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Biomedical subjects

D P Mikhailidis

Publications and source records attributed to D P Mikhailidis.

At least 19 recordsLinked to original sources
PubMed2006

Statin-associated adverse effects beyond muscle and liver toxicity.

Randomized controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have consistently demonstrated significant reductions in cardiovascular morbidity and mortality. Statins are currently the most widely used drugs in many countries. The most important adverse effects are associated with muscle and liver toxicity. However, with increased use and dose of statins and their over-the-counter availability in some countries more cases of other rare side effects may be seen in clinical practice. In the present article we review the literature concerning the statin-related adverse effects other than muscle and liver injury and we provide insight into their clinical relevance and possible underlying mechanisms.

Clinical Trials as Topic↗
PubMed2006

Can statins reduce perioperative morbidity and mortality in patients undergoing non-cardiac vascular surgery?

AIMS: To determine whether statins can reduce perioperative morbidity and mortality in patients undergoing non-cardiac vascular surgery. METHODS: A search using Pubmed was performed to identify reports in English. The search terms were: "statins", "perioperative morbidity", "perioperative mortality" and "vascular surgery". We excluded studies dealing with the effect of statins in cardiac surgery. Retrieved articles were manually searched. RESULTS: Current evidence shows that statins decrease perioperative morbidity and mortality in patients undergoing non-cardiac vascular surgery. Any benefit probably occurs soon (within a month) after initiating treatment. CONCLUSIONS: Appropriately designed trials need to confirm the beneficial effect of perioperative statin therapy in various patient categories. The optimal duration and dose of perioperative statin therapy should be defined.

Adrenergic beta-Antagonists↗
PubMed2006

Statins: another class of antihypertensive agents?

The assessment of global cardiovascular risk is an essential step in the management of atherosclerotic disease prevention. Among the risk factors to be addressed are hypertension and hyperlipidaemia; these commonly coexist. A neutral or lipid-friendly antihypertensive agent is probably useful in the presence of lipid abnormalities. Similarly, statins have been shown to decrease cardiovascular risk in hypertensive patients. There is also experimental and clinical evidence that statins have blood pressure (BP)-lowering effects. In this review, we discuss the beneficial effects of statins on BP, and provide an overview of the underlying pathophysiology. We also consider the evidence justifying the use of statins in the management of hypertensive patients.

Antihypertensive Agents↗
PubMed2006

Does meta-chlorophenylpiperazine (mCPP) activate human platelets?

mCPP (meta-chlorophenylpiperazine), an agonist at serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 receptors, has been used as a probe of serotonergic function. We assessed its effect on platelet activation by measuring median platelet volume (MPV), the Sonoclot (SCT) pattern and plasma and intraplatelet serotonin. (a) In vitro study: MPV was measured (n = 7) using a high-resolution channelyzer: Saline (median and range (5.23 fl; 5.10-6.18) vs. mCPP (5.36; 5.10-6.44) P = 0.03; ADP (5.42; 5.29-6.44) vs. ADP + mCPP (5.67; 5.42-6.63) P = 0.02; mCPP (5.36; 5.10-6.44) vs. ADP + mCPP (5.67; 5.42-6.63) P = 0.02. Therefore, mCPP increases the MPV and enhances the effect of ADP. (b) In vivo study: The SCT time to inflection (TI) and time to peak (TP) were measured following the oral administration of mCPP (0.5 mg/kg) or aspirin (300 mg) (n = 10). Ingestion of mCPP significantly shortened TI and TP indicating platelet activation. TI: 0 h (mean +/- SD: 10.2 +/- 2.0 min) vs. 6 h (9.3 +/- 1.5) P = 0.03; TP: 0 h (31.9 +/- 7.6) vs. 6 h (23.1 +/- 2.9) P = 0.01. Aspirin had no effect on TI or TP. There were no significant changes in plasma and intraplatelet 5-HT. It is concluded that mCPP activates human platelets via 5-HT receptors.

