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Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

Objective: We present the available data on the effects of combined therapy of fenofibrate with drugs affecting lipid metabolism other than statins. Methods: We consider studies evaluating the effects of combined therapy of fenofibrate with bile acid sequestrants (BAS), ezetimibe, niacin, n-3 fatty acids, plant sterols, orlistat, rimonabant, metformin and glitazones. Results: Combination of BAS (especially colesevelam) with fenofibrate had additional effects on metabolic parameters in patients with mixed hyperlipidemia. Combination of ezetimibe with fenofibrate may be a useful approach to improve the overall lipid profile of patients with mixed hyperlipidemia. There is a further reduction in triglyceride levels when n-3 fatty acids are administered with fenofibrate in patients with severe hypertriglyceridemia. Combined fenofibrate and orlistat treatment further improves metabolic parameters in overweight/ obese patients with metabolic syndrome. The fenofibrate/thiazolidinedione combination is an alternative for diabetic patients intolerant to statins, though differences exist between pioglitazone and rosiglitazone. Conclusions: For patients who cannot tolerate statins there are useful combinations of fenofibrate with other drugs affecting lipid metabolism. These combinations improve several metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular events.

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A2(Lp-PLA2) and levels of cytokines [interleukins (IL)-1β, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA2activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA2activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A2(Lp-PLA2) and levels of cytokines [interleukins (IL)-1β, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA2activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA2activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.

Metabolic syndrome (MetS) is a cluster of risk factors, each one individually associated with increased cardiovascular disease risk. Treatment of all components of MetS is expected to result in reduced risk. Treatment of MetS mainly includes lifestyle changes. In addition, drug therapy may be considered, especially combinations of different drugs, in order to tackle all the features of MetS. We review the therapeutic strategies currently used for obesity and dyslipidemia treatment in patients with MetS, with a focus on drug combinations.

Hypertension is one of the major risk factors for cardiovascular disease. Angiotensin receptor blockers (ARBs) are a class of antihypertensive drugs with established efficacy and favorable safety profile. Telmisartan, a member of the ARB family, holds some additional traits which differentiate it from the rest ARBs. A pivotal role in these characteristics plays its ability to partially activate the peroxisome proliferator activated receptor-, which in turn controls a number of metabolism-related genes. Indeed, telmisartan has shown a number of pleiotropic effects in experimental and clinical studies. These include the amelioration of insulin resistance, improvement of lipid profile and favorable fat redistribution. Moreover, telmisartan has been associated with beneficial effects on vascular function, cardiac remodeling and renal function. However, do all these pleiotropic effects translate into clinical benefit? Recent studies have tried to answer this question with promising but not definitive results.

To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke.

Fenofibrate represents the most commonly used fibric acid derivative. The drug exerts its metabolic effects by modulating the expression of several genes involved in lipoprotein metabolism. In addition, numerous studies suggest that fenofibrate may also affect the progression of the atherosclerotic process by several lipid-independent mechanisms. This review considers the clinical pharmacology of fenofibrate and the current evidence on the pleiotropic effects of this fibric acid derivative.

