All-cause mortality and cardiovascular events in a Spanish nonagenarian cohort according to type 2 diabetes mellitus status and established cardiovascular disease.

BACKGROUND: Despite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population. METHODS: We analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression). RESULTS: Mean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01). CONCLUSIONS: In Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.

[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention]. / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69 ≥ 70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

SEA 2022 Standards for Global Control of Cardiovascular Risk. / Estándares SEA 2022 para el control global del riesgo cardiovascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to better knowledge of vascular disease, its prevention and treatment. It is well known that cardiovascular diseases are the leading cause of death in our country and entail a high degree of disability and health care costs. Arteriosclerosis is a multifactorial disease and therefore its prevention requires a global approach that takes into account the different risk factors with which it is associated. Therefore, this document summarizes the current level of knowledge and includes recommendations and procedures to be followed in patients with established cardiovascular disease or at high vascular risk. Specifically, this document reviews the main symptoms and signs to be evaluated during the clinical visit, the laboratory and imaging procedures to be routinely requested or requested for those in special situations. It also includes vascular risk estimation, the diagnostic criteria of the different entities that are cardiovascular risk factors, and makes general and specific recommendations for the treatment of the different cardiovascular risk factors and their final objectives. Finally, the document includes aspects that are not usually referenced in the literature, such as the organization of a vascular risk consultation.

Performance of the Finnish Diabetes Risk Score and a Simplified Finnish Diabetes Risk Score in a Community-Based, Cross-Sectional Programme for Screening of Undiagnosed Type 2 Diabetes Mellitus and Dysglycaemia in Madrid, Spain: The SPREDIA-2 Study.

AIM: To evaluate the performance of the Finnish Diabetes Risk Score (FINDRISC) and a simplified FINDRISC score (MADRISC) in screening for undiagnosed type 2 diabetes mellitus (UT2DM) and dysglycaemia. METHODS: A population-based, cross-sectional, descriptive study was carried out with participants with UT2DM, ranged between 45-74 years and lived in two districts in the north of metropolitan Madrid (Spain). The FINDRISC and MADRISC scores were evaluated using the area under the receiver operating characteristic curve method (ROC-AUC). Four different gold standards were used for UT2DM and any dysglycaemia, as follows: fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1c, and OGTT or HbA1c. Dysglycaemia and UT2DM were defined according to American Diabetes Association criteria. RESULTS: The study population comprised 1,426 participants (832 females and 594 males) with a mean age of 62 years (SD = 6.1). When HbA1c or OGTT criteria were used, the prevalence of UT2DM was 7.4% (10.4% in men and 5.2% in women; p<0.01) and the FINDRISC ROC-AUC for UT2DM was 0.72 (95% CI, 0.69-0.74). The optimal cut-off point was ≥13 (sensitivity = 63.8%, specificity = 65.1%). The ROC-AUC of MADRISC was 0.76 (95% CI, 0.72-0.81) with ≥13 as the optimal cut-off point (sensitivity = 84.8%, specificity = 54.6%). FINDRISC score ≥12 for detecting any dysglycaemia offered the best cut-off point when HbA1c alone or OGTT and HbA1c were the criteria used. CONCLUSIONS: FINDRISC proved to be a useful instrument in screening for dysglycaemia and UT2DM. In the screening of UT2DM, the simplified MADRISC performed as well as FINDRISC.

Cardiovascular news 2013/2014. / Novedades cardiovasculares 2013/2014.

During 2013 and the first months of 2014, numerous studies have been published in the cardiovascular field. New guidelines have appeared for managing arterial hypertension and reducing cardiovascular risk by lowering cholesterol levels. New data have emerged on the considerable lipid-lowering efficacy of monoclonal antibodies against PCSK-9, in contrast, however, to the clinical trials directed towards raising HDL-cholesterol with nicotinic acid, which have not shown a reduction in the rate of cardiovascular complications. In the field of hypertension, neither stent placement in patients with renovascular hypertension nor sympathetic denervation in patients with resistant hypertension has been shown to be effective in reducing blood pressure. In terms of antithrombotic treatment, the pharmacogenetic tests do not seem useful for maintaining patients anticoagulated with warfarin within the therapeutic range for longer periods. Moreover, there is increasing evidence that, for patients with coronary artery disease and atrial fibrillation, antiplatelet therapy adds no benefit to anticoagulation therapy and is associated with a greater risk of bleeding. Lastly, a Mediterranean diet could prevent the onset of diabetes, while bariatric surgery could be a reasonable option for improving the disease in patients with obesity. Many of these studies have immediate practice applications in daily clinical practice.

