Differences between HIV-infected and uninfected adults in the contributions of smoking, diabetes and hypertension to acute coronary syndrome: two parallel case-control studies.

OBJECTIVES: The aim of the study was to assess the separate contributions of smoking, diabetes and hypertension to acute coronary syndrome (ACS) in HIV-infected adults relative to uninfected adults. METHODS: Two parallel case-control studies were carried out. In the first study, HIV-positive adults diagnosed with ACS between 1997 and 2009 (HIV+/ACS) were matched for age, gender and known duration of HIV infection with HIV-positive adults without ACS (HIV+/noACS), each individual in the HIV+/ACS group being matched with three individuals in the HIV+/noACS group. In the second study, each individual in the HIV+/ACS group in the first study was matched for age, gender and calendar date of ACS diagnosis with three HIV-negative individuals diagnosed with ACS between 1997 and 2009 (HIV-/ACS). Each individual in the HIV-/ACS group was then matched for age and gender with an HIV-negative adult without ACS (HIV-/noACS). After matching, the ratio of numbers of individuals in the HIV+/ACS, HIV+/noACS, HIV-/ACS and HIV-/noACS groups was therefore 1 : 3 : 3 : 3, respectively. We performed logistic regression analyses to identify risk factors for ACS in each case-control study and calculated population attributable risks (PARs) for smoking, diabetes and hypertension in HIV-positive and HIV-negative individuals. RESULTS: There were 57 subjects in the HIV+/ACS group, 173 in the HIV+/noACS group, 168 in the HIV-/ACS group, and 171 in the HIV-/noACS group. Independent risk factors for ACS were smoking [odds ratio (OR) 4.091; 95% confidence interval (CI) 2.086-8.438; P < 0.0001] and a family history of cardiovascular disease (OR 7.676; 95% CI 1.976-32.168; P = 0.0003) in HIV-positive subjects, and smoking (OR 4.310; 95% CI 2.425-7.853; P < 0.0001), diabetes (OR 5.778; 95% CI 2.393-15.422; P = 0.0002) and hypertension (OR 6.589; 95% CI 3.554-12.700; P < 0.0001) in HIV-negative subjects. PARs for smoking, diabetes and hypertension were 54.35 and 30.58, 6.57 and 17.24, and 9.07 and 38.81% in HIV-positive and HIV-negative individuals, respectively. CONCLUSIONS: The contribution of smoking to ACS in HIV-positive adults was generally greater than the contributions of diabetes and hypertension, and was almost twice as high as that in HIV-negative adults. Development of effective smoking cessation strategies should be prioritized to prevent cardiovascular disease in HIV-positive adults.

Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) and familial combined hyperlipidaemia (FCH) are common atherogenic disorders with great variability in cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have been performed between FH and FCH in relation to lipoprotein particle distribution. METHODS AND RESULTS: Risk factors and three measures of carotid intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and 200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR) spectroscopy. Compared with controls, IMT measures were increased in FH and FCH. FCH had the highest adjusted mean-maximum IMT. FH had twice low-density lipoprotein (LDL) particles than controls, but similar LDL subclass size and distribution. FCH subjects also had increased LDL particles and the highest number of small LDL (1519 ± 731 nmol l(-1) vs. 887 ± 784 nmol l(-1) in FH and 545 ± 409 nmol l(-1) in controls). Age, gender, cholesterol/high-density lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently associated with IMT in FH (r(2) = 0.38). The same variables, except cholesterol/HDL ratio, were associated with IMT in FCH (r(2) = 0.40). Among NMR lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%. CONCLUSION: FH and FCH subjects show increased carotid atherosclerosis in relation to classical risk factors. Lipoprotein subclasses do not substantially contribute to IMT variability.

