Hyperlipidemias: Greece

Dedoussis GV, Schmidt H, Genschel J. · Department of Science Dietetics-Nutrition, Harokopio University of Athens, Athens, Greece. · Hum Mutat. · Pubmed #15523646 No free full text.

Abstract: Familial hypercholesterolemia (FH) is a clinical definition for a remarkable increase of cholesterol serum concentration, presence of xanthomas, and an autosomal dominant trait of either increased serum cholesterol or premature coronary artery disease (CAD). The identification of the low-density lipoprotein (LDL)-receptor (LDLR) as the underlying cause and its genetic characterization in FH patients revealed more insights in the trafficking of LDL, which primarily transports cholesterol to hepatic and peripheral cells. Mutations within LDLR result in hypercholesterolemia and, subsequently, cholesterol deposition in humans to a variable degree. This confirms the pathogenetic role of LDLR and also highlights the existence of additional factors in determining the phenotype. Autosomal dominant FH is caused by LDLR deficiency and defective apolipoprotein B-100 (APOB), respectively. Heterozygosity of the LDLR is relatively common (1:500). Clinical diagnosis is highly important and genetic diagnosis may be helpful, since treatment is usually effective for this otherwise fatal disease. Very recently, mutations in PCSK9 have been also shown to cause autosomal dominant hypercholesterolemia. For autosomal recessive hypercholesterolemia, mutations within the so-called ARH gene encoding a cellular adaptor protein required for LDL transport have been identified. These insights emphasize the crucial importance of LDL metabolism intra- and extracellularly in determining LDL-cholesterol serum concentration. Herein, we focus on the published European LDLR mutation data that reflect its heterogeneity and phenotypic penetrance.

Yanni AE. · The Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Lab Anim. · Pubmed #15207035 No free full text.

Abstract: The aim of the present mini review is to describe the laboratory rabbit, an animal that has been widely used for the study of atherosclerosis, the leading cause of mortality in Western society. Due to the fact that the rabbit exhibits hypercholesterolaemia within a few days of an administration of a high cholesterol diet, it is very sensitive to the inducement of atheromatic lesions. The administration of different types of diets can cause different types of lesions. Although these lesions do not develop as tissue plaques, a great number of researchers use this animal model to test the effectiveness of drugs because of their similarity to human fatty streaks. The generation over recent years of transgenic rabbits with alterations in specific genes is expected to help with the elucidation of the mechanisms underlying the initial and developmental stages of the disease. The laboratory rabbit is significantly broadening our understanding on the pathogenesis of atherosclerosis.

Antoniades C, Tousoulis D, Tentolouris C, Toutouzas P, Stefanadis C. · Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece. · Herz. · Pubmed #14689123 No free full text.

Abstract: Oxidative stress is involved in the pathogenesis of atherosclerosis, while a variety of antioxidants has been used in clinical studies, during the past few years, for the prevention and treatment of atherosclerosis. In small clinical studies it was found that both vitamins C and E may improve endothelial function in patients with risk factors for atherosclerosis such as diabetes mellitus, smoking, hypertension, or hypercholesterolemia. However, the initial, hopeful reports regarding the beneficial role of antioxidant vitamins against atherosclerosis, derived from purely observational studies, were followed by the negative results of almost all large randomized trials. Therefore, treatment with antioxidant vitamins C and E should not be recommended for the prevention or treatment of coronary atherosclerosis. New antioxidant strategies are needed to clarify the exact role of antioxidant treatment in coronary atherosclerosis.

Tsiara S, Elisaf M, Mikhailidis DP. · Internal Medicine Department, University of Ioannina Medical School, Ioannina, Greece. · Curr Med Res Opin. · Pubmed #14594527 No free full text.

