Microvascular Structural Alterations Research Articles

Predictability of Nailfold Capillaroscopic Score in Diagnosing Retinopathy in Patients with Type 2 Diabetes Mellitus and its Utility as a Non-Invasive Tool for Differentiating from those Not Having Retinopathy: A Pilot Observational Cross-Sectional Analytical Study.

Diabetes mellitus (DM) is a chronic hyperglycaemic state associated with microvascular structural alterations. Nailfold capillaroscopy (NFC) is an in vivo study of microvascular circulation. This study aimed to investigate the diameters of capillary loops and morpho-structural changes using a handheld dermatoscope in patients with type 2 DM (T2DM) with and without diabetic retinopathy (DR) and to establish nailfold capillary changes and NFC score as a non-invasive method to identify microvascular complication in T2DM patients. A cross-sectional observational study was conducted in AIIMS Rishikesh for 6 months from August 2022 to February 2023. Our study participants were 100 adults more than 18 years of age diagnosed with T2DM, based on the American Diabetes Association (ADA) criteria. All patients were evaluated thoroughly for the presence of microvascular complications in the form of retinopathy. Based on this, they were divided into two groups-group 1 (T2DM with retinopathy) and group 2 (T2DM without retinopathy). Both groups were further subdivided into three subgroups based on haemoglobin A1c (HbA1c): the first group with HbA1c <7%, the second group with HbA1c 7-8.9% and the third group with HbA1c >=9%. For all the study participants, a detailed NFC was done for all 8 fingernails (excluding the thumb), using a handheld dermatoscope. Abnormal capillary shapes (ACS) were recorded by semi-quantitative score (NFC score). A significant association was seen in capillary density (loops/mm) (5.83 ± 0.72 in the DR group and 6.3 ± 0.89 in the no-DR group) (P value = 0.005), capillary density (loops/3 mm) (P value = 0.005), total number of microhaemorrhages/3 mm (P value < .0001), total number of giant capillaries/3 mm (P value = 0.0004), total number of avascular areas/3 mm (P value = 0.0005), enlarged capillaries/3 mm (P value = 0.002), tortuous capillaries/3 mm (P value < .0001), abrogated/bushy capillaries/3 mm (P value = 0.004), number of fingers involved excluding the thumb (P value < .0001) and total nailfold capillaroscopic score (P value < .0001) between the two groups, one with DR and another without DR. Furthermore, the proportion of patients with abnormal nailfold capillaroscopic findings, abnormal NFC score, was significantly higher in patients with DR as compared to patients without DR (51.85% vs 4.35%, respectively) (P value < 0.0001). Our results suggest that NFC could possibly be used as an adjunctive tool in diabetics for diagnosing or monitoring microvascular complications with total NFC score being the significant predictor of DR at a cut-off point of >0 with the area under the curve (AUC) of 0.745 for correctly predicting DR.

New Noninvasive Methods to Evaluate Microvascular Structure and Function.

The structural and functional alterations of microvessels are detected because of physiological aging and in several cardiometabolic diseases, including hypertension, diabetes, and obesity. The small resistance arteries of these patients show an increase in the media or total wall thickness to internal lumen diameter ratio (MLR or WLR), often accompanied by endothelial dysfunction. For decades, micromyography has been considered as a gold standard method for evaluating microvascular structural alterations through the measurement of MLR or WLR of subcutaneous small vessels dissected from tissue biopsies. Micromyography is the most common and reliable method for assessing microcirculatory endothelial function ex vivo, while strain-gauge venous plethysmography is considered the reference technique for in vivo studies. Recently, several noninvasive methods have been proposed to extend the microvasculature evaluation to a broader range of patients and clinical settings. Scanning laser Doppler flowmetry and adaptive optics are increasingly used to estimate the WLR of retinal arterioles. Microvascular endothelial function may be evaluated in the retina by flicker light stimulus, in the finger by tonometric approaches, or in the cutaneous or sublingual tissues by laser Doppler flowmetry or intravital microscopy. The main limitation of these techniques is the lack of robust evidence on their prognostic value, which currently reduces their widespread use in daily clinical practice. Ongoing and future studies will overcome this issue, hopefully moving the noninvasive assessment of the microvascular function and structure from bench to bedside.

