Hyperlipidemias: Lupattelli G

Poli A, Marangoni F, Paoletti R, Mannarino E, Lupattelli G, Notarbartolo A, Aureli P, Bernini F, Cicero A, Gaddi A, Catapano A, Cricelli C, Gattone M, Marrocco W, Porrini M, Stella R, Vanotti A, Volpe M, Volpe R, Cannella C, Pinto A, Del Toma E, La Vecchia C, Tavani A, Manzato E, Riccardi G, Sirtori C, Zambon A, Anonymous00119. · Nutrition Foundation of Italy, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #18258418 No free full text.

Abstract: The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Lupattelli G, Marchesi S, Lombardini R, Roscini AR, Trinca F, Gemelli F, Vaudo G, Mannarino E. · Section of Internal Medicine, Angiology and Atherosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Italy. · Life Sci. · Pubmed #15581909 No free full text.

Abstract: Artichoke extracts have been shown to produce various pharmacological effects, such as the inhibition of cholesterol biosynthesis and of LDL oxidation. Endothelial dysfunction represents the first stage of atherosclerotic disease; it is usually evaluated in humans by a noninvasive ultrasound method as brachial flow-mediated vasodilation (FMV) and by the determination of several humoral markers such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. Aim of the study was to investigate the effects of dietary supplementation with artichoke juice on brachial FMV of hyperlipemics. We studied 18 moderately hyperlipemic patients (LDL cholesterol > 130 <200 mg/dl and/or triglycerides >150 <250 mg/dl) of both genders and 10 hyperlipemic patients, matched for age, sex and lipid parameters. All subjects were under isocaloric hypolipidic diet. A basal determination of serum lipids, soluble VCAM-1, ICAM-1, E-selectin and brachial FMV was performed. Thereafter patients were given 20 ml/die of frozen artichoke juice. The same parameters were repeated after 6 weeks. After artichoke treatment there was an increase of triglycerides (156 +/- 54 vs 165 +/- 76 mg/dL, p <0.05) and a reduction of total cholesterol (261 +/- 37 vs 244 +/- 38 mg/dL, p <0.05) and LDL cholesterol (174 +/- 31 vs 160 +/- 34 mg/dL, p <0.05). Controls showed a significant decrease in total and LDL cholesterol (respectively: 267 +/- 22 vs 249 +/- 20 mg/dL and 180 +/- 24 vs 164 +/- 23 mg/dL, both p <0.001). After artichoke there was a decrease in VCAM-1(1633 +/- 1293 vs 1139 +/- 883 ng/mL, p <0.05) and ICAM-1(477 +/- 123 vs 397 +/- 102 ng/mL, p <0.05), brachial FMV increased (3.3 +/- 2.7 vs 4.5 +/- 2.4%, p <0.01), while controls did not exhibit significant changes in VCAM-1, ICAM-1, E-selectin and brachial FMV. Univariate analysis showed that, in artichoke patients, changes of VCAM-1 and ICAM-1 were significantly related to changes in brachial FMV (respectively: r=-0.66 and r=-0.62; both p <0.05). In conclusion, artichoke dietary supplementation seems to positively modulate endothelial function in hypercholesterolemia.

Lupattelli G, Scarponi AM, Vaudo G, Siepi D, Roscini AR, Gemelli F, Pirro M, Latini RA, Sinzinger H, Marchesi S, Mannarino E. · Internal Medicine, Angiology and Atherosclerosis, Department of Clinical and Experimental Medicine, University of, Perugia, Italy. · Metabolism. · Pubmed #15164322 No free full text.

Abstract: Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.

Marchesi S, Lupattelli G, Lombardini R, Roscini AR, Siepi D, Vaudo G, Pirro M, Sinzinger H, Schillaci G, Mannarino E. · Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy. · J Clin Pharm Ther. · Pubmed #14632967 No free full text.

