Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 +/- 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3-5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score.Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects

Hypercholesterolemia and the ageing subject.

Iversen et al. have recently dealt in this Journal, with the effects of total cholesterol (TC) levels on cardiovascular risk according to age in a healthy population from the Copenhagen City Heart Study. They conclude that the association between high TC and incident coronary heart disease (CHD) event rate declines progressively with advancing age and is no more valid above 80 years [1]. This thorough survey considers more than 10,000 men and women before statin introduction in Denmark; its conclusions are in agreement with other cohort investigations but rely simply on total cholesterol and not on other useful lipid parameters. On the other hand data from a recent meta-analysis (61 prospective observational studies), consisting of almost 900,000 adults without previous disease, disclose that 1 mmol/L lower TC was associated with a statistically significant hazard ratio of 0.72, 0.82 and 0.85 lower CHD mortality in both sexes at ages 60–69, 70–79 and 80–89 years, respectively, and that HDL-cholesterol (HDL-C) and TC to HDL-C ratio are more informative parameter than total cholesterol alone [2]. We agree with the latter conclusions, pointing out that the EPESE Study related the apparent adverse effects associated with low TC levels in very old patients (average baseline age of 79) to comorbidity and frailty, and that adjusting for potential confounders (among which HDL-C) restored the direct relationship between TC and CHD in this population characterized by a heterogeneous health state [3]. Also the experience matured by our study-group suggests a prominent effect related to HDL-C [4], showing that free-living healthy octo-nonagenarians (free from CHD and stroke) are not characterized by high HDL-C or low LDL-C levels, but by a very low prevalence of low HDL-C (3.9%) [5], while HDL-C levels associate also with functional status [6]. Besides, while we could not exclude that dyslipoproteinemic high-cholesterol value in old people is under-represented since abated by premature death in affected individuals, we maintain that also small increases in relative CHD risk in elderly individuals associate with a striking increase in absolute risk, given the high prevalence of CHD with advancing age. This suggests that excluding older persons from cholesterol screening may be inappropriate, but that a comprehensive lipid profile and clinical judgment is essential for deciding if pharmacological treatment is needed

Dyslipidemias in the older subject: features, significance and treatment dilemmas

Almost two thirds of major coronary events take place in subjects over 65 years of age. Old (65–75 years), very old (75–85 years), and oldest old (85+ years) individuals should be considered separately when addressing cardiovascular (CV) risk. Several observational investigations have shown that the relationship between plasma cholesterol and CV events is less stringent with advancing age, especially in the very old and oldest old subject. In this context, both a decrease in total cholesterol and low HDL-C levels may be linked to coronary morbidity and total mortality through an independent association with disability and frailty. On the other hand, although elevated plasma LDL-C might still represent a CV risk factor in older people, the potential benefits originating from its reduction may exceed those obtained in younger ages, given the higher prevalence of CV disease in late life. At present statins, which represent the most effective hypocholesterolemic drugs, have been shown to significantly reduce CV events up to 82 years of age in randomized controlled trials and epidemiological surveys. The occurrence of multiple chronic conditions (comorbidity), decreased life expectancy and polypharmacotherapy suggest the need for a careful assessment of indications for aggressive hypolipidemic treatment. Drug interactions and low-pharmacological adherence may concur, causing a failure of preventive measure or side effects. Specific guidelines do not always recommend special caution or prudence in the elderly, but the selection of older patients for hypolipidemic treatment requires a high grade of clinical judgment

Reversible hyperthyroidism and cardiomyopathy caused by consumption of iodocasein.

We report the case of a 52-year-old woman with recent diagnosis of acute myocarditis and pericarditis, admitted for fever, tachycardia, and dyspnea upon exertion. Hematochemical parameters and instrumental examinations suggested iatrogenic hyperthyroidism and secondary dilated cardiomyopathy. Although gathering information about the medication used at home was initially difficult because of the patient’s refusal to cooperate, she ended up by disclosing the regular assumption of an iodocasein drug. A complete and stable regression of the clinical picture was reached by suspending the iodine derivative and using cardiovascular drugs

Hypothyroidism prevalence in dyslipidemic females.

abstract - comunicatio

Post-prandial effects of gemfibrozil vs simvastatin in hypercholesterolemic subjects with borderline hypertriglyceridemia.

