The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice. However, safety concerns, especially regarding ...hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis , in which liver enzyme levels are elevated in the absence of proven hepatotoxicity. This class effect is usually asymptomatic, reversible, and dose-related. However, the increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment in patients with high cardiovascular risk. These diseases result in abnormally high liver biochemistry values, discouraging statin use by clinicians, fostering treatment discontinuation, and leaving a large number of at-risk patients untreated. A PubMed/MEDLINE search of the literature regarding statin safety (January 1, 1994-December 31, 2008) was performed, using the following search terms: statin safety , statin-related hepatotoxicity , and chronic liver disease and statin use , as well as the specific names of different statins and different liver diseases. Relevant clinical trials, review articles, panel discussions, and guideline recommendations were selected. This review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions. For each patient, the decision should be based on an individual assessment of risks and benefits.
Objective To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict ...neurodevelopmental outcome in extremely low birth weight infants. Study design Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin IL 1β; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. Results IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-β, soluble IL rα, macrophage inflammatory protein 1β) were found to be altered on days 0-4 in infants who developed CP. Conclusions CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.
Abstract The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density ...lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers C-reactive protein, lipoprotein-associated phospholipase A2 , apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk.
Adiponectin concentrations exhibit strong cross-sectional relationships with obesity, inflammation, and diabetes. Adiponectin concentrations have been extensively evaluated as epidemiologic markers ...of diabetes and cardiovascular disease risk. In the present review we will provide an overview of these epidemiologic relationships as the backdrop for an evaluation of the clinical applications of adiponectin measurements. These include using adiponectin as an indicator of need for preventive or therapeutic intervention, as a predictor of response to therapy, and as a marker of therapeutic effectiveness. These efforts are laying the groundwork for the transition of adiponectin measurements from the laboratory to the clinic.
Niacin (nicotinic acid), the most effective available pharmacotherapy for increasing high-density lipoprotein cholesterol, also lowers triglycerides and hence may be useful, alone or in combination ...with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), to offset residual cardiovascular risk in patients with mixed or diabetic dyslipidemia. We conducted a review of published consensus guidelines since 2000 and an English-language PubMed search of prospective, randomized controlled trials and open-label studies from January 1, 1990, through December 31, 2007, concerning the effects of niacin, alone or in combination with statins, on glycemic regulation in dyslipidemic patients (with or without diabetes mellitus). For search terms, we used the title words niacin or nicotinic acid and key words including diabetes, diabetic, dyslipidemia, glucose, glycemic, HbA1c , hemoglobin, hyperglycemia, human, insulin, postprandial, and safety. Retrospective and observational studies, case reports, and case studies were excluded. On the basis of our analysis, the effects of niacin (≤2.5 g/d), alone or in combination with statins, on fasting glucose (an increase of 4%-5%) and hemoglobin A1c levels (an increase of ≤0.3%) are modest, transient or reversible, and typically amenable to adjustments in oral hypoglycemic regimens without discontinuing niacin. Niacin therapy was infrequently associated with incident diabetes or the need for new insulin prescriptions. Studies showed important clinical benefits of niacin or niacin-statin regimens despite modest effects on glucose control. On a population basis, significant reductions in incidences of cardiovascular events and the degree of atherosclerotic progression associated with long-term niacin (or niacin-statin) therapy in patients with diabetic dyslipidemia outweigh the typically mild effects of this therapy on glycemic regulation. Consensus guidelines recommend monitoring glycemic control after initiating niacin treatment or increasing its dosage.