Optical coherence tomography angiography of retinal vasculature in recovered COVID-19 patients compared to age and ethnic matched controls

ABSTRACT Clinical relevance Understanding the impact of the COVID-19 virus on the retinochoroidal vasculature can provide valuable information regarding potential multi-organ ischaemic sequelae in COVID-19 patients, and can thus be a useful tool for optometrists, ophthalmologists, pulmonologists, infectious disease specialists and others. Background Assessment of retinochoroidal vasculature alterations in recovered mild COVID-19 patients using optical coherence tomography angiography (OCTA) when compared to age and ethnic matched controls. Methods Multimodal imaging was performed using OCTA, spectral domain (SD)-OCT (Optovue RTVue XR Avanti; Optovue, Inc, Fremont, CA), and colour fundus photography (Compass; iCare Inc, Raleigh, NC). Vessel flow density, foveal avascular zone, foveal perimeter circumference and retinal thickness were calculated automatically by the OCTA software on 6 × 6mm angiograms. Morphologic changes in the retinochoroidal vasculature on OCTA were assessed and compared with the findings on fundoscopy, SD-OCT and fundus photography and were evaluated by two trained graders. Results Mean vessel parafoveal density, superior and inferior hemispheric vessel density and perifoveal temporal vessel density on 6 × 6 angiograms of the superficial capillary plexus were lower among the COVID-19 patients when compared to their age and ethnic matched controls. Vessel flow density of the deep capillary plexus, foveal avascular zone size and circumference and retinal thickness did not illustrate statistical significance between the groups. Conclusion OCTA provides non-invasive high-resolution imaging of the retinochoroidal vascular network. Compared with conventional imaging, OCTA can demonstrate precise microvascular structural alterations in the retinal vessels before visible on SD-OCT or fundus examination. When matched for age and ethnicity, patients with a history of mild COVID illness manifested alterations in vessel density.

Microvascular Structural Alterations in Cancer Patients Treated With Antiangiogenic Drugs.

Objective: Antiangiogenic therapies (tyrosine kinase inhibitors-TKI and direct anti-VEGF monoclonal antibodies) are being increasingly used in the treatment of solid tumors; hypertension represents a common side effect of these agents. Several mechanisms are involved in the development of hypertension, including microvascular rarefaction and other microvascular alterations. Therefore, the aim of our study was to evaluate whether TKI and direct anti-VEGF agents may affect the structure of retinal arterioles or capillary density.Design and Methods: We investigated 20 patients with a diagnosis of cancer who underwent a treatment with either a TKI or an anti-VEGF antibody. Patients were submitted to ambulatory monitoring blood pressure for blood pressure evaluation. Basal and total capillary density were assessed by capillaroscopy whereas, retinal arteriole morphology was measured by Adaptive Optics. Patients were evaluated before starting the antiangiogenic therapy (T0) and re-evaluated after 3 (T3) and 6 (T6) months after treatment. Fourteen patients completed the study.Results: Systolic and diastolic blood pressure values were similar in all patients at T3 and T6 compared to T0. However, during the study antihypertensive treatment was optimized (increased dose and/or addition of drugs) in 57% of patients (n = 8). No differences were observed in retinal arteriole structural parameters and in large artery stiffness. Basal capillary density was reduced by antiangiogenic drugs after 3 or 6 months.Conclusions: Our data suggest that an increase of antihypertensive treatment is necessary in patients treated with a TKI or a direct VEGF inhibitor, confirming pro-hypertensive effects of these drugs. However, under adequate blood pressure control, microvascular structure seem to be partially preserved, since a worsening of basal capillary density but no changes in retinal arteriole morphology were observed.

Swept-source optical coherence tomography angiography findings in a patient with Behçet’s disease: a case report

We present the clinical case of a 28-year-old female patient with a diagnosis of Behcet’s disease and unilateral relapsing ocular involvement in systemic management with infliximab. Optical coherence tomography angiography with swept-source technology (DRI OCT Triton Plus™, Topcon Corporation, Tokyo, Japan) revealed asymmetric compromise between both eyes. Decreased foveal vascular density, asymmetrical foveal avascular zone enlargement at superficial and deep capillary plexuses, and focal areas of hypoperfusion at the deep capillary plexus around the macula with corresponding hyporreflective lesions in the en face slab in the left eye were noted. Swept-source OCT angiography (SS-OCTA) helped identify early asymmetrical microvascular structural alterations compatible with macular ischemia in a patient with systemic manifestations and unilateral ocular compromise.

The evaluation of nailfold videocapillaroscopy findings in patients with type 2 diabetes with and without diabetic retinopathy.

