Resumo Objetivo: Investigar anormalidades vasculares e perivasculares nas artérias carótidas por meio de ultrassonografia e avaliar sua associação com mortalidade e variáveis clínicas em pacientes hospitalizados com COVID-19. Materiais e Métodos: Neste estudo prospectivo, 53 pacientes hospitalizados com COVID-19 grave foram avaliados e submetidos a ultrassonografia de carótida. Descrevemos os achados ultrassonográficos de carótida nesses pacientes. As correlações de características clínicas, demográficas, laboratoriais e de imagem foram analisadas e comparadas por meio de análise estatística. Resultados: A ultrassonografia carotídea demonstrou irregularidade da superfície luminal em 29 pacientes (55%), placas carotídeas em 30 pacientes (57%), infiltração perivascular em quatro pacientes (7,5%) e aumento da espessura médio-intimal (EMI) em 31 pacientes (58%). Dos pacientes com EMI aumentada, 19 (61%) morreram, com associação observada entre EMI aumentada e mortalidade por COVID-19 (p = 0,03). Um modelo de regressão logística mostrou que a probabilidade de óbito foi de 85% em pacientes com EMI aumentada e história de nefropatia crônica ou lesão renal aguda na internação (p < 0,05). Conclusão: Aumento da EMI, irregularidade da superfície luminal, placas carotídeas e infiltrados perivasculares foram encontrados na ultrassonografia carotídea em pacientes hospitalizados com COVID-19 grave. O aumento da EMI associado a danos nos rins pode aumentar o risco de morte.

Abstract Objective: To investigate vascular and perivascular abnormalities in the carotid arteries using ultrasound, as well as to evaluate their association with mortality and clinical variables in hospitalized patients with coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study in which 53 hospitalized patients with severe COVID-19 were evaluated and underwent carotid ultrasound. We documented the carotid ultrasound findings in these patients. Clinical, demographic, laboratory, and imaging features were analyzed and compared by statistical analysis to detect correlations between them. Results: Carotid ultrasound demonstrated luminal surface irregularity in 29 patients (55%), carotid plaques in 30 (57%), perivascular infiltration in four (8%), and increased intima–media thickness (IMT) in 31 (58%). Of the 31 patients with increased IMT, 19 (61%) died, and the association between increased IMT and COVID-19–related mortality was significant (p = 0.03). Logistic regression showed that the risk of death was 85% in patients who had increased IMT in combination with acute kidney injury at admission or a history of chronic kidney disease (p < 0.05). Conclusion: In hospitalized patients with severe COVID-19, carotid ultrasound can show increased IMT, luminal surface irregularity, carotid plaques, and perivascular infiltrates. The combination of increased IMT and kidney damage appears to increase the risk of death in such patients.

ABSTRACT COVID-19 and obesity are two pandemic diseases that the world is currently facing. Both activate the immune system and mediate inflammation. A sequence of disease phases in patients with severe COVID-19 results in a cytokine storm, which amplifies the subclinical inflammation that already exists in patients with obesity. Pro-inflammatory cytokines and chemotactic factors increase insulin resistance in obesity. Therefore, a greater systemic inflammatory response is establishe, along with an increased risk of thrombotic phenomena and hyperglycemic conditions. These changes further impair pulmonary, cardiac, hepatic, and renal functions, in addition to hindering glycemic control in people with diabetes and pre-diabetes. This review explains the pathophysiological mechanisms of these two pandemic diseases, provides a deeper understanding of this harmful interaction and lists possible therapeutic strategies for this risk group.