Abstract: Large-scale trials established that statin administration in hypercholesterolaemic individuals and patients with coronary heart disease (CHD) significantly reduces the risk of vascular events and death. This benefit was primarily attributed to their actions on lipids. This review focuses on the benefits (clinical and experimental) of statins observed soon (approximately 12 weeks) after their administration. Statins rapidly increase nitric oxide production and improve endothelial function (e.g. increased flow-mediated dilatation). Similarly, antioxidant properties decrease the susceptibility of low density lipoprotein cholesterol to oxidation. Statins inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect and the stabilisation of atherosclerotic plaques. Anti-inflammatory effects include a reduction in serum C-reactive protein levels, inflammatory and proinflammatory cytokines (e.g. IL-6, IL-8), adhesion molecules (e.g. ICAM-1, VCAM-1) and other acute phase proteins. Statins influence the haemostatic system. They reduce tissue factor expression and platelet activity, whereas fibrinolysis can be enhanced. Statins improve microalbuminuria, renal function, hypertension and arterial wall stiffness. A significant reduction of the carotid intima media thickness (IMT) was also reported early after statin treatment. These early effects of statins probably contribute to the significant reduction in vascular events seen in some 'short-term' studies. There is a need to further elucidate the rapid and non-lipid lowering properties of statins.

Milionis HJ, Elisaf MS, Mikhailidis DP. · Department of Internal Medicine, Medical School, Universities of Ioannina, Greece. · Curr Pharm Des. · Pubmed #14529557 No free full text.

Abstract: There is growing evidence that the components of the haemostatic system play a significant role in the development and progression of atherosclerosis and its complications. Lipid-lowering interventions have been associated with a significant reduction of morbidity and mortality. However, the improvement in cardiovascular risk seen in several clinical trials is incompletely explained by cholesterol reduction. Therefore, the benefit from lipid lowering drugs may involve non-lipid mechanisms. These include beneficial effects on the arterial wall, improved endothelial function and a favourable influence on blood rheology and thrombogenesis. In this review, we consider the influence of lipid-lowering interventions on rheological and haemostatic parameters as well as the potential clinical relevance of these effects.

Tsimihodimos V, Karabina SA, Tambaki A, Bairaktari E, Achimastos A, Tselepis A, Elisaf M. · Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece. · J Cardiovasc Pharmacol. · Pubmed #12883336 No free full text.

Abstract: The authors investigated the effect of atorvastatin (40 mg qd) on low-density lipoprotein (LDL) particle distribution in patients with dyslipidemias of type IIA (n = 55) and IIB (n = 21). Atorvastatin therapy induced a significant decrease in total and LDL cholesterol in both patient groups. A significant reduction in triglyceride values, which was more profound in type IIB patients, was also observed. In type IIA patients, LDL-3 was the predominant subfraction. Atorvastatin therapy induced a significant reduction in total LDL mass in this group of patients that was mainly due to the reduction in large and intermediate subspecies (LDL-1 to LDL-3), whereas the mass of dense LDL particles (LDL-4 and LDL-5) remained unchanged. As a consequence, the percentage contribution of dense subfractions to the total LDL mass increased significantly after atorvastatin therapy. The dense LDL-4 subfraction was the predominant one in type IIB patients. In this group, atorvastatin therapy resulted in a significant reduction in the total LDL mass, which was due to the reduction in all LDL subfractions. Thus, the percentage mass distribution of LDL particles remained unaffected. These results suggest that the effect of atorvastatin on LDL subfractions is affected by the underlying genetic defect.

Anagnostopoulos GK, Tsiakos S, Margantinis G, Kostopoulos P, Arvanitidis D. · Gastroenterology Department, 251 Hellenic Air Force and Veterans General Hospital, Athens, Greece. · JOP. · Pubmed #12743419 links to  free full text

Abstract: CONTEXT: Few data exist about the incidence of drug-induced pancreatitis in the general population. Drugs are related to the etiology of pancreatitis in about 1.4-2% of cases. Statins are generally well tolerated. Acute pancreatitis has been reported in a few cases treated with atorvastatin, fluvastatin, lovastatin and simvastatin. CASE REPORT: We report the case of a 56-year-old patient who, after 6 months of treatment with pravastatin 20 mg once daily for hypercholesterolemia, presented with acute pancreatitis. Other causes of the disease were ruled out. Five months later, the patient, on his own initiative, reintroduced pravastatin and acute pancreatitis recurred after 3 days. CONCLUSION: To our knowledge this is the first report of pravastatin-induced pancreatitis and further strengthens the fact that statins may cause acute pancreatitis.

Elisaf M, Mikhailidis DP. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Angiology. · Pubmed #12365855 No free full text.

