Hyperlipidemias: Karagiannis A

Athyros VG, Kakafika A, Tziomalos K, Karagiannis A, Mikhailidis DP. · No affiliation provided · Expert Opin Investig Drugs. · Pubmed #18363511 No free full text.

Abstract: Statins effectively lower plasma low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of vascular events. However, this benefit might be improved by dealing with other vascular risk factors such as high-density lipoprotein cholesterol (HDL-C). It follows that there has been an interest in drugs that raise plasma HDL-C levels. Among these drugs are the cholesteryl ester transfer protein (CETP) inhibitors. The first CETP inhibitor to be evaluated in an event-based trial was torcetrapib. This drug can considerably elevate serum HDL-C levels (e.g., by 72%). However, a recently published trial (ILLUMINATE) showed that torcetrapib used in combination with atorvastatin was associated with significantly more vascular events and deaths than atorvastatin alone. This finding resulted in the discontinuation of the torcetrapib development programme. The cause(s) of the adverse outcome remain speculative. It has been suggested that a significant rise in systolic blood pressure and possibly the quality of the HDL produced may be relevant. Despite this disappointing outcome it seems to be too early to close the book on CETP inhibitors because two other members of this class are being evaluated. These drugs (JTT-705 and anacetrapib) may be devoid of the adverse effect on systolic blood pressure. Eventually only appropriately designed, event-based trials, will settle the issue of whether CETP inhibitors are clinically useful.

Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP. · Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, HippocrationHospital, Thessaloniki, Greece. · Curr Pharm Des. · Pubmed #19199976 No free full text.

Abstract: The present review considers the potential pleiotropic effects of statins and the evidence indicative of the "real world" benefit from these effects in patients with cardiovascular disease (CVD). Some of these cholesterol-independent effects of statins involve improved endothelial function, stability of atherosclerotic plaques, attenuation of oxidative stress and inflammation, as well as inhibition of the thrombogenic response. Clinical evidence from early statin administration in acute coronary syndromes and in revascularisation procedures is reported. Moreover, the "metabolic" effects of statin treatment, such as renal function improvement and reduction in serum uric acid levels, in patients with stable coronary heart disease are discussed. Evidence suggests that in high CVD risk patient groups pleiotropic effects of statins may play a role in the reduction of morbidity and mortality. However, this concept requires proof in appropriately designed trials that will include clinically relevant end points in order to set specific targets in new CVD-related biomarkers, in addition to lipid levels, that should be used to fully assess the statin contribution to CVD treatment.

Athyros VG, Tziomalos K, Mikhailidis DP, Pagourelias ED, Kakafika AI, Skaperdas A, Hatzitolios A, Karagiannis A. · Aristotle University of Thessaloniki, Second Propedeutic Department of Internal Medicine, Medical School, Thessaloniki, Greece. · Expert Opin Pharmacother. · Pubmed #17927482 No free full text.

Abstract: This review considers the treatment for combined hyperlipidaemia (CH) with a combination formulation of three drugs: a statin, nicotinic acid (NA) and aspirin--a mini-polypill. CH is a highly atherogenic dyslipidaemia manifested either as familial combined hyperlipidaemia or dyslipidaemia related to the metabolic syndrome or Type 2 diabetes mellitus. These types of dyslipidaemia are highly prevalent in the general population. Statin plus extended-release NA is a promising treatment option for the normalisation of these atherogenic lipid alterations, regression of atherosclerosis, as well as for primary or secondary prevention of cardiovascular disease (CVD) events. The addition of aspirin might prove a useful adjunct that might reduce the cutaneous side effects of NA while also acting as an antiplatelet agent in high-CVD-risk patients. However, the effective dose of aspirin may need to be at least 160 mg/day. This triple combination might improve patient compliance when compared with the three drugs administered separately.

Tziomalos K, Athyros VG, Karagiannis A, Mikhailidis DP. · University of London, Department of Clinical Biochemistry, Royal Free Hospital, Pond Street, London NW3 2QG, UK. · Expert Opin Ther Targets. · Pubmed #17845142 No free full text.

Abstract: The endothelium is a dynamic organ that plays a pivotal role in cardiovascular homeostasis. Alteration in endothelial function precedes the development of atherosclerosis and contributes to its initiation, perpetuation and clinical manifestations. It has been suggested that the assessment of endothelial function could represent a barometer of vascular health that could be used to gauge cardiovascular risk. This review summarises the various methods used to assess endothelium-dependent vasodilatation and their potential prognostic implications. In addition, the techniques used to evaluate arterial stiffness are discussed. The latter is to some extent controlled by the endothelium and has been the subject of considerable research in recent years. This paper also discusses the effects of lipid lowering treatment on both endothelial function and arterial stiffness.

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.

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.

Athyros VG, Kakafika AI, Papageorgiou AA, Paraskevas KI, Tziomalos K, Anagnostis P, Pagourelias E, Koumaras C, Karagiannis A, Mikhailidis DP. · Atherosclerosis and Metabolic Syndrome Units, Second Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. · Curr Med Res Opin. · Pubmed #18430270 No free full text.

Abstract: BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) levels to National Cholesterol Expert Panel (NCEP) goal is recommended. However, sex-specific effects may influence benefit. METHODS AND RESULTS: In this post hoc analysis of the GREek Atorvastatin and Coronary heart disease (CHD) Evaluation [GREACE] study we investigated the extent in vascular event reduction by statin treatment according to sex. From a total of 1600 patients with stable CHD, 624/176 and 632/168 were men/women on atorvastatin or on usual care, respectively. During 3-year follow-up, comparison of atorvastatin treatment with usual care demonstrated a relative risk reduction (RRR) of the primary end point (all vascular events) of 54% in women (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.24-0.87, p=0.003) and of 50% in men (HR 0.50, 95% CI 0.32-0.70, p<0.001). The fall in LDL-C levels played the key role in end point reduction in both sexes. However, in men there was an additional benefit related to the atorvastatin-induced increase in high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR), while in women end points were related to a substantial triglycerides (TG) reduction. CONCLUSIONS: Treatment with atorvastatin to the NCEP LDL-C goal compared with 'usual care' significantly reduced CHD morbidity and mortality in both men and women. Both men and women benefited from statin treatment possibly with different mechanisms making a contribution over and above LDL-C reduction.