Subclinical Carotid Atherosclerosis and Reduced DAD Score for Cardiovascular Risk Stratification in HIV-Positive Patients / Aterosclerose Carotídea Subclínica e DAD Escore Reduzido para Estratificação de Risco Cardiovascular em Pacientes HIV Positivos

Abstract Background: HIV-positive patients are twice as likely than the general population to have a heart attack and are four times at greater risk of sudden death. In addition to the increased risk, these individuals present with cardiovascular events on average approximately 10 years earlier than the general population. Objective: To compare Framingham and reduced DAD (Data Collection on Adverse Effects of Anti-HIV Drugs Cohort) scores for cardiovascular risk assessment in HIV-positive patients and potential impact on clinical decision after evaluation of subclinical carotid atherosclerosis. Methods: Seventy-one HIV-positive patients with no history of cardiovascular disease were clinically evaluated, stratified by the Framingham 2008 and reduced DAD scores and submitted to subclinical carotid atherosclerosis evaluation. Agreement between scores was assessed by Kappa index and p < 0.05 was considered statistically significant. Results: mean age was 47.2 and 53.5% among males. The rate of subclinical atherosclerosis was 39.4%. Agreement between scores was 49% with Kappa of 0.735 in high-risk patients. There was no significant difference between scores by ROC curve discrimination analysis. Among patients with intermediate risk and Framingham and reduced DAD scores, 62.5% and 30.8% had carotid atherosclerosis, respectively. Conclusion: The present study showed a correlation between the scores and medium-intimal thickening, besides a high correlation between patients classified as high risk by the Framingham 2008 and reduced DAD scores. The high prevalence of carotid atherosclerosis in intermediate risk patients suggests that most of them could be reclassified as high risk.

Resumo Fundamento: Pacientes HIV positivos possuem 2 vezes maior risco que a população geral de apresentarem infarto e 4 vezes maior de morte súbita. Além do risco aumentado, esses indivíduos apresentam eventos cardiovasculares, em média, aproximadamente, 10 anos antes que a população geral. Objetivo: Comparar os escores Framingham e DAD reduzido para avaliação de risco cardiovascular em pacientes HIV positivos e o potencial impacto na decisão clínica após avaliação de aterosclerose carotídea subclínica. Métodos: Foram avaliados clinicamente 71 pacientes HIV positivos sem antecedentes de doenças cardiovasculares, estratificados pelos escores Framingham 2008 e DAD reduzido e submetidos a avaliação de aterosclerose carotídea subclínica. A concordância entre os escores foi avaliada pelo índice Kappa e os valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: A idade média foi 47,2 e 53,5% do sexo masculino. A ocorrência de aterosclerose subclínica foi de 39,4%. A concordância entre os escores foi de 49% com Kappa de 0,735 nos pacientes de alto risco. Não houve diferença significativa entre os escores por meio de análise de discriminação com curva ROC. Dos pacientes com risco intermediário no Framingham e DAD reduzido, 62,5% e 30,8% respectivamente apresentavam aterosclerose carotídea. Conclusão: O presente estudo mostrou correlação entre os escores e espessamento médio-intimal e alta concordância entre os pacientes classificados como alto risco nos escores Framingham 2008 e DAD escore reduzido. A observação de alta prevalência de aterosclerose carotídea em pacientes de risco intermediário sugere que grande parte desses pacientes poderia ser reclassificada como alto risco.

Discordant Lipid Pattern and Carotid Atherosclerotic Plaque. Importance of Remnant Cholesterol / Padrão Lipídico Discordante e Placa Aterosclerótica Carotídea. Importância do Colesterol Remanescente