Abstract: Renal disease is often associated with an increased risk of vascular events. Moreover, an accelerated form of atherosclerosis commonly occurs in these patients. The reasons for these associations are not clearly defined but include the widespread presence of several established risk factors (eg, dyslipidemia, hypertension, and diabetes). Other predictors of atherosclerotic disease may also be abnormally elevated (eg, homocysteine, fibrinogen, and lipoprotein a). In addition, there is evidence that impaired renal function per se predicts vascular risk. Despite this high-risk background, the potential benefit of treatment with statins has not been widely investigated in these patients. The present review considers the evidence (experimental and clinical) that statins exert beneficial effects in patients with different types of renal disease. This includes improved renal function, decreased microalbuminuria, and a fall in blood pressure. Statins may also improve renal allograft survival. The potential mechanisms mediating these effects are considered. The interactions between statins and several risk factors that may be present in patients with impaired renal function are also considered. There is an urgent need to define the role of statins in these high-risk patients. Which is the statin of choice? This question is relevant because impaired renal function can interfere with statin pharmacokinetics. Furthermore, other drugs administered to these patients may cause serious interactions with statins.

Elisaf M. · Department of Internal Medicine, Medical School, University of Ioannina, Greece. · Curr Med Res Opin. · Pubmed #12240789 No free full text.

Abstract: Fibric 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 (PPARalpha). 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 (gammaGT) 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.

Kolovou GD, Cokkinos DV. · First Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece. · Curr Med Res Opin. · Pubmed #12240788 No free full text.

Abstract: Low serum levels of high-density lipoprotein (HDL) cholesterol is an independent risk factor for coronary artery disease. Raising HDL cholesterol should be an important therapeutic goal in patients with coronary artery disease. Fibrates can reduce the risk of cardiac events and death from coronary artery disease.

Tentolouris C, Tousoulis D, Goumas G, Stefanadis C, Davies G, Toutouzas P. · Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece. · Int J Cardiol. · Pubmed #11077122 No free full text.

Abstract: Nitric oxide is formed from the N-guanido terminal of the amino acid L-arginine and from molecular oxygen by nitric oxide synthase enzymes. L-arginine administration improves the coronary blood flow response to acetylcholine in patients with normal coronary arteries and hypercholesterolemia, reverses the defective endothelium-dependent vasodilation associated with an elevated plasma low-density lipoprotein level or hypercholesterolemia, dilates coronary epicardial arteries and stenoses, enhances nitric oxide generation, and inhibits lesion formation after balloon angioplasty. Stimulation of endogenous nitric oxide production could inhibit atherogenesis, and therefore may be of benefit in patients with risk factors for atherosclerosis.

Athyros VG, Tziomalos K, Kakafika AI, Koumaras H, Karagiannis A, Mikhailidis DP. · Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece. · Am J Cardiol. · Pubmed #18312762 No free full text.

Abstract: This study was undertaken to investigate the effect of ezetimibe (10 mg/day) alone or in combination with atorvastatin (10 mg twice a week) on hypercholesterolemia in 56 high-risk patients intolerant to daily statin use. Ezetimibe monotherapy was well tolerated (2 withdrawals) and induced a mean reduction in low-density lipoprotein (LDL) cholesterol of 20% (p <0.05) at the third month. However, of the 54 patients still taking ezetimibe, only 5 (9%) were at their LDL cholesterol targets. Atorvastatin 10 mg twice a week was then added to ezetimibe and was well tolerated (3 withdrawals). This combination reduced LDL cholesterol (in a treatment-based analysis) by 37% compared with baseline (p <0.001), with 43 (84%) patients reaching their LDL cholesterol goals. When patients (n = 34, 25 men) with baseline serum creatinine values in the upper 2 tertiles were analyzed separately, there was a significant (p = 0.041) decrease in serum creatinine levels after 6 months of treatment. In conclusion, the combination of ezetimibe plus atorvastatin 10 mg twice a week might be a therapeutic option for high-risk patients intolerant to daily statin monotherapy.

Kostapanos MS, Milionis HJ, Gazi I, Kostara C, Bairaktari ET, Elisaf M. · Department of Internal Medicine, School of Medicine, University of Ioannina, 451 10 Ioannina, Greece. · J Clin Pharmacol. · Pubmed #17050799 No free full text.