Objective: To assess the effect of rimonabant, micronised fenofibrate and their combination on anthropometric and metabolic parameters in overweight/obese patients with dyslipidaemia. Methods: All patients (n 30) received a hypocaloric diet (∼ 600 kcal/day deficit) and were randomly allocated to receive open-label rimonabant (R) 20 mg/day (n 10), micronised fenofibrate (F) 200 mg/day (n 10) or rimonabant 20 mg/day plus fenofibrate 200 mg/day (RF) (n 10). Anthropometric and metabolic parameters were assessed at baseline and 3 months after treatment initiation. Results: Compared with baseline similar significant reductions in body weight, body mass index and waist circumference were observed in the R (–6, –5 and –5%, respectively; p < 0.01) and RF group (–5% for all, p < 0.05), while improvements in these parameters were smaller in the F group (–2, –2.5 and –2%, respectively; p < 0.05). Triglycerides were reduced by 18% in the R group (p NS), by 39% in the F group (p < 0.001) and by 46% in the RF group (p < 0.05). Importantly, combination treatment resulted in a 42% increase in high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05), while HDL-C was not significantly altered in the two monotherapy groups. Subsequently, a more pronounced increase in apolipoprotein A-I (ApoA-I) levels (25%) was observed in the RF group compared with changes in both monotherapy groups (p < 0.0001 vs R and p < 0.005 vs F group). Low-density lipoprotein cholesterol (LDL-C) levels were not significantly altered in any group. Apolipoprotein B (apoB) levels were reduced in all groups and this reduction was significantly more pronounced in the RF group (p < 0.05 vs baseline as well as p < 0.005 and p < 0.01 for RF vs R and F groups, respectively). ApoB/apoA-I ratio decreased by 3% with R (p NS), by 18% with F (p < 0.05) and by 40% with RF treatment (p < 0.01). Total cholesterol to HDL-C ratio decreased by 20% with F (p < 0.0001) and by 33% with RF therapy (p < 0.005), while it was not significantly altered in R group. Conclusion: The combination of rimonabant and fenofibrate may further improve metabolic parameters in overweight/obese patients with dyslipidaemia compared with each monotherapy. This improvement is particularly pronounced for HDL-C levels.

Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are liver and muscle related. These effects are less well known but are clinically relevant.

Background: Visfatin [pre-B cell colony-enhancing factor (PBEF)] is a cytokine highly expressed in visceral fat that exhibits insulin-mimetic properties. However, its role in insulin-resistant states, such as in metabolic syndrome (MetS), remains largely unknown. Objective: To investigate the possible differences of plasma visfatin levels between obese and overweight subjects with and without MetS. Design and patients: Plasma visfatin concentrations were measured with enzyme-linked immunosorbent assay (ELISA) in 28 overweight and obese [body mass index (BMI)>28 kg/m2] subjects with Mets and 28 age- and sex-matched overweight and obese (BMI>28 kg/m2) individuals without MetS (control group). Results: Patients with MetS exhibited significantly elevated waist circumference (WCR) values, higher blood pressure readings, higher fasting glucose and triglyceride concentrations as well as lower levels of HDL cholesterol (HDL-C) compared with controls. Total and LDL cholesterol (LDL-C) concentrations did not differ significantly between the two groups. Plasma visfatin concentrations were significantly higher in subjects with MetS compared with controls [27 (16–65) ng/ml vs19 (10–47) ng/ml, p<0.05]. The same results were observed even after adjustment for age, sex and BMI. Plasma visfatin levels were positively correlated with age (r=0.32, p<0.05), WCR (r=0.31, p<0.05), triglyceride (r=0.59, p<0.01) and glucose (r=0.33, p<0.05) levels and were negatively correlated with HDL-C levels (r=−0.38, p<0.05). Multiple linear regression analysis revealed similar results. Conclusion: Plasma visfatin levels are increased in overweight and obese subjects with MetS compared with those individuals who do not fulfil the criteria for the diagnosis of MetS.

Dyslipidaemia is common in solid organ transplant recipients and its presence is associated with chronic rejection and accelerated atherosclerosis, leading to an increased prevalence of cardiovascular disease (CVD). CVD is a major cause of morbidity and mortality in transplant recipients. It is therefore of interest and clinical value to introduce agents that effectively and safely reduce the incidence of this outcome. In the present review we consider the potential benefits of statin administration in adults who have undergone solid organ (mainly renal, heart and liver) transplantation, as well as in paediatric transplant patients. We also briefly review the effects of combination therapy with ezetimibe and statins in this population. Overall, statins are efficient and safe drugs for the management of dyslipidaemias in transplant populations, and in most trials they had a beneficial effect on long-term survival rates, CVD events and rejection rates. The transplanted population is different from other patient groups, mostly due to concomitant immunosuppressive therapy. Statins, at an appropriate dosage, should be prescribed to dyslipidaemic transplanted patients but they should be closely monitored for adverse effects.

