Abstract 154: Diabetic Retinopathy and Risk of Stroke: A Secondary Analysis of Accord

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ka-ho Wong ◽  
Cecilia Peterson ◽  
Rock Theodore ◽  
Kinga aitken ◽  
Michael Dela Cruz ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Primary Outcome ◽  
Cox Model ◽  
Secondary Analysis ◽  
Cox Models ◽  
Interaction Terms ◽  
Increased Risk ◽  
Microvascular Pathology ◽  
Fundus Photographs

Background: Diabetic retinopathy is a common microvascular complication of diabetes. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with shared and, possibly, synergistic pathology. Methods: This is a secondary analysis of the subgroup of patients who enrolled in the ACCORD Eye study of ACCORD. The primary outcome is stroke during follow-up. The primary predictor was presence of diabetic retinopathy on the Early Treatment Diabetic Retinopathy Study Severity Scale as assessed from seven-field stereoscopic fundus photographs at study baseline. We fit adjusted Cox models to the primary outcome to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms. Results: We included 2,828 patients with a mean (SD) age of 62.1 years and 61.8% were male. The primary outcome of stroke was met by 117 patients during a mean (SD) of 5.4 (1.8) years of follow-up. Diabetic retinopathy was present in 874/2,828 (30.9%) of patients at baseline, and was more common in patients with stroke versus without stroke (41.0 vs 30.5%, p=0.016). In the Cox model, adjusted for baseline patient age, gender, race, total cholesterol, Hgb A1c, smoking, and randomization arm, we found that diabetic retinopathy remained associated with incident stroke (HR 1.60, 95% CI 1.10-2.32, p=0.015) (Figure 1). This association was not affected by randomization to the ACCORD glucose intervention (p=0.305), lipid intervention (p=0.546), or blood pressure intervention (p=0.422). Conclusion: Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications.

scholarly journals Diabetic Retinopathy and Risk of Stroke

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3733-3736
Author(s):  
Ka-Ho Wong ◽  
Katherine Hu ◽  
Cecilia Peterson ◽  
Nazanin Sheibani ◽  
Georgios Tsivgoulis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Retinopathy ◽  
Primary Outcome ◽  
Vision Loss ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Increased Risk

Background and Purpose: Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which causes damage to the retina and may lead to rapid vision loss. Previous research has shown that the macrovascular complications of diabetes, including stroke, are often comorbid with DR. We sought to explore the association between DR and subsequent stroke events. Methods: This is a secondary analysis of patients enrolled in the ACCORD Eye study (Action to Control Cardiovascular Risk in Diabetes). The primary outcome was stroke during follow-up. The exposure was presence of DR at study baseline. We fit adjusted Cox proportional hazards models to provide hazard ratios for stroke and included interaction terms with the ACCORD randomization arms. Results: We included 2828 patients, in whom the primary outcome of stroke was met by 117 (4.1%) patients during a mean (SD) of 5.4 (1.8) years of follow-up. DR was present in 874 of 2828 (30.9%) patients at baseline and was more common in patients with than without incident stroke (41.0% versus 30.5%; P =0.016). In an adjusted Cox regression model, DR was independently associated with incident stroke (hazard ratio, 1.52 [95% CI, 1.05–2.20]; P =0.026). This association was not affected by randomization arm in the ACCORD glucose ( P =0.300), lipid ( P =0.660), or blood pressure interventions ( P =0.469). Conclusions: DR is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to DR has larger cerebrovascular implications. This association appears not to be mediated by serum glucose, lipid, and blood pressure interventions.

Abstract 47: Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of MESA

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Ka-Ho Wong ◽  
J Scott McNally ◽  
Jennifer Majersik
Keyword(s):  
Ischemic Stroke ◽  
Total Cholesterol ◽  
Primary Outcome ◽  
Epidemiologic Study ◽  
Secondary Analysis ◽  
Serum Marker ◽  
Patient Age ◽  
Cox Models ◽  
Patient Âgé

