Serum uric acid levels: a useful but not absolute marker of compliance with fenofibrate treatment

The purpose of our study was to investigate whether measurement of serum uric acid levels is a reliable method to assess adherence to fenofibrate treatment. This was a 21 week, open-label study conducted in our lipid clinic. After an 8 week dietary baseline phase, we implemented a treatment phase, during which patients received 200 mg/day micronized fenofibrate for 3 months. Serum lipid profiles, including levels of lipoprotein(a) and fibrinogen, serum uric acid, as well as muscle and liver enzymes, were measured after the dietary phase, and at the end of the 3 month treatment period. Compliance was assessed using a clinical interview. A significant decrease in serum uric acid levels was observed in the compliant, while no significant change was noticed in the non-compliant. The compliant had lower serum uric acid concentrations compared to the non-compliant (P < 0.01) after fenofibrate treatment. Furthermore, they demonstrated lower levels of triglycerides and higher high-density lipoprotein (HDL) cholesterol concentrations (P < 0.05 for both parameters). The results show that serum uric acid concentrations may be used as a useful tool to assess compliance with fenofibrate therapy.     

Management of mixed dyslipidemia in patients with or at risk for cardiovascular disease: a role for combination fibrate therapy

Background: Lowering low-density lipoprotein cholesterol (LDL-C) is the primary focus of the management of dyslipidemia in patients with or at risk for cardiovascular disease. However, use of a statin alone may be insufficient for the treatment of mixed dyslipidemia, which is characterized by low levels of high-density lipoprotein cholesterol and elevated levels of triglycerides, with or without elevated levels of LDL-C. Objective: This report reviews the evidence for the efficacy and tolerability of different combination treatments for the management of mixed dyslipidemia, as supported by clinical-trial data and recommended by national guidelines. Methods: Using the terms lipid-modifying therapy, combination therapy, combination statin-fibrate therapy, and mixed dyslipidemia, a search of PubMed was conducted (completed in April 2007, updated to October 2007) to identify English-language publications and pertinent studies of fibrate combination therapy in patients with mixed dyslipidemia, including those with diabetes or the metabolic syndrome. Results: National guidelines recommend the addition of either niacin (nicotinic acid) or a fibrate to statin therapy in patients with mixed dyslipidemia to achieve better overall lipid control. Fibrates do not have detrimental effects on uric acid levels or glycemic control in patients with diabetes or the metabolic syndrome. Based on data from the US Food and Drug Administration Adverse Event Reporting System indicating that gemfibrozil plus a statin was associated with a 15-fold higher risk of rhabdomyolysis than fenofibrate plus a statin, fenofibrate may be the fi-brate of choice for use in combination with a statin. As reported by the Fenofibrate Intervention and Event Lowering in Diabetes study, fenofibrate treatment has also been associated with microvascular benefits in patients with type 2 diabetes, which is consistent with preliminary evidence from the Diabetes Atherosclerosis Intervention Study. Conclusion: The addition of fenofibrate to statin therapy may be a useful strategy for the management of mixed dyslipidemia in patients with or at risk for cardiovascular disease.     

Efficacy and tolerability of a "suprabioavailable" formulation of fenofibrate in patients with dyslipidemia: a pooled analysis of two open-label trials