Background: Type 2 diabetes mellitus (T2DM) is a common disease that is associated with an increased risk of vascular complications. The incidence of T2DM is also increasing. It follows that T2DM prevention is important. Methods: Relevant articles (review articles, randomised studies and large cohort and case-control studies) were identified through a Medline search (up to March 2005). Results: The first trials on T2DM prevention were based on lifestyle intervention. The results of these studies were impressive since they demonstrated that even a small reduction in weight could significantly reduce the incidence of T2DM. However, the main disadvantage of lifestyle measures is that they are difficult to achieve and sustain. Therefore, pharmacological interventions have also been evaluated. The results of trials using metformin, orlistat, nateglinide, acarbose, thiazolidinediones, hormone replacement therapy, statins or fibrates are either encouraging or require more extensive evaluation. In addition, studies using antihypertensive drugs (mainly angiotensinconverting enzyme inhibitors and angiotensin II receptor antagonists) showed that these drugs could also reduce the progression to T2DM in high risk individuals. Conclusions: T2DM has major quality of life and cost implications. Therefore, more research is needed to establish safe and cost effective ways to prevent this modern epidemic.

Beyond allopurinol and the well-established uricosuric drugs, several other agents can decrease serum uric acid (SUA) levels, such as losartan, fenofibrate and some non-steroidal anti-inflammatory drugs (NSAIDs). Some of these drugs increase renal urate excretion. Hyperuricaemia and gout are common problems (at least 1 of Western men are affected by gout). Raised SUA levels increase the incidence of acute gout and renal calculi. Hyperuricaemia may also predict an increased risk of vascular events. Therefore, lowering SUA levels is of clinical relevance. In this review we consider the effect on SUA levels of drugs that are prescribed for indications other than treating hyperuricaemia. These drugs may obviate the need for specific treatment (e.g. allopurinol) aimed at lowering SUA levels. Furthermore, because hyperuricaemic patients may already be on several drugs (e.g. due to associated dyslipidaemia, hypertension and/or arthritis) compliance may be improved by avoiding additional medication. The potential for adverse effects associated with polypharmacy would also be decreased.

ABSTRACTBackground:Obesity is becoming increasingly common worldwide and is strongly associated with the metabolic syndrome (MetS). MetS is considered to be a cluster of risk factors that increase the risk of vascular events.Objective:In an open-label randomised study (the FenOrli study) we assessed the effect of orlistat and fenofibrate treatment, alone or in combination on reversing the diagnosis of the MetS (primary end-point) as well as on anthropometric and metabolic parameters (secondary end-points) in overweight and obese patients with MetS but no diabetes.Methods:Overweight and obese patients (N= 89, body mass index (BMI) > 28 kg/m2) with MetS [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria] participated in the study. Patients were prescribed a low-calorie low-fat diet and were randomly allocated to receive orlistat 120 mg three times a day (tid) (O group), micronised fenofibrate 200 mg/day (F group), or orlistat 120 mg tid plus micronised fenofibrate 200 mg/day (OF group). Body weight, BMI, waist circumference, blood pressure, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL‐C), high-density lipoprotein cholesterol (HDL‐C), non-HDL‐C, triglyceride, creatinine (SCr) and uric acid (SUA) levels, as well as homeostasis model assessment (HOMA) index and liver enzyme activities were measured at baseline and after 3 months of treatment.Results:Of the 89 patients enrolled, three (one in each group) dropped out during the study due to side effects. After the 3‐month treatment period, 43.5% of patients in the O group, 47.6% in the F group and 50% in the OF group no longer met the MetS diagnostic criteria (primary end-point, p< 0.0001 vs. baseline in all treatment groups). No significant difference in the primary end-point was observed between the three treatment groups. Significant reductions in body weight, BMI, waist circumference, blood pressure, TC, LDL‐C, non-HDL‐C, triglyceride and SUA levels, as well as gamma-glutamyl transpeptidase activity and HOMA index were observed in all treatment groups. In the OF group a greater decrease in TC (–26%) and LDL‐C (–30%) was observed compared with that in the O and F groups ( p< 0.01) and a more pronounced reduction of triglycerides (–37%) compared with that in the O group ( p< 0.05). SUA levels and alkaline phosphatase activity decreased more in the F and OF groups compared with the O group ( p< 0.05). Moreover, SCr significantly increased and estimated creatinine clearance decreased in the F and OF groups but they were not significantly altered in the O group ( p< 0.01 for the comparison between O and either F or OF groups). Glucose (in groups O and OF), as well as insulin levels and HOMA index (in all groups), were significantly reduced after treatment ( p< 0.05 vs. baseline).Conclusion:The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.

