Lipoprotein(a) levels in children with suspected familial hypercholesterolaemia: a cross-sectional study.

AIMS: Familial hypercholesterolaemia (FH) predisposes children to the early initiation of atherosclerosis and is preferably diagnosed by DNA analysis. Yet, in many children with a clinical presentation of FH, no mutation is found. Adult data show that high levels of lipoprotein(a) [Lp(a)] may underlie a clinical presentation of FH, as the cholesterol content of Lp(a) is included in conventional LDL cholesterol measurements. As this is limited to adult data, Lp(a) levels in children with and without (clinical) FH were evaluated. METHODS AND RESULTS: Children were eligible if they visited the paediatric lipid clinic (1989-2020) and if Lp(a) measurement and DNA analysis were performed. In total, 2721 children (mean age: 10.3 years) were included and divided into four groups: 1931 children with definite FH (mutation detected), 290 unaffected siblings/normolipidaemic controls (mutation excluded), 108 children with probable FH (clinical presentation, mutation not detected), and 392 children with probable non-FH (no clinical presentation, mutation not excluded). In children with probable FH, 32% were found to have high Lp(a) [geometric mean (95% confidence interval) of 15.9 (12.3-20.6) mg/dL] compared with 10 and 10% [geometric means (95% confidence interval) of 11.5 (10.9-12.1) mg/dL and 9.8 (8.4-11.3) mg/dL] in children with definite FH (P = 0.017) and unaffected siblings (P = 0.002), respectively. CONCLUSION: Lp(a) was significantly higher and more frequently elevated in children with probable FH compared with children with definite FH and unaffected siblings, suggesting that high Lp(a) may underlie the clinical presentation of FH when no FH-causing mutation is found. Performing both DNA analysis and measuring Lp(a) in all children suspected of FH is recommended to assess possible LDL cholesterol overestimation related to increased Lp(a).

Lipoprotein(a) in patients with hepatocellular carcinoma and portal vein thrombosis.

BACKGROUND: The mechanism for hypercoagulability in malignancy is not entirely understood. Although several studies report contrasting finding about the link between elevated plasma levels of the lipoprotein(a) [Lp(a)] and the possible recurrence of venous thromboembolism, we perform a study to evaluate the impact of the Lp(a) in the development of portal vein thromboembolism (PVT) in patients with HCC. METHODS: We compared 44 PVT patients with 50 healthy subjects and 50 HCC patients. RESULTS: The comparison between PVT patients and HCC showed in the former the mean value of serum lipoprotein levels was higher than 37.3 mg/dl (p = 0.000). The comparison between PVT versus healthy controls showed that in the former, mean value of serum lipoprotein levels was higher than 75 mg/dl (p = 0.000). The predictive value test of serum lipoprotein(a) on PVT was 0.72 and on HCC was 0.83. The odds ratio of lipoprotein(a) was 9.21 on PVT and 6.33 on HCC. CONCLUSION: Patients with PVT and HCC showed a statistical significant serum lipoprotein(a) level higher than the subjects with HCC and no PVT or the healthy subject. So we assume a role of lipoprotein(a) as predictor of venous thromboembolism in neoplastic patients.

Lipoprotein (a): Structure, Pathophysiology and Clinical Implications / Lipoproteína (a): Estrutura, Metabolismo, Fisiopatologia e Implicações Clínicas

The chemical structure of lipoprotein (a) is similar to that of LDL, from which it differs due to the presence of apolipoprotein (a) bound to apo B100 via one disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma concentration, which can be determined by use of monoclonal antibody-based methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30 mg/dL are associated with a two-fold risk of developing coronary artery disease. Usually, black subjects have higher lipoprotein (a) levels that, differently from Caucasians and Orientals, are not related to coronary artery disease. However, the risk of black subjects must be considered. Sex and age have little influence on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead to interference with the fibrinolytic cascade, accounting for an atherogenic mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a) on arterial wall is also a possible mechanism, lipoprotein (a) being more prone to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as a predisposing factor to atherosclerosis. Statin treatment does not lower lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to reduce lipoprotein (a), although confirmation of ezetimibe effects is pending. The reduction in lipoprotein (a) concentrations has not been demonstrated to reduce the risk for coronary artery disease. Whenever higher lipoprotein (a) concentrations are found, and in the absence of more effective and well-tolerated drugs, a more strict and vigorous control of the other coronary artery disease risk factors should be sought.

