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Background and Aims: Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD., Methods: A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care., Results: A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities., Conclusions: We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In vitro experimental studies demonstrated that iron promotes free radical-induced low-density lipoprotein (LDL) oxidation., Objective: To test the hypothesis that circulating oxidized LDL (oxLDL) levels might be associated with body iron stores (serum ferritin) and iron-related genetic markers (hemochromatosis gene C282Y mutation, haptoglobin polymorphism)., Methods: We investigated 381 (176 males, 205 females, age 45 +/- 6 years) healthy Caucasians. Serum oxLDL, assayed by a mAb-4E6-based enzyme-linked immunosorbent assay (ELISA), was expressed as oxLDL/LDL ratio to adjust for serum LDL-cholesterol concentration. Hemochromatosis gene C282Y mutation analysis was performed by a Taqman-based polymerase chain reaction (PCR) assay. Haptoglobin (Hp) phenotypes (Hp 1-1, Hp 2-1, Hp 2-2) were determined by starch gel electrophoresis., Results: In stepwise multivariate regression analysis, gender (P < 0.0001), current smoking (P < 0.0001), HDL-cholesterol (P = 0.0001), ferritin (P = 0.0051), body mass index (BMI) (P = 0.0063), and Hp phenotype (P = 0.0331) independently predicted oxLDL/LDL ratio in the total group. In men, smoking (P < 0.0001), ferritin (P = 0.0052), Hp phenotype (P = 0.0063), and HDL-cholesterol (P = 0.0127) were independent determinants of oxLDL/LDL ratio. In women, only body mass index (P < 0.0001), HDL-cholesterol (P = 0.0005), and smoking (P = 0.0025) were significantly associated with oxLDL/LDL ratio. The C282Y mutation (wild-type versus C282Y heterozygotes) was not associated with oxLDL/LDL ratio in both sexes., Conclusion: Serum ferritin concentration and Hp polymorphism are independently associated with circulating oxLDL levels in males.

Background: Uric acid is frequently elevated in hypertension. In addition to renal and metabolic disturbances, lower limb ischemia might contribute to hyperuricemia among hypertensives complicated by peripheral arterial disease (PAD)., Objective: To test the hypothesis that uric acid status is related to lower limb function in hypertensives with PAD., Methods: Serum and 24-h urine uric acid levels and other risk factors were examined in 145 hypertensives free of PAD and 166 hypertensives with PAD. Ankle/brachial index (ABI) and absolute claudication distance (in PAD) on a treadmill test (ACD) were assessed., Results: In multiple regression analysis for serum uric acid in the total group, PAD emerged as an independent determinant (P=0.03) next to age (P=0.005), triglycerides (P=0.04), and insulin (P=0.02). Serum uric acid concentrations were higher in hypertensives with PAD (404+/-101 vs. 347+/-80 micromol/l, P<0.001) independent of components of the metabolic syndrome (body mass index, triglycerides, insulin) and of age, gender, diabetes mellitus, pulse pressure, cholesterol, C-reactive protein, and treatment. After adjustment for kidney function by uric acid/creatinine ratio, values remained higher in hypertensives with PAD (P=0.01). Uric acid excretion was higher in the PAD group (P<0.001), whereas uric acid clearance was comparable between both groups. In multiple regression analysis for ACD (357+/-183 m) in the PAD group, serum uric acid (P=0.02), C-reactive protein (P<0.0001), age (P=0.02), and smoking (P=0.004) were independently associated. ABI (0.62+/-0.17) was not related to uric acid in PAD patients., Conclusion: Hyperuricemia is more pronounced in hypertensives complicated by PAD and is associated with worse functional status of the peripheral circulation.

Objectives: the aim of our study was to evaluate the independent role of the haptoglobin (Hp) polymorphism as a risk factor for coronary heart disease (CHD) mortality., Methods: within the framework of the longitudinal part of the Belgian Interuniversity Research on Nutrition and Health (BIRNH) survey, a nested case-control study design was performed through matching the 107 deaths from CHD, occurring within a 10-year follow-up period, with three controls for age and gender., Results: the distribution of the Hp types was found to be in Hardy-Weinberg equilibrium. Conditional logistic regression analysis for matched sets revealed that the Hp polymorphism was significantly associated with CHD death. Rather surprisingly, the finding was that Hp 1-1 individuals were at doubled risk for CHD mortality compared with the others, the odds ratio being 2.09 (95% CI: 1.22-3.60). The association was independent from other classical cardiovascular risk factors and the Hp concentration, and of comparable magnitude between men and women. Moreover, evaluating the interaction term in a multiplicative model showed that the Hp type did not play a synergistic role in the prognostic value of established cardiovascular risk factors., Conclusion: in contrast to the findings from cross-sectionally based studies, the results from this longitudinal study show that Hp 1-1 individuals are at elevated risk for CHD mortality.