Editorial comment
Retinal microvascular damage and nocturnal hypertension: Therapeutic targets to bear in mind
Repercussão microvascular retineana e hipertensão noturna a alvos terapêuticos a não esquecer
José Braz Nogueira
Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
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There are three patterns of electrocardiographic abnormalities in the right precordial leads (V1-V3). Type 1 is considered to be diagnostic, unlike types 2 and 3 (in presence of which provocation tests with SCB must be performed). Other electrocardiographic abnormalities that may be present in BrS are: prolongation of the PR interval and right branch block. A definitive diagnosis is made in presence of type 1 ST-segment elevation in at least one V1-V3 lead and when one of the clinical criteria presented in the figure is met. AMI: acute myocardial infarction; ANS: autonomic nervous system; C/ARVD: cardiomyopathy/arrhythmogenic right ventricular dysplasia; CCB: calcium channel blockers; CNS: central nervous system; ECG: electrocardiogram; LVH: left ventricular hypertrophy; PTE: pulmonary thromboembolism; RV: right ventricle; RVOT: right ventricular outflow tract; SCB: sodium channel blockers; SSRIs: selective serotonin reuptake inhibitors; VF: ventricular fibrillation; VT: ventricular tachycardia; β-blockers: beta blockers. *May unmask genetic susceptibility to BrS.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Extracted and adapted from Berne and Brugada (2012).<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">51</span></a></p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Diana João Fonseca, Manuel Joaquim Vaz da Silva" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Diana João" "apellidos" => "Fonseca" ] 1 => array:2 [ "nombre" => 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"titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Repercussão microvascular retineana e hipertensão noturna a alvos terapêuticos a não esquecer" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Assessing the severity of hypertension entails study of damage to target organs, including the retina. Fundoscopy is an important test for this purpose, providing easy direct observation in vivo of the retinal microvasculature, which anatomically and physiologically bears close similarities to cerebral, coronary and renal microvasculature.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1,2</span></a> The relationship between alterations in the retinal vasculature, assessed qualitatively by fundoscopy using the Keith-Wagener-Barker or Scheie classification systems, and current or previous high blood pressure (BP) has been amply demonstrated, as has their prognostic value for cardiovascular and renal morbidity and mortality, especially in the case of exudative retinopathy.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">1,3</span></a> However, the predictive value of less severe alterations such as arteriolar narrowing, widening of the light reflex and arteriovenous nicking is more uncertain, given the subjective nature of their assessment.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,4</span></a> Recent studies using semi-automated computer-based retinal imaging programs applied to high-definition digital photographs and laser Doppler flowmetry, among other techniques, have provided detailed data, not only qualitative but, importantly, quantitative, on a range of parameters of the retinal vasculature including arteriolar wall-to-lumen ratio, caliber, tortuosity, vasomotricity, and branching patterns and relative diameters of arterioles and venules.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,3,5</span></a> These, in a more robust fashion than the subjective assessments of older methods, have established or confirmed significant associations between the early structural and functional alterations of the initial stages of hypertension and coronary artery disease, heart failure, stroke, cognitive dysfunction, microalbuminuria and renal dysfunction, left ventricular hypertrophy, and increased carotid intima-media thickness and arterial stiffness.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,3</span></a> Some studies have shown the value of these new techniques for predicting the development or worsening of hypertension,<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,3,6</span></a> and genetic studies have identified loci and polymorphisms that are associated with both changes in arteriolar caliber and regulation or elevation of BP.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Interestingly, some authors have described an association between increased venule caliber and the incidence of hypertension and risk of stroke, especially lacunar stroke.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,3,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Ambulatory blood pressure monitoring (ABPM) has shown the significance of certain abnormalities in the 24-hour circadian profile with regard to target organ damage and cerebral, cardiovascular and renal morbidity and mortality, as seen in both studies of hypertensives and population studies.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">1</span></a> Of these abnormalities, non-dipping and nocturnal hypertension are most often independently associated with increased risk of target organ damage and worse prognosis, with various studies having shown more severe cardiac, cerebral, renal and macrovascular repercussions in these patients.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">9-11</span></a> It should be noted that there have been few studies on the relationship between vascular abnormalities in hypertensive retinopathy and circadian patterns on ABPM, in particular nocturnal BP, and some are contradictory.