Adrenal incidentaloma: a diagnostic challenge.

The widespread application of abdominal imaging procedures has resulted in an increased frequency of clinically silent adrenal masses. Adrenal incidentaloma (AI) is a term applied to an accidentally discovered adrenal mass on imaging performed for the investigation of an unrelated complaint. Adrenal incidentalomas (AIs) are a cluster of different pathologies, the majority of which are benign and non-functioning adrenal adenomas. However, mild hormonal alterations as well as metabolic abnormalities may be present in patients with AIs. Thus, a multidisciplinary approach with biochemical and radiologic evaluation is needed to characterize these lesions and identify patients who are at high risk for hormonal or malignant evolution. Significant new information has helped resolve controversies regarding the most reliable approach to this clinical problem. The present review considers the prevalence, pathology and natural history of AIs. We also discuss the reliability of available screening methods and localization techniques and consider optimal management and follow-up strategies.

Medical treatment as an alternative to adrenalectomy in patients with aldosterone-producing adenomas.

Primary aldosteronism (PA) and, in particular, its two commonest subtypes (i.e. idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA)) have been recognized as the most common cause of secondary hypertension. While 'conservative' medical treatment with aldosterone receptor antagonists is the therapeutic approach of choice in controlling blood pressure in patients with PA due to IHA, the more invasive (laparoscopic) adrenalectomy seems to be the most suitable therapy for patients with APA. In this review, we focus on the medical approach for the management of APA in cases where surgical excision of the adrenal is not possible.

High density lipoprotein cholesterol and statin trials.

Epidemiological studies show that high density lipoprotein cholesterol (HDL-C) levels are inversely related to the risk of vascular events. Statins are the most widely prescribed drugs for the treatment of dyslipidaemias and their use for the prevention of vascular events is evidence based. Statins raise HDL-C but this effect seems to vary considerably between studies. We searched the literature to assess the relationship between statin-induced increases in HDL-C levels and surrogate and/or clinical endpoints. Based on the existing evidence, it is difficult to determine how much reduction, if any, in vascular risk is attributable to a statin-induced increment in HDL-C levels. Whether a statin that beyond its LDL-C lowering effect also raises HDL-C has additional benefits in the prevention of vascular events remains to be established.

Effectiveness of ezetimibe alone or in combination with twice a week Atorvastatin (10 mg) for statin intolerant high-risk patients.

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.

Statins for the prevention of first or recurrent stroke.

This review considers the evidence showing that statins can prevent first or recurrent stroke or improve its outcome in subjects at moderate or high risk for cardiovascular disease (CVD). Data are reviewed according to trial design (observational or prospective) and baseline CVD risk. Two (ASCOT, CARDS) out of five primary CVD prevention statin trials showed a considerable reduction in stroke rates. In two (MIRACL and PROVE IT) out of five acute coronary syndrome trials, the prevention of first stroke was significant. Most secondary prevention trials (4S, CARE, LIPID, HPS, GREACE and TNT) showed a beneficial effect of statins in stroke prevention. Finally, SPARCL, the only secondary stroke prevention trial in subjects without overt coronary heart disease (CHD), showed a significant reduction in total and ischaemic (fatal and nonfatal) stroke rate, although a small but significant increase in nonfatal haemorrhagic stroke was noted. There was also a significant reduction in CHD-related events. The possible mechanisms responsible for statin-associated stroke prevention are discussed. The evidence suggests the need to consider early and long-term statin treatment (with substantial low-density lipoprotein cholesterol reduction) in all patients at high risk of any type of major vascular event, without discriminating CHD from stroke. Thus, statins may be beneficial to both the heart and the brain.

The role of endocannabinoid system blockade in the treatment of the metabolic syndrome.

This review considers the use of the first selective blocker of the cannabinoid receptor type 1, rimonabant, to reduce weight and improve cardiovascular disease risk factors in obese patients with metabolic syndrome or multiple cardiovascular disease risk factors. In 4 large trials-Rimonabant in Obesity (RIO)-Lipids, RIO-Europe, RIO-North America, and RIO-Diabetes-after 1 to 2 years of treatment, rimonabant (20 mg/day) led to a significantly greater weight loss and reduction in waist circumference compared with placebo. Treatment with rimonabant was also associated with other favorable changes, including better glycemic control in type 2 diabetes mellitus, improved lipid profile, reduced blood pressure, increased adiponectin levels, fall in high-sensitivity C-reactive protein concentrations, and an overall decrease in the prevalence of the metabolic syndrome. Initial experience with rimonabant shows that it is generally well tolerated with the most common side effect of mild nausea. Rimonabant may be a useful adjunct to lifestyle and behavior modification in the treatment of obese subjects with metabolic syndrome or multiple cardiometabolic risk factors.