Adenosine Diphosphate↗
PubMed2006

Tangier disease four decades of research: a reflection of the importance of HDL.

Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a frequent lipoprotein disorder in coronary heart disease patients and can be caused by either genetic and/or environmental factors (sedentary lifestyle, diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates). Extremely low serum HDL-C levels occur in patients with Tangier disease (TD), which is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1). Clinical manifestations are related to the storage of cholesteryl esters in reticuloendothelial tissues and to peripheral neuropathy. This review focuses on the genetic and lipid abnormalities of TD, the consequence of these on clinical outcome and the possible treatment options. These abnormalities reflect the importance of HDL in the pathogenesis of vascular disease.

ATP Binding Cassette Transporter 1↗
PubMed2006

Statins and solid organ transplantation.

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.

Adolescent↗
PubMed2006

Preventing type 2 diabetes in high risk patients: an overview of lifestyle and pharmacological measures.

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 angiotensin-converting 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.

Anti-Obesity Agents↗
PubMed2005

Pathogenesis, detection and treatment of Achilles tendon xanthomas.

Tendon xanthomatosis often accompanies familial hypercholesterolaemia, but it can also occur in other pathologic states. Achilles tendons are the most common sites of tendon xanthomas. Low-density lipoprotein (LDL) derived from the circulation accumulates into tendons. The next steps leading to the formation of Achilles tendon xanthomas (ATX) are the transformation of LDL into oxidized LDL (oxLDL) and the active uptake of oxLDL by macrophages within the tendons. Although physical examination may reveal Achilles tendon xanthomas (ATX), there are several imaging methods for their detection. It is worth mentioning that ultrasonography is the method of choice in everyday clinical practice. Although several treatments for Achilles tendon xanthomas (ATX) have been proposed (LDL apheresis, statins, etc.), they target mostly in the treatment of the basic metabolic disorder of lipid metabolism, which is the main cause of these lesions. In this review we describe the formation, detection, differential diagnosis and treatment of ATX as well as the relationship between tendon xanthomas and atheroma.

Achilles Tendon↗
PubMed2005

Serum uric acid levels and risk for acute ischaemic non-embolic stroke in elderly subjects.

BACKGROUND: Elevated serum uric acid (SUA) levels have been proposed as an independent risk factor for cardiovascular (CV) morbidity and mortality. Recent evidence suggests that treatments with a hypouricaemic action have a favourable effect on CV event prevention. OBJECTIVES: The association between SUA and acute ischaemic/non-embolic stroke was assessed in a population-based case-control study in the prefecture of Ioannina, Epirus, Greece. SUBJECTS AND METHODS: A total of 163 patients aged older than 70 years (88 men and 75 women) admitted due to a first-ever-in-a-lifetime acute ischaemic/non-embolic stroke and 166 volunteers (87 men and 79 women) without a history of CV disease were included. The association between SUA and stroke was determined by multivariate logistic regression modelling after adjusting for potential confounding factors. RESULTS: Stroke patients showed higher concentrations of SUA compared with controls (333.1+/-101.1 micromol L(-1) vs. 285.5+/-83.3 micromol L(-1); P<0.001). In univariate analysis elevated SUA levels were associated with increased risk for ischaemic stroke [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.21-1.64, P<0.0001]. Compared to patients with SUA levels in the lowest quintile, those within the highest quintile had a 2.8-time increase in the odds of suffering an ischaemic stroke (OR 2.81, 95% CI 1.67-4.73, P<0.001). This association was strong even after controlling for gender, age, body mass index, the presence of hypertension and diabetes mellitus, drug treatment and lipids (OR 2.90, 95% CI 1.59-5.30, P=0.001). CONCLUSION: Elevated SUA is associated with an increased risk for acute ischaemic/non-embolic stroke in a strictly defined population of elderly individuals independently of concurrent metabolic derangements. This association may need to be considered when treating the elderly.

Aged↗
PubMed2005

The prevalence of the metabolic syndrome in Greece: the MetS-Greece Multicentre Study.

