A deep-learning system for the assessment of cardiovascular disease risk via the measurement of retinal-vessel calibre.

Retinal blood vessels provide information on the risk of cardiovascular disease (CVD). Here, we report the development and validation of deep-learning models for the automated measurement of retinal-vessel calibre in retinal photographs, using diverse multiethnic multicountry datasets that comprise more than 70,000 images. Retinal-vessel calibre measured by the models and by expert human graders showed high agreement, with overall intraclass correlation coefficients of between 0.82 and 0.95. The models performed comparably to or better than expert graders in associations between measurements of retinal-vessel calibre and CVD risk factors, including blood pressure, body-mass index, total cholesterol and glycated-haemoglobin levels. In retrospectively measured prospective datasets from a population-based study, baseline measurements performed by the deep-learning system were associated with incident CVD. Our findings motivate the development of clinically applicable explainable end-to-end deep-learning systems for the prediction of CVD on the basis of the features of retinal vessels in retinal photographs.

Ablation of Immunoproteasome ß5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit ß2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit ß5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, ß5i-knockout (KO) mice, or WT mice injected with either adenovirus-expressing ß5i (Ad-ß5i) or angiotensin II type 1 receptor (AT1R)-associated protein (Ad-ATRAP), which inhibits AT1R. The ß5i expression and chymotrypsin-like activity were most significantly elevated in Ang II-infused retinas and serum from patients with hypertensive retinopathy. Moreover, Ang II infusion-induced retinopathy was markedly attenuated in ß5i-KO mice but aggravated in Ad-ß5i-injected mice. Accordingly, ß5i KO markedly restored Ang II-induced downregulation of ATRAP and activation of AT1R downstream mediators, which was further enhanced in Ad-ß5i-injected mice. Interestingly, overexpression of ATRAP significantly abrogated Ang II-induced retinopathy in Ad-ß5i-injected mice. This study found that ß5i promoted Ang II-induced retinopathy by promoting ATRAP degradation and activation of AT1R-mediated signals.

Retinopathy and left ventricular hypertrophy in patients with chronic kidney disease: Interrelationship and impact on clinical outcomes.

BACKGROUND: Retinopathy and left ventricular hypertrophy (LVH) are representative markers of microvascular and cardiac dysfunction in patients with chronic kidney disease (CKD). However, their relationship and their combined effects on clinical outcomes are unknown. METHODS: We included 401 patients with nondialysis-dependent CKD stage 3-5 who had been examined with fundus photography for diabetic or hypertensive retinopathy. The presence of LVH was identified by echocardiography. The clinical significance of retinopathy and LVH was evaluated in terms of the rate of renal function decline and for any cardiovascular event (CVE)/death. RESULTS: CKD patients with retinopathy had a higher prevalence of LVH than those without retinopathy (38.9% vs. 27.6%, P=0.017). The presence of retinopathy was independently associated with LVH (odds ratio 1.69, 95% confidence interval [CI] 1.02, 2.80). Compared with subjects without either retinopathy or LVH, the coexistence of retinopathy and LVH was independently associated with rapid renal function decline (ß=-3.28; 95% CI -6.52, -0.04), whereas retinopathy or LVH alone were not. Patients with both retinopathy and LVH had a higher risk of CVE/death (adjusted hazard ratio 2.75; 95% CI 1.44, 5.26) than patients with either factor alone. A significant synergistic interaction was observed between retinopathy and LVH to predict CVE/death (P for interaction=0.049). CONCLUSIONS: Retinopathy was independently associated with LVH. The coexistence of retinopathy and LVH was associated with higher risks of CKD progression and CVE/death than was either factor alone, and their combined effects synergized to predict the risk of CVE/death.

Serum uric acid concentration is associated with hypertensive retinopathy in hypertensive chinese adults.

BACKGROUND: This cross sectional investigation included 12,966 subjects with hypertension, a cohort of the China Stroke Primary Prevention Trial (CSPPT), a randomized, multicenter clinical trial. This study aimed to explore the correlation between serum uric acid (SUA) concentration and hypertensive retinopathy in hypertensive adults. METHODS: Diagnosis of hypertensive retinopathy was determined by non-mydriatic fundus photography and classified with Keith-Wagener-Barker (KWB) system. The correlation of SUA levels with hypertensive retinopathy prevalence and severity was assessed by statistical analysis. RESULTS: 9848 (75.95%) subjects were diagnosed with hypertensive retinopathy with the following retinopathy grade distribution: grade 1: 58.80%, grade 2: 14.81%, and grade 3-4: 2.34%. SUA levels were significantly associated with hypertensive retinopathy prevalence. Patients with hypertensive retinopathy had higher SUA levels than those without hypertensive retinopathy. Patients in the highest uric acid quartile had an odds ratio for hypertensive retinopathy of 1.21 compared to patients in the lowest uric acid quartile (OR = 1.21, 95% CI: 1.05-1.40, P = 0.008). When compared to the non-hyperuricemia group, those in the hyperuricemia group had an odds ratio for hypertensive retinopathy of 1.18(OR = 1.18, 95% CI: 1.05-1.33, P = 0.004). Every 1 mg/dl increase in uric acid concentration was significantly associated with a 6% higher odds of hypertensive retinopathy (OR = 1.06, 95% CI: 1.02-1.10, P = 0.002). CONCLUSIONS: The prevalence of hypertensive retinopathy was high (75.95%) among hypertensives in our patients cohort. In addition, SUA concentration was significantly associated with hypertensive retinopathy.

Plasma N-Terminal Probrain Natriuretic Peptide, Vascular Endothelial Growth Factor, and Cardiac Troponin I as Novel Biomarkers of Hypertensive Disease and Target Organ Damage in Cats.

