Post-SARS-CoV-2 Acute Telogen Effluvium: An Expected Complication.

Post-SARS-CoV-2 telogen effluvium has been described in case reports of COVID-19 patients. We evaluated the prevalence of post-SARS-CoV-2 telogen effluvium in patients from a single medical center, exploring any causal links with the infection. Our hospital-based, cross-sectional study was conducted with patient participants discharged with a diagnosis of SARS-CoV-2 pneumonia from 1 March to 4 April 2020. All patients were evaluated by the same senior dermatologist; a clinical/dermatoscopic evaluation was performed. Alopecia was assessed in 31.3% of patients, with a significant difference in sex (females 73%, males 26.7%). The average time detected from the onset of the first symptoms to alopecia was 68.43 days. Overall, there were no significant associations between alopecia and COVID-19-related features (length of hospitalization, virologic positivity, or duration of fever), treatment characteristics, or laboratory findings. In this paper, we report that post-infection acute telogen effluvium occurs in a significant number of COVID-19 patients. The burden of this condition may impair the quality of life, with a significant impact on individuals.

Effect of antihypertensive treatment on circulating endothelial progenitor cells in patients with mild essential hypertension.

It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

Effects of insulin on endothelial and contractile function of subcutaneous small resistance arteries of hypertensive and diabetic patients.

The effect of insulin on the vasoconstriction induced by norepinephrine is at present controversial. We have previously demonstrated that high-concentration insulin may induce an increased reactivity to norepinephrine in mesenteric small resistance arteries of spontaneously hypertensive rats. The aim of the present study was to evaluate the effects of low- and high-concentration insulin on the concentration-response curves to norepinephrine and acetylcholine in subcutaneous small resistance arteries of hypertensive and diabetic patients. Twelve normotensive subjects (NT), 11 patients with essential hypertension (EH), 8 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 8 patients with both EH and NIDDM (EH + NIDDM) were included in the study. Subcutaneous small resistance arteries were dissected and mounted on an isometric myograph. Concentration-response curves to norepinephrine (from 10(-8) to 10(-5) mol/l) and acetylcholine (from 10(-9) to 10(-5) mol/l) were performed in the presence or absence of insulin 715 pmol/l (low concentration) and 715 nmol/l (high concentration). A significant reduction in the contractile response to norepinephrine was observed in NT after preincubation of the vessels with both low- and high-concentration insulin. No reduction was observed in NIDDM and EH + NIDDM, while a significant decrease was obtained in EH with high-concentration insulin. Moreover, a significant difference in reduction in contractile response at maximal concentration of norepinephrine in the presence of low-concentration insulin was observed in NT compared to EH (p = 0.03), NIDDM (p = 0.02), and EH + NIDDM (p = 0.05), whereas no difference was observed with high-concentration insulin. No differences in the concentration-response curves to acetylcholine before or after precontraction with either low- or high-concentration insulin were observed in any group. In conclusion, insulin at low (physiological) concentrations seems to induce a decreased reactivity to norepinephrine in subcutaneous small resistance arteries of NT, but this effect was lost in EH, NIDDM and EH + NIDDM. This effect does not seem to involve acetylcholine-stimulated nitric oxide release.

Structural alterations of subcutaneous small-resistance arteries may predict major cardiovascular events in patients with hypertension.

BACKGROUND: Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased tunica media to internal lumen ratio of subcutaneous small-resistance arteries (M:L) may predict the development of cardiovascular events in a high-risk population. However, it is not known whether structural alterations of small arteries may also predict major cardiovascular events. METHODS: Three hundred three subjects were included in the present study. There were 65 normotensive subjects, 111 patients with essential hypertension (33% of them with diabetes mellitus), 109 patients with secondary forms of hypertension, and 18 normotensive diabetic patients. Small-resistance arteries were dissected from subcutaneous fat biopsies and mounted on an isometric myograph, and the M:L was measured. Subjects were reevaluated after an average follow-up time of 6.9 years to assess the occurrence of cardio-cerebrovascular events. RESULTS: Eleven subjects died of a fatal cardio-cerebrovascular event (FCE), 14 had a major, nonfatal cardiovascular event (stroke or myocardial infarction) (SMI), 23 had a minor cardiovascular event (MCE), and 255 had no cardiovascular event (NCE). A significant difference was observed in M:L and in event-free survival between patients with FCEs+SMIs+MCEs and those with NCE and between patients with FCEs+SMIs and those with NCE. Similar results were obtained by restricting the analysis to patients with essential hypertension. CONCLUSIONS: Structural alterations of small-resistance arteries may predict FCE and SMI. The prognostic role of small-resistance artery structure also applies to medium-risk patients with essential hypertension, at least when MCEs are included in the analysis.

