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OBJECTIVE: Cardiovascular disease (CVD) is more prevalent and more likely to lead to death in patients with rheumatoid arthritis (RA). Single nucleotide polymorphisms of the genes for lymphotoxin-A (LT-A) and its regulatory protein galectin-2 (LGALS2) have been implicated as genetic risk factors for acute cardiovascular events in the general population: we hypothesised that their risk alleles/genotypes (a) may be more frequent among patients with RA compared with non-RA controls (thus explaining some of the increased CVD in RA), and (b) may be more frequent among patients with RA with prevalent CVD compared with patients with RA without CVD. METHODS: Genomic DNA samples were collected from 388 patients with RA and 399 local population controls without RA. LT-A gene intron 1 252A>G and LGALS2 intron 1 3279C>T single nucleotide polymorphisms were identified using real-time polymerase chain reaction and melting curve analysis. RESULTS: LT-A 252GG homozygotes were significantly more prevalent among patients with RA compared with controls (19.8% vs 11.8%, p = 0.002; OR(GG/GA,AA) = 1.85, 95% CI 1.25 to 2.75, p = 0.002). Patients with RA possessing LT-A 252 GG were significantly more likely to have had a myocardial infarction compared with those with LT-A 252 AA or GA (13% vs 5.5%, p = 0.02; adjusted OR(GG/GA,AA) = 3.03, 95% CI 1.2 to 7.68, p = 0.002). The frequency of LGALS2 polymorphisms was similar between RA and controls and was not associated with CVD among patients with RA. CONCLUSIONS: The LT-A 252GG genotype occurs more frequently among patients with RA than the general population. In RA, this genotype appears to associate with increased likelihood of suffering an myocardial infarction. Ann Rheum Dis

OBJECTIVE: In an observational study, we evaluated the association between postoperative statin therapy and long-term mortality among patients undergoing a first-ever coronary artery bypass grafting (CABG) surgery. METHODS: In an outpatient clinic setting, we assessed 1869 consecutive patients (age 58.7+/-9.6 years; 1657 men), who survived the 1st month after a first-ever CABG, within a 17-year period. Cox proportional hazard analysis was used to calculate the adjusted hazard ratios (adjusting for age, smoking, the presence of hypertension, diabetes mellitus, lipid profile at the time of the procedure, vessel disease, number and kind of grafts used, and concomitant treatment) for patients receiving statin treatment during follow-up and adjusted Kaplan-Meier survival curves were constructed. RESULTS: During a 9345 patient-years follow-up, 48% of the patients were on a statin. In a total of 222 deaths, 80.6% were because of cardiovascular causes. Total and cardiovascular mortality were significantly reduced in patients receiving statin therapy [adjusted hazard ratio, 0.48 (95% confidence interval, 0.28-0.82); P=0.007), and 0.43 (95% confidence interval, 0.23-0.80); P=0.007, respectively]. The estimated 16-year Kaplan-Meier survival curves diverged at 2 years and thereafter. CONCLUSION: Taking into account the potential limitations of observational data, statin treatment postoperatively is associated with a 50% reduction in total and cardiovascular mortality in patients undergoing a first-ever CABG. Coron Artery Dis

C-reactive protein (CRP) is an acute-phase protein, which has been used in clinical practice as a non specific marker of inflammation. Many studies have shown that CRP is associated with atherosclerotic cardiovascular disease. It is currently unknown if CRP plays an active role as an etiologic factor in cardiovascular disease. The mechanisms by which CRP may contribute to the pathogenesis of cardiovascular disease are poorly understood. The effect of CRP on atherogenesis may include interactions with other factors of immunity and inflammation, such as the complement system, as well as a direct effect of CRP on the cells involved in atherosclerotic lesions. We review the literature concerning the mechanisms by which CRP may influence the development of cardiovascular disease and discuss the findings of clinical studies assessing the association between CRP and cardiovascular disease. Curr Vasc Pharmacol

