Competing risks analysis for neutrophil to lymphocyte ratio as a predictor of diabetic retinopathy incidence in the Scottish population.

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 HbA1c 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.

Absence of potential gadolinium toxicity symptoms following 22,897 gadoteric acid (Dotarem®) examinations, including 3,209 performed on renally insufficient individuals.

OBJECTIVES: Recent 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). METHODS: Data 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. RESULTS: Of 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. CONCLUSIONS: These 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.

Prevalence and Distribution of Atherosclerosis in a Low- to Intermediate-Risk Population: Assessment with Whole-Body MR Angiography.

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.

Systemic arteriosclerosis is associated with left ventricular remodeling but not atherosclerosis: a TASCFORCE study.

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.

Epicardial adipose tissue is related to arterial stiffness and inflammation in patients with cardiovascular disease and type 2 diabetes.

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 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.001; group 3 EAT 15.1 ± 4.3 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, 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.

Effects of inaccuracies in arterial path length measurement on differences in MRI and tonometry measured pulse wave velocity.

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.-PWVEXT 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.-PWVEXT to give a cf.-PWVMRA. 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.-PWVEXT (MRI-PWV = 8.1 ± 2.9 vs. cf.-PWVEXT = 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.-PWVMRA 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.

3T MRI investigation of cardiac left ventricular structure and function in a UK population: The tayside screening for the prevention of cardiac events (TASCFORCE) study.

PURPOSE: To scan a volunteer population using 3.0T magnetic resonance imaging (MRI). MRI of the left ventricular (LV) structure and function in healthy volunteers has been reported extensively at 1.5T. MATERIALS AND METHODS: A population of 1528 volunteers was scanned. A standardized approach was taken to acquire steady-state free precession (SSFP) LV data in the short-axis plane, and images were quantified using commercial software. Six observers undertook the segmentation analysis. RESULTS: Mean values (±standard deviation, SD) were: ejection fraction (EF) = 69 ± 6%, end diastolic volume index (EDVI) = 71 ± 13 ml/m2 , end systolic volume index (ESVI) = 22 ± 7 ml/m2 , stroke volume index (SVI) = 49 ± 8 ml/m2 , and LV mass index (LVMI) = 55 ± 12 g/m2 . The mean EF was slightly larger for females (69%) than for males (68%), but all other variables were smaller for females (EDVI 68v77 ml/m2 , ESVI 21v25 ml/m2 , SVI 46v52 ml/m2 , LVMI 49v64 g/m2 , all P < 0.05). The mean LV volume data mostly decreased with each age decade (EDVI males: -2.9 ± 1.3 ml/m2 , females: -3.1 ± 0.8 ml/m2 ; ESVI males: -1.3 ± 0.7 ml/m2 , females: -1.7 ± 0.5 ml/m2 ; SVI males: -1.7 ± 0.9 ml/m2 , females: -1.4 ± 0.6 ml/m2 ; LVMI males: -1.6 ± 1.1 g/m2 , females: -0.2 ± 0.6 g/m2 ) but the mean EF was virtually stable in males (0.6 ± 0.6%) and rose slightly in females (1.2 ± 0.5%) with age. CONCLUSION: LV reference ranges are provided in this population-based MR study at 3.0T. The variables are similar to those described at 1.5T, including variations with age and gender. These data may help to support future population-based MR research studies that involve the use of 3.0T MRI scanners. J. Magn. Reson. Imaging 2016;44:1186-1196.

Whole body cardiovascular magnetic resonance imaging to stratify symptomatic and asymptomatic atherosclerotic burden in patients with isolated cardiovascular disease.

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 (ß 0.36 p = 0.002), smoking status (ß 0.34 p = 0.002), and LV mass (ß -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.

Cohort comparison study of cardiac disease and atherosclerotic burden in type 2 diabetic adults using whole body cardiovascular magnetic resonance imaging.

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.

The Impact of Different Magnetic Resonance Imaging Equipment and Scanning Parameters on Signal Intensity Ratio Measurements in Phantoms and Healthy Volunteers: Implications for Interpreting Gadolinium Signal Changes Within the Brain.

