Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure

Background: Systemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP. Methods: We conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures. Results: The mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (−2.57 dB change in MD per every 3 mmHg increase in VIMmap; P \u3c 0.001) and diurnal MAP dips (changes in the MD ranged from −2.56 to −3.19 dB; P \u3c 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with −1.14 dB changes in MD [95% confidence interval (CI), −1.90 to −0.40] and 0.01 larger optic disc cupping (95% CI, 0.01–0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022). Conclusion: Progression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG)

sj-docx-4-mde-10.1177_23821205241232497 - Supplemental material for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education

Supplemental material, sj-docx-4-mde-10.1177_23821205241232497 for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education by Willem Raat, Evelyne Housiaux, Miek Smeets, Stefan Janssens, Birgitte Schoenmakers and Bert Vaes in Journal of Medical Education and Curricular Development</p

sj-docx-3-mde-10.1177_23821205241232497 - Supplemental material for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education

Supplemental material, sj-docx-3-mde-10.1177_23821205241232497 for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education by Willem Raat, Evelyne Housiaux, Miek Smeets, Stefan Janssens, Birgitte Schoenmakers and Bert Vaes in Journal of Medical Education and Curricular Development</p

sj-docx-1-mde-10.1177_23821205241232497 - Supplemental material for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education

Supplemental material, sj-docx-1-mde-10.1177_23821205241232497 for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education by Willem Raat, Evelyne Housiaux, Miek Smeets, Stefan Janssens, Birgitte Schoenmakers and Bert Vaes in Journal of Medical Education and Curricular Development</p

sj-docx-2-mde-10.1177_23821205241232497 - Supplemental material for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education

Supplemental material, sj-docx-2-mde-10.1177_23821205241232497 for How to Evaluate Online Education for General Practitioners: Development of a Tailored Questionnaire for Heart Failure Education by Willem Raat, Evelyne Housiaux, Miek Smeets, Stefan Janssens, Birgitte Schoenmakers and Bert Vaes in Journal of Medical Education and Curricular Development</p

Low Cytochrome Oxidase 1 Links Mitochondrial Dysfunction to Atherosclerosis in Mice and Pigs

<div><p>Background</p><p>Cytochrome oxidase IV complex regulates energy production in mitochondria. Therefore, we determined the relation of COX genes with atherosclerosis in mice and pigs.</p><p>Methods and results</p><p>First, we compared atherosclerosis in the aortic arch of age-matched (24 weeks) C57BL/6J control (n = 10), LDL-receptor deficient (n = 8), leptin-deficient ob/ob (n = 10), and double knock-out (lacking LDL-receptor and leptin) mice (n = 12). Low aortic <i>mitochondria-encoded cytochrome oxidase 1</i> in obese diabetic double knock-out mice was associated with a larger plaque area and higher propensity of M1 macrophages and oxidized LDL. Caloric restriction increased <i>mitochondria-encoded cytochrome oxidase 1</i> and reduced plaque area and oxidized LDL. This was associated with a reduction of titer of anti-oxidized LDL antibodies, a proxy of systemic oxidative stress. Low of <i>mitochondria-encoded cytochrome oxidase 1</i> was related to low expression of peroxisome proliferative activated receptors α, δ, and γ and of peroxisome proliferative activated receptor, gamma, co-activator 1 alpha reflecting mitochondrial dysfunction. Caloric restriction increased them. To investigate if there was a diabetic/obesity requirement for <i>mitochondria-encoded cytochrome oxidase 1</i> to be down-regulated, we then studied atherosclerosis in LAD of hypercholesterolemic pigs (n = 37). Pigs at the end of the study were divided in three groups based on increasing LAD plaque complexity according to Stary (Stary I: n = 12; Stary II: n = 13; Stary III: n = 12). Low <i>mitochondria-encoded cytochrome oxidase 1</i> in isolated plaque macrophages was associated with more complex coronary plaques and oxidized LDL. Nucleus-encoded cytochrome oxidase <i>4I1</i> and cytochrome oxidase <i>10</i> did not correlate with plaque complexity and oxidative stress. In mice and pigs, <i>MT-COI</i> was inversely related to insulin resistance.</p><p>Conclusions</p><p>Low <i>MT-COI</i> is related to mitochondrial dysfunction, oxidative stress and atherosclerosis and plaque complexity.</p></div

Atherosclerotic plaques in coronary arteries and gene expressions in coronary plaque macrophages in high-fat diet-fed miniature pigs.

<p>A-C: Representative sections of Stary I (A), Stary II (B) and Stary III (C) atherosclerotic plaques in coronary arteries of pigs are shown. Oxidized LDL is stained with mAb4E6. D-I: Scatter plots showing coronary plaque area (D), percentage of plaque area with M1 macrophages (E), percentage of plaque area with oxidized LDL (F), percentage of plaque area with collagen (G), and <i>MT-COI</i> (H) and <i>TFAM</i> (I) expressions in coronary artery macrophages in Stary I (n = 5), Stary II (n = 8) and Stary III (n = 10) miniature pigs. Gene expression data are ratios compared to expressions in coronary artery tissue extracts of 16 control pigs without atherosclerosis. *P<0.05, ***P<0.001 compared to Stary I; ^†P<0.05, ^††P<0.01 compared to Stary II.</p

Blood variables, atherosclerosis and gene expression in aorta of lean and obese mice.

<p>Blood variables, atherosclerosis and gene expression in aorta of lean and obese mice.</p

Atherosclerosis and gene expressions in placebo DKO and caloric-restricted DKO mice.

<p>Scatter plots showing plaque volume, percentage of plaque area with oxidized LDL, percentage of plaque area with macrophages, <i>Mt-co1</i> and <i>Tfam</i> RNA expression, and titer of anti-oxidized LDL antibodies, as proxy of plasma oxidative stress in placebo (n = 12) and caloric restricted (n = 10) DKO mice. Gene expression data are ratios compared to expressions in aortic extracts of 10 C57BL/6J mice. **p<0.01 and ***p<0.001 compared to placebo DKO mice.</p

Western blot showing Mt-co1 and β-actin protein in representative extracts of aortas of LDLR^-/- and placebo DKO.

<p>The Mt-co1-to-β-actin ratio was higher in LDLR^-/- than in placebo DKO mice. **p<0.01 compared to LDLR^-/- mice.</p