Statins, in addition to their beneficial lipid modulation effects, exert a variety of several so-called "pleiotropic" actions that may result in clinical benefits. Rosuvastatin, the last agent of the class to be introduced, has proved remarkably potent in reducing low-density lipoprotein cholesterol levels. At present, no large-scale primary or secondary prevention clinical trials document either its long-term safety or its effectiveness in preventing cardiovascular events. A substantial number of experimental and clinical studies have indicate favorable effects of rosuvastatin on endothelial function, oxidized low-density lipoprotein, inflammation, plaque stability, vascular remodeling, hemostasis, cardiac muscle, and components of the nervous system. Available data regarding the effects of rosuvastatin on renal function and urine protein excretion do not seem to raise any safety concerns. Whether the established "pleiotropy" and/or lipid-lowering efficacy of rosuvastatin may translate into reduced morbidity and mortality remains to be shown in ongoing clinical outcome trials. J Cardiovasc Pharmacol Ther

BACKGROUND: To compare the relative value of metabolic syndrome (MetS) and cardiovascular risk score estimates in patients with acute coronary syndromes (ACS) aged 1.0% were identified. The mean 10-year FRS for patients and controls was 13.03% +/- 7.96% and 10.02 +/- 8.10%, respectively (P < .001), whereas only 22.5% of ACS patients had a 10-year risk >20.0% compared with 14.5% of controls (P = .04). After controlling for potential confounders, MetS was associated with 1.93 (95% CI 1.13-3.28, P = .01) higher odds of having an ACS. Moreover, the odds had a positive association with the increasing cumulative number of MetS components. Crude and adjusted ORs for the FRS were 1.05 (95% CI 1.029-1.08, P = .001) and 0.98 (95% CI 0.92-1.05, P = NS), respectively. CONCLUSION: Metabolic syndrome is highly associated with ACS in subjects

Visfatin is a novel adipokine involved in the process of atherosclerosis. We assessed the effect of rosuvastatin on plasma visfatin levels in patients with primary hyperlipidemia. Eighty hyperlipidemic patients without evidence of cardiovascular disease were randomized to receive either rosuvastatin 10 mg/day or therapeutic lifestyle changes intervention. Plasma visfatin levels were determined at baseline and after 12-weeks post-randomization. Rosuvastatin induced a significant decrease in plasma visfatin levels (17.1 +/- 2.1 versus 15.5 +/- 2.0 ng/ml, P = 0.03). This effect correlated with baseline visfatin levels (r=0.51, P

Background To assess the metabolic profile and the Prevalence of the metabolic triad (i.e. hyperinsulinaemia, hyperapobetalipoproteinaemia, and decreased low-density lipoprotein particle size) in women characterized by the hypertriglyceridaemic waist (HTGW) phenotype and to identify cut-off values for triglycerides and waist circumference, effectively discriminating women with the metabolic triad. Methods Two hundred and twenty-eight female subjects without any history of vascular disease or diabetes mellitus attending an Outpatient Lipid Clinic setting at the University Hospital of Ioannina, Greece were studied. Results Currently available HTGW criteria for women were unable to detect any significant differences in the metabolic profile either in the pre- or postmenopausal women, and proved similar in terms of sensitivity and specificity in identifying women with the metabolic triad. A cut-off value of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference were determined by Receiver-operating Curve evaluation. Women with both triglycerides and waist circumference above these thresholds had four-fold higher odds of presenting with the metabolic triad compared with women with non-HTGW phenotype. Conclusions AHTGW phenotype definition of 1.26 mmol/L for triglycerides and 84.5 cm for waist circumference may effectively identify Mediterranean women with the atherogenic metabolic triad. Whether these criteria are also associated with a higher incidence of vascular disease and/or new-onset diabetes in women remains to be investigated. Copyright (C) 2007 John Wiley & Sons, Ltd. Diabetes-Metabolism Research and Reviews