NUTR METAB CARDIOVASC DI

Risk of hospitalization for upper gastrointestinal tract bleeding

Objective: This study evaluates the hospitalization risk for upper gastrointestial bleeding (UGIB) with reference to the clinical characteristics of patients and drugs taken before admission. Methods: This study is based on the GIFA (Italian Group for the Pharmacosurveillance in the Elderly) database. Cases with an ICD-9 code of esophagus, stomach or duodenum bleeding, or acute esophago-gastroduodenal disease associated with anemia have been classified as UGIB. Sex, age, year of observation, drugs taken at home, comorbidity, smoking, alcohol, and use of gastroprotectants have been also taken into account. Statistical analysis has been conducted using multivariate logistic regression models. Results: 32,388 patients have been enrolled, 940 of which presented UGIB. Age, comorbidity, use of smoke and alcohol, hospitalization duration, and mortality during hospitalization were significantly higher in UGIB than nonUGIB patients. Increased UGIB risk has been found in patients taking NSAIDs(both when aspirin was included or excluded), acetaminophen, constipating agents, iron, ethacrynic acid, propranolol. Reduced UGIB risk has been found in patients taking nitrates. Conclusions: UGIB risk appears to correlate with clinical characteristics of the patient: it increases with age, comorbidity, and smoke and alcohol consumption. Among drugs, NSAIDs are associated with the highest UGIB risk, while nitrates with a reduction of risk

Role of antioxidants in atherosclerosis: Epidemiological and clinical update

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents

Tessuto adiposo e infiammazione sistemica.

SommARIo Numerose evidenze sperimentali hanno dimostrato che l’obesità, in particolare quella viscerale, è caratterizzata da uno stato di infiammazione cronica di basso grado. Di fronte ad un cronico eccesso di nutrienti il tessuto adiposo va incontro a modificazioni di tipo adattativo tese a soddisfare le esigenze metaboliche. Parallelamente all’ipertrofia degli adipociti si assiste ad una modificazione di tipo funzionale dell’adipocita caratterizzata da un alterato pattern di secrezione delle adipochine. L’organo adiposo in toto va incontro inoltre a modificazioni nella composizione cellulare, incluse alterazioni nel numero, fenotipo e localizzazione di cellule stromali e del sistema immunitario. Il tessuto adiposo dei soggetti obesi, ed in particolare dei soggetti obesi con disfunzione metabolica, è caratterizzato dalla presenza di un infiltrato infiammatorio con macrofagi attivati, linfociti T e adipociti disfunzionanti. Questa condizione si traduce in un aumento dell’espressione e della secrezione di adipochine ad azione pro infiammatoria in grado di determinare a livello sistemico uno stato di infiammazione di basso grado, di peggiorare la sensibilità insulinica e di contribuire allo sviluppo delle complicanze metaboliche e cardiovascolari associate all’obesità. L’insieme delle evidenze raccolte negli ultimi anni ha rivelato che l’alterazione del cross talk tra adipociti e cellule del sistema immunitario è fondamentale nel determinare l’infiammazione a livello del tessuto adiposo. La comprensione di questo complesso network cellulare potrà fornire nuovi target molecolari per il trattamento dell’obesità e delle sue complicanze

SEVERE HYPERCHOLESTEROLEMIA - UNUSUAL INHERITANCE IN AN ITALIAN PEDIGREE

A family presenting several cases of severe primary hypercholesterolaemia and/or premature sudden death was studied. This family is characterized by consanguinity, absence of vertical transmission, bimodal distribution of plasma cholesterol values, and reduction of reproductive fitness in affected individuals. The probands have clinical traits of homozygous familial hypercholesterolaemia, including hypercholesterolaemia, xanthomas and early coronary atherosclerosis, while the parents and grandparents are clinically normal. Eight relatives on the mother's side experienced premature sudden death, and in four cases hypercholesterolaemia was diagnosed. Haplotype segregation analysis of the inheritance of the LDL receptor and apo B genes in the probands' family excluded the involvement of these two genes in the pathogenesis of the disease. LDL receptor activity, as well as the ability of LDL to bind to the LDL receptor, and plasma vegetal sterols were within normal limits both in probands and in their relatives. The study of this pedigree suggests that hypercholesterolaemia is not produced by defects in the LDL receptor or LDL particles, and disease inheritance is consistent with an autosomal recessive trait