BACKGROUND: Newer fibrates such as micronized fenofibrate lower triglyceride (TG) levels, raise high-density lipoprotein cholesterol (HDL-C) levels, and lower fibrinogen levels, in addition to markedly lowering levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). A new microcoated "suprabioavailable" formulation of fenofibrate has demonstrated a superior pharmacokinetic profile compared with micronized fenofibrate 200 mg/d and may effectively reduce cardiovascular risk factors at the lower dose of 160 mg/d. OBJECTIVE: The goal of this study was to assess the efficacy and tolerability of the suprabioavailable" formulation of fenofibrate in patients with type IIa, type IIb, or type IV dyslipidemia. METHODS: This was a pooled analysis of data from 2 unpublished multicenter, open-label trials with a common protocol. After a 4-week washout period, patients with dyslipidemias not corrected by diet alone were assigned to receive microcoated fenofibrate 160 mg/d for 12 weeks. Changes in lipid profiles and safety variables (vital signs, body weight, and laboratory measures) were monitored throughout the study, and adverse events occurring between visits 1 and 5 were recorded by the study investigators. RESULTS: The 2 trials included 375 men and women (mean age, 55.2 years) with type IIa (n = 158), type IIb (n = 195), type IV (n = 21), or other (n = 1) dyslipidemias. At end point. HDL-C levels in patients with type IIa, IIb, or IV dyslipidemia were increased by a respective 10.9% (P < 0.001), 16.1% (P < 0.001), and 12.1% (P < 0.05), whereas TG levels were decreased by a respective 27.7% (P < 0.001), 46.4% (P < 0.001), and 40.2% (P < 0.05). In patients with type IIa or IIb dyslipidemia, TC decreased (-14.3% in each group), LDL-C decreased (-20.6% and -13.2%, respectively), and the LDL-C/HDL-C ratio decreased (-26.7% and -22.0%) (all, P < 0.001). Overall, 121 of 375 (32.3%) patients experienced > or = adverse event (AE) (202 nonserious, 8 serious). Of these, 10.1% were judged to be possibly drug related. The most common nonserious AEs were those affecting the body as a whole (2.7% of patients) and the digestive system (5.3% of patients). No serious AE was considered drug related. CONCLUSIONS: The new "suprabioavailable" microcoated, micronized formulation of fenofibrate appears to maintain the good efficacy and safety profile of micronized fenofibrate. In the study population with moderate dyslipidemia (types IIa and IIb), it promoted beneficial changes in major lipid risk factors for cardiovascular disease.     

Resolving hyperlipidemia after liver transplantation in a patient with primary sclerosing cholangitis

A 64-year-old man with primary sclerosing cholangitis (PSC) and resultant liver failure presented to our hospital with severe dyslipidemia (total cholesterol, 525 mg/dL; low-density lipoprotein (LDL) cholesterol, 489 mg/dL; high-density lipoprotein (HDL) cholesterol, 13 mg/dL; triglycerides, 114 mg/d) and coronary artery disease. The abnormal lipid profile of patients with cholestatic liver disease, such as PSC, includes an abnormal atherogenic LDL called lipoproteinX. The patient's dyslipidemia persisted despite treatment with a statin. Lipids normalized only after liver transplantation (total cholesterol, 135 mg/dL; LDL cholesterol, 60 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; triglycerides, 130 mg/dL). To the best of our knowledge, the dramatic improvement in the lipid profile after liver transplantation represents the first such published report for PSC. The recognition of dyslipidemia and atherosclerosis in those with cholestatic liver disease and the normalization of lipid profile after liver transplantation warrant further study. We present a review of dyslipidemia in cholestatic liver disease, its relationship to atherosclerosis, and its treatment.     

江苏省常州地区自然人群人体测量指标与血压、血脂关系的研究

目的调查常州地区自然人群的高血压和血脂紊乱的发病率,探讨并比较3种人体测量指标包括体重指数(BMI)、腰臀比(WHR)和体脂肪率(FAT%)及其与血压、血脂的关系。方法在常州市社区自然人群中采用临床横断面研究通过整群抽样抽取研究样本,采用格式化调查表收集人群信息,并检测血糖、血脂、血压、BMI、WHR、FAT%、尿酸、肝肾功能等指标。结果常州地区自然人群血脂紊乱、高血压、糖尿病的发病率分别为41.6%、28.2%和10.7%。调整年龄差异后男女的BMI、WHR和FAT%均有显著差异,其中男性的BMI、WHR高于女性,女性的FAT%显著高于男性。在自然人群中BMI和WHR在预测血脂紊乱和高血压的能力上没有显著差异,并都显著高于FAT%的预测能力,但在男女分层后无差别。3种人体测量指标的的独立影响因素包括SBP、HDL、LDL、UA。年龄是BMI和WHR的影响因素。结论常州地区自然人群高血压和血脂紊乱的发病率呈现高发趋势;BMI、WHR和FAT%不仅是肥胖的指标,对潜在的心血管疾病危险因素—血脂紊乱和高血压发生的危险性亦有预报作用。超重和肥胖的早期发现,指导人群改变生活习惯,控制BMI、WHR和FAT%的上升发展趋势的工作迫在眉睫。     