Resumo O SARS-CoV-2 é o responsável pela pandemia da COVID-19. O sistema imunológico é fator determinante no combate à infecção viral e, quando atua equilibrada e eficientemente, a doença é autolimitada e benigna. Uma parcela significativa da população, porém, apresenta resposta imune exacerbada. Os indivíduos diabéticos, hipertensos, obesos e com doenças cardiovasculares, infectados pelo vírus, apresentam maior chance de progredir para formas graves. Essas doenças estão relacionadas a processos inflamatórios crônicos e disfunção endotelial. Os receptores do tipo Toll estão presentes nas células de defesa e participam da imunopatologia de doenças cardiovasculares e metabólicas, levando à produção de citocinas pró-inflamatórias quando ativados. Devido à ação viral e à hiperativação do sistema imune, estados de hiperinflamação, hiperativação plaquetária, disfunção endotelial e hipercoagulabilidade são desenvolvidos, predispondo a tromboses venosas e arteriais. Discutiremos sobre a interação entre a COVID-19, a imunidade, o endotélio e a coagulação, como também sobre as possíveis causas de doenças cardiometabólicas impactarem negativamente na evolução da COVID-19.

Abstract SARS-CoV-2 is responsible for the COVID-19 pandemic. The immune system is a determinant factor in defense against viral infections. Thus, when it acts in a balanced and effective manner the disease is self-limited and benign. Nevertheless, in a significant proportion of the population, the immune response is exaggerated. When infected, patients with diabetes, hypertension, obesity, and cardiovascular disease are more likely to progress to severe forms. These diseases are related to chronic inflammation and endothelial dysfunction. Toll-like receptors are expressed on immune cells and play an important role in the physiopathology of cardiovascular and metabolic diseases. When activated, they can induce release of inflammatory cytokines. Hypercoagulability, hyperinflammation, platelet hyperresponsiveness, and endothelial dysfunction occur in immune system hyperactivity caused by viral activity, thereby increasing the risk of arterial and venous thrombosis. We discuss the interactions between COVID-19, immunity, the endothelium, and coagulation, as well as why cardiometabolic diseases have a negative impact on COVID-19 prognosis.

Resumo Fundamento: Pessoas que vivem com o HIV (HIV +) têm maior prevalência de aterosclerose e a desenvolvem mais precocemente do que a população geral. Objetivos: Foi avaliar e comparar as prevalências de aterosclerose avaliada pela medida da espessura mediointimal (EMI) das carótidas comuns e femorais, e do índice tornozelo-braquial (ITB) nos grupos controle e HIV com e sem inibidores de protease (IPs). Métodos: Foram incluídas 80 pessoas com HIV + [40 usavam IPs e 40 não] e 65 controles. O diagnóstico de aterosclerose foi determinado pela medição da EMI (carótidas e femorais) e do ITB. Fatores de risco clássicos para aterosclerose e específicos para o HIV foram comparados entre os grupos, usando testes estatístcos. O valor de p ≤ 0,05 foi cosiderado significativo. Resultados: A EMI > P75 ou presença de placa foi mais elevada no grupo de HIV sem IP que no controle (37,5% vs 19%, p = 0,04). A análise comparativa mostrou diferença significativa (p=0,014) na EMI nas artérias carótidas entre HIV + com IPs (0,71 ± 0,28 mm), sem IPs (0,63 ± 0,11 mm) e controles (0,59 ± 0,11 mm), A EMI na femoral não teve diferença significante entre os grupos. Não houve diferença significante entre os grupos controle e de HIV + quanto ao ITB. No entanto, observou-se uma diferença significativa (p=0,015) no ITB entre os grupos HIV + sem IPs (1,17 [1,08 - 1,23]), e controles [1,08 (1,07 - 1,17)]. Conclusão: Em pacientes com HIV, a aterosclerose é mais prevalente e parece ocorrer mais precocemente, com características distintas, em comparação a indivíduos HIV-negativos.