Abstract: BACKGROUND: Fasting and post-prandial hypertriglyceridemia have been associated with endothelial dysfunction. OBJECTIVE: To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load. METHODS: Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients. RESULTS: Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7 +/- 1 mmol/L at baseline vs. 4.2 +/- 1, 6.5 +/- 1, 6.6 +/- 2, and 5.3 +/- 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3 +/- 2% at baseline vs. 2.8 +/- 1, 2.2 +/- 1, and 1.3 +/- 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7 +/- 1.3 vs. 2.1 +/- 0.8 mmol/L), ICAM (480 +/- 113 vs. 269 +/- 65 ng/mL) and VCAM (1821 +/- 570 vs. 1104 +/- 376 ng/mL), and an increase in FMV (4.3 +/- 2 vs. 7.1 +/- 2%). Post-prandially triglycerides increased (2.1 +/- 1 at baseline vs. 2.4 +/- 2 and 3.6 +/- 1 mmol/L after 4 and 6 h), FMV decreased (7.1 +/- 2 at baseline vs. 5.8 +/- 2, 5.5 +/- 2, 5.9 +/- 2, 6.4 +/- 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = -0.34; P < 0.05) and ICAM (r = -0.66; P < 0.001). CONCLUSIONS: The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.

Chehne F, Oguogho A, Lupattelli G, Palumbo B, Sinzinger H. · Department of Nuclear Medicine, University of Vienna, Austria. · Prostaglandins Leukot Essent Fatty Acids. · Pubmed #12445494 No free full text.

Abstract: Cigarette smoking, a key risk factor for the development of vascular disease, is associated with an increased 8-epi-prostaglandin (PG) F(2alpha). Elevated 8-epi-PGF(2alpha) has been found in vascular tissue, blood and urine as well. We examined the influence of quitting cigarette smoking in 71 patients (38 males, 33 females; aged 32-67 a) with clinically manifested atherosclerosis and various risk factors. In addition, in eight patients with hypercholesterolemia without clinical manifestation of atherosclerosis quitting smoking was monitored as well. Twenty-six of the patients with manifested atherosclerosis and five with hypercholesterolemia restarted and the isoprostanes in plasma, serum and urine were monitored in these patients as well. Quitting cigarette smoking induces an immediate decline becoming significant after 1 or 2 weeks. Restarting smoking results in an increase in 8-epi-PGF(2alpha) reaching prevalues within almost 1 week. These findings indicate that the in vivo oxidation injury associated with cigarette smoking quickly decreases after quitting but increases soon after restarting immediately.

Marchesi S, Lupattelli G, Siepi D, Schillaci G, Vaudo G, Roscini AR, Sinzinger H, Mannarino E. · Department of Clinical and Experimental Medicine, University of Perugia, Italy. · J Cardiovasc Pharmacol. · Pubmed #11065222 No free full text.

Abstract: Endothelial dysfunction represents the earliest stage of atherosclerosis and is usually present in hypercholesterolemia. Treatment with statins has been shown to normalize endothelial function in middle-aged men with hypercholesterolemia. We evaluated the effect over time of atorvastatin on the endothelial reactivity in postmenopausal hypercholesterolemic women (mean age, 58 +/- 6 years), receiving atorvastatin, 10 mg daily (n = 20) or American Heart Association step 1 diet (n = 10) for 8 weeks. Lipid profile and brachial artery flow-mediated vasodilation (FMV) were determined at baseline and after 1, 2, 4, and 8 weeks. FMV increased progressively in subjects treated with atorvastatin, and the difference was significant (p < 0.05 vs. baseline) after the second week (baseline 3.8 +/- 3%; first week, 4.8 +/- 3%; second week, 9.2 +/- 3%; fourth week, 11.0 +/- 3%; eighth week, 11.7 +/- 3%). No significant changes were observed in subjects receiving diet (baseline, 3.1 +/- 4%; first week, 2.4 +/- 2%; second week, 2.9 +/- 2%; fourth week, 3.1 +/- 2%; eighth week, 3.3 +/- 2%; p = NS). In the atorvastatin group, low-density lipoprotein (LDL) cholesterol showed a significant decrease since the first week (baseline, 228 +/- 37 mg/dl; first week, 171 +/- 32; second week, 147 +/- 27; fourth week, 139 +/- 29; eighth week, 135 +/- 27; all p < 0.05). In the control group, LDL cholesterol showed a smaller but significant (p < 0.05) reduction after the second week (baseline, 226 +/- 17 mg/dl; first week, 225 +/- 16; second week, 220 +/- 17; fourth week, 203 +/- 27; eighth week, 198 +/- 27). In conclusion, hypercholesterolemic women treated with atorvastatin show a significant improvement in endothelial reactivity after as early as 2 weeks of therapy. The extent to which these beneficial effects are attributable to cholesterol reduction or to a direct effect of the drug remains to be established.

