Spontaneous functional changes in specific cerebral regions in patients with hypertensive retinopathy: a resting-state functional magnetic resonance imaging study.

This study investigated functional alterations in the cerebral network of patients with hypertensive retinopathy (HR) by resting-state functional magnetic resonance imaging (rs-fMRI) and degree centrality (DC) methods. 31 patients with HR along with 31 healthy controls (HC) closely matched in gender and age were enrolled for the research. All participants were examined by rs-fMRI, and the DC method was applied to evaluate alterations in spontaneous cerebral activity between the 2 groups. We used the independent samples t test to evaluate demographic and general information differences between HR patients and HCs. The 2-sample t test was used to compare the DC values of different cerebral regions between the 2 groups. The accuracy of differential diagnostic HR was analyzed by receiver operating characteristic (ROC) curve method for rs-fMRI DC values changes. Pearson's correlation coefficient was applied to determine the correlation between differences in DC in specific cerebral areas and clinical manifestation. Results showed that DC values were higher in the left cerebellum posterior lobe (LCPL), left medial occipital gyrus (LMOG), and bilateral precuneus (BP) of HR patients compared to HCs. Mean DC values were lower in the right medial frontal gyrus/bilateral anterior cingulate cortex of HR patients. Anxiety and depression scores were positively correlated with DC values of LMOG and LCPL, respectively. Bilateral best-corrected visual acuity in HR patients was negatively correlated with the DC value of BP. Hence, changes in DC in specific cerebral areas of patients with HR reflect functional alterations that provide insight into the pathophysiologic mechanisms of HR.

Diastolic left ventricular function in relation to the retinal microvascular fractal dimension in a Flemish population.

Fractal analysis provides a global assessment of vascular networks (e.g., geometric complexity). We examined the association of diastolic left ventricular (LV) function with the retinal microvascular fractal dimension. A lower fractal dimension signifies a sparser retinal microvascular network. In 628 randomly recruited Flemish individuals (51.3% women; mean age, 50.8 years), we measured diastolic LV function by echocardiography and the retinal microvascular fractal dimension by the box-counting method (Singapore I Vessel Assessment software, version 3.6). The left atrial volume index (LAVI), e', E/e' and retinal microvascular fractal dimension averaged (±SD) 24.3 ± 6.2 mL/m2, 10.9 ± 3.6 cm/s, 6.96 ± 2.2, and 1.39 ± 0.05, respectively. The LAVI, E, e' and E/e' were associated (P < 0.001) with the retinal microvascular fractal dimension with association sizes (per 1 SD), amounting to -1.49 mL/m2 (95% confidence interval, -1.98 to -1.01), 2.57 cm/s (1.31-3.84), 1.34 cm/s (1.07-1.60), and -0.74 (-0.91 to -0.57), respectively. With adjustments applied for potential covariables, the associations of E peak and E/e' with the retinal microvascular fractal dimension remained significant (P ≤ 0.020). Over a median follow-up of 5.3 years, 18 deaths occurred. The crude and adjusted hazard ratios expressing the risk of all-cause mortality associated with a 1-SD increment in the retinal microvascular fractal dimension were 0.36 (0.23-0.57; P < 0.001) and 0.57 (0.34-0.96; P = 0.035), respectively. In the general population, a lower retinal microvascular fractal dimension was associated with greater E/e', a measure of LV filling pressure. These observations can potentially be translated into new strategies for the prevention of diastolic LV dysfunction.

Retinal Microvascular Changes in Hypertensive Patients with Different Levels of Blood Pressure Control and without Hypertensive Retinopathy.