A partícula de lipoproteína (a) apresenta estrutura semelhante à da LDL, diferenciando-se pela presença da apolipoproteína (a) ligada por uma ponte dissulfeto à apolipoproteína B. Sua síntese ocorre no fígado e sua concentração plasmática varia de < 1 mg a > 1.000 mg/dL, podendo ser dosada de rotina em laboratório clínico por método baseado em anticorpos monoclonais. Acima de 20 a 30 mg/dL o risco de desenvolvimento de doença cardiovascular aumenta em cerca de duas vezes, o que não é válido para os afrodescendentes, que já apresentam normalmente níveis mais altos dessa lipoproteína, do que caucasianos e orientais. Entretanto, o risco para indivíduos negros também deve ser levado em conta. Gênero e idade exercem pouca influência na concentração de lipoproteína (a). A homologia com o plasminogênio, que interfere na cascata fibrinolítica, pode ser um mecanismo da aterogenicidade da lipoproteína (a). Entretanto, a deposição direta na parede da artéria também é um dos mecanismos possíveis, sendo a lipoprotrína (a) mais oxidável do que a LDL. De forma geral estudos prospectivos confirmam a lipoproteína (a) como fator predisponente à aterosclerose. O uso de estatinas não interfere no nível da lipoproteína (a), diferentemente da niacina e da ezetimiba, que promovem sua diminuição, embora essa última dependa de confirmação. Não está demonstrado que a redução de lipoproteína (a) resulte em diminuição de risco de doença arterial coronária. Diante de concentrações mais elevadas de lipoproteína (a) e na falta de medicações mais efetivas e de boa tolerabilidade, deve-se, pelo menos, procurar controlar, de forma mais rigorosa, os outros fatores de risco de doença arterial coronária.

Serum lipoprotein-A levels in healthy subjects indicate a lurking cerebro- and cardio-vascular risk in the younger population.

Lipoprotein-A (LpA) is an emerging independent risk factor for cerebro- and cardio-vascular diseases (CCVD). Recognizing its function and its normal distribution is of fundamental importance for a better understanding of CCVD patho-physiology. The present study evaluated plasma LpA levels of healthy university students using turbidimetric methods. Medians and inter-quartile differences obtained for male and female participants were 11.3mg/dL (3.1-30.7) and 20.9mg/dL (6.5-42.3), respectively, demonstrating a significant difference (P=0.017) between men and women. A third of students showed plasma concentrations above reference values. Our results indicate that 33% of students possess a hidden independent risk factor for CCVD. Multi-disciplinary evaluation and characterization of young individuals should be recommended in an attempt to take early preventive measures and to eliminate possible modifiable risk factors such as sedentary lifestyle, smoking, hypertension, obesity and atherogenic diet.

Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vasucular wall.

AIM: A new antibody reacted with an epitope in Lp(a) that has undergone oxidation treatment, but is not present in native Lp(a), was developed. Thus, we determined serum oxidized Lp(a) concentration in healthy volunteers, and coronary artery disease (CAD), diabetes mellitus (DM), and hypertensive patients. METHODS: We measured serum levels of oxidized Lp(a), Lp(a), LDL-cholesterol and HDL-cholesterol in 122 consecutive patients who underwent routine coronary angiography and had significant coronary artery stenosis (>75%), and 164 age-matched healthy volunteers. Moreover, serum native Lp(a), oxidized Lp(a) concentration, and pulse wave velocity (PWV) were determined in 181 hypertensive patients. RESULTS: Oxidized Lp(a) level in CAD patients with DM was significantly higher than in healthy volunteers (p<0.01). Moreover, serum oxidized Lp(a) concentration showed a significant positive correlation with pulse wave velocity, an index of arteriosclerosis (r=0.431, p<0.01). Of importance, the deposition of oxidized Lp(a) was readily detected in calcified areas of coronary arteries in patients with myocardial infarction. CONCLUSION: The present study demonstrated that oxidized Lp(a) may be a new risk factor for coronary artery disease. As the deposition of oxidized Lp(a) was detected in calcified areas of coronary arteries, oxidized Lp(a) might be implicated in endothelial dysfunction.

Risk factors for stroke and lipid-lowering effect of pravastatin on the risk of stroke in Japanese patients with hypercholesterolemia: analysis of data from the MEGA Study, a large randomized controlled trial.

