Hyperlipidemia

Coronary heart disease (CHD) is prevalent and often related to an unhealthy diet and hyperlipidemia. The diagnosis of hyperlipidemia should be carefully made, using more than one measurement in the manner described. An assessment of risks allows one to decide whom to treat. Patients with CHD should be treated aggressively but it is less clear how aggressive to be with patients without CHD. Diet and exercise recommendations are appropriate for almost all patients. For those for whom the benefit is greater than the potential risks, statins are first-line drug therapy and they appear to have beneficial effects aside from their lipid-lowering properties.     

Primary care issues in patients with mental illness

Family physicians commonly care for patients with serious mental illness. Patients with psychotic and bipolar disorders have more comorbid medical conditions and higher mortality rates than patients without serious mental illness. Many medications prescribed for serious mental illness have significant metabolic and cardiovascular adverse effects. Patients treated with second-generation antipsychotics should receive preventive counseling and treatment for obesity, hyperglycemia, diabetes, and hyperlipidemia. First- and second-generation antipsychotics have been associated with QT prolongation. Many common medications can interact with antipsychotics, increasing the risk of cardiac arrhythmias and sudden death. Drug interactions can also lead to increased adverse effects, increased or decreased drug levels, toxicity, or treatment failure. Physicians should carefully consider the risks and benefits of second-generation antipsychotic medications, and patient care should be coordinated between primary care physicians and mental health professionals to prevent serious adverse effects.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Statins (HMG-CoA reductase inhibitors)

Diabetic patients frequently show lipid abnormalities that include qualitative changes in lipid profile. Given the greatly increased risk of coronary heart disease (CHD) in diabetic patients with hyperlipidemia, most principal clinical guidelines recommend aggressively lowering lipid levels in such patients. In fact, several large-scale clinical intervention trials have successfully shown that lipid-lowering agents, particularly statins, could significantly reduce the CHD risk in diabetic patients with hyperlipidemia. According to our investigation on 9,000 Japanese diabetic patients, about a half had hyperlipidemia but only less than half of the hyperlipidemic patients received some lipid-lowering agents. Taken together, it should be concluded that more stringent and aggressive intervention should be recommended in the treatment of Japanese diabetic patients with hyperlipidemia.     

Treatment of diabetes in the elderly

Diabetes mellitus is one of the most common medical problems in elderly patients. There is a strong rationale for therapy in most patients with diabetes, even those who are asymptomatic. Family physicians should be aware of several age-associated differences in the management and treatment of diabetes in older patients. For elderly patients, dietary modifications may include an increase in the percentage of carbohydrates and a decrease in the percentage of fat. For obese patients, dietary therapy should also emphasize a decrease in overall calories. Oral hypoglycemic agents are generally used as the initial drug therapy. Insulin therapy should be instituted when oral agents fail to reduce the blood glucose level, when the blood glucose level is very high and in other special circumstances. A careful choice of medications for other common problems associated with diabetes, such as hypertension, hyperlipidemia and peripheral neuropathy, is also essential.     

Fenofibrate-induced rhabdomyolysis in a patient with chronic renal failure due to nephrotic syndrome: a rare case report

ObjectivesFenofibrate is a fibric acid derivative that is used alone or combination with statins in the treatment of hyperlipidemia. These drugs have potential risks, including rhabdomyolysis and acute renal failure. Despite reports of rhabdomyolysis with the use of fenofibrate alone or with statin-fibrate combinations, there have been no cases of rhabdomyolysis described when fenofibrate was used alone to treat patients with chronic renal failure owing to nephrotic syndrome.Design and methodsWe report on a 26-year-old male who presented with fenofibrate-induced rhabdomyolysis with chronic renal failure due to nephrotic syndrome.ResultsAfter the discontinuation of fenofibrate, the patient was treated with intravenous fluid replacement and urine alkalization. Subsequently, his clinical and biochemical findings improved.ConclusionsBefore starting fenofibrate therapy, the causes of secondary hyperlipidemia, especially nephrotic syndrome, should be investigated. In the presence of chronic renal failure and hypoalbuminemia, the fenofibrate dose should be adjusted. Physicians should be aware of the potential toxicities of fenofibrate, and patients should be informed about its potential side effects.     