OBJECTIVE:Diabetes mellitus (DM) is a chronic hyperglycemic state and is associated with microvascular structural alterations. This study aimed to investigate the diameters of capillary loops and morphostructural changes using nailfold video capillaroscopy (NVC) in patients with type 2 DM with and without diabetic retinopathy (DR).METHODS:This cross-sectional, single-center study was conducted in patients with type 2 DM who were followed in outpatient clinics of ophthalmology and internal medicine. General demographic data were collected from patients. An ophthalmologist examined all patients in terms of DR. A rheumatologist blinded to the clinical data performed NVC. The diameters of apical, arterial, and venous loop of capillaries were measured, and the microvascular changes of capillaries were scored.RESULTS:In this study, 44 patients with type 2 DM with DR (47.7% males) and 20 patients with type 2 DM without DR (55% males) were included. In our study, patients with type 2 DM with DR had more frequent capillary hemorrhage, more frequent ectasia, more frequent giant capillary, and more frequent neo-angiogenesis than patients with type 2 DM without DR. However, these findings were not statistically significant.CONCLUSION:Further controlled studies with large sample size are needed to determine the characteristic NVC findings of DR in patients with type 2 DM.

Analysis of Retinochoroidal Vasculature in Human Immunodeficiency Virus Infection Using Spectral-Domain OCT Angiography

To describe the retinochoroidal vascular alterations in patients with human immunodeficiency virus (HIV) infection using en face OCT angiography (OCTA). Cross-sectional study. Twenty-six patients with HIV infection (5 women, with and without HIV retinopathy) were included in the study. Nineteen healthy participants (7 women) with no known ocular disease were recruited as healthy controls. Multimodal imaging was performed using OCTA (Optovue RTVue XR Avanti; Optovue, Inc, Fremont, CA), enhanced-depth imaging OCT (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), color fundus photography, and fluorescein angiography (FA). Vessel flow density (VFD) was calculated automatically by the OCTA software. Morphologic changes in the retinochoroidal vasculature in the posterior pole on OCTA were assessed by 2 trained independent graders and were compared with the findings on clinical examination and other imaging techniques. Prevalence of microvascular alterations on OCTA among patients with HIV and differences in the VFD in different macular sectors compared with healthy controls. Among all eyes with clinically detectable HIV retinopathy, there was evidence of retinal vascular telangiectasia, capillary loops, and increased intercapillary spacing. The mean VFD values were lower among patients with HIV retinopathy compared with those with HIV and no retinopathy and healthy controls (both P < 0.05). Foveal avascular zone area was abnormally enlarged among patients with HIV compared with healthy controls (P= 0.05). Five eyes (23.53%) without clinical or angiographic evidence of retinopathy demonstrated retinal vascular telangiectasia and increased intercapillary spacing on OCTA. The inner choroidal vasculature appeared to be mostly unaffected in HIV. OCT angiography provides noninvasive high-resolution imaging of the retinochoroidal vascular network in patients with HIV. Compared with conventional imaging, OCTA can demonstrate precise microvascular structural alterations in the retinal vessels and seems to be a sensitive tool in detecting HIV retinopathy.

Hemodynamic Consequences of Changes in Microvascular Structure.

In hypertension, an increased media-to-lumen ratio of small resistance arteries might play an important role in the increase of vascular resistance, and may also be an adaptive response to the increased hemodynamic load. The presence of morphological alteration in the microvasculature may be associated to an impaired tissue perfusion and/or to the development of target organ damage. Structural alterations in the microcirculation might represent a predictor of the onset of cardio-cerebrovascular events and hypertension complications. A cross-talk between the small and large artery may exaggerate arterial damage, following a vicious circle. Therefore, in the present review, possible hemodynamic consequences of the presence of microvascular structural alterations will be considered, in terms of their time of onset, role in the development and/or maintenance of high blood pressure values, and interrelationships with structural/mechanical alterations of large conductance arteries.

Relationship Between Different Subpopulations of Circulating CD4+ T-lymphocytes and Microvascular Structural Alterations in Humans.

