Effects of cardiac rehabilitation on in vivo nailfold microcirculation in patients with cardiovascular disease.

This study aimed to explore the impact of cardiac rehabilitation (CR) on in vivo and ex vivo microcirculation, exercise capacity, and oxidative stress in patients with cardiovascular disease (CVD). The study included patients with acute coronary syndrome (ACS; n = 45; age, 69.0 ± 14.1 years) and heart failure (HF; n = 66; age, 77.3 ± 10.7 years) who underwent supervised CR during hospitalization. The control group comprised patients without CVD (NCVD; n = 20; age, 75.9 ± 11.2 years). In vivo microcirculatory observations using nailfold video capillary endoscopy at rest and during hyperemia, exercise capacity, and oxidative stress were assessed at baseline and 12 weeks after discharge. Baseline capillary densities were significantly lower in the ACS (5.0 ± 1.7 capillaries/mm2) and HF (4.9 ± 1.7 capillaries/mm2) groups than in the NCVD group (6.5 ± 1.1 capillaries/mm2, p < 0.01). Similarly, capillary density during reactive hyperemia was significantly lower in the ACS (5.8 ± 1.7 capillaries/mm2) and HF (5.4 ± 1.8 capillaries/mm2) groups than in the NCVD group (7.3 ± 1.4 capillaries/mm2, p < 0.01). Patients with ACS and HF had increased capillary densities at 12 weeks compared with at baseline (p < 0.05). This improvement was particularly pronounced among post-discharge outpatient CR participants (n = 20). Grip strength, exercise capacity, and oxidative stress improved at 12 weeks. Baseline capillary density changes were positively correlated with grip strength changes (r = 0.45, p < 0.001). CR significantly improved nailfold capillary density in patients with ACS and HF 12 weeks after discharge.

Vascular Endothelial Damage in COPD: Where Are We Now, Where Will We Go?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has higher rates among the general population, so early identification and prevention is the goal. The mechanisms of COPD development have not been completely established, although it has been demonstrated that endothelial dysfunction plays an important role. However, to date, the measurement of endothelial dysfunction is still invasive or not fully established. Nailfold video capillaroscopy (NVC) is a safe, non-invasive diagnostic tool that can be used to easily evaluate the microcirculation and can show any possible endothelial dysfunctions early on. The aim of this review is to evaluate if nailfold microcirculation abnormalities can reflect altered pulmonary vasculature and can predict the risk of cardiovascular comorbidities in COPD patients. METHODS: A systematic literature search concerning COPD was performed in electronic databases (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until March 2024. The following search words were searched in the databases in all possible combinations: chronic obstructive pulmonary disease (COPD), endothelial damage, vascular impairment, functional evaluation, capillaroscopy, video capillaroscopy, nailfold video capillaroscopy. Only manuscripts written in English were considered for this review. Papers were included only if they were able to define a relationship between COPD and endothelium dysfunction. RESULTS: The search selected 10 articles, and among these, only three previous reviews were available. Retinal vessel imaging, flow-mediated dilation (FMD), and skin autofluorescence (AF) are reported as the most valuable methods for assessing endothelial dysfunction in COPD patients. CONCLUSIONS: It has been assumed that decreased nitric oxide (NO) levels leads to microvascular damage in COPD patients. This finding allows us to assume NVC's potential effectiveness in COPD patients. However, this potential link is based on assumption; further investigations are needed to confirm this hypothesis.