Effect of paraoxonase 1 polymorphisms on the response of lipids and lipoprotein-associated enzymes to treatment with fluvastatin.

BACKGROUND: Decreased paraoxonase 1 (PON1) and increased total serum lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activities are suggested to be risk factors for vascular disease. Common PON1 genetic polymorphisms (Q192R and L55M) significantly affect PON1 activity and may also influence high-density lipoprotein (HDL)-associated Lp-PLA(2) activity. However, little is known about the possible effect of PON1 common genetic polymorphisms on the response of lipids as well as PON1 and Lp-PLA(2) activities to treatment with statins. METHODS: Two hundred two hypercholesterolemic patients were treated with fluvastatin 40 mg/day. Fasting serum lipids, Q192R and L55M PON1 polymorphisms as well as PON1 and Lp-PLA(2) (total serum and HDL-associated) activities were determined before and after 6 months of treatment. RESULTS: Fluvastatin treatment did not affect HDL-cholesterol or apolipoprotein (apo) AI but resulted in significant decreases in total cholesterol, triglycerides, low-density lipoprotein-cholesterol, apo B and apo E, as well as total serum Lp-PLA(2) activity. In contrast, PON1 activity significantly increased. None of these changes was influenced by Q192R or L55M PON1 polymorphisms. Overall, HDL-Lp-PLA(2) did not change but L55M polymorphism significantly influenced its response to fluvastatin. Specifically, LL homozygotes experienced a significant increase, while M carriers (LM or MM) experienced a non-significant decrease in HDL-Lp-PLA(2) activity (p = 0.030 between groups). CONCLUSIONS: Q192R and L55M PON1 polymorphisms did not affect the response of lipids, PON1 and total serum Lp-PLA(2) to treatment with a statin. However, L55M PON1 polymorphism significantly modulated the response of HDL-Lp-PLA(2). It should be noted that this is an association study and therefore provides no proof but only indication that PON1 may also exert Lp-PLA(2) activity in HDL.

Atorvastatin decreases triacylglycerol-associated risk of vascular events in coronary heart disease patients.

High triacylglycerol (TAG) levels may predict vascular risk. The effect of a statin-induced reduction in TAG levels, irrespective of HDL-C increase, on clinical outcome has not yet been addressed by an endpoint study in patients with coronary heart disease (CHD). The GREACE study compared usual with structured care aimed at achieving LDL-C = 100 mg/dL (2.6 mmol/L) by dose titration with atorvastatin. All patients had CHD and were followed for 3 years. This post hoc analysis of GREACE examines the effect of statins on TAG levels and their relation with cardiovascular disease (CVD) events in all patients and in the subgroup of patients with metabolic syndrome (MetS). Baseline TAG levels >150 mg/dL (1.7 mmol/L) were predictive of subsequent CVD events [cardiac mortality, non-fatal myocardial infarction (MI), unstable angina (UA), revascularisation, congestive heart failure (CHF), and stroke] only in statin untreated patients. Stepwise regression analysis showed that with every 20% statin-related TAG reduction there was a decrease in CVD risk by 12% (HR 0.88, 95% CI 0.75-0.95, P = 0.007) in the structured care group vs. the usual care group, by 8% (HR 0.92, 95% CI 0.81-0.97, P = 0.02) in all statin treated patients vs. the untreated ones and by 15% (HR 0.85, 95% CI 0.65-0.94, P = 0.005) in those with MetS treated with a statin vs. those untreated. Using the same analysis but only taking into consideration vascular events (cardiac mortality, non-fatal MI, UA, revascularisation, and stroke) there was a 18% (HR = 0.82, 95% CI 0.57-0.96, P = 0.03) decrease in risk in the MetS (+) patients treated with a statin vs. those not on a statin, and a decrease in risk by 16% (HR = 0.84, 95% CI 0.53-1.07, P = 0.08), when only hard vascular endpoints (cardiac mortality, non-fatal MI, and stroke) were considered. TAG levels are predictive of subsequent CVD events in statin untreated CHD patients. Statin (mainly atorvastatin)-induced decrease in TAG levels was related to a significant reduction in subsequent CVD events. This benefit was more pronounced in CHD MetS (+) patients.