BACKGROUND: Although the effect of statins on lowering low-density lipoprotein cholesterol (LDL-C) has been extensively studied, their hypotriglyceridemic capacity is not fully understood. OBJECTIVE: The present study examined clinical and laboratory factors potentially associated with the triglyceride (TG)-lowering effect of rosuvastatin. METHODS: Eligible patients had primary dyslipidemia and a moderate risk of heart disease. Patients were prescribed rosuvastatin 10 mg/d in an open-label fashion and kept 3-day food diaries. Laboratory measurements, performed at baseline and 12 weeks, included serum lipid parameters (total cholesterol [TC], TGs, LDL-C, high-density lipoprotein cholesterol [HDL-C], and apolipoprotein [apo] levels), non-lipid metabolic variables (including carbohydrate metabolism parameters and renal, liver, and thyroid function tests), and LDL-subfraction profile (by high-resolution 3% polyacrylamide gel electrophoresis). Tolerability was assessed at each visit. RESULTS: Participants were 75 hyperlipidemic patients (39 men and 36 women; mean age, 51.7 years). At 12 weeks, TC levels were reduced by 35.1% (P < 0.001), TGs by 15.2% (P < 0.001), LDL-C by 48.5% (P < 0.001), apoE by 35.4% (P < 0.001), and apoE by 17.3% (P < 0.001) from baseline, whereas HDL-C and apoA1 levels were not significantly changed. Stepwise linear regression analysis showed that baseline TG levels were most significantly correlated (R(2) = 42.0%; P < 0.001) with the TG-lowering effect of rosuvastatin, followed by the reduction in apoCIII levels (R(2) = 13.6%; P < 0.01). Rosuvastatin use was associated with a reduction in cholesterol mass of both large LDL particles (mean [SD], from 150.5 [36.6] to 90.5 [24.3] mg/dL; P < 0.001) and small, dense LDL (sdLDL) particles (from 11.5 [8.4] to 6.6 [4.5] mg/dL; P < 0.001). Rosuvastatin had no effect on cholesterol distribution of the LDL subfractions (mean [SD], large particles, from 90.8% [7.0%] to 91.8% [5.1%]; sdLDL, from 7.1% [4.7%] to 7.5% [4.8%]) or the mean LDL particle size (from 26.5 [4.2] to 26.6 [4.0] rim). A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels > or =120 mg/dL. No serious adverse events requiring study treatment discontinuation were reported. One patient who presented with headache and 2 patients who presented with fatigue quickly recovered without discontinuing rosuvastatin treatment. A posttreatment elevation in aminotransferase levels

OBJECTIVE: There is a paucity of data with regard to the association of the metabolic syndrome with cardiovascular risk in young adults. We investigated the association of the metabolic syndrome with acute coronary syndrome in adults aged 45 years or younger. PATIENTS AND METHODS: A total of 136 consecutive patients (128 men and eight women; mean age, 41.2+/-3.7 years) presenting with a first-ever acute coronary syndrome, and 136 age-matched and sex-matched controls were evaluated. The diagnosis of the metabolic syndrome was established according to the Adult Treatment Panel III criteria. RESULTS: The prevalence of the metabolic syndrome was significantly higher in the patients' group compared with the control group (40.4 versus 23.5%; P=0.003). Multivariate logistic regression analysis showed that smoking, positive family history of premature coronary artery disease, and the metabolic syndrome were associated with odds ratios 4.46 (95% confidence interval, 2.30-8.66; P