Nailfold Capillaroscopy Analysis Can Add a New Perspective to Biomarker Research in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which are characterised by inflammation of small-medium-sized vessels. Progressive understanding of these diseases has allowed researchers and clinicians to start discussing nailfold video capillaroscopy (NVC) as a future tool for many applications in daily practice. Today, NVC plays a well-established and validated role in differentiating primary from secondary Raynaud's phenomenon correlated with scleroderma. Nevertheless, there has not been sufficient attention paid to its real potential in the ANCA-associated vasculitis. In fact, the role of NVC in vasculitis has never been defined and studied in a multicentre and multinational study. In this review, we carried out a literature analysis to identify and synthesise the possible role of capillaroscopy for patients with ANCA-associated vasculitis. METHODS: Critical research was performed in the electronic archive (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until November 2023. The following search words were searched in the databases in all possible combinations: capillaroscopy, video capillaroscopy, nailfold-video capillaroscopy, ANCA-associated vasculitis, vasculitis, granulomatosis with polyangiitis, EGPA, and microscopic polyangiitis. RESULTS: The search identified 102 unique search results. After the evaluation, eight articles were selected for further study. The literature reported that capillaroscopy investigations documented non-specific abnormalities in 70-80% of AAV patients. Several patients showed neoangiogenesis, capillary loss, microhaemorrhages, and bushy and enlarged capillaries as the most frequent findings. Furthermore, the difference between active phase and non-active phase in AAV patients was clearly discernible. The non-active phase showed similar rates of capillaroscopy alterations compared to the healthy subjects, but the active phase had higher rates in almost all common abnormalities instead. CONCLUSIONS: Microvascular nailfold changes, observed in patients affected by vasculitis, may correlate with the outcome of these patients. However, these non-specific abnormalities may help in the diagnosis of vasculitis. As such, new analysis analyses are necessary to confirm our results.

Flow Mediated Dilation in Systemic Sclerosis: Association with clinical findings, capillaroscopic patterns and endothelial circulating markers.

AIM: Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. METHODS: 57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. RESULTS: Compared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. CONCLUSIONS: FMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.

Computerized nailfold video-capillaroscopy in type 2 diabetes: A cross-sectional study on 102 outpatients.

BACKGROUND: Type 2 diabetes (T2D) is a chronic disease that negatively affects vascular health. A careful assessment of chronic complications, including microcirculation, is mandatory. The computerized nailfold video-capillaroscopy (CNVC) accurately examines the nailfold microvasculature, but its suitability in T2D is currently under investigation. AIMS: To describe nailfold microvasculature in T2D patients regarding the level of glucose control and chronic microvascular and macrovascular complications. METHODS: This is a cross-sectional study on 102 consecutive and unselected outpatients with T2D who had undergone CNVC examination. The examination was carried out by using an electronic video-capillaroscope with 300x magnification. Capillaroscopic appearance and capillary changes were described according to well-established parameters. Capillaroscopic parameters were compared between patients with poor glucose control (HbA1c ≥7%) and those with better glucose control (HbA1c <7%) and between patients with chronic complications and those without. Chronic complications were deduced from the anamnestic, laboratory, and instrumental data and the five-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Nailfold capillaries in patients with HbA1c ≥7% were thicker (p = .019) and longer (p = .021) than in those with better glucose control. Ectasias (p = .017) and microaneurysms (p = .045) were more frequently observed in patients with HbA1c ≥7.0% than those with HbA1c <7.0%. Patients with ED, compared to those without, had a lower frequency of bizarre-shaped capillaries (p = .02). Microaneurysms (p = .02) were more frequently described in patients with carotid stenosis (>20%) than those without. CONCLUSION: Relevant nailfold microvascular alterations were observed in T2D, most of which were associated with poor glycemic control, ED, and carotid stenosis. Further investigation is needed to recognize the role of CNVC in predicting the onset and evolution of chronic complications and monitoring the effectiveness of antihyperglycemic treatments on microcirculation.

Utility of nailfold capillary assessment for predicting pustulotic arthro-osteitis in palmoplantar pustulosis based on a prospective cohort study.