When and how to treat hyperlipidemia

The recently completed NHLBI sponsored multicenter double-blind Coronary Heart Disease Prevention Trial has provided the long sought-after proof that hyperlipidemia is a major CAD risk factor and that the incidence of CHD and its complications can be favorable modified by control of hyperlipidemia with appropriate diet-drug therapy. This nationwide study confirms and validates the earlier reports on the feasibility to stabilize or to promote regression of atherosclerotic arterial lesions through hyperlipidemia control. Current investigations suggest that in most instances, simple differentiation of hyperlipidemias into hypercholesterolemia and hypertriglyceridemia (major components of low-density and very low-density lipoprotein) can supply adequate information for clinical practice. In difficult-to-control hyperlipidemias, the application of lipoprotein analysis may provide insight of the underlying genetic-metabolic abnormality for selection of more specific therapeutic modality. Before considering hypolipemic therapy, secondary hyperlipidemias should be excluded. In those cases, treatment should be directed to the primary disease(s) for the solution of the hyperlipemic problem. Life-long dietary modification is the key step to treatment of all types of hyperlipidemias, and especially the primary hyperlipidemias. In this latter group, both the patient and the family should be educated on the principles and the importance of dietary modification to boost compliance. In familial hyperlipidemias, a specifically effective hypolipemic drug, or a combination of drugs with minimal or no long-term toxic and side effects, should be prescribed to augment the therapeutic diet to lower the elevated plasma lipid levels and stabilize them at normal range. Early detection and control of atherosclerosis-prone hyperlipidemias in children and young adults should be vigorously promoted to improve cardiovascular health of the population and to reduce the escalation of health care expenses.     

Beneficial effects of atorvastatin in the treatment of hyperlipidemia after renal transplantation

Despite the availability of various lipid lowering drugs, the treatment of hyperlipidemia, one of the most important risk factors for morbidity and mortality after organ transplantation, remains a therapeutic challenge. We investigated the safety and efficacy of a new HMG-CoA reductase inhibitor, atorvastatin, in renal transplant patients whose serum lipids were insufficiently controlled by diet and treatment with other lipid lowering drugs. Twenty-four patients (14 males/10 females; mean age 51.2 +/- 2.3 years) were converted to low dose atorvastatin (10 mg/day) at a mean of 67.7 +/- 8.6 months after renal transplantation and prospectively followed for 3 months after initiation of the study drug. HDL, LDL, and total cholesterol, triglycerides, serum creatinine and CPK levels were evaluated pre (-3, -1, 0 months) and post conversion (+1, +3 months). In the eighteen patients who completed the study, low dose atorvastatin therapy led to a significant reduction in total cholesterol (304.6 +/- 13.2 vs. 247.6 +/- 12.0 mg/dl; p = 0.007) and LDL cholesterol (191.9 +/- 9.0 vs. 141.8 +/- 14.7 mg/dl; p < 0.0001) and a modest reduction in serum triglyceride levels at three months after conversion. We conclude that low dose atorvastatin (10 mg/day) can be successfully used and appears to be safe in the treatment of posttransplant hyperlipidemia. Its long-term effects on patient morbidity and mortality as well as graft survival should be investigated in larger and more prolonged prospective trials.     

农村居民高血脂症患者对疾病知识认知的现状调查与对策

目的 了解农村居民高血脂症患者对疾病知识的认知,提出对策.方法 自行设计调查问卷,对245例高血脂症患者进行调查,内容包括一般资料及疾病相关知识认知.结果 回收有效问卷224份.224例患者对高血脂症认知度总体较差,部分患者存在不良的生活方式.结论农村居民高血脂症患者缺乏疾病相关知识,必须加强健康教育.     