Abstract: The renoprotective effect of statins has been recently disputed because of observations of proteinuria associated with rosuvastatin treatment, the newest drug of the class. Statin-induced proteinuria findings were mainly based on crudely quantitative dipstick assays. The authors quantitatively evaluated the effect of rosuvastatin at the recommended starting dose of 10 mg/d, on urine protein excretion in patients with primary dyslipidemia. Serum lipid and nonlipid parameters as well as urinary electrolyte, creatinine, and protein (total, albumin, immunoglobulin G, and alpha-1 microglobulin) levels were measured in 40 patients treated with rosuvastatin and 30 controls at baseline and after 12 weeks. The protein-to-creatinine ratios were used to assess urinary protein excretion. Rosuvastatin improved the lipid profile, produced no deterioration of kidney function, but induced a small but significant increase in the excretion of alpha-1 microglobulin (by 16%, P < .05) indicating that statin-related proteinuria involves low-molecular-weight proteins and is of proximal tubular origin.

Tavridou A, Efthimiadis A, Efthimiadis I, Paschalidou H. · Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100, Alexandroupolis, Greece. · Eur J Clin Pharmacol. · Pubmed #16758266 No free full text.

Abstract: OBJECTIVE: The aim of the present study was to determine the effect of simvastatin on the levels of oxidized low-density lipoprotein (ox-LDL) and free radicals in hypercholesterolemic subjects undergoing primary and secondary prevention of coronary heart disease (CHD). METHODS: Fifteen subjects with hypercholesterolemia and no obvious CHD and 29 subjects with hypercholesterolemia and stable angina received 40 mg of simvastatin daily for 12 weeks. Serum total cholesterol, HDL-cholesterol and triglyceride concentrations were determined by automated enzymatic assays whereas LDL-cholesterol was calculated using the Friedwald formula. The ox-LDL levels were determined by a commercially available ELISA kit. Free radicals were assessed by the Free Radical Analytical System (FRAS). RESULTS: Both in primary and secondary prevention, subjects had borderline levels of free radicals but in neither group there was a significant reduction of free radicals after simvastatin treatment. In subjects undergoing primary prevention of CHD, ox-LDL levels were reduced by 31.1+/-5.0% (P < 0.001) whereas in secondary prevention were reduced by 6.5+/-5.2% (P < 0.02) after simvastatin treatment. The reduction of ox-LDL levels did not correlate with the reduction of total cholesterol levels in either group studied. In both groups, ox-LDL levels were not associated with free radical levels either before or after simvastatin treatment. CONCLUSION: This study demonstrates that simvastatin can significantly reduce circulating ox-LDL levels both in subjects undergoing primary and secondary prevention of CHD. These results could partly explain the slowing down of the progression of atherosclerosis caused by HMG-CoA reductase inhibitors.

Milionis HJ, Gazi IF, Filippatos TD, Tzovaras V, Chasiotis G, Goudevenos J, Seferiadis K, Elisaf MS. · Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece. · Angiology. · Pubmed #16193198 No free full text.

Abstract: The authors investigated the effects of rosuvastatin, beyond its lipid-lowering activity, on several nonlipid metabolic variables, along with its safety and tolerability, in patients treated for primary hyperlipidemia. Patients (n = 55) with primary hyperlipidemia were open-label assigned to the recommended starting dose of rosuvastatin 10 mg/day, and serum metabolic variables were measured at baseline and after 8 and 20 weeks. Treatment with rosuvastatin produced significant reductions in total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, nonhigh-density lipoprotein cholesterol (non HDL-C), and triglyceride concentrations, whereas HDL-C, apolipoprotein A-I, and lipoprotein(a) levels did not change significantly from baseline. The LDL-C treatment target was achieved in 71% of patients. No significant variations in renal function parameters (serum creatinine and creatinine clearance), insulin resistance estimates, and serum concentrations of uric acid, total homocysteine, vitamin B12, and folic acid were observed during the period of treatment. High-sensitivity C-reactive protein levels were significantly lowered by rosuvastatin therapy (median values, 3.1 vs 2.0 vs 1.9 mg/L, at 0, 8, and 20 weeks, respectively; p < 0.0001). In conclusion, rosuvastatin at 10 mg/day is a highly effective, safe, and well-tolerated monotherapy option for patients with primary hyperlipidemia, with a favorable antiinflammatory potential and nondeteriorating effects on renal function.

Athyros VG, Mikhailidis DP, Papageorgiou AA, Didangelos TP, Peletidou A, Kleta D, Karagiannis A, Kakafika AI, Tziomalos K, Elisaf M. · Atherosclerosis and Metabolic Syndrome Units, Aristotelian University, 55132 Thessaloniki, Greece. · Metabolism. · Pubmed #16092057 No free full text.