PURPOSE: To determine possible correlations between different levels of blood pressure (BP) control and retinal microvascular changes in the macula and optic nerve head, using coherence tomography angiography (OCTA) in hypertensive patients without hypertensive retinopathy. METHODS: This was an observational, cross-sectional study. Seventy-three patients and 40 healthy volunteers were included in this study. The patients and volunteers were divided into four groups and from each participant one eye was selected randomly: Group A comprised 32 hypertensive patients with intensive BP control; Group B comprised 26 hypertensive patients with standard BP control; Group C comprised 15 hypertensive patients with poor BP control; Group D comprised 40 control subjects. 6 × 6 mm macula scan and 4.5 × 4.5 mm optic nerve head scan were obtained using OCTA. RESULTS: In macula scans, most measured regions of retinal VD showed significant reduction in group C, compared to groups A, B, and D (all P < .05). Partial measured regions of retinal VD were significantly lower in group B than groups A and D (all P < .05). In ONH scans, RNFL thickness and inside disc capillary density were significantly thinner and lower in groups B and C than in group D (all P < .05). SBP was significantly correlated with RNFL thickness (R = 0.430, 95% CI -0.583 to -0.201, P ≤ 0.001). CONCLUSIONS: We demonstrated that the frequency of OCTA follow-up may improve detection of reduced retinal VD, thus avoiding further retinal damage in hypertensive patients; however, the clinical implications of this finding deserve further study. Moreover, further exploration is needed regarding the implication that reduced SBP may be beneficial for lowering the risk of glaucoma.

Retinal Neurovascular Impairment in Patients with Essential Hypertension: An Optical Coherence Tomography Angiography Study.

Purpose: To investigate retinal neurovascular structural changes in patients with essential hypertension. Methods: This observational cross-sectional study consisted of 199 right eyes from 169 nondiabetic essential hypertensive patients, divided into groups as follows: group A, 113 patients with hypertensive retinopathy (HTNR); group B, 56 patients without HTNR; and a control group of 30 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL), radial peripapillary segmented (RPC), ganglion cell-inner plexiform layer (GC-IPL), and superficial (SVP) and deep (DVP) vascular plexus density at the macula (6 × 6 mm2) were measured by optical coherence tomography angiography (OCTA). Results: DVP density was significantly reduced in groups A and B compared to the control group (group A DVP, P = 0.001; group B DVP P = 0.002). GC-IPL, RNFL thickness, and RPC and SVP density in group A were significantly decreased compared to the control group or group B (all P < 0.05). In hypertensive patients, GC-IPL and RNFL thickness were negatively correlated with severity of HTNR (GC-IPL, r = -0.331, P < 0.001; RNFL, r = -0.583, P < 0.001) and level of home blood pressure monitoring (HBPM) (GC-IPL, r = -0.160, P = 0.050; RNFL, r = -0.282, P = 0.001) and were positively correlated with SVP (GC-IPL, r = 0.267, P = 0.002; RNFL, r = 0.361, P < 0.001) and RPC density (GC-IPL, r = 0.298, P < 0.001; RNFL, r = 0.663, P < 0.001). Among subjects with grade 2 or 3 retinopathy, the superior RNFL was significantly thinner in patients with high HBPM level than in those with normal HBPM level (grade 2, P = 0.016; grade 3, P = 0.006). Conclusions: Reduction of retinal vessel density and RNFL thickness is observed in patients with HTNR and is inversely associated with level of HBPM.

Retinal Vascular and Anatomical Features in the Spontaneously Hypertensive Rat.

Purpose: To evaluate whether invivo optical imaging methods and histology can detect comparable vascular and neuronal damage in the retina due to the effects of progressive chronic hypertension on the retinal vasculature and neurons using the spontaneously hypertensive rat (SHR) model at young and old ages. Methods: Male SHR and normotensive Wistar Kyoto (WKY) rats were studied at 10 and 40 weeks of age (n = 6 each group). Arterial blood pressure was measured with a tail-cuff. Under anesthesia, fundus photography was used to measure retinal arterial diameters and optical coherence tomography was used to measure retinal layer thicknesses. Histology was then used to measure microvascular and cell density in different retinal layers. Results: Blood pressure was significantly higher in SHR than WKY in both age groups (p < .05). Fundus images showed no gross abnormalities, hemorrhage, or stenosis in all groups. Retinal vessels, however, appeared more tortuous in SHR compared to WKY at both ages. Retinal vessel diameters in SHR were significantly narrower than in WKY at both age groups (p < .05). Microvascular densities at 10 weeks were not significantly different (p > .05) but were markedly reduced in SHR at 40 weeks compared to WKY (p < .05). The outer nuclear layer thickness of SHR was significantly thinner than that of WKY at both ages (p < .05), consistent with histological cell density measurements (p < .05). The ganglion cell layer and inner nuclear layer thicknesses were not significantly different between SHR and WKY (p > .05), consistent with the corresponding histological cell density measurements (p > .05). Conclusion: In vivo optical imaging showed that systemic hypertension progressively reduces retinal arterial diameter and thicknesses of the outer retina in spontaneously hypertensive rats, with consistent vascular and neuronal findings from histology.