Abstract Background: Subjects with levels of non-HDL-C 30 mg/dL above those of LDL-C (lipid discordance) or with high remnant cholesterol levels could have a greater residual cardiovascular risk. Objectives: To determine the prevalence of lipid discordance in a primary prevention population and analyze the clinical variables associated with it; To investigate the association between lipid discordance and remnant cholesterol with the presence of carotid plaque. Methods: Primary prevention patients without diabetes or lipid-lowering therapy were included. Regardless of the LDL-C level, we define "lipid discordance" if the non-HDL-C value exceeded 30 mg/dL that of LDL-C. Remnant cholesterol was calculated as total cholesterol minus HDL-C minus LDL-C when triglycerides were < 4.0 mmol/L. Ultrasound was used to assess carotid plaque occurrence. Multiple regression logistic models were performed. Results: The study included 772 patients (mean age 52 ± 11 years, 66% women). The prevalence of lipid discordance was 34%. Male sex and body mass index were independently associated with discordant lipid pattern. The prevalence of carotid plaque was higher in subjects with lipid discordance (40.2% vs. 29.2, p = 0.002). The multivariate analysis showed that the discordant lipid pattern was associated with the greater probability of carotid plaque (OR 1.58, 95% CI 1.08-2.34, p = 0.02). Similarly, a significant association between calculated remnant cholesterol and carotid plaque was found. Conclusion: Lipid discordance and presence of a higher level of calculated remnant cholesterol are associated with subclinical atherosclerosis. Our findings could be used to improve the residual cardiovascular risk evaluation.

Resumo Fundamento: Indivíduos com níveis de não HDL-C excedendo em 30 mg/dl aqueles de LDL-C (discordância lipídica) ou com altos níveis de colesterol remanescente poderiam ter maior risco cardiovascular residual. Objetivos: determinar a prevalência de discordância lipídica em uma população de prevenção primária e analisar as variáveis clínicas com ela associadas; investigar a associação de discordância lipídica e colesterol remanescente calculado com a presença de placa carotídea. Métodos: Pacientes de prevenção primária sem diabetes ou sem terapia hipolipemiante foram incluídos. Independentemente do nível de LDL-C, definiu-se "discordância lipídica" como um valor de não HDL-C excedendo em 30 mg/dl aquele de LDL-C. Calculou-se o colesterol remanescente como colesterol total menos HDL-C menos LDL-C na presença de triglicerídeos < 4,0 mmol/l. Usou-se ultrassom para avaliar a presença de placa carotídea. Modelos de regressão logística múltipla foram construídos. Resultados: Este estudo incluiu 772 pacientes (idade média, 52 ± 11 anos; 66% mulheres). A prevalência de discordância lipídica foi de 34%. Sexo masculino e índice de massa corporal mostraram associação independente com padrão lipídico discordante. A prevalência de placa carotídea foi maior em indivíduos com discordância lipídica (40,2% vs. 29,2; p = 0,002). A análise multivariada mostrou associação do padrão lipídico discordante com maior probabilidade de placa carotídea (OR: 1,58; IC95%: 1,08-2,34; p = 0,02). Da mesma forma, identificou-se uma significativa associação entre colesterol remanescente calculado e placa carotídea. Conclusão: Discordância lipídica e presença de nível mais alto de colesterol remanescente calculado acham-se associados com aterosclerose subclínica. Nossos achados podem ser usados para aprimorar a avaliação de risco cardiovascular residual.

Association between Fibrinogen and Carotid Atherosclerosis According to Smoking Status in a Korean Male Population

PURPOSE: Although inconsistent, reports have shown fibrinogen levels to be associated with atherosclerosis. Accordingly, since cigarette smoking is associated with increased levels of fibrinogen and atherosclerosis, it may also affect the association between fibrinogen and atherosclerosis. We investigated the associations between fibrinogen and carotid intima-media thickness (IMT) according to smoking status in a Korean male population. MATERIALS AND METHODS: Plasma fibrinogen levels were measured in 277 men aged 40-87 years without a history of myocardial infarction or stroke. High-resolution B-mode ultrasonography was used to examine the common carotid arteries. IMT level was analyzed both as a continuous (IMT-max, maximum value; IMT-tpm, 3-point mean value) and categorical variable (higher IMT; presence of plaque). Serial linear and logistic regression models were employed to examine the association between fibrinogen and IMT according to smoking status. RESULTS: Fibrinogen levels were positively associated with IMT-max (standardized beta=0.25, p=0.021) and IMT-tpm (standardized beta=0.21, p=0.038), even after adjusting for age, body mass index, systolic blood pressure, fasting glucose, and total cholesterol to high-density lipoprotein cholesterol ratio in current smokers (n=75). No significant association between fibrinogen and IMT, however, was noted in former smokers (n=80) or nonsmokers (n=122). Adjusted odds ratios (95% confidence interval) for having plaque per one standard deviation higher fibrinogen level were 2.06 (1.09-3.89) for current smokers, 0.68 (0.43-1.10) for former smokers, and 1.06 (0.60-1.87) for nonsmokers. CONCLUSION: Our findings suggest that cigarette smoking may modify the association between fibrinogen and carotid atherosclerosis. Further studies are required to confirm this finding in different populations.