Different components of the immune system, including innate and adaptive immunity (T-effector lymphocytes and T-regulatory lymphocytes-TREGs) may be involved in the development of hypertension. In addition, it was demonstrated in animal models that TREGs may prevent angiotensin II-induced hypertension and vascular injury/inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular structural alterations. For this purpose, in the present study, we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and the media to lumen ratio (M/L) was calculated. In addition, retinal arteriolar structure was evaluated noninvasively by scanning laser Doppler flowmetry. Capillary density in the nailfold, dorsum of the finger, and forearm were evaluated by videomicroscopy. A peripheral blood sample was obtained before surgery for assessment of T-lymphocyte subpopulations by flow cytometry. Significant negative correlations were observed between indices of microvascular structure (M/L of subcutaneous small arteries and wall to lumen ratio of retinal arterioles) and circulating TREG lymphocytes. A direct correlation was observed between M/L of subcutaneous small arteries and circulating Th17 lymphocytes. In addition, total capillary density was correlated with a TREG effector memory subpopulation. Our data suggest that some lymphocyte subpopulations may be related to microvascular remodeling, confirming previous animal data, and opening therapeutic possibilities.

PP.21.05] RELATIONSHIP BETWEEN MICROVASCULAR STRUCTURE AND T REGULATORY LYMPHOCYTES OF SMALL RESISTANCE ARTERIES

Objective: Recently it has been demonstrated a role for adaptive immunity, particularly for T regulatory lymphocytes (Tregs), in the development of hypertension and in preventing of angiotensin II–induced vascular injury and inflammation in animal models (Barhoumi T et al, Hypertension 2011;57:469–476). However, no data are presently available in human beings about possible relationships between Tregs and microvascular structural alterations. Design and method: In the present study we enrolled 11 normotensive subjects and 8 hypertensive patients undergoing an election surgical intervention. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire myography and media to lumen ratio (M/L) was calculated. W/L of retinal arterioles was obtained by Scanning Laser Doppler Flowmetry. Functional (basal) and structural (total) microvascular density were studied by capillaroscopy before and after venous congestion. No sign of local or systemic inflammation was present in any subjects or patients. We extracted genomic DNA from small resistance arteries and analyzed methylation status of the FoxP3 gene promoter involved in Treg lymphocytes activation. Unmethylated FoxP3 has been demonstrated to be specific for Treg lymphocytes. A peripheral blood sample was obtained before surgery for routine chemistry Results: Results are summarized in the Table.A significant positive correlation was detected between Tregs in small resistance arteries and basal, total and delta gain capillary density in the forearm, whereas no correlations were observed with small resistance artery M/L and retinal arteriole W/L. In addition, a significant inverse correlation was detected between Treg in subcutaneous small vessels and C reactive protein. Conclusions: Our data suggest that Treg lymphocytes detected in subcutaneous small resistance artery wall are related with capillary density and inversely related with inflammatory markers suggesting a protecting role of Treg also, probably, in terms of angiogenetic properties.

Abstract P256: Structural Alterations of Subcutaneous Small Resistance Arteries in Resistant Hypertension

Background: It is was suggested that, in resistant hypertension, the presence of particularly pronounced microvascular alterations may contribute to explain the relative lack of response to treatment Patients and Methods: We investigated a population of 94 treated essential hypertensive patients. Secondary forms of hypertension were excluded, and in all patients a 24-hour blood pressure monitoring was performed in order to exclude a white coat effect. In all patients, we evaluated small resistance arteries morphology by a wire micromyographic approach. Subcutaneous tissue was obtained by local biopsy or during election surgery and subcutaneous small resistance arteries were dissected and mounted on a myograph; the media to lumen ratio (M/L) was then measured. We subdived our patents according to the presence or not of resistant hypertension (clinic blood pressure values above 140/90 mm Hg despite administration of three antihypertensive agent including a diuretic and 24-hour blood pressure values &gt;130/80 mm Hg). Sixteen patients had true resistant hypertension, and were compared with the remaining 78 patients with non-resistant hypertension. Results: are summarized in the Table, The two groups were also different in terms of mean age (57±12 vs. 67±7 years, p=0.016 and pulse pressure/stroke volume, a rough index of large artery distensibility: 0.63±0.31 vs. 0.90±0.33, p=0.02). Conclusion: Hypertensive patients with true resistant hypertension have greater microvascular structural alterations compared with non-resistant hypertensive patients. This could partly explain the resistance to treatment and the high cardiovascular risk observed in these patients.

Effects of a long-term treatment with aliskiren or ramipril on structural alterations of subcutaneous small-resistance arteries of diabetic hypertensive patients.

Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus.