Aortic stiffness is not only associated with structural but also functional parameters of retinal microcirculation.

OBJECTIVE: The aim of the study was to test the hypothesis that alterations in large arteries are associated with microvascular remodelling and decreased retinal capillary blood flow. METHODS: The study group comprised of 88 patients with essential hypertension and 32 healthy controls. Retinal microcirculation was evaluated by scanning laser Doppler flowmetry. Macrovascular changes were assessed on the basis of arterial stiffness measurement (carotid-femoral pulse wave velocity), its hemodynamic consequences (central pulse pressure, augmentation pressure, augmentation index) and intima media thickness of common carotid artery. RESULTS: Pulse wave velocity was inversely correlated to mean retinal capillary blood flow in hypertensive patients (R = -0.32, p < 0.01). This relationship remained significant in multivariate regression analysis after adjustment for age, sex, central systolic blood pressure (BP) and body mass index (ß = -31.27, p < 0.001). Lumen diameter (LD) of retinal arterioles was significantly smaller in hypertensive then normotensive subjects (79.4 vs. 83.8, p = 0.03). Central and brachial systolic, diastolic and mean BPs were significantly correlated with LD and outer diameter of retinal arterioles. The relationship between LD and central BPs remained significant in multivariate analysis (ß = -0.15, p = 0.03 for cSBP; ß = -0.22, p = 0.04 for cDBP; ß = -0.21, p = 0.03 for cMBP). Moreover, in a subgroup with cardiac damage central and brachial pulse pressure were positively associated with retinal wall thickness, wall cross sectional area, and wall to lumen ratio. CONCLUSION: In conclusion, the study provides a strong evidence that microcirculation is coupled with macrocirculation not only in terms of structural but also functional parameters.

Utility of optical coherence tomography angiography in detecting vascular retinal damage caused by arterial hypertension.

OBJECTIVE: To evaluate the potential utility of perfusion density measurements to discriminate patients with arterial hypertension by cardiovascular risk category. METHODS: In this cross-sectional study, one eye per subject was evaluated (N = 73). The study cohort was divided into three groups according to the clinical criteria established by the European Guidelines for Arterial Hypertension: 26 controls, 24 patients with low cardiovascular risk, and 23 patients with very high cardiovascular risk. All patients were examined using RS-3000 Advance optical coherence tomography angiography to analyze macular and peripapillary perfusion density. RESULTS: There were no differences among the three risk groups by sex or age. Decreased macular perfusion density was found at the level of the superficial and deep plexuses (p ⩽ 0.047). No differences were observed in peripapillary perfusion density (p = 0.18). CONCLUSION: Optical coherence tomography angiography can detect changes in macular perfusion density in patients with hypertension and high cardiovascular risk and might represent a supportive imaging method in the evaluation of the cardiovascular risk in hypertensive patients.

Increased rate of any retinopathy risk in patients with masked hypertension.

PURPOSE: Hypertension is a common chronic disorder with end organ damage. Hypertensive retinopathy is a response to elevated blood pressure characterized retinal arteriolar intimal thickening, hyperplasia of the intima-media end with sclerosis. There is a relationship between high blood pressure and retinopathy grade. Masked hypertension is a phenomenon of normal blood pressure in the office but high in out of office that associated with an increases risk of cardiovascular disease. In this study, we aimed to investigate retinopathy in masked hypertensive patients. METHODS: We enrolled 92 patients with masked hypertension and 87 healthy controls in to the study. We use ambulatory blood pressure monitoring (ABPM) to detect the masked hypertension. Bilateral fundus examination was performed. Hypertensive retinopathy (HTRP) grading was determined according to the Keith-Wagener-Barker classification. We examined retinopathy grade in patients with masked hypertension and without. RESULTS: 55 (11.6%) participants had signs of retinopathy. Fifty (54.3%) subjects had any retinopathy in patients with masked hypertension and five (5.7%) subjects had any retinopathy in controls (p < .001). Median of KWB grade was 1 (0-4) in patients with masked hypertension and 0 (0-2) in controls (p < .001). There were a positive significant correlation between KWB grade and day-time systolic blood pressure (r = 0.460, p < .001), day-time diastolic blood pressure (r = 0.448, p < .001), presence of masked hypertension (r = 0.527, p < .001). CONCLUSIONS: There was a considerable rate of any retinopathy in masked hypertension. Consequently, ophthalmoscopic examination should be as part of the care in patients who have a risk for masked hypertension.