Abstract Background: The prevalence of atherosclerosis is higher in HIV-positive people, who also experience it earlier than the general population. Objectives: To assess and compare the prevalence of atherosclerosis evaluated by the intima-media thickness of carotid and femoral arteries, and by the ankle-brachial pressure index (ABPI) in HIV patients treated or not treated with protease inhibitors (PIs) and controls. Methods: Eighty HIV+ subjects (40 using PIs and 40 not using PIs) and 65 controls were included in the study. Atherosclerosis was diagnosed by (carotid and femoral) ITM measurement and ABPI. Classical risk factors for atherosclerosis and HIV were compared between the groups by statistical tests. A p ≤ 0.05 was considered significant. Results: An IMT > P75 or the presence of plaque was higher in the HIV+ than in the control group (37.5% vs 19%, p = 0.04). Comparative analysis showed a significant difference (p=0.014) in carotid IMT between HIV+ with PIs (0.71 ± 0.28 mm), without PIs 0.63 ± 0.11 mm and, and controls (0.59 ± 0.11 mm). There was no significant difference in femoral IMT between the groups or in ABPI between HIV+ subjects and controls. However, a significant difference (p=0.015) was found between HIV+ patients not treated with PIs (1.17 [1.08 - 1.23]), and controls 1.08 [1.07 - 1.17]). Conclusion: In HIV patients, atherosclerosis is more prevalent and seems to occur earlier with particular characteristics compared with HIV-negative subjects.

Objective To compare automatic and manual measurements of intima-media complex (IMC) in common carotid, common femoral and right subclavian arteries of HIV-infected patients in relation to a control group, taking into consideration the classical risk factors for atherosclerosis. Materials and Methods The study sample comprised 70 HIV-infected patients and 70 non-HIV-infected controls paired according sex and age. Automatic (gold standard) and manual measurements of IMC were performed in the carotid arteries. Manual measurements were also performed in common femoral and right subclavian arteries. Bland-Altman graphs were utilized in the comparison and the adopted level significance was 5%. Results Intima-media complex alterations were not observed in any of the individuals as the mean automatic measurement in the right common carotid (RCC) artery was considered as the gold standard. As the gold standard was compared with the manual measurements (mean, maximum and minimum), no clinically significant alteration was observed. As the gold standard was compared with other sites, the difference was statistically and clinically significant at the origin of right subclavian artery (RCC: 0.51 mm vs. 0.91 mm) (p < 0.001). Conclusion HIV-infected individuals are not at higher risk for atherosclerosis than the control population.

OBJETIVOS: Identificar precocemente a prevalência de aterosclerose, por causa do espessamento do complexo médio-intimal das carótidas comuns e do índice tornozelo-braço. Essas medidas foram relacionadas com os fatores de risco clássicos de aterosclerose e os específicos dos infectados pelo HIV (tempo de doença, tempo de tratamento, tipo de tratamento, tipo de terapia antirretroviral utilizada, CD4 e carga viral). MÉTODOS: Setenta casos infectados com o HIV foram avaliados pela medida automática do complexo médio-intimal nas carótidas e do índice tornozelo-braço. Consideraram-se os fatores de risco clássicos de aterosclerose (idade, sexo, hipertensão arterial sistêmica, tabagismo, hipercolesterolemia, hipertrigliceridemia, obesidade e história familiar de evento cardiovascular), as medidas antropométricas e as variáveis relacionadas ao HIV. O nível de significância assumido foi de 5%. RESULTADOS: O tempo médio de diagnóstico do HIV foi de 104,9 meses e de tratamento foi de 97,9 meses. Quanto ao tipo de tratamento, 47 (67,1%) fizeram uso de inibidor de protease por mais de seis meses e 36 (51,4%) estão em uso atualmente. O índice tornozelo-braço estava aumentado em um único paciente (0,7%) e não se evidenciou espessamento do complexo médio-intimal em nenhum indivíduo. Não existiu associação significante da medida do complexo médio-intimal da carótida comum direita com nenhuma das variáveis analisadas. CONCLUSÕES: Indivíduos jovens, sob o uso de terapia antirretroviral por cinco anos ou mais, não apresentaram espessamento do complexo médio-intimal ou aumento do índice tornozelo-braço. Não houve diferença do espessamento do complexo médio-intimal associada ao tipo de esquema antirretroviral utilizado ou nível de carga viral.