BACKGROUND: The aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study. METHODS: Multivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated. RESULTS: In 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26-0.87] and 0.59 [0.38-0.92], respectively)--giving a negative PTE of -38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone. CONCLUSIONS: Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin's LDL-C-lowering effect alone, suggesting pleiotropic effects.

Effects of either tibolone or continuous combined transdermal estradiol with medroxyprogesterone acetate on coagulatory factors and lipoprotein(a) in menopause.

BACKGROUND/AIM: The aim of this prospective controlled study was to compare the effects of two therapies for menopause on factor VII (FVII) and hemostatic variables. METHODS: Postmenopausal women were assigned to receive one of the following treatments: transdermal estradiol (TTS E2; 50 microg) combined in a continuous sequential regimen with oral medroxyprogesterone acetate (MPA; 10 mg/day for 12 days) (group A; n = 20), tibolone (2.5 mg/day) (group B; n = 21) or placebo (group C; n = 19). Sixty women completed the 1-year treatment and underwent follow-up examinations after 3, 6 and 12 months. RESULTS: TTS E2/MPA induced various changes in procoagulatory factors. At 12 months, fibrinogen, activated FVII (FVIIa) and coagulative FVII (FVIIc) had increased by 10.7, 12.9 and 3.7%, respectively. Among the fibrinolytic factors, plasminogen and alpha2-antiplasmin increased by 11.3 and 7.2%, respectively. Lipoprotein(a) [Lp(a)] and antithrombin III (ATIII) did not show any significant variation. Tibolone induced some changes toward a more homogeneous antithrombotic profile. Fibrinogen, FVIIa and FVIIc decreased significantly by 7.5, 8.1 and 21.3%, respectively. Plasminogen increased (by 11.8%) and Lp(a) decreased (by 28.4%). ATIII was unchanged with tibolone therapy. CONCLUSION: Our results show that tibolone induces a significant reduction in FVIIc and Lp(a) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen.

Biochemical correlates of lipoprotein(a) in a general adult population. Possible implications for cardiovascular risk assessment.

BACKGROUND: Evidence has been provided that lipoprotein(a) (Lp(a)) may be an important cardiovascular risk factor. Recognition of potential Lp(a) variability associated with common diseases, such as diabetes, chronic renal dysfunction, impaired liver function and acute/chronic inflammation, is important to optimize the clinical usefulness of this measurement. METHODS: We performed a retrospective analysis on our Laboratory Information System to retrieve results of fasting plasma glucose (FPG), creatinine, albumin, high sensitivity-C reactive protein (Hs-CRP) and Lp(a) tests, which were performed on all outpatients referred by general practitioners for routine blood testing during the last 5 years. RESULTS: Cumulative results for all of the above parameters were retrieved for 1,195 adults. After stratifying Lp(a) results according to the respective threshold values of albumin, estimated glomerular filtration rate (e-GFR), FPG and Hs-CRP, a significant difference was observed only among subjects with increased Hs-CRP levels (170 mg/l vs. 125 mg/l; P < 0.001). The frequency of Lp(a) values > or =300 mg/l was greater in those with increased Hs-CRP levels (36 vs. 26%; P = 0.037)-but not in those with abnormal values of albumin, e-GFR or FPG-compared with their counterparts with normal values of these parameters. In multiple regression analysis, age (r = 0.112; P < 0.001), Hs-CRP (r = 0.102; P = 0.001) and e-GFR (r = 0.106; P = 0.003) were independent predictors of Lp(a). CONCLUSIONS: The evaluation of laboratory markers of glucose homeostasis and liver function seems unnecessary when measuring Lp(a) for cardiovascular risk assessment. Conversely, Hs-CRP and probably GFR might be of clinical value to identify individuals whose serum Lp(a) levels can be transiently or chronically increased.