Use of optical coherence tomography angiography for assessment of microvascular changes in the macula and optic nerve head in hypertensive patients without hypertensive retinopathy.

PURPOSE: To compare optical coherence tomography angiography (OCTA) screening parameters of the macula and optic nerve head (ONH) between healthy volunteers and chronic hypertensive patients without hypertensive retinopathy. METHODS: This was an observational, cross-sectional study. Fifty-seven chronic hypertensive patients without hypertensive retinopathy (22 men and 35 women) and 40 healthy volunteers (17 men and 23 women), ranging in age from 60 to 70 years, were included in this study. Patients and volunteers were divided into three groups and one eye was selected randomly from each participant. Group A comprised patients who had a history of hypertension for >10 years (n = 35); Group B comprised patients who had a history of hypertension for 5-10 years (n = 22); and Group C comprised 40 healthy volunteers who had no history of hypertension. A 3 × 3-mm macula scan and a 4.5 × 4.5-mm ONH scan were performed in each group by OCTA using prototype AngioVue software within the AngioVue device. Vessel density (VD), foveal avascular zone (FAZ) area, choriocapillaris flow area, ONH capillary density, retinal nerve fiber layer (RNFL) thickness, and demographic information were compared among the groups. RESULTS: Macula scans showed that superficial plexus VD was significantly lower in groups A and B than in group C (P < 0.05). In addition, FAZ area was significantly larger in group A than in group C (P < 0.05). Inner retinal layer thickness was significantly thinner in groups A and B than in group C (P < 0.05). In ONH scans, RNFL thickness was significantly thinner in group A than in groups B and C (P < 0.05); it was significantly thinner in group B than in group C (P < 0.05). Inside disc capillary density and peripapillary capillary density were significantly lower (P < 0.05) and greater (P < 0.05), respectively, in groups A and B than in group C. CONCLUSIONS: Superficial plexus VD, FAZ area, capillary density, and inner retinal thickness changed significantly in hypertensive patients without hypertensive retinopathy. However, only RNFL thickness was significantly thinner in patients who had >10 years of hypertension, compared to patients who had 5-10 years of hypertension. In addition, OCTA provided a method to prospectively assess changes in retinal microvasculature and thickness, thereby avoiding further long-term retinal damage in hypertensive patients.

Eye Drop Instillation of the Rac1 Modulator CNF1 Attenuates Retinal Gliosis and Ameliorates Visual Performance in a Rat Model of Hypertensive Retinopathy.

In hypertensive retinopathy, the retinal damage due to high blood pressure is accompanied by increased expression of Glial Fibrillary Acidic Protein (GFAP), which indicates a role of neuroinflammatory processes in such a retinopathy. Proteins belonging to the Rho GTPase family, particularly Rac1, are involved in the activation of Müller glia and in the progression of photoreceptor degeneration, and may thus represent a novel candidate for therapeutic intervention following central nervous system inflammation. In this paper, we have observed that topical administration as eye drops of Cytotoxic Necrotizing Factor 1 (CNF1), a Rho GTPase modulator, surprisingly improves electrophysiological and behavioral visual performances in aged spontaneously hypertensive rats. Furthermore, such functional improvement is accompanied by a reduction of Rac1 activity and retinal GFAP expression. Our results suggest that Rac1 inhibition through CNF1 topical administration may represent a new strategy to target retinal gliosis.

Relationship between nocturnal blood pressure profiles and the presence and severity of hypertensive retinopathy. / Relação entre o perfil tensional noturno e a prevalência e gravidade da retinopatia hipertensiva.