Lipid markers are well established predictors of vascular disease. The most frequently measured lipid variables are total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides. In this review we consider the predictive value of these variables and other more specialised related tests. We also discuss the effect of lipid altering drugs on these markers. The interaction of other vascular risk factors and the lipid effects of non-lipid altering drugs (e.g. blood pressure lowering agents) are also briefly described. Similarly, we discuss the effects of lipid lowering drugs on non-lipid vascular risk factors. Finally, we briefly consider the effect of altering the lipid profile on surrogate markers and events associated with atherosclerosis.

ABSTRACTBackground:Obesity is associated with an increased incidence of diabetes, hypertension, dyslipidaemia and coronary artery disease. Current management strategies of obesity include lifestyle interventions and pharmacotherapy. Sibutramine is a drug with established efficacy in weight reduction and maintenance of weight loss. It reduces food intake and attenuates the fall in metabolic rate associated with weight loss.Objective:To review the metabolic effects associated with sibutramine use.Methods:Relevant articles were identified through a Medline search (up to December 2004).Results:Weight loss with sibutramine treatment is associated with improved insulin sensitivity and a fall in glycosylated haemoglobin levels in type 2 diabetic patients. In most trials sibutramine exerted favourable effects on lipids, especially on high density lipoprotein (HDL) cholesterol and triglycerides, as well as on the total:HDL cholesterol ratio. Sibutramine also lowers serum uric acid concentrations. Furthermore, this drug seems to favourably influence adipocytokines; it reduces serum leptin and resistin levels and increases adiponectin levels. Sibutramine also exerts a beneficial effect on hyperandrogenaemia in obese women with polycystic ovary syndrome. Preliminary findings also suggest that weight loss following treatment with sibutramine is useful in patients with non-alcoholic fatty liver disease (NAFLD).Conclusion:Weight loss following sibutramine administration is associated with several favourable metabolic effects.

The aim of the study was to investigate the effect of fenofibrate on the concentration and relative distribution of low density lipoprotein (LDL) subfractions in patients with combined dyslipidemia. Micronised fenofibrate was administered in a single daily dose of 200 mg. Serum lipid parameters and LDL subfraction concentrations were determined at baseline as well as after 16 weeks of treatment. Fenofibrate administration resulted in a significant decrease in total LDL mass. This decrease was due to the reduction in all LDL subfractions. As a consequence, the relative distribution of LDL subfractions was not affected by fenofibrate administration.

SUMMARYThere is evidence showing that serum uric acid (SUA) levels predict the risk for vascular events. For example, up to 29% of the reduction in the primary composite endpoint seen in the LIFE trial (favouring losartan versus atenolol) can be attributed to a fall in SUA levels. We also discuss the findings of the GREACE study (treating to target with atorvastatin versus ‘usual’ care) in relation to SUA levels. In this brief comment we extend this argument to consider the SUA-lowering effect of other drugs commonly prescribed in patients with vascular disease (e.g. statins, fibrates and antihypertensive agents).

