Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional / Phenotype of haptoglobin and presence of subclinical vascular disease: Population study

Introducción y objetivos: La haptoglobina es una proteína implicada en la protección frente al daño oxidativo producido por el hierro de la hemoglobina. Esta proteína es polimórfica, con 3 isomorfas prevalentes en la población. Los portadores de la isoforma Hp2-2 tienen una menor capacidad antioxidante, y en la población con diabetes, un mayor riesgo de enfermedad vascular subclínica y de complicaciones cardiovasculares. Nuestro objetivo fue evaluar si dicha isomorfa se asocia con un mayor riesgo de arteriosclerosis carotídea en sujetos con y sin diabetes, libres de enfermedad cardiovascular. Pacientes y métodos: Estudio realizado en una población de entre 45 y 74años de edad seleccionada aleatoriamente del área noroeste de Madrid. Los participantes fueron caracterizados en cuanto a su estatus glucémico mediante una sobrecarga oral de glucosa y la determinación de la concentración de Hb1Ac. A todos ellos se les determinó el fenotipo de la haptoglobina mediante un ensayo inmunoenzimático y la presencia de arteriosclerosis carotídea mediante ecografía. Resultados: De los 1.256 participantes incluidos en el presente análisis (edad media 61,6 ± 6 años, 41,8% varones), la distribución de las isoformas de la haptoglobina fue la siguiente: Hp1-1: 13,3%, Hp1-2: 48,5% y Hp2-2: 38,2%. En comparación con los sujetos Hp1-1 y Hp1-2, aquellos con el fenotipo Hp2-2 tuvieron una mayor prevalencia de dislipemia (53,3% vs 43%, p < 0,0001) e hipertensión arterial (39,2% vs 32,2%, p = 0,012), y recibieron con más frecuencia tratamiento con estatinas (31,5% vs 21,6%, p < 0,0001) y con antihipertensivos (38,4% vs 30,8%, p = 0,006). Los portadores de la isoforma Hp2-2 tuvieron una mayor prevalencia de placas carotídeas (OR: 1,35; IC 95%: 1,07-1,69; p = 0,011), sin diferencias en dicha prevalencia en función del estatus glucémico. No existieron diferencias en el grosor íntima-media entre los diferentes fenotipos. La relación del fenotipo Hp2-2 con la presencia de placas en carótida fue independiente de la edad, del sexo, de la presencia de factores de riesgo (dislipemia, hipertensión y diabetes), de la concentración de colesterol LDL, proteína C reactiva y ácido úrico, de la presión arterial y del tratamiento con estatinas y antihipertensivos (OR: 1,31; IC 95%: 1,01-1,70; p = 0,044). Conclusión: Los sujetos con el fenotipo Hp2-2 de la haptoglobina tienen una mayor prevalencia de arteriosclerosis carotídea, que es independiente de la presencia de otros factores de riesgo cardiovascular y de su estatus glucémico

Introduction and objectives: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. Patients and methods: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. Results: Of the 1,256 participants included in the present analysis (mean age 61.6 ± 6 years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P < .0001) and arterial hypertension (39.2% vs. 32.2%, P = .012), and they more frequently received treatment with statins (31.5% vs 21.6%, P < .0001), and with antihypertensive agents (38.4% vs 30.8%, P = .006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P = .011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95% CI 1.01-1.70, P = .044). Conclusion: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status

Phenotype of haptoglobin and presence of subclinical vascular disease: Population study. / Fenotipo de la haptoglobina y presencia de enfermedad vascular subclínica: estudio poblacional.