Association of drinking pattern and alcohol beverage type with the prevalence of metabolic syndrome, diabetes, coronary heart disease, stroke, and peripheral arterial disease in a Mediterranean cohort.

The purpose of this study was to investigate the relationship between alcohol consumption and the prevalence of the metabolic syndrome (MetS), type 2 diabetes mellitus (DM), coronary heart disease (CHD), stroke, peripheral arterial disease (PAD), and overall cardiovascular disease (CVD) in a Mediterranean cohort. It consisted of a cross-sectional analysis of a representative sample of Greek adults (n = 4,153) classified as never, occasional, mild, moderate, or heavy drinkers. Cases with overt CHD, stroke, or PAD were recorded. In our population, 17% were never, 23% occasional, 27% mild, 24% moderate, and 9% heavy drinkers. Moderate alcohol consumption was associated with a lower trend for the prevalence of the MetS (P = .0001), DM (P < .0001), CHD (P = .0002), PAD (P = .005), and overall CVD (P = .001) but not stroke compared with no alcohol use. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Wine consumption was associated with a slightly better effect than beer or spirits consumption on the prevalence of total CVD, and beer consumption was associated with a better effect than spirits consumption. Alcohol intake was positively related with body weight, high-density lipoprotein cholesterol levels, and hypertension. Moderate alcohol consumption is associated with a lower prevalence of the MetS, DM, PAD, CHD, and overall CVD but not stroke compared with no alcohol use in a Mediterranean population. Heavy drinking was associated with an increase in the prevalence of all of these disease states. Advice on alcohol consumption should probably mainly aim at reducing heavy drinking.

Dyslipidaemia, hypercoagulability and the metabolic syndrome.

The metabolic syndrome is a clustering of risk factors including central obesity, insulin resistance, dyslipidaemia and hypertension. This syndrome is associated with increased risk of cardiovascular disease and is a common early abnormality in the development of type 2 diabetes. The pathogenesis of the syndrome has multiple origins. Obesity and sedentary lifestyle coupled with genetic factors interact to produce the syndrome. Here, we consider two components of the metabolic syndrome, dyslipidaemia and hypercoagulability.

Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome: a randomised study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD. AIM: To evaluate a multifactorial intervention in the treatment of NAFLD. METHODS: A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study. RESULTS: At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects. CONCLUSIONS: Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

The effect of apolipoprotein E polymorphism on the response to lipid-lowering treatment with atorvastatin or fenofibrate.

Although the effect of apolipoprotein E gene polymorphism on the response to treatment with statins has been studied, the results are conflicting. Moreover, little is known about the possible effect of apolipoprotein E alleles on the response to treatment with fibrates. The purpose of this study was to evaluate the effect of apolipoprotein E polymorphism on lipid-lowering response to treatment with atorvastatin and fenofibrate in patients with different types of dyslipidemia. The study population included 136 patients with heterozygous familial hypercholesterolemia (type IIA dyslipidemia) treated with atorvastatin (20 mg/day) and 136 patients with either primary hypertriglyceridemia (type IV dyslipidemia) or mixed hyperlipidemia (type IIB dyslipidemia) treated with micronized fenofibrate (200 mg/day). Overall, no significant associations were detected between apolipoprotein E genotype and response to treatment with atorvastatin. In patients treated with fenofibrate, significant associations were noted between apolipoprotein E genotype and changes in apolipoprotein B, apolipoprotein E and triglyceride levels. Specifically, in apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 individuals, apolipoprotein B reductions were 22%, 17%, and 8%, respectively (P = .003); apolipoprotein E reductions were 45%, 20%, and 15%, respectively (P = .006); whereas triglyceride reductions reached 53%, 36%, and 33%, respectively (P = .033). In conclusion, apolipoprotein E genotype had no significant effect on the response to treatment with atorvastatin in patients with heterozygous familial hypercholesterolemia, but in patients with primary hypertriglyceridemia or mixed hyperlipidemia, there was a clear association between apolipoprotein E genotype and response to treatment with fenofibrate.

Targeting vascular risk in patients with metabolic syndrome but without diabetes.

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.

Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia.