Management of peripheral arterial disease

Peripheral arterial disease is common, but the diagnosis frequently is overlooked because of subtle physical findings and lack of classic symptoms. Screening based on the ankle brachial index using Doppler ultrasonography may be more useful than physical examination alone. Noninvasive modalities to locate lesions include magnetic resonance angiography, duplex scanning, and hemodynamic localization. Major risk factors for peripheral arterial disease are cigarette smoking, diabetes mellitus, older age (older than 40 years), hypertension, hyperlipidemia, and hyperhomocystinemia. Nonsurgical therapy for intermittent claudication involves risk-factor modification, exercise, and pharmacologic therapy. Based on available evidence, a supervised exercise program is the most effective treatment. All patients with peripheral arterial disease should undergo aggressive control of blood pressure, sugar intake, and lipid levels. All available strategies to help patients quit smoking, such as counseling and nicotine replacement, should be used. Effective drug therapies for peripheral arterial disease include aspirin (with or without dipyridamole), clopidogrel, cilostazol, and pentoxifylline.     

Treatment of lipid disorders in obesity

Obesity is the most common cause of secondary hyperlipidemia. Atherogenic dyslipidemia refers to elevated triglycerides, low HDL-cholesterol and small dense LDL associated with visceral obesity and metabolic syndrome. Obesity may also be associated with isolated low HDL-cholesterol or high triglycerides and postprandial hyperlipidemia. While some obese patients have high LDL cholesterol concentrations, obesity has a more pronounced effect on other atherogenic lipids and lipoproteins. Obesity may aggravate familial lipid disorders. Lipid disorders in obesity are responsive to weight loss, pharmacotherapy and weight loss surgery. Statins are the lipid-lowering drug of choice, together with lifestyle change. Hard clinical end point data to support combinations of statins with other drugs is lacking. After weight loss surgery, the absolute risk of cardiovascular disease should be reassessed, but tools to facilitate risk assessment need to be developed.     

Other antihyperuricemic agents

It has been reported that hyperuricemia might be responsible for cardiovascular diseases as well as gout and renal injury. Hypertension and hyperlipidemia, which are also responsible for cardiovascular diseases, are often associated with hyperuricemia. Thus, the treatment of hypertension and hyperlipidemia associated with hyperuricemia is also important. Losartan, an antihypertensive agent, and fenofibrate, an antihyperlipidemic agent, are known to have uric acid lowering effects. Both agents are useful for hyperuricemia with associated with hypertension and hyperlipidemia. In this section, we reported the characteristics and usefulness of these two agents in hyperuricemic patients with hypertension and hyperlipidemia.     

Combinations of ezetimibe with nonstatin drug regimens affecting lipid metabolism

In this article we discuss the available data on the effects of combined therapy of ezetimibe with agents affecting lipid metabolism other than statins. We consider studies evaluating the effects of combined therapy of ezetimibe with bile acid sequestrants, fenofibrate, niacin, n-3 fatty acids, plant sterols, orlistat, metformin, acarbose and glitazones. Combination of ezetimibe with bile acid sequestrants (especially colesevelam) was shown to have additional effects on lipid parameters in patients with hyperlipidemia. Combination of ezetimibe with fenofibrate may be a good approach to improve the overall lipid profile of patients with mixed hyperlipidemia. The addition of ezetimibe to niacin-based therapy can be useful for high-risk patients with dyslipidemia who are not achieving their assigned treatment goals. For patients who cannot tolerate statins there are useful combinations of ezetimibe with other drugs affecting lipid metabolism. These combinations improve many metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular disease prevention.     

Combinations of ezetimibe with nonstatin drug regimens affecting lipid metabolism

In this article we discuss the available data on the effects of combined therapy of ezetimibe with agents affecting lipid metabolism other than statins. We consider studies evaluating the effects of combined therapy of ezetimibe with bile acid sequestrants, fenofibrate, niacin, n-3 fatty acids, plant sterols, orlistat, metformin, acarbose and glitazones. Combination of ezetimibe with bile acid sequestrants (especially colesevelam) was shown to have additional effects on lipid parameters in patients with hyperlipidemia. Combination of ezetimibe with fenofibrate may be a good approach to improve the overall lipid profile of patients with mixed hyperlipidemia. The addition of ezetimibe to niacin-based therapy can be useful for high-risk patients with dyslipidemia who are not achieving their assigned treatment goals. For patients who cannot tolerate statins there are useful combinations of ezetimibe with other drugs affecting lipid metabolism. These combinations improve many metabolic parameters, but more trials should be carried out to reach more robust conclusions about their effects on cardiovascular disease prevention.     

