Review of extended-release niacin/laropiprant fixed combination in the treatment of mixed dyslipidemia and primary hypercholesterolemia

Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins

Oral Lipid-Lowering Treatments Beyond Statins: Too Old and Outdated or Still Useful?

PURPOSE OF REVIEW For many years, the lipid-lowering armamentarium consisted of statins and/or ezetimibe and/or bile acid sequestrants and/or fibrates. Now, with the availability of new drugs mostly injectables, the field has changed and the role of oral non-statin drugs (including bempedoic acid) must be reevaluated. RECENT FINDINGS Ezetimibe remains a very important combination partner for statins with continuously increasing treatment numbers. Bempedoic acid is another interesting combination partner for statin/ezetimibe or ezetimibe alone but lacks in contrast to ezetimibe evidence from outcome trials. The role of fibrates is less clear as they have shown disappointing results in outcome trials but may still be used in selected, high-risk patients with combined dyslipidemia. Bile acid sequestrants are now rarely used as there are stronger, better tolerable ways to lower LDL-cholesterol. With the introduction of new injectable lipid-lowering drugs, some oral drugs such as ezetimibe and bempedoic acid still have an important spot in our treatment algorithm others such as fibrates have a less clear role while again others are now rarely used

Mipomersen: evidence-based review of its potential in the treatment of homozygous and severe heterozygous familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal-dominant inherited disease with a prevalence of one in 500 (heterozygous) to one in 1,000,000 (homozygous). Mutations of the low-density lipoprotein (LDL) receptor gene, the apolipoprotein B100 gene, or the PCSK9 gene may be responsible for the disease. The resulting LDL hypercholesterolemia results in premature atherosclerosis as early as childhood (homozygous FH) or in adulthood (heterozygous FH). Current treatment modalities include lifestyle modification, combination drug therapy (statin-based), and apheresis. Mipomersen is an antisense oligonucleotide which inhibits apolipoprotein B production independent of LDL receptor function and thus works in homozygous FH, heterozygous FH, and other forms of hypercholesterolemia. Mipomersen is given 200 mg/week subcutaneously. Phase III studies indicate that the LDL cholesterol concentration can be reduced by 25%–47%, lipoprotein(a) levels by 20%–40%, and triglyceride concentrations by approximately 10%. In general, mipomersen has no effect on high-density lipoprotein cholesterol concentrations. Although there is considerable interindividual variability, the observed lipid effects are largely independent of age, gender, concomitant statin therapy, and underlying dyslipoproteinemia. The most common side effects are injection site reactions (70%–100%), flu-like symptoms (29%–46%), and elevated transaminases associated with an increased liver fat content (6%–15%). Mipomersen may be an interesting addon drug in patients with heterozygous or homozygous FH not reaching treatment goals, either because baseline values are very high or because high-dose statins are not tolerated

Effect of the angiotensin receptor blocker irbesartan on metabolic parameters in clinical practice: the DO-IT prospective observational study

Aims: A number of intervention studies have shown that therapy with angiotensin receptor blockers, such as irbesartan, can improve metabolic parameters and reduce the incidence of diabetes mellitus. It is unknown whether this observation also holds true in routine clinical settings. Methods: We evaluated the effect of irbesartan (150 mg or 300 mg/d) together with or without hydrochlorothiazide (12.5 mg/d) in 3259 German patients. A total of 750 primary care physicians evaluated up to 5 subsequent patients with metabolic syndrome (58.9% diabetic), in whom irbesartan therapy was newly initiated (87%) or continued (13%). Results: Six months of irbesartan therapy decreased systolic blood pressure by 14% (157.4 +/- 14.7 vs. 135.0 +/- 10.7 mmHg) and diastolic blood pressure by 13% (92.9 +/- 9.2 vs. 80.8 +/- 6.8 mmHg). This was associated with a decrease in body weight (-2.3%), fasting glucose (-9.5%), HbA1c (-4.6%), LDL-cholesterol (-11%), triglycerides (-16%) and gamma-GT (-12%) and an increase in HDL-cholesterol (+5%). These changes were somewhat more pronounced in male than in female patients and in obese than in lean patients. Changes in glucose concentration and HbA1c were much more prominent in diabetic patients. Conclusion: Irbesartan therapy improves metabolic parameters in routine clinical settings. Thus, our study confirms previously published results from large intervention trials and extends the findings to routine clinical practice