Mannarino E, Pirro M, Cortese C, Lupattelli G, Siepi D, Mezzetti A, Bertolini S, Parillo M, Fellin R, Pujia A, Averna M, Nicolle C, Notarbartolo A. · Medicina Interna, Angiologia e Malattie da Arteriosclerosi, Università di Perugia, Perugia, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #18762410 No free full text.

Abstract: BACKGROUND AND AIMS: Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant beta-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved. METHODS AND RESULTS: The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated in a multicenter, randomized double blind study. Hypercholesterolemic patients consumed a FM daily for 6 weeks. Subjects were randomized to receive either 1.6g of plant sterol-enriched FM (n=60) or control FM product (n=56). After 6 weeks of plant sterol-enriched FM consumption, LDL cholesterol was reduced from 166.2+/-2.0 to 147.4+/-2.8 mg/dL (p=0.01). A significant reduction was observed for total cholesterol (from 263.5+/-2.6 to 231.0+/-3.2mg/dL, p=0.01). There was greater LDL cholesterol lowering among hypercholesterolemic patients with higher LDL cholesterol at baseline. We found a reduction of plasma 8-isoprostane in patients taking plant sterol-enriched FM (from 43.07+/-1.78 to 38.04+/-1.14 pg/ml, p=0.018) but not in patients taking the control product (from 42.56+/-2.12 to 43.19+/-2.0 pg/ml, p=NS). Campesterol and beta-sitosterol levels were not influenced by phytosterol consumption. CONCLUSIONS: Daily consumption of low-fat plant sterol dairy product favourably changes lipid profile by reducing LDL-cholesterol, and may also have an anti-oxidative effect through a reduction of plasma isoprostanes.

Lupattelli G, Marchesi S, Siepi D, Bagaglia F, Palumbo B, Roscini AR, Schillaci G, Vaudo G, Sinzinger H, Mannarino E. · Internal Medicine Angiology and Atherosclerosis Disease, University of Perugia, Italy. · Vasa. · Pubmed #17109362 No free full text.

Abstract: BACKGROUND: The natriuretic peptides, Brain Natriuretic Peptide (BNP), C-type Natriuretic Peptide (CNP), are mediators of cardiovascular homeostasis.The impairment of arterial ability to vasodilate, also known as endothelial dysfunction, represents the first stage of atherosclerotic damage and may be assessed as brachial flow mediated vasodilation (FMV) in human. Generally an altered brachial FMV is documented in association to several cardiovascular risk factors as hypercholesterolemia. Aim of the study was to evaluate the behaviour of BNP and CNP in hyperlipemia and the potential relationship to FMV. PATIENTS AND METHODS: Forty-four hyperlipemic patients (LDL-cholesterol > 130 mg/dl and/or triglycerides > 150, age 35-60 y) of both genders and 20 normolipemic patients, matched for age and sex were investigated. RESULTS: Patients had lower values of brachial FMV in comparison to controls (3.9 +/- 3.5 vs 7.5 +/- 0.5%, p < 0.005), no differences were observed in BNP (4.6 +/- 4.6 vs 5.9 +/- 3.4 ng/mL, p = n.s) and CNP (4.1 +/- 5.8 vs 5.7 +/- 3.3 ng/mL, p = n.s). Univariate analysis showed a positive correlation between BNP and HDL-cholesterol values (r = 0.36, p = 0.001). In the multivariate analysis, LDL-cholesterol (beta = -0.57), HDL-cholesterol (beta = 0.26) and brachial artery diameter (beta = -0.33) were predictors of brachial FMV. The only predictive variable for CNP was HDL-cholesterol (beta = 0.37). CONCLUSIONS: The present study suggested that natriuretic peptides, BNP and CNP, are not altered in patients affected by hypercholesterolemia. Nevertheless, the levels of HDL-cholesterol are strictly related to the values of CNP. This observation, in humans, adds another mechanism to the vascular control exerted by HDL.

