Inflammation and endothelial dysfunction are associated with retinopathy: the Hoorn Study.

AIMS/HYPOTHESIS: The exact pathogenesis of retinopathy in diabetic and non-diabetic individuals is incompletely understood, but may involve chronic low-grade inflammation and dysfunction of the vascular endothelium. The aim of this study was to investigate the association of inflammation and endothelial dysfunction with prevalent retinopathy in individuals with and without type 2 diabetes. METHODS: As part of a population-based cohort study, 625 individuals aged 50-74 years, stratified according to age, sex and glucose tolerance status, underwent an extensive physical examination. Retinopathy was assessed by an ophthalmological examination, including funduscopy and two-field 45 degrees fundus photography with mydriasis in both eyes. Levels of C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), von Willebrand factor, and soluble vascular adhesion molecule-1 (sVCAM-1) were assessed, together with the urinary albumin : creatinine ratio, and the results were combined to obtain summarising z scores for inflammation and endothelial dysfunction. RESULTS: The prevalence of retinopathy was positively associated with tertiles of CRP and sICAM-1. When compared with the lowest tertile, the highest tertile of the inflammatory z score was associated with retinopathy in all subjects (odds ratio [OR]=2.2, 95% CI 1.2-4.1, adjusted for age, sex and glucose tolerance status). The highest tertile of the endothelial dysfunction z score was associated with retinopathy among diabetic individuals (OR=4.4, 95% CI 1.2-15.9, adjusted for age and sex) but not in non-diabetic individuals. Additional adjustment for other risk factors, such as systolic and diastolic blood pressure, BMI, total cholesterol and triglycerides, or mutual adjustment of the inflammatory and endothelial dysfunction z scores did not change the results. CONCLUSIONS/INTERPRETATION: In this study, inflammatory activity and endothelial dysfunction were associated with retinopathy, which suggests their involvement in the pathogenesis of retinopathy.

Perfusion and functional abnormalities outside the septal region in patients with left bundle branch block assessed with gated SPECT.

BACKGROUND: The presence of a left bundle branch block (LBBB) pattern on the electrocardiogram may frequently lead to perfusion defects in the septum not necessarily due to ischemic heart disease, but probably due to abnormal septal wall motion. The introduction of gated single photon emission computed tomography (SPECT) allows the evaluation of myocardial perfusion and function in one study. Accordingly, we analysed perfusion and function and the relation between perfusion and regional function in the septal region in patients with a LBBB without evidence of a previously sustained myocardial infarction. METHODS: We selected 37 patients with a LBBB without a history of a previous myocardial infarction, which was confirmed by echocardiography and/or coronary angiography. All patients underwent technetium-99m tetrofosmin gated SPECT myocardial imaging. Twelve control patients with a low likelihood of coronary artery disease and a normal technetium-99m tetrofosmin gated SPECT myocardial perfusion scintigram were selected as a reference population. The left ventricle (LV) was divided into 18 segments, which were scored for perfusion and function (wall motion and wall thickening) on a 4-point scale. RESULTS: The average LV end-diastolic volume was higher and the average LV ejection fraction was lower in patients with LBBB as compared to controls (142+/-90 vs. 81+/-18 ml, and 48+/-19 vs 62+/-7%, p=0.03 and p=0.02, respectively). Not only in the septum, but also in the other segments, reduced myocardial perfusion and abnormal wall motion/wall thickening was observed in the patients with LBBB (p<0.0001 vs controls). Patients with LBBB showed no correlation between perfusion and function in the septum, and between perfusion in septum and global LV function (r=0.21, p=0.2; r=0.10, p=0.6, respectively). Conversely, a good correlation was found between perfusion and function, either regional or global, in the remote segments (both r=0.79, p<0.0001). CONCLUSIONS: We conclude that patients with LBBB without a previous myocardial infarction show cardiomyopathic changes with perfusion and wall motion abnormalities, involving the entire left ventricle. The severity of diminished septal perfusion is not directly associated with the severity of septal wall motion abnormalities or global LV function. However, in the myocardial segments remote from the septum, reduced perfusion is closely associated with functional abnormalities.