INTRODUCTION AND OBJECTIVES: Haptoglobin is a protein involved in the protection against oxidative damage caused by iron in haemoglobin. This protein is polymorphic, with 3 isomorphs prevalent in the population. The carriers of the Hp2-2 isoform have a lower antioxidant capacity and, in the population with diabetes, an increased risk of subclinical vascular disease and cardiovascular complications. The objective of this study was to evaluate whether this isomorphy is associated with an increased risk of carotid arteriosclerosis in subjects with and without diabetes, and free of cardiovascular disease. PATIENTS AND METHODS: A study was conducted in a population between 45 and 74years of age, randomly selected from the northwest area of Madrid. The participants were characterised in terms of their glycaemic status by oral glucose overload and the determination of the concentration of Hb1Ac. The haptoglobin phenotypes in all of them were determined by means of an immunoenzymatic assay, and the presence of carotid arteriosclerosis by ultrasound. RESULTS: Of the 1,256 participants included in the present analysis (mean age 61.6±6years, 41.8% males), the distribution of the isoforms of haptoglobin was as follows: Hp1-1: 13.3%, Hp1-2: 48.5%, and Hp2-2: 38.2%. In comparison with subjects Hp1-1 and Hp1-2, those with the Hp2-2 phenotype had a higher prevalence of dyslipidaemia (53.3% vs 43%; P<.0001) and arterial hypertension (39.2% vs. 32.2%, P=.012), and they more frequently received treatment with statins (31.5% vs 21.6%, P<.0001), and with antihypertensive agents (38.4% vs 30.8%, P=.006). The carriers of the Hp2-2 isoform had a higher prevalence of carotid plaques (OR: 1.35, 95%CI: 1.07-1.69, P=.011), with no differences in that prevalence as regards the glycaemic status. There were no differences in the intima-media thickness between the different phenotypes. The relationship of the Hp2-2 phenotype with the presence of plaques in the carotid was independent of age, gender, presence of risk factors (dyslipidaemia, hypertension and diabetes), the concentration of LDL-cholesterol, C-reactive protein and uric acid, blood pressure, and treatment with statins, and hypertensive drugs (OR: 1.31, 95%CI 1.01-1.70, P=.044). CONCLUSION: Subjects with the Hp2-2 phenotype of haptoglobin have a higher prevalence of carotid arteriosclerosis, which is independent of the presence of other cardiovascular risk factors and their glycaemic status.

R46L polymorphism in the PCSK9 gene: Relationship to lipid levels, subclinical vascular disease, and erectile dysfunction.

BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. RESULTS: The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). CONCLUSION: In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.

Factores de riesgo asociados con el grosor íntima-media y la presencia de placas en arteria carótida: Estudio ESPREDIA / Risk factors associated with the carotid intima-media thickness and plaques: ESPREDIA Study

Objetivo: Evaluar si existen diferencias en el perfil de factores de riesgo asociados con el grosor íntima-media (GIM) y la presencia de placas carotídeas. Métodos: Estudio transversal de base poblacional, en 1.475 sujetos de entre 45 y 75años de edad, seleccionados de forma aleatoria de los registros de Atención Primaria del área noroeste de Madrid. Se les realizó una exploración física, una analítica y se les determinó el GIM en carótida común y la presencia de placas mediante ecografía. Resultados: El GIM medio de la población fue de 0,725±0,132mm. El 47% presentaban placas carotídeas. En el análisis multivariante, los factores relacionados con el GIM fueron: edad (β0,227, p<0,0001), sexo (β0,104, p<0,0001), presencia de hipertensión (β0,082, p=0,002), diabetes (β0,130, p<0,0001) y tabaquismo activo (β0,107, p<0,0001), presión arterial sistólica (PAS) (β0,219, p<0,0001) y concentración de colesterol LDL (β0,074, p=0,003), y de forma inversa, presión arterial diastólica (PAD) (β−0,124, p=0,001) y concentraciones de colesterol HDL (β−0,111, p<0,0001) y triglicéridos (β−0,060, p=0,028). La presencia de placas se asoció de forma directa con edad (OR1,08; IC95%: 1,05-1,10), sexo (OR1,95; IC95%: 1,52-2,51), tabaquismo activo (OR2,75; IC95%: 1,92-3,95), antecedente de hipertensión (OR1,58; IC95%: 1,22-2,04) y de diabetes (OR1,84; IC95%: 1,31-2,58), consumo de estatinas (OR1,56; IC95%: 1,19-2,04) y PAS (OR1,03; IC95%: 1,02-1,05), y de forma inversa con PAD (OR0,98; IC95%: 0,96-0,99). Conclusión: Los factores de riesgo asociados con el GIM y la presencia de placas son similares, un dato que apoya el continuo entre la hipertrofia de la capa muscular y el desarrollo de arteriosclerosis (AU)