BACKGROUND: The Third Report (ATP III) of the National Cholesterol Education Program Expert Panel (NCEP) highlighted the importance of identifying and treating patients with the metabolic syndrome (MetS) to prevent cardiovascular disease (CVD) and progression to diabetes mellitus. Limited information is available about the prevalence of MetS, as defined by the NCEP ATP III, in Europe, especially in Greece. OBJECTIVE: To estimate the prevalence of the MetS in Greece, The MetS-Greece Study. DESIGN AND PARTICIPANTS: A cross-sectional analysis of a representative sample of Greek adults (4153 participants older than 18 years). One group consisting of military personnel (n = 300) and another one from a Greek Muslim Community (n = 300) were used for comparison. In all, 4753 subjects were included in the final analysis. RESULTS: All subjects from the general population were Caucasian men (49%) and women (51%), living in urban (n = 2243, 54%), semi-urban (n = 1038, 25%) and rural (n = 872, 21%) areas. The age-standardized prevalence of the MetS was 23.6%[95% confidence interval (CI): 22.4-25.1%]. This was similar in men (24.2%, 95% CI: 22.3-25.2%) and women (22.8%, 95% CI: 21.4-25.0%) (p = 0.3). The prevalence increased with age in both sexes, 4.8% among participants aged 19-29 years and 43% for participants over 70 years old (p for trend < 0.0001). There was a 14.7-fold increase in odds ratio for having MetS in the age group > 70 years old compared with that of 19-29 years old (p < 0.0001) Most of those with MetS had three components of the syndrome (61%), 29% had four and 10% had all five components. Abdominal obesity (82%) and arterial hypertension (78%) were the most common abnormalities in both sexes. The Greek Muslim Community, on a high-saturated fat diet, had the highest prevalence of the MetS (35.2%, 95% CI: 30.4-40.3%), and the military group, with a high physical activity level and a diet 'close' to Mediterranean, had the lowest (9.4%, 95% CI: 6.2-13.1%). According to the 2001 Census, about 2.3 million Greeks may have the MetS. CONCLUSIONS: These results show that the MetS is highly prevalent in the Greek adult population. This may have major implications for the incidence of CVD. Promoting healthy diets, low caloric intake and physical activity must be urgently undertaken.

Adolescent↗
PubMed2005

Diagnosis and management of the metabolic syndrome in obesity.

The metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for cardiovascular disease and progression to type 2 diabetes. The prevalence of this syndrome is increasing because of the 'obesity epidemic'. The National Cholesterol Education Program Adult Treatment Panel III defined practical criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. Also, the International Diabetes Federation recently proposed another definition. The metabolic syndrome is a secondary target for cardiovascular risk reduction. Clinicians should identify individuals with this condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted approach. The most effective therapeutic intervention in patients with the metabolic syndrome should focus on modest weight reduction and regular physical activity. Adoption of a healthier diet and smoking cessation are necessary. Drug therapy may be needed to achieve recommended goals if therapeutic lifestyle changes are not sufficient. Low-density lipoprotein cholesterol is the primary target of therapy (new aggressive goals should be achieved). Statins are probably the drugs of choice. Fibrates and nicotinic acid are also useful options. Hypertension should be managed aggressively probably starting with an inhibitor of the renin-angiotensin system or a calcium channel blocker and adding a low dose of a thiazide diuretic if necessary. Aspirin should be administered if the cardiovascular risk is high. In the future acarbose, metformin, meglitinides and thiazolidinediones may be used in patients with the metabolic syndrome to delay the onset of type 2 diabetes and reduce cardiovascular risk. Such an intense and multifactorial approach is likely to reverse the bad prognosis associated with the metabolic syndrome.