Lipoproteína (a) em pacientes portadores de doença arterial obstrutiva periférica e/ou diabetes mellitus tipo 2 / Lipoprotein (a) in patients with peripheral arterial obstructive disease and/or type 2 diabetes mellitus

INTRODUÇÃO: A doença arterial obstrutiva periférica (DAOP) constitui um excelente marcador para a aterosclerose sistêmica. Entre os fatores de risco para essa doença está o diabetes mellitus tipo 2 (DM2). Acredita-se que a lipoproteína (a) [Lp(a)] esteja ligada a risco aumentado de aterosclerose, embora os mecanismos que levem a esse aumento não sejam completamente conhecidos. Níveis elevados de Lp(a) parecem estar associados a risco aumentado de doença arterial coronariana (DAC), assim como DAOP e doença cerebrovascular. OBJETIVO: Avaliar os níveis plasmáticos de Lp(a) e outras variáveis lipídicas em um grupo de pacientes com DAOP e/ou DM2. MATERIAL E MÉTODOS: Níveis plasmáticos de Lp(a), colesterol total (CT), colesterol da lipoproteína de alta densidade (HDL-c), colesterol da lipoproteína de baixa densidade (LDL-c), triglicérides (TG) e apolipoproteínas A-I e B foram medidos em amostras de sangue de 12 indivíduos comprovadamente não-portadores de DAOP e DM2 (controles), 17 pacientes portadores de DAOP, 18 pacientes com DM2 e 19 pacientes portadores de DAOP e DM2 simultaneamente. Os participantes desse estudo foram selecionados buscando-se homogeneidade e semelhança estatística em relação às variáveis sexo, idade e nível socioeconômico. RESULTADOS: A Lp(a) apresentou tendência a elevação tanto no grupo de pacientes com DAOP quanto naquele com DM2 + DAOP. Foram encontradas diferenças significativas entre os grupos para as dosagens de HDL-c e Apo A-I, inclusive com correlação positiva entre esses parâmetros. A relação CT/HDL-c apresentou diferença estatística significativa entre os grupos. Foram observadas correlações positiva entre Lp(a) e LDL-c, e negativa entre o índice tornozelo-braquial (ITB) e a Lp(a). CONCLUSÃO: Para as variáveis lipídicas estudadas foram observadas diferenças estatísticas significativas apenas entre os níveis plasmáticos de HDL-c e Apo A-I. Para o parâmetro Lp(a) foram observados níveis plasmáticos mais elevados...

BACKGROUND: Peripheral arterial obstructive disease (PAOD) constitutes an excellent marker for systemic atherosclerosis and type 2 diabetes mellitus (DM2) is among the greatest risk factors for this disease. It is believed that lipoprotein (a) [Lp(a)] is linked to increased risk of atherosclerosis, although the mechanisms responsible for that are not widely known. Elevated levels of Lp(a) seem to be associated with a higher risk of coronary artery disease (CAD), as well as PAOD and cerebrovascular disease. OBJECTIVES: To assess the plasma levels of Lp(a) and other lipid parameters in patients with PAOD and/or DM2. Material and methods: Plasma levels of Lp(a), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and apolipoproteins A-I and B were measured in blood samples of 12 subjects carrying neither PAOD nor DM2 (control group), 17 patients with PAOD, 18 with DM2 and 19 with both PAOD and DM2. The subjects selected for this study showed homogeneity and no statistical difference for gender, age, and socioeconomic status. RESULTS: The Lp(a) showed a tendency to elevation both in groups PAOD only and PAOD + DM2 simultaneously. Significant differences were observed among the groups as to HDL-c and apolipoprotein A-I levels, with positive correlation between these two parameters. TC/HDL-c ratio showed significant difference among the groups. Positive correlation was found between Lp(a) and LDL-c, and negative one, between the ankle-arm index and LP(a). CONCLUSION: As to the lipid parameters studied, significant statistical differences were found between HDL-c and apolipoprotein A-I plasma levels only. For Lp(a) parameter, higher plasma levels were observed in PAOD and PAOD + DM2, which have also shown concomitant and significant HDL-c reduction.

Risk factors for ischemic stroke subtypes: the Atherosclerosis Risk in Communities study.