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

Hypouricemia in individuals admitted to an inpatient hospital-based facility.

BACKGROUND: Decreased serum uric acid levels resulting from renal urate wasting occasionally are reported in hospitalized patients because of isolated or generalized proximal tubular damage. There are limited recent findings with regard to the incidence and cause of hypouricemia in patients admitted to an internal medicine clinic. The aim of this study is to examine the prevalence of hypouricemia in individuals admitted to our inpatient hospital-based facility and identify underlying causes and pathogenetic mechanisms and any association of hypouricemia and uricosuria with other tubular defects. METHODS: A total of 7,250 serum urate measurements were available on patients' admission. Hypouricemia is defined as a serum urate level less than 2.5 mg/dL (149 micromo/L). In all hypouricemic cases, a detailed clinical and laboratory investigation was performed. RESULTS: Hypouricemia was found in 90 patients (1.24%). In all except one patient, hypouricemia was associated with inappropriate uricosuria (urate fractional excretion [FE] > 10%; range, 10.8% to 94%). There was an inverse correlation between serum uric acid level and its FE (r = -0.73; P < 0.0001). The most common causes of hypouricemia were obstructive jaundice of any cause (n = 18), solid or hematologic neoplasias (n = 17), diabetes mellitus (n = 12), drugs affecting urate homeostasis (n = 10), and intracranial diseases (n = 8). Seventeen patients with hypouricemia showed one or more other manifestations of proximal tubular damage, such as glucosuria, inappropriate phosphaturia leading to hypophosphatemia, and kaliuria resulting in hypokalemia. CONCLUSION: Hypouricemia caused by inappropriate uricosuria is not rare in patients admitted to an internal medicine clinic, is related to underlying diseases, and may be associated with other abnormalities of proximal tubular function.

Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia.

Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disease. Lipid-lowering agents, such as fibrates, can modify homocysteine levels. However, less is known about the effect of statin therapy on homocysteine. The authors compared the effects of atorvastatin (40 mg/day), simvastatin (40 mg/day), and micronized fenofibrate (200 mg/day) on the serum concentrations of total homocysteine, vitamin B12, and folic acid in patients with primary hyperlipidemia. A total of 128 patients with primary hyperlipidemia (total cholesterol > 240 mg/dL and triglycerides < 350 mg/dL) were assigned to atorvastatin, simvastatin, or fenofibrate. Serum lipid and metabolic parameters were measured at baseline and at 6 and 12 weeks of treatment. Homocysteine correlated positively with serum creatinine and uric acid levels and inversely with serum folic acid levels. All treatment modalities reduced total, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations. High-density lipoprotein (HDL) cholesterol levels significantly increased only in the fenofibrate-treated patients (47.9 +/- 12.5 vs. 50.7 +/- 12.6 vs. 51.2 +/- 12.8 mg/dL, p < 0.01). Atorvastatin and fenofibrate treatment resulted in a significant reduction of serum uric acid levels (5.3 +/- 1.6 vs. 4.9 +/- 1.4 vs. 4.8 +/- 1.4 mg/dL, p < 0.0001 for atorvastatin; 5.6 +/- 1.6 vs. 4.3 +/- 1.4 vs. 4.4 +/- 1.4 mg/dL, p < 0.0001 for fenofibrate). Homocysteine levels were significantly increased only by fenofibrate (10.3 +/- 3.3 vs. 14.1 +/- 3.8 vs. 14.2 +/- 3.6 microU/L, p < 0.001) but did not change from baseline following statin treatment. Neither statins nor fenofibrate had any effect on serum vitamin B12 and folic acid levels. In contrast to fenofibrate, therapeutic dosages of atorvastatin and simvastatin have a neutral effect on serum homocysteine levels, which is in favor of their "cardioprotective" properties.

Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia.