Abstract 379: Circulating T Regulatory Lymphocytes and Microvascular Structural Alterations in Hypertensive Patients and Normotensive Subjects

Background and Methods. Different components of the immune system, including innate immunity and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes: Tregs) may be involved in the development of hypertension. In addition, it was recently demonstrated that Tregs may prevent angiotensin II-induced vascular injury/inflammation, while Th1, Th2 and Th17 may play a role in the progression of vascular remodeling. However, no data are available in human beings about relationships between T-lymphocyte subtypes and microvascular structure. In the present, preliminary study, we enrolled 7 normotensive subjects and 3 hypertensive patients undergoing an election surgical intervention. No sign of local or systemic inflammation was present in any subjects or patients. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, morphological parameter were measured, in particular media to lumen ratio (M/L) was calculated. A peripheral blood sample was obtained before surgery for assessment of T lymphocytes subpopulations by flow cytometry. Results are summarized in the Table. RTE: recent thymus emigrant; naïve: no contact with antigens, TDEM: highly antigen-experienced cells that assume pro-apoptotic properties. Additional significant positive correlations were observed between M/L and Th17 effector lymphocytes: r=0.67, p&lt;0.05). Conclusion Our data suggest that some lymphocytes subpopulations may be related to microvascular remodeling, and open the possibility to regress small artery remodeling in human by specific drug modulation of lymphocyte subtypes.

Resistance-Sized Arteries Structure and Capillary Density Changes in Glioblastoma and Meningioma Peritumoral Brain Tissue

Background: Brain vessels play a relevant role in the development of malignant primary tumors. Previous studies performed in preclinical models of brain tumors demonstrated the irregular morphology of vessels in glioblastoma, characterized by multiple abnormalities in shape, permeability and relationship with the contacting structures, such as the basement membrane; however no data about microvascular structural alterations in the brain of patients affected by brain tumors have been previously reported. Methods: We studied small vessels structural alterations, microvascular rarefaction and vascular collagen content in the peritumoral brain tissue of two groups of patients, respectively affected by glioblastoma and by meningioma, who underwent a surgical operation in order to remove the tumor. The two groups of patients were matched for clinical, laboratory variables and risk factors, with the exception of sex. Results: Media to lumen ratio was significantly higher in patients with meningioma compared to patients affected by glioblastoma. Vessels in the brain surrounding glioblastomas show a less organized structure, as demonstrated by the thinner media, by the lower content in collagen and by the lower capillary density. Conclusions: For the first time, we used an in vitro ex vivo technique to analyze structural alterations of resistance sized arteries of peritumoral brain tissue at the radiological tumor-brain interface in patients affected by glioblastoma and meningioma. This approach, together with immunohistochemical evaluation of microvessel density, has supplied new data about the brain microcirculation. These findings can be the result of the aberrant angiogenic process that characterizes glioblastomas and can finally play a role in tumor growth. Further studies are needed to confirm our data, to identify the pathways that lead to this microvascular pattern and to identify possible clinical applications

Interrelationships between macro and microvascular structure and function

Macrovasculature and microvasculature are interrelated, and may influence each other. Microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure. Some index of large artery stiffness seems to be related with the media to lumen ratio of subcutaneous small resistance arteries of hypertensive patients. In addition, both microvascular structural alterations and changes in the mechanical properties of large arteries represent potent predictors of prognosis. In addition, drugs that may improve microvascular structure may also correct alterations in the mechanical properties of large arteries In fact, while β-blocking agents and diuretics have a negligible effect on microvascular structure, renin-angiotensin system antagonists and calcium entry blockers have favorable actions, improving also large artery mechanics and possibly reducing central wave reflections.

Effects of Melatonin and Pycnogenol on Small Artery Structure and Function in Spontaneously Hypertensive Rats

It was suggested that oxidative stress has a key role in the development of endothelial dysfunction, as well as microvascular structural alterations. Therefore, we have investigated 2 substances with antioxidant properties: melatonin and Pycnogenol. We treated 7 spontaneously hypertensive rats (SHRs) with melatonin and 7 with Pycnogenol for 6 weeks. We compared results obtained with those observed in 7 SHRs and 7 Wistar-Kyoto normotensive control rats kept untreated. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and a concentration-response curve to acetylcholine was performed. Aortic contents of metalloproteinase 2, Bax, inducible NO synthase, and cyclooxygenase 2 were evaluated, together with the aortic content of total collagen and collagen subtypes and apoptosis rate. A small reduction in systolic blood pressure was observed. A significant improvement in mesenteric small resistance artery structure and endothelial function was observed in rats treated with Pycnogenol and melatonin. Total aortic collagen content was significantly greater in untreated SHRs compared with Wistar-Kyoto control rats, whereas a full normalization was observed in treated rats. Apoptosis rate was increased in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; an even more pronounced increase was observed in treated rats. Bax and metalloproteinase 2 expressions changed accordingly. Cyclooxygenase 2 and inducible NO synthase were more expressed in the aortas of untreated SHRs compared with Wistar-Kyoto control rats; this pattern was normalized by both treatments. In conclusion, our data suggest that treatment with Pycnogenol and melatonin may protect the vasculature, partly independent of blood pressure reduction, probably through their antioxidant effects.