BACKGROUND AND PURPOSE: To evaluate risk factors for ischemic stroke by its subtypes may contribute to more effective prevention of ischemic stroke, but few prospective studies have characterized risk factors for specific subtypes of ischemic stroke. METHODS: Between 1987 and 1989, 14,448 men and women aged 45 to 64 years and free of clinical stroke took part in the first examination of the Atherosclerosis Risk in Communities study. The incidence of stroke was ascertained from hospital surveillance records. RESULTS: During an average follow-up of 13.4-years, 531 incident ischemic strokes occurred (105 lacunar, 326 nonlacunar, and 100 cardioembolic). Blacks had a 3-fold higher multivariate-adjusted risk ratio of lacunar stroke compared with whites. No racial difference in nonlacunar or cardioembolic strokes was found after adjusting for prevalent risk factors. In addition to traditional risk factors, nontraditional risk factors, such as waist-to-hip ratio, history of coronary heart disease, left ventricular hypertrophy, lipoprotein(a), and von Willebrand factor, were associated with increased risk for nonlacunar stroke, whereas lacunar stroke was related to only 1 nontraditional risk factor, white blood cell count. The population-attributable fraction (PAF) for hypertension was approximately 35% for all ischemic stroke subtypes. The respective PAFs for diabetes and current smoking were 26.3% and 22.0% for lacunar versus 11.3% and 11.4% for nonlacunar stroke. The PAF for elevated von Willebrand factor was greater than that for current smoking for cardioembolic stroke. CONCLUSIONS: The impact of traditional and nontraditional risk factors other than hypertension on the incidence of ischemic stroke varied according to its subtype.

Risk factors for cardiovascular event recurrence in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Numerous studies have identified risk factors and markers associated with incidence of cardiovascular disease (CVD). However, few studies have examined whether established risk factors, novel blood markers, carotid ultrasonography, or ankle-brachial index can predict recurrent CVD events. METHODS AND RESULTS: We analyzed the relation of established risk factors and markers of atherosclerosis with the risk of recurrent CVD in 766 participants. Over a mean of 8.7 years of follow-up, 70 women and 243 men had a recurrent CVD event (85.3% coronary heart disease and 23.7% stroke). Adjusting for age and sex, this study found that established risk factors were associated with recurrent CVD events in the anticipated direction. Being in the highest (vs lowest) quartiles of lipoprotein (a), fibrinogen, white blood cells, and creatinine at baseline were associated with 47%, 69%, 65%, and 81%, respectively, greater risk of a CVD event, and being in the highest quartile of albumin was associated with 39% lower risk. Being in the highest (vs lowest) quartile of carotid intima-media thickness (IMT) was associated with a doubling of risk, and having carotid plaque with acoustic shadowing (vs having no plaque) was associated with 83% increased risk of a CVD event. After adjustment for established risk factors, creatinine, albumin, and carotid IMT in the highest quartile (vs lowest quartile) and carotid plaque with acoustic shadowing (vs no plaque) were independently associated with recurrent CVD events. CONCLUSION: Established risk factors, but only a few of novel risk factors and markers, were independent predictors of recurrent CVD events.

Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies.

OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years). METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli. RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3% (n = 39 cases) and 0.2% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95% CI, 2.60-12.16), body mass index (OR, 3.88; 95% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95% CI, 1.44-6.84), systolic BP (OR, 3.46; 95% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound. CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.

Relevance of post-methionine homocysteine and lipoprotein (a) in evaluating the cardiovascular risk in young CAD patients.

BACKGROUND: Aims of our study were to evaluate the prevalence of high lipoprotein (a) [Lp(a)] and homocysteine levels - both in the fasting state (FHcy) and post-methionine (PMHcy) - in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia. MATERIALS AND METHODS: We studied 140 patients with angiographically documented CAD (24 women

Elevados niveles séricos de lipoproteína (a) en una población afro-venezolana / High serum (a) in a afro-venezuelan population

Altas concentraciones de Lipoproteína (a) [Lp)a)] son consideradas un factor de riesgo independiente para la enfermedad cardiovascular, sin embargo su determinación no se realiza como prueba de rutina en la evaluación de dicho riesgo. El propósito de este estudio fue determinar los niveles séricos de Lp(a) en individuos de las poblaciones de Maracaibo, una localidad con predominio blanco-hispánico, y de Bobures, una localidad afrovenezolana, ambas ubicadas en el Estado Zulia, Venezuela. para ello se seleccionaron al azar un total de 112 individuos, 57 de Maracaibo (edad promedio 41,8 ± 13,5 años), y 55 de Bobures (edad promedio 31,4 ± 17,4 años) a los cuales se les determinó en condiciones basales glicemia, perfil lípidico y Lp(a). Para la cuantificación sérica de Lp(a) fue utilizado un Kit comercial basado en ELISA de doble anticuerpo monoclonal contra apo-B100 y contra apo(a) (Heber Biotech BioSCREEN Lp(a), La Habana, Cuba). El colesterol total y el colesterol de HDL fueron significativamente más elevados en los individuos de Maracaibo que en los de Bobures (p<0.009 y p<0.001 respectivamente), mientras que los niveles de Lp(a) séricos fueron significativamente más elevados (p<0.001 en la población afrovenezolana (media de 59,0 mg/dl) que en los blancos hispánicos) (media de 29,0 mg/dl). Nuestros rsultados sugieren que la población afrovenezolana estudiada al tener concentraciones de Lp(a) dos veces más elevada que la muestra de blancos-hispánicos estudiados y por encima del rango normal de 30 mg/dl, tienen un mayor riesgo de enfermedad cardiovascular, por lo tanto deben ser realizados estudios destinados a determinar de los subtipos de Lp(a) presentes en esta población