Associação dos biomarcadores com aterosclerose e risco para doença coronariana em portadores de HIV / Association of biomarkers with atherosclerosis and risk for coronary artery disease in patients with HIV

FUNDAMENTO: O uso maciço da Terapia Antirretroviral (TARV) na população com vírus da imunodeficiência adquirida (HIV) coincidiu com um aumento das doenças cardiovasculares, causa importante de morbimortalidade nesse grupo. OBJETIVO: Determinar a frequência de aterosclerose carotídea e avaliar a associação entre os níveis dos biomarcadores e o espessamento da camada médio-intimal carotídea em indivíduos HIV positivos, atendidos em serviços de referência para HIV em Pernambuco. MÉTODOS: Corte transversal com 122 pacientes HIV positivos. Considerou-se aterosclerose carotídea subclínica o aumento da espessura da camada média intimal da carótida comum > 0,8 milímetros ou placas no ultrassom de carótidas. Os biomarcadores inflamatórios analisados foram IL6, IL1-β, TNF-α, PCR-ultrassensível, sVCAM-1 e sICAM-1. RESULTADOS: Dos 122 pacientes analisados, a maioria era de homens (60,7%), com > 40 anos (57,4%), em uso de TARV (81,1%). A prevalência de aterosclerose foi de 42,6% (52 casos). Pacientes com idade acima de 40 anos e Framingham intermediário ou alto apresentaram maior chance de desenvolver aterosclerose na análise univariada. Idade acima de 40 anos (OR = 6,57 IC 2,66 -16,2; p = 0,000), sexo masculino (OR = 2,76 IC 1,12-6,79; p = 0,027) e a condição de síndrome metabólica (OR = 2,27 IC 0,94-5,50; p = 0,070) mostraram-se associados à aterosclerose na análise multivariada. Níveis elevados de citocinas inflamatórias e moléculas de adesão não mostraram associação com a presença de aterosclerose. CONCLUSÃO: Não houve associação entre os biomarcadores inflamatórios, moléculas de adesão e presença de aterosclerose carotídea. Entretanto, evidenciou-se em homens, pessoas com mais de 40 anos, portadores de escore de Framingham intermediário/alto ou síndrome metabólica maior chance de aterosclerose subclínica.

BACKGROUND: The massive use of Highly-Active Antiretroviral Therapy (HAART) in individuals with human immunodeficiency virus (HIV) coincided with an increase in cardiovascular disease, a major cause of morbidity and mortality in this group. OBJECTIVE: To determine the frequency of carotid atherosclerosis and the association between biomarker levels and carotid intimal-medial thickening in HIV-positive individuals treated for HIV at referral centers in Pernambuco. METHODS: This was a cross-sectional study of 122 HIV-positive patients. Subclinical carotid atherosclerosis was considered with the presence of increased intimal-medial thickness of the common carotid artery > 0.8 mm or plaques in the carotid ultrasound. The following inflammatory biomarkers were analyzed: IL6, IL1-β, TNF-α, high-sensitivity CRP, sVCAM-1 and sICAM-1. RESULTS: Of the 122 patients analyzed, most were men (60.7%) aged > 40 years (57.4%) receiving HAART (81.1%). The prevalence of atherosclerosis was 42.6% (52 cases). Patients older than 40 years and intermediate or high Framingham score were more likely to develop atherosclerosis at the univariate analysis. Age older than 40 years (OR = 6.57, 95%CI: 2.66 to 16.2, p = 0.000), male gender (OR = 2.76, 95%CI: 1.12 to 6.79, p = 0.027) and presence of syndrome metabolic (OR = 2.27, 95%CI: 0.94 to 5.50, p = 0.070) were associated with atherosclerosis at the multivariate analysis. Elevated levels of inflammatory cytokines and adhesion molecules were not associated with the presence of atherosclerosis. CONCLUSION: There was no association between inflammatory biomarkers, adhesion molecules and presence of carotid atherosclerosis. However, a higher chance of subclinical atherosclerosis was observed in men, those older than 40 years, with intermediate / high Framingham score or metabolic syndrome.