Abstract: There are no prospective data on the effect of a multitargeted treatment approach on cardiovascular disease (CVD) risk reduction in nondiabetic patients with metabolic syndrome (MetS). Furthermore, the optimal hypolipidemic drug treatment in these patients remains controversial. In this prospective, randomized, open-label, intention-to-treat, and parallel study, 300 nondiabetic patients with MetS, free of CVD at baseline, were studied for a period of 12 months. Age- and sex-matched subjects without MetS (n = 100) acted as controls. All patients received lifestyle advice and a stepwise-implemented drug treatment of hypertension, impaired fasting glucose, and obesity. For hypolipidemic treatment, the patients were randomly allocated to 3 treatment groups: atorvastatin (n = 100, 20 mg/d), micronized fenofibrate (n = 100, 200 mg/d), and both drugs (n = 100). Clinical and laboratory parameters, including the lipid profile and C-reactive protein (CRP), were assessed at the baseline and at the end of the study. The primary end point was the proportion of patients not having MetS or its component features at the end of the 12-month treatment period. The secondary end points were the difference in 10-year CVD risk (Prospective Cardiovascular Munster risk calculator) and the degree of CRP reduction. By the end of the study, 76% of the patients no longer had MetS, and 46% had only one diagnostic MetS factor. The estimated 10-year (Prospective Cardiovascular Munster) risk of all patients with MetS at baseline was 14.6%. This was reduced in the atorvastatin group to 6.4%, in the fenofibrate group to 9.2%, and in the combination group to 5.5% (P < .0001 for all vs baseline). The 10-year risks of the atorvastatin and combination groups were not different from that of the control group (5.0%). C-reactive protein was significantly reduced in all treatment groups, with the atorvastatin and combination groups having the greatest reduction (65% and 68%, respectively, P < .01 vs the fenofibrate group, 44%). Lipid values were significantly improved in all 3 treatment groups, with those on the combined treatment attaining lipid targets to a greater extent than those in the other 2 groups. A target-driven and intensified intervention aimed at multiple risk factors in nondiabetic patients with MetS substantially offsets its component factors and significantly reduces the estimated CVD risk. The atorvastatin-fenofibrate combination had the most beneficial effect on all lipid parameters and significantly improved their CVD risk status. Atorvastatin and combination treatment were more effective than fenofibrate alone in reducing CRP levels.

Kyriakidis AV, Karydakis P, Neofytou N, Pyrgioti M, Vasilakakis D, Digenis P, Antsaklis G. · Department of Surgery, Renal Dialysis Unit, Sismanogleion Hospital, Athens, Greece. · Pancreatology. · Pubmed #15855816 No free full text.

Abstract: BACKGROUND/AIM: Hyperlipidemic pancreatitis is an acute and potentially life-threatening complication of hypertriglyceridemia that can be provoked when triglyceride levels (TGL) exceed 11.3 mmol/l (1,000 mg/dl). Except for standard symptomatic treatment, plasmapheresis has been performed to rapidly reduce TGL and chylomicron levels in the blood. In 5 patients with hyperlipidemic pancreatitis, treatment with plasmapheresis was evaluated. METHODS: Five male patients who suffered from acute pancreatitis with severe primary hyperlipidemia were studied. In addition to the standard treatment, they were treated with plasmapheresis. RESULTS: Plasma exchange lowered the lipid level and TGLs in all cases. It also improved abdominal pain, the clinical state of the patients, and signs and symptoms of the disease. Complications of treatment were not encountered, none of the patients died and only 1 patient underwent surgery. Follow-up of the patients lasted 4-28 months, and recurrence of pancreatitis was not noted. CONCLUSION: Our study showed that plasmapheresis was successfully applied in patients with hyperlipidemic pancreatitis, especially to improve the acute phase of the disease.

Athyros VG, Mikhailidis DP, Papageorgiou AA, Bouloukos VI, Pehlivanidis AN, Symeonidis AN, Kakafika AI, Daskalopoulou SS, Elisaf M. · Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, 49 Konstantinoupoleos St, Thessaloniki, 546 42, Greece. · Platelets. · Pubmed #15823861 No free full text.