BACKGROUND: Pustulotic arthro-osteitis (PAO) is 1 of the most serious comorbidities associated with palmoplantar pustulosis (PPP). Risk factors of PAO development are not well-known. OBJECTIVE: To evaluate the clinical significance of nailfold capillary (NFC) changes in patients with PPP. METHODS: We conducted a prospective cohort study in a population of 102 PPP patients. Correlations of NFC abnormalities, including nailfold bleeding and enlarged capillaries, with the prevalence of PAO, the incidence of new PAO, and serum levels of cytokines were analyzed. RESULTS: Detailed examination revealed that of 102 PPP patients, 52 without PAO and 50 with PAO. Both nailfold bleeding and enlarged capillaries were significantly more frequent in patients with PAO (50.0% vs 92.0%, P < .0001; 50.0% vs 94.0%, P < .0001). In addition, PPP patients without PAO were prospectively observed before they developed PAO (mean 28 months [1-52 months]). Multivariate analysis suggested that these NFC abnormalities were predictors of PAO development (hazard ratio 3.37, 95% confidence interval 1.13-10.07; 3.37, 1.13-10.07) and guselkumab prevent PAO development (0.093, 0.012-0.76). The degree of NFC abnormalities correlated with the severity of PAO and serum cytokine levels. LIMITATIONS: All participants were Japanese. CONCLUSION: NFC abnormalities could be predictors of PAO in PPP patients, and their degree indicators of disease severity.

Utility of nailfold capillary assessment for predicting psoriatic arthritis based on a prospective observational cohort study.

OBJECTIVES: PsA is one of the most serious comorbidities associated with psoriasis. While the early intervention in PsA is demanded, risk factors of PsA development are not well-known. This is the first prospective study to evaluate the clinical significance of nailfold capillary (NFC) changes in patients with psoriasis. METHODS: We conducted a prospective cohort study in a population of 449 psoriasis patients who had not been treated with systemic therapy or topical finger therapy. NFCs were observed by dermoscopy and capillaroscopy, and the correlation of NFC abnormalities, including nailfold bleeding (NFB) and enlarged capillaries, with the prevalence of PsA, incidence of new PsA, and serum levels of TNF-a, IL-17A and IL-23 were analysed. RESULTS: Detailed examination at the time of inclusion revealed that of 449 patients, 236 had Psoriasis vulgaris (PsV) and 213 had PsA. Both NFB and enlarged capillaries were significantly more frequent in patients with PsA (34.7% vs 84.5%, P < 0.0001; 25.4% vs 100%, P < 0.0001). In addition, PsV patients were prospectively observed before they developed PsA (mean 21 months, 95% CI 2, 77 months). Multivariate analysis suggested that the appearance of NFB and enlarged capillaries was a predictor of PsA development (HR 2.75, 95% CI 1.38, 5.47 and HR 4.49, 95% CI 2.25, 8.96, respectively). The degree of NFC abnormalities also correlated with the severity of PsA and serum cytokine levels. CONCLUSIONS: NFC abnormalities were suggested to be a predictor of PsA in psoriasis patients, and at the same time, its degree could be an indicator of disease severity.

Asymmetric dimethylarginine correlates with worsening peripheral microangiopathy in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease characterized primarily by micro-angiopathy and endothelial dysfunction which stimulate a fibrotic process. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor and represents a novel biomarker for vascular dysfunction. Nailfold video capillaroscopy (NVC) represents a non-invasive and reliable technique for the evaluation of microvasculopathy in SSc. OBJECTIVES: The aim of this study was to examine the possible association between ADMA and microvascular involvement in patients with SSc. METHODS: This was a cross-sectional study including consecutive SSc patients attending the Scleroderma Outpatient Clinic. ADMA was measured in serum samples using a commercial enzyme immunoassay. Participants underwent NVC with qualitative and semi-quantitative assessment and all NVC parameters were measured in the distal row of each finger. The findings were classified in one of the three qualitative NVC patterns: early, active, and late. RESULTS: Eighty-one (92,6 % women) SSc individuals with mean age 55.44 ± 13.4 years were included in this analysis. Within-groups comparisons revealed a trend between higher ADMA levels and progressive micro-vasculopathy (1,29 [2,1] vs 1,57 [1,95] vs 2,41 [3,87]; for early, active and late patterns respectively, p = 0.039). Furthermore, ADMA concentration was significantly associated with the number of capillaries/mm (r = -0.235; p = 0.035). CONCLUSIONS: Serum ADMA levels were significantly associated with advancing stages of microcirculatory abnormalities suggesting that ADMA may have a role in promoting microvascular endothelial dysfunction in SSc individuals.