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Nephrol Dial Transplant

OBJECTIVE: To evaluate the influence of clinical, biochemical and genetic markers on the response to antihypertensive treatment in patients with essential hypertension and the metabolic syndrome (MetS). METHODS: Measurements of anthropometric indices, blood pressure (BP), and metabolic parameters were obtained from the medical records of 132 (77 women) newly diagnosed, untreated hypertensive patients. Renin-angiotensin-aldosterone system (RAAS) genes polymorphisms (including ACE I/D, angiotensinogen M235T, angiotensin II type 1 receptor [AT1-receptor] A1166C) were determined. Response to treatment was defined as BP less than 140/90 mmHg. RESULTS: Patients with MetS (n=60) had higher systolic BP and pulse pressure and a more atherogenic lipid profile than patients without MetS. The frequencies of the ACE and the AT1-receptor gene polymorphisms were similar between patients with and without MetS. Response to treatment was positively associated with pulse pressure, and the presence of the C allele as well as the AC genotype of the AT1-receptor gene and inversely with age after adjustment for confounding factors. CONCLUSIONS: RAAS genes distribution does not differ between hypertensive patients with and without the MetS. Higher baseline pulse pressure levels, the presence of the C allele and/or the AC genotype may be in favour of a better response to structured antihypertensive treatment in patients with MetS. However, these findings need to be evaluated in future studies. J Renin Angiotensin Aldosterone Syst

Hypertension and hyperlipidemia, two powerful risk factors of cardiovascular disease (CVD), often coexist. Therefore, treatment should consider the beneficial properties of drugs used to treat either condition. Statins, the mainstay of lipid-lowering therapy, result in a significant clinical benefit both in primary and secondary CVD prevention. In addition to their hypolipidemic capacity, other properties may contribute to statin-induced benefits. Clinical and experimental evidence indicates that statins may modulate blood pressure (BP). The mechanisms by which statins reduce BP seem to be largely independent of their lipid effects. Although small, reductions in BP are possibly clinically relevant. Large landmark studies confirm that statins can reduce CVD risk in hypertensive patients. These findings suggest that statins could be prescribed as an adjunct in treating hypertension with dyslipidemia or even in patients with "normal" cholesterol levels. Whether the effect of statins on BP is accompanied by an additional decrease in clinical outcomes needs to be investigated in long-term, large-scale trials. Curr Hypertens Rep

The rising number of elderly people has a major impact on healthcare systems. Advancing age is a risk factor for the development of cardiovascular disease (CVD), which represents a major global healthcare problem. The clinical efficacy and safety of lipid lowering treatment (especially statins) is well established following a series of large-scale, randomised controlled trials, which mainly recruited patients under the age of 70 years. Subgroup analyses together with the findings of trials involving sufficient numbers of elderly participants, such as the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) and the Heart Protection Study (HPS) offer a basis for considering statin therapy in this population. Furthermore, since this population is at greater absolute risk of CVD, substantial benefits from adequate treatment may be anticipated. However, underevaluation and undertreatment appear to be common in the elderly. In this review, we provide a survey of potentially modifiable cardiovascular risk factors in association with old age, and discuss the relevant findings of large-scale end-point clinical studies as well as major considerations regarding lipid-lowering treatment in this population. It is concluded that the decision whether to treat hypercholesterolaemia in the elderly is currently individualised, depending upon the degree of risk, general health, willingness to receive treatment and financial concerns. Further, prospective randomised trials are required to guide physicians towards an effective management of older individuals at increased atherosclerotic risk. Curr Pharm Des

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. J Hum Hypertens

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Journal of Hypertension

In a population-based case-control study, we investigated the association of acute ischaemic stroke with lipoprotein(a) (Lp(a)) levels and apolipoprotein (Apo) (a) isoform size in subjects aged older than 70 years. A total of 163 patients with a first-ever-in-a-lifetime acute ischaemic/nonembolic stroke and 166 controls were included. Compared to controls, stroke patients exhibited higher Lp(a) concentrations (median value, 12.2 mg/dl versus 6.4 mg/dl, p < 0.001) and a higher frequency of small Apo(a) isoforms (44.2% versus 29.5%, p < 0.01). Multivariate logistic regression analysis showed a significant association 4 acute ischaemic stroke with Lp(a) levels [adjusted odds ratio (OR), 1.37, 95% CI (1.12-1.67); p = 0.002], and small Apo(a) isoform size [OR, 1.74 (1.10-3.03);p = 0.04]. Compared to subjects with Lp(a) levels in the lowest quintile, those within the highest quintile had a 3.2-times adjusted risk to suffer an acute ischaernic/nonembolic stroke (1.60-6.62, 95% CI; p < 0.001). Furthermore, analysis of interaction between lipid variables revealed that in the presence of elevated Lp(a) levels the inverse relationship between HDL-cholesterol levels and ischaemic stroke was negated [OR, 1.01 (1.00-1.03); p = 0.015]. Our study suggests that determination of Lp(a) levels and Apo(a) isoform size may be important in identifying elderly individuals at risk of ischaemic stroke independently of other risk factors and concurrent metabolic derangements. (c) 2005 Elsevier Ireland Ltd. All rights reserved. Atherosclerosis