Utilidad de las técnicas de imagen y biomarcadores en la predicción del riesgo cardiovascular en pacientes con enfermedad renal crónica en España: Proyecto NEFRONA* / Usefulness of imaging techniques and novel biomarkers in the prediction of cardiovascular risk in patients with chronic kidney disease in Spain: The NEFRONA project

Justificación: La enfermedad cardiovascular (ECV) es la primera causa de mortalidad en pacientes con enfermedad renal crónica (ERC). La valoración del riesgo cardiovascular a partir de los factores tradicionales es poco útil en esta población debido al fenómeno de «reverse epidemiology» y a la existencia de factores específicos derivados de la uremia. En este trabajo presentamos el protocolo del proyecto NEFRONA, un estudio prospectivo con el objetivo de evaluar la utilidad de técnicas de imagen y biomarcadores en la predicción de la ECV en la ERC. Métodos: A partir de noviembre 2009 se reclutarán 2.661adultos asintomáticos con ERC (estadios 3-5D) procedentes de consultas ambulatorias de nefrología y centros de diálisis distribuidos a lo largo del territorio español. Asimismo, se incluirán843 participantes sin ERC (grupo control). Además, semestralmente se registrará la aparición de acontecimientos cardiovasculares y mortalidad. Un equipo itinerante realizará una ecografía carotíde a para valorar el grosor íntima-media y la presencia de placas, y determinará el índice tobillo-brazo para la clasificación de la enfermedad ateromatosa. Para el estudio de las calcificaciones vasculares se utilizará un score basado en la presencia de calcificaciones en las arterias carótidas, femorales y braquiales, y en las válvulas cardíacas, mediante ecografía. Finalmente, se recogerán muestras de sangre para la determinación de biomarcadores. Discusión: El proyecto NEFRONA nos permitirá evaluar la utilidad de las técnicas de imagen y biomarcadores en la valoración de la enfermedad ateromatosa y su valor predictivo en la población española con ERC (AU)

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease(CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk, mainly due to the reverse epidemiology effect, and the presence of risk factors specifically related to uremia. Hereby, we present the protocol of a prospective study aimed to assess the predictive value of imaging techniques and biomarkers for CVD in patients with CKD. Methods: From November 2009, 2.661asymptomatic adult patients with stages 3-5D CKD will be recruited from nephrology services and dialysis units throughout Spain. Eighthundred forty-three participants without CKD (control group) will be also recruited. During the follow-up, CVD events and mortality will be recorded from all CKD patients. One trained itinerant team will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and ankle-brachialindex. Presence and type of calcifications will be assessed in carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. Finally, blood samples will be collected from all participants to study biomarkers. Discussion: The NEFRONA study will allow us to examine the usefulness of imaging techniques and biomarkers to assess atherosclerosis development and their predictive value in a Spanish population with CKD (AU)

[Usefulness of imaging techniques and novel biomarkers in the prediction of cardiovascular risk in patients with chronic kidney disease in Spain: the NEFRONA project]. / Utilidad de las técnicas de imagen y biomarcadores en la predicción del riesgo cardiovascular en pacientes con enfermedad renal crónica en España: Proyecto NEFRONA.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk, mainly due to the reverse epidemiology effect, and the presence of risk factors specifically related to uremia. Hereby, we present the protocol of a prospective study aimed to assess the predictive value of imaging techniques and biomarkers for CVD in patients with CKD. METHODS: From November 2009, 2.661 asymptomatic adult patients with stages 3-5D CKD will be recruited from nephrology services and dialysis units throughout Spain. Eight hundred forty-three participants without CKD (control group) will be also recruited. During the follow-up, CVD events and mortality will be recorded from all CKD patients. One trained itinerant team will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and ankle-brachial index. Presence and type of calcifications will be assessed in carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. Finally, blood samples will be collected from all participants to study biomarkers. DISCUSSION: The NEFRONA study will allow us to examine the usefulness of imaging techniques and biomarkers to assess atherosclerosis development and their predictive value in a Spanish population with CKD.