Regression of Small Resistance Artery Structural Alterations in Hypertension by Appropriate Antihypertensive Treatment

Regardless of the mechanisms that initiate the rise of blood pressure, the development of structural changes in the systemic vasculature is the end result of established hypertension. Indices of small resistance artery structure, such as the ratio of tunica media to internal lumen, may have a strong prognostic significance in hypertensive patients, over and above all other known cardiovascular risk factors. Hence, the regression of vascular alterations seems to be an appealing goal for antihypertensive treatment. Different antihypertensive drugs may have different effects on vascular structure. Complete normalization of small resistance artery structure was demonstrated in hypertensive patients after long-term and effective antihypertensive therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium antagonists. Little or no improvement was observed with beta-blockers or diuretics. Evidence from several studies suggests that some antihypertensive drugs are more effective than others in reversing microvascular structural alterations in hypertension.

Vascular remodeling, macro- and microvessels: Therapeutic implications

Macrovasculature and microvasculature are deeply interrelated, since microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure. In fact, preliminary data suggest that some index of large artery stiffness is related with the media to lumen ratio of subcutaneous small resistance arteries of hypertensive patients. Microvascular structural alterations and changes in the mechanical properties of the macrovessels represent potent predictors of prognosis. Hypertension-related damage to the micro- and macrovascular system may be corrected by pharmacological agents. Among them, beta-blocking agents and diuretics have a negligible effect on microvascular structure, while renin–angiotensin system antagonists and calcium entry blockers have favorable actions, improving large artery mechanics and possibly reducing central wave reflections.

Vascular remodeling, macro- and microvessels: Therapeutic implications

Macrovasculature and microvasculature are deeply interrelated, since microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure. In fact, preliminary data suggest that some index of large artery stiffness is related with the media to lumen ratio of subcutaneous small resistance arteries of hypertensive patients. Microvascular structural alterations and changes in the mechanical properties of the macrovessels represent potent predictors of prognosis. Hypertension-related damage to the micro- and macrovascular system may be corrected by pharmacological agents. Among them, beta-blocking agents and diuretics have a negligible effect on microvascular structure, while renin–angiotensin system antagonists and calcium entry blockers have favorable actions, improving large artery mechanics and possibly reducing central wave reflections.

Body mass index and its effects on retinal vessel diameter in 6-year-old children

To examine the relationship between body mass index (BMI) and other anthropometric measures with retinal vessel diameter in children. A random cluster sample of 34 schools was selected in the Sydney metropolitan area during 2003-04, and 1740 children aged 6 years participated in The Sydney Childhood Eye Study. Retinal images were taken and vessel diameter was measured using a computer-imaging program. Anthropometric measures, including weight, height, waist circumference, BMI and body surface area (BSA), were obtained and defined using standardized protocols. Data on confounders, including ocular parameters, ethnicity, birth parameters and blood pressure, were similarly collected. Mean BMI was 16.2 kg/m(2) (+/-2.1 s.d.) in 1608 (92.4%) children with complete data. After controlling for age, sex, ethnicity, axial length of the eyeball, birth weight and mean arterial blood pressure, children with BMI above the cardiovascular risk threshold (defined as BMI>16.1 kg/m(2) in boys and BMI>15.9 kg/m(2) in girls) had mean retinal venular diameter 2.1 microm larger than those with BMI below this threshold (P=0.026). Increasing weight and BSA were also positively associated with wider retinal venules. Children in the highest quartile of BMI had mean retinal arteriolar diameter 2.2 microm smaller than those in the lowest quartile. Increasing waist circumference and shorter height were also associated with narrower retinal arterioles. In this sample of 6-year-old children, greater BMI, weight and BSA were associated with wider retinal venules, while greater BMI and larger waist circumference were associated with narrower retinal arterioles. These findings suggest a possible effect of increased body mass and adiposity on early microvascular structural alterations in childhood, long before the development of cardiovascular disease.