OBJECTIVES: To precociously identify the prevalence of atherosclerosis caused by thickening of the intima-media complex of the common carotid arteries and of the ankle brachial index. These measurements were associated with the classical risk factors of atherosclerosis and the specific factors of those infected by HIV (duration of disease, length of treatment, kind of treatment, kind of antiretroviral therapy used, CD4 and viral load). METHODS: Seventy cases infected by HIV were assessed by automatic measurement of the intima-media complex in the carotids and of the ankle brachial index. The classical risk factors of atherosclerosis (age, gender, systemic arterial hypertension, smoking, hypercholesterolemia, hypertriglyceridemia, obesity, and family history of cardiovascular events), anthropometric measurements and the variables related to HIV were taken into consideration. The adopted level of significance was 5%. RESULTS: The mean time of HIV diagnosis was 104.9 months, mean duration of treatment was 97.9 months. As regard to the type of treatment, 47 (67.1%) used protease inhibitor for more than six months and 36 (51.4%) are using it recently. The ankle brachial index was increased in one patient (0.7%), and the intima-media complex was not thickened in any individual. There was no significant association of the measurement of the intima-media complex of the right common carotid with any of the variables analyzed. CONCLUSIONS: Young individuals under the use of antiretroviral therapy for five years or more did not show increase in thickness of the intima-media complex or increase in the ankle brachial index, and there was no difference in the intima-media complex thickness associated with the therapeutical scheme of antiretroviral used or the viral load level.

Este artigo tem como objetivo revisar os aspectos descritos na literatura sobre o acometimento da macrovasculatura na esclerose sistêmica e avaliar a ocorrência e distribuição das alterações macrovasculares nos pacientes com esclerose sistêmica através do eco-Doppler e do índice tornozelo-braço, além da associação desses achados com as características demográficas, forma clínica, tempo de evolução da doença, fenômeno de Raynaud (FR), alterações digitais, ulcerações de membros, reabsorção de falange, amputação, bem como fatores de risco e antecedentes da doença ateromatosa. O estudo foi prospectivo, do tipo série de casos, constituído de 20 pacientes, sendo 19 do sexo feminino, com idade média de 46,30 anos. Todos os pacientes tinham fenômeno de Raynaud objetivo, 85% a forma clínica difusa, 55% alteração de polpa digital, 15% úlcera atual de membros, 25% reabsorção de falange, nenhuma amputação e 70% de um a quatro fatores de risco. Foram estudadas pelo eco-Doppler as artérias aorta e carótida, dos membros inferiores e superiores, para a avaliação de espessamento do complexo íntimo-medial e presença de placas e aneurismas. Nas artérias dos membros inferiores, foi também realizado o índice tornozelo-braço. O índice tornozelo-braço foi normal em todos os pacientes; entretanto, 12 (60%) destes apresentaram doença macrovascular pelo eco-Doppler, sendo nove (45%) na aorta, seis (30%) nas carótidas, uma (5%) nas artérias dos membros superiores e sete (35%) nas dos membros inferiores. Observou-se associação entre doença macrovascular e alterações de polpas digitais (p = 0,0045). A doença macrovascular foi identificada em 60% dos pacientes através do eco-Doppler, mas não pelo índice tornozelo-braço, que foi normal em todos. Verificou-se associação significante da doença macrovascular com as alterações atuais de polpas digitais, o que não ocorreu com as demais variáveis estudadas.

The objectives of this article are to review aspects described in the literature on macrovasculature onset in systemic sclerosis and to assess occurrence and distribution of macrovascular alterations in patients with systemic sclerosis using Doppler ultrasound and ankle-brachial index. In addition, the article evaluates the association of these findings with demographic characteristics, clinical form, clinical course of the disease, Raynauds phenomenon, digital changes, limb ulcers, reabsorption of phalanges, amputation, and risk factors and antecedents of atheromatous disease. A prospective, case series study of 20 patients was performed. The sample was comprised of 19 women, with a mean age of 46.30 years. All patients had objective Raynauds phenomenon, 85% were diffuse, 55% had digital pulp changes, 15% current limb ulcer, 25% reabsorption of phalange, no amputations, and 70% presented one to four risk factors. Studies were performed by color Doppler ultrasound of the aortic and carotid arteries and lower and upper limb arteries to assess thickening of the intima-media complex, presence of plaques and aneurysms. Ankle-brachial index was also performed in lower limb arteries. Ankle-brachial index was normal in all patients, but 12 (60%) had macrovascular disease assessed by Doppler ultrasound, nine (45%) of these in the aorta, six (30%) in the carotid arteries, one (5%) in the upper limb arteries, and seven (35%) in lower limb arteries. There was an association between macrovascular disease and digital pulp changes (p = 0.0045). Macrovascular disease was identified in 60% of the patients via Doppler ultrasound, but not via ankle-brachial index, which resulted normal in all patients. There was a significant association between macrovascular disease and current digital pulp changes, which did not occur with the other variables.