OBJECTIVES: The aim of this study was to examine the variation in signal intensity ratio (SIR) values in Eurospin gel phantoms and healthy volunteer (HV) brain images in response to different magnetic resonance imaging hardware and software settings. MATERIALS AND METHODS: Gel phantoms with T1 relaxation times similar to the dentate nucleus (DN), pons (P), globus palladus (GP), and thalamus (Th) were scanned using a T1-weighted 2-dimensional spin-echo sequence on 2 magnetic resonance imaging scanners (3 T and 1.5 T). Imaging was performed by sequentially altering selected magnetic resonance (MR) parameters relative to a default pulse sequence, and the protocol was implemented repeatedly over 3 months. The experiment was also repeated on a cohort of 15 young HVs. Calculations of DN/P and GP/Th SIR values were derived for the images of the gels (GelDN/P and GelGP/Th) and the HVs (HVDN/P and HVGP/Th). RESULTS: For the default sequence, the mean SIR values of GelDN/P and GelGP/Th varied by ±2.20% and ±0.75%, respectively, when measured over multiple imaging sessions (3 T). Within a single imaging session, these variations were smaller (±0.17% for GelDN/P and ±0.15% for GelGP/Th). At 1.5 T, the equivalent SIR variations for GelDN/P were ±1.41% (multiple sessions) and ±0.41% (single session), and that for GelGP/Th were ±0.47% (multiple sessions) and ±0.33% (single session).Sequential changes to the MR sequence parameters resulted in gel SIR variations as follows: 14.07% ± 2.43% (with/without normalization filters), -7.80% ± 0.28% (different echo times, TE), and -5.06% ± 0.59% (selective activation of RF coil elements). The largest variations were noted when the gels were positioned below the scanner isocenter, where SIR measurements were different by 22%.For the HVs, the SIR values were found to be consistently within 0.64% (single session) for the default sequence. Sequential changes to the MR sequence parameters resulted in SIR variations of -24.47% ± 2.47% (with/without normalization filters), -15.32% ± 7.71% (different echo times, TE), and -2.90% ± 0.78% (selective activation of RF coil elements). CONCLUSIONS: This study has demonstrated that SIR percentage changes from baseline of a similar magnitude to brain gadolinium contrast agent signal hyperintensities can be replicated in phantom models and HVs by altering common MR acquisition parameters and hardware.

Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis.

AIMS: Unrecognized myocardial infarctions (UMIs) have been described in 19-30% of the general population using late gadolinium enhancement (LGE) on cardiac magnetic resonance. However, these studies have focused on an unselected cohort including those with known cardiovascular disease (CVD). The aim of the current study was to ascertain the prevalence of UMIs in a non-high-risk population using magnetic resonance imaging (MRI). METHODS AND RESULTS: A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a 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. CONCLUSION: Despite previous reports describing high prevalence of UMI in older populations, in a predominantly middle-aged cohort, those who are of intermediate or low cardiovascular risk have a very low risk of having an unrecognized myocardial infarct.

Left Ventricular Noncompaction: Anatomical Phenotype or Distinct Cardiomyopathy?

BACKGROUND: There is considerable overlap between left ventricular noncompaction (LVNC) and other cardiomyopathies. LVNC has been reported in up to 40% of the general population, raising questions about whether it is a distinct pathological entity, a remodeling epiphenomenon, or merely an anatomical phenotype. OBJECTIVES: The authors determined the prevalence and predictors of LVNC in a healthy population using 4 cardiac magnetic resonance imaging diagnostic criteria. METHODS: Volunteers >40 years of age (N = 1,651) with no history of cardiovascular disease (CVD), a 10-year risk of CVD < 20%, and a B-type natriuretic peptide level greater than their gender-specific median underwent magnetic resonance imaging scan as part of the TASCFORCE (Tayside Screening for Cardiac Events) study. LVNC ratios were measured on the horizontal and vertical long axis cine sequences. All individuals with a noncompaction ratio of ≥2 underwent short axis systolic and diastolic LVNC ratio measurements, and quantification of noncompacted and compacted myocardial mass ratios. Those who met all 4 criteria were considered to have LVNC. RESULTS: Of 1,480 participants analyzed, 219 (14.8%) met ≥1 diagnostic criterion for LVNC, 117 (7.9%) met 2 criteria, 63 (4.3%) met 3 criteria, and 19 (1.3%) met all 4 diagnostic criteria. There was no difference in demographic or allometric measures between those with and without LVNC. Long axis noncompaction ratios were the least specific, with current diagnostic criteria positive in 219 (14.8%), whereas the noncompacted to compacted myocardial mass ratio was the most specific, only being met in 61 (4.4%). CONCLUSIONS: A significant proportion of an asymptomatic population free from CVD satisfy all currently used cardiac magnetic resonance imaging diagnostic criteria for LVNC, suggesting that those criteria have poor specificity for LVNC, or that LVNC is an anatomical phenotype rather than a distinct cardiomyopathy.