Cisplatin-Based Chemotherapy for Pulmonary Metastasized Germ Cell Tumors of the Testis - Be Aware of Acute Respiratory Distress Syndrome

Background: Cisplatin-based combination chemotherapy is regarded as standard of care for patients with advanced germ cell tumors. In patients with lung metastases and a high tumor load, an association between induction chemotherapy and the development of a `tumor-associated' acute respiratory distress syndrome (ARDS) has been hypothesized. Case Report: We report the clinical course of a 19-year-old patient who rapidly developed fatal ARDS during the first cycle of chemotherapy using the PEI regimen (cisplatin, etoposide and ifosfamide) for a metastasized (lung, liver, lymph nodes) germ cell tumor of the testis. Conclusion: Further clinical research in order to better define risk factors for developing ARDS in this patient population as well as novel strategies for the prevention and treatment of ARDS in those patients are necessary

Differential effects of fenofibrate versus atorvastatin on the concentrations of E-selectin and vascular cellular adhesion molecule-1 in patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia: a randomized cross-over trial

BACKGROUND: Diabetic dyslipoproteinemia is characterized by hypertriglyceridemia, low HDL-cholesterol and often elevated LDL-cholesterol and is a strong risk factor for atherosclerosis. Adhesion molecule levels are elevated both in hyperlipoproteinemia and diabetes mellitus. It is unclear whether fibrate or statin therapy has more beneficial effects on adhesion molecule concentrations. METHODS: Atorvastatin (10 mg/d) was compared to fenofibrate (200 mg/d) each for 6 weeks separated by a 6 week washout period in 11 patients (6 male, 5 female; 61.8 ± 8.2 years; body mass index 29.8 ± 3.1 kg/m(2)) with type 2 diabetes mellitus (HbA(1c )7.3 ± 1.1 %) and mixed hyperlipoproteinemia using a randomized, cross-over design. Fasting blood glucose, HbA(1)c, lipid parameters, E-selectin, ICAM-1, VCAM-1, and fibrinogen concentrations were determined before and after each drug. RESULTS: Glucose and HbA(1)c concentrations remained unchanged during the whole study period. LDL cholesterol was reduced during atorvastatin therapy, triglycerides were lowered more effectively with fenofibrate. Comparison of pre- and postreatment concentrations of E-selectin showed a reduction during atorvastatin (-7 %, p = 0.11) and fenofibrate (-10 %, p < 0.05) therapy. Atorvastatin treatment reduced VCAM-1 levels by 4% (p < 0.05), while VCAM-1 concentrations remained unchanged (+1%, ns) during fenofibate therapy. However, direct comparisons of post-treatment levels during both forms of therapy were not of statistical significance. ICAM-1 levels were not influenced by either form of therapy. CONCLUSIONS: In addition to the different beneficial effects on lipid metabolism, both drugs appear to lower adhesion molecule plasma concentrations in a different manner in patients with type 2 diabetes and mixed hyperlipoproteinemia. Our observations should be confirmed in a larger cohort of such patients

Prevalence and sociodemographic determinants of adult obesity: A large representative household survey in a resource-constrained African setting with double burden of undernutrition and overnutrition

BACKGROUND The obesity epidemic has continued to spread across the globe involving even poor nations of the world. METHOD Household population survey of adults aged 20-60 years. Multistage stratified cluster randomised sampling involving both urban and rural statewide representative population samples. Anthropometric measurements were taken using standard methods. Prevalences were weighted and multinomial regression analyses were done. RESULTS A total of 6628 individuals from 2843 households were surveyed. The weighted overall prevalence for underweight was 9.1% (95% CI 8.1 to 10.1), 65.1% (95% CI 63.6 to 66.6) for normal weight, 19.0% (95% CI 17.8 to 20.3) for overweight and 6.8% (95% CI 6.0 to 7.5) for obese. Men were less likely to be overweight (adjusted OR (AOR) 0.79; 95% CI 0.68 to 0.92) and obese (AOR 0.24; 95% CI 0.19 to 0.31) than women. Urban residents were more likely to be overweight (AOR 1.42; 95% CI 1.18 to 1.71) and obese (AOR 2.09; 95% CI 1.58 to 2.76) than rural residents. Each additional 1-year increase in age increased the risk of overweight by 1.012 (AOR 1.012; 95% CI 1.005 to 1.018) and that of obesity by 1.03 (AOR 1.03; 95% CI 1.02 to 1.04). The low-income class was less likely to be overweight (AOR 0.694; 95% CI 0.507 to 0.951) and obese (AOR 0.44; 95% CI 0.28 to 0.67). CONCLUSION The prevalence of obesity and overweight in Enugu Nigeria is high and fast approaching that of underweight. Women, urban dwellers, older adults and high-income earners are at higher risk for obesity and overweight. The study provides robust information for public health policies towards the prevention of obesity in Nigeria