A review of combined hyperlipidaemia and its treatment with fenofibrate

Approximately 15% of myocardial infarction survivors less than 60 years of age have a plasma lipid abnormality defined as combined hyperlipidaemia. Patients with this condition are at substantial risk for future cardiovascular events. Combined hyperlipidaemia involves elevations in both plasma triglycerides and low-density lipoprotein (LDL) cholesterol and may share similarities with hyperapolipoproteinaemia, LDL-pattern B and the small LDL-pattern. Treatment is directed at reduction of LDL-cholesterol and plasma triglyceride values. Nicotinic acid and the fibric acid derivatives are useful therapeutic agents. Fenofibrate is a fibric acid derivative that lowers both triglycerides and LDL-cholesterol in combined hyperlipidaemia. In combined hyperlipidaemia, fenofibrate has been shown to reduce significantly plasma triglycerides by approximately 40%, LDL-cholesterol by 6%, and to increase high-density lipoprotein cholesterol by 15%. Apoproteins are favourably altered with increases in apoprotein-A, decreases in apoprotein-E and inconsistent decreases in apoprotein-B. Fenofibrate is well tolerated with primarily dermatological side-effects.     

Efficacy and Tolerability of Pitavastatin Versus Pitavastatin/Fenofibrate in High-risk Korean Patients with Mixed Dyslipidemia: A Multicenter,Randomized, Double-blinded,Parallel, Therapeutic Confirmatory Clinical Trial

PurposeDyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD.MethodsThis multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150–500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non–HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment.FindingsThe difference in the mean percentage change in non–HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was −12.45% (95% CI, −17.18 to −7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non–HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy.ImplicationsIn these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non–HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.     

原发性高血压伴高尿酸血症与冠心病发生的相关性研究

目的:探讨在原发性高血压病患者中,高尿酸血症与冠心病的关系。方法:观察121例原发性高血压病及原发性高血压病伴冠心病患者血尿酸浓度及总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇等冠心病危险因素,用冠状动脉造影方法确诊冠心病。结果:高血压伴冠心病组患者血尿酸浓度及高尿酸血症发生率高于单纯高血压组;血尿酸浓度越高,冠状动脉病变支数越多。结论:高尿酸血症是冠心病的一个危险因素,有必要监测及及时干预高血压患者的血尿酸浓度。     

Glycation of lipoproteins and accelerated atherosclerosis in non-insulin-dependent diabetes mellitus

Summary We used a new and remarkably simple method to examine the extent of in vivo lipoprotein glycation in type II diabetic patients with atherosclerosis and diabetic patients with no complications. Serum glycated lipoprotein levels were determined by agarose gel film electrophoresis in 48 non-diabetic control subjects and 39 diabetic patients, of whom 26 had no complications and 13 had atherosclerotic heart disease. Fasting serum glucose, glycohemoglobin and serum fructosamine concentrations (indicators of glycemia) and total cholesterol, triglyceride, low-density lipoprotein-, very low-density lipoprotein-and high-density lipoprotein-cholesterol concentrations and the low-density lipoprotein/high-density lipoprotein ratio (serum lipid profile) were also detewrmined in the control and diabetic subjects. Glycated low-density lipoprotein and very low-density lipoprotein concentrations were significantly increased in diabetic patients compared with controls; but only glycated very low-density lipoprotein was significantly increased in atherosclerotic patients compared with diabetics without complications. The lipid profile parameters were not significantly increased in patients compared with controls. In diabetics, especially those with poorly controlled hyperglycemia and atherosclerosis, glycation of lipoprotein fractions might be more important than serum lipid and lipoprotein abnormalities. The significant correlation between atherosclerosis and glycated very low-density lipoprotein, suggests that very low-density lipoprotein glycation could be responsible for the development of atherosclerosis in diabetes.     