Frequency and characteristics of metabolic syndrome in patients with symptomatic carotid atherosclerosis / Frecuencia y características del síndrome metabólico en pacientes con estenosis carotídea sintomática

Background: Metabolic syndrome (MetS) is associated with increased risk of carotid atherosclerosis. Aim: To estimate the frequency of MetS in patients with symptomatic carotid atherosclerotic disease, and to compare clinical, biochemical and ultrasonographic characteristics of patients with and without MetS. Material and methods: Cross-sectional study of 657 consecutive patients (412 males) with symptomatic carotid atherosclerotic disease. Carotid atherosclerosis was estimated by high resolution B-mode ultrasonography. National Cholesterol Education Program (NCEP) M criteria were used for estimation of MetS. Results: Metabolic syndrome was present in 55.6 percent of studied patients. Among patients with metabolic syndrome there was a significantly higher proportion of women, and mean values ofbody weight, body mass index, waist circumference, percentage of body fat, systolic and diastolic blood pressure, serum triglycerides, total cholesterol and glucose were significantly higher. Mean values of high density lipoprotein cholesterol and alcohol consumption were significantly lower in patients with MetS. No differences between patients with or without MetS, were observed for age, smoking, mean values of low density lipoprotein cholesterol, high sensitive C-reactive protein and fibrinogen, and for degree of carotidstenosis or severity of clinical manifestations. Conclusion: Half of these patients with carotid stenosis have features of the metabolic syndrome.

Antecedentes: El síndrome metabólico se asocia a un mayor riesgo de ateroesclerosis carotídea. Objetivo: Evaluar la frecuencia de síndrome metabólico en pacientes con ateroesclerosis carotídea sintomática y comparar las características clínicas, bioquímicas y ultrasonográficas en pacientes con y sin síndrome metabólico. Material y método: Estudio transversal de 657 pacientes consecutivos (412 varones) con ateroesclerosis carotídea sintomática. El síndrome metabólico fue diagnosticado de acuerdo a los criterios del National Cholesterol Education Program (NCEP) III. la ateroesclerosis carotídea se investigó mediante ultrasonografía de alta resolución modo B. Resultados: Se diagnosticó síndrome metabólico en 55.6 por ciento de los pacientes estudiados. Entre los sujetos portadores del síndrome había una mayor proporción de mujeres y el peso, índice de masa corporal, circunferencia de cintura, porcentaje de grasa corporal, presión arterial sistólica y diastólica y niveles séricos de triglicéridos, colesterol total y glicemia fueron mayores. los valores promedio de colesterol HDI y de consumo de alcohol fueron significativamente menores en los pacientes con síndrome metabólico. los pacientes con el síndrome consumían menos alcohol y tenían niveles de colesterol HDI más bajos. No se encontraron diferencias entre sujetos con y sin síndrome metabólico en edad, tabaquismo, lipoproteínas de baja densidad, proteína C reactiva ultrasensible, fibrinógeno, grado de estenosis carotídea o severidad de sus manifestaciones clínicas. Conclusiones: la mitad de estos pacientes con estenosis carotídea tiene un síndrome metabólico.

C-reactive Protein and Carotid Intima-media Thickness in a Population of Middle-aged Koreans / 예방의학회지

OBJECTIVES: This study was performed to evaluate the relationship between C-reactive protein (CRP) and carotid intima-media thickness (carotid IMT) in a population of middle-aged Koreans. METHODS: A total of 1,054 men and 1,595 women (aged 40-70 years) from Kanghwa County, Korea, were chosen for the present study between 2006 and 2007. We measured high-sensitivity CRP and other major cardiovascular risk factors including anthropometrics, blood pressure, blood chemistry, and carotid ultrasonography. Health related questionnaires were also completed by each study participant. Carotid IMT value was determined by the maximal IMT at each common carotid artery. The relationship between CRP level and carotid IMT was assessed using multiple linear and logistic regression models after adjustment for age, body mass index, menopause (women), systolic blood pressure, total/HDL cholesterol ratio, triglyceride level, fasting glucose, smoking, and alcohol consumption. RESULTS: Mean carotid IMT values from the lowest to highest quartile of CRP were 0.828, 0.873, 0.898, and 0.926 mm for women (p for trend<0.001), and 0.929, 0.938, 0.949, and 0.979 mm for men (p for trend=0.032), respectively. After adjustment for major cardiovascular risk factors, the relationship between CRP and carotid IMT was significant in women (p for trend=0.017), but not in men (p for trend=0.798). Similarly, adjusted odds ratio of increased IMT, defined as the sex-specific top quartile, for the highest versus lowest CRP quartiles was 1.55 (95% CI=1.06-2.26) in women, but only 1.05 (95% CI=0.69-1.62) in men. CONCLUSIONS: CRP and carotid IMT levels appear to be directly related in women, but not in men.