AbstractBackground/Aim: The type of heparin and membrane used might influence the lipids in patients on hemodialysis (HD). However, there are limited and debatable data concerning the lipid changes during an HD session. The aim of our study was to examine the changes in serum lipid parameters during the HD session in relation to the heparin and dialysis membrane used. Methods: Ten patients on HD 3 times/week participated in the study. The study was performed in three phases (A, B, C), each of 1 week’s duration. The types of membranes used were Hemophan (phase A), ethylene vinyl alcohol (phase B) and polyacrylonitrile (phase C), respectively, in a random order. During the midweek session of each phase we used classic heparin, while during the session at the end of the week low molecular weight heparin was administered. Serum total cholesterol, triglycerides, HDL cholesterol, Lp(a), albumin and total proteins were measured before and 5 min after the HD and hourly during the HD session. Results: In all phases, we found a progressive increase in all lipid parameters during the HD session, except Lp(a). This increase, however, was possibly due to hemoconcentration. Conclusions: This pilot study showed that (1) the type of heparin and membrane used does not seem to affect the serum lipid profile during a single HD procedure, and (2) the changes observed in serum lipid parameters are mainly due to hemoconcentration.Copyright © 2004 S. Karger AG, Basel

AbstractBackground: There are limited data regarding qualitative lipoprotein abnormalities in undialysed uremic patients without proteinuria. In this report, we focused on lipoprotein changes observed in uremic patients with proteinuria as well as on the susceptibility of low-density lipoprotein (LDL) of these patients to oxidative modification in vitro. Methods: 20 patients with chronic renal failure [serum creatinine >1.6 mg/dl (141.4 μmol/l)], but not yet on renal replacement therapy, and with heavy proteinuria (>2 g/24 h), and 18 age- and sex-matched healthy individuals participated in the study. In both patients and controls, venous blood was collected for determination of serum lipid and lipoprotein levels, lipoprotein subfraction profile and chemical composition, as well as the susceptibility of LDL subfractions to oxidation. Results: Patients exhibited a more atherogenic lipid profile compared with the control population. Furthermore, the total very LDL + intermediate-density lipoprotein mass was increased in patients compared with controls, while this subfraction was triglyceride enriched in uremic patients. The total LDL concentration was significantly higher in patients compared with controls due mainly to an increase in the mass of all lipoprotein subfractions. It is noteworthy that the mass of small dense LDL was significantly elevated in patients compared with controls (135 ± 12 vs. 115 ± 11 mg/dl, p = 0.01), an increase which was more pronounced in hypertriglyceridemic patients. Furthermore, the subfraction high-density lipoprotein-2 mass was significantly lower in uremic patients compared with controls. Finally, no significant differences in the lag time, the rate of oxidation and the relative electrophoretic mobility values in each LDL subfraction between the two groups were observed. Conclusion: We conclude that uremic patients with heavy proteinuria exhibit compositional lipoprotein changes that are less marked than those observed in nonuremic patients with nephrotic syndrome. However, there is no evidence that circulating LDL isolated from these patients is more susceptible to oxidation in vitro than lipoprotein isolated from age- and gender-matched controls.Copyright © 2003 S. Karger AG, Basel