BACKGROUND: In the absence of ocular target organ damage (ocular-TOD), diagnosis of hypertension is challenging in cats. Biomarkers would provide additional support for the diagnosis of hypertension. HYPOTHESIS: Vascular endothelial growth factor (VEGF), N-terminal probrain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), and urine protein-to-creatinine ratio (UPC) are predictors of systemic hypertension, will be increased in cats with hypertension with or without ocular-TOD, and will decrease with antihypertensive treatment. METHODS: Plasma VEGF, NT-proBNP, and cTnI concentrations and UPC were determined in healthy geriatric cats, normotensive cats with chronic kidney disease (CKD), hypertensive cats with evidence of hypertensive retinopathy (HT-ocular-TOD), and hypertensive cats without hypertensive ocular-TOD (HT-noTOD). Comparisons among groups were performed. Multivariable binary logistic regression models were built to identify independent biomarkers of hypertension and ocular-TOD. Receiver operator characteristic (ROC) curves were drawn to assess clinical use. RESULTS: Cats with HT-ocular-TOD had significantly higher VEGF than all other groups (P < .05) and significantly higher NT-proBNP than healthy cats (P < .001). Healthy cats had significantly lower cTnI than all other groups (P < .05). No differences were found among groups for UPC (P = .08). Cardiac troponin I and VEGF were independent predictors of hypertension (P < .05), but none of the biomarkers were independent predictors of ocular-TOD. N-terminal probrain natriuretic peptide concentrations decreased with antihypertensive treatment (P < .001). The ROC curves indicated that none of the biomarkers met the criteria to function as diagnostic tests for the diagnosis of hypertension or associated ocular-TOD. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Despite statistical significance and changes with ocular-TOD, antihypertensive treatment, or both, VEGF, NT-proBNP, and cTnI did not function as useful diagnostic tests for hypertension. Persistently increased systolic blood pressure (SBP) measurements in combination with fundoscopy remains the preferred method for diagnosis of feline hypertension.

The relationship between asymptomatic organ damage, and serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Interleukin-17A (IL-17A) levels in non-diabetic hypertensive patients.

BACKGROUND: This study aimed to measure the serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in hypertensive patients with/without asymptomatic organ damage (AOD), as well as to determine the relationship between the serum sTWEAK and IL17-A levels, and carotid intima media thickness (CIMT), proteinuria, retinopathy, and the left ventricle mass index (LVMI). METHODS: The study included 159 patients diagnosed with and followed-up for primary hypertension (HT); 79 of the patients had AOD (61 female and 18 male) and 80 did not (52 female and 28 male). sTWEAK and IL-17A levels were measured in all patients. RESULTS: The sTWEAK level was significantly lower in the patients with AOD than in those without AOD (858.4 pg/mL vs. 1151.58 pg/mL, P = 0.001). The sTWEAK level was negatively correlated with the mean microalbuminuria level and LVMI. The median IL-17A level was significantly higher in the patients with AOD than in those without AOD (2.34 pg/mL vs. 1.80 pg/mL, P = 0.001). There was a positive correlation between mean IL-17A level, and mean microalbuminuria level, CIMT, and LVMI. Multivariate logistic regression analysis showed that patient age, sTWEAK level, and mean 24-h systolic blood pressure were predictors of AOD. CONCLUSIONS: The sTWEAK level was lower and IL-17A level was higher in the patients with AOD. It remains unknown if sTWEAK and IL-17A play a role in the pathophysiology of AOD. Prospective observational studies are needed to determine the precise role of sTWEAK and IL-17A in the development of target organ damage.

The association of oxidative stress with hypertensive retinopathy.

This study was designed to answer the following questions: (i) Do levels of serum gamma-glutamyl transferase (GGT), a marker of oxidative stress, change in hypertensive retinopathy (HR)? (ii) Is there any relation between degree of HR and GGT levels? This study included 80 hypertensive patients with HR. Group 1 comprised 40 patients with grade I HR, and group 2 comprised 40 patients with grade II HR. We selected 40 healthy subjects for the control group. Level of GGT in group 2 was significantly higher than in group 1 (P = 0.005) and control group (P = 0.001); it was also higher in group 1 than in control group (P = 0.025). Our study suggests that oxidative stress, mechanisms known to be involved in vascular lesions, may promote the development of HR.

The association of low-grade systemic inflammation with hypertensive retinopathy.

High-sensitivity C-reactive protein (hs-CRP) is a marker of systemic low-grade inflammation. The pathophysiologic mechanism of hypertensive retiopathy (HR) is not fully established. Elevated blood pressure (BP) alone does not fully account for the extent of retinopathy, other pathogenic mechanisms may be involved, such as low-grade inflammation. Therefore, this study was designed to answer the following questions. (i) Do hs-CRP levels change in HR? (ii) Is there any relation between degree of HR and hs-CRP levels? This study included 84 hypertensive patients with HR. The hypertensive patients were divided into two groups according to the Keith-Wagener classification. Group 1 comprised 42 patients with grade I HR, and Group 2 comprised 42 patients with grade II HR. We selected 42 healthy subjects matched for age, sex, and body mass index (BMI) for control group. The level of hs-CRP in group 2 was significantly higher than in group 1 group (p = 0.018) and control group (p = 0.001), it was also higher in group 1 than in control group (p = 0.002). Also, hs-CRP showed positive correlations with degree of HR (r = 0.29, p = 0.017). Our study suggests that there is a relationship between HR and hs-CRP levels, which may be associated with systemic low- grade inflammation.