Detección de inflamación en placa aterosclerosa: rol de la tomografía por emisión de positrones y de la proteína C reactiva / Detection of inflammation in an atherosclerose plaque: the role of the positron emission tomography and C reactive protein

OBJECTIVES: To demonstrate that inflammatory atheromatose carotid plaques can be visualized with positron emission tomography with 18F-fluorodeoxyglucose (18FDG PET) in symptomatic patients, in order to correlate them with systemic inflammatory markers, such as CRP. METHOD: Fifteen patients with cerebral ischemia due to atherosclerotic carotid disease were studied. 18FDG uptake with PET was considered and blood samples were taken for determining high sensibility C reactive protein (HsCRP). RESULTS: The mean age of the patients was 66 years; 11 of them were males (73%) and 4 were females (27%). 18FDG PET was positive in 12 patients (80%), while 100% of the studied population had low risk HsCRP with normal white cell count. CONCLUSIONS: 18FDG PET proves active inflammation in carotid atheromatose plaques. There was no significant correlation between the presence of ahteromatose carotid plaques, HsCRP serum levels, and 18FDG PET study.

Circulating levels of interleukin-8 and vascular endothelial growth factor in patients with carotid stenosis

Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) are important factors that induce the migration and proliferation of endothelial cells, increase the vascular permeability, and the modulate chemotaxis of monocytes. These molecules have been found in human atherosclerotic plaques. However, it is not clear whether the circulating levels of IL-8 and VEGF correlate with the extents of carotid stenosis. In this study, we investigated the relationship between circulating levels of IL-8 as well as VEGF and the extents of carotid stenosis. Sera from 41 patients with carotid stenosis were assessed for concentrations of IL-8 and VEGF by enzyme-linked immunosorbent assay. The degree of stenosis of extracranial carotid artery was calibrated by carotid B- mode ultrasonography. The serum concentration of IL-8 (r=-0.04733, p>0.05) was not correlated with the degree of stenosis. However, the serum concentration of VEGF (r=0.4974, p<0.01) was significantly correlated with the degree of carotid stenosis. These findings suggest that increased serum level of VEGF might be a marker for higher degree of stenosis of extracranial carotid artery.

Study of extracranial blood flow and haemorhelogic factors in patients with cerebral vascular disease

This study was carried out to evaluate the role of extra- cranial blood vessels and hemorheological parameters in the pathogenesis of cerebral ischemia. So, a 50 patients with cerebrovascular disease and 20 healthy controls were subjected to assessment of vascular changes in the carotid arteries by ultrasonic Doppler flowmeter and some blood factors such as blood viscosity, red cell deformability and plasma fibrinogen. Blood vessel studies revealed vascular lesions in the carotid arteries in the form of atherosclerotic lesions with and without stenosis, while blood factors showed a significant increased level in patients with cerebral ischemia. There was a positive correlation between the vascular changes and the hemorheologic variables in patients suffering from cerebral ischemia. Also, extracranial blood vessels [Carotids] were demonstrated to have a role in the pathogenesis of cerebral ischemia

Risk factors in extracranial carotid disease.

One hundred patients with ischaemic cerebro vascular disease (TIA/RIND--67% and completed stroke--33%) were evaluated for various clinical and biochemical risk factors. Evidence of extra-cranial carotid vascular disease (ECCVD) was looked for by using Doppler scan and carotid angiography. Of the 28 patients with abnormal Dop scan, 27 were confirmed to have ECCVD by angiography. Though the history of hypertension was elicited in 40%, only 28% had BP of 160/95 mm Hg or more during hospital stay. Hypertension was twice more common in ECCVD group compared to the group with normal carotid vessels. Obesity was seen in 15%, diabetes mellitus in 10% and 1% had hyperuricaemia. Total cholesterol was elevated in 29% and HDL cholesterol fraction was decreased (less than 35 mg%) in 43%. The reduction of HDL cholesterol was more frequent in ECCVD group (63%) and in hypertensive (73%) patients. Lipoproteins, triglycerides, free fatty acids and phospholipids were not significantly affected.