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Clin Exp Rheumatol

OBJECTIVES: In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular disease-free subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL). METHODS: After a 6-week dietary lead-in period, patients were randomized to RSV 10 mg/day (n = 60) or ATV 20 mg/day (n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20 mg/day or ATV 40 mg/day) if the treatment goal was not achieved. A control group of healthy volunteers (n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL-C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters. RESULTS: A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C-reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL-C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect. CONCLUSIONS: RSV and ATV were equally efficacious in achieving LDL-C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL-C-raising effect, while ATV lowers serum uric acid levels. Current Medical Research and Opinion

Journal of Hypertension

Journal of Hypertension

Hellenic J Cardiol

Am Heart J

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Metabolism-Clinical and Experimental

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. Angiology

Clinica Chimica Acta

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

BACKGROUND AND AIM: A wide array of disturbances in electrolyte equilibrium is commonly seen in patients with acute leukemia (AL). These abnormalities present a potential hazard in these patients, as that of enhancing the cardiotoxic effects of certain chemotherapeutic regimens. The literature dealing with AL-related electrolyte abnormalities and their interactions in leukemic patients was reviewed. DATA SYNTHESIS: Sources included MEDLINE and EMBASE. The search strategy was based on the combination of 'acute leukemia', 'electrolyte abnormalities', 'acid-base disorders', 'potassium', 'sodium', 'magnesium', 'calcium', and 'phosphorus'. References of retrieved articles were also screened. A decrease in serum potassium, mainly owing to lysozyme-induced tubular damage, appears to be one of the most frequent and potentially hazardous abnormalities. Other clinically significant metabolic perturbations include hyponatremia and hypercalcemia. CONCLUSION: A broad spectrum of electrolyte abnormalities is encountered in the clinical setting of AL, which are related to the disease process per se and/or to the therapeutic interventions. Clinicians should be vigilant for early detection and appropriate management of these disorders before the initiation of chemotherapy regimens as well as during treatment. Eur J Haematol

BACKGROUND AND PURPOSE: Metabolic syndrome (MetSyn) represents a constellation of lipid and nonlipid risk factors for cardiovascular disease and is a recognized target for increased behavioral therapy. OBJECTIVE: The association between acute ischemic/nonembolic stroke and the MetSyn in elderly individuals was assessed in a population-based case-control study in the prefecture of Ioannina, Greece. STUDY POPULATION: A total of 163 patients aged older than 70 years admitted with first-ever-in-a-lifetime acute ischemic/nonembolic stroke and 166 controls were included. RESULTS: The prevalence of MetSyn (defined according to NCEP/ATP III criteria) was high in stroke patients (46.0% versus 15.7%, P

