Pedro Valdivielso

Current knowledge of hypertriglyceridemic pancreatitis

Severe hypertriglyceridemia (HTG) is a well established and the most common cause of acute pancreatitis (AP) after alcohol and gall stone disease. It is alleged to account for up to 10% of all pancreatitis episodes. Studies suggest that in patients with triglyceride (TG) levels>1000 mg/dL (>11.3 mmol/L), hypertriglyceridemia-induced acute pancreatitis (HTGP-AP) occurs in approximately 15-20% of all subjects referred to Lipid Clinics. Until now, there is no clear evidence which patients with severe HTG will develop pancreatitis and which will not. Underlying pathophysiological concepts include hydrolysis of TG by pancreatic lipase and excessive formation of free fatty acids with inflammatory changes and capillary injury. Additionally hyperviscosity and ischemia may play a decisive role. The clinical features of HTG-AP patients are supposed to be no different from patients with AP of other etiologies. Yet, there are well-conducted studies suggesting that HTG-AP is associated with a higher severity and complication rate. Therapeutic measurements in HTG-AP include dietary modifications, different antihyperlipidemic agents, insulin and/or heparin treatment. The beneficial use of plasmapheresis is repeatedly reported and suggested in many studies. Yet, due to the lack of randomized and controlled trials, it is currently unknown if plasmapheresis may improve morbidity and mortality in the clinical setting of HTG-AP. Since there are no commonly accepted clinical guidelines in the management of HTG-AP, there is a definite need for an international, multicenter approach to this important subject.

Occupation-Related Differences in the Prevalence of Metabolic Syndrome

OBJECTIVE—To investigate the prevalence of metabolic syndrome in the Spanish working population and determine how the prevalence varies according to occupation and sex. RESEARCH DESIGN AND METHODS—This was a cross-sectional study of 259,014 workers (mean age 36.4 years, range [16–74]; 72.9% male) who underwent a routine medical checkup. The Adult Treatment Panel III (2001) definition for metabolic syndrome was used. RESULTS—The prevalence of metabolic syndrome was 11.6% (95% CI 11.5–11.7) in male subjects and 4.1% (4.0–4.2) in female subjects and increased with age. The prevalence of metabolic syndrome varied in the different categories of occupational activity depending on the sex considered. Among female subjects, the age-adjusted prevalence of metabolic syndrome was higher in blue-collar than in white-collar workers, but this difference was not evident among male workers. CONCLUSIONS—The prevalence of metabolic syndrome varies in the different categories of occupational activity in the Spanish working population. This variation also depends on sex.

Omega 3 fatty acids induce a marked reduction of apolipoprotein B48 when added to fluvastatin in patients with type 2 diabetes and mixed hyperlipidemia: a preliminary report

BackgorundMixed hyperlipidemia is common in patients with diabetes. Statins, the choice drugs, are effective at reducing lipoproteins that contain apolipoprotein B100, but they fail to exert good control over intestinal lipoproteins, which have an atherogenic potential. We describe the effect of prescription omega 3 fatty acids on the intestinal lipoproteins in patients with type 2 diabetes who were already receiving fluvastatin 80 mg per day.MethodsPatients with type 2 diabetes and mixed hyperlipidemia were recruited. Fasting lipid profile was taken when patients were treated with diet, diet plus 80 mg of fluvastatin and diet plus fluvastatin 80 mg and 4 g of prescription omega 3 fatty acids. The intestinal lipoproteins were quantified by the fasting concentration of apolipoprotein B48 using a commercial ELISA.ResultsThe addition of 4 g of prescription omega 3 was followed by significant reductions in the levels of triglycerides, VLDL triglycerides and the triglyceride/HDL cholesterol ratio, and an increase in HDL cholesterol (P < 0.05). Fluvastatin induced a reduction of 26% in B100 (P < 0.05) and 14% in B48 (NS). However, the addition of omega 3 fatty acids enhanced this reduction to 32% in B100 (NS) and up to 36% in B48 (P < 0.05).ConclusionOur preliminary findings therefore suggest an additional benefit on postprandial atherogenic particles when omega 3 fatty acids are added to standard treatment with fluvastatin.

Childhood‐onset chylomicronaemia with reduced plasma lipoprotein lipase activity and mass: identification of a novel GPIHBP1 mutation

Abstract.  Coca‐Prieto I, Kroupa O, Gonzalez‐Santos P, Magne J, Olivecrona G, Ehrenborg E, Valdivielso P (Hospital Virgen de la Victoria, Malaga University, Malaga, Spain; Umea University, Umea; and Karolinska Institutet, Stockholm; Sweden). Childhood‐onset chylomicronaemia with reduced plasma lipoprotein lipase activity and mass: identification of a novel GPIHBP1 mutation. J Intern Med 2011; 270: 224–228.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

BackgroundHypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information.MethodsA subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption.ResultsWe found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG.ConclusionOur results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Higher red blood cell distribution width is associated with the metabolic syndrome: results of the Ibermutuamur CArdiovascular RIsk assessment study.