SummaryFibric acid derivatives are a class of hypolipidaemic drugs used in the treatment of patients with hypertriglyceridaemia, mixed hyperlipidaemia and diabetic dyslipidaemia. Fibrate therapy results in a significant decrease in serum triglycerides and an increase in high-density lipoprotein (HDL) cholesterol levels. The latest drugs of this class are also effective in lowering low-density (LDL) cholesterol levels and can change the distribution of LDL towards higher and larger particles. The effects of fibrates on lipid metabolism are mostly mediated through the activation of peroxisome proliferator-activated receptors (PPARα). A number of angiographic and clinical trials have confirmed that fibrates can slow the progression of atherosclerotic disease and decrease cardiovascular morbidity and mortality. Recently published data suggest that the ability of fibrates to prevent atherosclerosis is not related only to their hypolipidaemic effects but also to other 'pleiotropic effects', such as their anti-inflammatory, antioxidant and antithrombotic effects, as well as their ability to improve endothelial function. Interestingly, fibrates may favourably influence the thrombotic/fibrinolytic system. In fact, most of these drugs can significantly decrease plasma fibrinogen levels and inhibit tissue factor expression and activity in human monocytes and macrophages. Some studies have shown that fibrates can improve carbohydrate metabolism in patients with dyslipidaemia, including diabetic patients. Among fibrates only fenofibrate can significantly decrease serum uric acid levels by increasing renal urate excretion. Fibrates, with the possible exception of gemfibrozil, can significantly increase serum creatinine and homocysteine levels. Finally, a reduction in serum alkaline phosphatase and gamma glutamyltranspeptidase (γGT) activity is a well-documented effect of therapy with fibrates.The fibrates are generally well-tolerated drugs with few side-effects. The most important side-effect is myositis, which is observed in patients with impaired renal function or when statins are given concomitantly.

.Purpose:
Although there are few data on the underlying mechanisms of primary open-angle glaucoma (POAG), it has been suggested that metabolic diseases may play a role in the evolution of the disease. We carried out the present study to investigate the involvement of metabolic disturbances in POAG pathogenesis.
Material/methods:
Serum metabolic parameters were evaluated in 49 POAG patients without a known history of diabetes mellitus and 72 age and sex matched individuals without glaucoma (control group).
Results:
Among the metabolic parameters examined, only fasting serum glucose and uric acid levels were found significantly higher in patients with glaucoma compared to the control population (117±17 mg/dl vs 105±11 mg/dl, p=0.05 and 6.2±1.9 mg/dl vs 5±1.2 mg/dl, p=0.006, respectively). Additionally, a considerably greater proportion of patients had disturbances of the carbohydrate metabolism and hyperuricemia.
Conclusion:
We conclude that disturbances of carbohydrate and uric acid metabolism could play a role in glaucoma damage and pathogenesis.

SummaryWe conducted an open-label study to test the effects of atorvastatin on serum lipids, lipoprotein(a) [Lp(a)] and plasma fibrinogen levels. A total of 90 dyslipidaemic, nonsmoking patients (45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia) aged 48 ± 11 years were studied. The patients were treated with 20 mg of atorvastatin for 24 weeks, in a single nocturnal dose. At baseline and every eight weeks, the fasting lipid profile, together with serum Lp(a) and plasma fibrinogen levels (Clauss method), were measured. Atorvastatin was highly effective in normalising the serum lipid profile. No significant change in median serum Lp(a) levels was observed in the whole group of patients (0.14 g/l before, vs. 0.16 g/l after, treatment) as well as in patients with raised (> 0.30 g/l) baseline levels (n 32). A small non-significant increase of plasma fibrinogen was found (3.04 g/l vs. 3.14 g/l) after 24 weeks of atorvastatin administration. The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia.In conclusion, our findings suggest that the effect of atorvastatin on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinically relevant. Furthermore, any rise in fibrinogen levels that may occur is likely to be transient in nature. Further studies are necessary to clarify this issue. There was no evidence that atorvastatin influences serum Lp(a) levels.

Kearns-Sayre syndrome (KSS) is a multisystem mitochondrial disorder characterized by the invariant triad: onset before 20, progressive external ophthalmoplegia and pigmentary retinal degeneration, plus at least one of the following: complete heart block, cerebellar dysfunction and CSF protein >100 mg/dl. Autopsies from patients with KSS revealed widespread tissue distribution of mitochondrial (mt) DNA deletions. These deletions result in significantly lower activities of the enzymes of the respiratory chain. KSS has been associated with a variety of endocrine and metabolic disorders in <10% of patients, while renal tubular involvement is extremely rare. We present an 18-year-old girl with KSS who developed hypoparathyroidism and renal tubular dysfunction with inappropriate mangesiuria and kaliuria. We further discuss the renal tubular damage in KSS emphasizing its pathophysiology and clinical phenotype, and review the possible mechanisms of hypoparathyroidism in KSS.