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

BACKGROUND: Stroke is a leading cause of mortality and subsequent serious long-term physical and mental disability among survivors. In the elderly, ischemic stroke accounts for more than 80% of all strokes. OBJECTIVES: To identify major risk factors for a first-ever acute ischemic/non-embolic stroke in individuals older than 70 years. METHODS: A population-based case-control study of patients admitted to the University Hospital of Ioannina, Epirus, Greece, due to first-ever ischemic/non-embolic stroke from March 1997 to January 2002. All patients were subjected to brain CT and had their serum lipids and biochemical metabolic parameters determined within 24 h from the onset of symptoms. RESULTS: A total of 163 (aged>70 years) consecutive stroke patients and 166 apparently healthy volunteers were studied. An atherogenic lipid profile and metabolic disturbances were more prevalent in the patient group than in stroke-free controls. Multivariate logistic regression analysis identified diabetes mellitus (odds ratio (OR), 1.92; 95% CI, 1.02-3.63), triglycerides (TG) (OR, 1.16; 95% CI, 1.09-1.22), HDL-cholesterol (OR, 0.57; 95% CI, 0.43-0.76), apo A-I (OR, 0.80; 95% CI, 0.70-0.92), lipoprotein(a) [LP(a)] (OR, 1.51; 95% CI, 1.25-1.79), uric acid (OR, 1.30; 95% CI, 1.06-1.59) albumin (OR, 0.38; 95% CI, 0.20-0.70) fibrinogen (OR, 1.10; 95% CI, 1.05-1.13) and the metabolic syndrome (OR 2.48, 95% CI, 1.16-5.29) as significantly associated with ischemic/non-embolic stroke. CONCLUSION: Ischemic non-embolic stroke in the elderly is associated with dyslipidemia and several predictor metabolic factors, which could be substantially modified by lifestyle changes and therapeutic intervention. Int J Cardiol

Hyperglycaemic hyperosmolar syndrome is a major acute complication of decompensated diabetes mellitus. It represents the second most common aetiology of diabetic coma and is associated with excess mortality. It is characterised by severe hyperglycaemia, hyperosmolality and dehydration in the absence of significant ketosis, afflicting principally middle-aged-to-elderly patients. Early clinical diagnosis and prompt treatment, consisting of fluid replacement, insulin therapy, restoration of electrolyte disturbances and management of concurrent illnesses may improve the outcome. This review provides an outline of the diagnostic approach of patients with manifestations of hyperglycaemic hyperosmolar syndrome and discusses the contemporary therapeutic recommendations. Expert Opin Pharmacother

Background: Subclinical hypothyroidism (SH) has been associated with an increased risk of ischemic heart disease, which has been partly attributed to lipid abnormalities. Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with lipoproteins (both low-density lipoproteins [LDL], and high-density lipoproteins [HDL]). Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. Objective: To evaluate qualitative changes in lipoprotein metabolism with respect to PAF-AH and PON1 activities in patients with SH before and after the restoration of euthyroidism. Design and methods: We determined the PAF-AH activity in plasma and on HDL and PON1 activities as well as the lipid profile patients with SH at baseline and after 6 months of levothyroxine substitution therapy. Thirty normolipidemic healthy individuals comprised the control group. Results: Compared to controls, patients with SH showed higher levels of total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B. Triglycerides were significantly reduced after levothyroxine treatment. Patients with SH exhibited higher plasma baseline PAF-AH activity (63.0 +/- 16.5 versus 44.3 +/- 9.5 nmol/mL per minute p < 0.0001) and lower baseline HDL-associated PAF-AH (2.9 +/- 1.1 versus 3.6 +/- 0.9 nmol/mL per minute p = 0.02) compared to the control group. PON1 activities were similar in both groups. Levothyroxine treatment had no effect on plasma PAF-AH activity or PON1 activities but resulted in a significant elevation of HDL-associated PAF-AH activity (from 2.9 +/- 1.1 to 3.5 +/- 1.0 nmol/mL per minute, p = 0.003). Conclusions: Patients with SH exhibit increased plasma PAF-AH activity and low HDL-associated PAF-AH activity. Levothyroxine induces a significant increase in HDL-PAF-AH activity. This action may represent a potential antiatherogenic effect of thyroid replacement therapy. Thyroid