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile

Summary The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice. Finally, repeated lipid measurements are required to assess coronary heart disease risk accurately.     

Dyslipidemia in type 2 diabetes

Type 2 diabetes mellitus is associated with a cluster of lipid abnormalities:elevated plasma triglycerides, reduced high-density lipoprotein cholesterol, and smaller and denser low-density lipoproteins,which have been associated with an increased risk of cardiovascular disease. Insulin resistance may contribute to dyslipidemia associated with type 2 diabetes by increasing hepatic secretion of large,triglyceride-rich very low-density lipoprotein particles and by impairing the clearance of lipoprotein particles from plasma. Lifestyle interventions may be effective in improving the diabetic dyslipidemia syndrome. For patients who do not respond to lifestyle changes, pharmacologic therapies (lipid-lowering medications and anti-diabetic agents) are available. Clinical trials demonstrate that the use of such pharmaceutics to treat diabetic dyslipidemia concomitantly reduces the risk of coronary artery disease.     

The combination of nebivolol plus pravastatin is associated with a more beneficial metabolic profile compared to that of atenolol plus pravastatin in hypertensive patients with dyslipidemia: a pilot study

Nebivolol, a selective beta1-lipophilic blocker, achieves blood pressure control by modulating nitric oxide release in addition to b-blockade. This dual mechanism of action could result in minimum interference with lipid metabolism compared to atenolol, a classic beta1-selective blocker. Hypertensive patients commonly exhibit lipid abnormalities and frequently require statins in combination with the anti-hypertensive therapy. We conducted this trial in order to clarify the effect on the metabolic profile of beta-blocker therapy with atenolol or nebivolol alone, or in conjunction with pravastatin. Thirty hypertensive hyperlipidemic men and women (total cholesterol >240 mg/dL [6.2 mmol/L], low-density lipoprotein cholesterol >190 mg/dL [4.9 mmol/L], triglycerides <500 mg/dL [5.6 mmol/L]) were separated in two groups. One group consisted of 15 subjects on atenolol therapy (50 mg daily), and the other group included 15 subjects on nebivolol therapy (5 mg daily). After 12 weeks of beta-blocker therapy, pravastatin (40 mg daily) was added in both groups for another 12 weeks. Atenolol significantly increased triglyceride levels by 19% (P=.05), while nebivolol showed a trend to increase high-density lipoprotein cholesterol by 8% (NS) and to decrease triglyceride levels by 5% (NS). Atenolol significantly increased lipoprotein(a) by 30% (P=.028). Fibrinogen levels were equally and not significantly decreased in both groups by 9% and 7%, respectively. Furthermore, atenolol and nebivolol decreased serum high-sensitivity C-reactive protein levels by 14% (P=.05) and 15% (P=.05), respectively. On the other hand, both atenolol and nebivolol showed a trend to increase homocysteine levels (NS) by 13% and 11%, respectively. Although uric acid levels remained the same, atenolol significantly increased the fractional excretion of uric acid by 33% (P=.03). Following nebivolol administration, glucose levels remained the same, while insulin levels were reduced by 10% and the HOMA index (fasting glucose levels multiplied by fasting insulin levels and divided by 22.5) was reduced by 20% (P=.05). There were no significant differences between the two patient groups in the measured parameters after the administration of beta-blockers, except for triglycerides (P<.05) and the HOMA index (P=.05). The addition of pravastatin to all patients (n=30) decreased total cholesterol by 21% (P<.001), low-density lipoprotein cholesterol by 28% (P<.001), apolipoprotein-B by 22% (P<.001), apolipoprotein-E by 15% (P=.014) and lipoprotein(a) levels by 12% (P=.023). Moreover, homocysteine levels and C-reactive protein were reduced by 17% (P=.05) and 43% (P=.05), respectively. We conclude that nebivolol seems to be a more appropriate therapy in hypertensive patients with hyperlipidemia and carbohydrate intolerance. Finally, the addition of pravastatin could further correct the well-established predictors of cardiovascular events.     