OBJETIVO: Avaliar a ocorrência e a distribuição das alterações macrovasculares em uma população com esclerose sistêmica (ES) por meio da ultra-sonografia Doppler (USG Doppler) e do índice tornozelo-braço (ITB). Foi investigada a associação destes achados com as características demográficas e clínicas dos pacientes, bem como fatores de risco e antecedentes da doença ateromatosa. MÉTODOS: Estudo prospectivo, tipo série de casos, constituído de 20 pacientes, sendo 19 do sexo feminino, com idade média de 46,30 anos. A forma clínica difusa esteve presente em 85% dos pacientes. Todos tinham fenômeno de Raynaud (FR), 55% apresentaram alteração de polpas digitais, 15% úlcera atual de membros e 25% reabsorção de falange. Não houve amputação e 70% apresentaram de um a quatro fatores de risco de aterosclerose. A aorta, as carótidas, bem como as artérias dos membros superiores (MMSS) e inferiores (MMII) foram estudadas por USG Doppler para a avaliação de espessamento do complexo íntima-medial (CIM), presença de placas e aneurismas. Nas artérias dos MMII, foi também realizado o ITB. RESULTADOS: O ITB foi normal em todos os pacientes, entretanto 12 (60%) destes apresentaram doença macrovascular (DMV), sendo 9 (45%) na aorta, 7 (35%) nos MMII, 6 (30%) nas carótidas e 1 (5%) nas artérias dos MMSS. Observou-se associação entre DMV e alterações de polpas digitais (p = 0,0045). CONCLUSÕES: A USG Doppler identificou DMV em 60% dos pacientes com ES. Nenhum paciente apresentou ITB anormal. Verificou-se associação significante da DMV com as alterações atuais de polpas digitais. As alterações macrovasculares encontradas não estão necessariamente associadas à esclerose sistêmica e podem decorrer do processo aterosclerótico.

OBJECTIVE: To assess the occurrence and distribution of the macrovascular alterations in a population with Systemic Sclerosis (SS) by means of Doppler ultrasound (Doppler US) and ankle-arm index (AAI). To investigate the assotiation of these findings with both demographic and clinical characteristics in the patients as well as with risk factors and antecedents of atheromatous disease. METHODS: Prospective study, of the series of cases type, comprising 20 patients, 19 of whom were women with a median age of 46.30 years. Eighty-five percent were of the diffuse form. All the patients had the Raynaud's phenomenon, 55% presented alteration of digital pulps, 15% current limb ulcers and 25% phalanx resorption. There were no amputations and 70% presented from 1 to 4 risk factors for atherosclerosis. The aorta, carotids as well as upper (ULs) and lower (LLs) limbs arteries were evaluated by Doppler US to assess thickening of the medio-intimal complex (MIC), presence of plaques and aneurisms. In the arteries of the LLs, AAI was also undertaken. RESULTS: AAI was normal in all patients, 12 patients (60%) presented macrovascular disease (MVD) comprising 9 (45%) of these in the aorta, 7 (35%) in LLs arteries , 6 (30%) in the carotids and 1 (5%) in ULs arteries. MVD and alterations of digital pulps were positivily associated (p = 0.0045). CONCLUSIONS: Doppler US identified MVD in 60% of our SS patients. No patients had abnormal AAI. MDV was positivily associated with digital pulps alterations. The macrovascular alterations found are not necessarily associated with systemic sclerosis, and may be due to atherosclerosis process.