Morning rise of blood pressure and subcutaneous small resistance artery structure.

OBJECTIVES: It has been previously demonstrated that the morning rise (MoR) of blood pressure (BP) may predict major cardiovascular events in hypertensive patients. Structural alterations of small resistance arteries, as evaluated by the tunica media to internal lumen ratio (M/L) of subcutaneous small resistance arteries, may also predict cardiovascular events. Because an increased M/L may amplify the effect of hypertensive stimuli, the present study aimed to evaluate the possible relationships between MoR and M/L in a population of hypertensive patients. METHODS: Sixty-four patients with essential hypertension were included in the present study. All patients were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on an isometric myograph, and the M/L was measured. In addition, MoR was calculated from ambulatory blood pressure monitoring (ABPM) according to four previously published different methods (MoR1 to MoR4). RESULTS: A statistically significant correlation was observed between M/L and MoR1 (r = 0.52, P < 0.001), MoR2 (r = 0.32, P < 0.01), MoR3 (r = 0.25, P < 0.05) and MoR4 (r = 0.27, P < 0.05), as well as between internal diameter of subcutaneous small arteries and MoR1 (r = -0.45, P < 0.001) and MoR2 (r = -0.28, P < 0.05). CONCLUSION: Our results indicate that subcutaneous small artery structure is related to MoR, possibly because an altered vascular structure may amplify BP changes or, vice versa, because a greater MoR may further damage peripheral vasculature.

Changes in extracellular matrix in subcutaneous small resistance arteries of patients with primary aldosteronism.

CONTEXT AND OBJECTIVE: It has been previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. Our aim was to evaluate whether such a profibrotic action is present also in the human microcirculation. DESIGN AND PATIENTS: We investigated 13 patients with primary aldosteronism, seven patients with essential hypertension, and 10 normotensive controls. All subjects were submitted to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media to internal lumen ratio was measured. MAIN OUTCOME MEASURES: The total collagen content within the tunica media was detected (Sirius red staining and image analysis), and collagen subtypes were evaluated using polarized light microscopy; under this condition thicker type I collagen fibers appear orange or red, whereas thinner type III collagen fibers are yellow or green. RESULTS: Tunica media to internal lumen ratio was significantly increased in primary aldosteronism and in essential hypertension compared with normotensive controls. Clinic blood pressure values were similar in primary aldosteronism and in essential hypertension, and greater than in normotensive controls. Normotensive controls had less total and type III collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two hypertensive groups (P < 0.001). Total collagen and type III vascular collagen were significantly greater in primary aldosteronism (total collagen, 8.17 +/- 1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%). CONCLUSIONS: Our results indicate that, in small resistance arteries of patients with primary aldosteronism, a pronounced fibrosis may be detected, even more evident than in blood-pressure-matched patients with essential hypertension.

Lack of prognostic role of endothelial dysfunction in subcutaneous small resistance arteries of hypertensive patients.