Abstract: DECLARATION OF INTEREST: The GREACE study was conducted independently; no Company or Institution has supported it financially. Some of the authors have attended conferences and participated in other trials sponsored by various pharmaceutical companies.We assessed the possible 'synergy' of statins and aspirin (ASA) in reducing vascular events in patients with coronary heart disease, in a post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. All patients (n = 1600) were divided into four groups according to long-term treatment: Group A (n = 787; statin + ASA), B (n = 93; statin - no ASA), C (n = 599; no statin - on ASA) and D (n = 121; no statin - no ASA). From all patients 692 were either on a statin or ASA monotherapy (Groups B + C). Relative risk reductions (RRRs) in 'all events' (primary endpoint) between groups were assessed. During the 3-year follow-up there were 292 cardiovascular events; 92 (12% of patients) in Group A, 14 (15%) in group B, 144 in Group C (24%) and 42 events in Group D (35%). The total number of events in Group B + C was 158 (23%). The RRRs in the primary endpoint were: Group A versus B 24% (P = 0.1912), A versus C 51% (P < 0.0001), A versus B + C 49% (P < 0.0001) and A versus D 71% (P < 0.0001). The RRRs in Group B versus C was 36% (P = 0.0431) and B versus D 57% (P = 0.0012), while in C versus D 33% (P = 0.0084). Our findings show that statins and ASA have an additive effect in reducing cardiovascular events. Aggressive statin use in the absence of ASA also substantially reduced cardiovascular events. Treatment with ASA in the absence of statin use reduced clinical events in comparison to patients not treated with either drug.

Sbarouni E, Kyriakides ZS, Kremastinos DT. · 2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece. · J Womens Health (Larchmt). · Pubmed #15775733 No free full text.

Abstract: BACKGROUND: Homocysteine may be an independent risk factor for coronary artery disease (CAD), and the risk is at least as strong for women as for men. Homocysteine levels are lower in women compared with men, and homocysteine is lower during pregnancy and higher during menopause. PURPOSE: To investigate the effects of hormone replacement therapy (HRT), simvastatin, and their combination on plasma homocysteine levels, we treated 16 postmenopausal, hypercholesterolemic women with CAD with HRT (0.625 mg conjugated equine estrogens [CEE] combined continuously with 2.5 mg medroxyprogesterone), 20 mg simvastatin, and their combination in a randomized, placebo-controlled study. Each treatment period was 8 weeks long, with a 4-week washout interval. Plasma homocysteine levels were evaluated at the end of each treatment period. RESULTS: Only HRT, alone and in combination with simvastatin, significantly reduced homocysteine levels compared with placebo (11.82 +/- 0.74 and 12.22 +/- 0.71 vs 13.58 +/- 0.83 micromol/L, respectively, p < 0.05). Simvastatin had no effect (13.02 +/- 0.94 micromol/L), and the combination therapy was not better that monotherapy with HRT. CONCLUSIONS: Oral HRT reduces homocysteine plasma levels, whereas simvastatin has no effect. If confirmed by randomized, prospective studies with clinical end points, HRT may be considered for women with mild hypercholesterolemia and high homocysteine levels.

Kolovou GD, Anagnostopoulou KK, Pilatis ND, Giannopoulou M, Hoursalas IS, Pavlidis AN, Adamopoulou E, Valaora AI, Mikhailidis DP, Cokkinos DV. · 1st Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece. · J Womens Health (Larchmt). · Pubmed #15650345 No free full text.

Abstract: BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) is a genetic disease that leads to premature atherosclerosis. Natural menopause leads to an adverse lipid profile and an enhanced risk of coronary heart disease (CHD). Raised plasma triglyceride (TG) levels also contribute to the risk of vascular events. The aim of this study was to evaluate the postprandial TG levels (after a standardized fatty meal) in premenopausal and postmenopausal women with hFH. METHODS: Thirty-three Greek women with hFH were divided into the premenopausal group--n = 16, mean age 34(SD = 7), mean total cholesterol = 330(30) mg/dl--and the postmenopausal group--n = 17, mean age 62(5), mean total cholesterol = 346(63) mg/dl. Plasma TG concentrations were measured before and 2, 4, 6, and 8 hours after a standardized fat load. A value of >219 mg/dl (2.5 mmol/L) was taken as an abnormal response to the fat load, according to our previous studies. RESULTS: Postmenopausal women had higher TG levels at 2 (p = 0.001), 4 (p = 0.003), 6 (p = 0.003), and 8 hours (p = 0.005) after the fatty meal compared to premenopausal women. Forty-one percent of postmenopausal hFH women had abnormal TG response (hFH-A) after a fatty meal, and such women had higher fasting TG levels than postmenopausal hFH women with a normal response to the fatty meal (hFH-N) (p = 0.0014). CONCLUSIONS: Women with hFH tend to have an abnormal TG response to a fatty meal after the menopause. Fasting TG levels may be able to predict the abnormal response to a fatty meal.