Cardiovascular Diseases↗
PubMed2005

Heterozygote men with familial hypercholesterolaemia may have an abnormal triglyceride response post-prandially. Evidence for another predictor of vascular risk in familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is associated with premature coronary heart disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG) clearance may contribute to the heterogeneity in the risk of CHD in heterozygous (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in men with hFH. We studied 26 Greek men divided into two groups: the hFH group of 14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean age 43 (50:5) years. An increased TG response to the fatty meal was defined as a post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG concentration in any hour in any control individual. All hFH patients had normal baseline fasting TG levels. However, seven hFH men showed an abnormal TG response after the fatty meal; these patients had higher baseline fasting TG levels than others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a heterogeneous group regarding their TG response to the fatty meal compared with healthy men because 50% with higher, but nevertheless 'normal' basal TG levels, had an abnormal post-prandial TG response. The reduced activity of low-density lipoprotein receptors in hFH together with other defects in TG handling may explain the abnormal rise of TG levels post-prandially.

Adult↗
PubMed2005

CARDS on the table: should everybody with type 2 diabetes take a statin?

BACKGROUND: Vascular complications are a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The recently published Collaborative Atorvastatin Diabetes Study (CARDS) showed that atorvastatin (10 mg, once daily vs. placebo) markedly reduces vascular events in this high-risk population. The participants (n = 2838) were fairly typical T2DM = 2838) patients without cardiovascular disease and with at least one other risk factor: hypertension, retinopathy, albuminuria or current smoking. In the treatment group, coronary events were reduced by 36% (p = 0.001) and stroke by 48% (p = 0.001). The trial was terminated two years early on ethical grounds. The number needed to treat (NNT) was 27 for four years to prevent one event. However, the benefit may have been greater since a proportion of the placebo group received statin therapy. The benefit from statin treatment was independent of sex, age, baseline lipid levels, was independent of sex, age, baseline lipid levels, systolic blood pressure, retinopathy, albuminuria, systolic blood pressure, retinopathy, albuminuria, smoking or HbA smoking or HbA(1c). The frequency of adverse events did not differ between the groups. These findings support those of other statin trials. SCOPE: CARDS does not comment on renal function. However, other trials suggest that statins preserve renal function in those with and without DM. We discuss the CARDS study in this context in this brief overview paper. CONCLUSIONS: the evidence shows that we need to control glucose to prevent microvascular complications, to lower cholesterol to prevent macrovascular disease and to lower blood pressure to prevent both. It may be that the benefit of statins extends beyond a threshold low-density lipoprotein cholesterol level in patients with T2DM. More trials are needed in this field.

Atorvastatin↗
PubMed2005

A review of the metabolic effects of sibutramine.

BACKGROUND: Obesity is associated with an increased incidence of diabetes, hypertension, dyslipidaemia and coronary artery disease. Current management strategies of obesity include lifestyle management strategies of obesity include lifestyle interventions and pharmaco therapy. Sibutramine is a drug with established efficacy in weight reduction and maintenance of weight loss. It reduces food intake and attenuates the fall in 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 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 hyper androgenaemia 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.

Appetite Depressants↗
PubMed2005

The use of ezetimibe in achieving low density lipoprotein lowering goals in clinical practice: position statement of a United Kingdom consensus panel.

There is no doubt that lowering serum cholesterol levels reduces the risk of major coronary events. This evidence has led treatment guidelines to set progressively lower targets for low density lipoprotein cholesterol (LDL-C). However, despite widespread use of statins, substantial numbers of patients do not achieve the LDL-C goals. Using higher doses of statins in an attempt to achieve these targets may increase the risk of serious adverse effects. Furthermore, the use of combination therapy with agents such as bile acid sequestrants, niacin and fibrates has been limited by increased potential for side effects, drug interactions and poor compliance. Ezetimibe, a selective cholesterol transport inhibitor, reduces the intestinal uptake of cholesterol without affecting absorption of triglycerides or fat-soluble vitamins. In clinical studies, ezetimibe 10 mg, in combination with statins or as monotherapy, was well tolerated and reduced LDL-C by 34-53% and 17-18%, respectively. The available evidence for ezetimibe is reviewed. The role of ezetimibe in increasing the proportion of patients attaining LDL-C treatment goals is discussed.

Anticholesteremic Agents↗