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Background Diabetic retinopathy (DR) is a major sight-threatening microvascular complication in individuals with diabetes. Systemic inflammation combined with oxidative stress is thought to capture most of the complexities involved in the pathology of diabetic retinopathy. A high level of neutrophil–lymphocyte ratio (NLR) is an indicator of abnormal immune system activity. Current estimates of the association of NLR with diabetes and its complications are almost entirely derived from cross-sectional studies, suggesting that the nature of the reported association may be more diagnostic than prognostic. Therefore, in the present study, we examined the utility of NLR as a biomarker to predict the incidence of DR in the Scottish population. Methods The incidence of DR was defined as the time to the first diagnosis of R1 or above grade in the Scottish retinopathy grading scheme from type 2 diabetes diagnosis. The effect of NLR and its interactions were explored using a competing risks survival model adjusting for other risk factors and accounting for deaths. The Fine and Gray subdistribution hazard model (FGR) was used to predict the effect of NLR on the incidence of DR. Results We analysed data from 23,531 individuals with complete covariate information. At 10 years, 8416 (35.8%) had developed DR and 2989 (12.7%) were lost to competing events (death) without developing DR and 12,126 individuals did not have DR. The median (interquartile range) level of NLR was 2.04 (1.5 to 2.7). The optimal NLR cut-off value to predict retinopathy incidence was 3.04. After accounting for competing risks at 10 years, the cumulative incidence of DR and deaths without DR were 50.7% and 21.9%, respectively. NLR was associated with incident DR in both Cause-specific hazard (CSH = 1.63; 95% CI: 1.28–2.07) and FGR models the subdistribution hazard (sHR = 2.24; 95% CI: 1.70–2.94). Both age and HbA 1c were found to modulate the association between NLR and the risk of DR. Conclusions The current study suggests that NLR has a promising potential to predict DR incidence in the Scottish population, especially in individuals less than 65 years and in those with well-controlled glycaemic status.

Background Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. Methods One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. Results EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm 2 vs. group 4 EAT 11.8 ± 4.1 cm 2 , p  = 0.001; group 3 EAT 15.1 ± 4.3 cm 2 vs. group 4 EAT 11.8 ± 4.1 cm 2 , p  = 0.024). EAT was independently associated with IL-6 (beta 0.2, p  = 0.019). When added to clinical variables, both EAT (beta 0.16, p  = 0.035) and IL-6 (beta 0.26, p  = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. Conclusions In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.

ObjectivesRecent safety concerns regarding gadolinium-based contrast agents (GdCAs) concluded with the suspension of some agents from the European market, yet a clinical consequence remains unknown. We used electronic health records to investigate the incidence of potential toxicity to gadoteric acid (Dotarem®) within our local population, including those with renal insufficiency (RI).MethodsData for patients who underwent contrast-enhanced MRI were identified, stratified by renal function at time of scan and retrospectively followed using routinely collected health data. Searches performed were: records of hypersensitivity reactions; diagnoses of nephrogenic systemic fibrosis (NSF); onset of chronic pain, a symptom that has been associated with NSF and the theorised gadolinium deposition disease (GDD); and post-contrast acute kidney injury (PC-AKI). Comparisons were made between patients and controls (those who underwent non-contrast scans) via chi-square and ANOVA statistical tests.ResultsOf the 22,897 contrast-enhanced MRI scans performed locally from 2004–2016 (adult, n = 22,325 and paediatric, n = 572), 14% were performed on patients with RI (30 ≤ eGFR < 60, n = 2,622; 15 ≤ eGFR < 30, n = 464; eGFR < 15, n = 123). Two adult patients (0.01%) suffered hypersensitivity reactions. Zero cases of NSF were reported, with an average follow-up time of 6.0 ± 2.5 years (range, 8 months–15 years). Analysis failed to highlight statistically higher rates of chronic pain onset post-MRI (adult: p = 0.777, paediatric: p = 0.578), or PC-AKI (adult: p = 0.566, paediatric: p = 0.841), in the patient groups compared to controls.ConclusionsThese data indicate that administration of gadoteric acid to RI patients does not result in a higher rate of signs or symptoms that may be associated with gadolinium toxicity when compared to controls.Key Points• Following 22,897 administrations of gadoteric acid to a local population, there was no association with symptoms that may be associated with gadolinium toxicity.• Zero cases of nephrogenic systemic fibrosis were reported following 3,209 gadoteric acid administrations to a cohort of renally insufficient patients.• A low number of hypersensitivity reactions were observed (0.01%) and no higher rate of chronic pain or post-contrast acute kidney injury were noted when compared with a control cohort of non-contrast-enhanced examinations.