INTRODUCTION: Non-dipper and extreme dipper blood pressure (BP) profiles are associated with a worse cardiovascular prognosis. The relationship between nocturnal BP profile and hypertensive retinopathy (HR) is not fully established. AIM: To assess the association between the prevalence and severity of HR and nocturnal BP. METHODS: We prospectively studied hypertensive patients who underwent 24-hour ambulatory BP monitoring. The population was divided into two groups according to the presence or absence of lesions and compared according to baseline characteristics, nocturnal BP profile (dippers, non-dippers, inverted dippers/risers and extreme dippers) and mean nocturnal systolic (SBP) and diastolic (DBP) BP values. The presence and severity of HR were assessed using the Scheie classification. The relationship between nocturnal SBP and DBP values (and nocturnal BP profile) and the prevalence and severity of HR was determined. RESULTS: Forty-six patients (46% male, aged 63±12 years) were analyzed, of whom 91% (n=42) were under antihypertensive treatment. Seventy percent (n=33) had uncontrolled BP. HR was diagnosed in 83% (n=38). Patients with HR had higher mean systolic nocturnal BP (151±23 vs. 130±13 mmHg), p=0.008). Patients with greater HR severity (Scheie stage ≥2) had higher nocturnal BP (153±25 vs. 140±16 mmHg, p=0.04). There was no statistically significant association between DBP and nocturnal BP patterns and HR. CONCLUSIONS: The prevalence and severity of HR were associated with higher nocturnal SBP. No relationship was observed between nocturnal BP profile and the presence of HR.

Blood pressure profile is associated with microalbuminuria and retinopathy in hypertensive nondiabetic patients.

BACKGROUND: Target organ damage is important for global cardiovascular risk assessment. The aim of this study was to explore the association between the blood pressure profile and end-organ damage in a hypertensive non-diabetic cohort. METHODS: A total of 560 consecutive hypertensive nondiabetic patients (mean age: 58.2 ± 13.3 years, 221 men) were included in the study. All patients underwent thorough physical examination including fundoscopic examination. First morning urine samples were obtained from each patient and measurement of the albumin-to-creatinine ratio in first morning urine collection samples was used for diagnosis of microalbuminuria. All patients underwent a 24-h ambulatory blood pressure monitoring and were grouped as dippers and non-dippers according to the presence or absence of >10% decrease in blood pressure during the night, respectively. RESULTS: The non-dipper group consisted of 247 patients with a non-dipper blood pressure profile, 31 patients with reverse dipping and 4 patients with extreme dipping. Non-dipper patients were significantly older. Coronary artery disease, cerebrovascular disease, hypertensive retinopathy and microalbuminuria were significantly more prevalent in the non-dipper patients. Non-dipping hypertension increased the risk of hypertensive retinopathy by 1.89 times (95% confidence interval, CI:1.35-2.65, p < 0.001) and the risk of microalbuminuria by 2.23 times (95% CI:1.49-3.33, p < 0.001). Non-dipping hypertension was still significantly associated with hypertensive retinopathy and microalbuminuria when adjusted by age and sex. CONCLUSION: Non-dipping hypertension was associated with increased risk of hypertensive retinopathy and microalbuminuria. Blood pressure profiles should also be considered in assessing the risk for hypertensive patients.

Assessment of left atrium and diastolic dysfunction in patients with hypertensive retinopathy: A real-time three-dimensional echocardiography-based study.

The fundoscopic examination of hypertensive patients, which is established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time three-dimensional echocardiography (RT3DE). Our population consisted of 88 consecutive essential hypertensive patients (age 59.2 ± 1.2 years, 35 males). All subjects underwent a fundoscopy examination and were distributed into four groups according to the Keith-Wagener-Barker (KWB) classification. The four groups (KWB grades 0-3: including 26, 20, 26, and 16 patients, respectively) did not differ with regard to age, gender, or metabolic profile. There were no significant differences between groups with regard to parameters reflecting LV systolic function and diastolic dysfunction (DD) in two-dimensional echocardiography (2DE). Nevertheless, patients in the higher KWB category had higher values of LA volumes (LA maximal volume index, LA minimal volume index, preatrial contraction volume index, LA total stroke volume index, LA active stroke volume index, p < 0.001) regarding RT3DE. There is also a significant relationship between LA active stroke volume index (ASVI) and duration of hypertension (HT) (r: 0.68, p < 0.001). In the logistic regression analysis, ASVI was independent predictors of LV DD in patients with arterial hypertension (HT). Patients with arterial HT were found to have increased LA volumes and impaired diastolic functions. Assessment of the arterial HT patient by using RT3DE atrial volume analysis may facilitate early recognition of TOD, which is such a crucial determinant of cardiovascular mortality and morbidity.