A high level of erythrocyte distribution width (RDW) is a novel prognostic marker that may reflect an underlying inflammatory state (1–3). Metabolic syndrome (MetS) is a chronic inflammatory disorder (4). We investigated the potential association between high levels of RDW and MetS. This cross-sectional study is part of the Ibermutuamur CArdiovascular RIsk Assessment (ICARIA) plan. A detailed description has been published elsewhere (5). A total of 217,567 workers (73.1% male, mean age 35.8 years) who underwent a routine medical checkup were included in the study. The Adult Treatment Panel III (ATPIII, 2001) definition for MetS was used. The mean RDW in the whole sample was 13.4% (SD 0.82%; range 10.1–33.4%; 75th percentile 14.0%). The …

Association of moderate and severe hypertriglyceridemia with obesity, diabetes mellitus and vascular disease in the Spanish working population: results of the ICARIA study.

AIM To study the prevalence, risk factors, and vascular disease associated with moderate and severe hypertriglyceridemia in an active working population. DESIGN AND METHODS Cross-sectional study of 594,701 workers from all Spanish geographical areas, occupation sectors, ages, and sexes who underwent a yearly routine checkup. Data collected from participants included age, sex, anthropometric measurements, vascular risk factors, lipidic profile and basic biochemical analysis, from a fasting blood sample. A cardiovascular risk assessment was performed. RESULTS The study population included 428,334 males and 166,367 females, mean age 36+/-10 years. A total of 95,673 (16%) workers had mild hypertriglyceridemia (HTg) (Tg 150-399mg/dL), 7,081 (1.1%) had moderate HTg (400-999mg/dL), and 224 (0.03%) had severe HTg (>or=1000mg/dL). Of workers with hypertriglyceridemia, 90% were male. Age, obesity, type 1 and 2 diabetes, alcohol consumption, and vascular disease were associated with hypertriglyceridemia. Cardiovascular risk gradually increased for each HTg category. Amongst risk factors, the major independent predictor of mild-HTg was obesity (OR 2.42, CI 95% 2.37-2.48), whereas diabetes was a predictor of moderate HTg (OR 3.64, CI 95% 3.17-4.18) and severe HTg (OR 7.35, CI 95% 4.27-12.66). In multivariate analyses, HTg was gradually associated with vascular disease, even after adjusting for other risk factors. CONCLUSION In this working population, preventive programs for HTg and associated vascular disease should consider obesity-diabetes control as its first objective.

Parameters of oxidative stress are present in the circulation of PXE patients

Pseudoxanthoma elasticum (PXE) is an inherited disorder characterized by calcification of elastic fibres leading to dermatological and vascular alterations associated to premature aged features and to life threatening clinical manifestations. The severity of the disease is independent from the type of mutation in the ABCC6 gene, and it has been suggested that local and/or systemic factors may contribute to the occurrence of clinical phenotype. The redox balance in the circulation of 27 PXE patients and of 50 healthy subjects of comparable age was evaluated by measuring the advanced oxidation protein products (AOPP), the lipid peroxidation derivatives (LOOH), the circulating total antioxidant status (TAS), the thiol content and the extracellular superoxide dismutase activity (EC-SOD). Patients were diagnosed by clinical, ultrastructural and molecular findings. Compared to control subjects, PXE patients exhibited significantly lower antioxidant potential, namely circulating TAS and free thiol groups, and higher levels of parameters of oxidative damage, as LOOH and of AOPP, and of circulating EC-SOD activity. Interestingly, the ratio between oxidant and antioxidant parameters was significantly altered in PXE patients and related to various score indices. This study demonstrates, for the first time, that several parameters of oxidative stress are modified in the blood of PXE patients and that the redox balance is significantly altered compared to control subjects of comparable age. Therefore, in PXE patients the circulating impaired redox balance may contribute to the occurrence of several clinical manifestations in PXE patients, and/or to the severity of disease, thus opening new perspectives for their management.

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

BackgroundSevere hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia.MethodsTwenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed.ResultsOnly five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS).ConclusionPrimary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

Exploring the value of apoB48 as a marker for atherosclerosis in clinical practice.

Eur J Clin Invest 2012; 42 (7): 702–708