Background Carotid-femoral pulse wave velocity (cf-PWV) and aortic PWV measured using MRI (MRI-PWV) show good correlation, but with a significant and consistent bias across studies. The aim of the current study was to evaluate whether the differences between cf.-PWV and MRI-PWV can be accounted for by inaccuracies of currently used distance measurements. Methods One hundred fourteen study participants were recruited into one of 4 groups: Type 2 diabetes melltus (T2DM) with cardiovascular disease (CVD) ( n  = 23), T2DM without CVD ( n  = 41), CVD without T2DM ( n  = 25) and a control group ( n  = 25). All participants underwent cf.-PWV, cardiac MRI and whole body MR angiography(WB-MRA). 90 study participants also underwent aortic PWV using MRI. cf.-PWV EXT was performed using a SphygmoCor device (Atcor Medical, West Ryde, Australia). The true intra-arterial pathlength was measured using the WB-MRA and then used to recalculate the cf.-PWV EXT to give a cf.-PWV MRA . Results Distance measurements were significantly lower on WB-MRA than on external tape measure (mean diff = −85.4 ± 54.0 mm, p  < 0.001). MRI-PWV was significantly lower than cf.-PWV EXT (MRI-PWV = 8.1 ± 2.9 vs. cf.-PWV EXT  = 10.9 ± 2.7 ms −1 , p  < 0.001). When cf.-PWV was recalculated using the inter-arterial distance from WB-MRA, this difference was significantly reduced but not lost (MRI-PWV = 8.1 ± 2.9 ms −1 vs. cf.-PWV MRA 9.1 ± 2.1 ms −1 , mean diff = −0.96 ± 2.52 ms −1 , p  = 0.001). Recalculation of the PWV increased correlation with age and pulse pressure. Conclusion Differences in cf.-PWV and MRI PWV can be predominantly but not entirely explained by inaccuracies introduced by the use of simple surface measurements to represent the convoluted arterial path between the carotid and femoral arteries.

Background Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk. Methods One thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a < 20% 10 year cardiovascular risk score underwent a cardiovascular magnetic resonance (CMR) study and whole body CMR angiogram. Arteriosclerosis was measured using total arterial compliance (TAC) - calculated as the indexed stroke volume divided by the pulse pressure. Atherosclerosis was quantified using a standardised atheroma score (SAS) which was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Left ventricular remodelling was measured using left ventricular mass to volume ratio (LVMVR). Results One thousand five hundred fifteen (38% male, 53.8 ± 8.2 years old) completed the study. On univariate analysis TAC was associated with SAS but this was lost after accounting for cardiovascular risk factors in both males (B = − 0.001 (− 0.004–0.002), p  = 0.62) and females (B = 0.000(95%CI -0.002--0.002), p  = 0.78). In contrast compliance correlated with LVMVR after accounting for cardiovascular risk factors (B = − 0.12(95%CI -0.16--0.091), p  < 0.001 in males; B = − 0.12(95%CI -0.15--0.086), p  < 0.001 in females). Conclusion Systemic arteriosclerosis is associated with left ventricular remodelling but not atherosclerosis. Future efforts in cardiovascular risk prevention should thus seek to address both arteriosclerosis and atherosclerosis individually.

Background Whole body cardiovascular MR (WB CVMR) combines whole body angiography and cardiac MR assessment. It is accepted that there is a high disease burden in patients with diabetes, however the quantification of the whole body atheroma burden in both arterial and cardiac disease has not been previously reported. In this study we compare the quantified atheroma burden in those individuals with and without diabetes by clinical cardiovascular disease (CVD) status. Methods 158 participants underwent WB CVMR, and were categorised into one of four groups: (1) type 2 diabetes mellitus (T2DM) with CVD; (2) T2DM without CVD; (3) CVD without T2DM; (4) healthy controls. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cardiac MR and late gadolinium enhancement images of the left ventricle were obtained for assessment of mass, volume and myocardial scar assessment. Results 148 participants completed the study protocol—61 % male, with mean age of 64 ± 8.2 years. SAS was highest in those with cardiovascular disease without diabetes [10.1 (0–39.5)], followed by those with T2DM and CVD [4 (0–41.1)], then those with T2DM only [3.23 (0–19.4)] with healthy controls having the lowest atheroma score [2.4 (0–19.4)]. Both groups with a prior history of CVD had a higher SAS and left ventricular mass than those without (p < 0.001 for both). However after accounting for known cardiovascular risk factors, only the SAS in the group with CVD without T2DM remained significantly elevated. 6 % of the T2DM group had evidence of silent myocardial infarct, with this subcohort having a higher SAS than the remainder of the T2DM group [7.7 (4–19) vs. 2.8 (0–17), p = 0.024]. Conclusions Global atheroma burden was significantly higher in those with known cardiovascular disease and without diabetes but not in those with diabetes and cardiovascular disease suggesting that cardiovascular events may occur at a lower atheroma burden in diabetes.