Combined statin and fibrate therapy is often imperative for the improvement of the serum lipid profile in patients with mixed hyperlipidemia. However, the potential risk of myopathy has limited the widespread use of such therapy. Preferably this treatment should involve low optimally tolerable doses of hypolipidemic drugs. Thus, we undertook a study to determine the safety and efficacy of combination therapy with fibrates and small doses of atorvastatin. Twenty-two patients with mixed hyperlipidemia were started on a fibrate regimen (micronised fenofibrate 200mg/day or ciprofibrate 100 mg/day). Because after 12 weeks of therapy the fibrate failed to normalise the serum lipid profile, small doses of atorvastatin (5 mg/day) were added for a further 12 weeks. The administration of the fibrates resulted in a significant decrease in total and LDL-cholesterol levels, as well as in triglycerides, and an increase in HDL-cholesterol levels. The addition of atorvastatin (5 mg/day) resulted in a further decrease in total and LDL-cholesterol levels. Consequently, the hypolipidemic therapy target was achieved in most of the patents. Combination therapy was well tolerated and no significant increases in serum liver and muscle enzymes were noticed. We conclude that the careful administration of small doses of atorvastatin in patients with mixed dyslipidemia receiving fibrates is associated with a significant amelioration of lipid abnormalities.

Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study.

AIMS: To estimate the prevalence of vascular disease (coronary heart disease/stroke/peripheral arterial disease) in individuals with the metabolic syndrome (MetSyn) with or without diabetes mellitus (DM) when compared with subjects without the MetSyn. PATIENTS AND METHODS: A cross-sectional analysis of a representative sample of Greek adults (n = 4153), men and women (49% and 51%, respectively), living in urban, semi-urban and rural areas (54%, 25% and 21%, respectively). The National Cholesterol Education Program-Adult Treatment Panel III definition of the MetSyn was used. RESULTS: The age-adjusted prevalence of the MetSyn was 23.6% [95% confidence interval (CI) = 22.4%-25.1%]; this was similar in men and women. The fully adjusted prevalence of vascular disease in those with the MetSyn (n = 984) was 29.4%, significantly higher than in those without (n = 3169, 9.6%, p < 0.0001), while subjects without both the MetSyn and DM had the lowest vascular disease prevalence (n = 3035, 8.9%). Subjects with the MetSyn but no DM (n = 674) had a vascular disease prevalence of 24.1% (p < 0.0001 vs. those without the MetSyn), which was similar to that in subjects with DM without the MetSyn (n = 134, 25.4%), but lower than in those with both the MetSyn and DM (n = 310, 40.7%, p < 0.0001 vs. all). In comparison to those without the MetSyn [odds ratio (OR) = 1], the ORs of prevalent vascular disease, after multivariate analysis for age, sex and components of the MetSyn, and antiatherosclerotic drugs were: all MetSyn = 1.94 (95% CI = 1.35-2.47), with both MetSyn and DM = 3.04 (95% CI = 1.98-4.11) and with MetSyn but no DM = 1.48 (95% CI = 1.12-1.92). CONCLUSIONS: The prevalence of vascular disease was markedly increased in the presence of the MetSyn. Those with both the MetSyn and DM had the highest prevalence of vascular disease, followed by those with the MetSyn without DM. Probably MetSyn without DM should be considered as a coronary heart disease-risk equivalent in future guidelines. This initiative would reset treatment targets and potentially provide additional benefit in patients with the MetSyn.

Relationship between LDL-C and non-HDL-C levels and clinical outcome in the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.

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

Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values.

BACKGROUND: Atherosclerosis is the leading cause of death in developed countries. Although the mechanisms that underlie this process are not well defined, it has been proposed that atherosclerosis is mainly an inflammatory disease. In this context, a number of inflammatory markers have been studied for their ability to predict future cardiovascular events in asymptomatic individuals or patients with established atherosclerotic disease. METHODS AND RESULTS: The aim of our study was to evaluate the effect of micronized fenofibrate on serum inflammatory markers, such as C-reactive protein, fibrinogen, and plasma platelet-activating factor acetylhydrolase (PAF-AH) in patients with high triglyceride values. An analysis of baseline values revealed that hypertriglyceridemic patients (n = 58) exhibit an atherogenic phenotype, characterized not only by elevated lipid values but also by high concentrations of serum inflammatory markers. Along with the improvement in serum lipid profile (reduction in triglycerides and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein-cholesterol, with a concomitant increase in high-density lipoprotein-cholesterol levels), fenofibrate administration significantly reduced the values of serum inflammatory markers by 34%, 9.5%, and 24.8% for C-reactive protein, fibrinogen, and plasma PAF-AH, respectively. However, with the exception of PAF-AH, these reductions in inflammatory markers were not correlated with the changes in lipid values. CONCLUSIONS: In addition to its well-known hypolipidemic effects, fenofibrate may also possess significant anti-inflammatory properties that can contribute its antiatherogenic effect.