UMLS:C0020473 - FACTA Search

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Query: UMLS:C0020473 (hyperlipidemia)
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Combined hyperlipidemia results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins in association with reduced lipoprotein lipase activity. Thus, this condition is typically characterized by concurrent elevations in total cholesterol and triglycerides with decreased high-density lipoprotein cholesterol. High levels of apolipoprotein B-containing lipoproteins, most prominently carried by low-density lipoprotein (LDL) particles, are an important risk factor for coronary heart disease. Statin therapy is highly effective at lowering LDL cholesterol. Despite the benefits of statin treatment for lowering total and LDL cholesterol, many statin-treated patients still have initial or recurrent coronary heart disease events. In this regard, combined therapy with statins and fibrates is more effective in controlling atherogenic dyslipidemia in patients with combined hyperlipidemia than either drug alone. Furthermore, statins and fibrates activate PPARalpha in a synergistic manner providing a molecular rationale for combination treatment in coronary heart disease. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. However, there has been little published evidence that combined therapy is synergistic or even better than monotherapy alone in clinical studies. Therefore, there is a great need to study the effects of combination therapy in patients. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy.
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PMID:Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. 1765 32

Sirolimus (SRL) has become an option in kidney transplantation, especially among patients who develop chronic allograft nephropathy (CAN). This study sought to evaluate the safety and efficacy of SRL in 103 kidney recipients of mean age 40 years, including 78 recipients of organs from deceased donors. The major reason for conversion was calcineurin inhibitor (CNI) nephrotoxicity (42.3%) followed by CAN (35.4%). A preconversion kidney biopsy was performed in 89 patients with CAN diagnosed in 51. Mean time to conversion was 40.5 months. The new therapy was: SRL/mycophenolate mofetil (MMF)/prednisone (Pred) in 79 patients; SRL/tacrolimus (TAC)/Pred in 15; and other SRL combinations in 9. The target SRL trough level was 5.0 to 8.0 ng/mL. To evaluate the impact of conversion on renal function, we compared the proteinuria and inverse serum creatinine at 3 months before conversion, at conversion, and at 1, 3, 6, 12, and 24 months postconversion. The overall mean follow-up time was 13.2 months. The analysis showed significant improvement in renal function at month 1 postconversion (P<.05) with stabilization thereafter. The SRL/MMF combination frequently induced anemia and/or leukopenia (n=23). Infections included pneumonia (n=10), herpes zoster (n=7), herpes simplex (n=3), cytomegalovirus (n=2), histoplasmosis (n=2), tuberculosis (n=2), and neurocryptococcosis (n=1). Reasons for SRL discontinuation were myelotoxicity (n=4), infection (n=3), nephrotoxicity (n=3), gastrointestinal intolerance (n=3), myopathy (n=1), pneumonitis (n=1), hyperlipidemia (n=1), and other reasons (n=3). Graft loss occurred in 29 patients due to CAN (n=21) followed by death (cardiovascular, n=2; infectious, n=2), acute rejection (n=3), and infection following immunosuppression withdrawal (n=1). We concluded that SRL represented an option but reducing associated immunosuppression should strongly be considered to minimize the frequent side effects, especially infections.
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PMID:Posttransplantation conversion to sirolimus-based immunosuppression: a single center experience. 1808 30

Statins, 3-hydroxy-3-methlglutaryl coenzyme A reductase inhibitors, are commonly prescribed for patients who have hyperlipidemia. Statins were first approved in 1987. Statin therapy is well documented to reduce serum low-density lipoprotein levels, incidence of cardiovascular events, and mortality. Although statin therapy is well tolerated, serious adverse affects have been reported, including neuromuscular and hepatic complications. Myopathy is particularly concerning because of the potential for rhabdomyolysis and death. Recently, peripheral neuropathy also has been identified as a possible complication. The incidence of neuromuscular complications is expected to increase with the increased number of people using statin therapy. Clinicians should be aware of the potential neuromuscular complications. This article reviews epidemiology, possible mechanisms, risk factors, and management of statin-associated neuromuscular complications.
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PMID:Neuromuscular complications of statins. 1819 49