Hypertensive retinopathy in a transgenic angiotensin-based model.

Severe hypertension destroys eyesight. The RAS (renin-angiotensin system) may contribute to this. This study relied on an established angiotensin, AngII (angiotensin II)-elevated dTGR (double-transgenic rat) model and same-background SD (Sprague-Dawley) rat controls. In dTGRs, plasma levels of AngII were increased. We determined the general retinal phenotype and observed degeneration of ganglion cells that we defined as vascular degeneration. We also inspected relevant gene expression and lastly observed alterations in the outer blood-retinal barrier. We found that both scotopic a-wave and b-wave as well as oscillatory potential amplitude were significantly decreased in dTGRs, compared with SD rat controls. However, the b/a-wave ratio remained unchanged. Fluorescence angiography of the peripheral retina indicated that exudates, or fluorescein leakage, from peripheral vessels were increased in dTGRs compared with controls. Immunohistological analysis of blood vessels in retina whole-mount preparations showed structural alterations in the retina of dTGRs. We then determined the general retinal phenotype. We observed the degeneration of ganglion cells, defined vascular degenerations and finally found differential expression of RAS-related genes and angiogenic genes. We found the expression of both human angiotensinogen and human renin in the hypertensive retina. Although the renin gene expression was not altered, the AngII levels in the retina were increased 4-fold in the dTGR retina compared with that in SD rats, a finding with mechanistic implications. We suggest that alterations in the outer blood-retinal barrier could foster an area of visual-related research based on our findings. Finally, we introduce the dTGR model of retinal disease.

Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis.

BACKGROUND: Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. METHODS: For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. FINDINGS: We identified 19 trials including 44,989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0-8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% [95% CI 4-22]), myocardial infarction (13% [0-24]), stroke (22% [10-32]), albuminuria (10% [3-16]), and retinopathy progression (19% [0-34]). However, more intensive treatment had no clear effects on heart failure (15% [95% CI -11 to 34]), cardiovascular death (9% [-11 to 26]), total mortality (9% [-3 to 19]), or end-stage kidney disease (10% [-6 to 23]). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 [95% CI 0·93-1·97]). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 [1·21-5·89], p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). INTERPRETATION: Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. FUNDING: National Health and Medical Research Council of Australia.

P1113Relationship between left atrium and hypertensive retinopathy in patients with systemic hypertension: a real-time three-dimensional echocardiography-based study.

BACKGROUND: The fundoscopic examination of hypertensive patients, which is an established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time, three-dimensional echocardiography (RT3DE), which is the most pivotal predictor of diastolic dysfunction. METHODS: Our population consisted of 88 consecutive essential hypertensive patients (age 59.2 ± 1.2 years, 53 females) without overt cardiovascular disease. All subjects underwent a fundoscopy examination and were distributed into five groups according to the Keith-Wagener-Barker (KWB) classification. Comprehensive transthoracic echocardiographic and RT3DE measurements were performed to assess LA volumes and phasic functions. RESULTS: The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients, respectively) did not differ with regards to age, gender, or metabolic profile. There were no significant differences between groups with regards to parameters reflecting left ventricle (LV) systolic function and diastolic dysfunctions in conventional echocardiography, except isovolemic relaxation time (IVRT) and deceleration time (DT). Nevertheless, patients in the higher KWB category had higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001) regarding RT3DE (table 1). There is also a significant relationship between preatrial contraction volume and duration of HT (r: 0.67, p<0.001). CONCLUSION: Patients with arterial hypertension were found to have increased LA volume and impaired atrial compliance and contractility. Moreover, RT3DE identifies early functional LA changes in these patients better than conventional echocardiography. Assessment of the hypertensive patient by using RT3DE atrial volume analysis may facilitate early recognition of TOD, which is such a crucial determinant of cardiovascular mortality and morbidity in patients with systemic hypertension.

The Keith-Wagener-Barker and Mitchell-Wong grading systems for hypertensive retinopathy: association with target organ damage in individuals below 55 years.

