Associations between blood glucose and carotid intima-media thickness disappear after adjustment for shared risk factors: the KORA F4 study.

The association between blood glucose and carotid intima-media thickness (CIMT) is considered to be established knowledge. We aimed to assess whether associations between different measures of glycaemia and CIMT are actually independent of anthropometric variables and metabolic risk factors. Moreover, we checked published studies for the adjustment for shared risk factors of blood glucose and CIMT. Fasting glucose, 2-hour glucose, HbA1c, and CIMT were measured in 31-81-years-old participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study in Southern Germany (n = 2,663). CIMT was assessed according to the Rotterdam protocol. Linear and logistic regression models with adjustment for age, sex, anthropometric measures, hypertension, and dyslipidaemia were fitted to assess the association between continuous measures of glycaemia, and categories of glucose regulation, respectively, with CIMT. We found a 0.10 mm increase (95%-confidence interval: 0.08-0.12) in CIMT in subjects with compared to subjects without diabetes in crude analysis. This increase was not significant in age-sex adjusted models (p = 0.17). Likewise, neither impaired fasting glucose (p = 0.22) nor impaired glucose tolerance (p = 0.93) were associated with CIMT after adjustment for age, sex, and waist circumference. In multivariable adjusted models, age, sex, hypertension, waist circumference, HDL and LDL cholesterol, but neither fasting glucose nor 2-hour glucose nor HbA1c were associated with elevated CIMT. Literature findings are inconclusive regarding an independent association of glucose levels and CIMT. CIMT is highly dependent on traditional cardiovascular risk factors, but no relationships between blood glucose and CIMT were found after adjustment for age, sex, and anthropometric variables

Linking cardiorespiratory fitness classification criteria to early subclinical atherosclerosis in children

It is unclear if cardiorespiratory fitness (CRF) can be used as a screening tool for premature changes in carotid intima-media thickness (cIMT) in paediatric populations. The purpose of this cross-sectional study was 3-fold: (i) to determine if CRF can be used to screen increased cIMT; (ii) to determine an optimal CRF cut-off to predict increased cIMT; and (iii) to evaluate its ability to predict increased cIMT among children in comparison with existent CRF cut-offs. cIMT was assessed with high-resolution ultrasonography and CRF was determined using a maximal cycle test. Receiver operating characteristic analyses were conducted in boys (n = 211) and girls (n = 202) aged 11-12 years to define the optimal sex-specific CRF cut-off to classify increased cIMT (≥75th percentile). Logistic regression was used to examine the association between the CRF cut-offs with the risk of having an increased cIMT. The optimal CRF cut-offs to predict increased cIMT were 45.81 and 34.46 mL·kg(-1)·min(-1) for boys and girls, respectively. The odds-ratios for having increased cIMT among children who were unfit was up to 2.8 times the odds among those who were fit (95% confidence interval: 1.40-5.53). Considering current CRF cut-offs, only those suggested by Adegboye et al. 2011. (Br. J. Sports Med. 45(9): 722-728) and Boddy et al. 2012 (PLoS One, 7(9): e45755) were significant in predicting increased cIMT. In conclusion, CRF cut-offs (boys: ≤ 45.8; girls: ≤ 34.5 mL·kg(-1)·min(-1)) are associated with thickening of the arterial wall in 11- to 12-year-old children. Low CRF is an important cardiovascular risk factor in children and our data highlight the importance of obtaining an adequate CRF.info:eu-repo/semantics/publishedVersio

Ethnic Differences in Carotid Intima-Media Thickness Between UK Children of Black African-Caribbean and White European Origin.

BACKGROUND AND PURPOSE: UK black African-Caribbean adults have higher risks of stroke than white Europeans and have been shown to have increased carotid intima-media thickness (cIMT). We examined whether corresponding ethnic differences in cIMT were apparent in childhood and, if so, whether these could be explained by ethnic differences in cardiovascular risk markers. METHODS: We conducted a 2-stage survey of 939 children (208 white European, 240 black African-Caribbean, 258 South Asian, 63 other Asian, 170 other ethnicity), who had a cardiovascular risk assessment and measurements of cIMT at mean ages of 9.8 and 10.8 years, respectively. RESULTS: Black African-Caribbean children had a higher cIMT than white Europeans (mean difference, 0.014 mm; 95% CI, 0.008-0.021 mm; P<0.0001). cIMT levels in South Asian and other Asian children were however similar to those of white Europeans. Among all children, cIMT was positively associated with age, systolic and diastolic blood pressure and inversely with combined skinfold thickness and serum triglyceride. Mean triglyceride was lower among black African-Caribbeans than white Europeans; blood pressure and skinfold thickness did not differ appreciably. However, adjustment for these risk factors had little effect on the cIMT difference between black African-Caribbeans and white Europeans. CONCLUSIONS: UK black African-Caribbean children have higher cIMT levels in childhood; the difference is not explained by conventional cardiovascular risk markers. There may be important opportunities for early cardiovascular prevention, particularly in black African-Caribbean children

Causal relevance of blood lipid fractions in the development of carotid atherosclerosis: Mendelian randomization analysis.