Diagnosis and management of immunodeficiencies in adults by allergologists.

Primary immunodeficiencies (PIDs) are genetic diseases that cause alterations in the immune response and occur with an increased rate of infection, allergy, autoimmune disorders, and cancer. They affect adults and children, and the diagnostic delay, morbidity, effect on quality of life, and socioeconomic impact are important. Therapy (gamma-globulin substitution in most cases) is highly effective. We examine adult PIDs and their clinical presentation and provide a sequential and directed framework for their diagnosis. Finally, we present a brief review of the most important adult PIDs, common variable immunodeficiency, including diagnosis, pathogenesis, clinical signs, and disease management.

Kinetics of the chemical reduction of nitrate by zero-valent iron.

The use of reactive barriers is one of the preferred remediation technologies for the remediation of groundwater contamination. An adequate design of these barriers requires the understanding of the kinetics of the reaction between the target contaminant and the solid phase in the barrier. A study of the kinetics between metallic iron and aqueous nitrate is presented in this paper. Published literature regarding this reaction indicates that researchers are far from a consensus about the mechanism of this reaction. This paper presents the results obtained from experiments performed at different constant pH values and iron dosages, together with a mathematical analysis of the kinetic results. We have found that an Eley-Rideal kinetic model yields a good explanation of the relatively complicated dependence between rate of nitrate reduction and the pH value of the solution.

[Fibromuscular dysplasia. Asymptomatic dissection and occlusion of the basilar artery]. / Displasia fibromuscular, disección y oclusión asintomática de la arteria basilar.

INTRODUCTION: Historically, basilar artery occlusive disease has been considered to convey a poor prognosis and a high mortality rate. In contrast, recently prospective studies have shown a better prognosis. The basilar artery is most commonly affected by atherosclerosis, but may also be affected by embolisms, dissections, aneurysms, and other conditions like fibromuscular dysplasia. CASE REPORT: The case of a 46 year-old male who was admitted after suffering a transient episode of ataxic gait and dysarthria is reported. Transcranial Doppler showed a stenotic flow in the basilar artery with distal embolic signals. Magnetic resonance (MR) angiography demonstrated an isolated fibromuscular dysplasia of the basilar artery that caused a > 50% stenosis without parenchymal lesions. Oral anticoagulation treatment was initiated. The control MR angiography performed ten months later, and although the patient was asymptomatic, showed a dissection which evolved into a complete occlusion of the basilar artery. Its distal portion was filled via a reverse flow from both posterior communicating arteries. Anticoagulation treatment was discontinued. DISCUSSION: Fibromuscular dysplasia of the basilar artery is a rare and usually asymptomatic disease. It may develop into a dissection, but the usual clinical presentation is stenosis-related ischemic stroke. Intracranial artery dissections may be further complicated by subarachnoid hemorrhage. Many authors have recommended anticoagulant therapy for fibromuscular dysplasia. Basilar artery occlusion, as this case shows, does not always convey a poor prognosis. This is determined, at least partially, by the presence of good collateral circulation.

Perfusion computed tomography-guided subacute endovascular reperfusion in a patient with carotid occlusion.

Most patients with symptomatic internal carotid artery occlusion have a single minor or major hemispheric stroke. A minority of patients have ipsilateral retinal ischemia, recurrent strokes, or transient ischemic attacks. Whereas spontaneous carotid recanalization is rare, acute surgical recanalization has been attempted, with mixed results. Recently, acute endovascular recanalization has been performed and described as feasible and relatively safe. We describe a patient with symptom recurrence related to hemodynamic factors after occlusion of the carotid artery who was successfully treated 14 days after symptom onset.

Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis.