Pisciotta L, Calabresi L, Lupattelli G, Siepi D, Mannarino MR, Moleri E, Bellocchio A, Cantafora A, Tarugi P, Calandra S, Bertolini S. · Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, I-16132 Genoa, Italy. · Atherosclerosis. · Pubmed #16115486 No free full text.

Abstract: We studied a three generation family with co-dominant monogenic hypercholesterolemia and hypoalphalipoproteinemia. The proband, a 48 year-old male, was found to be heterozygous for a previously reported mutation in LDL receptor (LDL-R) gene (IVS15-3 c>a) and a novel mutation in exon 6 of lecithin cholesterol acyltransferase (LCAT) gene (c.803 G>A) causing a non-synonymous amino acid substitution (p.R244H). These mutations segregated independently in the family. The LDL-R mutation was associated with high levels of LDL-C (6.20-9.85 mmol/L) and apo B (170-255 mg/dL), comparable to those previously reported in carriers of the same mutation. The LCAT mutation was associated with low levels of HDL-C (0.67-0.80 mmol/L) and apo A-I (96-110 mg/dL). The proband had reduced LCAT function, as measured by cholesterol esterification rate (29 nmol/(mL/h) versus 30-60 nmol/(mL/h)), LCAT activity (10 nmol/(mL/h) versus 20-55 nmol/(mL/h)) and LCAT mass (2.87 microg/mL versus 3.1-6.7 microg/mL). Carriers of LCAT mutation had lower LCAT activity and a tendency to reduced cholesterol esterification rate (CER) and LCAT mass as compared to non-carrier family members. The LCAT mutation was not found in 80 control subjects and 60 patients with primary hypoalphalipoproteinemia. Despite the unfavourable lipoprotein profile, the proband had only mild clinical signs of atherosclerosis. This unexpected finding is probably due to the intensive lipid lowering treatment the patient has been on over the last decade.

Vaudo G, Marchesi S, Siepi D, Bagaglia F, Paltriccia R, Pirro M, Schillaci G, Lupattelli G, Mannarino E. · Unit of Internal Medicine, Angiology and Arteriosclerosis, University of Perugia School of Medicine, via Brunamonti 51, 06122 Perugia, Italy. · Am J Cardiol. · Pubmed #15165928 No free full text.

Abstract: The relevance of homocysteine to brachial flow-mediated vasodilatation and carotid and femoral intima-media thickness was investigated in 192 patients with hypercholesterolemia. Low-density lipoprotein cholesterol and homocysteine levels predicted brachial flow-mediated vasodilatation, internal carotid mean intima-media thickness, and intima-media thickening at all femoral sites. Homocysteine levels seem to be an additional factor in the initial atherosclerotic damage of patients with hypercholesterolemia.

Lupattelli G, Marchesi S, Lombardini R, Siepi D, Bagaglia F, Pirro M, Ciuffetti G, Schillaci G, Mannarino E. · Department of Clinical and Experimental Medicine, University of Perugia, Italy. · Metabolism. · Pubmed #14506626 No free full text.