Cardiovascular disease remains the leading cause of mortality in elderly patients. While coronary heart disease (CHD) morbidity and mortality have decreased over the last 25 years, the percentage reduction in elderly patients is nearly 50% lower than that for the general adult population. Therefore, aggressive primary and secondary prevention of CHD is imperative for our society, and hyperlipidaemia remains the major modifiable risk factor in the elderly population. However, there appears to be a reluctance among practitioners to treat hyperlipidaemia in elderly patients, a bias that is particularly important given the absolute benefits of treating such patients. While many of the major clinical trials involving HMG-CoA reductase inhibitors (statins) in patients with CHD focused on younger individuals, subsequent subgroup analyses of elderly patients have shown consistent reductions in all-cause mortality, major CHD events and numbers of revascularization procedures. Intensive statin therapy in the setting of acute myocardial infarction (MI) has also been shown to reduce the risk of death, MI, unstable angina, revascularization and stroke in elderly patients. Furthermore, three recent articles that have evaluated intensive lipid-lowering in the elderly population have extended the known benefits of such therapy to elderly patients with acute coronary syndrome and stable CHD.Elderly patients often take multiple medications and are at significant risk of drug-drug interactions. Several available statin medications are metabolized by cytochrome P450 (CYP) 3A4 and can therefore interact with commonly used medications such as amiodarone, macrolide antibacterials, calcium channel antagonists, fibric acid derivatives and ciclosporin. These interactions can result in an increased frequency of statin-related hepatotoxicity and myopathy.There are currently six commercially available statin medications on the US market, three of which, lovastatin, simvastatin and pravastatin, are available in generic formulations, and are thus less expensive. Of the commercially available statins, rosuvastatin, atorvastatin and simvastatin have the highest potency. While rosuvastatin currently lacks clinical event data, atorvastatin has the most clinical event data for CHD and even stroke prevention. Although pravastatin has lower potency than other described statins, it also has the lowest risk of drug-drug interactions involving CYP.
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PMID:Secondary prevention of coronary heart disease in elderly patients following myocardial infarction: are all HMG-CoA reductase inhibitors alike? 1866 58

Medications inhibiting 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase are commonly used as lipid-lowering therapy. Myopathy has been reported as a rare adverse effect in up to 0.2% of patients; however, this complication appears to be more common in patients who are concurrently receiving cyclosporin A(CsA). We present a case of a 74-year-old woman tolerating a stable dose of simvastatin 80 mg daily for hyperlipidemia. After the addition of CsA for a corneal stem limbal cell transplant, the patient experienced a cholesterol-lowering agent myopathy syndrome (CLAMS), with creatine phosphokinase values up to 78,472 U/L. We explore the interaction between simvastatin and CsA, including effects on hepatic microsomal metabolism via the cytochrome P-450 pathway, cholestasis, and myoblast histology, with a review of previous literature regarding HMG-CoA reductase inhibitors (HMGRIs) and rhabdomyolysis. Caution should be exercised in patients receiving concomitant simvastatin and CsA, and a reduced dose of simvastatin is suggested. Inhibition of HMG-CoA reductase is an accepted therapy for hyperlipidemias. The development of a CLAMS is a known potential adverse effect (1), with an increased incidence during coadministration of lovastatin and CsA, first reported by Norman et al. and East et al. in 1988 (2, 3). The interaction between the HMGRIs and CsA, which leads to this muscle toxicity, appears to be related to altered clearance of the HMGRIs with resultant increased tissue exposure (4). The majority of experience with rhabdomyolysis has been in cardiac and renal transplant patients requiring lovastatin and CsA. Theoretically, however, any of the HMGRIs may predispose a patient requiring CsA to develop myositis. In particular, there is a suggestion of an increased sensitivity of myoblasts to both lovastatin and simvastatin (5). We present a case of rhabdomyolysis in a corneal stem cell transplant patient receiving simvastatin and CsA, with a review of the literature.
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PMID:Rhabdomyolysis in a patient taking simvastatin after addition of cyclosporine therapy. 1907 94

Statins are regarded as a well-tolerated class of drugs, particularly when compared with some of the older lipid-modifying agents, which have poor rates of compliance. Despite some early concern, the incidence of lens opacities observed in clinical studies involving statin use is no different from that in a normal ageing population. Similarly, the occurrence of insomnia with lipophilic agents appears to have been overemphasised and is not a clinically significant problem, irrespective of the statin under study. Fluvastatin is the newest representative of this class of agents; it has already been evaluated in thousands of patients who have hyperlipidaemia with and without additional risk factors. In controlled clinical studies, the incidence of the majority of adverse events observed with fluvastatin therapy is no higher than that seen with placebo, with the exception of gastrointestinal disturbances (known to be common to all stains). Nonetheless, the incidence of these effects seen with fluvastatin treatment is noted to be lower than that associated with cholestyramine or fibrate use. Elevations in levels of liver transaminases (aspartate aminotransferase and alanine aminotransferase) have been reported with fluvastatin therapy but have led to discontinuation of treatment with the same frequency as with placebo. Elevations in creatine kinase levels as a cause of discontinuing fluvastatin are not more frequent than with placebo. Myopathy and rhabdomyolysis have not been reported with fluvastatin therapy, and myalgia does not occur more frequently than with placebo. In terms of drug interactions, fluvastatin does not interfere with the efficacy of antihypertensive agents. In controlled clinical trials, the overall reported discontinuation rate due to adverse events noted with fluvastatin therapy is 3.3%, which is not significantly distingushable from the rate associated with placebo (3.5%)2.
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PMID:Safety profile of fluvastatin. 872 86