The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidaemic hypertensive patients

It is now well documented that hypertension is associated with a chronic low-grade inflammatory state. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Our objective was to evaluate the effect of fenofibrate on the levels of hs-CRP in dyslipidaemic hypertensive patients. We selected 30 dyslipidaemic hypertensive patients and 20 normolipidemic normotensive healthy subjects. Dyslipidaemic hypertensive patients were treated with fenofibrate 200 mg/day for 3 months. Serum hs-CRP and metabolic parameters were evaluated at baseline in both groups and after fenofibrate treatment in dyslipidaemic hypertensive patients. At baseline, significantly higher hs-CRP levels were found in dyslipidaemic hypertensive patients than normal subjects (0.48 +/- 0.3 vs. 0.15 +/- 0.1 mg/dl, p < 0.01). Total cholesterol, low-density lipoprotein cholesterol and triglyceride significantly decreased (p < 0.05, p < 0.05 and p < 0.01, respectively), and levels of high-density lipoprotein cholesterol significantly increased (p < 0.05) after treatment with fenofibrate in dyslipidaemic hypertensive group. Levels of hs-CRP significantly decreased after fenofibrate treatment from a mean of 0.48 +/- 0.3 mg/dl to vs. 0.16 +/- 0.2 mg/dl, p < 0.01). Our findings suggest that fenofibrate may be used as a first-line therapy for improving the plasma lipids profile as well as the chronic low-grade inflammatory state in dyslipidaemia and hypertension.     

Laboratory approaches for predicting and managing the risk of cardiovascular disease: postanalytical opportunities of lipid and lipoprotein testing

Abstract Lipoprotein-related risk of cardiovascular disease (CVD) can be adequately predicted in subjects with elevated total cholesterol and low-density lipoprotein (LDL-)cholesterol using the available guidelines. However, individuals with dyslipidemia can have normal total- and LDL-cholesterol concentrations. Many statin-treated patients remain at high residual risk of CVD despite achieving LDL goals. The small dense LDL phenotype, frequently presenting with hypertriglyceridemia and low high-density lipoprotein (HDL-)cholesterol (lipid triad), may contribute to failure to identify and treat high-risk individuals. Therefore, calculated non-HDL-cholesterol is recommended as secondary therapeutic target to LDL-cholesterol in patients with hypertriglyceridemia and mixed dyslipidemia. On-treatment apolipoprotein B adds prognostic information to LDL- and non-HDL-cholesterol by indicating the total number of atherogenic lipoproteins, regardless of their cholesterol content. Risk may be higher than indicated in the risk estimation systems in additional subjects with elevated lipoprotein(a) and homocysteine concentrations. To improve the (post-)post-analytical phase of lipid tests, aiming for maximal health outcome effectiveness of test interpretation and utilization, laboratory professionals should deliver clinical added value services by providing readily interpreted and guideline-adjusted test reports, interpretative commenting, proactive reflex testing or recommending additional tests, and joining multidisciplinary cooperations in guideline development and cost/benefit studies.     

Effect of Melothria maderaspatana leaf-tea consumption on blood pressure, lipid profile, anthropometry, fibrinogen, bilirubin, and albumin levels in patients with hypertension

OBJECTIVE: To determine the effect of Melothria maderaspatana (Linn.) leaf-tea on blood pressure, plasma lipid profile, fibrinogen, albumin together with serum bilirubin and anthropometric measurements in volunteer participants with hypertension, because all these variables have been shown to influence vascular events. SUBJECTS AND DESIGN: A total of 50 subjects-25 (mean age of 58 +/- 9.0 years; 12 were women) with mild-to-moderate hypertension (systolic blood pressure [SBP] >or= 140 mm Hg; diastolic blood pressure [DBP] >or= 90 mm Hg) and 25 normotensives (mean age of 48 +/- 8.0 years; 11 women)-were selected for this study. Plasma lipid profile, fibrinogen, albumin, serum bilirubin, and anthropometric measurements were measured at baseline and after leaf-tea consumption by the patient with hypertension for 45 days. RESULTS: SBP and DBP gradually decreased and pulse rate decreased. The total cholesterol, low-density lipoprotein cholesterol and triglycerides, and phospholipids levels decreased significantly and high-density lipoprotein cholesterol and serum bilirubin levels increased after tea consumption in patients with hypertension. We also observed significant body weight loss and reduction in fibrinogen levels. There was no significant difference in plasma level of albumin. CONCLUSIONS: Thus, M. maderaspatana leaf-tea consumption gradually decreased BP and showed beneficial effects on blood lipid profile, fibrinogen, bilirubin, and body mass index in patients with hypertension.     