It has been reported that micronized fenofibrate and losartan can significantly decrease serum uric acid levels by augmenting uric acid excretion. We undertook this study to evaluate the effects of the combination treatment with micronized fenofibrate and losartan in nondiabetic hypertensive dyslipidemic patients with hyperuricemia (serum uric acid, >7 mg/dl). A total of 25 patients (15 men, 10 women) aged 21-66 years was studied. In all patients, serum lipid parameters, including Lp(a), fibrinogen, and uric acid levels, as well as fractional excretion of uric acid (FEUA) were obtained before treatment, 8 weeks after micronized fenofibrate treatment (200 mg daily), and 8 weeks after combination therapy with micronized fenofibrate (200 mg daily) and losartan (50 mg daily). Fenofibrate alone significantly decreased total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, Apo B, Lp(a), fibrinogen, and uric acid levels (from 7.6 ± 0.55 to 5.6 ± 0.5 mg/dl; p < 0.0001) and increased high-density lipoprotein (HDL) cholesterol, Apo A1, and FEUA (from 6.5 ± 1.8% to 12.2 ± 4%; p < 0.0001). The addition of losartan beyond the decrease in blood pressure values did not significantly alter serum metabolic parameters. However, a small additional decrease in serum uric acid levels (from 5.6 ± 0.5 to 4.9 ± 1 mg/dl; p < 0.05) was found because of a further increase in FEUA (from 12.2 ± 4% to 14 ± 5.5%; p < 0.05). It is concluded that the combination of micronized fenofibrate and losartan is useful for the management of patients with multiple metabolic abnormalities, including hyperuricemia.

Hemorrhagic fever with renal syndrome is an acute febrile nephropathy caused by several viruses of the genus Hantavirus of the family Bunyaviridae. During the past 8 years, 32 cases of hemorrhagic fever with renal syndrome have been diagnosed. Nine out of the 32 patients (28) had raised (twofold upper normal limits) trans-aminases during hospitalization. Four out of the nine patients (44) died. In contrast, only three out of the 23 patients (13) without raised transaminases died. Five patients had slightly increased serum alkaline phospha-tase and γ-glutamyl-transpeptidase, whereas six patients had prolonged prothrombin time. Liver histology showed midzonal necrosis in hepatic lobules with extravasation of red cells and mild mononuclear infiltrate. Liver involvement seems to be an ominous prognostic factor in such patients and is correlated with severe renal failure and thrombocytopenia.

The aims of our study were: (1) to detect the prevalence of cigarette smoking among female students in Northwestern Greece, and (2) to assess the relation of cigarette smoking with other harmful lifestyles (such as alcohol consumption, obesity, type of dietary fat), fasting lipids and blood pressure. A total of 590 female students in the last class of the local senior high schools was studied. Seventy-seven (13%) of the students were smokers. Interestingly, in this cohort of young female students clustering of the smoking habit with dyslipidemia and alcohol use was observed. However, smoking was associated with signif icantly lower levels of blood pressure, as well as with lower mean body weight and body mass index. In conclusion, a considerable though apparently decreasing number of Greek female students are smokers. The smoking habit is strongly associated with dyslipidemia and alcohol consumption in this population.

The aim of our study was to describe the possible pathophysiologic mechanisms of hypomagnesemia in alcoholic patients. A total of 127 chronic alcoholic patients admitted to our university hospital for causes related to alcohol abuse were studied. Hypomagnesemia was the most common electrolyte disturbance observed in 38 patients (29.9 %). In 18 of them inappropriate magnesiuria was evident, possibly due to hypophosphatemia, to metabolic acidosis or to a direct magnesiuric effect of acute alcohol consumption. The causes of hypomagnesemia in the remaining 20 patients were alcohol withdrawal syndrome and diarrhea. Respiratory alkalosis was evident in 10 hypomagnesemic patients and could have played a role in the development of hypomagnesemia. A decreased magnesium intake could also have contributed to the hypomagnesemia, especially in malnourished alcoholic patients. Hypomagnesemic patients more frequently had other acid — base and electrolyte abnormalities, such as hypophosphatemia, hypokalemia, hypocalcemia, and respiratory alkalosis, as compared with the normomagnesemic patients. Moreover, in hypomagnesemic patients serum magnesium levels were correlated with the indices of potassium and phosphorus excretion, suggesting that serum magnesium levels play a central role in the homeostasis of the other electrolytes. In conclusion, hypomagnesemia is the most common electrolyte abnormality observed in alcoholic patients, as a result of various pathophysiologic mechanisms.