Am J Med

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Journal of Hypertension

Journal of Hypertension

Chemistry and Physics of Lipids

BACKGROUND: Little is known about the effect of dyslipidemia on serum uric acid (SUA) levels, and less is known about the effect of statin treatment on them. The GREek Atorvastatin and Coronary-heart-disease Evaluation study suggested that a mean atorvastatin dose of 24 mg/d achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality in patients with coronary heart disease (CHD) in comparison to the usual care. Here, we report the time course of SUA levels in usual-care patients undertreated for their dyslipidemia (12% were administered statins) in comparison to structured-care patients treated with atorvastatin in the vast majority (98%). METHODS: Mean on-study SUA levels (up to 48 months) were compared with those at baseline by using analyses of variance to assess differences over time within and between treatment groups. Cox multivariate analysis was used to investigate whether changes in SUA levels during the study were clinically relevant. RESULTS: All patients had normal renal function at baseline; serum creatinine (SCr) levels less than 1.3 mg/dL (

Objective: Lipoprotein (a) [Lp(a)] is considered an atherogenic lipoprotein, which is also implicated in thrombosis. Lp(a) binds to platelets and modulates the effects of various platelet agonists. Platelet activating factor (PAF) is a potent platelet agonist degraded and inactivated by PAF-acetylhydrolase (PAF-AH), which in plasma is associated with lipoproteins. Lp(a) is enriched in PAF-AH, thus a functional characteristic of this lipoprotein is its capability to hydrolyze and inactivate PAF. In the present study, we investigated the effect of Lp(a) on PAF-incluced platelet activation. The potential roles of the apo(a) moiety and especially of the PAF-AH content of Lp(a) on the above effect were also addressed. Methods: Lp(a) was isolated by affinity chromatography from plasma of apparently healthy fasting donors with serum Lp(a) concentrations 20 mg/dl. Reduced Lp(a) [Lp(a-)] was prepared by incubation of Lp(a) with dithiothreitol (DTT), whereas inactivation of Lp(a)-associated PAF-AH was performed by incubation of Lp(a) with pefabloc [pefa-Lp(a)]. Platelet-rich plasma (PRP) or washed platelets were prepared from peripheral venous blood samples of normolipidemic, apparently healthy fasting donors with their serum Lp(a) levels lower than 0.8 mg/dl. The surface expression of the platelet integrin-receptor alpha(11b)beta(3) and the fibrinogen binding to the activated alpha(11b)beta(3) was studied by flow cytometry. Results: Lp(a), at doses higher than 20 mug/ml, inhibits PAF-induced platelet activation in a dose-dependent manner. Pefa-Lp(a), lacking PAF-AH activity, exhibited a similar to Lp(a) inhibitory effect. Importantly, the Lp(a) inhibitory effect was not influenced by the apo(a) isoform size, whereas Lp(a-) was a more potent inhibitor compared to Lp(a). Similarly to PAT, Lp(a) inhibits platelet aggregation induced by ADP or Calcium ionophore A23187. Lp(a), pefa-Lp(a) or Lp(a-) effectively inhibited PAF- or ADP-induced surface expression of alpha(11b)beta(3), the Lp(a-) being more potent compared to Lp(a) or to pefa-Lp(a). Finally, Lp(a) significantly inhibited fibrinogen binding to platelets activated with PAK Conclusions: Lp(a) inhibits PAF-induced platelet activation in a non-specific manner. The Lp(a)-associated PAF-AH does not play any important role in this effect, whereas the apo(a) moiety of Lp(a) significantly reduces its inhibitory effect. The inhibition of alpha(11b)beta(3) activation and fibrinogen binding to the activated platelets may represent the major mechanism by which Lp(a) inhibits PAF-induced platelet aggregation. (C) 2004 European Society of Cardiology. Published by Elsevier BN. All rights reserved. Cardiovasc Res

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. Acta Paediatr

The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.0081). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms. Thyroid

Arch Intern Med

Nephrol Dial Transplant

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. Curr Pharm Des