Abstract: High-density lipoprotein-cholesterol (HDL-c) has a favorable influence on the endothelial function, but the mechanisms of this protective action are not fully understood. We studied lipid parameters, soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule [ICAM-1], E-selectin) oxidized low-density lipoproteins (LDL), and brachial-artery flow-mediated vasodilation (FMV) in 184 hyperlipemic patients (90 men, age 54 +/- 10 years, waist/hip circumference ratio 0.89 +/- 0.07, LDL-cholesterol [LDL-c] 4.9 +/- 1.3 mmol/L, triglycerides 1.8 +/- 0.9 mmol/L, HDL-c 1.3 +/- 0.5 mmol/L) after excluding those with current smoking, diabetes, hypertension, and vascular diseases. Patients were divided into 2 groups on the basis of HDL-c levels: < 1.03 mmol/L (n = 53) v >or= 1.03 mmol/L (n = 131). Patients with low HDL-c showed significantly lower LDL-c (P <.05), higher triglycerides (P <.001), higher body mass index (P <.02), lower FMV (3.7% +/- 2.0% v 4.9% +/- 3.4%, P <.002), higher VCAM-1 (1,195 +/- 395 ng/mL v 984 +/- 303 ng/mL, P <.01), and higher ICAM-1 (406 +/- 78 ng/mL v 364 +/- 68 ng/mL, P <.01). E-selectin and oxidized LDL showed no significant differences. In a multivariate age, oxidized LDL and brachial artery diameter predicted a lower FMV, while HDL-c was an independent predictor of a greater FMV (P =.003). Increasing levels of VCAM-1 and ICAM-1 were predicted by lower HDL-c, while higher oxidized LDL predicted higher VCAM-1 (P <.05). Our data suggest that in hyperlipemic subjects free of cardiovascular disease low HDL-c negatively modulates endothelial function through a lack of oxidation inhibition and a concomitant overexpression of adhesion molecules.

Pirro M, Siepi D, Lupattelli G, Roscini AR, Schillaci G, Gemelli F, Vaudo G, Marchesi S, Pasqualini L, Mannarino E. · Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Italy. · Metabolism. · Pubmed #12701054 No free full text.

Abstract: Hypoalphalipoproteinemia (Hypo-A), a lipid disorder characterized by low high-density lipoprotein (HDL)-cholesterol (HDL-C) levels, is frequently associated with an increased risk of suffering future coronary heart disease (CHD). Conversely, hyperalphalipoproteinemia (Hyper-A) is a characterized by high HDL-C concentrations and is possibly associated with longevity and protection against CHD. Whether plasma C-reactive protein (CRP) level, an emerging marker of CHD risk, may be influenced by either extremely low or high HDL-C concentrations is yet to be determined. Plasma levels of lipids and CRP have been measured in 52 middle-aged men and women, clinically free of CHD, including 20 subjects with Hypo-A, 12 with Hyper-A, and 20 healthy normolipemic age-matched controls. CRP levels were the highest in Hypo-A [0.22 mg/dL (interquartile range, 0.15 to 0.44)], the lowest in Hyper-A [0.03 mg/dL (0.02 to 0.07)], and intermediate in the control group [0.10 mg/dL (0.05 to 0.20)]. Differences in plasma CRP concentrations were significant between Hypo-A and the other 2 groups, as well as between Hyper-A and controls. Plasma CRP levels showed a particularly strong correlation with plasma HDL-C concentrations (r = -.66, P <.001). In multivariate models, HDL-C represented the only significant predictor of circulating levels of CRP. In conclusion, in subjects with Hypo-A or Hyper-A, HDL-C levels may account for plasma CRP variations independent of other potential cardiovascular risk factors.

Sinzinger H, Chehne F, Lupattelli G. · Wilhelm Auerswald Atherosclerosis Research Group (ASF), Vienna, Austria. · Drug Saf. · Pubmed #12241128 No free full text.