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">12-15</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The study by Duarte et al. published in this issue of the <span class="elsevierStyleItalic">Journal</span><a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">16</span></a> does in fact analyze precisely this relationship between 24-hour and nocturnal BP by ABPM and the presence and severity of hypertensive retinopathy, assessed qualitatively by fundoscopy and graded using the Scheie classification, in a group of 46 hypertensives, most of them medicated but only a third controlled.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Despite the limitations pointed out by the authors, mainly related to the small study population, the study clearly showed not only the high prevalence of retinopathy in these hypertensives but also the crucial role of nocturnal BP, especially systolic, in the presence and severity of retinopathy. There were also associations between retinopathy and age and duration of hypertension, as described elsewhere,<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">2,3</span></a> particularly when the same classification system was used, and in which most patients were in the sclerotic stage of retinopathy (37 patients in the present study). Regarding the mean daytime and nocturnal BP levels of this patient group, unusually, mean nocturnal values were higher than daytime levels, which raises the question whether they included a large number of inverted dippers (which was not the case), or that some may have suffered from obstructive sleep apnea or other sleep disorders, which the authors do not mention. It would have been interesting to know the nocturnal BP levels of dippers and non-dippers in this group, since nocturnal BP can be high even in dippers,<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">17</span></a> which may be why there were no differences in the presence and severity of retinopathy between dippers and non-dippers.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The small sample size is probably the reason that no association was found between the presence of retinopathy and cardiac involvement, as has been described in other studies.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">3</span></a> Similarly, medicated and controlled patients were no different in terms of the presence of retinopathy, although improvements in structural alterations of the retinal vasculature have been reported following BP control,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">3,18</span></a> particularly with drugs that act on the renin-angiotensin-aldosterone system and with calcium channel blockers, which were used in this study. Such improvements have been amply demonstrated, especially in cases of exudative retinopathy (which only one patient presented in the study by Duarte et al.) and when the assessment of retinopathy is quantitative as well as qualitative, using sophisticated and precise computer algorithms, which was not the case in the present study. The apparent lack of improvement seen in this study may thus be because BP control had not been achieved for sufficient time to take effect, or due to the methods used to assess retinopathy, or to the patients age and duration of hypertension, leading to a larger proportion of sclerotic lesions that are less likely to regress. If patient numbers had permitted such an analysis, it would have been interesting to assess whether there were significant differences in retinal findings or in nocturnal BP levels between non-medicated and medicated but not controlled subjects.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Furthermore, the study does not report office BP measurements, and thus cannot clarify whether some patients had masked hypertension and if so, whether retinopathy in this group was similar to that of the other hypertensives, as has been reported for other organ damage,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">9</span></a> or how it related to nocturnal BP.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, despite the limitations pointed out above with regard to population size and the methodology for assessing the fundoscopy findings, the present study has the merit of demonstrating the importance of nocturnal BP in alterations in the retinal vasculature, and of calling attention to these alterations, which are frequently underestimated and are potential therapeutic targets. They may also play an important role in early assessment of the severity of hypertension, particularly with regard to cardiovascular and renal risk, as well as in monitoring the efficacy of and adherence to antihypertensive medication; when such lesions are detected but the patient has apparently normal BP levels, they may reflect inadequate control of nocturnal BP.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Further studies are awaited, with larger samples and more detailed assessment of the retinal vascular architecture,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">19</span></a> that could widen our understanding of hypertensive microvascular alterations, both arteriolar and venular, and their relationship with changes in circadian BP profiles, therapeutic efficacy, the possible benefits of chronotherapy, and for example in cases of white-coat hypertension the decision whether to initiate antihypertensive therapy.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "." 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