BACKGROUND: Carotid intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. METHODS AND RESULTS: Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in >100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01-0.04) and 0.04 mm (95% confidence interval, 0.02-0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. CONCLUSIONS: Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study

Why Deporting Immigrants for “Crimes Involving Moral Turpitude” is Now Unconstitutional

In the best of times, immigrants should only be deported according to the rule of law and not by the whim of executive branch officials. Now, it is imperative. Yet the statute authorizing removal of immigrants for “crimes involving moral turpitude” invites officials to base their prosecutorial choices on political or personal views. As a result, defense attorneys advising their clients on the immigration consequences of pleas have no basis for prediction. Although the Supreme Court long ago rejected the argument that the “moral turpitude” clause was void for vagueness, one of the Court’s most recent decisions now makes that conclusion unsupportable. The notion that due process permits officials to banish legal permanent residents based on “moral turpitude,” which never comported with common sense, is now legally incorrect

Why Deporting Immigrants for “Crimes Involving Moral Turpitude” is Now Unconstitutional

In the best of times, immigrants should only be deported according to the rule of law and not by the whim of executive branch officials. Now, it is imperative. Yet the statute authorizing removal of immigrants for “crimes involving moral turpitude” invites officials to base their prosecutorial choices on political or personal views. As a result, defense attorneys advising their clients on the immigration consequences of pleas have no basis for prediction. Although the Supreme Court long ago rejected the argument that the “moral turpitude” clause was void for vagueness, one of the Court’s most recent decisions now makes that conclusion unsupportable. The notion that due process permits officials to banish legal permanent residents based on “moral turpitude,” which never comported with common sense, is now legally incorrect

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

&lt;br&gt;Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.&lt;/br&gt; &lt;br&gt;Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.&lt;/br&gt; &lt;br&gt;Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).&lt;/br&gt; &lt;br&gt;Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.&lt;/br&gt

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

&lt;br&gt;Background: Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes.&lt;/br&gt; &lt;br&gt;Methods: We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307.&lt;/br&gt; &lt;br&gt;Findings: We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI −0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI −0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5).&lt;/br&gt; &lt;br&gt;Interpretation: Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population.&lt;/br&gt

Automating Carotid Intima-Media Thickness Video Interpretation with Convolutional Neural Networks

Cardiovascular disease (CVD) is the leading cause of mortality yet largely preventable, but the key to prevention is to identify at-risk individuals before adverse events. For predicting individual CVD risk, carotid intima-media thickness (CIMT), a noninvasive ultrasound method, has proven to be valuable, offering several advantages over CT coronary artery calcium score. However, each CIMT examination includes several ultrasound videos, and interpreting each of these CIMT videos involves three operations: (1) select three end-diastolic ultrasound frames (EUF) in the video, (2) localize a region of interest (ROI) in each selected frame, and (3) trace the lumen-intima interface and the media-adventitia interface in each ROI to measure CIMT. These operations are tedious, laborious, and time consuming, a serious limitation that hinders the widespread utilization of CIMT in clinical practice. To overcome this limitation, this paper presents a new system to automate CIMT video interpretation. Our extensive experiments demonstrate that the suggested system significantly outperforms the state-of-the-art methods. The superior performance is attributable to our unified framework based on convolutional neural networks (CNNs) coupled with our informative image representation and effective post-processing of the CNN outputs, which are uniquely designed for each of the above three operations.Comment: J. Y. Shin, N. Tajbakhsh, R. T. Hurst, C. B. Kendall, and J. Liang. Automating carotid intima-media thickness video interpretation with convolutional neural networks. CVPR 2016, pp 2526-2535; N. Tajbakhsh, J. Y. Shin, R. T. Hurst, C. B. Kendall, and J. Liang. Automatic interpretation of CIMT videos using convolutional neural networks. Deep Learning for Medical Image Analysis, Academic Press, 201