BACKGROUND: The usefulness of the hypertensive retinopathy classification by Keith-Wagener-Barker (KWB) in clinical practice remains controversial. The simplified Mitchell-Wong grading, combining the two initial KWB' grades in one stage, is proposed as an alternative method; both systems are poorly validated regarding their association with target organ damage. OBJECTIVE: In a population free of cardiovascular disease and diabetes, we aimed to investigate the interobserver and intraobserver agreement of both grading systems, their association with aortic stiffness, carotid hypertrophy or plaques and the role of age and sex on this association. METHODS: Digital retinal images were obtained and graded - according to both classifications - by two independent and blinded observers; aortic stiffness (carotid-femoral pulse wave velocity, m/s) and common carotid hypertrophy (cross-sectional area, mm) or plaques were assessed by tonometry and ultrasound, respectively. RESULTS: From the gradable retinal photos obtained by 200 eyes of 107 consecutive patients (age: 54 ±â€Š13 years, 51% men, 79% hypertensive patients) and after adjustments for confounders, the intraobserver and interobserver level of agreement was as following: KWB 88/64% and Mitchell-Wong 91/71%, respectively; exclusively in younger, not older, individuals aortic stiffness, carotid hypertrophy, but not plaques, were significantly associated with both systems, independently from confounders; no differences regarding target organ damage were found between stages 1 and 2 of KWB. CONCLUSION: Detecting early signs of hypertensive retinopathy may be of value in young individuals; the Mitchell-Wong seems preferable to the KWB classification system only for reasons of simplifying clinical practice.

Is Daytime Systolic Load an Important Risk Factor for Target Organ Damage in Pediatric Hypertension?

The aim of this study was to compare ambulatory blood pressure (BP) monitoring (ABPM) data and determine which hypertension type is a risk factor in target organ damage. A total of 82 children (47 boys) with suspected hypertension based on office BP measurements and considered hypertensive by ABPM were studied. Target organ damage included the following: 35.3% hypertensive retinopathy, 25.6% microalbuminuria, 15.8% increased left ventricular mass index, 29.2% increased carotid intima-media thickness (cIMT), 24.3% high augmentation index (AIx), and 19.5% high pulse wave velocity (PWV). The association between BP load, PWV, and cIMT was statistically significant. There were significant correlations between daytime systolic BP load, PWV, AIx, and cIMT. A statistically significant difference was also detected between nighttime systolic BP load, PWV, and cIMT values and nighttime diastolic BP load levels and values of AIx and cIMT. There was also a statistically significant difference between the high level of nighttime diastolic BP load and cIMT. The authors found that target organ damage was seen more often in children with primary hypertension who had systolic loads.

Um novo olhar da retinopatia hipertensiva: a aplicação prática de novas tecnologias / A new look at hypertensive retinopathy: the practical application of new technologies

O exame de fundo de olho tem importância histórica e mantém sua relevância nos dias atuais, por possibilitar de maneira não invasiva, observar e avaliar o “interior” do corpo humano, além de ser um importante marcador de lesão de órgão-alvo em hipertensos. O surgimento de tecnologias de aquisição de imagens digitais permitiu acessar o fundo de olho de maneira mais simples, com grande definição, muitas vezes não necessitando dilatação da pupila. Isso tornou a observação do fundo de olho, que outrora era realizada apenas por pessoas com treinamento especial, fosse feita com extrema facilidade e quase sem treinamento. Estas “facilidades” permitiram que inúmeros artigos científicos fossem realizados, estabelecendo características do fundo de olho como relevante marcador de lesão de órgão-alvo em hipertensos. A incorporação de tecnologias virtuais na prática da medicina facilitará o acesso dos pacientes, reduzirá custos e certamente irá revolucionar a relação médico-paciente nos próximos anos.

Eye fundus examination is of historical importance, and maintains its relevance nowadays, by enabling non-intrusive observation and evaluation “inside” the human body, as well as being an important marker of target organ damage in hypertensive patients. The emergence of technologies for digital image acquisition have enabled easier access to the eye fundus, with greater definition, and often without having to dilate the pupil. As a result, eye fundusexamination, once carried out only by people with special training, is now performed with extreme ease and almost no training. These “facilities” have led to numerous scientific articles, establishing the characteristics of the eye fundus as a relevant marker of target organ damage in hypertensive patients. The incorporation of virtual technologies into the practiceof medicine will facilitate patient access, reduce costs, and without doubt, revolutionize the doctor-patient relationship in the coming years.