Diameter stenosis at follow-up according to plasma concentrations of asymmetric dimethylarginine and trimethyllysine^a.

<p>DS, Diameter Stenosis; ADMA, asymmetric dimethylarginine; TML, trimethyllysine.</p>a<p>Non-parametric linear quantile mixed-effects models of diameter stenosis at follow-up using Laplace distribution.</p>b<p>Effect estimate given as regression coefficient (95% confidence interval) and p-value for change in percentage point diameter stenosis.</p>c<p>The fixed effect in this model is ADMA and DS measured at baseline while the random effect is the clustering of arterial segments within a single patient. Estimates are presented as median (95% confidence interval). Standard error is estimated using bootstrapping.</p>d<p>The fixed effect in this model is TML and DS measured at baseline while the random effect is the clustering of arterial segments within a single patient. Estimates are presented as median (95% confidence interval). Standard error is estimated using bootstrapping.</p>e<p>The fixed effect in this model is DS measured at baseline, follow-up time in days, presence of diabetes, randomization (folic acid/B₁₂ vs no folic acid/B₁₂) status at baseline, plasma TML at baseline, smoking status, age, gender, plasma ADMA at baseline, systolic blood pressure, body mass index, kidney function, apolioprotein B100 and C-reactive protein while the random effect is the clustering of arterial segments within a single patient. Standard error is estimated using bootstrapping.</p

Baseline Characteristics and Laboratory Findings in Patients with Angiographic Coronary Lesions (n = 183).

<p>For continuous variables, mean and standard deviation or median and interquartile range within each group is calculated. Student's T-test or Mann-Withney U-test was used to compare the two groups. For categorical variables, number and percentage is presentend and a Chi square test was used to compare the four groups. Fisher's exact test was used when appropriate. All biochemical parameteres are prestented as median (interquartile range). FA, folic acid (0.8 mg); B₁₂, vitamin B₁₂ (0.4 mg); B₆, vitamin B₆ (40 mg); PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft surgery; NSTACS, composite syndrom consisting of acute coronary syndrome including both ST-elevated and non-ST-elevated myocardial infarction; AMI, acute myocardial infarction; CHD, coronary heart disease; LMS, left main stem; LAD, left anterior descending artery; CX, circumflex branch; RCA, right coronary artery; ACE, Angiotensin I converting enzyme; LDL, low-density lipoprotein; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; ADMA, asymmetric dimethylarginine. Percentages may not add up due to rounding of numbers.</p>a<p>Ejection fraction was measured during ventriculography for the majority of the patients. When this was not performed, ultrasonic echocardiography was used.</p>b<p>A prior diagnosis of any peripheral or cerebrovascular disease.</p>c<p>Medication at discharge.</p>d<p>Including ARB - angiotensin receptor blockers.</p

Asymmetric dimethylarginine, trimethyllysine and angiographic progression of coronary artery disease.

<p>The graph shows the regression line from a linear quantile mixed model. The two left panels show the relation between the asymmetric dimethylarginine (ADMA) and DS measured at follow-up, whereas the two right panels show the relation between trimethyllysine (TML) and DS at follow-up. The bivariate models (adjusted for baseline DS measurement) are on the top and the multivariate (adjusted for age, sex, folic acid/B₁₂ intervention status, follow-up time, diabetes, smoking, systolic blood pressure, body mass index, estimated glomerular filtration rate (eGFR), apolipoprotein B100, C-reactive protein, ADMA or TML) at the bottom. The plasma level of either ADMA or TML is shown on the x-axis, with DS at follow-up on the y-axis. The solid line represents the regression line for the effect on median DS, while the others are displayed according to the legend.</p

Baseline Angiographic Characteristics of the 309 Coronary Lesions (from n = 183 patients).

<p>For continuous variables, mean and standard deviation within each group is calculated. Student's T-test was used to compare the two groups. For categorical variables, number and percentage is presentend and a Chi square test used to compare the two groups. Fisher's exact test was used when appropriate. ). FA, folic acid (0.8 mg); B₁₂, vitamin B₁₂ (0.4 mg); B₆, vitamin B₆ (40 mg); LMS, left main stem artery; LAD, left anterior descending artery; CX; circumflex artery; RCA, right coronary artery; mm, millimeters.</p

Asymmetric dimethylarginine and trimethyllysine before and after supplementation with folic acid/vitamin B₁₂.

<p>The graph shows empirical cumulative distribution frequencies for asymmetric dimethylarginine on the left and trimethyllysine on the right. Patients receiving folic acid/B₁₂ are displayed on the top, while patients receiving placebo or B₆ on the bottom. Time of measurement is shown as baseline (solid line) and follow-up (dashed line) after a median of 10.5 month.</p

Grayscale IVUS and Virtual Histology of TCFA.

<p>A thin cap fibroatheroma (asterisk) in the proximal left anterior descending coronary artery of one of the study patients. The left panel shows an intravascular ultrasound radiofrequency image which is subsequently used to make the virtual histology image in the right panel. Green is fibrous tissue, yellow is fibro-fatty, red is necrotic core and white is calcified tissue. </p

MCP-1 and Presence of Occult Thin-Cap Fibroatheroma at VH–IVUS Study Inclusion.

<p>Cumulative distribution frequency plots of Monocyte Chemotactic Protein-1 (MCP-1) in patients with (solid line) and without (dashed line) Virtual Histology Thin-Cap Fibroatheroma (VH-TCFA).</p

Flow-chart of patient inclusion.

<p>The chart shows the flow of patients from the WENBIT-trial (n=3090) to inclusion in the current IVUS-VH study (n=105). All patients were randomized to B-vitamin treatment at WENBIT-baseline. Of the 1359 patients who had PCI at WENBIT-baseline, 371 had new, scheduled angiography at the WENBIT-one year follow-up. Of these 371 patients, 231 had received IVUS in a non-intervened vessel. IVUS-VH analysis and MCP-1 measurements were performed on 102 of these 231 patients and constituted our current study population. MCP-1 measurements were performed both at WENBIT-baseline (B-vitamin randomization) and at IVUS-VH study inclusion. Abbreviations are FA, folic acid (0.8 mg); B12, vitamin B₁₂ (0.4 mg); B6, vitamin B6 (40 mg); WENBIT, Western Norway B-vitamin Intervention Trial; IVUS, intravascular ultrasound; IVUS-VH, intravascular ultrasound – virtual histology; PCI, Percutaneous coronary intervention and MCP-1, monocyte chemoattractant protein-1.</p

MCP-1 Levels According to Folic Acid Supplementation at VH–IVUS Study Inclusion.

<p>Cumulative distribution frequency plots showing plasma Monocyte Chemotactic Protein-1 (MCP-1) on the x-axis in patients receiving folic acid/vitamin B₁₂ (solid line) and placebo or B₆ (dashed line).</p

Baseline characteristics after matching.

<p>Continuous variables are shown as means (standard deviation) and medians (interquartile range) and categorical variables as numbers (percentage). Abbreviations: WENBIT = WEstern Norway B-vitamin Trial; CAD = coronary artery disease; PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft; PVD = peripheral vascular disease; DVT = deep venous thrombosis; NYHA = New York Heart Association; BP = blood pressure; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin; WBC = white blood cell count; ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; COPD = chronic obstructive pulmonary disease; NSAID = non-steroid anti-inflammatory drug.</p><p>Baseline characteristics after matching.</p