Renal tubular acidosis (RTA) is a frequent extraglandular manifestation of Sjögren's syndrome; however, no distinction on the incidence of this renal tubular defect between primary and secondary Sjögren's syndrome has been reported. This study was undertaken in order to define the frequency of RTA and the possible pathogenetic mechanisms in a group of 21 randomly selected primary Sjögren's syndrome patients. RTA was found in 7 (33%) patients. The incomplete type of the disorder was the most frequent. It seems that the etiology of RTA is multifactorial. Renal excretion of monoclonal proteins and the immunologically-induced interstitial inflammation are the main possible factors of this renal tubular defect.

Patients with heterozygous familial hypercholesterolaemia (FH) have elevated plasma concentrations of low-density lipoprotein (LDL) and develop premature atherosclerosis. There is increasing evidence that oxidative modification of LDL is important for the pathogenesis of atherosclerosis, and the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the distribution of PAF-AH activity among three LDL subfractions isolated by gradient ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic control subjects. We also determined the lyso-PC production in each LDL subfraction during Cu 2+ -induced oxidation in vitro . The total serum PAF-AH activity in heterozygous FH patients was significantly higher than in control subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage of total serum PAF-AH activity, was significantly lower in the FH patients than in control subjects (13.9 ± 6.6% vs. 30.6 ± 4.4%, P &lt; 0.001). Among the LDL subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH patients, expressed as nmol mg -1 protein min -1 , was significantly higher in the LDL3 subfraction (33.1 ± 4.8 and 53.4 ± 11.5 respectively) than in the LDL2 (18.6 ± 5.3 and 26.8 ± 10.4 respectively, P &lt; 0.0001 for both comparisons) and LDL1 subfractions (5.1 ± 1.5 and 7.8 ± 2.6, respectively, P &lt; 0.0001 for both comparisons). Additionally, the enzyme activity in each LDL subfraction of the heterozygous FH patients was significantly higher than in control subjects ( P &lt; 0.02 for LDL1, P &lt; 0.03 for LDL2 and P &lt; 0.0001 for LDL3). No difference was observed in the susceptibility to oxidation of each LDL subfraction among the heterozygous FH patients and the normolipidaemic control subjects. During oxidation, the PAF-AH activity decreased, whereas the lyso-PC levels significantly increased in all subfractions of both groups. The lyso-PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after the onset of the oxidation was significantly higher than in control subjects [0.38 ± 0.05 and 0.27 ± 0.04, respectively, for LDL1 ( P &lt; 0.006), 0.47 ± 0.08 and 0.39 ± 0.03, respectively, for LDL2 ( P &lt; 0.04), 0.55 ± 0.11 and 0.42 ± 0.06, respectively, for LDL3 ( P &lt; 0.02)]. Our results show that heterozygous FH patients exhibit higher PAF-AH activity than control subjects in all LDL subfractions, resulting in higher lyso-PC production during oxidation, which confers on these subfractions higher biological potency. This phenomenon, in combination with the diminished anti-atherogenic and antioxidant capability of HDL in these patients due to the relatively low HDL-cholesterol levels compared with LDL-cholesterol levels and, consequently, the relatively low HDL-associated PAF-AH activity, could contribute to the higher atherogenicity and incidence of coronary artery disease observed in FH patients.