Abstract: BACKGROUND: Myopathy in its severe forms including rhabdomyolysis is a very rare adverse effect occurring during monotherapy with the HMG-CoA reductase inhibitors ('statins') and is associated with pronounced signs of oxidation injury. This has been found at a local (muscle) as well as at a systemic level (blood). Several lines of evidence indicate that even mild forms of myopathy during statin treatment may be associated with in vivo oxidation injury. In contrast, statin therapy has been shown to be associated with a decrease in oxidation injury. OBJECTIVE: The aim of this study was to investigate whether patients with heterozygous familial hypercholesterolaemia who did not exhibit any symptoms or abnormalities in safety parameters during 6 months of treatment with various statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin) did exhibit a change in oxidation injury as assessed by the isoprostane levels. METHODS: Blood (plasma and serum) as well as urine was tested before and 1, 3 and 6 months after starting statin therapy. Results: Out of 111 treated patients (63 males, 48 females; aged 19 to 58 years) who did not experience any adverse effects during statin treatment, 11 (seven males, four females; aged 24 to 51 years) showed a pronounced increase in 8-epi-prostaglandin (PG) F(2alpha) in all the compartments examined. In the remaining 100 patients (56 males, 44 females; aged 19 to 58 years) there was either no change in or even an apparent decrease in 8-epi-PGF(2alpha). This increase was monitored with all the statins administered. If elevated, the increase in 8-epi-PGF(2alpha) remained without change throughout the entire follow-up period. No sex difference or differential response between smokers and nonsmokers was observed. DISCUSSION: These findings indicate that in the absence of other clinically observable adverse effects, in some of the patients, for an as yet unknown reason, statin therapy may be associated with increased oxidation injury. The fact that changing to another statin is apparently not necessarily associated with an identical response raises the question of a specific predisposition for certain compounds in a given patient. These data add a further piece of evidence that mild adverse effects of statins that are difficult to assess might be much more prevalent than widely considered. The clinical relevance and consequence of these findings still remains to be assessed.

Lupattelli G, Marchesi S, Roscini AR, Siepi D, Gemelli F, Pirro M, Sinzinger H, Schillaci G, Mannarino E. · Unit of Internal Medicine, Angiology and Atherosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. · Am J Cardiol. · Pubmed #12231097 No free full text.

This publication has no abstract.

Sinzinger H, Lupattelli G, Chehne F, Oguogho A, Furberg CD. · Department of Nuclear Medicine, University of Vienna, Austria. · J Clin Pharm Ther. · Pubmed #11493374 No free full text.

Abstract: BACKGROUND: Muscle pains with or without CK-elevation are among the most frequently observed side-effects in patients with hyperlipoproteinemia on various statins. The pathophysiological background, however, remains obscure. METHODS: We examined isoprostane 8-epi-PGF2alpha, a marker of in-vivo oxidation injury, in plasma, serum and urine in these patients at baseline, when muscle problems manifested and different time intervals after withdrawing the respective statin. A healthy control group and a group of untreated patients with hyperlipoproteinemia were run as controls. RESULTS: The majority of patients with muscular side-effects show elevated 8-epi-PGF2alpha in plasma and urine, whereas serum values were elevated only to a lesser extent. Stopping statin therapy or successfully changing to another member of this family of compounds resulted in a normalization of the values in all patients. CONCLUSION: These findings indicate a significant involvement of oxidative injury in the muscular side-effects of statins in patients suffering from hyperlipoproteinemia.

Chehne F, Oguogho A, Lupattelli G, Budinsky AC, Palumbo B, Sinzinger H. · Department of Nuclear Medicine, University of Vienna, A-1090 Vienna, Austria. · Prostaglandins Leukot Essent Fatty Acids. · Pubmed #11427039 No free full text.