Lekakis JP, Papamichael CM, Papaioannou TG, Dagre AG, Stamatelopoulos KS, Tryfonopoulos D, Protogerou AD, Stamatelopoulos SF, Mavrikakis M. · Vascular Laboratory, Department of Clinical Therapeutics, "Alexandra" Hospital, National & Kapodistrian University of Athens, Greece. · Eur J Cardiovasc Prev Rehabil. · Pubmed #15616416 No free full text.

Abstract: BACKGROUND: Folic acid therapy has been shown to improve endothelial function in patients with familial hypercholesterolaemia via a possible antioxidant mechanism. Data on the possible role of folic acid in hypercholesterolaemic patients receiving statins are lacking. In the present study we tested the hypothesis that folic acid supplementation improves endothelial function in patients with hypercholesterolaemia and treatment with statins. METHODS: Thirty-four hypercholesterolaemic patients receiving statins participated in the study; all subjects underwent measurement of endothelium-dependent, flow-mediated dilatation of the brachial artery and subsequently randomized to receive 5 mg of the folic acid (n=17) or placebo (n=17) for 4 weeks. Flow-mediated dilatation of the brachial artery was repeated at the end of the 4-week period. RESULTS: Folic acid and placebo groups were comparable regarding age, sex, smoking, hypertension, coronary artery disease, obesity, family history and blood lipids. Folic acid administration resulted in an improvement of flow-mediated dilatation (4.7+/-3.2% to 7.1+/-3.1%, P=0.02), whereas there was no improvement after placebo administration (5.7+/-3.8% to 5.6+/-2.2%, ns). No significant change in nitrate-induced, endothelium- independent dilatation was observed after folic acid or placebo (ns). CONCLUSIONS: Oral administration of folic acid (5 mg) for 4 weeks improves endothelial function in patients with hypercholesterolaemia treated with statins, with possible beneficial effects on the prognosis of these patients.

Paschos GK, Rallidis LS, Liakos GK, Panagiotakos D, Anastasiadis G, Votteas V, Zampelas A. · Department of Nutrition and Dietetics, Harokopio University, 70 El Venizelou Street, Athens 17671, Greece. · Br J Nutr. · Pubmed #15522134 No free full text.

Abstract: Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects. We evaluated the effect of alpha-linolenic acid (ALA), precursor of n-3 fatty acids, on serum inflammatory markers and soluble cellular adhesion molecules (sCAM) of dyslipidaemic males, relative to their background diet. Participants were assigned to two groups, based upon food intake patterns: (a) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet; (b) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet. All were supplemented with 8.1 g ALA/d for 12 weeks. We determined serum amyloid A (SAA), C-reactive protein (CRP), macrophage colony-stimulating factor (MCSF), IL-6, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period. Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups. Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation. The Westernised Greek diet group showed a reduction in SAA (P<0.001), CRP (P=0.002), MCSF (P=0.005) and IL-6 (P=0.04) concentrations. The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations (P=0.003). The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group (P=0.001) and the Mediterranean-Cretan-type diet group (P<0.001). The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA.

Milionis HJ, Kakafika AI, Tsouli SG, Athyros VG, Bairaktari ET, Seferiadis KI, Elisaf MS. · Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece. · Am Heart J. · Pubmed #15459594 No free full text.