Many patients who receive statin therapy for hyperlipidemia-such as patients with diabetes mellitus and metabolic syndrome--have residual cardiovascular risk. These patients often have dyslipidemia, including low levels of HDL cholesterol and elevated levels of triglycerides and small, dense LDL. For such patients, combination treatment with statins and fibrates is a potentially useful strategy to improve lipid and lipoprotein profiles and reduce cardiovascular risk. However, statin-fibrate combination regimens have potential adverse effects on skeletal muscle, including myopathy. To date, no large-scale, prospective, randomized, controlled trial has evaluated the safety and efficacy of statin-fibrate combination therapy; one such trial is underway but will not report data until 2010. Until then, clinicians need to consider pharmacokinetic, pharmacodynamic, metabolic, pathophysiologic and other factors that can increase the systemic exposure of statins and/or fibrates and hence heighten the risk of toxic effects on muscles, as well as data from clinical trials and recommendations of consensus panels to optimize the safety of such combination regimens. On the basis of currently available data, fenofibrate or fenofibric acid is the fibrate of choice when used in combination with a statin because each is, in theory, associated with a lower risk of myopathy than gemfibrozil.
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PMID:Myopathy with statin-fibrate combination therapy: clinical considerations. 1963 24

Despite its low frequency, endogenous Cushing's syndrome is not an exceptional clinical entity. A growing number of cases are currently derived to specialized centers suggesting an increasing knowledge of the clinical features of hypercortisolism by specialists of diverse branches of clinical medicine. Clinical signs derive from an exaggeration of the physiological actions of cortisol inducing protein breakdown, hyperglycemia, fat mobilization, dyslipidemia, hydrosaline retention, immunosuppression and increased susceptibility to infection. Despite its low specificity, symptoms such as unexplained development of central obesity, mood changes, fatigue, weakness, myopathy, easy bruisability, red striae, arterial hypertension, diabetes and hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of view, Cushing's syndrome is to be suspected and consequently searched for among patients with uncontrolled high blood pressure or diabetes mellitus, metabolic syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal incidentaloma. True Cushing's syndrome has to be differentiated from pseudo syndromes. Most sensitive physical signs for discriminating Cushing's syndrome from pseudo-Cushing states are the presence of supraclavicular fat pads, myopathy, thin skin and easy bruising. The recognition of the clinical manifestations of Cushing's syndrome and of the sub-populations at risk of contracting the disease should be improved through medical education at the medical school and at postgraduate levels. Clinical detection of Cushing's syndrome must be performed mainly by non-endocrinologists, yet its etiological diagnosis and therapeutic management is to be carried out in highly experienced and specialized centers, to ensure the best results in the treatment of this really challenging endocrine disturbance.
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PMID:In what clinical settings should Cushing's syndrome be suspected? 2005 13

Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.
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PMID:Effects of statins on skeletal muscle: a perspective for physical therapists. 2068 75

Coronary heart disease (CHD) is the leading cause of death in Western civilizations, in particular in chronic kidney disease (CKD) patients. Serum total cholesterol and LDL have been linked to the development of atherosclerosis and progression to CHD in the general population. However, the reductions of total and LDL cholesterol in the dialysis population have not demonstrated the ability to reduce the morbidity, mortality, and cost burden associated with CHD. The patients at greatest risk include those with pre-existing CHD, a CHD-risk equivalent, or multiple risk factors. However, data in the dialysis population are much less impressive, and the relationship between plasma cholesterol, cholesterol reduction, use of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and reduction in incidence of CHD or effect on progression of renal disease have not been proven. Adverse event information from published trials indicates that agents within this class share similar tolerability and adverse event profiles. Hepatic transaminase elevations may occur in 1 to 2% of patients and is dose related. Myalgia, myopathy, and rhabodmyolysis occur infrequently and are more common in kidney transplant patients and patients with CKD. This effect appears to be dose related and may be precipitated by administration with agents that inhibit cytochrome P-450 isoenzymes. Caution should be exercised when coadministering any statin with drugs that metabolize through cytochrome P-450 IIIA-4 in particular fibrates, cyclosporine, and azole antifungals. Elderly patients with CKD are at greater risk of adverse drug reactions, and therefore the lowest possible dose of statins should be used for the treatment of hyperlipidemia.
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PMID:The efficacy and safety of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in chronic kidney disease, dialysis, and transplant patients. 2139 88

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