with type 2 diabetes, HbA_1c levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm.

Trial Registration:

ClinicalTrial.gov NCT00145925

Funding:

Servier and the National Health and Medical Research Council of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281)     

Pulmonary nodules: computer-aided detection in digital chest images

Currently, radiologists fail to detect pulmonary nodules in up to 30% of cases with actually positive findings. Diagnoses may be missed due to camouflaging effects of anatomic background, subjective and varying decision criteria, or distractions in clinical situations. We developed a computerized method to detect locations of lung nodules in digital chest images. The method is based on a difference-image approach and feature-extraction techniques, including growth, slope, and profile tests. Computer results were used to alert 12 radiologists to possible nodule locations in 60 clinical cases. Preliminary results suggest that computer aid can improve the detection performance of radiologists.     

Image feature analysis of false-positive diagnoses produced by automated detection of lung nodules.

RATIONALE AND OBJECTIVES. To reduce the number of false-negative diagnoses by radiologists, the authors are developing a computer-aided diagnosis scheme for detection of lung nodules in digital chest images. In this study, the authors attempted to reduce the number of false-positive diagnoses obtained with a previous computer scheme by incorporating additional knowledge from experienced chest radiologists into the computer scheme. METHODS. The authors applied their previous computer scheme, using less-strict criteria, to 60 clinical chest radiographs; this yielded 735 candidate nodules (23 true nodules and 712 false-positive diagnoses). These candidates were analyzed using region-growing, trend-correction, and edge-gradient techniques to determine measures by which to quantify image features of candidate nodules. RESULTS. The 712 false-positive diagnoses represented various anatomic structures that were located throughout the chest image. From this analysis, we were able to decrease the number of false-positive errors from an average of 12 to approximately 5 per image without eliminating any true nodules. CONCLUSION. Our results show that incorporating knowledge from experienced chest radiologists into the computer algorithm will play an important role in the development of computerized schemes for the detection of pulmonary nodules.     

Lymphatic and portal venous transport of alpha-tocopherol and cholesterol

The absorption of ³H-α-tocopherol was studied in rats after intraduodenal administration in micellar solutions. Net absorption from mixed micelles in lymph fistula rats was 66%, but only 42% appeared in lymph and 3% was excreted in urine. Administration of ³H-α-tocopherol in taurocholate micelles reduced both the rate of absorption into lymph and the proportion carried in chylomicrons. In studies with lymph and bile duct cannulated rats, up to 8% of the radioactivity was excreted in bile, irrespective of whether the cannula was in the mesenteric or thoracic lymph duct. These findings suggested that radioactivity was being absorbed via the portal vein, which was confirmed by demonstrating a higher concentration in portal than in aortic plasma. Radioactivity in plasma partly consisted of polar metabolites, in contrast to lymph where over 90% was free α-tocopherol. In parallel experiments with ¹⁴C-cholesterol, significant amounts of radioactivity were excreted in bile and the ratio of portal: aortic radioactivity again suggested absorption via the portal route. The majority of ¹⁴C-cholesterol in portal plasma was free sterol, in contrast to lymph where it was mainly esterified. These results suggest that small amounts of both α-tocopherol and free cholesterol can be transported from the intestine via the portal vein, although under normal circumstances absorption of both compounds occurs mainly via the lymphatic pathway.     

Whole-body MRI in neurofibromatosis: incidental findings and prevalence of scoliosis

Objective

To demonstrate incidental findings and scoliosis on whole-body MRI (WBMRI) in patients with neurofibromatosis type 1 and 2 (NF1 &; NF2, respectively), and schwannomatosis.

Materials and methods

Institutional review board approval and written informed consent were obtained for this prospective HIPAA-compliant study. A total of 247 subjects (141 with NF1, 55 with NF2, 51 with schwannomatosis; 132 women (53.5%); mean age, 41?years, range, 18–97?years) underwent WBMRI using coronal STIR (TR/TE: 4190/111?ms, TI: 150?ms) and T1-weighted images (TR/TE: 454/10?ms), 10-mm slice thickness, imaging time ~40 min. Images were reviewed for the presence of incidental findings, outside of nerve sheath tumors. The presence of scoliosis was recorded and curve morphology was assessed and quantified.

Results

Incidental findings other than scoliosis were recorded in 104/247 (42%) patients, most often affecting the musculoskeletal system (65/247 patients, 26%). We found 16/247 (6.5%) significant incidental findings likely to affect clinical management, including avascular necrosis of bone in eight patients (five with NF2), eight insufficiency fractures, and four non-neurogenic neoplasms (Hodgkin's lymphoma, liposarcoma, dermoid cyst, large uterine myoma requiring excision). Scoliosis was seen in 50/247 patients (20%), including 8/55 with NF2 (15%) and 11/51 with schwannomatosis (22%).

Conclusions

Incidental findings in the neurofibromatoses frequently involve the skeleton. Given the relatively high incidence of unsuspected osteonecrosis and stress fractures, close attention to the skeleton on WBMRI is advised. In addition, knowledge of common incidental findings can help clinicians prepare patients who undergo WBMRI for potential unexpected findings.