Abstract: Isoprostanes are known as reliable markers of in vivo oxidation injury. Cigarette smoking has been shown to be associated with a significant increase in 8-epi-PGF(2alpha), a major member of this family of compounds. Quitting smoking reduces 8-epi-PGF(2alpha) values to normal within a couple of weeks only. In this follow-up we checked the 8-epi-PGF(2alpha), values in plasma, serum and urine in 28 people who restarted smoking after a quitting attempt of various duration. 8-epi-PGF(2alpha)shows a certain increase after restarting smoking reaching a maximum after already 1 week. Continuation of smoking does not significantly further increase 8-epi-PGF(2alpha). These data indicate a fast response of restarting as on quitting smoking on in vivo oxidation injury. The oxidation injury reflected by 8-epi-PGF(2alpha)may be a key pathogenetic mechanism in smoking-induced vascular injury.

Lupattelli G, Palumbo B, Sinzinger H. · Institute of Internal Medicine, University of Perugia, Italy. · Nucl Med Commun. · Pubmed #11388581 No free full text.

Abstract: Statin induced myopathy is the most commonly seen side effect in users of this family of drugs. Their different forms present with either creatine phosphokinase (CK) elevation or not, signs of in vivo oxidation injury or not or a combination of both. The pathogenetic background, however, still remains obscure. As MIBI, beside myocardial and tumour scintigraphy, is useful in detecting muscle metabolic abnormalities, an increased uptake of MIBI in the diseased muscular segments could be expected. We investigated seven patients (five males, two females; aged 36-56 years) with statin induced myopathy with either elevated CK, isoprostanes or muscle pains at varying combinations. MIBI whole-body imaging was done immediately, the patients still being on the respective statin. Sixteen patients (six males, 10 females) suffering from lung or breast cancer and being on statins served as controls. No uptake abnormalities in any muscular segment either in the patients or the control group were seen. Thus, MIBI scintigraphy is not useful, apparently, in diagnosing and eventually localizing statin induced myopathy. These findings indicate that MIBI scintigraphy is of no help for diagnosis and gaining further insight into statin induced myopathy.

Pirro M, Lupattelli G, Siepi D, Palumbo B, Roscini AR, Marchesi S, Schillaci G, Mannarino E. · Unit of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. · Metabolism. · Pubmed #11230787 No free full text.

Abstract: The increased risk for coronary artery disease observed in postmenopausal women is partly explained by a more atherogenic fasting lipoprotein profile. Moreover, natural menopause has been associated with an altered postprandial lipid profile. To better characterize the interaction between fasting and postprandial lipid profile after menopause, we examined postprandial changes in several lipid parameters in three age-matched groups of postmenopausal women (16 affected by mixed hyperlipemia, 17 by common hypercholesterolemia, and 17 normolipemic), who underwent a standardized oral fat-loading test. The magnitude of postprandial lipemia, expressed as 8-hour triglyceride incremental area under the curve, was greater in women with mixed hyperlipemia (1,326 +/- 372 mg x dL(-1) x h(-1)) than in normal (484 +/- 384 mg x dL(-1) x h(-1)) and hypercholesterolemic (473 +/- 223 mg x dL(-1) x h(-1); both P <.0001) women, and the differences held after adjustment for body mass index and fasting insulin. Women with mixed hyperlipemia showed a significant postprandial decrease in high-density lipoprotein 2 (HDL(2)) cholesterol, lipoprotein (a), and low-density lipoprotein (LDL) particle size. Both hypercholesterolemic and normolipemic women showed a significant postprandial decrease in HDL cholesterol and lipoprotein (a) levels but not in LDL size. In a multiple linear regression analysis, fasting triglyceride levels, insulin level, and waist-hip ratio were all independent predictors of the magnitude of postprandial lipemia. In conclusion, postmenopausal women with mixed hyperlipemia show a greater postprandial triglyceride increase and a more pronounced reduction in HDL cholesterol level and LDL size than hypercholesterolemic and normolipemic subjects. The presence of the features of insulin resistance syndrome could contribute to the deterioration of postprandial lipemic response in these subjects.

Sinzinger H, Lupattelli G, Chehne F. · Institute for Diagnosis and Treatment of Lipid Disorders and Atherosclerosis (ATHOS), Nadlergasse 1, A-1090, Vienna, Austria. · Atherosclerosis. · Pubmed #11058722 No free full text.