Rhabdomyolysis with concurrent atorvastatin and diltiazem

OBJECTIVE: To report a case of rhabdomyolysis and acute hepatitis associated with the coadministration of atorvastatin and diltiazem. CASE SUMMARY: A 60-year-old African American man with a significant past medical history presented to the emergency department with acute renal failure secondary to rhabdomyolysis. In addition, liver enzymes were elevated to greater than 3 times normal. The only change in medication was the initiation of diltiazem 3 weeks earlier for atrial fibrillation to a complicated medication regimen that included atorvastatin. DISCUSSION: Rhabdomyolysis has been reported in patients receiving hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors when coadministered with agents that may inhibit their metabolism. Atorvastatin is the most potent of this class of agents currently available and is commonly used in the treatment of hyperlipidemia. Rhabdomyolysis resulting from the drug interaction between diltiazem and other HMG-CoA reductase inhibitors has been described in the literature. However, no report has specifically associated this adverse event with atorvastatin and diltiazem. We describe a patient with a complex medication regimen who was admitted for rhabdomyolysis and accompanying acute renal failure, along with acute hepatitis, thought to be secondary to a drug interaction between atorvastatin and diltiazem. CONCLUSIONS: While optimizing the patient's lipid profile should be the primary factor in choosing one statin over another, the potential for drug interactions requires close attention. All patients beginning HMG-CoA reductase inhibitor therapy should be counseled regarding the signs and symptoms of muscle injury; particular attention should be paid to those patients who are taking medications that may interact.     

瑞舒伐他汀钙对脑梗死患者血脂、超敏C-反应蛋白水平的影响

目的观察瑞舒伐他汀钙干预后对脑梗死患者血脂和C-反应蛋白水平的影响。方法选取96例脑梗死合并高脂血症的患者,随机分为观察组49例和对照组47例。分别予以瑞舒伐他汀钙、阿托伐他汀钙治疗,用药6周后检测血清脂蛋白、超敏C反应蛋白(hs-CRP)水平。结果观察组较对照组血清低密度脂蛋白、超敏C反应蛋白(hs-CRP)显著降低(P<0.05),从而降低脑血管疾病的发生。结论瑞舒伐他汀钙可降低脑梗死患者的血脂及hs-CRP水平,对预防脑血管疾病具有较好的作用。     

清芝灵治疗老年高脂血症的疗效观察

目的 探讨清芝灵治疗老年高脂血症的临床疗效.方法 符合高脂血症的老年患者116例,随机分为治疗组60例,对照组56例,治疗组口服清芝灵0.2 g,3次/d;对照组口服氟伐他汀20 mg,每晚1次.用药前及用药后12周采血测验,观察疗效和不良反应.结果 两组治疗后血脂指标均有显著改善(P＜0.05),两组组间比较无显著差异(P＞0.05),治疗组未发现肝肾功能异常,而对照组9例(16.1%)出现肝功能异常和肌肉酸痛、肌酶升高等不良反应.结论 清芝灵治疗老年高脂血症安全有效,依从性良好,适合长期服用治疗老年高脂血症患者.     