BACKGROUND: Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC(4)) and bronchoprotective (prostaglandin E(2); PGE(2)) lipid mediators. METHODS: We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE(2), and LTC(4) were measured by enzyme immunoassays. RESULTS: The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma), IL-2, vascular endothelial growth factor and transforming growth factor beta were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-gamma and tumor necrosis factor alpha (TNF-alpha) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE(2) concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 +/- 612 pg/ml) when compared with asthmatic (7.54 +/- 2.14 pg/ml) and healthy subjects (4 +/- 1.3 pg/ml). CONCLUSION: This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE(2) production in the airways.

Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease.

OBJECTIVE: To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease. SUBJECTS/METHODS: A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay. RESULTS: After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1). CONCLUSIONS: The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.

Allergy to dermatophagoides in a group of Spanish gypsies: genetic restrictions.

BACKGROUND: Spanish gypsies have traditionally lived as nomads, a reason why few epidemiological studies were done in this ethnic group. However, the high prevalence of asthmatic diseases demonstrated in a population residing in the North of Spain induces us to analyse whether it was due to the influence of genetic loci previously implicated in other population studies as causing the disorders. METHODS: DRB1* and DQB1* HLA class II, TCR-Valpha8.1, FcepsilonRI-beta Rsa I exon 7 and intron 2, TNF-beta (LTalpha-Nco I) and CD14, were tested for association with asthma and atopy by multiple regression analysis, in 5 families comprising 87 individuals. RESULTS: Significant associations were found with DQB1*02 (p = 0.02) and DQB1*0301 (p = 0.008) and elevated levels of total serum IgE. A negative association (p = 0.02) was found between total serum IgE and DRB1*14. FcepsilonRI-beta Rsa I-In2 allele 1 was associated with high levels of total serum IgE (p = 0.04). Levels of Der p 1 IgE antibodies were negatively associated with DRB1*11-DQB1*0301 (p = 0.007), and positively with TCR Valpha-8 allele 1 (p = 0.04) and with FcepsilonRI-beta Rsa I-In2 allele 1 (p = 0.009). CONCLUSIONS: Our results do not show any association between asthma and the genetic loci studied although they do suggest the existence of multiple genetic influences on the allergic response in these families.

[Proliferative granulomatous arachnoiditis: an infrequent form of tuberculous myeloradioculopathy]. / Aracnoiditis granulomatosa proliferativa: una forma infrecuente de mielorradiculopatía tuberculosa.

Proliferative granulomatous arachnoiditis is an infrequent manifestation of central nervous system tuberculosis. The mortality rate is 30%, and there are functional sequels in almost all patients. We present the case of a 22-year-old woman, immunocompetent that suffered form tuberculous radiculo-myelopathy with fatal evolution, which allowed us to confront neuroimaging and neuropathological findings. Although serial MR imaging illustrated evolution of lesions, autopsy revealed more extensive lesions that those observed in neuroimaging studies. The characteristic pathological lesion was an intradural inflammatory exudate with a global medullar necrosis. Even through duration of medical treatment is still discussed, early diagnosis, complete antituberculous drug regimen and prolonged corticosteroid therapy are essential to avoid fatal evolution as occurred in this case.

Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study.

BACKGROUND: Apolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. The apo E4 (Arg112-Cys) polymorphism has been associated with dementia and hypercholesterolemia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study. METHODS AND RESULTS: DNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E3/4 (Group E4); 14.1% had apo E2/2 or E2/3 (Group E2) and 63.9% had the apo E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) was related to APOE genotype. Age adjusted period prevalence of CVD in men was 18.6% for Group E4, 18.2% for Group E2 and 12.7% for Group E3 (P=0.004); while in women these rates were 9.9, 4.9, and 6.6%, respectively (P=0.037). After adjustment for non-lipid risk factors the relative odds for CVD in Group E2 men was 1.79 (P=0.0098) and in Group E4 it was 1.63 (P=0.0086) compared with the Group E3; while in Group E4 women it was 1.56 (P=0.054). After adjustment for all CVD risk factors, the relative odds in Group E2 men was 1.94 (P=0.004) and in Group E4 men it was 1.51 (P=0.0262). CONCLUSIONS: The presence of the apo E2 or apo E4 alleles in men is associated with significantly greater CVD risk. This genotypic information may help to identify individuals at increased risk for CVD events.