OBJECTIVE: The presence of endothelial dysfunction in the coronary circulation or in the brachial artery has been found to be associated with a greater incidence of cardiovascular events. However, no data are presently available about the prognostic role of endothelial dysfunction in human small resistance arteries. DESIGN AND METHODS: Ninety subjects were included in the present study. They were: 10 normotensive subjects, 36 patients with essential hypertension, 10 patients with phaeochromocytoma, 11 patients with primary aldosteronism, 10 patients with renovascular hypertension, and 13 normotensive patients with non-insulin-dependent diabetes mellitus (NIDDM). All subjects were submitted to a biopsy of subcutaneous fat from the gluteal or the anterior abdominal region. Small resistance arteries were dissected and mounted on an isometric myograph, and the concentration-response curves to acetylcholine (from 10 to 10 mol/l) (endothelium-dependent vasodilatation) and sodium nitroprusside (from 10 to 10 mol/l) (endothelium-independent vasodilatation) after precontraction of the vessels with norepinephrine were evaluated. The subjects were re-evaluated (by clinical visits or telephone interviews) after an average follow-up time of 5.5 years. RESULTS: Twenty-nine subjects had a documented fatal or non-fatal cardiovascular event (5.87%/year). The endothelium-dependent vasodilatation in the subcutaneous small arteries was similar in subjects with or without cardiovascular events. Also, endothelium-independent vasodilatation to sodium nitroprusside was similar in the two groups. Similar results were obtained by subdividing patients in the different subgroups (essential hypertension, secondary hypertension, etc.). CONCLUSIONS: Our results indicate that endothelial dysfunction in the microcirculation does not predict cardiovascular events. It is possible that a prognostic role of endothelial dysfunction may be observed when other vascular districts prone to atherosclerosis are evaluated, or it might be detected only in patients at low to medium cardiovascular risk, in whom endothelial dysfunction is less advanced.

Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus.

Structural alterations of subcutaneous small resistance arteries are associated with a worse clinical prognosis in hypertension and noninsulin-dependent diabetes mellitus (NIDDM). However, no data are presently available about the effects of antihypertensive therapy on vascular structure in hypertensive patients with NIDDM. Therefore, we have investigated the effect of an angiotensin-converting enzyme inhibitor, enalapril, and a highly selective angiotensin receptor blocker, candesartan cilexetil, on indices of subcutaneous small resistance artery structure in 15 patients with mild hypertension and NIDDM. Eight patients were treated with candesartan (8 to 16 mg per day) and 7 with enalapril (10 to 20 mg per day) for 1 year. Each patient underwent a biopsy of the subcutaneous fat from the gluteal region at baseline and after 1 year of treatment. Small arteries were dissected and mounted on a micromyograph and the media-to-internal lumen ratio was evaluated; moreover, endothelium-dependent vasodilation to acetylcholine was assessed. A similar blood pressure-lowering effect and a similar reduction of the media-to-lumen ratio of small arteries was observed with the 2 drugs. Vascular collagen content was reduced and metalloproteinase-9 was increased by candesartan, but not by enalapril. Changes of circulating indices of collagen turnover and circulating matrix metalloproteinase paralleled those of vascular collagen. The 2 drugs equally improved endothelial function. In conclusion, antihypertensive treatment with drugs that inhibit the renin-angiotensin-aldosterone system activity is able to correct, at least in part, alterations in small resistance artery structure in hypertensive patients with NIDDM. Candesartan may be more effective than enalapril in reducing collagen content in the vasculature.

Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in humans.

BACKGROUND: Vascular structural alterations in small resistance arteries of patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. In fact, no difference in the smooth muscle cell volume (CV) between normotensive subjects (NT) and essential hypertensive patients was observed. However, experimental models of hypertension with chronic infusion of agonists of adrenergic receptors were characterized by the presence of smooth muscle cell hypertrophy or hyperplasia. Recently, we have observed the presence of vascular smooth muscle cell hypertrophy in patients with renovascular hypertension. OBJECTIVE: The aim of the study to investigate the structural characteristics of subcutaneous small resistance arteries of NT, of EH, and of patients with phaeochromocytoma (Phaeo). PATIENTS AND METHODS: Thirty Phaeo, 30 NT and 30 EH were included in the study. A biopsy of subcutaneous fat was taken from all subjects. Small resistance arteries (relaxed diameter 160-280 microm) were dissected and mounted on a micromyograph and the media : lumen ratio was calculated. In nine Phaeo, nine NT and 13 EH the cell volume was measured by an unbiased stereological principle, the 'disector' method. RESULTS No difference in smooth muscle cell volume was observed between groups. However, inward remodeling in Phaeo was less marked than in EH, although the increase in media : lumen ratio was similar compared with NT. However, the lack of changes in media cross-sectional area, compared with NT, suggest that there has been little hypertrophy, the changes observed thus being eutrophic. CONCLUSIONS: Our data show, based on a reasonably large sample, that a pronounced activation of the adrenergic system is not associated with vascular smooth muscle cell hypertrophy or hyperplasia in humans. It is therefore possible that adrenergic mechanisms may have a relevant role in the development of eutrophic remodeling in small vessels.