Background: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large prospective epidemiologic study of the clinical factors that can predict transition from asymptomatic to symptomatic cardiovascular disease. Although prior studies have looked at ischemic stroke, they have not systematically examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary stroke risk. Methods: The primary outcome is incident ischemic stroke during follow-up. The predictors are 9 ultrasound-derived measurements and 5 serum measurements related to inflammation. We fit Cox models to ischemic stroke and adjusted for patient age, hypertension, diabetes, total cholesterol, and smoking. Using DeLong’s method, we compared the AUC of the baseline adjusted model to the AUC of the model with predictor variables that were significant in the Cox models, to determine if they improved stroke prediction. Results: We included 6,095 patients with an average age of 61.9 years. The primary outcome of ischemic stroke was seen in 107 patients (1.8%) and the mean follow-up time was 7.7 years. In the Cox models, we found that small artery elasticity (SAE), carotid distensibility (CD), carotid stenosis (CS), and interleukin-6 (IL6) were associated with incident stroke. The AUC of the baseline model to predict stroke, which included patient age, hypertension, diabetes, total cholesterol, and smoking, was 0.745. When we added tertiles of SAE, CD, IL6 and categories of CS, the AUC improved to 0.765 (p=0.021 for difference). Conclusions: In a multiethnic cohort of patients without CVD at baseline, we found several ultrasound measurements and a serum marker of inflammation which predicted the occurrence of a primary ischemic stroke. Adding these basic ultrasound and serum measurements significantly improved the prediction of stroke, which could have implications for primary prevention efforts.

scholarly journals Low levels of circulating anti-ageing hormone Klotho predict the onset and progression of diabetic retinopathy

2020 ◽  
Vol 17 (6) ◽  
pp. 147916412097090
Author(s):  
Antonella Corcillo ◽  
Nikolaos Fountoulakis ◽  
Angela Sohal ◽  
Frederick Farrow ◽  
Salma Ayis ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Primary Outcome ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Diabetic Eye Disease ◽  
Circulating Levels

Background: Klotho is a circulating anti-ageing hormone that predicts progression of cardiovascular and renal disease. The role of Klotho in diabetic retinopathy is unknown. Methods: We performed a single-centre observational study of 81 people (males 62%) with type 2 diabetes followed for a median of 44 months. Circulating levels of Klotho and other markers, were measured from stored samples. The primary outcome was progression of retinopathy defined as new onset retinopathy or step change in retinopathy grading. Results: During follow-up, 46 (57%) people reached the primary outcome. People with progression of retinopathy had lower levels of serum Klotho as compared to those without (median (interquartile range) 226.9 (171.1–394.0) vs 484.5 (221.8–709.9) pg/ml, p = 0.001). In multivariable logistic regression analyses, baseline Klotho level was the only variable independently associated with reduced risk of progression of retinopathy. Our results suggest that a halving of circulating Klotho levels increases the risk of retinopathy progression by 44%. Conclusion: In people with type 2 diabetes, lower circulating levels of the vascular protective hormone Klotho are associated with increased risk of progression of diabetic retinopathy. Klotho may be a novel biomarker and potential treatment target for diabetic eye disease.

Abstract TMP99: White Matter Hyperintensity Progression and Subsequent Incident Stroke: A Secondary Analysis of the ACCORD Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Tanya Turan ◽  
Natalia Rost ◽  
...  
Keyword(s):  
Risk Factor ◽  
White Matter ◽  
Primary Outcome ◽  
Cox Model ◽  
Secondary Analysis ◽  
Exposure Period ◽  
White Matter Hyperintensity ◽  
Diabetic Patients ◽  
Cox Models ◽  
Recurrent Strokes

Introduction: Studies have shown that the volume of white matter hyperintensity (WMH) is a risk factor for stroke, but there are scarce data exploring the relationship between WMH progression on serial MRIs and subsequent risk of stroke. Hypothesis: We hypothesize that WMH progression in the ACCORD trial increases the risk of subsequent incident stroke. Methods: The exposure period was from baseline to month 40, during which an MRI was performed at both baseline and month 40. The primary outcome was incident ischemic stroke after the month 40 MRI until study completion. We fit Cox models to the primary outcome and included both the baseline and month 40 WMH volume as covariates, with the hazard ratio for the month 40 WMH volume of primary interest because it represents WMH progression in this model. Results: We included 497 patients, of whom 53.3% were male and the mean (SD) age was 62.7 (5.7) years at enrollment. Mean (SD) follow-up after the month 40 MRI was 5.2 (1.8) years. Incident stroke occurred in 17 (3.4%) patients, in whom 2 were recurrent strokes and 15 were first-ever strokes. WMH progression was associated with subsequent stroke in the Cox model (HR 1.27, 95% CI 1.03-1.57, p=0.024) and remained significant after adjusting for patient age, history of prior stroke, and cigarette smoking (HR 1.33, 95% CI 1.07-1.65, p=0.010). Conclusions: Although this preliminary analysis is underpowered, WMH progression, independent of absolute WMH burden, may be a risk factor for future stroke in diabetic patients. This novel finding could have translational implications - specifically that interventions which reduce the progression of WMH could, in turn, reduce future risk of stroke.