Alcohol drinking determines the effect of the APOE locus on LDL-cholesterol concentrations in men: the Framingham Offspring Study.

BACKGROUND: The effect of alcohol drinking on LDL-cholesterol concentrations is unclear. The reported variability may be due to interactions between genetic factors and alcohol intake. OBJECTIVE: The purpose of the study was to examine whether variation at the apolipoprotein E gene (APOE) locus modulates the association between alcohol drinking and LDL cholesterol. DESIGN: We used a cross-sectional design in a healthy population-based sample of 1014 men and 1133 women from the Framingham Offspring Study. RESULTS: In male nondrinkers (n = 197), LDL cholesterol was not significantly different across APOE allele groups [APOE*E2 (E2), APOE*E3 (E3), and APOE*E4 (E4)]. However, in male drinkers (n = 817), differences were observed (P: < 0.001); those with the E2 allele had the lowest concentrations. LDL cholesterol in men with the E2 allele was significantly lower in drinkers than in nondrinkers but was significantly higher in drinkers than in nondrinkers in men with the E4 allele. This APOE-alcohol interaction remained significant (P < 0.001) after age, body mass index, smoking status, and fat and energy intakes were controlled for. In women, the expected effect of APOE alleles on LDL cholesterol occurred in both drinkers (n = 791; P < 0.001) and nondrinkers (n = 342; P < 0.001). Multiple linear regression models showed a negative association (P < 0.05) between alcohol and LDL cholesterol in men with the E2 allele but a positive association in men with the E4 allele. No significant associations were observed in men or women with the E3 allele. CONCLUSION: In men, the effects of alcohol intake on LDL cholesterol are modulated in part by variability at the APOE locus.

Expression on human eosinophils of CD148: a membrane tyrosine phosphatase. Implications in the effector function of eosinophils.

The role of protein tyrosine phosphatases (PTP) is crucial in regulating the phosphorylation status of cells. CD148 is a recently described membrane-type PTP. In this study, we have demonstrated that this molecule is expressed on human eosinophils and eosinophilic cell line EoL-3. Interestingly, our data also showed that this molecule acts as a transduction molecule on these cells. Thus, the crosslinking of CD148 was able to induce the degranulation and the induction of superoxide anion generation. By using specific inhibitor and by western blotting, we have shown that tyrosine kinase activation is involved in this transduction pathway. In addition, we have shown the presence of a serine/threonine kinase activity associated with CD148. In conclusion, the activation capacity of CD148 on eosinophils suggests a potential role of this molecule on inflammatory diseases, such as allergic and parasitic diseases, associated with eosinophilia.

Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (P<0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.

DR2 antigens are associated with severity of disease in toxic oil syndrome (TOS).

Toxic oil syndrome (TOS) was an epidemic which broke out in Spain in 1981, caused by the ingestion of rapeseed oil denatured with 2% aniline and sold illegally as edible oil. More than 20,000 people were affected and mortality rate was 8.4%. Genetic susceptibility appears to be involved in the pathology of this disease. Several reports have described association between the chronic stage of the disease and DR-DQ antigens (DR3, DR4, DR2 and DQ8). In the present work, we have reassessed the HLA class II antigens in a well-designed case-control study. Triplets of subjects (n=265) composed by chronic patients (n=117), non-affected family members (n=71) and non-related controls (n=77) were studied. Also, HLA class II antigens were analyzed in patients who had died from TOS (n= 34) and in TOS control patients who died from other non-TOS related causes (n=13). Regarding surviving patients no significant association was found between HLA and disease. In contrast, an increase in phenotypic frequency of DR2 antigen, was found in patients who had died from TOS (73.5%) compared with the whole study group: TOS-affected alive patients (25.6%, corrected P<0.001), non-affected family members (28.5%, corrected P<0.001), non-related controls (23.9%, corrected P<0.001) and dead controls (38.4%, P=0.03).

Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles: The Framingham Offspring Study.

Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the -514T allele was due to an increase in the HDL(2)-C subfraction, and this association was stronger in women compared with men (P=0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C-514T polymorphism contributed significantly to the variability of HDL particle size in men and women (P<0.04). Thus, our results show that the C-514T polymorphism in the hepatic lipase gene is associated with significant variations in the lipoprotein profile in men and women.