Haben die Konzentrationen von Interleukin 6, Procalcitonin und CRP bei Intensivpatienten während des ersten Fieberanstieges eine prognostische Bedeutung?

Serum levels of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were measured in 38 critically ill patients immediately after an increase in body temperature above 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison to healthy control subjects. However, only IL-6 levels were significantly higher (p&lt;0.05) in nonsurvivors compared with survivors. Sensitivity, specificity, positive, and negative predictive values for survival were higher for IL-6 in comparison to levels of PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 compared to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of prognosis and mortality in patients with the onset of fever

Effect of sleeve gastrectomy on postprandial lipoprotein metabolism in morbidly obese patients

Background: Obesity is associated with abnormal fasting and postprandial lipids, which may link obesity with atherosclerosis. We explored fasting and postprandial lipids in morbidly obese patients treated with sleeve gastrectomy and in control subjects. Methods: After fasting for 12 h 15 morbidly obese patients (BMI 51.4 +/- 6.5 kg/m(2), 43.7 +/- 12.6 years) received a standardized oral fat load before and 3 months after bariatric surgery (sleeve gastrectomy). Controls (n=9, BMI 23.1 +/- 1.4 kg/m(2)) were studied once. Plasma was obtained fasting and then postprandially every 2 h for 8 h. Triglycerides (TG), chylomicron-TG (CM-TG), VLDL/chylomicron-remnant (VLDL/CR)-TG, cholesterol, LDL-cholesterol, VLDL/CR-cholesterol and HDL-cholesterol were isolated by ultracentrifugation at each time point. Postprandial values were expressed as area under the curve (AUC) and incremental area under the curve (iAUC). In addition, fasting glucose and insulin values and HOMA-IR-Index was measured (n=14). Results: Compared to controls morbidly obese patients had elevated TG and slightly altered postprandial lipids. Following surgery (weight loss 23.4 kg +/- 6.2 kg; 150 mg/dl) a similar pattern was observed. Fasting insulin and HOMA were reduced significantly (-51.9%; p=0.004 and -47.9%; p=0.011). Conclusions: Three months after sleeve gastrectomy fasting and postprandial lipoprotein metabolism and glucose metabolism is improved in morbidly obese patients. The potential mechanisms may relate to decreased caloric intake but also to hormonal changes

Contribution of socioeconomic status, stature and birth weight to obesity in Sub-Saharan Africa: cross-sectional data from primary school-age children in Cameroon

Background: The pattern of obesity in relation to socioeconomic status is of public health concern. This study investigates whether the association between height and obesity in children is affected by their socioeconomic background. It also explores the relationship between high birth weight and obesity. Methods: School children, (N = 557; 5 to 12 years old) were recruited from randomly selected primary schools in a cross-sectional study including 173 rural and 384 urban children in the North West Region of Cameroon. Socioeconomic status (SES) and birth weight were obtained using a self administered questionnaire. Anthropometric measures included height, weight, BMI, waist circumference and percentage body fat. These measures were transformed into age and sex-standardized variables. Then participants were divided according to quartiles of height SDS. Results: The highest frequencies of overweight/obesity (18.8%), abdominal overweight/obesity (10.9%) and high body fat/obesity (12.3%) were observed among the tallest children from a high socioeconomic background. Univariate analyses indicate that children of high SES (39.9%), fourth height quartile (33.1%) and of high birth weight (54.8%) were significantly (p&lt;0.001) more likely to be overweight/obese. Multivariate analyses showed high SES (OR 8.3, 95% CI 3.9 - 15.4), fourth height quartile (OR 9.1, 95% CI 3.4 - 16.7) and high birth weight (OR 0.1, 95% CI 0.06 - 0.2) as independent predictors of overweight/obesity. Conclusions: This study confirms that children coming from a high socioeconomic background and being tall are at particular risk of becoming obese