scholarly journals THE RELATIONSHIP BETWEEN INFLAMMATORY DIETARY PATTERN AND INCIDENCE OF PERIODONTITIS

2021 ◽  
pp. 1-36
Author(s):  
Ahmed A. Alhassani ◽  
Frank B. Hu ◽  
Bernard A. Rosner ◽  
Fred K. Tabung ◽  
Walter C. Willett ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Periodontal Disease ◽  
Secondary Analysis ◽  
Hazard Ratio ◽  
Reduced Rank Regression ◽  
Rank Regression ◽  
Increased Risk ◽  
Cox Proportional Hazard Models ◽  
Study Population

ABSTRACT The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.

scholarly journals Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of the Multi-Ethnic Study of Atherosclerosis

2021 ◽  
pp. 37-43
Author(s):  
Hediyeh Baradaran ◽  
Alen Delic ◽  
Ka-Ho Wong ◽  
Nazanin Sheibani ◽  
Matthew Alexander ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Goodness Of Fit ◽  
Primary Outcome ◽  
Stroke Risk ◽  
Secondary Analysis ◽  
Predictor Variables ◽  
Baseline Model ◽  
Fit Statistics ◽  
Ischemic Stroke Risk

Introduction: Current ischemic stroke risk prediction is primarily based on clinical factors, rather than imaging or laboratory markers. We examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary ischemic stroke risk. Methods: In this secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), the primary outcome is the incident ischemic stroke during follow-up. The predictor variables are 9 carotid ultrasound-derived measurements and 6 serum inflammation measurements from the baseline study visit. We fit Cox regression models to the outcome of ischemic stroke. The baseline model included patient age, hypertension, diabetes, total cholesterol, smoking, and systolic blood pressure. Goodness-of-fit statistics were assessed to compare the baseline model to a model with ultrasound and inflammation predictor variables that remained significant when added to the baseline model. Results: We included 5,918 participants. The primary outcome of ischemic stroke was seen in 105 patients with a mean follow-up time of 7.7 years. In the Cox models, we found that carotid distensibility (CD), carotid stenosis (CS), and serum interleukin-6 (IL-6) were associated with incident stroke. Adding tertiles of CD, IL-6, and categories of CS to a baseline model that included traditional clinical vascular risk factors resulted in a better model fit than traditional risk factors alone as indicated by goodness-of-fit statistics. Conclusions: In a multiethnic cohort of patients without cerebrovascular disease at baseline, we found that CD, CS, and IL-6 helped predict the occurrence of primary ischemic stroke. Future research could evaluate if these basic ultrasound and serum measurements have implications for primary prevention efforts or clinical trial inclusion criteria.

scholarly journals Timing of orchidopexy and its relationship to postoperative testicular atrophy: results from the ORCHESTRA study

BJS Open ◽  
2021 ◽  
Vol 5 (1) ◽  
Author(s):  
◽  
C Skerritt ◽  
C Bradshaw ◽  
N Hall ◽  
L McCarthy ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Testicular Atrophy ◽  
Wound Infections ◽  
Atrophy Rate ◽  
Younger Age ◽  
Increased Risk ◽  
Hospital Stays ◽  
Reoperation Rates ◽  
International Audit

Abstract Background In 2011 a consensus statement from the British Association of Paediatric Urologists recommended lowering the age at orchidopexy to under 1 year. There are concerns that a younger age at operation may increase postoperative testicular atrophy. The ORCHESTRA study aimed to establish the current age at orchidopexy in a multicentre, international audit and to see whether testicular atrophy was affected by age at operation. Methods The study was undertaken over a 3-month period in 28 centres in boys undergoing orchidopexy for unilateral, palpable undescended testes. Data collection was done using a standardized, predetermined protocol. The primary outcome was postoperative testicular atrophy. Secondary outcomes were wound infections, reoperations, and unplanned hospital stays related to anaesthetic events. Results A total of 417 patients were included, of whom only 48 (11.5 per cent) underwent orchidopexy before 1 year of age. There was no difference in anaesthetic complications in boys aged less than 1 year versus older patients: 0 of 48 (0 per cent) versus 6 of 369 (1.6 per cent) (P = 0.999). Complete follow-up was available for 331 patients (79.4 per cent). There was no difference in atrophy rate between those aged less than 1 year and older boys: 1 of 37 (3 per cent) versus 9 of 294 (3.1 per cent) (P = 0.999). Reoperation rates were 0 of 37 (0 per cent) and 7 of 294 (2.4 per cent) respectively (P = 1.000). There were more wound infections in boys under 1 year of age: 4 of 37 (11 per cent) versus 7 of 294 (2.4 per cent) (P = 0.025). Conclusion Only 11.5 per cent of boys underwent surgery before the age of 1 year. There was no increased risk of postoperative testicular atrophy with early surgery, although there was a higher rate of wound infection. Further study is required to demonstrate that early orchidopexy is not inferior to orchidopexy undertaken in boys aged over 1 year.