Nailfold video capillaroscopy as a useful diagnostic tool in systemic vasculitis.

BACKGROUND: Nailfold video capillaroscopy (NVC) enables us a direct view of the microvasculature. Only several capillaroscopy studies in adult patients with vasculitis have been reported. AIM: To characterize NVC changes in vasculitis. METHODS: Vasculitis patients and healthy controls were evaluated by NVC. NVC changes associated with vasculitis were assessed retrospectively in a cohort of 100 patients with Raynaud's phenomenon (RP). RESULTS: 17 patients with active vasculitis and 8 patients with vasculitis in remission were compared to 25 age and sex-matched healthy controls. Active vasculitis patients demonstrated higher rates of neoangiogenesis and capillary loss in comparison to other groups. Two novel NVC abnormalities were observed in patients with vasculitis: "Rolling" (slow capillary flow) and "peri-capillary stippling" (PCS), small deposits that may represent capillary leak. PCS was observed exclusively in 5 of 17 patients with active vasculitis. Retrospectively, we were able to detect PCS also in 14 % of 100 patients that were evaluated for RP, of whom 64 % were diagnosed with scleroderma or a related disorder. CONCLUSIONS: Patients with active vasculitis demonstrate frequent capillary abnormalities. Although these abnormalities are non-specific, we suggest that their combination may aid the diagnosis of vasculitis. Future studies are needed to validate our findings.

Nailfold Video Capillaroscopy in Pregnant Women With and Without Cardiovascular Risk Factors.

Objective: To evaluate microvasculature in pregnant women with and without cardiovascular risk factors. Design: Cross-sectional, observational study. Population: Women were recruited at the outpatient clinic for high risk prenatal care. Out of a total of 345 women assessed at first and/or second and/or third trimester, 169 women without and 176 with cardiovascular risk factors were included. Methods: Nailfold video capillaroscopy (NVC) measurements were performed at magnification of 200x at all fingers except thumbs. Images were stored for offline measurement of capillary density (CDe) and capillary diameters (CDi). Maternal anthropometrics, obstetric, and medical history were used for categorization in low and high cardiovascular risk. Comparison between groups and trimesters, with respect to pregnancy outcome, was performed using linear mixed model analysis. Results: Women with a high risk cardiovascular profile show higher CDe, regardless of pregnancy outcome. CDi drops during pregnancy, with lowest CDi in third trimester in patients with preeclampsia. Capillary bed (CB), as a composite of CDe and CDi, is stable during pregnancy in women with low risk cardiovascular profile. In women with high risk cardiovascular profile, CB drops from the first to the second trimester, regardless of pregnancy outcome. Only in women with pre-eclampsia, the CB is lower in the third trimester as compared to the first trimester.There is an inverse association between CDe and mean arterial pressure (MAP) in women with high cardiovascular risk and pre-eclampsia. Conclusion: Microcirculation is altered during the course of pregnancy and microcirculatory behavior is different in patients with low and high cardiovascular risk profile, as well as in patients with preeclampsia.

Corrigendum: Nailfold video capillaroscopy in pregnant women with and without cardiovascular risk factors.

[This corrects the article DOI: 10.3389/fmed.2022.904373.].

Use of nailfold video capillaroscopy in polycythemia vera.