Changes in endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism.

OBJECTIVE: This case-control study was carried out to assess the alteration of endothelium-dependent arterial dilation before and after subtotal thyroidectomy in subjects with hyperthyroidism. PATIENTS AND METHODS: The study subjects included 12 patients with hyperthyroidism and 39 apparently healthy individuals. We performed a subtotal thyroidectomy on the hyperthyroid patients. The endothelium-dependent arterial dilation was determined with a high-resolution ultrasound method in each patient at the hyperthyroid stage before treatment (stage H), the euthyroid stage induced immediately before surgery (stage E), and the transient hypothyroid stage 1 or 2 months after surgery (stage L). RESULTS: The flow-mediated arterial dilation decreased significantly from H to E and from E to L (P < 0.001). As compared with H, baseline blood flow decreased markedly at stages E and L (P < 0.001). The flow-mediated arterial dilation and baseline blood flow in the control subjects were very close to those at stage E of the hyperthyroid patients. The absolute change in the flow-mediated arterial dilation showed significant negative correlation with the changes in TSH (r =-0.86, P < 0.001), lipoprotein (a) [Lp(a)] (r =-0.77, P < 0.001) and low density lipoprotein (LDL) (r =-0.79, P < 0.001), and significant positive correlation with changes in fT3 (r =+0.88, P < 0.001). The absolute change in the baseline blood flow showed significant positive correlation with the change in fT3 (r =+0.85, P < 0.001) and significant negative correlation with the change in TSH (r =-0.63, P < 0.01). CONCLUSION: The endothelium-dependent arterial dilation increases significantly in untreated hyperthyroid patients, and decreases markedly after a subtotal thyroidectomy. Therefore, we conclude that the endothelium is more responsive to reactive hyperaemia in the hyperthyroid than the euthyroid state.

Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study.

Risk prediction functions for incident coronary heart disease (CHD) were estimated using data from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of CHD in 15,792 persons recruited in 1987-1989 from four U.S. communities, with follow-up through 1998. Predictivity of which individuals had incident CHD was assessed by increase in area under ROC curves resulting from adding nontraditional risk factors and markers of subclinical disease to a basic model containing only traditional risk factors. We also assessed the increase in population attributable risk. The additional factors were body mass index; waist-hip ratio; sport activity index; forced expiratory volume; plasma fibrinogen, factor VIII, von Willebrand factor, and Lp(a); heart rate; Keys score; pack-years smoking; and subclinical disease marker carotid intima-media thickness. These factors substantially improved prediction of future CHD for men, less for women, and also increased attributable risks.

Estudo de parâmetros bioquímicos e biológicos no hipotireoidismo sub-clínico / Study of biochemical and biological parameters in subclinical hypothyroidism

O objetivo deste trabalho foi o estudo de parametros bioquimicos (homocisteina,Lp(a), ApoA e ApoB) e biologicos (dilatação arterial endotélio dependente e dilatação arterial após nitrato sublingual) em mulheres com hipotireoidismo sub-clinico;nas pacientes que apresentaram alteração nos parametros biologicos foram estudados novamente todos os parametros,bioquimicos e biologicos após o tratamento com levotiroxina.Os resultados mostraram alteração na dilatação arterial endotélio / The objective of this work was to study biochemical ( homocysteine,Lp(a),ApoA and ApoB) and biological ( endothelium-dependent arterial dilation and arterial dilation after sublingual nitrate) parameters in women with subclinical hypothyroidism;in patients with abnormal biological parameters,biochemical and biological parameters were studied again after levothyroxine therapy.Results show abnormal endothelium-dependent arterial dilation...