Background The aim of this study was to use whole body cardiovascular magnetic resonance imaging (WB CVMR) to assess the heart and arterial network in a single examination, so as to describe the burden of atherosclerosis and subclinical disease in participants with symptomatic single site vascular disease. Methods 64 patients with a history of symptomatic single site vascular disease (38 coronary artery disease (CAD), 9 cerebrovascular disease, 17 peripheral arterial disease (PAD)) underwent whole body angiogram and cardiac MR in a 3 T scanner. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cine and late gadolinium enhancement images of the left ventricle were obtained. Results Asymptomatic atherosclerotic disease with greater than 50 % stenosis in arteries other than that responsible for their presenting complain was detected in 37 % of CAD, 33 % of cerebrovascular and 47 % of PAD patients. Unrecognised myocardial infarcts were observed in 29 % of PAD patients. SAS was significantly higher in PAD patients 24 (17.5-30.5) compared to CAD 4 (2–11.25) or cerebrovascular disease patients 6 (2-10) (ANCOVA p < 0.001). Standardised atheroma score positively correlated with age (β 0.36 p = 0.002), smoking status (β 0.34 p = 0.002), and LV mass (β -0.61 p = 0.001) on multiple linear regression. Conclusion WB CVMR is an effective method for the stratification of cardiovascular disease. The high prevalence of asymptomatic arterial disease, and silent myocardial infarctions, particularly in the peripheral arterial disease group, demonstrates the importance of a systematic approach to the assessment of cardiovascular disease.

IntroductionArteriosclerosis (arterial stiffening) and atherosclerosis (plaque formation) are pathophysiological processes afflicting the vasculature, both of which are associated with future cardiovascular events. However the degree to which they overlap or simply co-exist is poorly understood. The aim of the current study is to determine if these two processes are significantly associated with one another.Methods1651 volunteers with no clinical manifestation of cardiovascular disease and <20% 10-year cardiovascular risk underwent a cardiac MRI and whole body MR angiogram as part of the TASCFORCE study. Systemic arterial stiffness was measured using total arterial compliance (TAC) – calculated as the indexed stroke volume divided by the pulse pressure. Systemic atheroma burden (AB) was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments.Results1515 (574 male, 53.8±8.2 years-old) completed the study.?On multiple linear regression age (B=–0.001 (95%CI –?0.002–−0.000), p=0.004), heart rate (B=–0.003 (95%CI –?0.003–−0.002), p<0.001) and blood pressure (B=–0.008 (95%CI –0.009–−0.008), p<0.001) were independently associated with TAC, while age (B=0.061 (95%CI 0.04–0.08), p<0.001), and smoking pack-year history (B=0.003 (95%CI 0.005), p=0.022) were independently associated with AB. TAC and AB?demonstrated a significant correlation with each other (Spearman rho=–0.12, p<0.001), however on multivariable analysis accounting for age, blood pressure, sex, BMI, smoking status and cholesterol no significant association persisted (B=–?0.001 (95%CI –0.004–0.002), p=0.62).ConclusionSystemic arteriosclerosis and atherosclerosis are separate entities with each determined by different risk factors. Future efforts in cardiovascular risk prevention should seek to address both of these pathophysiological entities.

IntroductionUnrecognised myocardial infarctions (UMIs) have been described in 19–30% of the population using late gadolinium enhancement (LGE). However these studies have focussed on unselected cohorts including those with known cardiovascular disease. The aim of the current study was to ascertain the prevalence of UMIs in a non-high risk population and their physiological significance.Methods5,000 volunteers >40 years with no history of cardiovascular disease (CVD) and a 10 year risk of CVD of less than 20% were recruited to the Tayside Screening for Cardiac Events (TASCFORCE) study. Those with a BNP level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE. LGE was classed as absent, UMI, or non-specific.Results1,529 completed the imaging study with 53 (3.6%) excluded due to missing data or inadequate LGE image quality. 10 of the remaining 1476 (0.67%) displayed LGE. Of these, 3 (0.2%) were consistent with UMI, while 7 were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1) or right ventricular insertion points (n = 2). Those with UMI had significantly higher BNP(median 116 (range 31–133) vs 22.6 (5–175) pg/ml, p = 0.015), lower ejection fraction (54.6 (36–62) vs 68.9 (38–89) %, p = 0.007) and larger end systolic volume (36.3 (27–61) vs 21.7 (5–65) ml/m2, p = 0.014). Those with non-specific LGE had lower diastolic blood pressure (68 (54–70) vs 72 (46–98) mmHg, p = 0.013), but no differences in their cardiac function.ConclusionDespite previous reports describing high prevalence of UMI, those who are of low-intermediate cardiovascular risk have a very low prevalence of UMI. LGE typical of UMI is associated with significantly impaired cardiac function, while LGE atypical of UMI has no adverse effect on function.