The effects of ABCG5/G8 polymorphisms on HDL-cholesterol concentrations depend on ABCA1 genetic variants in the Boston Puerto Rican Health Study.

BACKGROUND AND AIMS: ATP-binding cassette transporters G5/G8 (ABCG5/G8) are associated with HDL-C concentrations. To assess whether the effect of ABCG5/G8 genetic variants on HDL-C concentrations is dependent on ATP-binding cassette transporters A1 (ABCA1), we studied potential interactions between single nucleotide polymorphisms (SNPs) at ABCG5/G8 (i7892T > C, 5U145A > C, T54CA > G, T400KC > A) and ABCA1 (i27943G > A, i48168G > A, K219RG > A, i125970G > C, 3U8995A > G) genes with HDL-C concentrations. METHODS AND RESULTS: ABCG5/G8 and ABCA1 SNPs were genotyped in 788 subjects (228 men and 560 women) who participated in the Boston Puerto Rican Health Study. Biochemical measurements were determined by standard procedures. Genotyping was performed using TaqMan assays according to routine laboratory protocols. Significant gene-gene interactions for HDL-C were found between ABCG8 (5U145A > C, T54CA > G, T400KC > A) SNPs and ABCA1_i48168G > A genetic variant (P = 0.009, P = 0.042 and P = 0.036, respectively), in which carriers of the 5U145C and 54C alleles, and homozygotes for the T400 allele at ABCG8 genetic variants displayed lower HDL-C concentrations than homozygotes for the 5U145A and T54 alleles, and heterozygotes for the 400K allele at ABCG8 SNPs, only if they were also homozygous for the minor allele (A) at the aforementioned ABCA1 SNP. CONCLUSIONS: The gene-gene interactions reported in the present study support the hypothesis that the effect of ABCG5/G8 genetic variants on HDL-C concentrations is dependent on ABCA1 expression. Replication of these analyses to further populations, particularly with low HDL-C, is clearly warranted.

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study.

BACKGROUND AND AIMS: The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA). METHODS AND RESULTS: ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5) CONCLUSION: These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake.

A composite scoring of genotypes discriminates coronary heart disease risk beyond conventional risk factors in the Boston Puerto Rican Health Study.

BACKGROUND AND AIMS: Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs). METHODS AND RESULTS: We studied 11 SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1 unit (high-risk allele homozygous), 0.5 units (heterozygous) and 0 units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements. The mean score was higher in participants with prior CHD than those CHD-free (P=0.015), and the OR for CHD with a GPS>5 was 2.90 (P<0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (

The effect of a novel intergenic polymorphism (rs11774572) on HDL-cholesterol concentrations depends on TaqIB polymorphism in the cholesterol ester transfer protein gene.

BACKGROUND AND AIMS: Several genes have been shown to individually affect plasma lipoprotein metabolism in humans. Studies on gene-gene interactions could offer more insight into how genes affect lipid metabolism and may be useful in predicting lipid concentrations. We tested for gene-gene interactions between TaqIB SNP in the cholesterol ester transfer protein (CETP) and three novel single nucleotide polymorphisms (SNPs), namely rs11774572, rs7819412 and rs6995374 for their effect on metabolic syndrome (MetS) components and related traits. METHODS AND RESULTS: The aforementioned SNPs were genotyped in 1002 subjects who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Lipids were measured by standard procedures and lipoprotein subfractions, by proton nuclear magnetic resonance spectroscopy. Polymorphism rs11774572 was significantly associated with MetS (P=0.020), mainly driven by the association of the C allele with lower HDL-C (P=0.043) and higher triglycerides (P=0.049) and insulin (P=0.040) concentrations than TT subjects. A significant interaction between SNPs rs11774572 and CETP-TaqIB SNPs was found for HDL-C concentrations (P=0.006) and for HDL (P=0.008) and LDL particle sizes (P=0.009), small LDL (P=0.004), and VLDL concentrations (P=0.021), in which TT homozygotes displayed higher HDL-C concentrations and for HDL and LDL particle sizes, and lower small LDL and VLDL concentrations than C carriers, if they were CETP B2 allele carriers (P values ranging from <0.001 to 0.001). CONCLUSIONS: The rs11774572 polymorphism may play a role in the dyslipidemia that characterizes MetS. The interaction between rs11774572 and CETP-TaqIB SNPs on HDL-C concentrations provides some insights into the underlying mechanisms.