Objective To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants. Study design This was a cohort study of infants with a birth weight ...≤1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida . Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI). Results A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes. Conclusion Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
Abstract Background Niacin is an anti-dyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in non-diabetic statin-treated ...subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods This was a pre-specified, intent-to-treat analysis of 3414 participants in the Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes trial randomized at 92 centers in the United States and Canada to ERN plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, non-diabetic subjects with 2 annual follow up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results Compared to placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9±15.8 vs 4.3±10.3 mg/dl; p<0.001) and impaired fasting glucose (4.1±18.7 vs 1.4±14.9 p<0.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336 cases (58.6%) versus placebo 135/325 cases (41.5%) p<0.001) over time, but no difference in diabetes development in the two treatment groups except in those with normal fasting glucose at baseline. Conclusions The addition of ERN to simvastatin/ezetemibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new onset diabetes. In addition ERN increased the risk of developing impaired fasting glucose which may have deleterious consequences over time and warrants further study.
Relationship of Lipoproteins to Cardiovascular Events Guyton, John R., MD; Slee, April E., MS; Anderson, Todd, MD ...
Journal of the American College of Cardiology,
10/2013, Letnik:
62, Številka:
17
Journal Article
Recenzirano
Odprti dostop
Objectives This study sought to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes in this secondary analysis of the AIM-HIGH (Atherothrombosis ...Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial. Background During a 3-year follow-up in 3,414 patients with established CV disease and low high-density lipoprotein cholesterol (HDL-C) levels, combined niacin + low-density lipoprotein cholesterol (LDL-C)–lowering therapy did not reduce CV events compared with LDL-C–lowering therapy alone. Methods Subjects taking simvastatin and/or ezetimibe were randomized to receive extended-release (ER) niacin 1,500 to 2,000 mg or minimal immediate-release niacin (≤150 mg) as placebo at bedtime. LDL-C levels in both groups were maintained from 40 to 80 mg/dl. Hazard ratios were estimated by using Cox proportional hazards models for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Results CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (≥198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (hazard ratio: 0.74, p = 0.073). In-trial LDL-C levels, non–HDL-C levels, and the total cholesterol/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group. Conclusions Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-C–lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could affect risk. (Niacin Plus Statin to Prevent Vascular Events AIM-HIGH; NCT00120289 )
Abstract Background: In people without diabetes, ∼50% of daily insulin secretion is basal and the remainder is postprandial. Hence, it would be expected that insulin replacement therapy in a 50/50 ...ratio with each meal would mimic physiologic insulin secretion better than treatment with once-daily basal insulin in patients with diabetes mellitus. Using lispro mix (LM) 50/50 before meals may be a logical approach to achieving glycemic targets (glycosylated hemoglobin HbAlc and pre- and postprandial blood glucose BG concentrations) in these patients. Objective: The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus. Methods: This 24-week, randomized, open-label, parallel-group trial was conducted at 38 sites across Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States. Male and female patients aged 35 to 75 years with type 2 diabetes mellitus and an HbA1c level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injections over the previous 3 months were eligible. Patients were randomly assigned to receive LM50/50 (50% insulin lispro protamine suspension ILPS and 50% lispro) TID plus metformin (to a maximally tolerated daily dosage of 500-1000 mg BID) (LM50/50 + Met) or insulin glar-gine QD at bedtime plus metformin (500-1000 mg BID) (G + Met) for 24 weeks. With LM50/50 + Met, the insulin dose was titrated to target a fasting BG (FBG) level of <6.7 mmol/L (<120 mg/dL) and a 2-hour post-prandial BG (PPBG) level of <8.0 mmol/L (<144 mg/dL)
Abstract Cumulative evidence suggests that lipoprotein(a) Lp(a) exerts an independent effect on the initiation and progression of atherosclerotic cardiovascular disease. The genetically mediated ...expression of apolipoprotein(a), which is the key structural and functional component of Lp(a), occurs in hepatocytes with subsequent extracellular Lp(a) assembly at the hepatic cell surface. Here, we describe a case of elevated Lp(a) concentrations identified after (and likely acquired by) orthotopic liver transplantation that contributed to accelerated atherosclerotic cardiovascular disease despite intensive therapeutic interventions. This case study represents an important example to include Lp(a) screening in routine lipid panel testing for all liver transplant donors and recipients; to reduce unanticipated and debilitating cardiovascular morbidity and mortality.
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