Objectives: In this study, we aimed to investigate capillary vessel diameters and structural changes of capillaries by using nailfold video capillaroscopy (NVC) in patients with polycythemia vera (PV). Patients and methods: This cross-sectional study included a total of 24 patients (19 males, 5 females; mean age: 59.8±12.9 years; range, 50.2 to 68 years) who were diagnosed with PV and 15 healthy controls (11 males, 4 females; mean age: 40.7±5.1 years; range, 36 to 44 years) between June 2016 and February 2017. Nailfold video capillaroscopy was performed by an experienced rheumatologist who was blinded to clinical data. The apical, arterial, and venous limb diameters of capillaries were measured and microvascular changes of capillaries were scored. Results: When capillaries were evaluated in terms of morphological structures, giant capillary was detected in 67% of the patients with PV and 0% in the control group (p<0.05). The arterial, venous, and apical diameters of the capillaries were significantly higher in the patients with PV compared to the control group (p<0.001). Conclusion: The presence of giant capillaries and the marked increase of arterial, venous, and apical diameters of capillaries seem to be related to PV. As it additionally plays an important role in diagnosis, prognosis, and treatment monitoring of certain diseases, capillaroscopy can be considered to be a promising microcirculation biomarker.

Raynaud's phenomenon in a drummer player: Microvascular disorder and nailfold video capillaroscopic findings.

Drummers are usually exposed to intensive physical stress and occupational diseases that have been only partially investigated. The majority of studies focus on musculoskeletal problems while microvascular abnormalities have been less considered. We report on a case of a 19-year-old drummer affected by Raynaud's phenomenon. The patient underwent nailfold video capillaroscopy that showed a non-specific pattern, with granular flow, dyshomogeneous capillary morphology, increased efferent/afferent loop ratio and many enlarged capillaries. The continuous exposition to vibration in drummers could determinate microvascular abnormalities with related cold induced disorders and Raynaud's phenomenon. Nailfold video capillaroscopy is a tool that allows to detect the alterations of the microcirculation and to carry out the follow-up of the patients with low cost, non-invasiveness, repeatability, high sensibility and specificity.

Capillaroscopic Evidence of Microvascular Damage in Volleyball Players.

Volleyball players experience repetitive stress that involves their hands and, in particular, their fingers. Literature reports that repetitive trauma can lead to local vascular abnormalities, such as reduced capillarization and lower resting blood flow. These anomalies could be related to the presence of dysfunctional endothelium. The aim of this study is to correlate the capillaroscopic findings by nailfold video capillaroscopy (NVC) to volleyball practice in order to early detect possible anomalies and perform an adequate follow-up to avoid damages that could negatively affect sport practice and the players' health status. In this study, 38 subjects were enrolled, 19 volleyball players and 19 healthy non-players as a comparison group. In almost all the players, we found capillaroscopic alterations of the "aspecific pattern" type without substantial gender differences. We may assume that the repeated traumas involving players' fingers can negatively modify their microcirculation. Based on these observations, it could be a desirable clinical practice to screen professional volleyball players with NVC in order to implement preventive strategies aimed at protecting the health of athletes.

Patients with Systemic Sclerosis with and without Overlap Syndrome Show Similar Microvascular Abnormalities.

INTRODUCTION: Nailfold video capillaroscopy (NVC) is a useful tool for measuring capillary density (CD) and capillary morphology parameters and is mainly used in systemic sclerosis (SSc). OBJECTIVE: We aimed to assess the prevalence of an SSc pattern and CD in different connective tissue diseases (CTDs). METHODS: NVC was performed on 268 patients with CTDs. Control groups consisted of 104 healthy volunteers (HVs) and 36 primary Raynaud's patients (PRPs). RESULTS: Decreased CD was more prevalent in SSc, systemic lupus erythematosus (SLE), inflammatory myopathies (IIM), and overlap CTD patients compared with both controls. Average CD, the prevalence of decreased CD, and the prevalence of an SSc pattern did not differ significantly between SSc patients with (n = 39) and without (n = 50) overlap syndrome. An SSc pattern was significantly more prevalent in SLE (23%), SSc (82%), IIM (35%), and rheumatoid arthritis (17%) compared with both control groups. The prevalence of an elevated microangiopathy evaluation score (MES) was significantly higher in SLE, SSc, and IIM than in the HVs. CONCLUSION: The presence of another CTD in SSc did not influence CD or morphology. An SSc pattern may also be present in CTDs other than SSc. The MES is a useful instrument to distinguish between patients with CTDs and controls.