Increased intestinal cholesterol absorption in autosomal dominant hypercholesterolemia and no mutations in the low-density lipoprotein receptor or apolipoprotein B genes.

CONTEXT: Autosomal dominant hypercholesterolemia (ADH) is frequently caused by functional mutations in the low-density lipoprotein receptor (LDLR) or apolipoprotein B-100 (APOB) genes, but approximately 40% of ADH subjects disclose no such molecular defects, possibly pointing to alternative genetic mechanisms. OBJECTIVE: Our objective was to test the hypothesis that increased intestinal cholesterol absorption might play a role in the lipid abnormalities of subjects with ADH without identified genetic defects. DESIGN AND SETTING: This is a cross-sectional study of consecutive subjects with primary hyperlipidemia identified during an 18-month period in two lipid clinics. STUDY SUBJECTS: A total of 52 subjects with a clinical diagnosis of ADH were examined for molecular defects in LDLR and APOB. No APOB defects were found. Functional LDLR mutations occurred in 31 (60%) subjects, who received a diagnosis of familial hypercholesterolemia (FH). Those for whom no mutations could be identified were labeled as non-FH ADH. In addition, 38 subjects with familial combined hyperlipidemia (FCH) and 45 normolipidemic control subjects were studied. INTERVENTIONS: Interventions were diagnostic. MAIN OUTCOME MEASURES: Serum noncholesterol sterols were used as markers for the efficiency of intestinal cholesterol absorption. RESULTS: Adjusted campesterol to cholesterol ratios increased in the order non-FH ADH more than FH more than controls more than FCH, with mean values (95% confidence interval) in 10(2) mmol/mol cholesterol of 505 (424-600), 397 (345-458), 335 (294-382), and 284 (247-328), respectively. Thus, cholesterol absorption was lowest in FCH and highest in non-FH ADH. CONCLUSIONS: Increased intestinal cholesterol absorption may partially explain the high cholesterol levels of non-FH ADH subjects. Serum noncholesterol sterols are a useful tool for the differential diagnosis of genetic hypercholesterolemias, especially FCH and ADH unrelated to LDLR or APOB defects.

Comparación de la utilización de los servicios de urgencias hospitalarios entre la población inmigrante y la población autóctona / Emergency room use: comparison between immigrant population and autochthonous population

Objetivo: Cuantificar la demanda asistencial a un Servicio de urgencias hospitalario (SUH) de la población inmigrante (PI), describir sus características sociodemográficas y determinar si existen diferencias en la utilización de los servicios sanitarios entre la PI y la población autóctona (PA). Métodos: Durante el mes de febrero 2004, se incluyeron de forma prospectiva a todos los inmigrantes que acudieron a la sección de urgencias de Medicina (SUM), apareándolos por sexo y década de edad con pacientes autóctonos. Se analizaron variables sociodemográficas (en la PI) y clínicas, sanitarias y grado de satisfacción percibida (en ambos colectivos). Resultados: De un total de 2.829 pacientes visitados, 181 eran inmigrantes (6,4%). La mayoría eran jóvenes iberoamericanos, con predominio de mujeres, con estudios primarios, sin trabajo y con situación administrativa regularizada. Existía barrera idiomática en un 11% de los casos. Cuando se comparó con la PA, con mayor frecuencia la PI había consultado previamente a su llegada a la SUM con un facultativo (p<0,05) y, una vez en la SUM, se les practicó pruebas complementarias más a menudo (p<0,001). La satisfacción percibida fue mayor en la PI (p<0,05). No se obtuvieron diferencias en ambos colectivos respecto a los motivos de consulta y el destino final de los mismos. Conclusiones: Existe una demanda asistencial urgente cuantitativamente importante entre la PI, si bien cualitativamente no difiere en gran medida de la PA (AU)