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Lupattelli G, Lombardini R, Schillaci G, Ciuffetti G, Marchesi S, Siepi D, Mannarino E. · Section of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy. · Am Heart J. · Pubmed #10966556 No free full text.

Abstract: BACKGROUND: Endothelial dysfunction is considered one of the earliest events in the process of atherosclerosis, and an impaired vasodilatory response has been reported in patients with dyslipidemias. However, the independent association between hypertriglyceridemia and endothelial dysfunction is controversial, and the relation between endothelium-dependent vasodilation and circulating cell adhesion molecules as markers of endothelial dysfunction has not been fully determined. METHODS: Brachial artery flow mediated vasodilation (FMV) and the soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) were determined after overnight fasting in 16 men with hypertriglyceridemia (age 33 +/- 6 years) and in 16 age-matched healthy men with normal triglycerides and cholesterol. Subjects who smoked and those with known cardiovascular disease, diabetes, hypertension, recent or active infections, or any other disease that could affect leukocyte activation were excluded from the study. RESULTS: Compared with normal subjects, subjects with hypertriglyceridemia showed a higher level of sVCAM-1 and sICAM-1 (both P <.001), a reduced FMV (P <.01), and a smaller LDL particle size (P <.05). FMV had a significant inverse correlation with sVCAM-1 (r = -0.61, P <.001) and sICAM-1 (r = -0.38, P <.03). LDL particle size had a strong, direct association with FMV (r = 0.75, P <.001) and an inverse association with adhesion molecules. By multiple regression analysis, triglycerides (P <.001) and small LDL particle size (P <.002) predicted a reduced FMV. CONCLUSIONS: Serum level of cell adhesion molecules is increased and FMV is impaired in young healthy men with hypertriglyceridemia compared with age-matched men with normal lipid levels. Small, dense LDL particles may play a role in determining endothelial dysfunction in these subjects.

Lupattelli G, Rufini S, Locati EH, Lombardini R, Ciuffetti G, Siepi D, Mannarino E. · Internal Medicine, Angiology, and Atherosclerosis Unit, University of Perugia, Italy. freddy@.unipg.it · Angiology. · Pubmed #10535721 No free full text.

Abstract: The atherogenicity of homocyst(e)ine--H(e) --emerged from many studies showing an association between moderately elevated levels and vascular occlusive disease. The aim of this study was to evaluate whether high homocyst(e)ine levels were associated with carotid atherosclerosis. Carotid atherosclerosis was defined as an intimal media thickness of internal and carotid bifurcation of at least 2 mm on the near and far walls as determined by B-mode ultrasonography. The study population included 91 patients: group 1 (61% males, mean age 64+/-10 years, 57% with history of hypertension) with ultrasound evidence of carotid atherosclerosis and 100 with normal carotid walls--group 2 (36% males, mean age 52+/-15 years, 27% with history of hypertension). Homocyst(e)ine levels (mol/L) were determined by high-performance liquid chromatography with a fluorescent detector. Body mass index, dyslipidemia, smoking, diabetes, serum creatinine, plasma folic acid and vitamin B12 were not significantly different in the two groups. Homocyst(e)ine levels (micromol/L) were significantly higher in patients with carotid ather osclerosis than in those with normal arteries (11.7+/-6.5 micromol/L, 95% CI 10.4-13.1 vs 8.07+/-4.4 micromol/L, 95% CI 7.2-8.9, p<0.0001). By multiple regression analysis H(e) levels were positively correlated with male gender (p<0.02), age (p<0.001), and negatively with folic acid (p<0.0001). By logistic regression the independent predictors of carotid atherosclerosis were male gender (OR 2.65), hypertension (OR 2.55), age (x10 years, OR 2.15) and H(e) levels (x1 micromol/L, OR 1.11). This study confirmed homocyst(e)ine is associated with carotid atherosclerosis. Consequently the authors recommend H(e) levels be screened in all patients at risk for atherosclerosis.