Pitavastatin calcium: clinical review of a new antihyperlipidemic medication

BackgroundPitavastatin calcium is a new addition to the class of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (“statins”) approved for use in the United States for the treatment of primary hyperlipidemia and mixed dyslipidemia.ObjectiveThe purpose of this review was to evaluate the literature related to the medicinal chemistry, pharmacology, pharmacokinetic properties, clinical efficacy, and tolerability of pitavastatin in the treatment of hyperlipidemia.MethodsA search of MEDLINE, EMBASE, and the Journal Archive for English-language literature was conducted for articles published through January 2011 using the following search terms: itavastatin, Livalo, nisvastatin, NK 104, and pitavastatin. Articles were reviewed if they pertained to the clinical efficacy, pharmacology, pharmacokinetic properties, or tolerability of pitavastatin. Clinical trials were systematically included in the analysis of clinical efficacy if they used a randomized design to study the effects of the drug on hyperlipidemia, hypercholesterolemia, or heart disease. Trials were excluded if they did not signify the statin used, did not pertain to clinical efficacy, or enrolled <20 patients.ResultsA total of 16 studies were identified and reviewed for clinical efficacy. Based on findings from pharmacokinetic studies, pitavastatin may be given at any time of the day, with or without food. The drug had a mean plasma elimination t_1/2 of 12 hours, is expected to be associated with minimal drug–drug interactions because it is not metabolized by the cytochrome P450 3A4 isozyme, and is primarily excreted unchanged in the bile with little renal elimination. Clinical trials described the effects of pitavastatin on cholesterol, high-sensitivity C-reactive protein (hs-CRP), and progression of atherosclerosis. Pitavastatin at doses of 1 to 4 mg/d was reported to be associated with reductions in LDL-C of 38% to 44% and in triglycerides of 14% to 22%, and with increases in HDL-C of 5% to 8% (all, P < 0.05). Overall, the effect of pitavastatin on cholesterol was comparable to those of atorvastatin and simvastatin at low to intermediate doses. Studies on the effects of pitavastatin on cardiovascular outcomes were lacking. The adverse-events (AE) profile of pitavastatin compared favorably with those of other available statins. AEs included gastrointestinal symptoms (0.7%–2.2%), myopathies (0.3%–1.1%), and elevated hepatic enzyme concentrations (0.0%–8.8%).ConclusionsBased on the findings from previously published clinical trials, pitavastatin is an effective lipid lowering agent and is another therapeutic option of currently available statins.     

Stroke risk, cholesterol and statins.

The natural statins should be used as first line agents in the prevention of stroke. The effects of the synthetic statins on the prevention of coronary events and stroke have not been reported at this time. The National Stroke Association's Stroke Prevention Advisory Board has prepared a consensus statement on risk reducing intervention. The Board identified hypertension, MI, atrial fibrillation, hyperlipidemia and asymptomatic carotid artery stenosis (60% to 99% occlusion) as proven stroke risk factors. The Board's recommendations for the prevention of a first stroke are: 1. Hypertension should be treated with lifestyle, pharmacologic and multidisciplinary management strategies. 2. Aspirin post MI and warfarin (international normalized ratio, 2 to 3) for patients with atrial fibrillation, left ventricular thrombus or significant left ventricular dysfunction. Statin agents should be used post MI. 3. Atrial fibrillation patients age 75 or older should be treated with warfarin. Younger patients 65 to 75 with atrial fibrillation and risk factors should be treated with warfarin [corrected]. Younger patients 65 to 75 with atrial fibrillation without risk factors should be treated with warfarin or aspirin [corrected]. 4. Patients with hyperlipidemia and coronary artery disease should be on statin agents. 5. Carotid endarterectomy is recommended for asymptomatic carotid stenosis (60% to 99%) when surgical morbidity and mortality are less than 3%. 6. Adherence to a low-fat diet, smoking avoidance, mild alcohol use, and physical activity should follow published guidelines.     

秋水仙碱对高脂血症新西兰兔血浆CRP和一氧化氮水平的影响

目的：探讨秋水仙碱对高脂血症新西兰兔血浆CRP和一氧化氮水平的影响。方法通过给予高脂饮食构建新西兰兔高脂血症模型,模型构建成功后干预组给予0.01 mg/kg秋水仙碱治疗,共2周。评估空白组、高脂血症对照组和高脂血症干预组3组新西兰兔血脂、CRP及一氧化氮水平。结果经8周高脂饮食饲养后,与空白组相比,高脂血症组新西兰兔血脂指标水平均明显升高,差异有统计学意义（均P＜0.05）;与空白组相比,血浆CRP水平在高脂血症组也明显升高,而一氧化氮水平则明显降低（P＜0.05）。高脂血症干预组与高脂血症对照组血脂水平无明显差异,但高脂血症干预组血浆CRP水平明显降低,而一氧化氮水平则明显升高,与高脂血症对照组比较差异有统计学意义（均P＜0.05）。结论秋水仙碱能够通过下调血浆CRP水平从而改善高脂血症新西兰兔血管内皮细胞功能,这可能是秋水仙碱能够减少冠心病患者心血管事件的其中一个作用机制。