Objective: To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. Methods: Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. Results: Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (β0.227, P<.0001), sex (β0.104, P<.0001), presence of hypertension (β0.082, P=.002), diabetes (β0.130, P<.0001) and current smoking (β0.107, P<.0001), systolic blood pressure (SBP) (β0.219, P<.0001) and LDL-cholesterol levels (β0.074, P=.003), and inversely, diastolic blood pressure (DBP) (β−0.124, P=.001), HDL-cholesterol (β−0.111, P<.0001) and triglyceride levels (β−0.060, P=.028). The presence of plaques was directly associated with age (OR1.08; 95%CI: 1.05-1.10), sex (OR1.95; 95%CI: 1.52-2.51), current smoking (OR2.75; 95%CI: 1.92-3.95), history of hypertension (OR1.58; 95%CI: 1.22-2.04) or diabetes (OR1.84; 95%CI: 1.31-2.58), statin treatment (OR1.56; 95%CI: 1.19-2.04) and SBP (OR1.03; 95%CI: 1.02-1.05), and inversely with DBP (OR0.98; 95%CI: 0.96-0.99). Conclusion: Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development (AU)

Relationship of the Adherence to a Mediterranean Diet and Its Main Components with CRP Levels in the Spanish Population.

Background: Adherence to a Mediterranean diet seems to be inversely associated with C-reactive protein (CRP) concentration. A 14-point Mediterranean Diet Adherence Screener (MEDAS) has been developed to assess dietary compliance. Objective: The aim of this study was to assess whether each of the MEDAS questions as well as their final score were associated with the levels of CRP in general Spanish population. METHODS: Cross-sectional analysis of 1411 subjects (mean age 61 years, 43.0% males) randomly selected from the general population. CRP levels were determined by a commercial ELISA kit. Adherence to the Mediterranean diet was measured by the 14-point MEDAS. Results: There was an inverse correlation between adherence to the Mediterranean diet and the CRP concentration, even after adjusting by age, gender, hypertension, metabolic syndrome, body mass index, statin treatment and hypertension treatment (p = 0.041). Subjects who consume ≥2 servings of vegetables per day (p = 0.003), ≥3 pieces of fruit per day (p = 0.003), ≥1 serving of butter, margarine, or cream per day (p = 0.041) or ≥3 servings of fish/seafood per week (p = 0.058) had significantly lower levels of CRP. Conclusions: Adherence to a Mediterranean-type diet measured by a simple questionnaire is associated with lower CRP concentration. However, this association seems to be particularly related to a higher consumption of vegetables, fruits, dairy products, and fish.

Risk factors associated with the carotid intima-media thickness and plaques: ESPREDIA Study. / Factores de riesgo asociados con el grosor íntima-media y la presencia de placas en arteria carótida: Estudio ESPREDIA.

OBJECTIVE: To evaluate whether there were any differences in the risk factor profile associated with either the intima-media thickness (IMT) or the presence of carotid plaques. METHODS: Cross-sectional study in 1475 subjects between 45 and 75years, randomly selected from the population of the Northwest area of Madrid (Spain). They had a physical exam, blood analysis, and ultrasound measurement of the IMT and of the presence of plaques. RESULTS: Mean IMT was 0.725±0.132mm. Forty seven percent of the participants had carotid plaques. In multivariate analysis, factors directly associated with the IMT were, age (ß0.227, P<.0001), sex (ß0.104, P<.0001), presence of hypertension (ß0.082, P=.002), diabetes (ß0.130, P<.0001) and current smoking (ß0.107, P<.0001), systolic blood pressure (SBP) (ß0.219, P<.0001) and LDL-cholesterol levels (ß0.074, P=.003), and inversely, diastolic blood pressure (DBP) (ß-0.124, P=.001), HDL-cholesterol (ß-0.111, P<.0001) and triglyceride levels (ß-0.060, P=.028). The presence of plaques was directly associated with age (OR1.08; 95%CI: 1.05-1.10), sex (OR1.95; 95%CI: 1.52-2.51), current smoking (OR2.75; 95%CI: 1.92-3.95), history of hypertension (OR1.58; 95%CI: 1.22-2.04) or diabetes (OR1.84; 95%CI: 1.31-2.58), statin treatment (OR1.56; 95%CI: 1.19-2.04) and SBP (OR1.03; 95%CI: 1.02-1.05), and inversely with DBP (OR0.98; 95%CI: 0.96-0.99). CONCLUSION: Factors associated with the IMT and the presence of plaques are similar, a finding that support a continuum between muscular layer hypertrophy and arteriosclerosis development.