Abstract: BACKGROUND: Epidemiologic studies have shown that serum uric acid is a risk factor of coronary artery disease. In addition to fenofibrate, there is some evidence that atorvastatin may have a hypouricemic action, but the underlying mechanisms remain speculative. METHODS: This randomized trial was conducted to investigate the effects of atorvastatin and simvastatin on uric acid homeostasis in patients treated for primary hyperlipidemia. A total of 180 patients were enrolled; patients were randomly assigned to 40 mg/d of either atorvastatin or simvastatin. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment; random urine samples were simultaneously obtained for creatinine, sodium, and uric acid determinations. RESULTS: Baseline serum uric acid levels correlated positively with the body mass index, serum insulin, creatinine, and triglyceride levels and inversely with serum HDL cholesterol levels. Both statins caused a favorable effect on lipids and a significant decrease in fibrinogen and high-sensitivity CRP levels. However, only atorvastatin reduced serum uric acid levels (from 5.6 +/- 1.7 to 4.9 +/- 1.5 mg/dL, P <.0001) by augmenting its urinary fractional excretion (from 10.4% +/- 7.9% to 12.0% +/- 7.4%, P <.01). In a multivariate logistic regression analysis, the reduction of uric acid levels was independently associated with baseline serum uric acid concentration but not to other variables, including lipid parameters (OR, 1.65; 95% CI, 1.14 to 2.40; P =.008). CONCLUSIONS: Atorvastatin (but not simvastatin) significantly lowered serum uric acid levels. This result may be in favor of a preferable choice of atorvastatin for the treatment of hyperlipidemic patients presenting with hyperuricemia.

Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Daskalopoulou SS, Kakafika AI, Pehlivanidis AN, Bouloukos VI, Langer A, Anonymous00343. · Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. · Curr Med Res Opin. · Pubmed #15383187 No free full text.

Abstract: BACKGROUND: Although available guidelines suggest reducing low-density lipoprotein cholesterol (LDL-C) to below 100 mg/dL (2.6 mmol/L), the importance of target-oriented therapy remains controversial. To assess whether achieving guideline-based targets is of benefit, the relationship between clinical outcomes and lipid levels (baseline and on-study) was evaluated in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. This study demonstrated significant reductions in morbidity and mortality associated with active dose titration of atorvastatin and structured management of dyslipidaemia. METHODS AND RESULTS: Intention-to-treat analysis (Cox proportional hazards model) was used to assess the relationship between lipid values and coronary events. Higher levels of LDL-C at baseline were associated with a greater risk of subsequent events among patients randomized to usual care. Reducing the LDL-C and the non-high density lipoprotein cholesterol (non-HDL-C) level to the National Cholesterol Educational Program (NCEP) Adult Treatment Panel (ATP) III goals required greater doses of atorvastatin for the higher baseline quartile of LDL-C. During the study there was a greater reduction in the risk of coronary heart disease (CHD) events in atorvastatin-treated patients who were in the highest quartile of LDL-C at baseline, after achieving the LDL-C treatment goal, in comparison to the usual care patients in the highest baseline LDL-C quartile. CONCLUSIONS: Achieving the NCEP ATP III LDL-C and non-HDL-C goals by titrating up the dose of atorvastatin was associated with a significant reduction in vascular events in patients with CHD. The greatest benefit was seen in those patients with the highest baseline LDL-C levels.

Panagiotakos DB, Pitsavos C, Chrysohoou C, Bratsas A, Toutouzas P, Stefanadis C. · Cardiology Department, School of Medicine, University of Athens, Greece. · Acta Cardiol. · Pubmed #15368799 No free full text.

Abstract: OBJECTIVE: In this work we assessed a risk score for developing a first event of acute coronary syndrome (ACS) based on the family history of the cardiovascular risk factors. METHODS AND RESULTS: The studied population consisted of 848 randomly selected middle-aged patients with first event of ACS and 1078 sex-age-region matched controls admitted to the same hospitals for minor operations and without any clinical suspicion of cardiovascular disease in their life. A Family History Score (FHS) was developed based on the presence of coronary heart disease, hypertension, hypercholesterolaemia and diabetes mellitus, among first-degree relatives of the participants after adjusting for the family size. The evaluation of FHS was based on conditional logistic regression analysis, after controlling for demographic variables as well as for the mutual confounding effects of other risk factors. Family history of CHD, hypercholesterolaemia and diabetes was highly associated with the development of the disease. The introduced FHS was also highly associated with the development of ACS among participants who had no family history of CHD (odds ratio = 10.9, p < 0.001), whereas it was not associated with the development of the disease among participants who had a family history of CHD (odds ratio = 1.41, p = 0.543). CONCLUSIONS: The suggested FHS could be a useful tool in the primary prevention of ACS, as well as in detecting and understanding associations between genetic vulnerability and cardiovascular risk factors.