Aim: To quantify immigrant population (IP) demand for medical care emergency room (ER), to assess their social and demographic characteristics and to determine the differences between the IP and the autochthonous population (AP) in the ER use. Methods: During february 2004, all immigrant patients attending ER were prospectively included. They were matched by sex and age decade with ER patients from the AP. Social and demographic characteristics from IP and clinical variables and satisfaction level from both groups were analyzed. Results: The total ER census was 2829 patients, with 181 from IP (6.4%). Most of them were young South Americans women with a primary school grade, unemployed and with a legal residence permission. There was an idiomatic barrier in 11% of cases. Compared to AP, IP went to see a physician before ER attendance more frequently (p<0.05), and once in the ER, had more testings done (p<0.001). The satisfaction was higher in IP (p<0.05) than in AP. Regarding chief complaint and final disposition, no differences between groups were obtained. Conclusions: IP demand for medical care at Ers is quantitatively important, but no qualitatively different from AP demand (AU)

[Medical emergencies in the adult immigrant]. / Urgencias médicas del inmigrante adulto.

The need for medical care of the immigrant population is growing in proportion to the increase in the number of immigrants resident in Spain. This article reviews the socio-demographic characteristics of the immigrant population that come for consultations in the emergency services and discusses those particularities, both medical (neurocysticercosis, tuberculosis, infection by the AIDS virus, hepatitis, malaria, parasitosis, Ulysses syndrome) and paramedical (knowledge of the health card, concept of medicine, language barrier), that differentiate them from the native population. Nonetheless, since we are dealing with a young population that is in principle healthy, their reasons for consultation do not greatly differ from the general population. It is worth drawing attention to the high level of satisfaction of this population with the care afforded them in the hospital emergency services.

Urgencias médicas del inmigrante adulto / Medical emergencies in the adult immigrant

La necesidad de atención médica de la población inmigrante crece en la misma proporción en que aumenta el número de inmigrantes residentes en España. En el presente trabajo se revisan las características sociodemográficas de la población inmigrante que consulta en urgencias y se discuten cuáles son las particularidades médicas (neurocisticercosis, tuberculosis, infección por el virus de la inmunodeficiencia adquirida, hepatitis, paludismo, parasitosis, síndrome de Ulises) y paramédicas (conocimiento de la tarjeta sanitaria, concepto de la medicina, barrera idiomática) que los diferencian de la población autóctona. No obstante, por tratarse de población joven, y en un principio sana, sus motivos de consulta no difieren en gran manera de la población general. Es de destacar la elevada satisfacción de esta población con la atención dispensada en los servicios de urgencias hospitalarios

The need for medical care of the immigrant population is growing in proportion to the increase in the number of immigrants resident in Spain. This article reviews the socio-demographic characteristics of the immigrant population that come for consultations in the emergency services and discusses those particularities, both medical (neurocysticercosis, tuberculosis, infection by the AIDS virus, hepatitis, malaria, parasitosis, Ulysses syndrome) and paramedical (knowledge of the health card, concept of medicine, language barrier), that differentiate them from the native population. Nonetheless, since we are dealing with a young population that is in principle healthy, their reasons for consultation do not greatly differ from the general population. It is worth drawing attention to the high level of satisfaction of this population with the care afforded them in the hospital emergency services

Ecografía del tendón de Aquiles en el diagnóstico de la hipercolesterolemia familiar / Ultrasonography of the Achilles’ tendon in the diagnosis of familial hypercholesterolemia

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