Peripheral Atherosclerosis in Patients With Erectile Dysfunction: A Population-Based Study.

INTRODUCTION: The presence of erectile dysfunction (ED) could be a warning of vascular disease in different arterial territories. AIM: The aim of this study was to investigate the association between ED and the presence of atherosclerosis in 2 different vascular beds: carotid and lower limbs. METHODS: A total of 614 volunteers between 45 and 74 years of age (mean age 61.0 years) were randomly selected from the general population. ED was assessed using the International Index of Erectile Function (IIEF-5). Ankle-brachial index (ABI) measurement and carotid atherosclerosis were evaluated by echo-Doppler. MAIN OUTCOME MEASURES: Mean carotid intima-media thickness (IMT), prevalence of carotid plaques, mean ABI, and prevalence of ABI < 0.9 were the main outcome measures. RESULTS: ED was present in 373 subjects (59.7%). Mean carotid IMT was significantly higher in men with ED (0.762 ± 0.151 mm vs 0.718 ± 0.114 mm, P < .001). Also the global prevalence of carotid plaques was more frequent in men with ED (63.8% vs 44.8%, P < .001), even after adjusting by age, cardiovascular risk factors, and ongoing treatment (P = .039). Both the IMT and the prevalence of carotid plaques increased significantly with ED severity (P trend .004 and <.001, respectively). There were no significant differences between groups neither in mean ABI nor in the prevalence of subjects with ABI < 0.9. However, there was a trend to a lower ABI and a higher prevalence of ABI < 0.9 with increasing ED severity. CONCLUSION: In the general population, the presence of ED identifies subjects with higher atherosclerosis burden in carotid arteries but not in the lower extremities.

Carotid atherosclerosis severity in relation to glycemic status: a cross-sectional population study.

OBJECTIVE: Intima-media thickness (IMT) is increased in subjects with prediabetes or newly diagnosed diabetes. However, no previous studies have evaluated the relationship between the severity of carotid atherosclerosis, assessed by the presence of carotid plaques or stenosis, and the glycemic status, assessed either by fasting glucose, an oral glucose tolerance test (OGTT) or A1C levels. METHODS: Cross-sectional analysis of 1475 subjects (mean age 62 years, 44% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and A1C levels. An OGTT was performed in non-diabetic subjects. Carotid atherosclerosis was evaluated by echo-doppler. RESULTS: A 10.5% of the population had a previous diagnosis of diabetes. Of the 1320 non-diabetic participants, 349 (26.4%) had normal fasting glucose, normal glucose tolerance and A1C < 5.7%, and were considered controls. Prediabetes was diagnosed in 850 subjects (64.4%), and diabetes was newly diagnosed in 121 (9.2%). The prevalence of patients with carotid plaques was 34.2% in controls, 45.1% in prediabetics, 64.2% in newly diagnosed diabetics, and 72.9% in established diabetic patients. These numbers were 0.3%, 1.1%, 5.0% and 7.7% for carotid stenosis, respectively. In multivariate analysis, glycemic status remained significantly associated with the prevalence of carotid plaques after adjusting for age, sex, statin treatment, and cardiovascular risk factors. CONCLUSIONS: Glycemic status is associated with all grades of carotid atherosclerosis, from early signs, as demonstrated by the IMT, to intermediate degrees, as demonstrated by the presence of carotid plaques, to advance atherosclerosis, as established by the presence of carotid stenosis.