Non-cardiac vascular markers in patients with angina like symptoms and CAD or normal coronary arteries.

<p>Illustrated are carotid IMT (A), plaque score (B), reactive hyperaemia index (C), reflection magnitude (D), pulse wave velocity (E) and carotid distensibility (F). The continuous lines represent the mean±SD (————) and the dotted lines represent the median + interquartile range (— — —). CAD, coronary artery disease; NCA, normal coronary arteries; IMT, carotid intima media thickness; RHI, reactive hyperaemia index; PWV, pulse wave velocity; DC, distensibility coefficient; ns, non-significant.</p

Illustration of reactive hyperaemia peripheral arterial tonometry (PAT).

<p>Depicted are a measurement (A) with colour-coded intervals corresponding to parameters required for the reactive hyperaemia index equation (B). Tracings derive from beat-to-beat finger volume changes captured by plethysmographic finger cuffs on the index fingers of both hands. The interval 60–120 seconds post cuff release is best linked to coronary microvasculature dysfunction as published by Bonnetti et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178412#pone.0178412.ref017" target="_blank">17</a>]. Additionally the comparison of a pathologic (C) and a normal (D) hyperaemia responses as recorded by fingertip plethysmography is shown. RHI, reactive hyperaemia index.</p

ROC-analysis for CAD estimation.

<p>Depicted are ROC-curves for pre- (A) and post-test probability (B) and added vascular markers. RHI^-1, inverse reactive hyperaemia index.</p

Demographic data and angina history.

<p>Demographic data and angina history.</p

Markers in the cardiovascular continuum.

<p>The inner circle (yellow) states the stage of the cardiovascular continuum. The middle circle (blue) states the different pathophysiological process or categorises of the cardiovascular continuum stage. The outer circle (black) summarises a range of markers quantifying the pathophysiological process. Investigated markers (<b><i>bold & italic</i></b>) capable of differentiating between patients with CAD and NCA in our study are highlighted red. Investigated markers (<b><i>bold & italic</i></b>) without statistical significant differences between patients with CAD and NCA are highlighted orange. SNP, single nucleotide polymorphism; CRP, C-reactive protein; IL-6, interleukin 6; TNFα, tumour necrosis factor α; ICAM-1, intercellular adhesion molecule-1; LDL, low density lipoprotein; RH-PAT, reactive hyperaemia pulse amplitude tonometry; EPCs, endothelial progenitor cells; IMT, intima media thickness; ABI, ankle brachial index; LVH, left ventricular hypertrophy; ECG, electrocardiography; ACS, acute coronary syndrome; CAD, coronary artery disease; NCA, normal coronary arteries; TIA, transitory ischaemic attack; CT, computer tomography; MRI, magnet resonance imaging; GFR, glomerular filtration rate; BNP, brain natriuretic peptide. Adapted from Dzau et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178412#pone.0178412.ref015" target="_blank">15</a>].</p

Significant expression results for hexadecanedioate in adipocytes.

<p>Significant expression results for hexadecanedioate in adipocytes.</p

Flowchart of the study design.

<p>Flowchart of the study design.</p

Manhattan plot showing genome-wide P values from association analysis of hexadecanedioate in the TwinsUK-KORA meta-analysis.

<p>The y axis shows the −log10 P values of SNPs, and the x axis shows their chromosomal positions.</p

Alcohol intake and BP stratified by hexadecanedioate levels adjusting for age, age², BMI and family relatedness.

<p>Alcohol intake and BP stratified by hexadecanedioate levels adjusting for age, age², BMI and family relatedness.</p

Association between SNPs in the <i>SLCO1B1</i> gene and <i>CYP4</i> cluster and hexadecanedioate levels in the meta analysis carried out by Shin et al (2014)[7], in the extremes of BP carried out by Padmanabhan et al (2010)[11], in the ICBP consortium GWAS(2011)[10] and with risk of statin associated myopathy as reported (SEARCH collaborative group 2008)[14].

<p>Association between SNPs in the <i>SLCO1B1</i> gene and <i>CYP4</i> cluster and hexadecanedioate levels in the meta analysis carried out by Shin et al (2014)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175479#pone.0175479.ref007" target="_blank">7</a>], in the extremes of BP carried out by Padmanabhan et al (2010)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175479#pone.0175479.ref011" target="_blank">11</a>], in the ICBP consortium GWAS(2011)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175479#pone.0175479.ref010" target="_blank">10</a>] and with risk of statin associated myopathy as reported (SEARCH collaborative group 2008)[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0175479#pone.0175479.ref014" target="_blank">14</a>].</p