Lipid and lipoprotein profile in physiological pregnancy

Physiologic pregnancy is associated with a broad series of metabolic adaptations which may also influence the metabolism of lipids and lipoproteins. Although the modification of serum lipids and lipoproteins has been exhaustively investigated during and after pregnancy, the relative changes recorded vary widely among the different studies. A comprehensive lipid and lipoprotein profile was evaluated in 57 women with uncomplicated pregnancies at different gestational ages (20 in the first, 20 in the second, and 17 in the third trimester of pregnancy) and compared to that of 21 non-pregnant women. Conventional lipid parameters, including total cholesterol, high-density lipoprotein cholesterol and triglycerides, were evaluated on the Modular System P. Low-density lipoprotein cholesterol was quantified by the formula of Friedewald, the atherogenic index of plasma was quantified by the formula log (triglycerides/high-density lipoprotein cholesterol), whereas lipoprotein(a) was assayed on the BN II nephelometric analyzer. We observed that all the lipid parameters tested were significantly modified by the gestational age; in particular, women in the second and third trimester displayed significantly increased total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total to high-density lipoprotein cholesterol ratio, lipoprotein(a) and atherogenic index of plasma (third trimester only) when compared to either the control population or the subgroup of women in the first trimester of pregnancy. The value distributions and the relative percentage of women with undesirable or abnormal values according to the current NCEP or AHA/ACC goals were comparable between controls and women in the first trimester. However, when compared with either controls or women in the first trimester, advanced pregnancy was associated with an increased prevalence of undesirable or abnormal values for total cholesterol, low-density lipoprotein cholesterol and triglycerides in the second trimester, and total cholesterol, low-density lipoprotein cholesterol, triglycerides, total to high-density lipoprotein cholesterol ratio and lipoprotein(a) (only from non-pregnant women) in the third trimester. The results of this case-control study demonstrate that physiological pregnancy is associated with a substantial modification of the lipid and lipoprotein metabolism from the second trimester, providing reference ranges for traditional and emerging cardiovascular risk predictors throughout the gestational period.     

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

INTRODUCTION: The relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls. METHODS: Thirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroid-related medication. RESULTS: Serum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 microIU/ml and TSH <10 microIU/ml (in SCH patients, P>0.05). CONCLUSION: Our results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject's TSH level.     

Fenofibrate in the treatment of dyslipidemia: a review of the data as they relate to the new suprabioavailable tablet formulation