Accelerated atherosclerosis with apolipoprotein(a) and oxidized low-density lipoprotein deposition in acute rejection of transplanted kidney: analogous to atherosclerosis.

Atherosclerosis is a chronic inflammatory process affecting mainly elastic and muscular arteries. Although small arteries and arterioles are usually spared, atherosclerosis can occur in these small vasculatures for a very short period. Here we report a case of atherosclerosis-like lesions that occurred in a transplanted kidney showing acute accelerated rejection in a 43-year-old man. Histologically, biopsy specimens at 14 and 28 days and nephrectomy material at 52 days post-transplantation showed atherosclerosis-like lesions in various-sized arteries. The lesions were characterized by the intimal infiltration of inflammatory cells, including foamy macrophages and a variable number of T-lymphocytes, with smooth muscle cell proliferation. Immunohistochemistry disclosed that the foam cells expressing CD68 contained oxidized LDL. In addition, apolipoprotein(a) (Lp(a)), another major atherogenic lipoprotein, was found in the intimal smooth muscle layer, suggesting that Lp(a) induced smooth muscle cell proliferation in the rejected kidney as a mechanism of atherosclerosis. This case shows that immunoinflammatory reactions during a relatively short period can mimic the chronic atherosclerotic process even in small arteries and arterioles. Furthermore, the deposition of atherogenic lipoproteins, Lp(a) and oxidized LDL in lesions of rejected tissue present an analogy between vascular rejection in transplanted kidney and atherosclerosis.

An ELISA procedure for human Lp(a) quantitation using monoclonal antibodies.

The present study describes a monoclonal antibody-based enzyme immunoassay (ELISA) for the quantitation of lipoprotein(a), Lp(a), in human plasma. Two antibodies to Lp(a), 2F4E7 and 8G12G7, were produced and characterized as specific and high affinity antibodies against Lp(a). A reference control serum was utilized to prepare the standard curve in a Lp(a) concentration range from 0.015 to 0.5 ug/ml. A biotinylated monoclonal antibody against apoB-LDL was used as the second antibody. The comparison of the standardized ELISA using mAb 2F4E7 with an ELISA using a characterized mAb against Lp(a) (clone KO9) as capture antibody showed that the Lp(a) concentration of two standard sera was similar with both assays. Furthermore, when compared with an electroimmunoassay kit, similar Lp(a) concentrations for the standard were also obtained.

Increased plasminogen activator inhibitor-1 and apolipoprotein (a) in coronary atherectomy specimens in acute coronary syndromes.

BACKGROUND: Although increased tissue factor expression is known in vulnerable plaques, there is no reported study to compare plaque fibrinolysis in stable and unstable plaques. This study investigates the extent of plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein (a) [apo(a)] in the plaques of different types of coronary artery disease as well as the correlation between these molecules and infiltration of macrophages to plaques. METHODS: Using immunohistochemical staining, we examined PAI-1 expression and apo(a) deposition in coronary atherosclerotic specimens obtained by directional coronary atherectomy from 19 patients with acute myocardial infarction (AMI), 12 with unstable angina pectoris (UAP), and 13 with stable angina pectoris (SAP). The percentages of the total areas of specimens stained with PAI-1 or apo(a) were estimated by an NIH image program. The proportion of macrophages as a percentage of all cells in plaques was calculated as the macrophage density. RESULTS: We found significantly higher percentages of total areas of specimens stained with PAI-1 in AMI (25.5 +/- 8.6%, P < 0.001) and UAP (22.2 +/- 10.4%, P < 0.005) than in SAP (9.5 +/- 5.0%), as well as with apo(a) (AMI; 11.7 +/- 7.1%, P < 0.005, UAP; 11.1 +/- 5.5%, P < 0.01 versus SAP; 3.9 +/- 1.5%). Linear regression analysis of all the samples showed a correlation between PAI-1 or apo(a) and macrophage density (PAI-1: r = 0.75, P < 0.001 and apo(a): r = 0.56, P < 0.001). CONCLUSIONS: Our results suggest a possible contribution of increased PAI-1 and apo(a) in plaques to the pathogenesis of acute coronary syndromes including impaired fibrinolysis.