scholarly journals Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3381
Author(s):  
Sang Heon Suh ◽  
Tae Ryom Oh ◽  
Hong Sang Choi ◽  
Chang Seong Kim ◽  
Eun Hui Bae ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Body Weight ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Body Weight Gain ◽  
Absolute Difference ◽  
Composite Outcome ◽  
Increased Risk ◽  
All Cause Mortality

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.

scholarly journals Association of Long-Term Change and Variability in Glycemia with Risk of Incident Heart Failure among Patients with Type 2 Diabetes Mellitus – A Secondary Analysis of the ACCORD Trial

2020 ◽  
Author(s):  
Matthew W. Segar ◽  
Kershaw V. Patel ◽  
Muthiah Vaduganathan ◽  
Melissa C. Caughey ◽  
Javed Butler ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Secondary Analysis ◽  
Glycemic Variability ◽  
Baseline Risk ◽  
Absolute Difference ◽  
Cox Models ◽  
Term Change ◽  
Alternative Measures

<b>Objective</b>: Evaluate the associations between long-term change and variability in glycemia with risk of HF among patients with T2DM. <p><b>Research Design and Methods: </b>Among participants with T2DM enrolled in the ACCORD trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV=average absolute difference between successive values), coefficient of variation (CV=standard deviation/mean), and standard deviation. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of % change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF.</p> <p><b>Results</b>: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF [HR (95% CI) for ≥10% decrease = 1.32 (1.08-1.75), ≥10% increase = 1.55 (1.19-2.04), ref: <10% change in HbA1c]. Higher long-term variability in HbA1c was significantly associated with higher risk of HF [HR (95% CI) per 1 SD of ASV = 1.34 (1.17-1.54)] independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed using alternative measures of glycemic variability.</p> <p><b>Conclusions:</b> Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.</p>

Abstract 133: White Matter Hyperintensity and Cardiovascular Disease Outcomes: A Secondary Analysis of the SPRINT MIND Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Tanya Turan ◽  
Sharon Yeatts ◽  
Rebecca Gottesman ◽  
Shyam Prabhakaran ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Outcome ◽  
Stroke Risk ◽  
Secondary Analysis ◽  
White Matter Hyperintensity ◽  
Secondary Outcome ◽  
Cox Models ◽  
Disease Outcomes ◽  
Hazard Ratios ◽  
The Mean

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) randomized patients to a goal SBP <120 mm Hg vs. <140 mm Hg . A subset of patients enrolled in SPRINT MIND, which performed a baseline MRI and measured white matter hyperintensity volume (WMHv). We evaluated the association between WMHv and cardiovascular events. Methods: The primary outcome was a composite of stroke, MI, ACS, decompensated CHF, or CVD death. The secondary outcome was stroke. The WMHv was divided into quartiles. We fit Cox models to the outcomes and report adjusted hazard ratios for the quartiles of WMHv, and stratified by SPRINT treatment arm. Results: Among 719 included patients, the mean WMHv in the quartiles was 0.34, 1.09, 2.61, and 10.8 mL. The primary outcome occurred in 51/719 (7.1%) and the secondary outcome in 10/719 (1.4%). The WMHv was associated with both outcomes (Table 1, Figure 1). After stratifying by treatment arm, we found the association persisted in the standard, but not intensive, treatment arm (Table 2). However, the interaction term between WMHv and treatment arm was not significant. Conclusions: We observed that degree of WMH was associated with CVD and stroke risk in SPRINT MIND. The risk may be attenuated in patients randomized to intensive BP lowering. Trials are needed to determine if intensive BP lowering can prospectively reduce the high cardiovascular risk in patients with WMH.

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