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Biomedical subjects

M S Elisaf

Publications and source records attributed to M S Elisaf.

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

The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome.

BACKGROUND: Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS). OBJECTIVE: The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS. METHODS: Patients (n=89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group) for 6 months. RESULTS: Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p<0.05) together with a greater increase in LDL particle diameter (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05). CONCLUSION: Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
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

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

The effects of orlistat on metabolic parameters and other cardiovascular risk factors.

Orlistat is an antiobesity drug with a well documented efficacy in weight reduction and weight maintenance. Weight reduction with orlistat has been associated with a favourable effect on obesity-related cardiovascular risk factors. Orlistat treatment is associated with a reduction in serum insulin levels. Moreover, orlistat reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance and lowers the required dose of metformin, sulfonylureas and insulin in patients with type 2 diabetes. Furthermore, orlistat can reduce total and low density lipoprotein (LDL) cholesterol levels and improve postprandial triglyceridemia, as well as the low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDL/HDL ratio). Moreover, orlistat appears to have a favourable effect on some inflammatory markers, such as TNF-alpha and interleukin-6 and has a time-depended effect on some haemostatic factors.

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

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

Serum potassium and acid-base parameters in severe dialysis-associated hyperglycemia treated with insulin therapy.

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 +/- 1.3 mmol/L; NKH 5.2 +/- 1.5 mmol/L) and anion gap [AG] (DKA 27.2 +/- 6.4 mEq/L; NKH 15.4 +/- 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2 ] (DKA 12.0 +/- 4.6 mmol/L; NKH 22.5 +/- 3.1 mmol/L), arterial blood pH (DKA 7.15 +/- 0.09; NKH 7.43 +/- 0.07) and arterial blood PaCO2 (DKA 26.2 +/- 12.3 mm Hg; NKH 34.5 +/- 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 +/- 0.7 mmol/L, NKH 4.0 +/- 0.5 mmol/L), [AG] (DKA 16.3 +/- 5.4 mEq/L, NKH 14.9 +/- 3.0 mEq/L), [TCO2 ] (DKA 23.5 +/- 5.0 mmol/L, NKH 24.1 +/- 4.2 mmol/L), arterial blood pH (DKA 7.42 +/- 0.09, NKH 7.51 +/- 0.14) and arterial blood PaCO2 (DKA 31.8 +/- 6.7 mm Hg, NKH 34.2 +/- 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (Delta[K]), on the presenting serum [K] concentration,([K]2 ), was: DKA, Delta[K] = 2.78 - 0.81 x [K]2 , r = -0.85, p < 0.001; NKH, Delta[K] = 2.44 - 0.71 x [K]2 , r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2 ] value during treatment as the predictors of Delta[K] (R2 = 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2 ] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.

Acid-Base Equilibrium↗
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

Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study.

BACKGROUND: 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.

Adult↗
PubMed2005

Syndrome of inappropriate antidiuretic hormone secretion due to recurrent oral cancer.

Hyponatremia is a common metabolic disorder in clinical practice and is associated with significant morbidity and mortality, especially among the elderly. Hyponatremia resulting from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported in association with neoplasia (including a few reports in patients with head and neck malignancies) and may represent a paraneoplastic condition. Patients with SIADH present with signs and symptoms that cannot be explained by the primary tumour mass effect or its metastases. We describe a 67-year-old male patient with oral squamous-cell carcinoma of recent recurrence admitted because of symptomatic severe hyponatremia resulting from SIADH and discuss the principles of the diagnostic approach and appropriate management.

Aged↗
PubMed2003

Lipoprotein (a) and acute-phase response in patients with vestibular neuronitis.

BACKGROUND: Vestibular neuronitis (VN) is a relatively common condition characterized by the acute onset of vertigo, nausea and vomiting, in the absence of auditory or central nervous system involvement. The exact aetiology (inflammatory, viral or vascular?) remains obscure. Lipoprotein (a) [Lp(a)] is an atherogenic particle. Its serum levels are mainly genetically determined and vary widely between individuals. Whether Lp(a) is consistently a positive acute-phase reactant is controversial. PURPOSE: We evaluated the alterations in lipidaemic parameters and serum biological markers (including acute-phase reactants) in adult patients presenting acutely with VN. SUBJECTS AND METHODS: A total of 34 consecutive VN patients (24 men and 11 women) and 37 apparently healthy controls (25 men and 12 women) were studied. Laboratory evaluation was performed during the acute episode and 6 months later (stable state). RESULTS: Serum Lp(a) concentrations were significantly lower at the time of presentation (median value 6.4 vs. 16.4 mg dL-1 in the stable state, P < 0.001), whereas fibrinogen levels were significantly higher during the acute episode than in the stable state (median value 293.0 vs. 202.0 mg dL-1, respectively, P < 0.0001). During the acute episode, plasma fibrinogen correlated with CRP levels (Spearman r = 0.84, P < 0.0001). By contrast, inverse correlations were noted between Lp(a) levels and CRP (Spearman r = -0.47, P = 0.007) as well as between Lp(a) and fibrinogen levels (Spearman r = -0.35, P = 0.05). CONCLUSION: Vestibular neuronitis episodes are associated with evidence of an acute inflammatory response as reflected by significant elevations in plasma fibrinogen and CRP concentrations, whereas Lp(a) behaves as a negative acute-phase reactant.

Acute Disease↗
PubMed2003

Pinpoint skin lesions in a familial hypercholesterolaemia homozygote.

UNLABELLED: The case is reported of a 2-y-old girl referred to the outpatient lipid clinic because of a tiny cutaneous xanthoma on the dorsum of the left foot and a family history of hyperlipidaemia and coronary heart disease (CHD). Fasting serum total cholesterol levels were remarkably high (27.1 mmol l(-1), 1050 mg dl(-1)) and DNA analysis confirmed homozygous familial hypercholesterolaemia (class II mutation). Serum lipids were not affected by dietary intervention and cholestyramine treatment, so low-density lipoprotein apheresis was scheduled to commence at the age of 4 y. CONCLUSION: An early lipid profile determination should be performed in children with a family history of premature CHD, since the physical examination may be unremarkable even in cases of severe hyperlipidaemia during the first years of life.

Child, Preschool↗