BACKGROUND: The fibric acid derivative fenofibrate is indicated as an adjunct to dietary modification in adults with primary hypercholesterolemia or mixed dyslipidemia (types IIa and IIb hyperlipidemia, Fredrickson classification) to reduce levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and apolipoprotein (apo) B, and to increase levels of high-density lipoprotein cholesterol (HDL-C) and apo A. It is also indicated as adjunctive therapy to diet for the treatment of hypertriglyceridemia (types IV and V hyperlipidemia). Initially approved in the United States in a micronized capsule formulation, fenofibrate is now available in a new "suprabioavailable" tablet formulation that has increased bioavailability, achieving equivalent plasma concentrations at lower doses. The 67- and 200-mg micronized capsules can be considered equivalent to the 54- and 160-mg suprabioavailable tablets, respectively. OBJECTIVE: This paper reviews the pharmacologic properties, clinical usefulness, and safety profile of fenofibrate in the management of dyslipidemias. METHODS: Recent studies, abstracts, reviews, and consensus statements published in the English-language literature were identified through searches of MEDLINE (1966-January 2002), International Pharmaceutical Abstracts (1970-January 2002), and PharmaProjects (1990-January 2002) using the search terms fenofibrate, fibrates, hyperlipidemia, hypertriglyceridemia, and dyslipidemia. RESULTS: Fenofibrate is well absorbed after oral administration, with peak plasma levels attained in 6 to 8 hours. The absolute bioavailability of fenofibrate cannot be determined due to its being virtually insoluble in aqueous media suitable for injection; however, after oral administration of a single dose of radiolabeled fenofibrate, approximately 60% of the dose appeared in urine, primarily as fenofibric acid and its glucuronated conjugate, and approximately 25% was excreted in the feces. The apparent volume of distribution is 0.89 L/kg in healthy volunteers, and protein binding is approximately 99% in healthy and hyperlipidemic patients. Neither fenofibrate nor fenofibric acid appears to undergo significant oxidative metabolism in vivo. Fenofibric acid has a half-life of 20 hours. Fenofibrate is effective in lowering TG levels and increasing HDL-C levels. Its LDL-C-lowering effect is greater than that of gemfibrozil. Adverse effects of fenofibrate appear to be similar to those of other fibrates, including gastrointestinal symptoms, cholelithiasis, hepatitis, myositis, and rash. Fenofibrate therapy has been associated with increases in serum aminotransferase levels, and clinical monitoring of these markers of liver function should be performed regularly. CONCLUSIONS: Fenofibrate is effective in reducing levels of TG, TC, and LDL-C, and increasing levels of HDL-C in patients with dyslipidemias. Its efficacy and tolerability in the treatment of hypertriglyceridemia and combined hyperlipidemia have been demonstrated in numerous clinical trials. Its use is accompanied by a low incidence of adverse effects and laboratory abnormalities. Fenofibrate protects against coronary heart disease not only through its effects on lipid parameters but also by producing alterations in LDL structure and, possibly, alterations in the various hemostatic parameters. Its uricosuric property may prove to be a useful adjunctive attribute.     

Serum lipoprotein profile in patients with cancer. A comparison with non-cancer subjects

The association of cancer with low serum total cholesterol is well established. Less clear is the relationship of cancer with the cholesterol distribution among the different lipoprotein classes. Conflicting results have been reported on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and serum triglyceride levels in different types of tumor. Total serum cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and serum triglycerides were analyzed in 530 patients with newly diagnosed cancer (97 with hematological malignancies, 92 with tumor of the lung, 108 of the upper digestive system, 103 of colon, 32 of breast, and 98 of the genitourinary system) and in 415 non-cancer subjects. Anthropometric (body mass index) and biochemical (serum albumin) indices of nutritional status were also determined in all subjects. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum albumin, and body mass index were significantly lower in cancer than in non cancer-subjects. The lowest values of total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were recorded in patients with hematological malignancies and the highest in patients with breast tumor. All the cancer groups, with the exception of women with breast cancer, showed significantly lower total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol than age- and sex-matched non-cancer subjects. Multiple regression analysis with low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides as dependent variables and sex, age, body mass index, albumin, and cancer (dummy variable) as independent variables, showed that cancer was independently associated with low levels of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol and with high values of serum triglycerides. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum triglycerides, body mass index and serum albumin were significantly lower in patients with metastatic than in patients with non-metastatic solid tumor. The significant difference in low-density lipoprotein-cholesterol and serum triglycerides between patients with metastatic and non-metastatic cancer was lost when lipoprotein cholesterol and serum triglyceride levels were adjusted for nutritional variables. The lipid profile in cancer patients is characterized by low low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol and relatively high serum triglycerides. The abnormality is a common feature of both hematological and solid tumors and is not entirely explained by poor nutrition.     

Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol.

In a retrospective analysis, 63 participants in a cardiac rehabilitation-preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time-release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty-four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)