Peripheral microcirculatory abnormalities are associated with cardiovascular risk in systemic sclerosis: a nailfold video capillaroscopy study.

INTRODUCTION: Microvascular dysfunction is the key element in the pathogenesis of systemic sclerosis (SSc), whereas the contribution of large and medium size vessel abnormalities is yet to be established. The aim of the present study is to assess the association between micro- and macrovascular function by utilizing a broad spectrum of assessments of vascular performance. METHODS: We included consecutive, consenting SSc patients who underwent nailfold video capillaroscopy (NVC) for microcirculation evaluation. Peripheral and central systolic and diastolic blood pressure, carotid intima-media thickness (cIMT), aortic augmentation index (AIx) corrected for a heart rate of 75 beats per minute (AIx-75), and carotid-femoral pulse wave velocity (PWV) were also performed to assess macrovascular function. Cardiovascular risk disease (CVD) algorithms were also calculated and included in the analysis. RESULTS: A total of 81 patients (6 males) were studied with mean age 55.44 ± 13.40 years. Reduced capillary density was inversely correlated with arterial stiffness (Alx-75) and augmentation pressure (r = - 0.262, p = 0.018, and r = - 0.249, p = 0.025 respectively). Alx was significantly lower in the early compared to late pattern (28.24 ± 11.75 vs 35.63 ± 10.47, p = 0.036). A significant trend was found among NVC patterns with Alx-75 values being higher with the progression of microangiopathy towards the "late" group (26.36 ± 10.90 vs 30.81 ± 11.59 vs 35.21 ± 7.90, p = 0.027 for trend). Similarly, Framingham risk score and Atherosclerotic Cardiovascular Disease score were progressively higher across the worsening NVC patterns (4.10 ± 4.13 vs 2.99 ± 2.72 vs 6.36 ± 5.65, p = 0.023, and 6.99 ± 7.18 vs 5.63 ± 4.41 vs 12.09 ± 9.90, p = 0.019, respectively, for trends). Finally, QRISK3 (10-year cardiovascular disease risk) and ASCVD (Atherosclerotic Cardiovascular Disease) scores were inversely correlated with the number of capillaries (r = - 0.231, p = 0.048, and r = - 0.260, p = 0.038 respectively). CONCLUSION: These data suggest that CVD risk scores and macrovascular parameters are strongly correlated with microvasculopathy in patients with SSc. Key Points • Microangiopathy is the hallmark of SSc, but the relationship between subclinical atherosclerosis and small vessel disease remains unknown. • Arterial stiffening and CVD risk scores are positively associated with the degree of progression of peripheral microvasculopathy assessed with NVC. • The results of the study suggest an association between NVC abnormalities and higher CVD risk in SSc patients.

Peripheral microangiopathy in Eisenmenger syndrome: A nailfold video capillaroscopy study.

BACKGROUND: Eisenmenger syndrome (ES) comprises a severe phenotype of pulmonary arterial hypertension characterized by angiopathy of the lung circulation. The aim of the present study was to demonstrate the presence of systemic microvascular abnormalities in patients with ES using nailfold video-capillaroscopy (NVC) and to identify potential correlations of nailfold capillaroscopic characteristics with non-invasive markers of systemic organ function. METHODS: Α cross-sectional NVC study was performed in 17 consecutive patients with ES and 17 healthy controls matched for age and sex. NVC quantitative (capillary density, capillary dimensions, haemorrhages, thrombi, shape abnormalities) and qualitative (normal, non-specific or scleroderma pattern) parameters were evaluated. RESULTS: Patients with ES [median age 40 (18-65) years, 11 women] presented reduced capillary density [8.8 (7.2-10.2) loops/mm vs. 9.9 (8.3-10.9) loops/mm, p = .004] and increased loop width [15.9 (10.3-21.7) µm vs. 12.3 (7.6-15.2) µm, p < .001], while they had significantly more abnormal capillaries than healthy controls [2.5 (0.9-5.4) abnormal loops/mm vs. 1.0 (0.0-1.7) abnormal loops/mm, p < .001]. NVC shape abnormalities in ES were positively correlated with NT-proBNP (r = 0.52, p = .03) and were negatively associated with estimated glomerular filtration rate (r = -0.60, p = .02). Additionally, capillary loop diameter was positively correlated with increased haemoglobin levels (r = 0.55, p = .03) and negatively correlated with reduced peripheral oxygen saturation (r = - 0.56, p = .02). CONCLUSIONS: This study supports the hypothesis of peripheral microvascular involvement in ES parallel to pulmonary microangiopathy detected by NVC. Further longitudinal studies are needed to confirm our preliminary results.

Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study.

BACKGROUND: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity. METHODS: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test). RESULTS: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 µm and 15.8 ± 1.9 µm vs. 11.5 ± 2.3 µm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001). CONCLUSION: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Association Between Uric Acid and Worsening Peripheral Microangiopathy in Systemic Sclerosis.

Objective: The key element in the pathogenesis of systemic sclerosis (SSc) is microcirculatory changes in several vascular beds. Uric acid is associated with endothelial dysfunction and therefore, microvascular damage. The aim of this study was to examine the association between uric acid (UA) and peripheral microvascular involvement in patients with SSc. Methods: We included consecutive, consenting patients with SSc. Serum UA, urea and creatinine were measured, and glomerular filtration rate (GFR) was calculated with CKD-EPI. All participants underwent nailfold video-capillaroscopy (NVC) to evaluate the microcirculation. Results: A total of 64 patients (95.3% women) were included in the study. UA levels were significantly associated with the number of avascular areas (r = 0.290; p = 0.020), whereas no correlation was shown for the GFR (r = -0.065; p = 0.609). A significant trend of UA in the three capillaroscopic patterns was shown (3.90 ± 1.52 vs. 4.15 ± 0.98 vs. 5.38 ± 2.26; for early, active, and late patterns respectively, p = 0.028). Multivariate analysis showed that male gender (ß = 3.049; 95% CI = 0.997-5.101) and UA (ß = 0.352; 95% CI = 0.117-0.588) were independently associated with the number of avascular areas. Conclusion: These data suggest that UA levels are significantly associated with the capillaroscopic patterns, reflecting a progressive microvasculopathy.

The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease.

OBJECTIVE: Endothelial dysfunction has been associated with increased cardiovascular events and overall mortality. Microvascular damage is prevalent both in diabetes mellitus (DM) and chronic kidney disease (CKD). Our aim was to compare microcirculatory function parameters in diabetic and non-diabetic CKD patients via nailfold video-capillaroscopy. METHODS: We included 48 diabetic and 48 non-diabetic adult CKD patients. All participants underwent nailfold video-capillaroscopy, during which capillary density was measured at normal conditions (baseline), after a 4-minute arterial occlusion (postocclusive reactive hyperemia), and at the end of a 2-minute venous occlusion (congestion phase). RESULTS: Diabetic patients presented significantly lower capillary density during reactive hyperemia (36.3 ± 3.8 vs 38.3 ± 4.3 capillaries/mm2 , P = .022) and at venous congestion (37.8 ± 4.0 vs 39.8 ± 4.2 capillaries/mm2 , P = .015). When stratified according to CKD stages, only in stage 3b capillary density was significantly lower in diabetic compared to non-diabetic subjects at baseline, during postocclusive hyperemia (36.8 ± 2.7 vs 40.0 ± 4.3 capillaries/mm2 , P = .037) and venous congestion (38.3 ± 2.8 vs 41.5 ± 3.5 capillaries/mm2 , P = .022). CONCLUSIONS: Capillary density during postocclusive hyperemia and after venous congestion is lower in diabetic compared to non-diabetic CKD patients, a finding indicative that diabetes is an additional factor contributing to microcirculatory structural and functional impairment in CKD. These differences are more prominent in CKD stage 3b.